Predictive value of first fasting plasma glucose compared with admission plasma glucose for undiagnosed diabetes in a stable cardiology population.

PubMed

Wen, Zhu-zhi; Zhang, Xin-mei; Mai, Zun; Geng, Deng-feng; Wang, Jing-feng

2012-09-01

The study compared the predictive value of admission plasma glucose (APG) and first fasting plasma glucose (FPG) in stratifying patients meriting an oral glucose tolerance test (OGTT). Characteristics of APG, FPG and OGTT 2-hour glucose as well as other blood measurements, physical examinations and medical information were assessed in 994 patients without known diabetes. The prevalences of diabetes and impaired glucose tolerance were 24.6% and 37.9%, according to an OGTT, respectively. The first FPG demonstrated stronger predictive value in diagnosing diabetes than APG did both in overall and in patients with less clinical value. Compared to the first FPG, APG provided less value to coronary artery disease, hypertension and high-sensitivity C-reactive protein for diabetes screening. The first FPG exerted more predictive value than APG did and was still a preferable reference prior to APG in stratifying patients for undiagnosed diabetes by an OGTT. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Regional body fat distribution and metabolic profile in postmenopausal women.

PubMed

Piché, Marie-Eve; Lapointe, Annie; Weisnagel, S John; Corneau, Louise; Nadeau, André; Bergeron, Jean; Lemieux, Simone

2008-08-01

The aim of the study was to examine how body fat distribution variables were associated with metabolic parameters in a sample of 113 postmenopausal women not receiving hormone therapy (56.9 +/- 4.4 years, 28.4 +/- 5.1 kg/m(2)). Body fat distribution variables (visceral adipose tissue [AT], subcutaneous AT, and total midthigh AT) were measured using computed tomography; body fat mass was assessed by hydrostatic weighing; insulin sensitivity was determined with the euglycemic-hyperinsulinemic clamp; fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) concentrations were measured by a 75-g oral glucose load; and (high-sensitivity) C-reactive protein (hs-CRP) was measured using a highly sensitive assay. After controlling for fat mass, visceral AT was positively associated with plasma triglyceride, hs-CRP, FPG, and 2hPG, and negatively associated with high-density lipoprotein cholesterol (HDL-C) and insulin sensitivity. Total midthigh AT was negatively associated with apolipoprotein B, FPG, and 2hPG, and positively associated with insulin sensitivity. Stepwise multiple regression analyses including abdominal visceral AT, subcutaneous AT and total midthigh AT as independent variables showed that abdominal visceral AT best predicted the variance in plasma triglyceride, HDL-C, low-density lipoprotein peak particle size, hs-CRP, FPG, 2hPG, and insulin sensitivity. Abdominal subcutaneous AT was a significant predictor of only insulin sensitivity, whereas total midthigh AT predicted HDL-C, low-density lipoprotein peak particle size, and apolipoprotein B. These multivariate analyses also indicated that total midthigh AT was favorably related to these outcomes, whereas abdominal visceral AT and subcutaneous AT were unfavorably related. These results confirmed that abdominal visceral fat is a critical correlate of metabolic parameters in postmenopausal women. In addition, a higher proportion of AT located in the total midthigh depot is associated with a favorable metabolic profile.

Molecular dynamics simulation of the opposite-base preference and interactions in the active site of formamidopyrimidine-DNA glycosylase.

PubMed

Popov, Alexander V; Endutkin, Anton V; Vorobjev, Yuri N; Zharkov, Dmitry O

2017-05-08

Formamidopyrimidine-DNA glycosylase (Fpg) removes abundant pre-mutagenic 8-oxoguanine (oxoG) bases from DNA through nucleophilic attack of its N-terminal proline at C1' of the damaged nucleotide. Since oxoG efficiently pairs with both C and A, Fpg must excise oxoG from pairs with C but not with A, otherwise a mutation occurs. The crystal structures of several Fpg-DNA complexes have been solved, yet no structure with A opposite the lesion is available. Here we use molecular dynamic simulation to model interactions in the pre-catalytic complex of Lactococcus lactis Fpg with DNA containing oxoG opposite C or A, the latter in either syn or anti conformation. The catalytic dyad, Pro1-Glu2, was modeled in all four possible protonation states. Only one transition was observed in the experimental reaction rate pH dependence plots, and Glu2 kept the same set of interactions regardless of its protonation state, suggesting that it does not limit the reaction rate. The adenine base opposite oxoG was highly distorting for the adjacent nucleotides: in the more stable syn models it formed non-canonical bonds with out-of-register nucleotides in both the damaged and the complementary strand, whereas in the anti models the adenine either formed non-canonical bonds or was expelled into the major groove. The side chains of Arg109 and Phe111 that Fpg inserts into DNA to maintain its kinked conformation tended to withdraw from their positions if A was opposite to the lesion. The region showing the largest differences in the dynamics between oxoG:C and oxoG:A substrates was unexpectedly remote from the active site, located near the linker joining the two domains of Fpg. This region was also highly conserved among 124 analyzed Fpg sequences. Three sites trapping water molecules through multiple bonds were identified on the protein-DNA interface, apparently helping to maintain enzyme-induced DNA distortion and participating in oxoG recognition. Overall, the discrimination against A opposite to the lesion seems to be due to incorrect DNA distortion around the lesion-containing base pair and, possibly, to gross movement of protein domains connected by the linker.

Vitamin A and C compounds permitted in supplements differ in their abilities to affect cell viability, DNA and the DNA nucleoside deoxyguanosine.

PubMed

Bergström, Therese; Bergman, Jan; Möller, Lennart

2011-11-01

In accordance with the European Parliament and Council's directive, vitamin A and C supplements can include any of four (vitamin A) or five (vitamin C) specified compounds. This study focuses on these compounds and compares their abilities to affect the DNA and viability of cells in culture, but also their potencies to chemically oxidise the DNA nucleoside deoxyguanosine (dG). To study the vitamins' strict chemical oxidation potencies, dG was exposed to vitamin solution and the amount of the oxidation product 8'-hydroxydeoxyguanosine (8-oxodG) formed was estimated using a high-performance liquid chromatography system with electrochemical and ultraviolet detection. The vitamin's ability to cause DNA damage to promyelocytic leukaemia cells (HL-60), as detected by strand breaks, alkaline labile sites and formamido pyrimidine DNA glycosylase (FPG)-sensitive sites was, after vitamin exposure, measured using the comet assay and cytotoxicity was estimated using trypan blue staining. The results highlight that vitamin A and C compounds found in supplements do have different properties, chemically as well as in a cellular system. Among the vitamin C compounds, ascorbic acid, sodium ascorbate and calcium ascorbate stood out causing both oxidation to dG and cytotoxicity to cells. The vitamin A compounds retinol, retinyl acetate and retinal (a breakdown product found in vivo) caused oxidation of dG, while retinal was the only compound causing cytotoxicity, giving rise to an almost complete cell death. β-carotene caused, as the only vitamin compound, a small increase in FPG-sensitive sites. It is concluded that even though the compounds are found under the same name (vitamin A or C), they do have different properties linked to oxidation, cytotoxicity and DNA damage.

Detecting Prediabetes among Hispanics/Latinos from Diverse Heritage Groups: Does the Test Matter? Findings from the Hispanic Community Health Study/Study of Latinos

PubMed Central

Avilés-Santa, M. Larissa; Pérez, Cynthia M.; Schneiderman, Neil; Savage, Peter J.; Kaplan, Robert C.; Teng, Yanping; Suárez, Erick L.; Cai, Jianwen; Giachello, Aida L.; Talavera, Gregory A.; Cowie, Catherine C.

2017-01-01

The objectives of this analysis were to compare the ability of fasting plasma glucose (FPG), post oral load plasma glucose (2hPG), and hemoglobin A1c (HbA1c) to identify U.S. Hispanic/Latino individuals with prediabetes, and to assess its cardiovascular risk factor correlates. This is a cross-sectional analysis of baseline data from 15,507 adults without self-reported diabetes mellitus from six Hispanic/Latino heritage groups, enrolled in the Hispanic Community Health Study/Study of Latinos, which takes place in four U.S. communities. The prevalence of prediabetes was determined according to individual or combinations of ADA-defined cut points: FPG = 5.6–7.0 mmol/L, 2hPG = 7.8–11.1 mmol/L, and HbA1c = 5.7%-6.4% (39–46 mmol/mol). The sensitivity of these criteria to detect prediabetes was estimated. The prevalence ratios (PRs) for selected cardiovascular risk factors were compared among alternative categories of prediabetes versus normoglycemia [FPG < 5.6 mmol/L and 2hPG < 7.8 mmol/L and HbA1c < 5.7% (39 mmol/mol)]. Approximately 36% of individuals met any of the ADA prediabetes criteria. Using 2hPG as the gold standard, the sensitivity of FPG was 40.1%, HbA1c was 45.6%, and that of HbA1c+FPG was 62.2%. The number of significant PRs for cardiovascular risk factors was higher among individuals with isolated 2hPG = 7.8–11.1 mmol/L, FPG = 5.6–7.0 mmol/L + HbA1c = 5.7%-6.4%, or those who met the three prediabetes criteria. Assessing FPG, HbA1c, and cardiovascular risk factors in Hispanics/Latinos at risk might enhance the early prevention of diabetes mellitus and cardiovascular complications in this young and growing population, independent of their heritage group. PMID:27956225

Evaluation of Glycated Hemoglobin (HbA1c) for Diagnosing Type 2 Diabetes and Prediabetes among Palestinian Arab Population

PubMed Central

Kharroubi, Akram T.; Darwish, Hisham M.; Abu Al-Halaweh, Ahmad I.; Khammash, Umaiyeh M.

2014-01-01

The purpose of the study is to compare the potential of HbA1c to diagnose diabetes among Palestinian Arabs compared to fasting plasma glucose (FPG). A cross-sectional sample of 1370 Palestinian men (468) and women (902) without known diabetes and above the age of 30 years were recruited. Whole blood was used to estimate HbA1c and plasma for FPG and total lipid profile. Fasting plasma glucose was used as a reference to diagnose diabetes (≥ 126 mg/dL) and prediabetes (100–125 mg/dL). The area under the receiver operating characteristic curve (AUC) for HbA1c was 81.9% to diagnose diabetes and 63.9% for prediabetes. The agreement between HbA1c and diabetes as diagnosed by FPG was moderate (ĸ  =  0.498) and low with prediabetes (ĸ = 0.142). The optimal cut-off value for HbA1c to diagnose diabetes was ≥ 6.3% (45 mmol/mol). The sensitivity, specificity and the discriminant ability were 65.6% (53.1–76.3%), 94.5% (93.1–95.6%), 80.0% (72.8–87.3%), respectively. However, using cut-off value of ≥ 6.5% (48 mmol/mol) improved specificity. At this cut-off value, the sensitivity, specificity and the discriminant ability were 57.4% (44.9–69.0%), 97.1% (96.0–97.9%) and 77.3% (71.0–83.5%). For diagnosing prediabetes with HbA1c between 5.7–6.4% (39–46 mmol/mol), the sensitivity, specificity and the discriminant ability were 62.7% (57.1–67.9%), 56.3% (53.1–59.4%) and 59.5% (56.3–62.5%), respectively. HbA1c at cut-off value of ≥ 6.5% (48 mmol/mol) by itself diagnosed 5.3% and 48.3% as having diabetes and prediabetes compared to 4.5% and 24.2% using FPG, respectively. Mean HbA1c and FPG increase significantly with increasing body mass index. In conclusion, the ROC curves showed HbA1c could be used for diagnosing diabetes when compared to FPG but not for prediabetes in Palestinians Arabs even though only about 50% of the diabetic subjects were identified by the both HbA1c and FPG. PMID:24505401

Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration

PubMed Central

Karnchanasorn, Rudruidee; Huang, Jean; Feng, Wei; Chuang, Lee-Ming

2016-01-01

To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m2, P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

Comparative influence study of gate-formation structuring on Al0.22Ga0.78As/In0.16Ga0.84As/Al0.22Ga0.78As double heterojunction high electron mobility transistors

NASA Astrophysics Data System (ADS)

Hsu, M. K.; Chiu, S. Y.; Wu, C. H.; Guo, D. F.; Lour, W. S.

2008-12-01

Pseudomorphic Al0.22Ga0.78As/In0.16Ga0.84As/Al0.22Ga0.78As double heterojunction high electron mobility transistors (DH-HEMTs) fabricated with different gate-formation structures of a single-recess gate (SRG), a double-recess gate (DRG) and a field-plate gate (FPG) were comparatively investigated. FPG devices show the best breakdown characteristics among these devices due to great reduction in the peak electric field between the drain and gate electrodes. The measured gate-drain breakdown voltages defined at a 1 mA mm-1 reverse gate-drain current density were -15.3, -19.1 and -26.0 V for SRG, DRG and FPG devices, respectively. No significant differences in their room-temperature common-source current-voltage characteristics were observed. However, FPG devices exhibit threshold voltages being the least sensitive to temperature. Threshold voltages as a function of temperature indicate a threshold-voltage variation as low as -0.97 mV K-1 for FPG devices. According to the 2.4 GHz load-pull power measurement at VDS = 3.0 V and VGS = -0.5 V, the saturated output power (POUT), power gain (GP) and maximum power-added efficiency (PAE) were 10.3 dBm/13.2 dB/36.6%, 11.2 dBm/13.1 dB/39.7% and 13.06 dBm/12.8 dB/47.3%, respectively, for SRG, DRG and FPG devices with a pi-gate in class AB operation. When the FPG device is biased at a VDS of 10 V, the saturated power density is more than 600 mW mm-1.

Type 2 Diabetes: When Does It Start?

PubMed

Sagesaka, Hiroyuki; Sato, Yuka; Someya, Yuki; Tamura, Yoshifumi; Shimodaira, Masanori; Miyakoshi, Takahiro; Hirabayashi, Kazuko; Koike, Hideo; Yamashita, Koh; Watada, Hirotaka; Aizawa, Toru

2018-05-01

We aimed to clarify the onset of diabetes. Data from 27,392 nondiabetic health examinees were retrospectively analyzed for a mean of 5.3 years. Trajectories of fasting plasma glucose (FPG), body mass index (BMI), and the single point insulin sensitivity (Si) estimator (SPISE), an index of Si, 10 years before diagnosis of prediabetes (PDM; n = 4781) or diabetes (n = 1061) were separately assessed by a mixed effects model. Diabetes and PDM were diagnosed by the American Diabetes Association definition on the basis of FPG and glycosylated hemoglobin A1c values. In individuals who developed diabetes, mean FPG and BMI were significantly higher ( P < 0.01 each) and SPISE lower than those who did not at -10 years: FPG 101.5 mg/dL vs 94.5 mg/dL, BMI 24.0 kg/m 2 vs 22.7 kg/m 2 , and SPISE 7.32 vs 8.34, P < 0.01 each. These measurements, in subjects who developed prediabetes, were slightly but definitely different from those who did not, already at -10 years: FPG 91.8 mg/dL vs 89.6 mg/dL, BMI 22.6 kg/m 2 vs 22.1 kg/m 2 , and SPISE 8.44 vs 8.82, P < 0.01 each. In both cases, the differences were progressively greater toward year 0, the time of diabetes, or PDM diagnosis. FPG was significantly elevated in those who developed diabetes at least 10 years before diagnosis of diabetes, and this was also the case in those who developed PDM. Glucose dysregulation precedes diagnosis of diabetes at least for 20 years.

Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies.

PubMed

Wong, Tien Y; Liew, Gerald; Tapp, Robyn J; Schmidt, Maria Inês; Wang, Jie Jin; Mitchell, Paul; Klein, Ronald; Klein, Barbara E K; Zimmet, Paul; Shaw, Jonathan

2008-03-01

The WHO and American Diabetes Association criteria for diagnosing diabetes mellitus assume the presence of a glycaemic threshold with high sensitivity for identifying retinopathy. However, this assumption is based on data from three previous studies that had important limitations in detecting retinopathy. We aimed to provide updated data for the relation between fasting plasma glucose (FPG) and retinopathy, and to assess the diagnostic accuracy of current FPG thresholds in identifying both prevalent and incident retinopathy. We examined the data from three cross-sectional adult populations: those in the Blue Mountains Eye Study (BMES, Australia, n=3162), the Australian Diabetes, Obesity and Lifestyle Study (AusDiab, Australia, n=2182), and the Multi-Ethnic Study of Atherosclerosis (MESA, USA, n=6079). Retinopathy was diagnosed from multiple retinal photographs of each eye, and graded according to the modified Airlie House Classification system. Plasma glucose concentrations were measured from fasting venous blood samples. The overall prevalence of retinopathy was 11.5% in BMES (95% CI 10.4-12.6%), 9.6% in AusDiab (8.4-10.9), and 15.8% in MESA (14.9-16.7). However, we found inconsistent evidence of a uniform glycaemic threshold for prevalent and incident retinopathy, with analyses suggesting a continuous relation. The widely used diabetes FPG cutoff of 7.0 mmol/L or higher had sensitivity less than 40% (range 14.8-39.1) for detecting retinopathy, with specificity between 80.8% and 95.8%. The area under receiver operating characteristic curves for FPG and retinopathy was low and ranged from 0.56 to 0.61. We saw no evidence of a clear and consistent glycaemic threshold for the presence or incidence of retinopathy across different populations. The current FPG cutoff of 7.0 mmol/L used to diagnose diabetes did not accurately identify people with and without retinopathy. These findings suggest that the criteria for diagnosing diabetes could need reassessment.

Evaluation of basal DNA damage and oxidative stress in Wistar rat leukocytes after exposure to microwave radiation.

PubMed

Garaj-Vrhovac, Vera; Gajski, Goran; Trosić, Ivancica; Pavicić, Ivan

2009-05-17

The aim of this study was to assess whether microwave-induced DNA damage is basal or it is also generated through reactive oxygen species (ROS) formation. After having irradiated Wistar rats with 915MHz microwave radiation, we assessed different DNA alterations in peripheral leukocytes using standard and formamidopyrimidine DNA-glycosylase (Fpg)-modified comet assay. The first is a sensitive tool for detecting primary DNA damage, and the second is much more specific for detecting oxidative damage. The animals were irradiated for 1h a day for 2 weeks at a field power density of 2.4W/m(2), and the whole-body average specific absorption rate (SAR) of 0.6W/kg. Both the standard and the Fpg-modified comet assay detected increased DNA damage in blood leukocytes of the exposed rats. The significant increase in Fpg-detected DNA damage in the exposed rats suggests that oxidative stress is likely to be responsible. DNA damage detected by the standard comet assay indicates that some other mechanisms may also be involved. In addition, both methods served proved sensitive enough to measure basal and oxidative DNA damage after long-term exposure to 915MHz microwave radiation in vivo.

The effect of lowering the threshold for diagnosis of impaired fasting glucose.

PubMed

Kim, So Hun; Shim, Wan Sub; Kim, Eun A; Kim, Eun Joo; Lee, Seung Hee; Hong, Seong Bin; Kim, Yong Seong; Park, Shin Goo; Leem, Jong Han; Lim, Jong Whan; Lee, Hun-Jae; Nam, Moonsuk

2008-04-30

The aim of this study was to evaluate the effect of lowering the fasting plasma glucose (FPG) criteria for impaired fasting glucose (IFG) on the prevalence of IFG and the risk for the development of diabetes associated with IFG in Koreans. A total of 7,211 subjects who had normal glucose tolerance (NGT) or IFG were recruited. Subjects were evaluated at baseline and after two years follow up. Clinical data including total cholesterol, FPG and blood pressure were examined. Lowering the criteria for IFG from 6.1 mmol/L (110 mg/dL) to 5.6 mmol/L (100 mg/dL) increased the prevalence of IFG from 6.6% (494 subjects) to 24.4% (1829 subjects). After the 2 years follow up period, 91 subjects (1.3%) developed diabetes. Twenty one (0.3%) subjects developed diabetes among 5,382 NGT subjects and 70 (3.8%) subjects developed diabetes among 1,829 IFG (5.6-7.0 mmol/L) subjects. Lowering the IFG threshold from 6.1 mmol/L to 5.6 mmol/L resulted in a 18.4% decrease in specificity and 23.9% increase in sensitivity for predicting diabetes. The baseline FPG for predicting the development of diabetes after 2 years at a point on the receiver operating characteristic curve that was closest to the ideal 100% sensitivity and 100% specificity was 5.7 mmol/L (103 mg/dL). Lowering the FPG criterion of IFG should have benefits in predicting new onset type 2 diabetes mellitus in Koreans. The economic and health benefits of applying the new IFG criteria should be evaluated in future studies.

Screening obese children and adolescents for prediabetes and/or type 2 diabetes in pediatric practices: a validation study.

PubMed

Brar, Preneet C; Mengwall, Lisa; Franklin, Bonita H; Fierman, Arthur H

2014-07-01

Increased prevalence of type 2 diabetes mellitus (T2DM) makes it important for pediatricians to use effective screening tools for risk assessment of prediabetes/T2DM in children. Children (n = 149) who had an oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) were studied. American Diabetes Association recommended screening criteria-HbA1c ≥5.7% and fasting plasma glucose (FPG) ≥100 mg/dL-were compared against OGTT. The homeostatic model assessment of insulin resistance (HOMA-IR), a mathematical index derived from fasting insulin and glucose, was compared with OGTT. We studied whether combining screening tests (HbA1c and fasting glucose or HbA1c and HOMA-IR) improved accuracy of prediction of the OGTT. HbA1c of ≥5.7% had a sensitivity of 75% and specificity of 57% when compared with the OGTT. Combining screening tests (HbA1c ≥5.7% and FPG ≥100 mg/dL; HbA1c ≥5.7% and HOMA-IR ≥3.4) resulted in improved sensitivity (95.5% for each), with the HbA1c-FPG doing better than the HbA1c-HOMA-IR combination in terms of ability to rule out prediabetes (likelihood ratio [LR]) negative. 0.07 vs 0.14). HbA1c of ≥5.7% provided fair discrimination of glucose tolerance compared with the OGTT. The combination of HbA1c and FPG is a useful method for identifying children who require an OGTT. © The Author(s) 2014.

Glycated haemoglobin (HbA1c ) and fasting plasma glucose relationships in sea-level and high-altitude settings.

PubMed

Bazo-Alvarez, J C; Quispe, R; Pillay, T D; Bernabé-Ortiz, A; Smeeth, L; Checkley, W; Gilman, R H; Málaga, G; Miranda, J J

2017-06-01

Higher haemoglobin levels and differences in glucose metabolism have been reported among high-altitude residents, which may influence the diagnostic performance of HbA 1c . This study explores the relationship between HbA 1c and fasting plasma glucose (FPG) in populations living at sea level and at an altitude of > 3000 m. Data from 3613 Peruvian adults without a known diagnosis of diabetes from sea-level and high-altitude settings were evaluated. Linear, quadratic and cubic regression models were performed adjusting for potential confounders. Receiver operating characteristic (ROC) curves were constructed and concordance between HbA 1c and FPG was assessed using a Kappa index. At sea level and high altitude, means were 13.5 and 16.7 g/dl (P > 0.05) for haemoglobin level; 41 and 40 mmol/mol (5.9% and 5.8%; P < 0.01) for HbA 1c ; and 5.8 and 5.1 mmol/l (105 and 91.3 mg/dl; P < 0.001) for FPG, respectively. The adjusted relationship between HbA 1c and FPG was quadratic at sea level and linear at high altitude. Adjusted models showed that, to predict an HbA 1c value of 48 mmol/mol (6.5%), the corresponding mean FPG values at sea level and high altitude were 6.6 and 14.8 mmol/l (120 and 266 mg/dl), respectively. An HbA 1c cut-off of 48 mmol/mol (6.5%) had a sensitivity for high FPG of 87.3% (95% confidence interval (95% CI) 76.5 to 94.4) at sea level and 40.9% (95% CI 20.7 to 63.6) at high altitude. The relationship between HbA 1c and FPG is less clear at high altitude than at sea level. Caution is warranted when using HbA 1c to diagnose diabetes mellitus in this setting. © 2017 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Optimal Cut-Off Points of Fasting Plasma Glucose for Two-Step Strategy in Estimating Prevalence and Screening Undiagnosed Diabetes and Pre-Diabetes in Harbin, China

PubMed Central

Sun, Bo; Lan, Li; Cui, Wenxiu; Xu, Guohua; Sui, Conglan; Wang, Yibaina; Zhao, Yashuang; Wang, Jian; Li, Hongyuan

2015-01-01

To identify optimal cut-off points of fasting plasma glucose (FPG) for two-step strategy in screening abnormal glucose metabolism and estimating prevalence in general Chinese population. A population-based cross-sectional study was conducted on 7913 people aged 20 to 74 years in Harbin. Diabetes and pre-diabetes were determined by fasting and 2 hour post-load glucose from the oral glucose tolerance test in all participants. Screening potential of FPG, cost per case identified by two-step strategy, and optimal FPG cut-off points were described. The prevalence of diabetes was 12.7%, of which 65.2% was undiagnosed. Twelve percent or 9.0% of participants were diagnosed with pre-diabetes using 2003 ADA criteria or 1999 WHO criteria, respectively. The optimal FPG cut-off points for two-step strategy were 5.6 mmol/l for previously undiagnosed diabetes (area under the receiver-operating characteristic curve of FPG 0.93; sensitivity 82.0%; cost per case identified by two-step strategy ¥261), 5.3 mmol/l for both diabetes and pre-diabetes or pre-diabetes alone using 2003 ADA criteria (0.89 or 0.85; 72.4% or 62.9%; ¥110 or ¥258), 5.0 mmol/l for pre-diabetes using 1999 WHO criteria (0.78; 66.8%; ¥399), and 4.9 mmol/l for IGT alone (0.74; 62.2%; ¥502). Using the two-step strategy, the underestimates of prevalence reduced to nearly 38% for pre-diabetes or 18.7% for undiagnosed diabetes, respectively. Approximately a quarter of the general population in Harbin was in hyperglycemic condition. Using optimal FPG cut-off points for two-step strategy in Chinese population may be more effective and less costly for reducing the missed diagnosis of hyperglycemic condition. PMID:25785585

[The value of fasting plasma glucose and lipid profiles between 7 and 15 gestational weeks in the prediction of gestational diabetes mellitus].

PubMed

Zhao, M; Li, G H

2016-11-25

Objective: To explore the value of using fasting plasma glucose (FPG) and lipid profiles between 7 and 15 gestational weeks to predict gestational diabetes mellitus (GDM). Methods: The medical records of 2 138 pregnant women who had prenatal care in Beijing Obstetrics and Gynecology Hospital from August 2011 to February 2012 were analyzed retrospectively. According to results of the oral glucose tolerance tests, women were devided into the GDM group ( n =240) and the normal group ( n= 1 898). Maternal characteristics, FPG and lipid levels between 7 and 15 gestational weeks were compared between the two groups. Logistic regression analysis and receiver operator characteristics(ROC) curve were used in the analysis. Results: Potential markers for the prediction of GDM included total cholesterol, triglyceride (TG) , low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratios (LDL-C/HDL-C) , triglyceride to high-density lipoprotein cholesterol ratios (TG/HDL-C) and FPG. After adjustment of confounding factors, age ( OR= 1.046, 95% CI: 1.003-1.090), pre- pregnancy body mass index ( OR= 1.104, 95% CI: 1.049-1.161), gravidity>3 ( OR= 1.768, 95% CI: 1.071-2.920), FPG ( OR= 8.137, 95% CI: 5.412-12.236), TG ( OR= 1.460, 95% CI: 1.148-1.858) were independently associated with the risk of developing GDM. Equation, P GDM =1/{1+exp[-(-16.542+0.045×age+0.103×pre-pregnancy body mass index+0.551×gravidity>3+2.110×FPG+0.372×TG)]}, was constructed by the logistic regression analysis. Sensitivity (67.5%) and specificity (70.5%) were determined by the calculated risk score, with a cut-off value of 0.11 (area under the curve: 0.751, 95% CI: 0.718-0.783, P< 0.001). Conclusions: FPG and TG, together with clinical characteristics may have a better predictive value for the risk of GDM.

Development of a new scoring system for predicting the 5 year incidence of type 2 diabetes in Japan: the Toranomon Hospital Health Management Center Study 6 (TOPICS 6).

PubMed

Heianza, Y; Arase, Y; Hsieh, S D; Saito, K; Tsuji, H; Kodama, S; Tanaka, S; Ohashi, Y; Shimano, H; Yamada, N; Hara, S; Sone, H

2012-12-01

The aims of this study were to assess the clinical significance of introducing HbA(1c) into a risk score for diabetes and to develop a scoring system to predict the 5 year incidence of diabetes in Japanese individuals. The study included 7,654 non-diabetic individuals aged 40-75 years. Incident diabetes was defined as fasting plasma glucose (FPG) ≥7.0 mmol/l, HbA(1c) ≥6.5% (48 mmol/mol) or self-reported clinician-diagnosed diabetes. We constructed a risk score using non-laboratory assessments (NLA) and evaluated improvements in risk prediction by adding elevated FPG, elevated HbA(1c) or both to NLA. The discriminative ability of the NLA score (age, sex, family history of diabetes, current smoking and BMI) was 0.708. The difference in discrimination between the NLA + FPG and NLA + HbA(1c) scores was non-significant (0.836 vs 0.837; p = 0.898). A risk score including family history of diabetes, smoking, obesity and both FPG and HbA(1c) had the highest discrimination (0.887, 95% CI 0.871, 0.903). At an optimal cut-off point, sensitivity and specificity were high at 83.7% and 79.0%, respectively. After initial screening using NLA scores, subsequent information on either FPG or HbA(1c) resulted in a net reclassification improvement of 42.7% or 52.3%, respectively (p < 0.0001). When both were available, net reclassification improvement and integrated discrimination improvement were further improved at 56.7% (95% CI 47.3%, 66.1%) and 10.9% (9.7%, 12.1%), respectively. Information on HbA(1c) or FPG levels after initial screening by NLA can precisely refine diabetes risk reclassification.

Genotoxicity of tungsten carbide-cobalt (WC-Co) nanoparticles in vitro: mechanisms-of-action studies.

PubMed

Moche, Hélène; Chevalier, Dany; Vezin, Hervé; Claude, Nancy; Lorge, Elisabeth; Nesslany, Fabrice

2015-02-01

We showed previously that tungsten carbide-cobalt (WC-Co) nanoparticles (NP) can be used as a nanoparticulate positive control in some in vitro mammalian genotoxicity assays. Here, we investigate the mechanisms of action involved in WC-Co NP genotoxicity in L5178Y mouse lymphoma cells and primary human lymphocytes, in vitro. Data from the micronucleus assay coupled with centromere staining and from the chromosome-aberration assay show the involvement of both clastogenic and aneugenic events. Experiments with the formamidopyrimidine DNA glycosylase (FPG)-modified comet assay showed a slight (non-significant) increase in FPG-sensitive sites in the L5178Y mouse lymphoma cells but not in the human lymphocytes. Electron paramagnetic resonance spin-trapping results showed the presence of hydroxyl radicals (•OH) in WC-Co NP suspensions, with or without cells, but with time-dependent production in the presence of cells. However, a significant difference in •OH production was observed between human lymphocytes from two different donors. Using H2O2, we showed that WC-Co NP can participate in Fenton-like reactions. Thus, •OH might be produced either via intrinsic generation by WC-Co NP or through a Fenton-like reaction in the presence of cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Alterations of GSH and MDA levels and their association with bee venom-induced DNA damage in human peripheral blood leukocytes.

PubMed

Gajski, Goran; Domijan, Ana-Marija; Garaj-Vrhovac, Vera

2012-07-01

Bee venom (BV) has toxic effects in a variety of cell systems and oxidative stress has been proposed as a possible mechanism of its toxicity. This study investigated the in vitro effect of BV on glutathione (GSH) and malondialdehyde (MDA) levels, and their association with BV-induced DNA strand breaks and oxidative DNA damage in human peripheral blood leukocytes (HPBLs). Blood samples were treated with BV at concentrations ranging from 0.1 to 10 μg/ml over different lengths of time, and DNA damage in HPBLs was monitored with the alkaline and formamidopyrimidine glycoslyase (FPG)-modified comet assays, while GSH and MDA levels were determined in whole blood. Results showed a significant increase in overall DNA damage and FPG-sensitive sites in DNA of HPBLs exposed to BV compared with HPBLs from controls. An increase in DNA damage (assessed with both comet assays) was significantly associated with changes in MDA and GSH levels. When pretreated with N-acetyl-L-cysteine, a source of cysteine for the synthesis of the endogenous antioxidant GSH, a significant reduction of the DNA damaging effects of BV in HPBLs was noted. This suggests that oxidative stress is at least partly responsible for the DNA damaging effects of BV. Copyright © 2012 Wiley Periodicals, Inc.

Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal analysis from the Whitehall II cohort study.

PubMed

Hulman, Adam; Simmons, Rebecca K; Brunner, Eric J; Witte, Daniel R; Færch, Kristine; Vistisen, Dorte; Ikehara, Satoyo; Kivimaki, Mika; Tabák, Adam G

2017-07-01

South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes. In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI 0,120 ) among 120 South Asian and 867 white participants who developed diabetes during follow-up (1991-2013). We fitted cubic mixed-effects models to longitudinal data with adjustment for a wide range of covariates. Compared with white individuals, South Asians had a faster increase in FPG before diagnosis (slope difference 0.22 mmol/l per decade; 95% CI 0.02, 0.42; p = 0.03) and a higher FPG level at diagnosis (0.27 mmol/l; 95% CI 0.06, 0.48; p = 0.01). They also had higher FSI and 2hSI levels before and at diabetes diagnosis. South Asians had a faster decline and lower HOMA2-S (log e -transformed) at diagnosis compared with white individuals (0.33; 95% CI 0.21, 0.46; p < 0.001). HOMA2-B increased in both ethnic groups until 7 years before diagnosis and then declined; the initial increase was faster in white individuals. ISI 0,120 declined steeply in both groups before diagnosis; levels were lower among South Asians before and at diagnosis. There were no ethnic differences in 2hPG trajectories. We observed different trajectories of plasma glucose, insulin sensitivity and secretion prior to diabetes diagnosis in South Asian and white individuals. This might be due to ethnic differences in the natural history of diabetes. South Asian individuals experienced a more rapid decrease in insulin sensitivity and faster increases in FPG compared with white individuals. These findings suggest more marked disturbance in beta cell compensation prior to diabetes diagnosis in South Asian individuals.

Effects of melatonin on DNA damage induced by cyclophosphamide in rats

PubMed Central

Ferreira, S.G.; Peliciari-Garcia, R.A.; Takahashi-Hyodo, S.A.; Rodrigues, A.C.; Amaral, F.G.; Berra, C.M.; Bordin, S.; Curi, R.; Cipolla-Neto, J.

2013-01-01

The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP), an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water). Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg)-sensitive sites by the comet technique and of Xpf mRNA expression by qRT-PCR. The number (mean ± SE) of chromosomal aberrations in pinealectomized (PINX) animals treated with melatonin and CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy. PMID:23471360

The changing relationship between HbA1c and FPG according to different FPG ranges.

PubMed

Guan, X; Zheng, L; Sun, G; Guo, X; Li, Y; Song, H; Tian, F; Sun, Y

2016-05-01

Since the American Diabetes Association included hemoglobin A1c (HbA1c) in the diagnostic criteria for diabetes in 2010, the clinical use of HbA1c has remained controversial. We explored the use of HbA1c for diagnosing diabetes and intermediate hyperglycemia in comparison with fasting plasma glucose (FPG). We screened 3710 adult subjects (mean age = 55.24 years) comprising 1704 males and 2006 females. We drew an receiver operating characteristic (ROC) curve to evaluate the ability of HbA1c to diagnose diabetes and intermediate hyperglycemia according to FPG. We used Kappa coefficient and Pearson's correlation coefficient to evaluate the relationship between HbA1c and FPG in different FPG ranges. The areas under ROC curve to diagnose diabetes and intermediate hyperglycemia were 0.859 (95 % CI 0.827-0.892) and 0.633 (95 % CI 0.615-0.651). The kappa coefficients between FPG and HbA1c for diagnosis of diabetes and intermediate hyperglycemia were 0.601 (P < 0.001) and 0.104 (P < 0.001). The Pearson's correlation coefficient of FPG and HbA1c was 0.640 (P < 0.001), but when we classified FPG as normal, intermediate hyperglycemia and diabetes, the coefficients became 0.07 (P = 0.002), 0.185 (P < 0.001) and 0.760 (P < 0.001), respectively. The relationship between HbA1c and FPG changed according to the different FPG ranges. When FPG was higher, the relationship was stronger. HbA1c and FPG were highly consistent in diagnosing diabetes, but they were not in predicting intermediate hyperglycemia.

Value of EZSCAN parameters for diabetes screening in Chinese.

PubMed

Lin, Yanhui; Chen, Zhiheng; Guo, Xu; Deng, Yulin

2017-05-23

To study the parameters of EZSCAN as a screening tool for diabetes in Chinese. A total of 6,270 subjects participated in the study. All subjects underwent tests of EZSCAN, fasting plasma glucose (FPG), oral glucose tolerance test and HbA 1c . 1. All subjects were divided into 4 groups: the normal group, sugar metabolic abnormalities as low-risk group, middle-risk group and high-risk group. The difference of diabetes incidence among the 4 groups was statistically significant. With the increase of EZSCAN score, the prevalence of diabetes increased significantly. But there is no statistically difference between the low-risk group and the middle-risk group. 2. After adjustment for other variables, there is significantly positive relationship among EZSCAN risk score and the risk of diabetes. Meanwhile there is no statistically difference between the low-risk group and the middle-risk group. 3. The cut-off point of EZSCAN for diabetes was 44.5% with the sensitivity was 73.2% which was higher than of FPG and HbA 1c . As EZSCAN-diabetes risk score increases, the risk of diabetes increases. EZSCAN can be used as a tool for screening for diabetes. At the best screening diabetes cut-off point value 44.5%, the sensitivity is higher than traditional method of FPG and HbA 1c . Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

The association of longitudinal trend of fasting plasma glucose with retinal microvasculature in people without established diabetes.

PubMed

Hu, Yin; Niu, Yong; Wang, Dandan; Wang, Ying; Holden, Brien A; He, Mingguang

2015-01-22

Structural changes of retinal vasculature, such as altered retinal vascular calibers, are considered as early signs of systemic vascular damage. We examined the associations of 5-year mean level, longitudinal trend, and fluctuation in fasting plasma glucose (FPG) with retinal vascular caliber in people without established diabetes. A prospective study was conducted in a cohort of Chinese people age ≥40 years in Guangzhou, southern China. The FPG was measured at baseline in 2008 and annually until 2012. In 2012, retinal vascular caliber was assessed using standard fundus photographs and validated software. A total of 3645 baseline nondiabetic participants with baseline and follow-up data on FPG for 3 or more visits was included for statistical analysis. The associations of retinal vascular caliber with 5-year mean FPG level, longitudinal FPG trend (slope of linear regression-FPG), and fluctuation (standard deviation and root mean square error of FPG) were analyzed using multivariable linear regression analyses. Multivariate regression models adjusted for baseline FPG and other potential confounders showed that a 10% annual increase in FPG was associated independently with a 2.65-μm narrowing in retinal arterioles (P = 0.008) and a 3.47-μm widening in venules (P = 0. 0.004). Associations with mean FPG level and fluctuation were not statistically significant. Annual rising trend in FPG, but not its mean level or fluctuation, is associated with altered retinal vasculature in nondiabetic people. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Effect of Chlorogenic Acid Administration on Glycemic Control, Insulin Secretion, and Insulin Sensitivity in Patients with Impaired Glucose Tolerance.

PubMed

Zuñiga, Laura Y; Aceves-de la Mora, Martha C Aceves-de; González-Ortiz, Manuel; Ramos-Núñez, Julia L; Martínez-Abundis, Esperanza

2018-05-01

Chlorogenic acid has been described as a novel polyphenol with metabolic effects on glucose homeostasis. The aim of this study was to evaluate the effect of chlorogenic acid administration on glycemic control, insulin secretion, and insulin sensitivity in patients with impaired glucose tolerance (IGT). A randomized, double-blind, placebo-controlled clinical trial was performed in 30 patients with IGT; 15 patients randomly assigned to oral chlorogenic acid received 400 mg three times per day for 12 weeks, and the other 15 patients received placebo in the same way. Before and after the intervention, anthropometric and metabolic measurements, including fasting plasma glucose (FPG), glycated hemoglobin A1c, and a lipid profile, were performed. Area under the curve of glucose and insulin as well as the insulinogenic, Stumvoll, and Matsuda indices were calculated. Wilcoxon, Mann-Whitney U, and chi-square tests were performed, and P ≤ .05 was considered statistically significant. There were significant decreases in FPG (5.7 ± 0.4 vs. 5.5 ± 0.4 mmol/L, P = .002), insulinogenic index (0.71 ± 0.25 vs. 0.63 ± 0.25, P = .028), body weight, body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein levels in the chlorogenic acid group, with an increment in the Matsuda index (1.98 ± 0.88 vs. 2.30 ± 1.23, P = .002). There were no significant differences in the placebo group. In conclusion, chlorogenic acid administration in patients with IGT decreased FPG and insulin secretion, while increasing insulin sensitivity and improving both anthropometric evaluations and the lipid profile.

[Nephro-protective effects of total triterpenoids from Psidium guajava leaves on type 2 diabetic rats].

PubMed

Kuang, Qiao-Ting; Zhao, Jing-Jing; Ye, Chun-Ling; Wang, Jing-Ru; Ye, Kai-He; Zhang, Xiao-Qi; Wang, Ying; Ye, Wen-Cai

2012-01-01

To investigate the nephro-protective effects of total triterpenoids from Psidium guajava leaves (TTPGL) on type 2 diabetic rats. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) and a high-fat diet. Diabetic rats were divided into five groups: diabetic model control, low-dose TTPGL-treated (60 mg/kg, L-TTPGL), medium-dose TTPGL-treated (120 mg/kg, M-TTPGL), high-dose TTPGL-treated (240 mg/kg, H-TTPGL) and rosiglitazone-treated (3 mg/kg, RSG). The rats received daily treatment for six weeks. At the end of the period,the levels of fasting blood glucose (FPG), fasting insulin (FINS), creatinine (Cr) and blood urea nitrogen (BUN) in serum were measured. Kidneys for histopathological evaluation were stained with Hematoxylin and Eosin (HE). Compared with normal control group, the level of FPG was increased, the insulin and insulin sensitivity index were decreased in the model group; The levels of BUN and Cr were increased with histopathological changes related to diabetic nephropathy in the kidney, which were the glomerular endothelium and mesangial cell proliferation, capillary narrowed, the base-membrane incrassation, glomerular swelling, cysts narrowed and tubules edema. Compared with the model group, the levels of FPG were decreased, serum insulin and insulin sensitivity index were increased significantly in M-TTPGL and H-TTPGL groups (P<0.01 or P<0.05); The levels of BUN and Cr were decreased significantly (P<0.01 or P<0.05) and the renal structural damages were improved significantly. TTPGL could decrease the level of blood glucose of diabetic rat effectively, increase the insulin sensitivity index and protect renal lesions in diabetic rats.

The oxidative DNA glycosylases of Mycobacterium tuberculosis exhibit different substrate preferences from their Escherichia coli counterparts

PubMed Central

Guo, Yin; Bandaru, Viswanath; Jaruga, Pawel; Zhao, Xiaobei; Burrows, Cynthia J.; Iwai, Shigenori; Dizdaroglu, Miral; Bond, Jeffrey P.; Wallace, Susan S.

2010-01-01

The DNA glycosylases that remove oxidized DNA bases fall into two general families: the Fpg/Nei family and the Nth superfamily. Based on protein sequence alignments, we identified four putative Fpg/Nei family members, as well as a putative Nth protein in Mycobacterium tuberculosis H37Rv. All four Fpg/Nei proteins were successfully overexpressed using a bicistronic vector created in our laboratory. The MtuNth protein was also overexpressed in soluble form. The substrate specificities of the purified enzymes were characterized in vitro with oligodeoxynucleotide substrates containing single lesions. Some were further characterized by gas chromatography/mass spectrometry (GC/MS) analysis of products released from γ-irradiated DNA. MtuFpg1 has a substrate specificity similar to that of EcoFpg. Both EcoFpg and MtuFpg1 are more efficient at removing spiroiminodihydantoin (Sp) than 7,8-dihydro-8-oxoguanine (8-oxoG). However, MtuFpg1 shows a substantially increased opposite base discrimination compared to EcoFpg. MtuFpg2 contains only the C-terminal domain of an Fpg protein and has no detectable DNA binding activity or DNA glycosylase/lyase activity and thus appears to be a pseudogene. MtuNei1 recognizes oxidized pyrimidines on both double-stranded and single-stranded DNA and exhibits uracil DNA glycosylase activity. MtuNth recognizes a variety of oxidized bases, including urea, 5,6-dihydrouracil (DHU), 5-hydroxyuracil (5-OHU), 5-hydroxycytosine (5-OHC) and methylhydantoin (MeHyd). Both MtuNei1 and MtuNth excise thymine glycol (Tg); however, MtuNei1 strongly prefers the (5R) isomers, whereas MtuNth recognizes only the (5S) isomers. MtuNei2 did not demonstrate activity in vitro as a recombinant protein, but like MtuNei1 when expressed in Escherichia coli, it decreased the spontaneous mutation frequency of both the fpg mutY nei triple and nei nth double mutants, suggesting that MtuNei2 is functionally active in vivo recognizing both guanine and cytosine oxidation products. The kinetic parameters of the MtuFpg1, MtuNei1 and MtuNth proteins on selected substrates were also determined and compared to those of their E. coli homologs. PMID:20031487

The effects of synbiotic supplementation on insulin resistance/sensitivity, lipid profile and total antioxidant capacity in women with gestational diabetes mellitus: A randomized double blind placebo controlled clinical trial.

PubMed

Nabhani, Zohoor; Hezaveh, Seyed Jamal Ghaemmaghami; Razmpoosh, Elham; Asghari-Jafarabadi, Mohammad; Gargari, Bahram Pourghassem

2018-04-01

The role of gut microbiota in the management of diabetes is shown. In this randomized clinical trial we assessed the effects of synbiotic supplementation on insulin, lipid profile and antioxidative status among women with gestational diabetes mellitus (GDM). Ninety pregnant women with GDM were randomly assigned into two groups to receive either a daily synbiotic capsule - consisting of L. acidophilus, L. plantarum, L. fermentum, L. gasseri (1.5-7.0 × 10 9-10  CFU/g) - with fructooligosaccharide (38.5 mg), or placebo for 6 weeks. Fasting plasma glucose (FPG), insulin, homeostasis model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), high- and low density lipoprotein cholesterol (HDL-C, LDL-C), total cholesterol (TC), triglycerides (TG), total antioxidant capacity (TAC), and systolic and diastolic blood pressure (SBP, DSP) were assessed before and after the intervention. No significant changes in FPG, insulin resistance/sensitivity, lipid profile and TAC indices were seen in synbiotic group compared to the placebo one (p > 0.05). Significant within group increases for HDL-C and TAC levels in synbiotic group were observed (p < 0.05). LDL-C showed significant increment in the placebo group compared to the baseline of the study (6.9 mg/dL, p < 0.05). Between group comparison showed significant decrease in SBP and DBP in synbiotic group compared to placebo (-2.5 vs. 8.6 mmHg, and -1.8 vs. 2.1 mmHg, p < 0.05). The results showed that, in women with GDM, synbiotic supplementation had no effect on FPG and insulin resistance/sensitivity indices. Lipid profile and TAC status may be affected by synbiotic supplementation. Synbiotic is effective in reducing of blood pressure in women with GDM. Copyright © 2018 Elsevier B.V. All rights reserved.

Confirming Glycemic Status in the Diabetes Prevention Program: Implications for Diagnosing Diabetes in High Risk Adults

PubMed Central

Christophi, C. A.; Resnick, H. E.; Ratner, R. E.; Temprosa, M.; Fowler, S.; Knowler, W. C.; Shamoon, H.; Barrett-Connor, E.; Kahn, S. E.

2012-01-01

Aims To examine the ability of FPG and/or 2-hr glucose to confirm diabetes and to determine the proportion of participants with HbA1c ≥6.5%. Methods Diabetes confirmation rates were calculated after a single elevated FPG and/or 2-hr glucose on an oral glucose tolerance test (OGTT) using a confirmatory OGTT performed within 6 weeks. Results 772 (24%) participants had elevated FPG or 2-hr glucose on an OGTT that triggered a confirmation visit. There were 101 triggers on FPG alone, 574 on 2-hr glucose alone, and 97 on both. Only 47% of participants who triggered had confirmed diabetes. While the confirmation rate for FPG was higher than that for 2-hr glucose, the larger number of 2-hr glucose triggers resulted in 87% of confirmed cases triggering on 2-hr glucose. Confirmation rates increased to 75% among persons with FPG ≥126 mg/dl and HbA1c ≥6.5%. Conclusions Only half of persons with elevated FPG and IGT were subsequently confirmed to have diabetes. At current diagnostic levels, more persons trigger on 2-hr glucose than on FPG, but fewer of these persons have their diagnoses confirmed. In individuals with FPG ≥126 mg/dl and HbA1c ≥6.5%, the confirmation rate was increased. PMID:23140912

Confirming glycemic status in the Diabetes Prevention Program: implications for diagnosing diabetes in high risk adults.

PubMed

Christophi, C A; Resnick, H E; Ratner, R E; Temprosa, M; Fowler, S; Knowler, W C; Shamoon, H; Barrett-Connor, E; Kahn, S E

2013-01-01

To examine the ability of fasting plasma glucose (FPG) and/or 2-h glucose to confirm diabetes and to determine the proportion of participants with HbA1c ≥6.5%. Diabetes confirmation rates were calculated after a single elevated FPG and/or 2-h glucose on an oral glucose tolerance test (OGTT) using a confirmatory OGTT performed within 6 weeks. 772 (24%) participants had elevated FPG or 2-h glucose on an OGTT that triggered a confirmation visit. There were 101 triggers on FPG alone, 574 on 2-h glucose alone, and 97 on both. Only 47% of participants who triggered had confirmed diabetes. While the confirmation rate for FPG was higher than that for 2-h glucose, the larger number of 2-h glucose triggers resulted in 87% of confirmed cases triggering on 2-h glucose. Confirmation rates increased to 75% among persons with FPG ≥126 mg/dl and HbA1c ≥6.5%. Only half of the persons with elevated FPG and IGT were subsequently confirmed to have diabetes. At current diagnostic levels, more persons trigger on 2-h glucose than on FPG, but fewer of these persons have their diagnoses confirmed. In individuals with FPG ≥126 mg/dl and HbA1c ≥6.5%, the confirmation rate was increased. Copyright © 2013 Elsevier Inc. All rights reserved.

Cryopreservation of human blood for alkaline and Fpg-modified comet assay.

PubMed

Pu, Xinzhu; Wang, Zemin; Klaunig, James E

2016-01-01

The Comet assay is a reproducible and sensitive assay for the detection of DNA damage in eukaryotic cells and tissues. Incorporation of lesion specific, oxidative DNA damage repair enzymes (for example, Fpg, OGG1 and EndoIII) in the standard alkaline Comet assay procedure allows for the detection and measurement of oxidative DNA damage. The Comet assay using white blood cells (WBC) has proven useful in monitoring DNA damage from environmental agents in humans. However, it is often impractical to performance Comet assay immediately after blood sampling. Thus, storage of blood sample is required. In this study, we developed and tested a simple storage method for very small amount of whole blood for standard and Fpg-modified modified Comet assay. Whole blood was stored in RPMI 1640 media containing 10% FBS, 10% DMSO and 1 mM deferoxamine at a sample to media ratio of 1:50. Samples were stored at -20 °C and -80 °C for 1, 7, 14 and 28 days. Isolated lymphocytes from the same subjects were also stored under the same conditions for comparison. Direct DNA strand breakage and oxidative DNA damage in WBC and lymphocytes were analyzed using standard and Fpg-modified alkaline Comet assay and compared with freshly analyzed samples. No significant changes in either direct DNA strand breakage or oxidative DNA damage was seen in WBC and lymphocytes stored at -20 °C for 1 and 7 days compared to fresh samples. However, significant increases in both direct and oxidative DNA damage were seen in samples stored at -20 °C for 14 and 28 days. No changes in direct and oxidative DNA damage were observed in WBC and lymphocytes stored at -80 °C for up to 28 days. These results identified the proper storage conditions for storing whole blood or isolated lymphocytes to evaluate direct and oxidative DNA damage using standard and Fpg-modified alkaline Comet assay.

HbA1c and the Prediction of Type 2 Diabetes in Children and Adults

PubMed Central

Vijayakumar, Pavithra; Nelson, Robert G.; Hanson, Robert L.; Knowler, William C.

2017-01-01

OBJECTIVE Long-term data validating glycated hemoglobin (HbA1c) in assessing the risk of type 2 diabetes in children are limited. HbA1c, fasting plasma glucose (FPG), and 2-h postload plasma glucose (2hPG) concentrations were measured in a longitudinal study of American Indians to determine their utility in predicting incident diabetes, all of which is thought to be type 2 in this population. RESEARCH DESIGN AND METHODS Incident diabetes (FPG ≥126 mg/dL [7.0 mmol/L], 2hPG ≥200 mg/dL [11.1 mmol/L], HbA1c ≥6.5% [8 mmol/mol], or clinical diagnosis) was determined in 2,095 children without diabetes ages 10–19 years monitored through age 39, and in 2,005 adults ages 20–39 monitored through age 59. Areas under the receiver operating characteristic (ROC) curve for HbA1c, FPG, and 2hPG in predicting diabetes within 10 years were compared. RESULTS During long-term follow-up of children and adolescents who did not initially have diabetes, the incidence rate of subsequent diabetes was fourfold (in boys) as high and more than sevenfold (in girls) as high in those with HbA1c ≥5.7% as in those with HbA1c ≤5.3%—greater rate ratios than experienced by adults in the same HbA1c categories. Analyses of ROCs revealed no significant differences between HbA1c, FPG, and 2hPG in sensitivity and specificity for identifying children and adolescents who later developed diabetes. CONCLUSIONS HbA1c is a useful predictor of diabetes risk in children and can be used to identify prediabetes in children with other type 2 diabetes risk factors with the same predictive value as FPG and 2hPG. PMID:27810987

HbA1c and the Prediction of Type 2 Diabetes in Children and Adults.

PubMed

Vijayakumar, Pavithra; Nelson, Robert G; Hanson, Robert L; Knowler, William C; Sinha, Madhumita

2017-01-01

Long-term data validating glycated hemoglobin (HbA 1c ) in assessing the risk of type 2 diabetes in children are limited. HbA 1c , fasting plasma glucose (FPG), and 2-h postload plasma glucose (2hPG) concentrations were measured in a longitudinal study of American Indians to determine their utility in predicting incident diabetes, all of which is thought to be type 2 in this population. Incident diabetes (FPG ≥126 mg/dL [7.0 mmol/L], 2hPG ≥200 mg/dL [11.1 mmol/L], HbA 1c ≥6.5% [8 mmol/mol], or clinical diagnosis) was determined in 2,095 children without diabetes ages 10-19 years monitored through age 39, and in 2,005 adults ages 20-39 monitored through age 59. Areas under the receiver operating characteristic (ROC) curve for HbA 1c , FPG, and 2hPG in predicting diabetes within 10 years were compared. During long-term follow-up of children and adolescents who did not initially have diabetes, the incidence rate of subsequent diabetes was fourfold (in boys) as high and more than sevenfold (in girls) as high in those with HbA 1c ≥5.7% as in those with HbA 1c ≤5.3%-greater rate ratios than experienced by adults in the same HbA 1c categories. Analyses of ROCs revealed no significant differences between HbA 1c , FPG, and 2hPG in sensitivity and specificity for identifying children and adolescents who later developed diabetes. HbA 1c is a useful predictor of diabetes risk in children and can be used to identify prediabetes in children with other type 2 diabetes risk factors with the same predictive value as FPG and 2hPG. © 2017 by the American Diabetes Association.

A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial

PubMed Central

Liu, Yuejun; Cotillard, Aurélie; Vatier, Camille; Bastard, Jean-Philippe; Fellahi, Soraya; Stévant, Marie; Allatif, Omran; Langlois, Clotilde; Bieuvelet, Séverine; Brochot, Amandine; Guilbot, Angèle; Clément, Karine; Rizkalla, Salwa W.

2015-01-01

Background Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue. Objectives Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed. Methods In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥25 kg/m2, unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization. Results Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24±0.50 vs +0.12±0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement. Conclusions Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes. Trial Registration ClinicalTrials.gov NCT01530685 PMID:26406981

A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial.

PubMed

Liu, Yuejun; Cotillard, Aurélie; Vatier, Camille; Bastard, Jean-Philippe; Fellahi, Soraya; Stévant, Marie; Allatif, Omran; Langlois, Clotilde; Bieuvelet, Séverine; Brochot, Amandine; Guilbot, Angèle; Clément, Karine; Rizkalla, Salwa W

2015-01-01

Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue. Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed. In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥ 25 kg/m(2), unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization. Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24 ± 0.50 vs +0.12 ± 0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement. Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes. ClinicalTrials.gov NCT01530685.

Fasting plasma glucose in young adults free of diabetes is associated with cognitive function in midlife.

PubMed

Cohen-Manheim, Irit; Sinnreich, Ronit; Doniger, Glen M; Simon, Ely S; Pinchas-Mizrachi, Ronit; Kark, Jeremy D

2018-06-01

Evidence for an association of fasting plasma glucose (FPG) with cognitive function in adults free of diabetes is scarce and based on middle-aged and older adults. We examined the association of FPG, measured at age 30, and of change in FPG from age 30 to 43, with cognitive function at age 50. 505 nondiabetic participants of the population-based Jerusalem Lipid Research Clinic (LRC) cohort study had baseline FPG, 2-h post-oral challenge plasma glucose (OGTT) and insulin determined at ages 28-32, and FPG and OGTT again at ages 41-46. Subsequently at ages 48-52, global cognitive function and its five specific component domains were assessed with a NeuroTrax computerized test battery, using multiple linear regression and multivariable logistic models. Hyperglycemia (FPG ≥ 5.6 mmol/l vs. <5.6 mmol/l) at baseline was associated with poorer global cognitive function in midlife (predominantly in the visual spatial and attention domains), independent of socio-demographic characteristics, life style variables, body mass index (BMI), and inflammatory and biochemical variables (standardized Beta = -0.121, P = 0.002, plinear trend(FPG continuous) =0.016). Similarly, increased odds for low-ranked (lowest fifth) global cognition was evident (ORper mmol/l FPG=2.31, 95% CI = 1.30-4.13, P = 0.005). Baseline OGTT, insulin resistance (HOMA-IR) and change in FPG and OGTT over 13 years were not associated with cognition. A higher FPG in young adults was associated with lower cognitive performance in midlife. Although we cannot dismiss the possibility of reverse causation, hyperglycemia at a young age may be a modifiable risk factor for low-ranked cognitive function in midlife.

A single blueberry (Vaccinium corymbosum) portion does not affect markers of antioxidant defence and oxidative stress in healthy volunteers following cigarette smoking.

PubMed

Del Bo', Cristian; Porrini, Marisa; Campolo, Jonica; Parolini, Marina; Lanti, Claudia; Klimis-Zacas, Dorothy; Riso, Patrizia

2016-03-01

We previously reported that a portion of blueberries reversed endothelial dysfunction induced by acute cigarette smoking. Since smoking-induced endothelial dysfunction is associated with a condition of oxidative stress, we evaluated whether the observed effect was mediated by modulation of markers of oxidative stress and antioxidant defence. Fourteen out of 16 male healthy smokers previously enrolled, participated in a three-armed randomized controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300g of blueberries) + smoking (one cigarette); control treatment (300ml of water with sugar) + smoking (one cigarette). The cigarette was smoked 100min after blueberry/control/water consumption. Each treatment was separated by 1 week of washout period. Plasma vitamin (C, B12 and folate) and aminothiol concentrations, endogenous [formamidopyrimidine-DNA glycosylase (FPG)-sensitive sites] and oxidatively induced DNA damage (resistance to H2O2-induced DNA damage) in peripheral blood mononuclear cells (PBMCs) were measured at baseline and 20, 60, 90, 120min and 24h after smoking. On the whole, analysis of variance did not show a significant effect of treatment on the modulation of markers of oxidative stress and antioxidant defence but revealed an effect of time for plasma concentrations of vitamin C (P = 0.003), B12 (P < 0.001), folate (P < 0.001), total cysteine (P = 0.007) and cysteine-glycine (P = 0.010) that increased following the three treatments after smoking. No significant effect of treatment was observed for the levels of FPG-sensitive sites (P > 0.05) and H2O2-induced DNA damage (P > 0.05) in PBMCs. In conclusion, the consumption of a single blueberry portion failed to modulate markers of oxidative stress and antioxidant defence investigated in our experimental conditions. Further studies are necessary to elucidate this finding and help clarifying the mechanisms of protection of blueberries against smoking-induced endothelial dysfunction. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evaluating the transferability of 15 European-derived fasting plasma glucose SNPs in Mexican children and adolescents

PubMed Central

Langlois, Christine; Abadi, Arkan; Peralta-Romero, Jesus; Alyass, Akram; Suarez, Fernando; Gomez-Zamudio, Jaime; Burguete-Garcia, Ana I.; Yazdi, Fereshteh T.; Cruz, Miguel; Meyre, David

2016-01-01

Genome wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) that are associated with fasting plasma glucose (FPG) in adult European populations. The contribution of these SNPs to FPG in non-Europeans and children is unclear. We studied the association of 15 GWAS SNPs and a genotype score (GS) with FPG and 7 metabolic traits in 1,421 Mexican children and adolescents from Mexico City. Genotyping of the 15 SNPs was performed using TaqMan Open Array. We used multivariate linear regression models adjusted for age, sex, body mass index standard deviation score, and recruitment center. We identified significant associations between 3 SNPs (G6PC2 (rs560887), GCKR (rs1260326), MTNR1B (rs10830963)), the GS and FPG level. The FPG risk alleles of 11 out of the 15 SNPs (73.3%) displayed significant or non-significant beta values for FPG directionally consistent with those reported in adult European GWAS. The risk allele frequencies for 11 of 15 (73.3%) SNPs differed significantly in Mexican children and adolescents compared to European adults from the 1000G Project, but no significant enrichment in FPG risk alleles was observed in the Mexican population. Our data support a partial transferability of European GWAS FPG association signals in children and adolescents from the admixed Mexican population. PMID:27782183

Impact of HbA1c criterion on the definition of glycemic component of the metabolic syndrome: the China health and nutrition survey 2009.

PubMed

Sun, Xingxing; Du, Tingting; Huo, Rui; Yu, Xuefeng; Xu, Lixian

2013-11-05

In 2009, a unified definition of metabolic syndrome (MetS) was proposed, of which, the glycemic component is defined on the basis of fasting plasma glucose (FPG) level. Recently, the American Diabetes Association (ADA) recommended the use of glycated hemoglobin (HbA1c) as an alternative to FPG to define prediabetes. Hence, we aim to compare the performance of HbA1c and FPG in the definition of glycemic component of the MetS among Chinese adults. We conducted a cross-sectional analysis of 7641 Chinese participants aged ≥18 years using data from the China Health and Nutrition Survey 2009. MetS was defined according to the consensus criteria in 2009. We compared the use of HbA1c versus FPG in the definition of the glycemic component of MetS. Increased HbA1c value was defined following the criterion of HbA1c cut-off point of ≥5.7% recommended by the ADA. Overall, 1136 (14.9%) had MetS according to FPG ≥ 5.6 mmol/l, and 1640 (21.5%) had MetS according to HbA1c ≥ 5.7%. Compared with individuals with FPG-based diagnosis of MetS, individuals with HbA1c-based diagnosis of MetS were older, had higher levels of LDL-C, magnesium, and transferrin, and lower levels of uric acid. Of those found to have MetS according to either FPG or HbA1c (n = 2008), overlap between HbA1c- and FPG-based diagnosis of MetS was limited (n = 768, 38.2%). The overlap index regarding MetS diagnosed by FPG or HbA1c persisted low in each evaluated subgroup (≤ 50.0%). We note limited overlap and poor agreement between FPG- and HbA1c-based diagnosis of MetS. Screening MetS through introduction of HbA1c in addition to FPG could contribute to identification of more people with MetS.

Association of A1C and Fasting Plasma Glucose Levels With Diabetic Retinopathy Prevalence in the U.S. Population

PubMed Central

Cheng, Yiling J.; Gregg, Edward W.; Geiss, Linda S.; Imperatore, Giuseppina; Williams, Desmond E.; Zhang, Xinzhi; Albright, Ann L.; Cowie, Catherine C.; Klein, Ronald; Saaddine, Jinan B.

2009-01-01

OBJECTIVE To examine the association of A1C levels and fasting plasma glucose (FPG) with diabetic retinopathy in the U.S. population and to compare the ability of the two glycemic measures to discriminate between people with and without retinopathy. RESEARCH DESIGN AND METHODS This study included 1,066 individuals aged ≥40 years from the 2005–2006 National Health and Nutrition Examination Survey. A1C, FPG, and 45° color digital retinal images were assessed. Retinopathy was defined as a level ≥14 on the Early Treatment Diabetic Retinopathy Study severity scale. We used joinpoint regression to identify linear inflections of prevalence of retinopathy in the association between A1C and FPG. RESULTS The overall prevalence of retinopathy was 11%, which is appreciably lower than the prevalence in people with diagnosed diabetes (36%). There was a sharp increase in retinopathy prevalence in those with A1C ≥5.5% or FPG ≥5.8 mmol/l. After excluding 144 people using hypoglycemic medication, the change points for the greatest increase in retinopathy prevalence were A1C 5.5% and FPG 7.0 mmol/l. The coefficients of variation were 15.6 for A1C and 28.8 for FPG. Based on the areas under the receiver operating characteristic curves, A1C was a stronger discriminator of retinopathy (0.71 [95% CI 0.66–0.76]) than FPG (0.65 [0.60 – 0.70], P for difference = 0.009). CONCLUSIONS The steepest increase in retinopathy prevalence occurs among individuals with A1C ≥5.5% and FPG ≥5.8 mmol/l. A1C discriminates prevalence of retinopathy better than FPG. PMID:19875604

Changes in Fasting Plasma Glucose Levels with Ribavirin and Pegylated Interferon Treatment in Normal and Impaired Glucose Tolerant Patients with Chronic Hepatitis C

PubMed Central

Sarasombath, Ongkarn; Suwantarat, Nuntra; Tice, Alan D

2012-01-01

Background Patients with Hepatitis C Virus (HCV) infection have increased rates of glucose intolerance, and studies have shown the improvement of fasting plasma glucose (FPG) levels after clearance of HCV infection with standard ribavirin plus pegylated interferon treatment. The purpose of this study was to examine glycemic changes with standard HCV treatment in patients with impaired fasting glucose (IFG) and normal fasting glucose (NFG). Methods A retrospective study of FPG changes in HCV patients with IFG and NFG treated with standard HCV therapy was conducted. Baseline characteristics and viral responses were assessed; FPG levels before treatment, at the end of treatment, and more than one-month post treatment were compared. Results The mean FPG levels increased by 8.68 mg/dl at the end of treatment in the NFG group but decreased by 9.0 mg/dl in the IFG group, a statistically significant difference (P=0.019). The change in FPG levels remained significantly different after adjusting for weight change (P=0.009) and weight changes and initial weight (P=0.039). FPG change from baseline at more than one month after treatment were similar in both groups (P=0.145). The change in FPG levels was not associated with sustained viral response. Conclusions In HCV-infected patients, standard ribavirin plus pegylated interferon treatment reduced FPG levels in patients with IFG and increased FPG levels in NFG individuals; independent of initial weight, weight change, or viral response. Standard HCV treatment modulates fasting plasma glucose levels which supports the need for a prospective study to determine the clinical significance of this finding. PMID:22737650

Associations of HbA1c and fasting plasma glucose with incident diabetes: Implications for pre-diabetes thresholds in a Japanese population.

PubMed

Nakagami, Tomoko; Tanaka, Yuki; Oya, Junko; Kurita, Moritoshi; Isago, Chisato; Hasegawa, Yukiko; Ito, Arata; Hirota, Naoki; Tsuzura, Reika; Uchigata, Yasuko

2016-12-01

This study assessed pre-diabetes (pre-DM) cutoffs for HbA1c and fasting plasma glucose (FPG) that were associated with an increased risk of incident DM. We evaluated 2267 non-diabetic Japanese health-check examinees (HbA1c: <6.5% [<48mmol/mol] and FPG: <7.0mmol/L) who were 30-79 years old and were followed-up for 5 years. Incident DM was defined as HbA1c of ≥6.5% (≥48mmol/mol), FPG of ≥7.0mmol/L, or physician-diagnosed DM. During 11047 person-years, we identified 99 incident DM cases (4.3%). The incidence of DM increased with increasing baseline HbA1c or FPG levels, and the change points (95% confidence intervals) were 5.7% (5.6-5.7%; 39mmol/mol [38-39mmol/mol]) for HbA1c and 5.5mmol/L (5.5-5.6mmol/L) for FPG. The adjusted hazard ratios (HRs) for incident DM per one standard deviation-increase in HbA1c and FPG were 5.5 (4.4-6.8) and 4.0 (3.2-4.8), respectively. The adjusted HRs for incident DM were significantly higher at HbA1c of 5.7-6.4% (39-46mmol/mol) or FPG of 5.5-6.9mmol/L, compared to HbA1c of <5.7% (<39mmol/mol) or FPG of <5.5mmol/L. The lower cut-offs for pre-DM may be 5.7% (39mmol/mol) for HbA1c and 5.5mmol/L for FPG in this Japanese population. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Depressive symptoms, antidepressant medication use, and new onset of diabetes in participants of the diabetes prevention program and the diabetes prevention program outcomes study.

PubMed

Marrero, David G; Ma, Yong; de Groot, Mary; Horton, Edward S; Price, David W; Barrett-Connor, Elizabeth; Carnethon, Mercedes R; Knowler, William C

2015-04-01

To assess in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study whether diagnosis of diabetes predicted elevated depressive symptoms (DS) or use of antidepressant medicine (ADM) following diagnosis; whether diabetes status or duration had significant effect on DS or ADM use; and to determine the associations between A1C, fasting plasma glucose (FPG), normalization of FPG, and DS or ADM use after diagnosis. Diabetes Prevention Program participants in three treatment arms (intensive life style, metformin, placebo) were assessed for diabetes, glucose control, ADM use, and DS, measured using the Beck Depression Inventory (BDI). Among 3234 participants, 1285 developed diabetes. Depression levels were measured before and after diabetes diagnosis. Neither DS nor use of ADM increased after diagnosis; higher FPG was associated with greater ADM use in the intensive life style arm; a 10-mg/dl rise in FPG is associated with greater odds of ADM use. Higher FPG and A1C were associated with higher BDI scores in all three arms; A 10-mg/dl rise in FPG had a 0.07 increase in BDI. A 1% higher A1c was associated with a 0.21-point increase in BDI. Normalization of FPG was associated with lower BDI. When FPG had normalized, there was a decrease of 0.30 points in the BDI score compared when FPG had not normalized. Contrary to clinical attributions, diabetes diagnosis did not show an immediate impact on BDI scores or ADM use. Higher glucose levels after diagnosis were associated with a small but significantly higher BDI score and more ADM use. DPPOS: NCT00038727; DPP: NCT00004992.

Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort.

PubMed

Cederberg, Henna; Stančáková, Alena; Yaluri, Nagendra; Modi, Shalem; Kuusisto, Johanna; Laakso, Markku

2015-05-01

The aim of this work was to investigate the mechanisms underlying the risk of type 2 diabetes associated with statin treatment in the population-based Metabolic Syndrome in Men (METSIM) cohort. A total of 8,749 non-diabetic participants, aged 45-73 years, were followed up for 5.9 years. New diabetes was diagnosed in 625 men by means of an OGTT, HbA1c ≥6.5% (48 mmol/mol) or glucose-lowering medication started during the follow-up. Insulin sensitivity and secretion were evaluated with OGTT-derived indices. Participants on statin treatment (N = 2,142) had a 46% increased risk of type 2 diabetes (adjusted HR 1.46 [95% CI 1.22, 1.74]). The risk was dose dependent for simvastatin and atorvastatin. Statin treatment significantly increased 2 h glucose (2hPG) and glucose AUC of an OGTT at follow-up, with a nominally significant increase in fasting plasma glucose (FPG). Insulin sensitivity was decreased by 24% and insulin secretion by 12% in individuals on statin treatment (at FPG and 2hPG <5.0 mmol/l) compared with individuals without statin treatment (p < 0.01). Decreases in insulin sensitivity and insulin secretion were dose dependent for simvastatin and atorvastatin. Statin treatment increased the risk of type 2 diabetes by 46%, attributable to decreases in insulin sensitivity and insulin secretion.

Comparison of diagnostic criteria to detect undiagnosed diabetes in hyperglycaemic patients with acute coronary syndrome.

PubMed

de Mulder, Maarten; Oemrawsingh, Rohit M; Stam, Frank; Boersma, Eric; Umans, Victor A

2012-01-01

Elevated plasma glucose levels on admission (APG) are very common in patients with acute coronary syndrome (ACS) and can be the first indication of diabetes mellitus. To provide insight into the prevalence of previously undiagnosed diabetes and to compare different methods of diagnosing diabetes in patients with ACS. Patients with ACS with elevated APG who participated in the BIOMArCS 2 glucose trial underwent an oral glucose tolerance test (OGTT) prior to discharge. 130 patients were included who underwent metabolic assessment. Of these, 109 had an OGTT and 13 patients had pre-existing diabetes. The OGTT results were categorised as (previously) undiagnosed diabetes in 35% of patients (fasting plasma glucose (FPG) ≥7.0 mmol/l or 2-h post-load glucose ≥11.1 mmol/l) and impaired glucose metabolism in 44% (FPG 6.1-6.9 mmol/l or post-load glucose 7.8-11.0 mmol/l), so only 21% had a normal glucose metabolism. Undiagnosed diabetes could not be adequately predicted with APG, FPG or HbA1c (area under the ROC curve 0.61, 0.75 and 0.72, respectively). Patients with abnormal glucose metabolism were significantly older, had higher admission HbA1c values, a higher Killip classification and more often had a prior stroke than patients with normal glucose metabolism. 79% of hyperglycaemic patients with ACS were found to have abnormal glucose metabolism. As APG, HbA1c and FPG had a low sensitivity to detect undiagnosed diabetes, an OGTT appears to be the best test to assess the presence of previously undiagnosed diabetes or impaired glucose metabolism in hyperglycaemic patients with ACS.

Pancreatic islet amyloidosis, β-cell apoptosis, and α-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons

PubMed Central

Guardado-Mendoza, Rodolfo; Davalli, Alberto M.; Chavez, Alberto O.; Hubbard, Gene B.; Dick, Edward J.; Majluf-Cruz, Abraham; Tene-Perez, Carlos E.; Goldschmidt, Lukasz; Hart, John; Perego, Carla; Comuzzie, Anthony G.; Tejero, Maria Elizabeth; Finzi, Giovanna; Placidi, Claudia; La Rosa, Stefano; Capella, Carlo; Halff, Glenn; Gastaldelli, Amalia; DeFronzo, Ralph A.; Folli, Franco

2009-01-01

β-Cell dysfunction is an important factor in the development of hyperglycemia of type-2 diabetes mellitus, and pancreatic islet amyloidosis (IA) has been postulated to be one of the main contributors to impaired insulin secretion. The aim of this study was to evaluate the correlation of IA with metabolic parameters and its effect on islets of Langerhans remodeling and relative endocrine-cell volume in baboons. We sequenced the amylin peptide, determined the fibrillogenic propensities, and evaluated pancreatic histology, clinical and biochemical characteristics, and endocrine cell proliferation and apoptosis in 150 baboons with different metabolic status. Amylin sequence in the baboon was 92% similar to humans and showed superimposable fibrillogenic propensities. IA severity correlated with fasting plasma glucose (FPG) (r = 0.662, P < 0.001) and HbA1c (r = 0.726, P < 0.001), as well as with free fatty acid, glucagon values, decreased homeostasis model assessment (HOMA) insulin resistance, and HOMA-B. IA severity was associated with a decreased relative β-cell volume, and increased relative α-cell volume and hyperglucagonemia. These results strongly support the concept that IA and β-cell apoptosis in concert with α-cell proliferation and hypertrophy are key determinants of islets of Langerhans “dysfunctional remodeling” and hyperglycemia in the baboon, a nonhuman primate model of type-2 diabetes mellitus. The most important determinants of IA were age and FPG (R2 = 0.519, P < 0.0001), and different FPG levels were sensitive and specific to predict IA severity. Finally, a predictive model for islet amyloid severity was generated with age and FPG as required variables. PMID:19666551

Decision tree-based modelling for identification of potential interactions between type 2 diabetes risk factors: a decade follow-up in a Middle East prospective cohort study.

PubMed

Ramezankhani, Azra; Hadavandi, Esmaeil; Pournik, Omid; Shahrabi, Jamal; Azizi, Fereidoun; Hadaegh, Farzad

2016-12-01

The current study was undertaken for use of the decision tree (DT) method for development of different prediction models for incidence of type 2 diabetes (T2D) and for exploring interactions between predictor variables in those models. Prospective cohort study. Tehran Lipid and Glucose Study (TLGS). A total of 6647 participants (43.4% men) aged >20 years, without T2D at baselines ((1999-2001) and (2002-2005)), were followed until 2012. 2 series of models (with and without 2-hour postchallenge plasma glucose (2h-PCPG)) were developed using 3 types of DT algorithms. The performances of the models were assessed using sensitivity, specificity, area under the ROC curve (AUC), geometric mean (G-Mean) and F-Measure. T2D was primary outcome which defined if fasting plasma glucose (FPG) was ≥7 mmol/L or if the 2h-PCPG was ≥11.1 mmol/L or if the participant was taking antidiabetic medication. During a median follow-up of 9.5 years, 729 new cases of T2D were identified. The Quick Unbiased Efficient Statistical Tree (QUEST) algorithm had the highest sensitivity and G-Mean among all the models for men and women. The models that included 2h-PCPG had sensitivity and G-Mean of (78% and 0.75%) and (78% and 0.78%) for men and women, respectively. Both models achieved good discrimination power with AUC above 0.78. FPG, 2h-PCPG, waist-to-height ratio (WHtR) and mean arterial blood pressure (MAP) were the most important factors to incidence of T2D in both genders. Among men, those with an FPG≤4.9 mmol/L and 2h-PCPG≤7.7 mmol/L had the lowest risk, and those with an FPG>5.3 mmol/L and 2h-PCPG>4.4 mmol/L had the highest risk for T2D incidence. In women, those with an FPG≤5.2 mmol/L and WHtR≤0.55 had the lowest risk, and those with an FPG>5.2 mmol/L and WHtR>0.56 had the highest risk for T2D incidence. Our study emphasises the utility of DT for exploring interactions between predictor variables. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Metabolic and Inflammatory Changes with Orlistat and Sibutramine Treatment in Obese Malaysian Subjects.

PubMed

Al-Tahami, Belqes Abdullah Mohammad; Al-Safi Ismail, Ab Aziz; Sanip, Zulkefli; Yusoff, Zurkurnai; Shihabudin, Tg Muzaffar Tm; Singh, Taran Singh Pall; Rasool, Aida Hanum Ghulam

2017-01-01

Obesity is associated with numerous health problems, particularly metabolic and cardiovascular complications. This study aimed to assess the effects that, nine months of pharmacological intervention with orlistat or sibutramine, on obese Malaysians' body weight and compositions, metabolic profiles and inflammatory marker. Seventy-six obese subjects were randomly placed into two groups. The first group received three daily 120 mg dosages of orlistat for nine months (n=39), and the second group received a once daily 10 or 15 mg dosage of sibutramine for nine months (n=37). Baseline measurements for weight, body mass index (BMI), waist circumference (WC), body fat percentage (BF), visceral fat (VF), adiponectin, fasting plasma glucose (FPG), fasting insulin, pancreatic B cell secretory capacity (HOMA%B), insulin sensitivity (HOMA%S), insulin resistance (HOMA-IR) and serum high sensitivity C-reactive protein (hs-CRP) were performed and repeated during the sixth and ninth months of treatment. Twenty-four subjects completed the trial in both groups. For both groups, weight, BMI, WC, BF, VF, HOMA-IR and hs-CRP were significantly lower at the end of the nine month intervention. However, there were no significant differences between the two groups for these parameters with nine months treatment. There was a significant decrease in FPG in orlistat group; while fasting insulin and HOMA%B reduced in sibutramine group. For both groups, there were also significant increases in adiponectin levels and HOMA%S at the end of the nine month intervention. Nine months of treatment with orlistat and sibutramine not only reduced weight but also significantly improved BMI, WC, BF, VF, FPG, adiponectin, fasting insulin, HOMA%B, HOMA%S, HOMA-IR and hs-CRP. These improvements could prove useful in the reduction of metabolic and cardiovascular risks in obese subjects.

Impaired osteogenic differentiation and enhanced cellular receptor of advanced glycation end products sensitivity in patients with type 2 diabetes.

PubMed

Phimphilai, Mattabhorn; Pothacharoen, Peraphan; Kongtawelert, Prachya; Chattipakorn, Nipon

2017-11-01

Preclinical studies have demonstrated impaired osteoblast differentiation in type 2 diabetes (T2DM), which is related to skeletal accumulation of advanced glycation end products (AGEs). However, the role of AGE in osteoblast differentiation in patients with T2DM is unclear. This cross-sectional study was performed to investigate osteoblast differentiation and its association with serum pentosidine and soluble receptor of AGEs (sRAGE). Twenty-seven patients with T2DM and 15 age-matched controls were included to measure sRAGE and osteogenic differentiation in mononuclear cells derived from peripheral blood. The mononuclear cells isolated from patients with T2DM showed a significantly lower rate of osteogenic differentiation (7.4% vs 86.7%, p < 0.0001) with a lower level of ALPL, COL1A1, and BGLAP expression than those of controls by 11-, 44-, and 15-fold respectively, together with nonvisualized mineralization by alizarin red S staining. The levels of pentosidine and sRAGE were comparable in both groups. AGER expression was significantly higher in the T2DM group. BAX expression was also significantly higher in the T2DM group, and showed a strong correlation with AGER expression (r = 0.86, p < 0.0001). Fasting plasma glucose (FPG) level, AGER expression, and BAX expression showed a strong correlation with osteogenic differentiation defects on univariate analysis. However, only FPG showed a correlation with this defect in a multivariate analysis. In conclusion, patients with T2DM showed impairment of osteoblast differentiation, and FPG was an independent risk factor for this impairment. Moreover, T2DM showed a higher cellular sensitivity for activation of receptor of AGEs and higher cellular apoptosis, which may contribute to the defect in osteoblast differentiation.

Postchallenge hyperglycemia in subjects with low body weight: implication for small glucose volume.

PubMed

Sakuma, Takahiro; Yamashita, Koh; Miyakoshi, Takahiro; Shimodaira, Masanori; Yokota, Naokazu; Sato, Yuka; Hirabayashi, Kazuko; Koike, Hideo; Yamauchi, Keishi; Shimbo, Takuro; Aizawa, Toru

2017-12-01

A hypothesis that postchallenge hyperglycemia in subjects with low body weight (BW) may be due, in part, to small glucose volume (G V ) was tested. We studied 11,411 nondiabetic subjects with a mean BW of 63.3 kg; 5,282 of them were followed for a mean of 5.3 yr. In another group of 1,537 nondiabetic subjects, insulin sensitivity, secretion, and a product of the two (index of whole body insulin action) were determined. Corrected 2 h-plasma glucose (2hPG corr ) during a 75-g oral glucose tolerance test in subjects with BW ≤ 59 kg was calculated as 2hPG corr = δPG 2h · ECW/[16.1 (males) or 15.3 (females)] + fasting PG (FPG), where δPG 2h is plasma glucose increment in 2 h; ECW is extracellular water (surrogate of G V ); FPG is fasting plasma glucose; and 16.1 and 15.3 are ECW of men and women, respectively, with BW = 59 kg. Multivariate analyses for BW with adjustment for age, sex, and percent body fat were undertaken. BW was, across its entire range, positively correlated with FPG ( P < 0.01). Whereas BW was correlated with 2hPG and δPG in a skewed J-shape, with inflections at around 60 kg ( P for nonlinearity < 0.01 for each). Nonetheless, in those with BW ≤ 59 kg, insulin sensitivity, secretion, and action were unattenuated, and incident diabetes was less compared with heavier counterparts. BW was linearly correlated with 2hPG corr , i.e., the J-shape correlation was mitigated by the correction. In conclusion, postchallenge hyperglycemia in low BW subjects is in part due to small G V rather than impaired glucose metabolism. Copyright © 2017 the American Physiological Society.

Validation of a Type 2 Diabetes Screening Tool in Rural Honduras

PubMed Central

Milton, Evan C.; Herman, William H.; Aiello, Allison E.; Danielson, Kris R.; Mendoza-Avelarez, Milton O.; Piette, John D.

2010-01-01

OBJECTIVE To validate a low-cost tool for identifying diabetic patients in rural areas of Latin America. RESEARCH DESIGN AND METHODS A regression equation incorporating postprandial time and a random plasma glucose was used to screen 800 adults in Honduras. Patients with a probability of diabetes of ≥20% were asked to return for a fasting plasma glucose (FPG). A random fifth of those with a screener-based probability of diabetes <20% were also asked to return for follow-up. The gold standard was an FPG ≥126 mg/dl. RESULTS The screener had very good test characteristics (area under the receiver operating characteristic curve = 0.89). Using the screening criterion of ≥0.42, the equation had a sensitivity of 74.1% and specificity of 97.2%. CONCLUSIONS This screener is a valid measure of diabetes risk in Honduras and could be used to identify diabetic patients in poor clinics in Latin America. PMID:19918008

Risk of progression to diabetes from prediabetes defined by HbA1c or fasting plasma glucose criteria in Koreans.

PubMed

Kim, Chul-Hee; Kim, Hong-Kyu; Kim, Eun-Hee; Bae, Sung-Jin; Choe, Jaewon; Park, Joong-Yeol

2016-08-01

To examine the abilities of HbA1c and fasting plasma glucose (FPG) criteria predicting 5-year progression rate to diabetes in Korean adults with prediabetes. Participants included 17,971 Koreans (aged 20-79years) who underwent routine medical check-ups at a mean interval of 5.2years (3.1-6.7years). Prediabetes was defined as FPG 5.6-6.9mmol/l or HbA1c 5.7-6.4% (39-46mmol/mol). Incident diabetes was defined as FPG⩾7.0mmol/l, HbA1c⩾6.5% (48mmol/mol), or initiation of antidiabetic medications. At baseline, the prevalence of prediabetes was 30.6% (n=5495) by FPG and 20.4% (n=3664) by HbA1c criteria. The 5-year progression rate to diabetes was significantly higher in prediabetes identified by HbA1c than by FPG tests (14.7% vs. 10.4%, P<0.001). Of individuals diagnosed with prediabetes by only one test, those by HbA1c alone had a higher risk of progression to diabetes than those diagnosed by FPG alone (6.0% vs. 3.9%, P<0.001). Receiver operating characteristic curve analysis showed that area under the curve was greater for HbA1c (0.855, 95% CI 0.840-0.870) than for FPG (0.830, 0.813-0.846) (P=0.016). After adjustment for conventional risk factors, the odds ratio (OR) of developing diabetes was higher in participants with prediabetes identified by HbA1c (OR 9.91, 8.24-11.9) than by FPG (OR 7.29, 5.97-8.89) (P=0.026). Although fewer individuals with prediabetes were identified by HbA1c than by FPG criteria, the ability to predict progression to diabetes was stronger for HbA1c than for FPG in Koreans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Depressive symptoms, antidepressant medication use and new onset of diabetes in participants of the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study

PubMed Central

Marrero, David G.; Ma, Yong; de Groot, Mary; Horton, Edward S.; Price, David W.; Barrett-Connor, Elizabeth; Carnethon, Mercedes R.; Knowler, William C.

2015-01-01

Objective To assess in participants in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study (DPP/DPPOS) whether diagnosis of diabetes predicted: elevated depressive symptoms (DS) or antidepressant medicine (ADM) use after diagnosis; diabetes status or duration had significant effect on DS or ADM use; and associations between A1C, fasting plasma glucose (FPG), normalization of FPG and DS or ADM use post diagnosis. Methods DPP participants in 3 treatment arms [intensive lifestyle (ILS), metformin (MET), placebo (PLC)] were assessed semiannually or annually for diabetes, glucose control, ADM use, and DS. DS was measured using Beck Depression Inventory (BDI) questionnaire. Among the total 3234 enrolled participants, 1285 developed diabetes whose levels of depression were measured before and after their diabetes diagnosis. Results Neither DS nor ADM use increased significantly following diabetes diagnosis. After diabetes diagnosis, higher FPG was associated with greater ADM use in the ILS arm independent of potential confounders; a 10 mg/dl higher in FPG is associated with 8.8% more odds of ADM use. Higher FPG, and higher A1C were associated with higher BDI scores in all three arms. On average, a participant with 10 mg/dl higher rise in FPG had a 0.07 increase in BDI score. Similarly, 1% higher A1c was associated with a 0.21 point increase in BDI score. On contrary, normalization of FPG was associated with lower BDI scores. In participants with FPG that had normalized, there was a decrease of 0.30 points in the BDI score compared to those whose FPG had not normalized. Conclusions Contrary to clinical attributions, the diagnosis of diabetes did not show an immediate impact on BDI scores or ADM use. However, higher glucose levels after diagnosis were associated with small but significant higher BDI score and more ADM use. PMID:25775165

[Valuation and prospect of function preserving gastrectomy].

PubMed

Wang, Shuchang; Yu, Site; Xu, Jia; Zhao, Gang

2017-10-25

Preserving gastric function and improving quality of life (QOL) is the tendency of surgery for early gastric cancer. Function preserving gastrectomy (FPG) is applied to modify the extent of surgery and to achieve better quality of life at the premise of radical resection. Pylorus-preserving gastrectomy is the most favorable approach of FPG with oncological safety, which can improve nutritional status and QOL via preserving pylorus and vagal nerve. Proximal gastrectomy is widely accepted as FPG for early upper 1/3 gastric cancer. However, the most optimal way of anastomosis is not yet solved. Sentinel node navigation is currently the most accurate approach for intraoperative diagnosis of lymph node metastasis, which stimulates the development of many kinds of FPG procedures for individual treatment. Nevertheless, more efforts should be made to reduce false negative rate of sentinel node biopsy. Herein we discuss the valuation and prospect of FPG.

Gestational diabetes mellitus: Screening with fasting plasma glucose.

PubMed

Agarwal, Mukesh M

2016-07-25

Fasting plasma glucose (FPG) as a screening test for gestational diabetes mellitus (GDM) has had a checkered history. During the last three decades, a few initial anecdotal reports have given way to the recent well-conducted studies. This review: (1) traces the history; (2) weighs the advantages and disadvantages; (3) addresses the significance in early pregnancy; (4) underscores the benefits after delivery; and (5) emphasizes the cost savings of using the FPG in the screening of GDM. It also highlights the utility of fasting capillary glucose and stresses the value of the FPG in circumventing the cumbersome oral glucose tolerance test. An understanding of all the caveats is crucial to be able to use the FPG for investigating glucose intolerance in pregnancy. Thus, all health professionals can use the patient-friendly FPG to simplify the onerous algorithms available for the screening and diagnosis of GDM - thereby helping each and every pregnant woman.

The Fpg/Nei family of DNA glycosylases: substrates, structures, and search for damage.

PubMed

Prakash, Aishwarya; Doublié, Sylvie; Wallace, Susan S

2012-01-01

During the initial stages of the base excision DNA repair pathway, DNA glycosylases are responsible for locating and removing the majority of endogenous oxidative base lesions. The bifunctional formamidopyrimidine DNA glycosylase (Fpg) and endonuclease VIII (Nei) are members of the Fpg/Nei family, one of the two families of glycosylases that recognize oxidized DNA bases, the other being the HhH/GPD (or Nth) superfamily. Structural and biochemical developments over the past decades have led to novel insights into the mechanism of damage recognition by the Fpg/Nei family of enzymes. Despite the overall structural similarity among members of this family, these enzymes exhibit distinct features that make them unique. This review summarizes the current structural knowledge of the Fpg/Nei family members, emphasizes their substrate specificities, and describes how these enzymes search for lesions. Copyright © 2012 Elsevier Inc. All rights reserved.

Efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose: Results of a randomized controlled trial.

PubMed

Göke, R; Eschenbach, P; Dütting, E D

2015-06-01

This study compared the efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose (FPG) as single-pill combinations (SPCs) with metformin. The randomized crossover, open-label, active-controlled study design assessed the FPG-lowering abilities of a vildagliptin/metformin (50/1000 mg twice daily) SPC compared with a sitagliptin/metformin (50/1000 mg twice daily) SPC after 2 weeks of treatment in 99 type 2 diabetes patients uncontrolled by stable metformin therapy (1000-2000 mg/day). The change in FPG from baseline to day 14 was significantly greater (P < 0.02, Wilcoxon) with vildagliptin [-21.9 mg/dL (SD 27.0)] than with sitagliptin [-14.5 mg/dL (SD 23.0)]. After 14 days of treatment, the mean FPG was 137.8 mg/dL (SD 28.5) with vildagliptin and 140.1mg/dL (SD 26.5) with sitagliptin (P < 0.05, Wilcoxon). Both of these DPP-4 inhibitors, given as SPCs twice daily with metformin, lowered FPG after 14 days of treatment. However, vildagliptin produced a significantly greater reduction in FPG vs baseline compared with sitagliptin, which may translate into clinical relevance. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Visit-to-visit glycemic variability is a strong predictor of chronic obstructive pulmonary disease in patients with type 2 diabetes mellitus: Competing risk analysis using a national cohort from the Taiwan diabetes study.

PubMed

Chiu, Hsien-Tsai; Li, Tsai-Chung; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Lin, Cheng-Chieh

2017-01-01

This study aims to examine the association between visit-to-visit glucose variability, which was measured by coefficient of variation (CV) of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c), and risk of chronic obstructive pulmonary disease (COPD) in a large number of patients with type 2 diabetes with an average follow-up of 7.58 years. We conducted a retrospective cohort study on 27,257 patients with type 2 diabetes who participated in the National Diabetes Case Management Program in Taiwan. Visit-to-visit variability in HbA1c and FPG at baseline and the incidence of COPD were analyzed using a modified Cox proportional hazards model considering competing risks. A total of 2,346 incident cases of COPD. Patients were grouped into tertiles of FPG-CV and HbA1c-CV. The incidence rates in the first, second, and third tertiles were 9.87, 11.06, and 13.19, respectively, for FPG-CV and 10.2, 11.81, and 12.07, for HbA1c-CV per 1000 person-years. After adjusting for age, gender, diabetes duration, treatment type, smoking, hypertension, hyperlipidemia, baseline FPG and HbA1c levels, and complications, both FPG-CV and HbA1c-CV were independently associated with COPD. The hazard ratios of COPD for the third terile compared with the first tertile of FPG-CV were 1.26 (95% confidence interval [CI]: 1.13-1.40). Moreover, the hazard ratios of COPD for the third and second tertiles compared with the first tertile of HbA1c-CV were 1.13 (1.02-1.25) and 1.13 (1.02-1.26), respectively. Patients with FPG-CV higher than 34.6% or HbA1c-CV higher than 8.4% exhibited an increased risk of COPD. This finding confirmed the linear relationship of FPG-CV and HbA1c-CV to COPD. Visit-to-visit variability in FPG and HbA1c levels are strong predictors of COPD in patients with type 2 diabetes. Future studies should focus on lung dysfunction in diabetes, and adequate glucose control strategy in regular clinical practices must be established for COPD prevention.

Normal fasting plasma glucose predicts type 2 diabetes and cardiovascular disease in elderly population in Taiwan.

PubMed

Huang, C-L; Chang, H-W; Chang, J-B; Chen, J-H; Lin, J-D; Wu, C-Z; Pei, D; Hung, Y-J; Lee, C-H; Chen, Y-L; Hsieh, C-H

2016-08-01

Hyperglycemia increases prevalence of metabolic syndrome (MetS), type 2 diabetes (T2D) and cardiovascular disease (CVD). But the role of normoglycemia on the development of T2D and CVD in elderly population remains unclear. To determine an optimal cut-off for fasting plasma glucose (FPG) to predict MetS and subsequent risk of T2D and CVD in an elderly Taiwanese population with normal FPG levels. Two stages included cross-sectional (Stage 1) and prospective (Stage 2) cohort study. In Stage 1 18 287 subjects aged  ≥60 years were enrolled; of these, 5039 without T2D and CVD advanced to Stage 2 and a mean follow-up of 3.8 years. MetS components were analysed, and in Stage 1, FPG cut-offs for MetS risk were calculated using receiver operating characteristic (ROC) curve analyses. In Stage 2, subjects without T2D and CVD in Stage 1 were classified into high-FPG and low-FPG groups based on cut-offs, and sex specific differences in incidence for T2D and CVD were calculated. ROC curve analysis gave an optimal FPG cut-off for MetS of 93 mg/dl and 92 mg/dl for males and females, respectively. The high-FPG group had a 1.599- and 1.353-fold higher chance of developing T2D compared with the low-FPG group for males and females, respectively (95% CI: 1.606-2.721 and 1.000-1.831, P  =  0.015 and 0.05). The high-FPG group had a 1.24-fold higher chance of developing CVD for females (95% CI: 1.015-1.515, P  =  0.035); however, there was no difference for males. Our results suggest that FPG within the normal range was associated with MetS, and elderly subjects with high normal levels have a higher incidence of developing T2D for both sexes, and CVD for females, over the short-term. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

In vitro and in vivo genotoxicity investigations of differently sized amorphous SiO2 nanomaterials.

PubMed

Maser, Elena; Schulz, Markus; Sauer, Ursula G; Wiemann, Martin; Ma-Hock, Lan; Wohlleben, Wendel; Hartwig, Andrea; Landsiedel, Robert

2015-12-01

In vitro and in vivo genotoxic effects of differently sized amorphous SiO2 nanomaterials were investigated. In the alkaline Comet assay (with V79 cells), non-cytotoxic concentrations of 300 and 100-300μg/mL 15nm-SiO2 and 55nm-SiO2, respectively, relevant (at least 2-fold relative to the negative control) DNA damage. In the Alkaline unwinding assay (with V79 cells), only 15nm-SiO2 significantly increased DNA strand breaks (and only at 100μg/mL), whereas neither nanomaterial (up to 300μg/mL) increased Fpg (Formamidopyrimidine DNA glycosylase)-sensitive sites reflecting oxidative DNA base modifications. In the Comet assay using rat precision-cut lung slices, 15nm-SiO2 and 55nm-SiO2 induced significant DNA damage at ≥100μg/mL. In the Alkaline unwinding assay (with A549 cells), 30nm-SiO2 and 55nm-SiO2 (with larger primary particle size (PPS)) induced significant increases in DNA strand breaks at ≥50μg/mL, whereas 9nm-SiO2 and 15nm-SiO2 (with smaller PPS) induced significant DNA damage at higher concentrations. These two amorphous SiO2 also increased Fpg-sensitive sites (significant at 100μg/mL). In vivo, within 3 days after single intratracheal instillation of 360μg, neither 15nm-SiO2 nor 55nm-SiO2 caused genotoxic effects in the rat lung or in the bone marrow. However, pulmonary inflammation was observed in both test groups with findings being more pronounced upon treatment with 15nm-SiO2 than with 55nm-SiO2. Taken together, the study shows that colloidal amorphous SiO2 with different particle sizes may induce genotoxic effects in lung cells in vitro at comparatively high concentrations. However, the same materials elicited no genotoxic effects in the rat lung even though pronounced pulmonary inflammation evolved. This may be explained by the fact that a considerably lower dose reached the target cells in vivo than in vitro. Additionally, the different time points of investigation may provide more time for DNA damage repair after instillation. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Selective enzymatic cleavage and labeling for sensitive capillary electrophoresis laser-induced fluorescence analysis of oxidized DNA bases.

PubMed

Li, Cuiping; Wang, Hailin

2015-08-07

Oxidatively generated DNA damage is considered to be a significant contributing factor to cancer, aging, and age-related human diseases. It is important to detect oxidatively generated DNA damage to understand and clinically diagnosis diseases caused by oxidative damage. In this study, using selective enzymatic cleavage and quantum dot (QD) labeling, we developed a novel capillary electrophoresis-laser induced fluorescence method for the sensitive detection of oxidized DNA bases. First, oxidized DNA bases are recognized and removed by one DNA base excision repair glycosylase, leaving apurinic and apyrimidinic sites (AP sites) at the oxidized positions. The AP sites are further excised by the AP nicking activity of the chosen glycosylase, generating a nucleotide gap with 5'- and 3'- phosphate groups. After dephosphorylation with one alkaline phosphatase, a biotinylated ddNTP is introduced into the nucleotide space within the DNA strand by DNA polymerase I. The biotin-tagged DNA is further labeled with a QD-streptavidin conjugate via non-covalent interactions. The DNA-bound QD is well-separated from excess DNA-unbound QD by highly efficient capillary electrophoresis and is sensitively detected by online coupled laser-induced fluorescence analysis. Using this method, we can assess the trace levels of oxidized DNA bases induced by the Fenton reaction and UV irradiation. Interestingly, the use of the formamidopyrimidine glycosylase (FPG) protein and endonuclease VIII enables the detection of oxidized purine and pyrimidine bases, respectively. Using the synthesized standard DNA, the approach has low limits of detection of 1.1×10(-19)mol in mass and 2.9pM in concentration. Copyright © 2015 Elsevier B.V. All rights reserved.

IDENTIFYING PROBABLE DIABETES MELLITUS AMONG HISPANICS/LATINOS FROM FOUR U.S. CITIES: FINDINGS FROM THE HISPANIC COMMUNITY HEALTH STUDY/STUDY OF LATINOS.

PubMed

Avilés-Santa, M Larissa; Schneiderman, Neil; Savage, Peter J; Kaplan, Robert C; Teng, Yanping; Pérez, Cynthia M; Suárez, Erick L; Cai, Jianwen; Giachello, Aida L; Talavera, Gregory A; Cowie, Catherine C

2016-10-01

The aim of this study was to compare the ability of American Diabetes Association (ADA) diagnostic criteria to identify U.S. Hispanics/Latinos from diverse heritage groups with probable diabetes mellitus and assess cardiovascular risk factor correlates of those criteria. Cross-sectional analysis of data from 15,507 adults from 6 Hispanic/Latino heritage groups, enrolled in the Hispanic Community Health Study/Study of Latinos. The prevalence of probable diabetes mellitus was estimated using individual or combinations of ADA-defined cut points. The sensitivity and specificity of these criteria at identifying diabetes mellitus from ADA-defined prediabetes and normoglycemia were evaluated. Prevalence ratios of hypertension, abnormal lipids, and elevated urinary albumin-creatinine ratio for unrecognized diabetes mellitus-versus prediabetes and normoglycemia-were calculated. Among Hispanics/Latinos (mean age, 43 years) with diabetes mellitus, 39.4% met laboratory test criteria for probable diabetes, and the prevalence varied by heritage group. Using the oral glucose tolerance test as the gold standard, the sensitivity of fasting plasma glucose (FPG) and hemoglobin A1c-alone or in combination-was low (18, 23, and 33%, respectively) at identifying probable diabetes mellitus. Individuals who met any criterion for probable diabetes mellitus had significantly higher (P<.05) prevalence of most cardiovascular risk factors than those with normoglycemia or prediabetes, and this association was not modified by Hispanic/Latino heritage group. FPG and hemoglobin A1c are not sensitive (but are highly specific) at detecting probable diabetes mellitus among Hispanics/Latinos, independent of heritage group. Assessing cardiovascular risk factors at diagnosis might prompt multitarget interventions and reduce health complications in this young population. 2hPG = 2-hour post-glucose load plasma glucose ADA = American Diabetes Association BMI = body mass index CV = cardiovascular FPG = fasting plasma glucose HbA1c = hemoglobin A1c HCHS/SOL = Hispanic Community Health Study/Study of Latinos HDL-C = high-density-lipoprotein cholesterol NGT = normal glucose tolerance NHANES = National Health and Nutrition Examination Survey OGTT = oral glucose tolerance test TG = triglyceride UACR = urine albumin-creatinine ratio.

Diabetes screening in overweight and obese children and adolescents: choosing the right test.

PubMed

Ehehalt, Stefan; Wiegand, Susanna; Körner, Antje; Schweizer, Roland; Liesenkötter, Klaus-Peter; Partsch, Carl-Joachim; Blumenstock, Gunnar; Spielau, Ulrike; Denzer, Christian; Ranke, Michael B; Neu, Andreas; Binder, Gerhard; Wabitsch, Martin; Kiess, Wieland; Reinehr, Thomas

2017-01-01

Type 2 diabetes can occur without any symptoms, and health problems associated with the disease are serious. Screening tests allowing an early diagnosis are desirable. However, optimal screening tests for diabetes in obese youth are discussed controversially. We performed an observational multicenter analysis including 4848 (2668 female) overweight and obese children aged 7 to 17 years without previously known diabetes. Using HbA1c and OGTT as diagnostic criteria, 2.4% (n = 115, 55 female) could be classified as having diabetes. Within this group, 68.7% had HbA1c levels ≥48 mmol/mol (≥6.5%). FPG ≥126 mg/dl (≥7.0 mmol/l) and/or 2-h glucose levels ≥200 mg/dl (≥11.1 mmol/l) were found in 46.1%. Out of the 115 cases fulfilling the OGTT and/or HbA1c criteria for diabetes, diabetes was confirmed in 43.5%. For FPG, the ROC analysis revealed an optimal threshold of 98 mg/dl (5.4 mmol/l) (sensitivity 70%, specificity 88%). For HbA1c, the best cut-off value was 42 mmol/mol (6.0%) (sensitivity 94%, specificity 93%). HbA1c seems to be more reliable than OGTT for diabetes screening in overweight and obese children and adolescents. The optimal HbA1c threshold for identifying patients with diabetes was found to be 42 mmol/mol (6.0%). What is Known: • The prevalence of obesity is increasing and health problems related to type 2 DM can be serious. However, an optimal screening test for diabetes in obese youth seems to be controversial in the literature. What is New: • In our study, the ROC analysis revealed for FPG an optimal threshold of 98 mg/dl (5.4 mmol/l, sensitivity 70%, specificity 88%) and for HbA1c a best cut-off value of 42 mmol/mol (6.0%, sensitivity 94%, specificity 93%) to detect diabetes. Thus, in overweight and obese children and adolescents, HbA1c seems to be a more reliable screening tool than OGTT.

Fasting plasma glucose levels and coronary artery calcification in subjects with impaired fasting glucose.

PubMed

Eun, Young-Mi; Kang, Sung-Goo; Song, Sang-Wook

2016-01-01

Prediabetes is associated with an increased risk of cardiovascular disease (CVD). While the association of impaired glucose tolerance with CVD has been shown in many studies, the relationship between impaired fasting glucose (IFG) and CVD remains unclear. The purpose of this study was to compare the coronary artery calcium (CAC) scores of participants with normal fasting glucose versus those with IFG, according to fasting plasma glucose (FPG) levels, and to assess whether differences in CAC scores were independent of important confounders. Retrospective study. Health Promotion Center of the University Hospital (Gyeonggi-do, South Korea), during the period 2010-2014. Participants were enrolled from the general population who visited for a medical check-up. CAC was assessed in asymptomatic individuals by multidetector computed tomography. Anthropometric parameters and metabolic profiles were also recorded. Subjects were divided into four fasting glucose groups. Participants with a history of CVD or diabetes mellitus were excluded. Correlation between FPG and CAC scores, CAC score categories, and association between CAC score and FPG categories. Of 1112 participants, 346 (34.2%) had a CAC score > 0. FPG values in the IFG patients were positively but weakly correlated with CAC scores (r=0.099, P=.001). The incidence of CAC differed according to FPG level (P < .001) and in Kruskal-Wallis test the mean CAC score differed by FPG group (P < .001). After adjustment for other factors in a multiple logistic regression analysis, those subjects with FPG >=110 mg/dL had a significantly higher risk of CAC than did subjects with normal fasting glucose (110.

Relationship between glycaemic levels and arterial stiffness in non-diabetic adults.

PubMed

Cavero-Redondo, Iván; Martínez-Vizcaíno, Vicente; Álvarez-Bueno, Celia; Recio-Rodríguez, José Ignacio; Gómez-Marcos, Manuel Ángel; García-Ortiz, Luis

2018-01-23

To examine, in a non-diabetic population, whether the association between arterial stiffness and glycaemic levels depends on the test used as a glycaemic indicator, fasting plasma glucose (FPG) or glycated haemoglobin A1c (HbA1c). A cross-sectional analysis of a 220 non-diabetic subsample from the EVIDENT II study in which FPG, HbA1c and arterial stiffness-related parameters (pulse wave velocity, radial and central augmentation index, and central pulse pressure) were determined. Mean differences in arterial stiffness-related parameters by HbA1c and FPG tertiles were tested using analysis of covariance. All means of arterial stiffness-related parameters increased by HbA1c tertiles, although mean differences were only statistically significant in pulse wave velocity (p ≤.001), even after controlling for potential confounders (HbA1c <5.30% = 6.88 m/s; HbA1c 5.30%-5.59% = 7.06 m/s; and HbA1c ≥5.60% = 8.16 m/s, p =.004). Conversely, mean differences in pulse wave velocity by FPG tertiles did not reach statistically significant differences after controlling for potential confounders (FPG 4.44 mmol/l = 7.18 m/s; FPG 4.44 mmol/l-4.87 mmol/l = 7.26 m/s; and FPG ≥4.88 mmol/l = 7.93 m/s, p =.066). Glucose levels in a non-diabetic population were associated with arterial stiffness but better when levels were determined using HbA1c. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Osteocalcin as a marker of metabolic risk in healthy postmenopausal women.

PubMed

García-Martín, Antonia; Cortés-Berdonces, María; Luque-Fernández, Inés; Rozas-Moreno, Pedro; Quesada-Charneco, Miguel; Muñoz-Torres, Manuel

2011-05-01

Several studies have reported the role of osteocalcin on glucose and fat metabolism. In this study, we analyzed the relationship between the concentration of osteocalcin and metabolic risk factors in healthy postmenopausal women. Cross-sectional analyses of 54 postmenopausal women aged 56 ± 3.5 years were conducted. We recorded clinical and biochemical data of metabolic risk including fasting plasma glucose (FPG) level and evaluated the relationship between serum osteocalcin and bone formation markers. Serum osteocalcin concentration was negatively correlated with FPG (β = -0.328, P = 0.035). When osteocalcin levels were divided into tertiles, we found significant differences in FPG between the highest and the lowest tertiles (84 ± 11 vs 98 ± 30 mg/dL, respectively; P = 0.029). We found significantly lower osteocalcin levels in women with impaired fasting glucose levels than in those with normoglycemia (10.7 ± 6.1 vs 17.1 ± 7.4 ng/mL, respectively; P = 0.006). We also found lower concentrations of osteocalcin in obese women versus nonobese women (14.4 ± 8.8 vs 17.3 ± 6.2 ng/mL; P = 0.034) and women with increased low-density lipoprotein cholesterol levels versus those with low LDL-c levels (14.1 ± 5.4 vs 18.9 ± 9.1 ng/mL; P = 0.045). A concentration of 13.5 ng/ mL or lower showed a sensitivity of 85.7% and a specificity of 63.8% to detect increased risk for diabetes (FPG ≥100 mg/dL). In contrast, serum levels of bone alkaline phosphatase did not correlate with any variable. In this population, there is a consistent association between osteocalcin and markers of metabolic syndrome. We suggest potential usefulness of serum osteocalcin as a predictor for increased risk of diabetes in postmenopausal women.

Discordance in the diagnosis of diabetes: Comparison between HbA1c and fasting plasma glucose.

PubMed

Ho-Pham, Lan T; Nguyen, Uyen D T; Tran, Truong X; Nguyen, Tuan V

2017-01-01

HbA1c has been introduced as a complementary diagnostic test for diabetes, but its impact on disease prevalence is unknown. This study evaluated the concordance between HbA1c and fasting plasma glucose (FPG) in the diagnosis of diabetes in the general population. The study was designed as a population based investigation, with participants being sampled from the Ho Chi Minh City, Vietnam. Blood samples were collected after overnight fasting and analyzed within 4 hours after collection. HbA1c was measured with high pressure liquid chromatography (Arkray Adams, Japan). FPG was measured by the hexokinase method (Advia Autoanalyzer; Bayer Diagnostics, Germany). Diabetes was defined as HbA1c ≥ 6.5% or FPG ≥ 7.0 mmol/L. Prediabetes was classified as HbA1c between 5.7% and 6.4%. The study included 3523 individuals (2356 women) aged 30 years and above. Based on the HbA1c test, the prevalence of diabetes and prediabetes was 9.7% (95%CI, 8.7-10.7%; n = 342) and 34.6% (33.0-36.2; n = 1219), respectively. Based on the FPG test, the prevalence of diabetes and prediabetes was 6.3% (95%CI, 5.5-7.2%; n = 223) and 12.1% (11.1-13.2; n = 427). Among the 427 individuals identified by FPG as "pre-diabetes", 28.6% were classified as diabetes by HbA1c test. The weighted kappa statistic of concordance between HbA1c and FPG was 0.55, with most of the discordance being in the prediabetes group. These data indicate that there is a significant discordance in the diagnosis of diabetes between FPG and HbA1c measurements, and the discordance could have significant impact on clinical practice. FPG appears to underestimate the burden of undiagnosed diabetes.

4D micro-CT using fast prospective gating

NASA Astrophysics Data System (ADS)

Guo, Xiaolian; Johnston, Samuel M.; Qi, Yi; Johnson, G. Allan; Badea, Cristian T.

2012-01-01

Micro-CT is currently used in preclinical studies to provide anatomical information. But, there is also significant interest in using this technology to obtain functional information. We report here a new sampling strategy for 4D micro-CT for functional cardiac and pulmonary imaging. Rapid scanning of free-breathing mice is achieved with fast prospective gating (FPG) implemented on a field programmable gate array. The method entails on-the-fly computation of delays from the R peaks of the ECG signals or the peaks of the respiratory signals for the triggering pulses. Projection images are acquired for all cardiac or respiratory phases at each angle before rotating to the next angle. FPG can deliver the faster scan time of retrospective gating (RG) with the regular angular distribution of conventional prospective gating for cardiac or respiratory gating. Simultaneous cardio-respiratory gating is also possible with FPG in a hybrid retrospective/prospective approach. We have performed phantom experiments to validate the new sampling protocol and compared the results from FPG and RG in cardiac imaging of a mouse. Additionally, we have evaluated the utility of incorporating respiratory information in 4D cardiac micro-CT studies with FPG. A dual-source micro-CT system was used for image acquisition with pulsed x-ray exposures (80 kVp, 100 mA, 10 ms). The cardiac micro-CT protocol involves the use of a liposomal blood pool contrast agent containing 123 mg I ml-1 delivered via a tail vein catheter in a dose of 0.01 ml g-1 body weight. The phantom experiment demonstrates that FPG can distinguish the successive phases of phantom motion with minimal motion blur, and the animal study demonstrates that respiratory FPG can distinguish inspiration and expiration. 4D cardiac micro-CT imaging with FPG provides image quality superior to RG at an isotropic voxel size of 88 µm and 10 ms temporal resolution. The acquisition time for either sampling approach is less than 5 min. The radiation dose associated with the proposed method is in the range of a typical micro-CT dose (256 mGy for the cardiac study). Ignoring respiration does not significantly affect anatomic information in cardiac studies. FPG can deliver short scan times with low-dose 4D micro-CT imaging without sacrificing image quality. FPG can be applied in high-throughput longitudinal studies in a wide range of applications, including drug safety and cardiopulmonary phenotyping.

Radioprotective effects of honeybee venom (Apis mellifera) against 915-MHz microwave radiation-induced DNA damage in wistar rat lymphocytes: in vitro study.

PubMed

Gajski, Goran; Garaj-Vrhovac, Vera

2009-01-01

The aim of this study is to investigate the radioprotective effect of bee venom against DNA damage induced by 915-MHz microwave radiation (specific absorption rate of 0.6 W/kg) in Wistar rats. Whole blood lymphocytes of Wistar rats are treated with 1 microg/mL bee venom 4 hours prior to and immediately before irradiation. Standard and formamidopyrimidine-DNA glycosylase (Fpg)-modified comet assays are used to assess basal and oxidative DNA damage produced by reactive oxygen species. Bee venom shows a decrease in DNA damage compared with irradiated samples. Parameters of Fpg-modified comet assay are statistically different from controls, making this assay more sensitive and suggesting that oxidative stress is a possible mechanism of DNA damage induction. Bee venom is demonstrated to have a radioprotective effect against basal and oxidative DNA damage. Furthermore, bee venom is not genotoxic and does not produce oxidative damage in the low concentrations used in this study.

Change in fasting plasma glucose and incident type 2 diabetes mellitus: results from a prospective cohort study.

PubMed

Mozaffary, Amirhossein; Asgari, Samaneh; Tohidi, Maryam; Kazempour-Ardebili, Sara; Azizi, Fereidoun; Hadaegh, Farzad

2016-05-23

To investigate the association between changes in fasting plasma glucose (FPG) values and incident type 2 diabetes (T2D) in a cohort of the Iranian population. Prospective cohort study. This study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) to investigate the association between change in FPG between baseline examination (1999-2001) and the second visit (2002-2005) with incident T2D. A total of 3981 non-diabetic participants aged ≥20 years. T2D was defined if the participant was using antidiabetic drugs or if FPG was ≥7 mmol/L or if the 2 h post-challenge plasma glucose (2-hPCG) was ≥11.1 mmol/L. During a median follow-up of 6.17 years, after the second examination, 288 new cases of T2D were identified. In a multivariate Cox proportional hazard analysis using age as timescale, we presented a simple model including FPG change (HR 1.19, 95% CI 1.07 to 1.33) and baseline waist circumference (WC) (HR 1.004, 95% CI 1.001 to 1.008) with a discriminative power (C-index) of 72%. Furthermore, we showed that the highest quartile of FPG change enhanced the T2D risk to 1.65 (95% CI 1.2 to 2.27) compared with the lowest quartile (p for trend=0.004).The independent risk of FPG change resisted further adjustment with 2-hPCG change. Adding the 2-hPCG change only slightly increased the discriminative power of the model including FPG change and baseline value of WC (0.73% vs 0.72%). After the study population had been limited to those with normal fasting glucose/normal glucose tolerance, FPG change remained an independent predictor (HR 1.57, 95% CI 1.31 to 1.88). Two measurements of FPG obtained about 3 years apart can help to identify populations at risk of incident T2D independently of important traditional risk factors and their changes, including 2-hPCG change. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Evaluation of safety and efficacy of a fixed olmesartan/amlodipine combination therapy compared to single monotherapies.

PubMed

Derosa, Giuseppe; Cicero, Arrigo Francesco Giuseppe; Carbone, Anna; Querci, Fabrizio; Fogari, Elena; D'Angelo, Angela; Maffioli, Pamela

2013-09-01

Hypertension is known to be one of the main risk factors for cardiovascular disease. To evaluate the safety and efficacy of a fixed olmesartan/amlodipine (Olme/Amlo) combination in improving blood pressure control, lipid profile, insulin sensitivity and some inflammatory and insulin resistance markers. Two hundred and seventy-six hypertensive patients were randomly assigned to olmesartan 20 mg, amlodipine 10 mg or a single pill containing an Olme/Amlo combination 20/5 mg for 12 months. We evaluated after 6 and 12 months: body weight, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP, respectively), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, vaspin, visfatin, interleukins 8 and 10 (IL-8 and IL-10, respectively). Patients also underwent an euglycemic, hyperinsulinemic clamp. Olme/Amlo combination was more effective in decreasing SBP, and DPB compared to single monotherapies after 12 months. Olme/Amlo combination, but not amlodipine, decreased FPG after 12 months. FPI and HOMA index were decreased, and M value increased by Olme/Amlo combination compared to olmesartan monotherapy, and to amlodipine monotherapy. Olme/Amlo significantly decreased IL-8 and IL-10 better than each monotherapy. Olme/Amlo single pill combination can be a safe and effective option to reduce blood pressure, improve insulin sensitivity and decrease inflammatory markers.

New Fpg probe chemistry for direct detection of recombinase polymerase amplification on lateral flow strips.

PubMed

Powell, Michael L; Bowler, Frank R; Martinez, Aurore J; Greenwood, Catherine J; Armes, Niall; Piepenburg, Olaf

2018-02-15

Rapid, cost-effective and sensitive detection of nucleic acids has the ability to improve upon current practices employed for pathogen detection in diagnosis of infectious disease and food testing. Furthermore, if assay complexity can be reduced, nucleic acid amplification tests could be deployed in resource-limited and home use scenarios. In this study, we developed a novel Fpg (Formamidopyrimidine DNA glycosylase) probe chemistry, which allows lateral flow detection of amplification in undiluted recombinase polymerase amplification (RPA) reactions. The prototype nucleic acid lateral flow chemistry was applied to a human genomic target (rs1207445), Campylobacter jejuni 16S rDNA and two genetic markers of the important food pathogen E. coli O157:H7. All four assays have an analytical sensitivity between 10 and 100 copies DNA per amplification. Furthermore, the assay is performed with fewer hands-on steps than using the current RPA Nfo lateral flow method as dilution of amplicon is not required for lateral flow analysis. Due to the simplicity of the workflow, we believe that the lateral flow chemistry for direct detection could be readily adapted to a cost-effective single-use consumable, ideal for use in non-laboratory settings. Copyright © 2017. Published by Elsevier Inc.

Elevated glucose concentrations during an oral glucose tolerance test are associated with the presence of metabolic syndrome in childhood obesity.

PubMed

Sabin, M A; Hunt, L P; Ford, A L; Werther, G A; Crowne, E C; Shield, J P H

2008-03-01

To investigate whether changes in glucose concentrations during an OGTT in obese children reflect the presence of peripheral insulin resistance and/or cardiovascular risk factors more closely than single measurements of fasting plasma glucose (FPG). One hundred and twenty-two obese children attending our Paediatric Obesity Service underwent formal OGTTs, following the measurement of blood pressure and fasting levels of insulin, glucose and lipid profiles in the majority. Fasting insulin was used as a surrogate measure of insulin sensitivity. Three different child-specific definitions for metabolic syndrome were used to identify clustering of cardiovascular risk factors in 65 of these children. In the whole group, 10.7% had IGT but changes in glucose during the OGTT were not influenced by age, sex, pubertal status or raw (or age- and sex-adjusted) body mass index (BMI). During the OGTT, FPG, glucose at 60 min and area under the glucose curve correlated highly with fasting insulin. Children with metabolic syndrome (defined using any of three definitions) had comparable FPG levels to those without metabolic syndrome, but they demonstrated significantly elevated glucose levels at 60 min. On sub-group analysis, obese children with normal carbohydrate metabolism were significantly more likely to have a 1 h glucose level > or = 7.8 mmol/l if they had metabolic syndrome (P = 0.026). These data suggest that an elevated 1 h post-load glucose measurement is seen in obese children who have a coexistent clustering of cardiovascular risk factors.

Incompatibility between fasting and postprandial plasma glucose in patients with Cushing's syndrome.

PubMed

Otsuki, Michio; Kitamura, Tetsuhiro; Tamada, Daisuke; Tabuchi, Yukiko; Mukai, Kosuke; Morita, Shinya; Kasayama, Soji; Shimomura, Iichiro; Koga, Masafumi

2016-11-30

It is shown that glucocorticoids have discordant effects on plasma glucose concentration through their effects on hepatic glycogen deposition, gluconeogenesis and peripheral insulin resistance. Cushing's syndrome caused by cortisol overproduction is frequently accompanied with diabetes mellitus, but fasting plasma glucose (FPG) and post-glucose load plasma glucose levels are not examined in patients with Cushing's syndrome. The aim of this study was to investigate FPG, HbA1c and oral glucose tolerance test (OGTT) 2-h PG and their relationship in patients with Cushing's syndrome, in comparison with control subjects. Sixteen patients with Cushing's syndrome (ACTH-dependent 31%, ACTH-independent 69% and diabetes mellitus 50%) and 64 controls (32 patients with type 2 diabetes mellitus and 32 non-diabetic subjects matched for age, sex and BMI) were enrolled in this study. HbA1c and FPG in the patients with Cushing's syndrome were not different from the controls, whereas the FPG/HbA1c ratio was significantly lower in the patients with Cushing's syndrome than the controls. OGTT 2-h PG was significantly higher in the non-diabetic patients with Cushing's syndrome than the non-diabetic controls, while HbA1c was not different between both groups and FPG was significantly lower in the patients with Cushing's syndrome than the controls. HOMA-β but not HOMA-R was significantly higher in the patients with Cushing's syndrome than the controls. In conclusion, FPG was rather lower in the patients with Cushing's syndrome than the controls. Postprandial PG or post-glucose loaded PG, but not FPG, is useful to evaluate the abnormality of glucose metabolism in patients with Cushing's syndrome.

Early pregnancy fasting plasma glucose and lipid concentrations in pregnancy and association to offspring size: a retrospective cohort study.

PubMed

Liu, Bin; Geng, Huizhen; Yang, Juan; Zhang, Ying; Deng, Langhui; Chen, Weiqing; Wang, Zilian

2016-03-17

Hyperlipidemia and high fasting plasma glucose levels at the first prenatal visit (First Visit FPG) are both related to gestational diabetes mellitus, maternal obesity/overweight and fetal overgrowth. The purpose of the present study is to investigate the correlation between First Visit FPG and lipid concentrations, and their potential association with offspring size at delivery. Pregnant women that received regular prenatal care and delivered in our center in 2013 were recruited for the study. Fasting plasma glucose levels were tested at the first prenatal visit (First Visit FPG) and prior to delivery (Before Delivery FPG). HbA1c and lipid profiles were examined at the time of OGTT test. Maternal and neonatal clinical data were collected for analysis. Data was analyzed by independent sample t test, Pearson correlation, and Chi-square test, followed by partial correlation and multiple linear regression analyses to confirm association. Statistical significance level was α =0.05. Analyses were based on 1546 mother-baby pairs. First Visit FPG was not correlated with any lipid parameters after adjusting for maternal pregravid BMI, maternal age and gestational age at First Visit FPG. HbA1c was positively correlated with triglyceride and Apolipoprotein B in the whole cohort and in the NGT group after adjusting for maternal age and maternal BMI at OGTT test. Multiple linear regression analyses showed neonatal birth weight, head circumference and shoulder circumference were all associated with First Visit FPG and triglyceride levels. Fasting plasma glucose at first prenatal visit is not associated with lipid concentrations in mid-pregnancy, but may influence fetal growth together with triglyceride concentration.

Association of urinary metal profiles with altered glucose levels and diabetes risk: a population-based study in China.

PubMed

Feng, Wei; Cui, Xiuqing; Liu, Bing; Liu, Chuanyao; Xiao, Yang; Lu, Wei; Guo, Huan; He, Meian; Zhang, Xiaomin; Yuan, Jing; Chen, Weihong; Wu, Tangchun

2015-01-01

Elevated heavy metals and fasting plasma glucose (FPG) levels were both associated with increased risk of cardiovascular diseases. However, studies on the associations of heavy metals and essential elements with altered FPG and diabetes risk were limited or conflicting. The objective of this study was to evaluate the potential associations of heavy metals and essential trace elements with FPG and diabetes risk among general Chinese population. We conducted a cross-sectional study to investigate the associations of urinary concentrations of 23 metals with FPG, impaired fasting glucose (IFG) and diabetes among 2242 community-based Chinese adults in Wuhan. We used the false discovery rate (FDR) method to correct for multiple hypothesis tests. After adjusting for potential confounders, urinary aluminum, titanium, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, antimony, barium, tungsten and lead were associated with altered FPG, IFG or diabetes risk (all P< 0.05); arsenic was only dose-dependently related to diabetes (P< 0.05). After additional adjustment for multiple testing, titanium, copper, zinc, selenium, rubidium, tungsten and lead were still significantly associated with one or more outcomes (all FDR-adjusted P< 0.05). Our results suggest that multiple metals in urine are associated with FPG, IFG or diabetes risk. Because the cross-sectional design precludes inferences about causality, further prospective studies are warranted to validate our findings.

Efficacy of Chinese patent medicine Tian Gui Capsule in patients with polycystic ovary syndrome: a randomized controlled trial.

PubMed

Kuek, Susuana; Wang, Wen-jun; Gui, Sui-qi

2011-09-01

Polycystic ovary syndrome (PCOS) is a complex hormonal disorder and one of the most common reproductive endocrinology abnormalities in women. Recently, many studies have been conducted assessing Chinese herbal medicine as an alternative treatment for women with PCOS, it is, therefore, worthwhile to analyze and observe the curative effects of traditional Chinese medicine treatment in PCOS. To evaluate the efficacy of the Chinese patent medicine Tian Gui Capsule, in women with PCOS and compare its effects with metformin and ethinyl estradiol plus cyproterone acetate (Diane-35). A total of 47 PCOS outpatients from the Obstetrics and Gynecology Hospital of Fudan University were randomly divided into 3 groups. Patients in group A (n=19) were given Tian Gui Capsule, patients in group B (n=17) were given metformin, and patients in group C (n=11) were given Diane-35. The 3 groups of patients were treated for 3 months. Serum testosterone (T), sex hormone binding globulin (SHBG) and dehydroepiandrosterone sulfate (DHEA-S) levels, free androgen index (FAI), fasting blood glucose (FPG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitive index (ISI) and left and right ovary volumes of the 3 groups were evaluated before and after treatment . After 3 months of treatment, when compared with before treatment data, group A patients showed decreased serum T and SHBG levels, FAI, FINS, and left and right ovary volumes (P<0.05), and increased serum DHEA-S (P<0.05), while the FPG level showed no significant change. Although the level of serum T and FINS among the 3 groups after the treatment were similar, group A demonstrated better results than group B in reducing the FAI and increasing the serum SHBG, but less significant results than group C besides, group B was the only group showed improved insulin sensitivity. Although the level of FPG of the 3 groups after treatment were similar, group C had the most increased FPG. The effects of Tian Gui Capsule on hyperandrogenism are not as significant as Diane-35, but more effective than metformin. The effects of Tian Gui Capsule on hyperinsulinemia are not as significant as metformin but better than Diane-35. Tian Gui Capsule treats PCOS by regulating ovarian functions and reducing blood insulin level without inhibiting the function of the hypothalamic-pituitary-ovarian axis. Further studies with larger sample size are needed to confirm the above results.

DNA glycosylases search for and remove oxidized DNA bases.

PubMed

Wallace, Susan S

2013-12-01

This review article presents, an overview of the DNA glycosylases that recognize oxidized DNA bases using the Fpg/Nei family of DNA glycosylases as models for how structure can inform function. For example, even though human NEIL1 and the plant and fungal orthologs lack the zinc finger shown to be required for binding, DNA crystal structures revealed a "zincless finger" with the same properties. Moreover, the "lesion recognition loop" is not involved in lesion recognition, rather, it stabilizes 8-oxoG in the active site pocket. Unlike the other Fpg/Nei family members, Neil3 lacks two of the three void-filling residues that stabilize the DNA duplex and interact with the opposite strand to the damage which may account for its preference for lesions in single-stranded DNA. Also single-molecule approaches show that DNA glycosylases search for their substrates in a sea of undamaged DNA by using a wedge residue that is inserted into the DNA helix to probe for the presence of damage. Copyright © 2013 Wiley Periodicals, Inc.

Genetic and Functional Assessment of the Role of the rs13431652-A and rs573225-A Alleles in the G6PC2 Promoter That Are Strongly Associated With Elevated Fasting Glucose Levels

PubMed Central

Bouatia-Naji, Nabila; Bonnefond, Amélie; Baerenwald, Devin A.; Marchand, Marion; Bugliani, Marco; Marchetti, Piero; Pattou, François; Printz, Richard L.; Flemming, Brian P.; Umunakwe, Obi C.; Conley, Nicholas L.; Vaxillaire, Martine; Lantieri, Olivier; Balkau, Beverley; Marre, Michel; Lévy-Marchal, Claire; Elliott, Paul; Jarvelin, Marjo-Riitta; Meyre, David; Dina, Christian; Oeser, James K.; Froguel, Philippe; O'Brien, Richard M.

2010-01-01

OBJECTIVE Genome-wide association studies have identified a single nucleotide polymorphism (SNP), rs560887, located in a G6PC2 intron that is highly correlated with variations in fasting plasma glucose (FPG). G6PC2 encodes an islet-specific glucose-6-phosphatase catalytic subunit. This study examines the contribution of two G6PC2 promoter SNPs, rs13431652 and rs573225, to the association signal. RESEARCH DESIGN AND METHODS We genotyped 9,532 normal FPG participants (FPG <6.1 mmol/l) for three G6PC2 SNPs, rs13431652 (distal promoter), rs573225 (proximal promoter), rs560887 (3rd intron). We used regression analyses adjusted for age, sex, and BMI to assess the association with FPG and haplotype analyses to assess comparative SNP contributions. Fusion gene and gel retardation analyses characterized the effect of rs13431652 and rs573225 on G6PC2 promoter activity and transcription factor binding. RESULTS Genetic analyses provide evidence for a strong contribution of the promoter SNPs to FPG variability at the G6PC2 locus (rs13431652: β = 0.075, P = 3.6 × 10−35; rs573225 β = 0.073 P = 3.6 × 10−34), in addition to rs560887 (β = 0.071, P = 1.2 × 10−31). The rs13431652-A and rs573225-A alleles promote increased NF-Y and Foxa2 binding, respectively. The rs13431652-A allele is associated with increased FPG and elevated promoter activity, consistent with the function of G6PC2 in pancreatic islets. In contrast, the rs573225-A allele is associated with elevated FPG but reduced promoter activity. CONCLUSIONS Genetic and in situ functional data support a potential role for rs13431652, but not rs573225, as a causative SNP linking G6PC2 to variations in FPG, though a causative role for rs573225 in vivo cannot be ruled out. PMID:20622168

Prevalence and phenotype of diabetes and prediabetes using fasting glucose vs HbA1c in a Caribbean population.

PubMed

Unwin, Nigel; Howitt, Christina; Rose, Angela Mc; Samuels, T Alafia; Hennis, Anselm Jm; Hambleton, Ian R

2017-12-01

Both fasting plasma glucose (FPG) and HbA1c are recommended for the diagnosis of diabetes and prediabetes by the American Diabetes Association (ADA), and for diabetes by the World Health Organization. The ADA guidance is influential on clinical practice in many developing countries, including in the Caribbean and Latin America. We aimed to compare the prevalence and characteristics of individuals identified as having diabetes and prediabetes by FPG and HbA1c in a predominantly African ancestry Caribbean population. A representative population-based sample of 1234 adults (≥25 years of age) resident in Barbados was recruited. Standard methods with appropriate quality control were used to collect data on height, weight, blood pressure, fasting lipids and history of diagnosed diabetes, and to measure fasting glucose and HbA1c. Those with previously diagnosed diabetes (n = 192) were excluded from the analyses. Diabetes was defined as: FPG ≥7.0 mmol/L or HbA1c ≥6.5%; prediabetes as: FPG ≥5.6 to <7mmol/L or HbA1c ≥5.7 to <6.5%. Complete data were available on 939 participants without previously diagnosed diabetes. The prevalence of undiagnosed diabetes was higher, but not significantly so, by HbA1c (4.9%, 95% CI 3.5, 6.8) vs FPG (3.5%, 2.4, 5.1). Overall 79 individuals had diabetes by either measure, but only 21 on both. The prevalence of prediabetes was higher by HbA1c compared to FPG: 41.7% (37.9, 45.6) vs 15.0% (12.8, 17.5). Overall 558 individuals had prediabetes by either measure, but only 107 on both. HbA1c, but not FPG, was significantly higher in women than men; and FPG, but not HbA1c, was significantly associated with raised triglycerides and low HDL cholesterol. The agreement between FPG and HbA1c defined hyperglycaemia is poor. In addition, there are some differences in the phenotype of those identified, and HbA1c gives a much higher prevalence of prediabetes. The routine use of HbA1c for screening and diagnosis in this population would have major implications for clinical and public health policies and resources. Given the lack of robust evidence, particularly for prediabetes, on whether intervention in the individuals identified would improve outcomes, this approach to screening and diagnosis cannot be currently recommended for this population.

Prevalence and phenotype of diabetes and prediabetes using fasting glucose vs HbA1c in a Caribbean population

PubMed Central

Unwin, Nigel; Howitt, Christina; Rose, Angela MC; Samuels, T Alafia; Hennis, Anselm JM; Hambleton, Ian R

2017-01-01

Background Both fasting plasma glucose (FPG) and HbA1c are recommended for the diagnosis of diabetes and prediabetes by the American Diabetes Association (ADA), and for diabetes by the World Health Organization. The ADA guidance is influential on clinical practice in many developing countries, including in the Caribbean and Latin America. We aimed to compare the prevalence and characteristics of individuals identified as having diabetes and prediabetes by FPG and HbA1c in a predominantly African ancestry Caribbean population. Methods A representative population–based sample of 1234 adults (≥25 years of age) resident in Barbados was recruited. Standard methods with appropriate quality control were used to collect data on height, weight, blood pressure, fasting lipids and history of diagnosed diabetes, and to measure fasting glucose and HbA1c. Those with previously diagnosed diabetes (n = 192) were excluded from the analyses. Diabetes was defined as: FPG ≥7.0 mmol/L or HbA1c ≥6.5%; prediabetes as: FPG ≥5.6 to <7mmol/L or HbA1c ≥5.7 to <6.5%. Results Complete data were available on 939 participants without previously diagnosed diabetes. The prevalence of undiagnosed diabetes was higher, but not significantly so, by HbA1c (4.9%, 95% CI 3.5, 6.8) vs FPG (3.5%, 2.4, 5.1). Overall 79 individuals had diabetes by either measure, but only 21 on both. The prevalence of prediabetes was higher by HbA1c compared to FPG: 41.7% (37.9, 45.6) vs 15.0% (12.8, 17.5). Overall 558 individuals had prediabetes by either measure, but only 107 on both. HbA1c, but not FPG, was significantly higher in women than men; and FPG, but not HbA1c, was significantly associated with raised triglycerides and low HDL cholesterol. Conclusion The agreement between FPG and HbA1c defined hyperglycaemia is poor. In addition, there are some differences in the phenotype of those identified, and HbA1c gives a much higher prevalence of prediabetes. The routine use of HbA1c for screening and diagnosis in this population would have major implications for clinical and public health policies and resources. Given the lack of robust evidence, particularly for prediabetes, on whether intervention in the individuals identified would improve outcomes, this approach to screening and diagnosis cannot be currently recommended for this population. PMID:28959440

[Associations of insulin resistance and pancreatic beta-cell function with plasma glucose level in type 2 diabetes].

PubMed

Nian, Xiaoping; Sun, Gaisheng; Dou, Chunmei; Hou, Hongbo; Fan, Xiuping; Yu, Hongmei; Ma, Ling; He, Bingxian

2002-06-10

To investigate the influence of insulin resistance and pancreatic beta-cell function on plasma glucose level in type 2 diabetes so as to provide theoretical basis for reasonable selection of hypoglycemic agents. The plasma non-specific insulin (NSINS), true insulin (TI) and glucose in eight-one type 2 diabetics, 38 males and 43 females, with a mean age of 53 years, were examined 0, 30, 60 and 120 minutes after they had 75 grams of instant noodles. The patients were divided into two groups according to their fasting plasma glucose (FPG): group A (FPG < 8.89 mmol/L) and group B (FPG> = 8.89 mmol/L). The insulin resistance was evaluated by HOMA-IR, the beta-cell function was evaluated by HOMA-beta formula and the formula deltaI(30)/deltaG(30) = (deltaI(30)-deltaI(0))/(deltaG(30)-deltaG(0)). The insulin area under curve (INSAUC) was evaluated by the formula INSAUC=FINS/2+INS(30)+INS(60)+INS(120)/2. The mean FPG was 6.23 mmol/L in group A and 12.6 mmol/L in group B. PG2H was 11.7 mmol/L in group A and 19.2 mmol/L in group B. The TI levels in group B at 0, 30, 60, 120 min during standard meal test were significantly higher than those in group A: 6.15 +/- 1.06 vs 4.77 +/- 1.06, 9.76 +/- 1.1 vs 5.88 +/- 1.1,14.68 +/- 1.11 vs 6.87 +/- 1.1 and 17.13 +/- 1.12 vs 8.0 +/- 1.1 microU/dl (all P< 0.01). The NSINS showed the same trend. The insulin resistance in group B was 1.5 times that in group A. With the insulin resistance adjusted, the beta cell function in group A was 5 to 6 times that in group B. The INSAUC in group A was 1.66 times larger than that in group B, especially the INSAUC for true insulin (2 times larger). The contribution of insulin resistance and beta cell function to PG2H was half by half in group A and 1:8 in group B. beta cell function calculated by insulin (Homa-beta) explained 41% of the plasma glucose changes in group A and 54% of the plasma glucose changes in group B. The contribution of insulin deficiency to plasma glocose was 3.3.times that of insulin resistance in group A and was 9.5 times that of insulin resistance in group B. Insulin sensitivity explained 12% of the plasma glucose changes in group A, and only 5.7% of the plasma glucose changes in group B. Diabetics with FPG greater than 8.89 mmol/L have both higher insulin resistance and poorer beta-cell function, their hyperglycemia being caused mainly by beta-cell failure, The combined use of insulin sensitizer and insulin or insulintropic agents during the initial stage of treatment is effective.

Relationship between Hb and HbA1c in Japanese adults: an analysis of the 2009 Japan Society of Ningen Dock database.

PubMed

Takahashi, Eiko; Moriyama, Kengo; Yamakado, Minoru

2014-06-01

We investigated the effect of Hb on HbA1c levels in 265,427 Japanese individuals. The divergence between fasting plasma glucose (FPG) and HbA1c levels increased with lower Hb, resulting in HbA1c levels that were higher in relation to than the FPG levels. Similarly, the correlation between FPG and HbA1c levels, stratified by Hb, weakened as Hb decreased. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Is Xanthine oxidase activity in polycystic ovary syndrome associated with inflammatory and cardiovascular risk factors?

PubMed

Isık, Hatice; Aynıoglu, Oner; Tımur, Hakan; Sahbaz, Ahmet; Harma, Muge; Can, Murat; Guven, Berrak; Alptekin, Husnu; Kokturk, Furuzan

2016-08-01

The aim of this study is to examine women with polycystic ovary syndrome (PCOS) to determine the relationship between xanthine oxidase (XO) and oxidative stress, inflammatory status, and various clinical and biochemical parameters. In this cross-sectional study a total of 83 women including 45 PCOS patients and 38 healthy women were enrolled. We collected blood samples for XO and superoxide dismutase (SOD) activity, hormone levels, cholesterol values, and inflammatory markers. Body mass index (BMI) , waist-to-hip ratio (WHR), and blood pressure were assessed. Blood samples were taken for hormonal levels, cholesterol levels, fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostatic model assessment-insulin resistance (HOMA-IR) index, quantitative insulin sensitivity check index (QUICKI), C-reactive protein (CRP), white blood cell and neutrophil counts, XO and SOD activities. The basal hormone levels, triglyceride (TG) levels, TG/HDL-C (high density lipoprotein-cholesterol) ratios FPG, FPI and HOMA-IR levels were higher in PCOS patients compared to controls (p<0.05). Platelet and plateletcrit (PCT) values, CRP, and XO activity were significantly increased, however SOD activity was decreased in PCOS patients (p<0.001). XO activity was positively correlated with LH/FSH and TG/HDL ratios, CRP, PCT, FPG, FPI, and HOMA-IR, and negatively correlated with QUICKI levels. In conclusion, XO is a useful marker to assess oxidative stress in PCOS patients. Positive correlations between XO and inflammatory markers and cardiovascular disease risk factors suggest that XO plays an important role in the pathogenesis of PCOS and its metabolic complications. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Changes in body weight are significantly associated with changes in fasting plasma glucose and HDL cholesterol in Japanese men without abdominal obesity (waist circumference < 85 cm).

PubMed

Oda, Eiji; Kawai, Ryu

2011-06-01

The aims are to examine whether changes in body weight (dBW) are associated with changes in cardiovascular risk factors in Japanese men without abdominal obesity (waist circumference (WC) < 85 cm) and which anthropometric index, dBW or changes in WC (dWC), is more strongly associated with changes in cardiovascular risk factors in men without abdominal obesity. It is a retrospective study in 692 Japanese men without abdominal obesity who took annual health screening tests consecutively over one year. Standardized linear regression coefficients (SRCs) of dBW and dWC were calculated for changes in systolic blood pressure (dSBP), diastolic blood pressure (dDBP), fasting plasma glucose (dFPG), triglycerides (dTG), HDL cholesterol (dHDL), and high-sensitivity C-reactive protein (dCRP). The SRCs of dBW for dFPG and dHDL were significant in all men and in men with each risk factor corresponding to the component of metabolic syndrome (MetS). The SRCs of dWC for dTG and dCRP were significant in all men but not in men with each risk factor corresponding to the MetS component. In conclusions, dBW were significantly associated with dFPG and dHDL in Japanese men without abdominal obesity. Therefore, abdominal obesity should not be considered as a necessary component of MetS in Japanese men. dBW may be more useful than dWC as a marker of changes in cardiovascular risk factors in lifestyle intervention programs.

HbA1c Alone Is a Poor Indicator of Cardiometabolic Risk in Middle-Aged Subjects with Pre-Diabetes but Is Suitable for Type 2 Diabetes Diagnosis: A Cross-Sectional Study

PubMed Central

Millar, Seán R.; Perry, Ivan J.; Phillips, Catherine M.

2015-01-01

Objectives Glycated haemoglobin A1c (HbA1c) measurement is recommended as an alternative to fasting plasma glucose (FPG) for the diagnosis of pre-diabetes and type 2 diabetes. However, evidence suggests discordance between HbA1c and FPG. In this study we examine a range of metabolic risk features, pro-inflammatory cytokines, acute-phase response proteins, coagulation factors and white blood cell counts to determine which assay more accurately identifies individuals at increased cardiometabolic risk. Materials and Methods This was a cross-sectional study involving a random sample of 2,047 men and women aged 46-73 years. Binary and multinomial logistic regression were employed to examine risk feature associations with pre-diabetes [either HbA1c levels 5.7-6.4% (39-46 mmol/mol) or impaired FPG levels 5.6-6.9 mmol/l] and type 2 diabetes [either HbA1c levels >6.5% (>48 mmol/mol) or FPG levels >7.0 mmol/l]. Receiver operating characteristic curve analysis was used to evaluate the ability of HbA1c to discriminate pre-diabetes and diabetes defined by FPG. Results Stronger associations with diabetes-related phenotypes were observed in pre-diabetic subjects diagnosed by FPG compared to those detected by HbA1c. Individuals with type 2 diabetes exhibited cardiometabolic profiles that were broadly similar according to diagnosis by either assay. Pre-diabetic participants classified by both assays displayed a more pro-inflammatory, pro-atherogenic, hypertensive and insulin resistant profile. Odds ratios of having three or more metabolic syndrome features were also noticeably increased (OR: 4.0, 95% CI: 2.8-5.8) when compared to subjects diagnosed by either HbA1c (OR: 1.4, 95% CI: 1.2-1.8) or FPG (OR: 3.0, 95% CI: 1.7-5.1) separately. Conclusions In middle-aged Caucasian-Europeans, HbA1c alone is a poor indicator of cardiometabolic risk but is suitable for diagnosing diabetes. Combined use of HbA1c and FPG may be of additional benefit for detecting individuals at highest odds of type 2 diabetes development. PMID:26266799

Dysregulation of glucose metabolism even in Chinese PCOS women with normal glucose tolerance.

PubMed

Li, Weiping; Li, Qifu

2012-01-01

To clarify the necessity of improving glucose metabolism in polycystic ovary syndrome (PCOS) women as early as possible, 111 PCOS women with normal glucose tolerance and 92 healthy age-matched controls were recruited to investigate glucose levels distribution, insulin sensitivity and β cell function. 91 PCOS women and 33 controls underwent hyperinsulinemic-euglycemic clamp to assess their insulin sensitivity, which was expressed as M value. β cell function was estimated by homeostatic model assessment (HOMA)-β index after adjusting insulin sensitivity (HOMA-βad index). Compared with lean controls, lean PCOS women had similar fasting plasma glucose (FPG), higher postprandial plasma glucose (PPG) (6.03±1.05 vs. 5.44±0.97 mmol/L, P<0.05), lower M value but similar HOMA-βad index, while overweight/obese PCOS women had higher levels of both FPG (5.24±0.58 vs. 4.90±0.39, P<0.05) and PPG (6.15±0.84 vs. 5.44±0.97 mmol/L, P<0.05), and lower levels of both M value and HOMA-βad index. Linear regression and ROC analysis found BMI was independently associated with M value and HOMA-βad index in PCOS women separately, and the cutoff of BMI indicating impaired β cell function of PCOS women was 25.545kg/m². In conclusion, insulin resistance and dysregulation of glucose metabolism were common in Chinese PCOS women with normal glucose tolerance. BMI ≥ 25.545kg/m² indicated impaired β cell function in PCOS women with normal glucose tolerance.

The "metabolic syndrome" is less useful than random plasma glucose to screen for glucose intolerance.

PubMed

El Bassuoni, Eman A; Ziemer, David C; Kolm, Paul; Rhee, Mary K; Vaccarino, Viola; Tsui, Circe W; Kaufman, Jack M; Osinski, G Eileen; Koch, David D; Narayan, K M Venkat; Weintraub, William S; Phillips, Lawrence S

2008-09-01

To compare the utility of metabolic syndrome (MetS) to random plasma glucose (RPG) in identifying people with diabetes or prediabetes. RPG was measured and an OGTT was performed in 1155 adults. Test performance was measured by area under the receiver-operating-characteristic curve (AROC). Diabetes was found in 5.1% and prediabetes in 20.0%. AROC for MetS with fasting plasma glucose (FPG) was 0.80 to detect diabetes, and 0.76 for diabetes or prediabetes--similar to RPG alone (0.82 and 0.72). However, the AROC for MetS excluding fasting plasma glucose was lower: 0.69 for diabetes (p<0.01 vs. both RPG and MetS with FPG), and 0.69 for diabetes or prediabetes. AROCs for MetS with FPG and RPG were comparable and higher for recognizing diabetes in blacks vs. whites, and females vs. males. MetS with FPG was superior to RPG for identifying diabetes only in subjects with age <40 or BMI <25. MetS features can be used to identify risk of diabetes, but predictive usefulness is driven largely by FPG. Overall, to identify diabetes or prediabetes in blacks and whites with varying age and BMI, MetS is no better than RPG--a more convenient and less expensive test.

Elevated HbA1c and Fasting Plasma Glucose in Predicting Diabetes Incidence Among Older Adults

PubMed Central

Lipska, Kasia J.; Inzucchi, Silvio E.; Van Ness, Peter H.; Gill, Thomas M.; Kanaya, Alka; Strotmeyer, Elsa S.; Koster, Annemarie; Johnson, Karen C.; Goodpaster, Bret H.; Harris, Tamara; De Rekeneire, Nathalie

2013-01-01

OBJECTIVE To determine which measures—impaired fasting glucose (IFG), elevated HbA1c, or both—best predict incident diabetes in older adults. RESEARCH DESIGN AND METHODS From the Health, Aging, and Body Composition study, we selected individuals without diabetes, and we defined IFG (100–125 mg/dL) and elevated HbA1c (5.7–6.4%) per American Diabetes Association guidelines. Incident diabetes was based on self-report, use of antihyperglycemic medicines, or HbA1c ≥6.5% during 7 years of follow-up. Logistic regression analyses were adjusted for age, sex, race, site, BMI, smoking, blood pressure, and physical activity. Discrimination and calibration were assessed for models with IFG and with both IFG and elevated HbA1c. RESULTS Among 1,690 adults (mean age 76.5, 46% men, 32% black), 183 (10.8%) developed diabetes over 7 years. Adjusted odds ratios of diabetes were 6.2 (95% CI 4.4–8.8) in those with IFG (versus those with fasting plasma glucose [FPG] <100 mg/dL) and 11.3 (7.8–16.4) in those with elevated HbA1c (versus those with HbA1c <5.7%). When FPG and HbA1c were considered together, odds ratios were 3.5 (1.9–6.3) in those with IFG only, 8.0 (4.8–13.2) in those with elevated HbA1c only, and 26.2 (16.3–42.1) in those with both IFG and elevated HbA1c (versus those with normal FPG and HbA1c). Addition of elevated HbA1c to the model with IFG resulted in improved discrimination and calibration. CONCLUSIONS Older adults with both IFG and elevated HbA1c have a substantially increased odds of developing diabetes over 7 years. Combined screening with FPG and HbA1c may identify older adults at very high risk for diabetes. PMID:24135387

Low pulmonary function in individuals with impaired fasting glucose: the 2007-2009 Korea national health and nutrition examination survey.

PubMed

Lee, Yun Jeong; Kim, Na Kyung; Yang, Ju Yean; Noh, Jung Hyun; Lee, Sung-Soon; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Dong-Jun

2013-01-01

To investigate the association between fasting plasma glucose level and pulmonary function. Nutritional information, pulmonary function data, and laboratory test data from 9,223 subjects from the fourth Korea National Health and Nutrition Examination Survey were examined. The participants were divided into five groups according to fasting plasma glucose (FPG) level: normal fasting glucose (NFG)1, FPG <90 mg/dl; NFG2, FPG 90-99 mg/dl; impaired fasting glucose (IFG)1: FPG 100-109 mg/dl; IFG2, FPG 110-125 mg/dl; and diabetes, FPG ≥126 mg/dl and/or current anti-diabetes medications. After adjustment for several variables, the percentage of predicted forced vital capacity(FVC%) decreased with increasing fasting plasma glucose level in both sexes[men: (mean ± SEM) 92.0±0.3 in NFG1; 91.9±0.3 in NFG2; 92.0±0.4 in IFG1; 90.2±0.7 in IFG2; and 89.9±0.5 in diabetes, P = 0.004; women: 93.7±0.3 in NFG1; 93.7±0.3 in NFG2; 93.1±0.5 in IFG1; 91.1±0.9 in IFG2; and 90.7±0.6 in diabetes, P<0.001]. A logistic regression analysis found that IFG2 and diabetes were independently associated with the lowest quintile of predicted FVC% (IFG2: odds ratio [95%CI], 1.50 [1.18-1.89], P = 0.001; diabetes: 1.56 [1.30-1.88], P<0.001) using NFG1 as a control. The current data suggest that forced vital capacity may begin to decrease in the higher range of IFG.

Refractive errors in patients with newly diagnosed diabetes mellitus.

PubMed

Yarbağ, Abdülhekim; Yazar, Hayrullah; Akdoğan, Mehmet; Pekgör, Ahmet; Kaleli, Suleyman

2015-01-01

Diabetes mellitus is a complex metabolic disorder that involves the small blood vessels, often causing widespread damage to tissues, including the eyes' optic refractive error. In patients with newly diagnosed diabetes mellitus who have unstable blood glucose levels, refraction may be incorrect. We aimed to investigate refraction in patients who were recently diagnosed with diabetes and treated at our centre. This prospective study was performed from February 2013 to January 2014. Patients were diagnosed with diabetes mellitus using laboratory biochemical tests and clinical examination. Venous fasting plasma glucose (fpg) levels were measured along with refractive errors. Two measurements were taken: initially and after four weeks. The last difference between the initial and end refractive measurements were evaluated. Our patients were 100 males and 30 females who had been newly diagnosed with type II DM. The refractive and fpg levels were measured twice in all patients. The average values of the initial measurements were as follows: fpg level, 415 mg/dl; average refractive value, +2.5 D (Dioptres). The average end of period measurements were fpg, 203 mg/dl; average refractive value, +0.75 D. There is a statistically significant difference between after four weeks measurements with initially measurements of fasting plasma glucose (fpg) levels (p<0.05) and there is a statistically significant relationship between changes in fpg changes with glasses ID (p<0.05) and the disappearance of blurred vision (to be greater than 50% success rate) were statistically significant (p<0.05). Also, were detected upon all these results the absence of any age and sex effects (p>0.05). Refractive error is affected in patients with newly diagnosed diabetes mellitus; therefore, plasma glucose levels should be considered in the selection of glasses.

The contribution of Nth and Nei DNA glycosylases to mutagenesis in Mycobacterium smegmatis.

PubMed

Moolla, Nabiela; Goosens, Vivianne J; Kana, Bavesh D; Gordhan, Bhavna G

2014-01-01

The increased prevalence of drug resistant strains of Mycobacterium tuberculosis (Mtb) indicates that significant mutagenesis occurs during tuberculosis disease in humans. DNA damage by host-derived reactive oxygen/nitrogen species is hypothesized to be critical for the mutagenic process in Mtb thus, highlighting an important role for DNA repair enzymes in maintenance of genome fidelity. Formamidopyrimidine (Fpg/MutM/Fapy) and EndonucleaseVIII (Nei) constitute the Fpg/Nei family of DNA glycosylases and together with EndonucleaseIII (Nth) are central to the base excision repair pathway in bacteria. In this study we assess the contribution of Nei and Nth DNA repair enzymes in Mycobacterium smegmatis (Msm), which retains a single nth homologue and duplications of the Fpg (fpg1 and fpg2) and Nei (nei1 and nei2) homologues. Using an Escherichia coli nth deletion mutant, we confirm the functionality of the mycobacterial nth gene in the base excision repair pathway. Msm mutants lacking nei1, nei2 and nth individually or in combination did not display aberrant growth in broth culture. Deletion of nth individually results in increased UV-induced mutagenesis and combinatorial deletion with the nei homologues results in reduced survival under oxidative stress conditions and an increase in spontaneous mutagenesis to rifampicin. Deletion of nth together with the fpg homolgues did not result in any growth/survival defects or changes in mutation rate. Furthermore, no differential emergence of the common rifampicin resistance conferring genotypes were noted. Collectively, these data confirm a role for Nth in base excision repair in mycobacteria and further highlight a novel interplay between the Nth and Nei homologues in spontaneous mutagenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

DNA Glycosylases Search for and Remove Oxidized DNA Bases

PubMed Central

Wallace, Susan S.

2014-01-01

The following mini review summarizes recent research from the Author’s laboratory as presented to the Environmental Mutagen Society in October 2012. It provides an overview of the DNA glycosylases that recognize oxidized DNA bases using the Fpg/Nei family of DNA glycosylases as models for how structure can inform function. For example, even though human NEIL1 and the plant and fungal orthologs lack the zinc finger shown to be required for binding, DNA crystal structures revealed a “zincless finger” with the same properties. Also the “lesion recognition loop” is not involved in lesion recognition rather stabilization of 8-oxoG in the active site pocket. Unlike the other Fpg/Nei family members, Neil3 lacks two of the three void-filling residues that stabilize the duplex and interact with the opposite strand which may account for its preference for lesions in single stranded DNA. We also showed, using single molecule approaches, that DNA glycosylases search for their substrates in a sea of undamaged DNA by using a wedge residue that is inserted into the DNA helix to probe for the presence of damage. PMID:24123395

Size and shape of the associations of glucose, HbA1c, insulin and HOMA-IR with incident type 2 diabetes: the Hoorn Study.

PubMed

Ruijgrok, Carolien; Dekker, Jacqueline M; Beulens, Joline W; Brouwer, Ingeborg A; Coupé, Veerle M H; Heymans, Martijn W; Sijtsma, Femke P C; Mela, David J; Zock, Peter L; Olthof, Margreet R; Alssema, Marjan

2018-01-01

Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA 1c , fasting insulin and HOMA-IR with incident type 2 diabetes mellitus. The study population included 1349 participants aged 50-75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations. After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA 1c , 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA 1c with incident diabetes were non-linear, rising more steeply at higher values. FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA 1c , HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers.

Two-hour post-challenge glucose is a better predictor of adverse outcome after myocardial infarction than fasting or admission glucose in patients without diabetes.

PubMed

Chattopadhyay, Sudipta; George, Anish; John, Joseph; Sathyapalan, Thozhukat

2018-05-01

We evaluate prevalence of new abnormal glucose tolerance (AGT) in post-MI survivors without known diabetes (DM) if guidelines are followed and compare the ability of admission (APG), fasting (FPG) and 2-h post-load plasma glucose (2h-PG) to predict prognosis. A total of 674 patients were followed up for 4 years for incidence of major adverse cardiovascular events (MACE) of cardiovascular death, non-fatal re-infarction or non-haemorrhagic stroke. Ability of models including APG, FPG and 2h-PG to predict MACE was compared. Of the total, 93-96% of impaired glucose tolerance and 64-75% of DM would be missed with current guidelines. MACE was higher in the upper quartiles of 2h-PG. When 2h-PG and FPG were included simultaneously in models, only 2h-PG predicted MACE (HR 1.12, CI 1.04-1.20, p = 0.0012), all cause mortality (HR 1.17, CI 1.05-1.30, p = 0.0039), cardiovascular mortality (HR 1.17, CI 1.02-1.33, p = 0.0205) and non-fatal MI (HR 1.10, CI 1.01-1.20, p = 0.0291). Adding 2h-PG significantly improved ability of models including FPG (χ 2  = 16.01, df = 1, p = 0.0001) or FPG and APG (χ 2  = 17.36, df = 1, p = 0.000) to predict MACE. Model including 2h-PG only had the lowest Akaike's information criteria and highest Akaike weights suggesting that this was the best in predicting events. Adding 2h-PG to models including FPG or APG with other co-variates yielded continuous net reclassification improvement (NRI) of 0.22 (p = 0.026) and 0.27 (p = 0.005) and categorical NRI of 0.09 (p = 0.032) and 0.12 (p = 0.014), respectively. Adding 2 h-PG to models including only FPG, only APG and both yielded integrated discrimination improvement of 0.012 (p = 0.015), 0.022 (p = 0.001) and 0.013 (p = 0.014), respectively. AGT is under-diagnosed on current guidelines. 2h-PG is a better predictor of prognosis compared to APG and FPG.

The association of long-term glycaemic variability versus sustained chronic hyperglycaemia with heart rate-corrected QT interval in patients with type 2 diabetes.

PubMed

Su, Jian-Bin; Yang, Xiao-Hua; Zhang, Xiu-Lin; Cai, Hong-Li; Huang, Hai-Yan; Zhao, Li-Hua; Xu, Feng; Chen, Tong; Cheng, Xing-Bo; Wang, Xue-Qin; Lu, Yan

2017-01-01

Prolonged heart rate-corrected QT(QTc) interval is related to ventricular arrhythmia and cardiovascular mortality, with considerably high prevalence of type 2 diabetes. Additionally, long-term glycaemic variability could be a significant risk factor for diabetic complications in addition to chronic hyperglycaemia. We compared the associations of long-term glycaemic variability versus sustained chronic hyperglycaemia with the QTc interval among type 2 diabetes patients. In this cross-sectional study, 2904 type 2 diabetes patients were recruited who had undergone at least four fasting plasma glucose (FPG) and 2-hour postprandial plasma glucose (PPG) measurements (at least once for every 3 months, respectively) during the preceding year. Long-term glycaemic variabilities of FPG and 2-hour PPG were assessed by their standard deviations (SD-FPG and SD-PPG, respectively), and chronic fasting and postprandial hyperglycaemia were assessed by their means (M-FPG and M-PPG, respectively). HbA1c was also determined upon enrolment to assess current overall glycaemic control. QTc interval was estimated from resting 12-lead electrocardiograms, and more than 440 ms was considered abnormally prolonged. Patients with prolonged QTc interval (≥440 ms) had greater M-FPG, M-PPG, SD-PPG and HbA1c than those with normal QTc interval but comparable SD-FPG. QTc interval was correlated with M-FPG, M-PPG, SD-PPG and HbA1c (r = 0.133, 0.153, 0.245 and 0.207, respectively, p = 0.000) but not with SD-FPG (r = 0.024, p = 0.189). After adjusting for metabolic risk factors via multiple linear regression analysis, SD-PPG, M-PPG and HbA1c (t = 12.16, 2.69 and 10.16, respectively, p = 0.000) were the major independent contributors to the increased QTc interval. The proportion of prolonged QTc interval increased significantly from 10.9% to 14.2% to 26.6% for the first (T1) to second (T2) to third (T3) tertiles of SD-PPG. After adjusting via multiple logistic regression analysis, the odd ratios of prolonged QTc interval of the T2 and T3 versus the T1 of SD-PPG were 1.15 (95% CI, 0.82-1.60) and 2.62 (1.92-3.57), respectively. Increased long-term variability of PPG is a strong independent risk factor for prolonged QTc interval in type 2 diabetes patients, in addition to long-term postprandial hyperglycaemia and current HbA1c.

Enhanced external counterpulsation (EECP) improves biomarkers of glycemic control in patients with non-insulin-dependent type II diabetes mellitus for up to 3 months following treatment.

PubMed

Sardina, Paloma D; Martin, Jeffrey S; Avery, Joseph C; Braith, Randy W

2016-10-01

The purpose of the present study was to evaluate the potential clinical benefits of EECP on glycemic parameters [fasting plasma glucose (FPG), postprandial glucose (PPG120), glycosylated hemoglobin (HbA1c)] in patients with a clinical diagnosis of type II diabetes mellitus (T2DM). Thirty subjects (60.7 ± 1.9 years) with T2DM were randomly assigned (2:1 ratio) to receive either 35 1-h sessions of EECP (n = 20) or time-matched control of standard care (n = 10). FPG, PPG120, and HbA1c were evaluated before and at 48 h, 2 weeks, 3 and 6 months following EECP treatment or time-matched control. EECP significantly decreased FPG (-14.6 and -12.0 %), PPG120 (-14.6 and -13.5 %), and HbA1c (-11.5 and -19.6 %) 48 h following EECP and 2 weeks following EECP, respectively. HbA1c remained significantly reduced at 3 months following EECP (-14.3 %). The homeostasis model assessment of insulin resistance (-31.1 %) and whole-body composite insulin sensitivity index (+54.2 %) were significantly improved 48 h following EECP. Nitrite/nitrate (NO x ) was significantly increased 48 h following EECP (+48.4 %) and 2 weeks (+51.9 %) following EECP treatment. Our findings provide novel evidence that EECP improves glycemic control in patients with T2DM that persist for up to 3 months following treatment.

Clinical, Hormonal, and Metabolic Parameters in Women with Subclinical Hypothyroidism and Polycystic Ovary Syndrome: A Cross-Sectional Study.

PubMed

Bedaiwy, Mohamed A; Abdel-Rahman, Mohamed Y; Tan, Justin; AbdelHafez, Faten F; Abdelkareem, Amr O; Henry, Drisana; Lisonkova, Sarka; Hurd, William W; Liu, James H

2018-05-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in reproductive age women, yet its clinical presentation shares similarities with several other endocrine disorders such as thyroid disease. Hence, the objective of this study was to further evaluate this association by investigating the clinical, hormonal, and metabolic parameters between subclinical hypothyroidism (SCH) and PCOS. This is a cross-sectional study conducted in a tertiary care clinic at Cleveland, Ohio, USA. A total of 137 women diagnosed with PCOS by Rotterdam criteria were examined. SCH was defined as thyroid-stimulating hormone >2.5 mIU/L in the absence of symptoms of overt hypothyroidism. The mean age, body mass index (BMI), fasting plasma glucose (FPG), glucose tolerance test, hemoglobin A1c, fasting insulin, a 2 hours insulin level after 75 g glucose load, cholesterol, LDL, HDL, and homeostatic model assessment (HOMA) were compared between women with and without SCH. Logistic regression was used to adjust for age and BMI. Among 137 women with PCOS, 21.9% had SCH. Comparison groups were similar in both age and BMI and there was no difference in the mean values of all endocrine and metabolic parameters tested. However, abnormal FPG levels (OR 3.01; CI: 1.12-8.07. p = 0.03) and abnormal HOMA (OR 3.7; CI: 1.14-12.00. p = 0.03) were more likely in women who had SCH than in women without SCH independent of age and BMI. Women with PCOS and SCH are more likely to have impaired FPG values and impaired insulin sensitivity even after adjusting for age and BMI. Hence, close monitoring of PCOS patients for SCH may be beneficial.

The effect of linagliptin on glycaemic control and tolerability in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

PubMed

Singh-Franco, D; McLaughlin-Middlekauff, J; Elrod, S; Harrington, C

2012-08-01

Linagliptin is a new dipeptidyl peptidase-4 inhibitor recently approved for use in the USA. The objective of this systematic review and meta-analysis was to assess effect of linagliptin on glycaemic control, biomarkers and incidence of adverse events (AEs) in patients with type 2 diabetes mellitus. Five published and four unpublished randomized, clinical trials were identified from multiple databases. Qualitative assessments and quantitative analyses were performed. Nine studies included 4246 participants with 53% men, 59.4% Caucasians, 38.7% Asians, and age range 45-69 years. Linagliptin was given as monotherapy (vs. placebo) or combined with metformin (vs. metformin + placebo), sulphonylurea (vs. sulphonylurea + placebo) or pioglitazone (vs. pioglitazone + placebo). Linagliptin 5 mg/day for 12-24 weeks, significantly reduced haemoglobin A1c (HbA1c) (-0.63%, p < 0.00001), fasting plasma glucose (FPG) (-1.01 mmol/l, p < 0.00001) and improved disposition index (DI, product of insulin sensitivity and acute insulin secretion) (p = 0.0001). Linagliptin monotherapy was not more effective than metformin at reducing HbA1c or FPG. Similar proportion of patients in linagliptin and placebo groups reported AEs including upper respiratory tract infections, headaches, nausea, hypertension and back pain. Linagliptin was associated with modest but significant reduction in HbA1c and FPG and improved DI after 12-24 weeks. Patients who would probably benefit most are those with HbA1c <9%, already on an active agent, compliant with weight reduction strategies, and can recognize and manage hypoglycaemia, fluid retention and upper respiratory tract infections. Long-term studies are needed to determine durability of response, incidence of microvascular and macrovacular complications, cost-effectiveness and safety. © 2012 Blackwell Publishing Ltd.

Combined use of fasting plasma glucose and glycated hemoglobin A1c in a stepwise fashion to detect undiagnosed diabetes mellitus.

PubMed

Nakagami, Tomoko; Tominaga, Makoto; Nishimura, Rimei; Daimon, Makoto; Oizumi, Toshihide; Yoshiike, Nobuo; Tajima, Naoko

2007-09-01

Type 2 diabetes mellitus (DM) is a common and serious condition related with considerable morbidity. Screening for DM is one strategy for reducing this burden. In Japan National Diabetes Screening Program (JNDSP) guideline, the combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) in a stepwise fashion has been recommended to identify the group of people needing life-style counseling or medical care. However, the efficacy of this program has not been fully evaluated, as an oral glucose tolerance test (OGTT) is not mandatory in the guideline. The aim of this study was to assess the validity of the screening test scenario, in which an OGTT would be applied to people needing life-style counseling or medical care on this guideline: FPG 110-125 mg/dl and HbA1c over 5.5%. Subjects were 1,726 inhabitants without a previous history of DM in the Funagata study, which is a population-based survey conducted in Yamagata prefecture to clarify the risk factors, related conditions, and consequences of DM. DM was diagnosed according to the 1999 World Health Organization criteria. The prevalence of undiagnosed DM was 6.6%. The tested screening scenario gave a sensitivity of 55.3%, a specificity of 98.4%, a positive predictive value of 70.8%, and a negative predictive value of 96.9% for undiagnosed DM. In conclusion, the screening test scenario, in which an OGTT would be followed by the combined use of FPG and HbA1c in a stepwise fashion according to the JNDSP guideline, was not effective in identifying people with undiagnosed DM.

The prediction of resting energy expenditure in type 2 diabetes mellitus is improved by factoring for glycemia.

PubMed

Gougeon, R; Lamarche, M; Yale, J-F; Venuta, T

2002-12-01

Predictive equations have been reported to overestimate resting energy expenditure (REE) for obese persons. The presence of hyperglycemia results in elevated REE in obese persons with type 2 diabetes, and its effect on the validity of these equations is unknown. We tested whether (1) indicators of diabetes control were independent associates of REE in type 2 diabetes and (2) their inclusion would improve predictive equations. A cross-sectional study of 65 (25 men, 40 women) obese type 2 diabetic subjects. Variables measured were: REE by ventilated-hood indirect calorimetry, body composition by bioimpedance analysis, body circumferences, fasting plasma glucose (FPG) and hemoglobin A(1c). Data were analyzed using stepwise multiple linear regression. REE, corrected for weight, fat-free mass, age and gender, was significantly greater with FPG>10 mmol/l (P=0.017) and correlated with FPG (P=0.013) and hemoglobin A(1c) as percentage upper limit of normal (P=0.02). Weight was the main determinant of REE. Together with hip circumference and FPG, it explained 81% of the variation. FPG improved the predictability of the equation by >3%. With poor glycemic control, it can represent an increase in REE of up to 8%. Our data indicate that in a population of obese subjects with type 2 diabetes mellitus, REE is better predicted when fasting plasma glucose is included as a variable.

Survey Examines Experiences of Families Entering Early Intervention. FPG Snapshot #14

ERIC Educational Resources Information Center

FPG Child Development Institute, University of North Carolina, 2004

2004-01-01

A recent FPG study looked at families' initial experiences in determining their child's eligibility for early intervention (EI) services as mandated by Part C (IDEA), interactions with medical professionals, effort required to get services, participation in planning for services, satisfaction with services, and interactions with professionals. A…

Examining Social Acceptance & Rejection. FPG Snapshot #44

ERIC Educational Resources Information Center

FPG Child Development Institute, 2007

2007-01-01

This FPG Snapshot summarizes the findings of a study, published in the November 2006 issue of the "Journal of Educational Psychology," that examined whether children with disabilities are accepted or rejected by their classmates in inclusive classrooms. Specifically, the study examined two sets of related questions: (1) Are individual…

Ethnic dependent differences in diagnostic accuracy of glycated hemoglobin (HbA1c) in Canadian adults.

PubMed

Booth, Ronald A; Jiang, Ying; Morrison, Howard; Orpana, Heather; Rogers Van Katwyk, Susan; Lemieux, Chantal

2018-02-01

Previous studies have shown varying sensitivity and specificity of hemoglobin A1c (HbA1c) to identify diabetes and prediabetes, compared to 2-h oral glucose tolerance testing (OGTT) and fasting plasma glucose (FPG), in different ethnic groups. Within the Canadian population, the ability of HbA1c to identify prediabetes and diabetes in First Nations, Métis and Inuit, East and South Asian ethnic groups has yet to be determined. We collected demographic, lifestyle information, biochemical results of glycemic status (FPG, OGTT, and HbA1c) from an ethnically diverse Canadian population sample, which included a purposeful sampling of First Nations, Métis, Inuit, South Asian and East Asian participants. Sensitivity and specificity using Canadian Diabetes Association (CDA) recommended cut-points varied between ethnic groups, with greater variability for identification of prediabetes than diabetes. Dysglycemia (prediabetes and diabetes) was identified with a sensitivity and specificity ranging from 47.1% to 87.5%, respectively in Caucasians to 24.1% and 88.8% in Inuit. Optimal HbA1c ethnic-specific cut-points for dysglycemia and diabetes were determined by receiver operating characteristic (ROC) curve analysis. Our sample showed broad differences in the ability of HbA1c to identify dysglycemia or diabetes in different ethnic groups. Optimal cut-points for dysglycemia or diabetes in all ethnic groups were substantially lower than CDA recommendations. Utilization of HbA1c as the sole biochemical diagnostic marker may produce varying degrees of false negative results depending on the ethnicity of screened individuals. Further research is necessary to identify and validate optimal ethnic specific cut-points used for diabetic screening in the Canadian population. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Biomarkers of early genotoxicity and oxidative stress for occupational risk assessment of exposure to styrene in the fibreglass reinforced plastic industry.

PubMed

Cavallo, Delia; Tranfo, Giovanna; Ursini, Cinzia Lucia; Fresegna, Anna Maria; Ciervo, Aureliano; Maiello, Raffaele; Paci, Enrico; Pigini, Daniela; Gherardi, Monica; Gatto, Maria Pia; Buresti, Giuliana; Iavicoli, Sergio

2018-06-10

This study aimed to identify sensitive and not-invasive biomarkers of early genotoxic/oxidative effect for exposure to styrene in the fibreglass reinforced plastic manufacture. We studied 11 workers of a plastic manufacture using open molding process (A), 16 workers of a manufacture using closed process (B) and 12 controls. We evaluated geno/cytotoxic effects on buccal cells by Buccal Micronucleus Cytome (BMCyt) assay and genotoxic/oxidative effects on lymphocytes by Fpg-comet test. On A workers we also evaluated urinary 8oxoGua, 8oxodGuo and 8oxoGuo to investigate oxidative stress. Personal inhalation exposure to styrene was monitored by passive air sampling and GC/MS. Biological monitoring included urinary metabolites mandelic acid (MA) and phenylglyoxylic acid (PGA). The findings show higher styrene exposure, urinary MA + PGA levels and micronucleus frequency in manufacture A. Higher buccal karyolytic cell frequency vs controls were found in both exposed populations. We found in exposed workers, no induction of direct DNA damage but oxidative DNA damage. Fpg-comet assay and urinary oxidized guanine seem to be sensitive biomarkers of oxidative stress and BMCyt assay a good-not invasive biomarker of cyto-genotoxicity at target organ. The study, although limited by the small number of studied subjects, shows the usefulness of used biomarkers in risk assessment of styrene-exposed workers. Copyright © 2018 Elsevier B.V. All rights reserved.

Basal damage and oxidative DNA damage in children with chronic kidney disease measured by use of the comet assay.

PubMed

Aykanat, Banu; Demircigil, Gonca Cakmak; Fidan, Kibriya; Buyan, Necla; Gulleroglu, Kaan; Baskin, Esra; Bayrakci, Umut Selda; Sepici, Aylin; Buyukkaragoz, Bahar; Karakayali, Hamdi; Haberal, Mehmet; Burgaz, Sema

2011-10-09

One consequence of chronic kidney disease (CKD) is an elevated risk for cancer. There is sufficient evidence to conclude that there is an increased incidence of at least some cancers in kidney-dialysis patients. Cancer risk after kidney transplantation has mainly been attributed to immunosuppressive therapy. There are no data evaluating DNA damage in children with CKD, in dialysis patients, or following kidney transplantation. In this study, the comet assay and the enzyme-modified comet assay - with the use of endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) enzymes - were conducted to investigate the basal damage and the oxidative DNA damage as a result of treatment in peripheral blood lymphocytes of children. Children at various stages of treatment for kidney disease, including pre-dialysis patients (PreD) (n=17), regular hemodialysis patients (HD) (n=15), and those that received kidney transplants (Tx) (n=17), comprised the study group. They were compared with age- and gender-matched healthy children (n=20) as a control group. Our results show that the %DNA intensity, a measure of basal damage, was significantly increased in children with CKD (mean ± SD) (5.22 ± 1.57) and also in each of the PreD, HD, and Tx groups [(4.92 ± 1.23), (4.91 ± 1.35), and (5.79 ± 1.94), respectively, vs the healthy children (2.74 ± 2.91) (p<0.001). Significant increases in oxidative DNA damage were only found in the FPG-sensitive sites for the PreD and Tx groups, compared with control and HD groups (p<0.05), suggesting that basal DNA damage was more evident for the PreD, HD, and Tx groups. The findings of the present study indicate a critical need for further research on genomic damage with different endpoints and also for preventive measures and improvements in treatment of pediatric patients, in order to improve their life expectancy. 2011 Elsevier B.V. All rights reserved.

Fragile X Syndrome. Early Developments. Volume 8, Number 2, Summer 2004

ERIC Educational Resources Information Center

Manuel, John

2004-01-01

Eleven years ago, FPG Child Development Institute (FPG) launched a longitudinal study of a little known form of mental retardation known as fragile X syndrome (FXS). The Carolina Fragile X Project has since grown into a multidisciplinary team studying diverse aspects of the condition, ranging from early identification to school performance. The…

Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: standard and Fpg-modified comet assay.

PubMed

Gajski, Goran; Garaj-Vrhovac, Vera; Orescanin, Visnja

2008-08-15

To investigate the genotoxic potential of atorvastatin on human lymphocytes in vitro standard comet assay was used in the evaluation of basal DNA damage and to investigate possible oxidative DNA damage produced by reactive oxygen species (ROS) Fpg-modified version of comet assay was also conducted. In addition to these techniques the new criteria for scoring micronucleus test were applied for more complete detection of baseline damage in binuclear lymphocytes exposed to atorvastatin 80 mg/day in different time periods by virtue of measuring the frequency of micronuclei, nucleoplasmic bridges and nuclear buds. All parameters obtained with the standard comet assay and Fpg-modified comet assay were significantly higher in the treated than in control lymphocytes. The Fpg-modified comet assay showed a significantly greater tail length, tail intensity, and tail moment in all treated lymphocytes than did the standard comet assay, which suggests that oxidative stress is likely to be responsible for DNA damage. DNA damage detected by the standard comet assay indicates that some other mechanism is also involved. In addition to the comet assay, a total number of micronuclei, nucleoplasmic bridges and nuclear buds were significantly higher in the exposed than in controlled lymphocytes. Regression analyses showed a positive correlation between the results obtained by the comet (Fpg-modified and standard) and micronucleus assay. Overall, the study demonstrated that atorvastatin in its highest dose is capable of producing damage on the level of DNA molecule and cell.

Function-preserving surgery for gastric cancer: current status and future perspectives

PubMed Central

Hiki, Naoki

2017-01-01

The number of early gastric cancer (EGC) cases has been increasing because of improved diagnostic procedures including endoscopy and screening systems. Therefore, function-preserving gastrectomy (FPG) for EGC with the expectation of better quality of life (QOL) after surgery may be increasingly utilized, due to its association with low rate of lymph node metastasis and excellent survival and the possibility of employing less invasive procedures such as laparoscopic gastrectomy in combination. Pylorus-preserving gastrectomy (PPG) with curative intent lymph node dissection is a representative FPG that has been used in EGC, and its superiorities, indications, limitations, and survival benefits have already been reported in several retrospective studies. Laparoscopic proximal gastrectomy (LAPG) has also been employed in EGC of the upper third of the stomach; however, LAPG was found to be associated with major issues in achieving a balance between swallowing and reflux prevention. In patients with EGC in the upper third of the stomach, laparoscopy-assisted subtotal gastrectomy with a preserved, albeit very small, stomach may provide a better QOL and fewer postoperative complications. FPG is recommended as a surgical treatment for EGC if the indication is accurately diagnosed and strictly confirmed; however, these techniques in laparoscopic surgery present technical difficulties to surgeons without a certain degree of skills. Although many retrospective studies revealed the functional benefits or oncological safety with FPG, further prospective studies using large case series are necessary to reveal the value of FPG compared with the conventional procedures. PMID:29034350

Continuous relationships between non-diabetic hyperglycaemia and both cardiovascular disease and all-cause mortality: the Australian Diabetes, Obesity, and Lifestyle (AusDiab) study.

PubMed

Barr, E L M; Boyko, E J; Zimmet, P Z; Wolfe, R; Tonkin, A M; Shaw, J E

2009-03-01

Hyperglycaemia is a risk factor for cardiovascular disease (CVD) and all-cause mortality in individuals without diabetes. We investigated: (1) whether the risk of all-cause and CVD mortality extended continuously throughout the range of fasting plasma glucose (FPG), 2 h plasma glucose (2hPG) and HbA(1c) values; and (2) the ability of these measures to improve risk prediction for mortality. Data on 10,026 people aged >or=25 years without diagnosed diabetes were obtained from the population-based Australian Diabetes, Obesity and Lifestyle study. Between 1999 and 2000, FPG, 2hPG and HbA(1c) were assessed and all-cause (332 deaths) and CVD (88 deaths) mortality were obtained after 7 years. Both 2hPG and HbA(1c) exhibited linear relationships with all-cause and CVD mortality, whereas FPG showed J-shaped relationships. The adjusted HR (95% CI) for all-cause mortality per SD increase was 1.2 (1.1-1.3) for 2hPG and 1.1 (1.0-1.2) for HbA(1c). The HR for FPG <5.1 mmol/l (per SD decrease) was 2.0 (1.3-3.0); for FPG >or=5.1 mmol/l (per SD increase) the HR was 1.1 (1.0-1.2). Corresponding HRs for CVD mortality were 1.2 (1.0-1.4), 1.2 (1.0-1.3), 4.0 (2.1-7.6) and 1.3 (1.1-1.4). The discriminative ability of each measure was similar; no measure substantially improved individual risk identification over traditional risk factors. In individuals without diagnosed diabetes, 2hPG and FPG, but not HbA(1c) were significant predictors of all-cause mortality, whereas all measures were significant predictors of CVD mortality. However, these glucose measures did not substantially improve individual risk identification.

Visit-to-Visit Variations in Fasting Plasma Glucose and HbA1c Associated With an Increased Risk of Alzheimer Disease: Taiwan Diabetes Study.

PubMed

Li, Tsai-Chung; Yang, Chun-Pai; Tseng, Shih-Ting; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Hwang, Kai-Lin; Yang, Sing-Yu; Chiang, Jen-Huai; Lin, Cheng-Chieh

2017-09-01

The relationship between glycemic variability and the incidence of Alzheimer disease (AD) in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to examine visit-to-visit variations in fasting plasma glucose (FPG) and glycated hemoglobin (HbA 1c ) represented by the coefficient of variation (CV) and to determine whether they were independently associated with AD, irrespective of HbA 1c and other traditional risk factors in such patients. Patients with T2DM enrolled in the National Diabetes Care Management Program, age ≥60 years, and without diagnosis of AD ( n = 16,706) were included in the study. Potential risk factors were analyzed using extended Cox proportional hazards regression models for competing risk of mortality on AD incidence. During a median follow-up of 8.88 years, 831 incident cases of AD were identified, with a crude incidence rate of 3.5/1,000 person-years. After adjustment for sociodemographic factors, lifestyle behaviors, diabetes-related variables, FPG and HbA 1c , drug-related variables, and comorbidities, both FPG CV and HbA 1c CV were found to be significant predictors of AD, with corresponding hazard ratios of 1.27 (95% CI 1.06-1.52) for the third tertile in FPG CV and 1.32 (95% CI 1.11-1.58) for the third tertile in HbA 1c CV. FPG CV and HbA 1c CV are independently associated with AD. The associations between glycemic variability and AD demonstrated in this study suggest a linked pathophysiological mechanism, which is worthy of further investigation. Further research is required to confirm our results and to evaluate whether FPG CV and HbA 1c CV can be valuable therapeutic targets for patients with T2DM at risk. © 2017 by the American Diabetes Association.

[Prognostic value of first fasting glucose measurement compared with admission glucose level in patients with acute coronary syndrome].

PubMed

Vivas, David; García-Rubira, Juan C; González-Ferrer, Juan J; Núñez-Gil, Iván; del Prado, Náyade; Fernández-Ortiz, Antonio; Macaya, Carlos

2008-05-01

The admission plasma glucose (APG) level is a recognized prognostic factor in patients with acute coronary syndrome (ACS). However, little is known about the prognostic value of the first fasting plasma glucose (FPG) measurement. The aim of this study was to determine the prognostic value of the first FPG measurement relative to that of the APG level in patients with ACS. The study involved 547 consecutive patients who were admitted to our center with a diagnosis of ACS in 2006. Patients were divided into three groups according to their first FPG or APG level (i.e., <126 mg/dL, 126-200 mg/dL, or >200 mg/dL). The primary endpoint was the combined outcome of death or reinfarction during hospitalization. The primary endpoint was observed in 46 patients, 25 of whom died. Patients in this group were older, were more often diabetics or smokers, more often had had a prior myocardial infarction, were in a higher admission Killip class, showed more than one vessel disease on catheterization, had a lower left ventricular ejection fraction, and had higher admission creatinine, APG, and first FPG levels. Multivariate analysis, adjusted for previously identified factors, revealed that the first FPG level was an independent risk factor for death or reinfarction (126-200 mg/dL, odds ratio [OR]=5.26; 95% confidence interval [CI], 1.09-25.45; >200 mg/dL, OR=6.66; 95% CI, 2.05-21.63), but that the APG level was not (126-200 mg/dL, OR=0.84; 95% CI, 0.63-1.05; >200 mg/dL, OR=1.14; 95% CI, 0.29-4.51). The first FPG level was found to be a better predictor of an adverse outcome (i.e., death or reinfarction) during hospitalization in ACS patients than the APG level.

Association of hemoglobin A1c and glycated albumin with carotid atherosclerosis in community-dwelling Japanese subjects: the Hisayama Study.

PubMed

Mukai, Naoko; Ninomiya, Toshiharu; Hata, Jun; Hirakawa, Yoichiro; Ikeda, Fumie; Fukuhara, Masayo; Hotta, Taeko; Koga, Masafumi; Nakamura, Udai; Kang, Dongchon; Kitazono, Takanari; Kiyohara, Yutaka

2015-06-24

It is not clear which glucose measure is more useful in the assessment of atherosclerosis. We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), 1,5-anhydroglucitol (1,5-AG), fasting plasma glucose (FPG), and 2-hour postload glucose (PG) with carotid intima-media thickness (IMT) in community-dwelling Japanese subjects. A total of 2702 subjects aged 40-79 years underwent a 75-g oral glucose tolerance test and measurements of HbA1c, GA, 1,5-AG, and carotid IMT by ultrasonography in 2007-2008. Carotid wall thickening was defined as a maximum IMT of >1.0 mm. The crude and multivariable-adjusted linear and logistic regression models were used to analyze cross-sectional associations between levels of glycemic measures and carotid IMT. The crude average of the maximum IMT increased significantly with rising quartiles of HbA1c, GA, FPG, and 2-hour PG levels in subjects with and without glucose intolerance (GI), while no clear association was observed for 1,5-AG. After adjustment for other confounding factors, positive trends for HbA1c, GA, and FPG (all p for trend < 0.05), but not 2-hour PG (p = 0.07) remained robust in subjects with GI, but no such associations were found in those without GI. When estimating multivariable-adjusted β values for the associations of 1 SD change in glycemic measures with the maximum IMT in subjects with GI, the magnitude of the influence of HbA1c (β = 0.021), GA (β = 0.024), and FPG (β = 0.024) was larger than that of 2-hour PG (β = 0.014) and 1,5-AG (β = 0.003). The multivariable-adjusted odds ratios for the presence of carotid wall thickening increased significantly with elevating HbA1c, GA, and FPG levels only in subjects with GI (all p for trend < 0.001). Among subjects with GI, the area under the receiver operating characteristic curve significantly increased by adding HbA1c (p = 0.04) or GA (p = 0.04), but not 1,5-AG, FPG, or 2-hour PG, to the model including other cardiovascular risk factors. In community-dwelling Japanese subjects with GI, elevated HbA1c, GA, and FPG levels were significantly associated with increased carotid IMT, and HbA1c and GA provided superior discrimination for carotid wall thickening compared to 1,5-AG, FPG, and 2-hour PG, suggesting that HbA1c and GA are useful for assessing carotid atherosclerosis.

Further characterization of benzo[a]pyrene diol-epoxide (BPDE)-induced comet assay effects.

PubMed

Bausinger, Julia; Schütz, Petra; Piberger, Ann Liza; Speit, Günter

2016-03-01

The present study aims to further characterize benzo[a]pyrene diol-epoxide (BPDE)-induced comet assay effects. Therefore, we measured DNA effects by the comet assay and adduct levels by high-performance liquid chromatography (HPLC) in human lymphocytes and A549 cells exposed to (±)-anti-benzo[a]pyrene-7,8-diol 9,10-epoxide [(±)-anti-BPDE] or (+)-anti-benzo[a]pyrene-7,8-diol 9,10-epoxide [(+)-anti-BPDE]. Both, the racemic form and (+)-anti-BPDE, which is the most relevant metabolite with regard to mutagenicity and carcinogenicity, induced DNA migration in cultured lymphocytes in the same range of concentrations to a similar extent in the alkaline comet assay after exposure for 2h. Nevertheless, (+)-anti-BPDE induced significantly enhanced DNA migration after 16 and 18h post-cultivation which was not seen in response to (±)-anti-BPDE. Combination of the comet assay with the Fpg (formamidopyrimidine-DNA glycosylase) protein did not enhance BPDE-induced effects and thus indicated the absence of Fpg-sensitive sites (oxidized purines, N7-guanine adducts, AP-sites). The aphidicolin (APC)-modified comet assay suggested significant excision repair activity of cultured lymphocytes during the first 18h of culture after a 2 h-exposure to BPDE. In contrast to these repair-related effects measured by the comet assay, HPLC analysis of stable adducts did not reveal any significant removal of (+)-anti-BPDE-induced adducts from lymphocytes during the first 22h of culture. On the other hand, HPLC measurements indicated that A549 cells repaired about 70% of (+)-anti-BPDE-induced DNA-adducts within 22h of release. However, various experiments with the APC-modified comet assay did not indicate significant repair activity during this period in A549 cells. The conflicting results obtained with the comet assay and the HPLC-based adduct analysis question the real cause for BPDE-induced DNA migration in the comet assay and the reliability of the APC-modified comet assay for the determination of DNA excision repair activity in response to BPDE in different cell types. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Culture and Parenting: Family Models Are Not One-Size-Fits-All. FPG Snapshot #67

ERIC Educational Resources Information Center

FPG Child Development Institute, 2012

2012-01-01

Family process models guide theories and research about family functioning and child development outcomes. Theory and research, in turn, inform policies and services aimed at families. But are widely accepted models valid across cultural groups? To address these gaps, FPG researchers examined the utility of two family process models for families…

Can Child Care Impact Risk for Depression? FPG Snapshot #46

ERIC Educational Resources Information Center

FPG Child Development Institute, 2007

2007-01-01

Children living in poverty often have less than ideal home environments and are at an increased risk for depression in adulthood. Because we know from existing research that experiences in child care can have long-term affects for children socially, FPG researchers wondered if such experiences could temper the mental health impact of lower quality…

Effect of chromium supplementation on glycated hemoglobin and fasting plasma glucose in patients with diabetes mellitus.

PubMed

Yin, Raynold V; Phung, Olivia J

2015-02-13

Chromium (Cr) is a trace element involved in glucose homeostasis. We aim to evaluate and quantify the effects of Cr supplementation on A1C and FPG in patients with T2DM. A systematic literature search of Pubmed, EMBASE and the Cochrane Library (from database inception to 11/2014) with no language restrictions sought RCTs or cohort studies evaluating Cr supplementation in T2DM vs control and reporting either change in glycated hemoglobin (A1C) or fasting plasma glucose (FPG). Meta-analysis was conducted on each subtype of Cr supplement separately, and was analyzed by random effects model to yield the weighted mean differences (WMD) and 95% confidence intervals (CIs). Heterogeneity was assessed by using the I(2) statistic. A total of 14 RCTs (n=875 participants, mean age range: 30 to 83 years old, 8 to 24 weeks of follow-up) were identified (Cr chloride: n=3 study, Cr picolinate: n=5 study, brewer's yeast: n=4 study and Cr yeast: n=3 study). Compared with placebo, Cr yeast, brewer's yeast and Cr picolinate did not show statistically significant effects on A1C. Furthermore, compared to control, Cr chloride, Cr yeast and Cr picolinate showed no effect on FPG, however, brewer's yeast showed a statistically significant decrease in FPG -19.23 mg/dL (95% CI=-35.30 to -3.16, I(2)=21%, n=137). Cr supplementation with brewer's yeast may provide marginal benefits in lowering FPG in patients with T2DM compared to placebo however it did not have any effect on A1C.

Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: Standard and Fpg-modified comet assay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gajski, Goran; Garaj-Vrhovac, Vera; Orescanin, Visnja

2008-08-15

To investigate the genotoxic potential of atorvastatin on human lymphocytes in vitro standard comet assay was used in the evaluation of basal DNA damage and to investigate possible oxidative DNA damage produced by reactive oxygen species (ROS) Fpg-modified version of comet assay was also conducted. In addition to these techniques the new criteria for scoring micronucleus test were applied for more complete detection of baseline damage in binuclear lymphocytes exposed to atorvastatin 80 mg/day in different time periods by virtue of measuring the frequency of micronuclei, nucleoplasmic bridges and nuclear buds. All parameters obtained with the standard comet assay andmore » Fpg-modified comet assay were significantly higher in the treated than in control lymphocytes. The Fpg-modified comet assay showed a significantly greater tail length, tail intensity, and tail moment in all treated lymphocytes than did the standard comet assay, which suggests that oxidative stress is likely to be responsible for DNA damage. DNA damage detected by the standard comet assay indicates that some other mechanism is also involved. In addition to the comet assay, a total number of micronuclei, nucleoplasmic bridges and nuclear buds were significantly higher in the exposed than in controlled lymphocytes. Regression analyses showed a positive correlation between the results obtained by the comet (Fpg-modified and standard) and micronucleus assay. Overall, the study demonstrated that atorvastatin in its highest dose is capable of producing damage on the level of DNA molecule and cell.« less

Comparison of characteristics between frequent participants and non-participants in screening program for stomach cancer.

PubMed

Fukao, A; Hisamichi, S; Komatsu, S; Shimizu, H; Satoh, H; Nakatsuka, H; Watanabe, T; Fujisaku, S; Ichinowatari, Y; Kuroda, S

1992-04-01

To clarify the differences in characteristics between participants and non-participants in the screening program for stomach cancer, life-style and medical histories were compared among 20, 169 subjects who lived in an urban area (Sendai) and a rural area (Wakuya and Tajiri) in Miyagi Prefecture, Japan. All subjects were classified into three groups according to the frequency of participation in the screening program during the last 5 years; i.e., frequent participating group (FPG) for 4 or 5 times, reference group (RG) for 1-3 times and non-participating group (NPG) for 0 times. Subjects in the FPG consumed more milk and green-yellow vegetable whereas those in the NPG consumed less these foods. The age-adjusted proportions of present smokers were higher in the NPG but lower in the FPG significantly. The proportions of subjects who had parental histories of all cancers and stomach cancer and past history of gastro-duodenal ulcer were higher in the FPG and lower in the NPG. To control influences among the variables a stepwise multiple regression analysis was done, and it revealed that smoking and parental history of cancers were strong predictors to explain the frequency of participation.

The product of fasting plasma glucose and triglycerides improves risk prediction of type 2 diabetes in middle-aged Koreans.

PubMed

Lee, Joung-Won; Lim, Nam-Kyoo; Park, Hyun-Young

2018-05-30

Screening for risk of type 2 diabetes mellitus (T2DM) is an important public health issue. Previous studies report that fasting plasma glucose (FPG) and triglyceride (TG)-related indices, such as lipid accumulation product (LAP) and the product of fasting glucose and triglyceride (TyG index), are associated with incident T2DM. We aimed to evaluate whether FPG or TG-related indices can improve the predictive ability of a diabetes risk model for middle-aged Koreans. 7708 Koreans aged 40-69 years without diabetes at baseline were eligible from the Korean Genome and Epidemiology Study. The overall cumulative incidence of T2DM was 21.1% (766 cases) in men and 19.6% (797 cases) in women. Therefore, the overall cumulative incidence of T2DM was 20.3% (1563 cases). Multiple logistic regression analysis was conducted to compare the odds ratios (ORs) for incident T2DM for each index. The area under the receiver operating characteristic curve (AROC), continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI) were calculated when each measure was added to the basic risk model for diabetes. All the TG-related indices and FPG were more strongly associated with incident T2DM than WC in our study population. The adjusted ORs for the highest quartiles of WC, TG, FPG, LAP, and TyG index compared to the lowest, were 1.64 (95% CI, 1.13-2.38), 2.03 (1.59-2.61), 3.85 (2.99-4.97), 2.47 (1.82-3.34), and 2.79 (2.16-3.60) in men, and 1.17 (0.83-1.65), 2.42 (1.90-3.08), 2.15 (1.71-2.71), 2.44 (1.82-3.26), and 2.85 (2.22-3.66) in women, respectively. The addition of TG-related parameters or FPG, but not WC, to the basic risk model for T2DM (including age, body mass index, family history of diabetes, hypertension, current smoking, current drinking, and regular exercise) significantly increased cNRI, IDI, and AROC in both sexes. Adding either TyG index or FPG into the basic risk model for T2DM increases its prediction and reclassification ability. Compared to FPG, TyG index was a more robust T2DM predictor in the stratified sex and fasting glucose level. Therefore, TyG index should be considered as a screening tool for identification of people at high risk for T2DM in practice.

Evaluation of mental stress by physiological indices derived from finger plethysmography.

PubMed

Minakuchi, Emiko; Ohnishi, Eriko; Ohnishi, Junji; Sakamoto, Shigeko; Hori, Miyo; Motomura, Miwa; Hoshino, Junichi; Murakami, Kazuo; Kawaguchi, Takayasu

2013-10-12

Quantitative evaluation of mental stress is important to prevent stress-related disorders. Finger plethysmography (FPG) is a simple noninvasive method to monitor peripheral circulation, and provides many physiological indices. Our purpose is to investigate how FPG-derived indices reflect on mental stress, and to clarify any association between these physiological indices and subjective indices of mental stress. Thirty-one healthy women (mean age, 22 years ± 2) participated. The participants rested by sitting on a chair for 10 min. They then performed a computerized version of the Stroop color-word conflict test (CWT) for 10 min. Finally, they rested for 10 min. FPG was recorded throughout the experiment. The participants completed a brief form of the Profile of Mood States (POMS) questionnaire before and after the test. Using the FPG data, we conducted chaos analysis and fast Fourier transform analysis, and calculated chaotic attractors, the largest Lyapunov exponent, a high-frequency (HF) component, a low-to-high-frequency (LF/HF) ratio, finger pulse rate and finger pulse wave amplitude. The HF component decreased and the LF/HF ratio increased significantly during the test (P < 0.01), while the confusion subscale of POMS increased after the test (P < 0.05). During testing, finger pulse rate significantly increased (P < 0.001), and the finger pulse wave amplitude decreased (P < 0.001). The attractor size reduced during testing and returned to a baseline level afterwards. Although the largest Lyapunov exponent showed no significant change during testing, significant negative correlation with the tension-anxiety subscale of POMS was observed at the beginning (P < 0.01). A significant negative correlation between the LF/HF ratio and two subscales was also observed in the beginning and middle of the test (P < 0.05). There were no correlations during the rest periods. The physiological indices derived from FPG were changed by mental stress. Our findings indicate that FPG is one of the easiest methods to evaluate mental stress quantitatively. In particular, the largest Lyapunov exponent and the LF/HF ratio might be associated with acute mental stress. Farther examination is needed to find any association between the physiological indices and various types of mental stress.

Evaluation of mental stress by physiological indices derived from finger plethysmography

PubMed Central

2013-01-01

Background Quantitative evaluation of mental stress is important to prevent stress-related disorders. Finger plethysmography (FPG) is a simple noninvasive method to monitor peripheral circulation, and provides many physiological indices. Our purpose is to investigate how FPG-derived indices reflect on mental stress, and to clarify any association between these physiological indices and subjective indices of mental stress. Methods Thirty-one healthy women (mean age, 22 years ± 2) participated. The participants rested by sitting on a chair for 10 min. They then performed a computerized version of the Stroop color-word conflict test (CWT) for 10 min. Finally, they rested for 10 min. FPG was recorded throughout the experiment. The participants completed a brief form of the Profile of Mood States (POMS) questionnaire before and after the test. Using the FPG data, we conducted chaos analysis and fast Fourier transform analysis, and calculated chaotic attractors, the largest Lyapunov exponent, a high-frequency (HF) component, a low-to-high-frequency (LF/HF) ratio, finger pulse rate and finger pulse wave amplitude. Results The HF component decreased and the LF/HF ratio increased significantly during the test (P < 0.01), while the confusion subscale of POMS increased after the test (P < 0.05). During testing, finger pulse rate significantly increased (P < 0.001), and the finger pulse wave amplitude decreased (P < 0.001). The attractor size reduced during testing and returned to a baseline level afterwards. Although the largest Lyapunov exponent showed no significant change during testing, significant negative correlation with the tension-anxiety subscale of POMS was observed at the beginning (P < 0.01). A significant negative correlation between the LF/HF ratio and two subscales was also observed in the beginning and middle of the test (P < 0.05). There were no correlations during the rest periods. Conclusions The physiological indices derived from FPG were changed by mental stress. Our findings indicate that FPG is one of the easiest methods to evaluate mental stress quantitatively. In particular, the largest Lyapunov exponent and the LF/HF ratio might be associated with acute mental stress. Farther examination is needed to find any association between the physiological indices and various types of mental stress. PMID:24119254

Clinical characteristics of type 2 diabetes patients with discordance between HbA1c and fasting plasma glucose in the real world: An analysis of the ORBIT study.

PubMed

Shu, Hua; Lu, Juming; Zhang, Puhong; Zhu, Dongshan; Li, Xian; Ji, Jiachao; Zhao, Fang; Ji, Linong

2018-05-01

We aimed to determine the clinical characteristics of type 2 diabetes patients on basal insulin therapy with inadequate glucose control due to discordance between glycated haemoglobin (HbA 1c ) and fasting plasma glucose (FPG) in the real world. This was a retrospective analysis of data from the ORBIT study in China. Clinical characteristics of patients with discordance between HbA 1c and FPG at baseline and at the end of 6 months of follow-up were analysed using multinomial logistic regression in 4 study groups divided by HbA 1c and FPG. Overall, of 6721 patients initiated on basal insulin, 853 achieved HbA 1c  < 7% but FPG ≥ 7 mmol/L (group 2), while 997 had FPG < 7 mmol/L but HbA 1c  ≥ 7% (group 3) at the end of follow-up. Patients in group 3 had a longer duration of type 2 diabetes compared with those in group 2 (7.22 ± 5.30 vs 6.00 ± 4.80 y, P < .05). Patients on glargine (32.90%) or detemir (36.88%) treatment accounted for a higher proportion of patients with both HbA 1c and FPG controlled than those on neutral protamine Hagedorn therapy (23.45%; P < .05). Per the multinomial logistic analysis, higher frequency of self-monitoring of blood glucose (SMBG) and use of glargine or detemir therapy were significantly inversely associated with risk of discordance between HbA 1c and FPG, while dose of insulin was a risk factor for discordance at the end of follow-up (all P < .05). Patients treated with insulin analogues (glargine or detemir), instead of neutral protamine Hagedorn, and with more frequent SMBG are more likely to exhibit concordance between HbA 1c and FPG. Copyright © 2018 John Wiley & Sons, Ltd.

Lipoprotein(a) concentrations in non-insulin-dependent diabetes mellitus and borderline hyperglycemia: a population-based study.

PubMed

Imperatore, G; Rivellese, A; Galasso, R; Celentano, E; Iovine, C; Ferrara, A; Riccardi, G; Vaccaro, O

1995-10-01

The objective of the study was to compare lipoprotein(a) [Lp(a)] concentrations in population-based samples of individuals with non-insulin-dependent diabetes mellitus (NIDDM), borderline hyperglycemia, and normoglycemia. From 2,740 male Italian Telephone Company employees aged 40 to 59 years participating in a health screening, we selected all those with NIDDM (n = 100) plus a random sample of 950 nondiabetic individuals. Diabetes was defined as fasting plasma glucose (FPG) of at least 140 mg/dL or current use of hypoglycemic drugs. Among nondiabetic individuals, 854 were defined as normoglycemic (FPG < 115 mg/dL) and 95 were defined as borderline hyperglycemic (115 < FPG < 140 mg/dL). Lp(a) level was measured on frozen plasma by enzyme-linked immunosorbent assay. Lp(a) concentrations were similar in people with NIDDM, borderline hyperglycemia, and normoglycemia: 11.2 +/- 14, 14.1 +/- 20, and 13.9 +/- 18 mg/dL, respectively (F = 1.03). Accordingly, the proportion of subjects with Lp(a) levels of at least 30 mg/dL was comparable in the three groups (12%, 15%, and 14%; chi 2 = 3.95, P = .41). Results were not confounded by differences in age, body mass index (BMI), waist to hip ratio, plasma lipids, alcohol consumption, physical activity, and use of drugs. Furthermore, within the diabetic group Lp(a) levels were not significantly different for those on diet only versus those on oral agents (10.8 +/- 14.1 v 11.7 +/- 14.7, P = .7) or for people with FPG of at least 180 as compared with people with FPG less than 180 mg/dL (9.9 +/- 12.8 v 11.5 +/- 14.8, P = .5).(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Genetic Risk Score Modifies Effect of Bisphenol A Exposure on Deterioration in Glucose Metabolism.

PubMed

Bi, Yufang; Wang, Weiqing; Xu, Min; Wang, Tiange; Lu, Jieli; Xu, Yu; Dai, Meng; Chen, Yuhong; Zhang, Di; Sun, Wanwan; Ding, Lin; Chen, Ying; Huang, Xiaolin; Lin, Lin; Qi, Lu; Lai, Shenghan; Ning, Guang

2016-01-01

Epidemiology studies showed inconsistent results regarding the relationship between bisphenol A (BPA) exposure and risk of type 2 diabetes (T2D). This study sought to prospectively investigate associations of BPA with incident T2D risk and the longitudinal changes in glycemic traits, particularly examining the interaction between gene and BPA exposure on the associations. A community-based study was conducted at baseline in 2009, including 2209 nondiabetic middle-age and elderly subjects followed for 4 y. Urinary BPA levels were measured at baseline. A genetic risk score (GRS) based on 34 T2D common variants that identified and validated in East Asians was created. Incident T2D was defined according to the 1999 World Health Organization criteria. Fasting (FPG) and 2-h post-loading plasma glucose were measured at baseline and followup. Multivariable logistic regression analysis demonstrated no significant association of risk of incident T2D with BPA while with increase in the weighted T2D-GRS (odds ratio, 1.89; 95% confidence interval, 1.31-2.72 for each 10-point increment). Similar results were found in 4-y changes of FPG and 2-h post-loading plasma glucose. The GRS modified the effect of BPA exposure on 4-y changes in FPG (P for interaction = .01). Each 1 unit of Log_BPA was associated with 0.1 mmol/L increase in FPG (P = .007) in the highest quartile of GRS; no associations were found in the lower three quartiles of GRS. The T2D genetic susceptibility significantly modulated the association of BPA exposure with longitudinal increase in FPG levels.

Absolute change in fasting plasma glucose over 12 months is associated with 2-year and 5-year major adverse cardiovascular events in patients with drug-eluting stent implants.

PubMed

Kang, Dong Oh; Seo, Hong Seog; Choi, Byung Geol; Lee, Eunmi; Kim, Ji Park; Lee, Sun Ki; Im, Sung Il; Na, Jin Oh; Choi, Cheol Ung; Lim, Hong Euy; Kim, Jin Won; Kim, Eung Ju; Rha, Seung-Woon; Park, Chang Gyu; Oh, Dong Joo

2015-01-20

Major adverse cardiovascular events (MACEs) in patients with or without cardiovascular disease (CVD) are greatly affected by various factors associated with metabolism and inflammation. To determine which clinical parameters at treatment are associated with the development of 2-year and 5-year MACEs in high-risk patients with CVD who have undergone drug-eluting stent (DES) implantation. The present study involved a total of 432 patients who underwent percutaneous coronary intervention with DES. Variables representing the average and absolute amount of change in clinical parameters over the 12-month follow-up were assessed for association with 2-year and 5-year development of MACE. The study population was divided into quartiles for the variable showing the highest correlation to MACE development. Estimated incidence of 2-year and 5-year MACEs for each of the quartiles was determined by survival curve analysis, and subgroup analysis was performed for patients with diabetes and statin users. Absolute change in fasting plasma glucose (FPG) over 12 months showed the highest correlation with 2-year and 5-year MACE development. The estimated incidence of MACE increased with increasing quartiles for absolute change in FPG. The association between absolute change in FPG and MACE development exhibited a stronger relationship for the specific subgroups of patients with diabetes and statin users. Increases and decreases in FPG had a comparable contribution to MACE development. A greater absolute change in FPG over 12 months post-PCI is an independent risk factor for 2-year and 5-year MACE development in DES-implanted patients, especially in the diabetes and statin users. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Fasting plasma glucose, oral glucose tolerance test, and the risk of first-time venous thromboembolism. A report from the VEINS cohort study.

PubMed

Johansson, Magdalena; Lind, Marcus; Jansson, Jan-Håkan; Fhärm, Eva; Johansson, Lars

2018-05-01

It remains unclear whether high plasma glucose levels are associated with venous thromboembolism (VTE). This study investigated the association between fasting plasma glucose (FPG), oral glucose tolerance test (two-hour post-load plasma glucose (2HPG)), diabetes, and VTE. The population-based, prospective Venous thromboEmbolism In Northern Sweden (VEINS) cohort study included 108,025 residents of Västerbotten County in northern Sweden. The participants were aged 30 to 60 years and had no previous VTE events. They were included from 1985 onwards and were followed until a VTE event, death, emigration, or the study end on September 5, 2014. All underwent a health examination that measured weight, height, FPG, and 2HPG and included a questionnaire regarding smoking, education level, and history of diabetes. Potential VTE events were identified by an extensive diagnosis registry search and were validated by reviewing medical records and radiology reports. An objectively verified first-time VTE event was experienced by 2054 participants during 1,496,669 person-years of follow-up. In univariable analysis, there were associations between FPG, 2HPG, diabetes, and the risk of VTE. These associations disappeared after adjustment for potential confounders (age, sex, body mass index, cancer at inclusion, education level, smoking, and hypertension). The adjusted hazard ratios were 1.01 (95% confidence interval 0.83-1.23) for diabetes, 1.01 for each standard deviation of FPG (95% confidence interval 0.97-1.05), and 0.96 for each standard deviation of 2HPG (95% confidence interval 0.91-1.00). There were no independent associations between FPG, 2HPG, diabetes, and future risk of VTE. Copyright © 2018 Elsevier Ltd. All rights reserved.

Saxagliptin improves glycemic control by modulating postprandial glucagon and C-peptide levels in Chinese patients with type 2 diabetes.

PubMed

Sjöstrand, Mikaela; Iqbal, Nayyar; Lu, Jane; Hirshberg, Boaz

2014-08-01

Saxagliptin reduced glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial glucose (PPG) in Asian patients with type 2 diabetes mellitus (T2DM). To understand the physiology of this effect, indices of α- and β-cell function were measured in a subpopulation of Chinese patients following a noodle mixed-meal tolerance test. Data from Chinese patients were pooled from two phase 3, 24-week studies of saxagliptin 5mg/d as monotherapy in drug-naive patients and as add-on to metformin in patients inadequately controlled with metformin alone. The end points for β- and α-cell function were change from baseline in C-peptide, insulin, and glucagon areas under the curve from 0 to 180 min (AUC0-180), insulinogenic index, and insulin sensitivity from Matsuda index after a mixed meal. Also glycemic variables, HbA1c, FPG, and PPG (AUC0-180), and homeostasis model assessment (HOMA) 2β were measured. At 24 weeks, greater improvements in adjusted mean change from baseline HbA1c (difference vs placebo [95% CI], -0.33% [-0.50%, -0.17%], [-4 (-5.5, -1.9) mmol/mol], P<0.0001), FPG (-0.41 [-0.78, -0.03] mmol/L, P=0.03), PPG AUC0-180 (-168 [-245, -91.8] mmol min/L, P<0.0001), C-peptide AUC0-180 (19.7 [5.2, 34.2] nmol min/L, P=0.008), insulinogenic index (0.06% [0.02%, 0.09%], P=0.002), and greater suppression of glucagon secretion (glucagon AUC0-180, -322 [-493.6, -150.7] pmol min/L, P=0.0003) were observed with saxagliptin versus placebo. In Chinese patients with T2DM, saxagliptin as monotherapy or as add-on to metformin improved glycemic control by modulating α- and β-cell function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of high-dose pitavastatin on glucose homeostasis in patients at elevated risk of new-onset diabetes: insights from the CAPITAIN and PREVAIL-US studies.

PubMed

Chapman, M J; Orsoni, A; Robillard, P; Hounslow, N; Sponseller, C A; Giral, P

2014-05-01

Statin treatment may impair glucose homeostasis and increase the risk of new-onset diabetes mellitus, although this may depend on the statin, dose and patient population. We evaluated the effects of pitavastatin 4 mg/day on glucose homeostasis in patients with metabolic syndrome in the CAPITAIN trial. Findings were validated in a subset of patients enrolled in PREVAIL-US. Participants with a well defined metabolic syndrome phenotype were recruited to CAPITAIN to reduce the influence of confounding factors. Validation and comparison datasets were selected comprising phenotypically similar subsets of individuals enrolled in PREVAIL-US and treated with pitavastatin or pravastatin, respectively. Mean change from baseline in parameters of glucose homeostasis (fasting plasma glucose [FPG], glycated hemoglobin [HbA1c], insulin, quantitative insulin-sensitivity check index [QUICKI] and homeostasis model of assessment-insulin resistance [HOMA-IR]) and plasma lipid profile were assessed at 6 months (CAPITAIN) and 3 months (PREVAIL-US) after initiating treatment. In CAPITAIN (n = 12), no significant differences from baseline in HbA1c, insulin, HOMA-IR and QUICKI were observed at day 180 in patients treated with pitavastatin. A small (4%) increase in FPG from baseline to day 180 (P < 0.05), was observed. In the validation dataset (n = 9), no significant differences from baseline in glycemic parameters were observed at day 84 (all comparisons P > 0.05). Similar results were observed for pravastatin in the comparison dataset (n = 14). Other than a small change in FPG in the CAPITAIN study, neutral effects of pitavastatin on glucose homeostasis were observed in two cohorts of patients with metabolic syndrome, independent of its efficacy in reducing levels of atherogenic lipoproteins. The small number of patients and relatively short follow-up period represent limitations of the study. Nevertheless, these data suggest that statin-induced diabetogenesis may not represent a class effect.

Effects of canrenone in patients with metabolic syndrome.

PubMed

Derosa, Giuseppe; Bonaventura, Aldo; Bianchi, Lucio; Romano, Davide; D'Angelo, Angela; Fogari, Elena; Maffioli, Pamela

2013-11-01

Metabolic syndrome is becoming a common disease due to a rise in obesity rates among adults. The aim was to evaluate the effects of canrenone compared to placebo on metabolic and inflammatory parameters in patients affected by metabolic syndrome. A total of 145 patients were treated with placebo or canrenone, 50 mg/day, for 3 months and then 50 mg b.i.d. till the end of the study. Blood pressure, body weight, body mass index, fasting plasma glucose (FPG), fasting plasma insulin, HOMA-IR, lipid profile, plasma aldosterone, brain natriuretic peptide, high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α) and M value were evaluated. A decrease of blood pressure was observed in canrenone group compared to baseline; moreover, systolic blood pressure value recorded after 6 months of canrenone therapy was lower than the one recorded with placebo. Canrenone gave a significant decrease of FPI and HOMA index, and an increase of M value both compared to baseline and to placebo. Canrenone also decreased triglycerides and FPG was not observed with placebo. Canrenone also decreased plasma aldosterone, Hs-CRP and TNF-α compared to baseline and to placebo. Canrenone seems to be effective in reducing some factors involved in metabolic syndrome and in improving insulin-resistance and the inflammatory state observed in these patients.

Comparison of metformin and repaglinide monotherapy in the treatment of new onset type 2 diabetes mellitus in China.

PubMed

Ma, J; Liu, L Y; Wu, P H; Liao, Y; Tao, T; Liu, W

2014-01-01

This study was designed to compare the effects of metformin and repaglinide on the fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) in newly diagnosed type 2 diabetes in China. A total of 107 newly diagnosed type 2 diabetic patients (46 women and 61 men) participated in the study. All patients received 3-month treatment of metformin or repaglinide. Fasting blood glucose and HbA1c were determined at baseline and at the end of the 3-month of treatment. FPG and HbA1c decreased in both metformin and repaglinide groups after 3 months treatment (P < 0.01). The reduction of HbA1c was significantly greater in the repaglinide group (P < 0.01). Metformin decreases fasting insulin concentration and HOMA-IR (P < 0.01), and repaglinide improves HOMA-β(P < 0.01). Triglycerides (TG) were reduced in both groups (P < 0.01 in metformin group; P < 0.05 in repaglinide group), but total cholesterol (TC) and low-density lipoprotein (LDL) were decreased only after metformin treatment (P < 0.05). Both repaglinide and metformin were effective in glycaemic control in new onset patients with type 2 diabetes in China. Repaglinide had no effect on insulin sensitivity, but it improved β-cell function.

[Effect of early high fat diet on pancreatic β cellularity and insulin sensibility in young rats].

PubMed

Xie, Kun-Xia; Xiao, Yan-Feng; Xu, Er-Di; Yin, Chun-Yan; Yi, Xiao-Qing; Chang, Ming

2010-09-01

To study the effects of early high fat diet on sugar metaboliam, insulin sensibility and pancreatic β cellularity in young rats. Sixty male weaned young rats were randomly fed with high fat diet (high fat group) and normal diet (control group). The body weight, viscus fattiness and fasting plasma glucose (FPG) were measured after 3, 6 and 9 weeks. Serum insulin level was measured with radioimmunoassay. The ultrastructure of pancreas was observed under an electricmicroscope. The high fat group had significantly higher body weight and visceral fat weight than the control group after 3 weeks. There were no significant differences in the FPG level between the two groups at all time points. The levels of fasting insulin and HOMAIR in the high fat group were significantly higher than those in the control group after 3, 6 and 9 weeks (P<0.01). Dilation of rough endoplasmic reticulum and mild swelling of mitochondria of islet β-cells were observed in the high fat group after 6 weeks. Early high fat diet may induce a reduction in insulin sensitivity and produce insulin resistance in young rats. Endoplasmic reticulum expansion in β-cells may be an early sign of β-cell damage due to obesity.

Vitamin C intake reduces the cytotoxicity associated with hyperglycemia in prediabetes and type 2 diabetes.

PubMed

Franke, Silvia Isabel Rech; Müller, Luiza Louzada; Santos, Maria Carolina; Fishborn, Arcênio; Hermes, Liziane; Molz, Patrícia; Pereira, Camila Schreiner; Wichmann, Francisca Maria Assmann; Horta, Jorge André; Maluf, Sharbel Weidner; Prá, Daniel

2013-01-01

Hyperglycemia leads to the formation of free radicals and advanced glycation end-products (AGEs). Antioxidants can reduce the level of protein glycation and DNA damage. In this study, we compared the levels of vitamin C intake, which is among the most abundant antioxidants obtained from diet, with the levels of fasting plasma glucose (FPG), glycated hemoglobin (A1C), DNA damage, and cytotoxicity in prediabetic subjects and type 2 diabetic subjects. Our results indicated that there was no significant correlation between FPG or A1C and DNA damage parameters (micronuclei, nucleoplasmic bridges, and nuclear buds). FPG and A1C correlated with necrosis (r = 0.294; P = 0.013 and r = 0.401; P = 0.001, resp.). Vitamin C intake correlated negatively with necrosis and apoptosis (r = -0.246; P = 0.040, and r = -0.276; P = 0.021, resp.). The lack of a correlation between the FPG and A1C and DNA damage could be explained, at least in part, by the elimination of cells with DNA damage by either necrosis or apoptosis (cytotoxicity). Vitamin C appeared to improve cell survival by reducing cytotoxicity. Therefore, the present results indicate the need for clinical studies to evaluate the effect of low-dose vitamin C supplementation in type 2 diabetes.

Balneotherapy and platelet glutathione metabolism in type II diabetic patients

NASA Astrophysics Data System (ADS)

Ohtsuka, Yoshinori; Yabunaka, Noriyuki; Watanabe, Ichiro; Noro, Hiroshi; Agishi, Yuko

1996-09-01

Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r=0.692, P<0.02). After 4 weeks of balneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG <150 mg/dl), the level increased ( P<0.01) and in poorly controlled patients (FPG >150 mg/dl), the value decreased ( P<0.05). There was a negative correlation between glutathione peroxidase (GPX) activities and the levels of FPG ( r=-0.430, P<0.05). After balneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within ±3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

[Relationship between high-sensitivity C-reactive protein and obesity/metabolic syndrome in children].

PubMed

Chen, Fangfang; Wang, Wenpeng; Teng, Yue; Hou, Dongqing; Zhao, Xiaoyuan; Yang, Ping; Yan, Yinkun; Mi, Jie

2014-06-01

To explore the relationship between high-sensitivity C-reactive protein (hsCRP) and obesity/metabolic syndrome (MetS) related factors in children. 403 children aged 10-14 and born in Beijing were involved in this study. Height, weight, waist circumference, fat mass percentage (Fat%), blood pressure (BP), hsCRP, triglyceride (TG), total cholesterol (TC), fasting plasma glucose (FPG), high and low density lipoprotein cholesterol (HDL-C, LDL-C) were observed among these children. hsCRP was transformed with base 10 logarithm (lgCRP). MetS was defined according to the International Diabetes Federation 2007 definition. Associations between MetS related components and hsCRP were tested using partial correlation analysis, analysis of covariance and linear regression models. 1) lgCRP was positively correlated with BMI, waist circumference, Fat%,BP, FPG, LDL-C and TC while negatively correlated with HDL-C. With BMI under control, the relationships disappeared, but LDL-C (r = 0.102). 2) The distributions of lgCRP showed obvious differences in all the metabolic indices, in most groups, respectively. With BMI under control, close relationships between lgCRP and high blood pressure/high TG disappeared and the relationship with MetS weakened. 3) Through linear regression models, factors as waist circumference, BMI, Fat% were the strongest factors related to hsCRP, followed by systolic BP, HDL-C, diastolic BP, TG and LDL-C. With BMI under control, the relationships disappeared, but LDL-C(β = 0.045). hsCRP was correlated with child obesity, lipid metabolism and MetS. Waist circumference was the strongest factors related with hsCRP. Obesity was the strongest and the independent influencing factor of hsCRP.

The gene-treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes: Fukuoka diabetes registry.

PubMed

Sumi, Akiko; Nakamura, Udai; Iwase, Masanori; Fujii, Hiroki; Ohkuma, Toshiaki; Ide, Hitoshi; Jodai-Kitamura, Tamaki; Komorita, Yuji; Yoshinari, Masahito; Hirakawa, Yoichiro; Hirano, Atsushi; Kubo, Michiaki; Kitazono, Takanari

2017-12-12

Although statins deteriorate glucose metabolism, their glucose-lowering effects have emerged in some situations. Here, we assessed whether these effects are a consequence of statins' interaction with paraoxonase (PON)1 enzyme polymorphism. Adult Japanese type 2 diabetes patients (n = 3798) were enrolled in a cross-sectional study. We used Q192R polymorphism of the PON1 gene as a representative single-nucleotide polymorphism and focused on the effects of the wild-type Q allele, in an additive manner. For patients with and without statin therapy, the associations of this allele with fasting plasma glucose (FPG), HbA 1c , C-peptide, HOMA2-%β, and HOMA2-IR were investigated separately using a linear regression model, and were compared between groups by testing interactions. Sensitivity analyses were performed using propensity score to further control the imbalance of characteristics between groups. Among patients with statin therapy, there were linear associations of the number of Q alleles with decreased FPG and HbA 1c , and with increased serum C peptide and HOMA2-%β (all P < 0.01 for trends), while such associations were not observed among those without statin therapy. These differences were statistically significant only for serum C peptide and HOMA2-%β (P < 0.01 for interactions). These associations remained significant after multiple explanatory variable adjustment. Sensitivity analyses using propensity score showed broad consistency of these associations. Patients with the Q allele of the PON1 Q192R polymorphism who were treated with statins exhibited improvement in glucose metabolism, especially in insulin secretion, suggesting the importance of genotyping PON1 Q192R to identify those who could benefit from statin therapy.

Fetal Genotype and Maternal Glucose Have Independent and Additive Effects on Birth Weight.

PubMed

Hughes, Alice E; Nodzenski, Michael; Beaumont, Robin N; Talbot, Octavious; Shields, Beverley M; Scholtens, Denise M; Knight, Bridget A; Lowe, William L; Hattersley, Andrew T; Freathy, Rachel M

2018-05-01

Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The fetal genetic score influenced birth weight independently of maternal FPG and impacted growth at all levels of maternal glycemia. For mothers with FPG in the top tertile, the frequency of large for gestational age (birth weight ≥90th centile) was 31.1% for offspring with the highest tertile genetic score and only 14.0% for those with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic score was not associated with cord insulin or C-peptide. Similar results were seen for HAPO participants of non-European ancestry ( n = 2,842 pairs). This work demonstrates that for any level of maternal FPG, fetal genetics has a major impact on fetal growth and acts predominantly through independent mechanisms. © 2018 by the American Diabetes Association.

Improvements of ambient hyperglycemia and glycemic variability are associated with reduction in oxidative stress for patients with type 2 diabetes.

PubMed

Ohara, Makoto; Nagaike, Hiroe; Goto, Satoshi; Fukase, Ayako; Tanabe, Yuki; Tomoyasu, Masako; Yamamoto, Takeshi; Hayashi, Toshiyuki; Fukui, Tomoyasu; Hirano, Tsutomu

2018-05-01

We aimed to evaluate which parameters of improvement in glucose metabolism reduce oxidative stress for patients with Type 2 diabetes mellitus (T2DM). Sixty-seven outpatients with T2DM underwent 72 h of continuous glucose monitoring (CGM) and were measured for oxidative stress before and after a 24-week intervention with the following targets: fasting plasma glucose (FPG), <130 mg/dl; postprandial plasma glucose (PPG), <180 mg/dl; and glycated hemoglobin (HbA1c), <7% (53 mmol/mol). The mean glucose level (MGL), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), percentage coefficient of variation for glucose (%CV) and area under the postprandial plasma glucose curve (AUC PP ) were calculated from the CGM data. Oxidative stress was estimated using the diacron-reactive oxygen metabolites (d-ROMs) test. Finally, the association between the improvements in glucose metabolism and oxidative stress was evaluated. FPG, MGL, HbA1c, MAGE, MODD, %CV, AUC PP , and d-ROMs significantly improved after 24 weeks of intervention. The change in d-ROMs was significantly correlated with that in FPG (r = 0.414), MGL (r = 0.402), HbA1c (r = 0.271), MAGE (r = 0.457), MODD (r = 0.371), and AUC PP (r = 0.352). The correlation of the change in d-ROMs with that in FPG, MAGE, and MODD and the use of glucose-like peptide 1 receptor agonists and statins remained significant after adjustment for other markers of diabetes control (multiple R 2 = 0.406). Improvements in glucose metabolism, including FPG and daily and day-to-day glucose variability, were all correlated with reduced oxidative stress for patients with T2DM. Published by Elsevier B.V.

Alternative indices of glucose homeostasis as biochemical diagnostic tests for abnormal glucose tolerance in an African setting.

PubMed

Kengne, Andre Pascal; Erasmus, Rajiv T; Levitt, Naomi S; Matsha, Tandi E

2017-04-01

Accurate diabetes diagnosis is important in Africa, where rates are increasing, and the disease largely undiagnosed. The cumbersome oral glucose tolerance test (OGTT) remains the reference standard, while alternative diagnostic methods are not yet established in Africans. We assessed the ability of fasting plasma glucose (FPG), HbA1c and fructosamine, to diagnose OGTT-based abnormal glucose tolerance in mixed-ancestry South Africans. Mixed-ancestry adults, residing in Cape Town were examined between February and November 2015. OGTT values were used to classify glucose tolerance status as: screen-detected diabetes, prediabetes, dysglycaemia (combination of diabetes and prediabetes) and normal glucose tolerance. Of the 793 participants included, 65 (8.2%) had screen-detected diabetes, 157 (19.8%) prediabetes and 571 (72.0%) normal glucose tolerance. Correlations of FPG and 2-h glucose with HbA1c (r=0.51 and 0.52) were higher than those with fructosamine (0.34 and 0.30), both p<0.0001. The highest c-statistic for the prediction of abnormal glucose tolerance was recorded with 2-h glucose [c-statistic=0.997 (screen-detected diabetes), 0.979 (prediabetes) and 0.984 (dysglycaemia)] and the lowest with fructosamine (0.865, 0.596 and 0.677). At recommended or data-specific optimal cut-offs, no combination of FPG, HbA1c and fructosamine did better than 2-h glucose, while FPG was better than HbA1c and fructosamine on a range of performance measures. Abnormal glucose tolerance in this population is overwhelmingly expressed through 2-h glucose's abnormalities; and no combination of FPG, HbA1c and fructosamine was effective at accurately discriminating OGTT-defined abnormal glucose tolerance. Tested non-glucose based strategies are unreliable alternatives to OGTT for dysglycaemia diagnosis in this population. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Fasting plasma glucose and variation in cardiometabolic risk factors in people with high-risk HbA1c-defined prediabetes: A cross-sectional multiethnic study.

PubMed

Srivanichakorn, Weerachai; Godsland, Ian F; Thomson, Hazel; Misra, Shivani; Phisalprapa, Pochamana; Charatcharoenwitthaya, Phunchai; Pramyothin, Pornpoj; Washirasaksiri, Chaiwat; Snehalatha, Chamukuttan; Ramachandran, Ambady; Alberti, K George M M; Johnston, Desmond G; Oliver, Nick S

2017-12-01

Variation in cardiometabolic risk in prediabetes and any impacts of ethnicity on such variation have been little studied. In an ethnically diverse dataset, selected according to a high-risk HbA1c-based definition of prediabetes, we have investigated relationships between glycaemia and cardiometabolic risk factors and the influence of ethnicity on these relationships. We undertook a cross-sectional analysis of baseline data from a diabetes prevention study in the UK and a chronic care clinic in Thailand, selected for people without diabetes (fasting plasma glucose <7.0 mmol/l) with HbA1c 6.0-6.4% (42-47 mmol/mol). Thai (n=158) and UK White (n=600), South Asian (n=112), Black (n=70) and other/mixed (n=103) groups were distinguished and measurements included fasting plasma glucose (FPG), blood pressure (BP), lipids and insulin resistance-related risk factors (IRFs). Independently of individual characteristics including ethnicity, only systolic BP was weakly associated with FPG (beta coefficient 1.76 (95%CI 0.10-3.42), p 0.03) and only LDL-c with IFG (FPG 5.6 to <7) (adjusted -0.14 (-0.27, -0.003) p 0.04). There were no significant independent associations with cardiometabolic risk factors when categories of impaired fasting glucose (FPG ≥ 6.1 to <7.0 mmol/L) were considered. Relative to White, South Asian ethnicity was independently associated with lower systolic and diastolic BP, Black with lower triglycerides, cholesterol/HDL-c ratio and having 2 or more IRFs, and Thai with lower cholesterol/HDL-c ratio and all three non-white ethnicities with lower total and LDL cholesterol. In high-risk HbA1c-defined prediabetes additional measurement of FPG will add little to evaluation of cardiometabolic risk. Additionally, UK Whites tend to have the most adverse cardiometabolic profile of any ethnic group. Copyright © 2017 Elsevier B.V. All rights reserved.

Kepler Commissioning Data for Measurement of the Pixel Response Function and Focal Plane Geometry

NASA Technical Reports Server (NTRS)

Bryson, Stephen T.

2017-01-01

This document describes the Kepler PRF/FPG data release. This data was taken on April 27-29, 2009, during Kepler's commissioning phase in order to measure the pixel response function (PRF) (Bryson et al., 2010a) and focal plane geometry (FPG) (Tenenbaum and Jenkins, 2010). 33,424 stellar targets were observed for 243 long cadences, each with a duration of 14.7 minutes (half the duration of a normal Kepler long cadence). During these 243 cadences the Kepler photometer was moved, pointing in a dither pattern to facilitate PRF measurement. Motion occurred during the even cadences (second, fourth, etc.), with the telescope in stable fine point at each pointing in the dither pattern during the odd cadences (first, third, etc.). The first and last cadences were at the center of the dither pattern. Motion cadences are included in this release, but they do not contain any data. For details on how this data was used to derive the Kepler PRF and FPG models, see Bryson et al. (2010a) and Tenenbaum and Jenkins (2010). Descriptions of the PRF and FPG models are found in Thompson et al. (2016), x2.3.5.17 and x2.3.5.16 respectively. The data in this release can be used to recompute the Kepler PRF and FPG. Such a reconstruction, however, would not reflect measured seasonal changes in the PRF described in Van Cleve et al. (2016b), x5.2.The dither pattern is shown in Figure 1. The crosses show the commanded pointings and the circles show the measured pointings. Measured pointings are different from the commanded pointings due to the early state of calibration of the fine guidance sensors during commissioning (Van Cleve et al., 2016a). The measured offsets from the center of the pattern are given in RADEC offsets and pixel offsets in Table 1. The order of the offsets was randomized during data collection to avoid time-dependent systematics.

Exposure to Ultrafine Particles from Ambient Air and Oxidative Stress–Induced DNA Damage

PubMed Central

Bräuner, Elvira Vaclavik; Forchhammer, Lykke; Møller, Peter; Simonsen, Jacob; Glasius, Marianne; Wåhlin, Peter; Raaschou-Nielsen, Ole; Loft, Steffen

2007-01-01

Background Particulate matter, especially ultrafine particles (UFPs), may cause health effects through generation of oxidative stress, with resulting damage to DNA and other macromolecules. Objective We investigated oxidative damage to DNA and related repair capacity in peripheral blood mononuclear cells (PBMCs) during controlled exposure to urban air particles with assignment of number concentration (NC) to four size modes with average diameters of 12, 23, 57, and 212 nm. Design Twenty-nine healthy adults participated in a randomized, two-factor cross-over study with or without biking exercise for 180 min and with exposure to particles (NC 6169-15362/cm3) or filtered air (NC 91-542/cm3) for 24 hr. Methods The levels of DNA strand breaks (SBs), oxidized purines as formamidopyrimidine DNA glycolase (FPG) sites, and activity of 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1) in PBMCs were measured by the Comet assay. mRNA levels of OGG1, nucleoside diphosphate linked moiety X-type motif 1 (NUDT1), and heme oxygenase-1 (HO1) were determined by real-time reverse transcriptase–polymerase chain reaction. Results Exposure to UFPs for 6 and 24 hr significantly increased the levels of SBs and FPG sites, with a further insignificant increase after physical exercise. The OGG1 activity and expression of OGG1, NUDT1, and HO1 were unaltered. There was a significant dose–response relationship between NC and DNA damage, with the 57-nm mode as the major contributor to effects. Concomitant exposure to ozone, nitrogen oxides, and carbon monoxide had no influence. Conclusion Our results indicate that UFPs, especially the 57-nm soot fraction from vehicle emissions, causes systemic oxidative stress with damage to DNA and no apparent compensatory up-regulation of DNA repair within 24 hr. PMID:17687444

Biochemical and bioaccumulation approaches for investigating marine pollution using Mediterranean rainbow wrasse, Coris julis (Linneaus 1798).

PubMed

Tomasello, Barbara; Copat, Chiara; Pulvirenti, Valentina; Ferrito, Venera; Ferrante, Margherita; Renis, Marcella; Sciacca, Salvatore; Tigano, Concetta

2012-12-01

A multibiomarkers approach was used in order to estimate and monitor marine pollution. Coris julis (Linneaus, 1758) was chosen as a sentinel organism, and the specimens were collected from three well-known sites along the Ionic coast of Sicily: the protected marine area (P.M.A) "Cyclop's Islands" of Acitrezza (CT), used as a control site, Riposto (CT), and the industrial site of Augusta (SR). Abiotic levels of contaminants were also detected. High levels of biotic and abiotic accumulation were found at the industrial site in which the presence of genotoxic and oxidative damage were also evidenced, measured by Micronuclei, Alkaline and Fpg-modified Comet assays. The protein expression analysis showed metallothioneins (MTs) as good tissue-specific markers of metal accumulation. Their levels were significantly higher in muscle than in liver tissue for all the sampling sites, with a positive correlation among tissue levels and the degree of pollution at the sites. Conversely, heat shock proteins 70 (HSP70) expression was higher in Augusta and Riposto than in the control site, but no significant difference was found between the examined tissues among all sites. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of Metformin and Repaglinide Monotherapy in the Treatment of New Onset Type 2 Diabetes Mellitus in China

PubMed Central

Ma, J.; Liu, L. Y.; Wu, P. H.; Liao, Y.; Tao, T.; Liu, W.

2014-01-01

Objective. This study was designed to compare the effects of metformin and repaglinide on the fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) in newly diagnosed type 2 diabetes in China. Methods. A total of 107 newly diagnosed type 2 diabetic patients (46 women and 61 men) participated in the study. All patients received 3-month treatment of metformin or repaglinide. Fasting blood glucose and HbA1c were determined at baseline and at the end of the 3-month of treatment. Results. FPG and HbA1c decreased in both metformin and repaglinide groups after 3 months treatment (P < 0.01). The reduction of HbA1c was significantly greater in the repaglinide group (P < 0.01). Metformin decreases fasting insulin concentration and HOMA-IR (P < 0.01), and repaglinide improves HOMA-β  (P < 0.01). Triglycerides (TG) were reduced in both groups (P < 0.01 in metformin group; P < 0.05 in repaglinide group), but total cholesterol (TC) and low-density lipoprotein (LDL) were decreased only after metformin treatment (P < 0.05). Conclusions. Both repaglinide and metformin were effective in glycaemic control in new onset patients with type 2 diabetes in China. Repaglinide had no effect on insulin sensitivity, but it improved β-cell function. PMID:24772445

Relationship between insulin sensitivity index and cognitive function in diet-induced insulin resistant rats.

PubMed

Chen, Sisi; Xie, Hao; Wu, Jing; Hong, Hao; Jin, Jianwen; Fang, Jinbo; Huang, Ji; Fu, Ying Zhou; Ji, Hui; Li, Yong Qi; Long, Yan; Xia, Yuan Zheng

2009-06-01

Clinical and animal studies have revealed significant cognitive impairment in type II diabetic subjects. However, whether there is a relationship between insulin resistance and cognitive function is poorly understood. In the present study, we used a high fat diet to induce insulin resistance (IR) in rats, insulin sensitivity index (ISI) (= FINS x FPG/22.5) to assess the extent of insulin resistance and the Morris Water Maze Task to judge cognitive function. The relationship between insulin sensitivity index and cognitive function was determined by analysing the correlation between ISI and the time rat spent in targeted quadrant, as well as between ISI and the times the rat swam across the very point where a platform was previously placed, using Pearson's method. Perfect negative correlation between ISI and cognitive function existed when ISI fell within a certain range, which indicates that insulin resistance is associated with cognitive function impairment in some cases where ISI might be an indicator.

Measuring Pressure Has a New Standard

NASA Technical Reports Server (NTRS)

2002-01-01

The Force-Balanced Piston Gauge (FPG) tests and calibrates instrumentation operating in the low pressure range. The system provides a traceable, primary calibration standard for measuring pressures in the range of near 0 to 15 kPa (2.2 psi) in both gauge and absolute measurement modes. The hardware combines a large area piston-cylinder with a load cell measuring the force resulting from pressures across the piston. The mass of the piston can be tared out, allowing measurement to start from zero. A pressure higher than the measured pressure, which keeps the piston centered, lubricates an innovative conical gap located between the piston and the cylinder, eliminating the need for piston rotation. A pressure controller based on the control of low gas flow automates the pressure control. DHI markets the FPG as an automated primary standard for very low-gauge and absolute pressures. DHI is selling the FPG to high-end metrology laboratories on a case by case basis, with a full commercial release to follow.

HOMA-IR Values are Associated With Glycemic Control in Japanese Subjects Without Diabetes or Obesity: The KOBE Study.

PubMed

Hirata, Takumi; Higashiyama, Aya; Kubota, Yoshimi; Nishimura, Kunihiro; Sugiyama, Daisuke; Kadota, Aya; Nishida, Yoko; Imano, Hironori; Nishikawa, Tomofumi; Miyamatsu, Naomi; Miyamoto, Yoshihiro; Okamura, Tomonori

2015-01-01

Several studies have reported that insulin resistance was a major risk factor for the onset of type 2 diabetes mellitus in individuals without diabetes or obesity. We aimed to clarify the association between insulin resistance and glycemic control in Japanese subjects without diabetes or obesity. We conducted a community-based cross-sectional study including 1083 healthy subjects (323 men and 760 women) in an urban area. We performed multivariate regression analyses to estimate the association between the homeostasis model assessment of insulin resistance (HOMA-IR) values and markers of glycemic control, including glycated haemoglobin (HbA1c), 1,5-anhydroglucitol (1,5-AG), and fasting plasma glucose (FPG) levels, after adjustment for potential confounders. Compared with the lowest tertile of HOMA-IR values, the highest tertile was significantly associated with HbA1c and FPG levels after adjustment for potential confounders, both in men (HbA1c: β = 1.83, P = 0.001; FPG: β = 0.49, P < 0.001) and women (HbA1c: β = 0.82, P = 0.008; FPG: β = 0.39, P < 0.001). The highest tertile of HOMA-IR values was inversely associated with 1,5-AG levels compared with the lowest tertile (β = -18.42, P = 0.009) only in men. HOMA-IR values were associated with markers of glycemic control in Japanese subjects without diabetes or obesity. Insulin resistance may influence glycemic control even in a lean, non-diabetic Asian population.

Anti-Mullerian hormone and insulin resistance in classic phenotype lean PCOS.

PubMed

Caglar, Gamze Sinem; Kahyaoglu, Inci; Pabuccu, Recai; Demirtas, Selda; Seker, Rabia

2013-10-01

This study is designed to explore the correlation between AMH levels and IR in normal weight PCOS women. This prospective study was conducted on 55 patients, who were admitted to obstetrics and gynecology department of a university clinic. Study group was consisted of 34 patients diagnosed as polycystic ovary syndrome (PCOS) according to the Rotterdam Criteria, whereas control group was consisted of 21 healthy volunteers without any features of clinical or biochemical hyperandrogenism, who had regular menstrual cycles. BMI ≥ 25 kg/m(2) were considered overweight and obese and excluded. Blood samples were obtained during days 2-3 after spontaneous menses or progesterone-induced withdrawal bleeding after overnight fasting for at least 12 h. The weight, height, hip and waist circumferences of the patients were measured. Fasting insulin and glucose (FPG) levels were used for calculating different insulin resistance indexes (Homeostatic Model Assessment (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI)). No significant difference was found between PCOS and control groups regarding the mean age, BMI, waist to hip ratio (WHR), mean values of FPG, FPG/insulin ratio and HOMA B (p > 0.05). AMH values were significantly higher in PCOS cases when compared with controls (4.7 vs. 3.4 ng/mL) (p < 0.05).The mean values of HOMA-IR and QUICKI indexes were significantly higher among PCOS cases when compared with controls. E2 levels were significantly lower and Total-T were significantly higher in PCOS patients. When PCOS cases are categorized according to the existence of IR, no difference in Total-T and AMH levels between both groups. Although not statistically significant, a negative correlation of AMH with HOMA-IR and a positive correlation with QUICKI index were found. Among the hormone parameters, AMH was found to be positively correlated with Total-T (r = 0.332, p = 0.013). Although the relation between AMH and androgen production is supported by current evidence, the mechanism underlying the relation between AMH and insulin resistance is not clear yet.

Young overweight and obese women with lower circulating osteocalcin concentrations exhibit higher insulin resistance and concentrations of C-reactive protein.

PubMed

Lucey, Alice J; Paschos, Georgios K; Thorsdottir, Inga; Martínéz, J Alfredo; Cashman, Kevin D; Kiely, Máireád

2013-01-01

The role of the skeleton in the regulation of energy metabolism in humans is not clear. This study investigates the hypothesis that biomarkers of bone turnover are associated with indices of glucose homeostasis and systemic inflammation in young adults. A cross-sectional study investigating the relationships between biomarkers of bone turnover (serum total and uncarboxylated osteocalcin, bone-specific alkaline phosphatase, C-telopeptide of type I collagen, urinary N-telopeptide of type I collagen) and glucose metabolism (fasting plasma glucose [FPG], insulin, insulin resistance [homeostatic model assessment of insulin resistance]), systemic inflammation (high-sensitivity C-reactive protein [hsCRP] and interleukin-6), adipokines (leptin and adiponectin), and body composition was conducted in 268 young, nondiabetic overweight and obese adults aged 20 to 40 years (116 men, 152 women; body mass index, 27.5-32.5 kg/m(2)). Data on diet, physical activity, serum 25-hydroxyvitamin D, and parathyroid hormone were also collected. In women, there was a stepwise increase in lean body mass (P < .05) and a decrease in serum hsCRP (P < .001) across tertiles of total osteocalcin. Multiple linear regression analysis showed significant inverse associations between total osteocalcin and FPG (β = -0.350; P = .016; 95% confidence interval [CI], -0.35 to -0.04), insulin (β = -0.455; P = .002; 95% CI, -1.9 to -0.46), and homeostatic model assessment of insulin resistance (β = -0.508; P = .001; 95% CI, -10.93 to -3.17) in women with total osteocalcin concentrations below the group median. Men in the lowest tertile of uncarboxylated osteocalcin had twice the concentration of hsCRP than did other men (P = .05). In this sample, women with less lean body mass had lower circulating total osteocalcin concentrations and exhibited higher FPG, insulin resistance, and hsCRP compared with their similarly sized counterparts, suggesting that associations between osteocalcin and systemic inflammation, glucose homeostasis, and insulin resistance may be influenced by differences in sex and body composition. Copyright © 2013 Elsevier Inc. All rights reserved.

A Novel Index Using Soluble CD36 Is Associated with the Prevalence of Type 2 Diabetes Mellitus: Comparison Study with Triglyceride-Glucose Index.

PubMed

Kim, Ho Jin; Moon, Jun Sung; Park, Il Rae; Kim, Joong Hee; Yoon, Ji Sung; Won, Kyu Chang; Lee, Hyoung Woo

2017-09-01

Plasma soluble cluster determinant 36 (sCD36) level is closely related with insulin resistance and atherosclerosis, but little is known whether it could be a surrogate for estimating risk of developing diabetes or not. To address this, we evaluated association between sCD36 index, the product of sCD36 and fasting plasma glucose (FPG), and the prevalence of type 2 diabetes mellitus (T2DM), and then compared with triglyceride-glucose (TyG) index which has been suggested simple index for insulin resistance. This was cross-sectional study, and participants were classified as normal glucose tolerance (NGT), prediabetes, and T2DM according to glucose tolerance. The formula of TyG index was 'ln [FPG (mg/dL)×triglyceride (mg/dL)/2],' and the sCD36 index was 'ln [sCD36 (pg/mL)×FPG (mg/dL)/2].' One hundred and fifty-five subjects (mean age, 55.2 years) were enrolled, and patients with T2DM were 75. Both indexes were significantly increased in prediabetes and T2DM rather than NGT, and sCD36 index was positively correlated with both glycosylated hemoglobin and homeostasis model assessment of insulin resistance (r=0.767 and r=0.453, respectively; P<0.05) and negatively with homeostasis model assessment estimate of β-cell function (r=-0.317). The odds ratio (OR) of sCD36 index for T2DM was 4.39 (95% confidential interval, 1.51 to 12.77) after adjusting age, gender, blood pressure, smoking, alcohol, non-high density lipoprotein cholesterol and high-sensitivity C-reactive protein. However, OR of TyG index did not remained significance after adjustment. sCD36 index has an independent association with the risk of T2DM, and showed better correlation than TyG index. These results suggest sCD36 index might be useful surrogate marker for the risk of diabetes. Copyright © 2017 Korean Endocrine Society

Impact of ethnicity on gestational diabetes identified with the WHO and the modified International Association of Diabetes and Pregnancy Study Groups criteria: a population-based cohort study.

PubMed

Jenum, Anne K; Mørkrid, Kjersti; Sletner, Line; Vangen, Siri; Vange, Siri; Torper, Johan L; Nakstad, Britt; Voldner, Nanna; Rognerud-Jensen, Odd H; Berntsen, Sveinung; Mosdøl, Annhild; Skrivarhaug, Torild; Vårdal, Mari H; Holme, Ingar; Yajnik, Chittaranjan S; Birkeland, Kåre I

2012-02-01

The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recently proposed new criteria for diagnosing gestational diabetes mellitus (GDM). We compared prevalence rates, risk factors, and the effect of ethnicity using the World Health Organization (WHO) and modified IADPSG criteria. This was a population-based cohort study of 823 (74% of eligible) healthy pregnant women, of whom 59% were from ethnic minorities. Universal screening was performed at 28±2 weeks of gestation with the 75 g oral glucose tolerance test (OGTT). Venous plasma glucose (PG) was measured on site. GDM was diagnosed as per the definition of WHO criteria as fasting PG (FPG) ≥7.0 or 2-h PG ≥7.8 mmol/l; and as per the modified IADPSG criteria as FPG ≥5.1 or 2-h PG ≥8.5 mmol/l. OGTT was performed in 759 women. Crude GDM prevalence was 13.0% with WHO (Western Europeans 11%, ethnic minorities 15%, P=0.14) and 31.5% with modified IADPSG criteria (Western Europeans 24%, ethnic minorities 37%, P< 0.001). Using the WHO criteria, ethnic minority origin was an independent predictor (South Asians, odds ratio (OR) 2.24 (95% confidence interval (CI) 1.26-3.97); Middle Easterners, OR 2.13 (1.12-4.08)) after adjustments for age, parity, and prepregnant body mass index (BMI). This increased OR was unapparent after further adjustments for body height (proxy for early life socioeconomic status), education and family history of diabetes. Using the modified IADPSG criteria, prepregnant BMI (1.09 (1.05-1.13)) and ethnic minority origin (South Asians, 2.54 (1.56-4.13)) were independent predictors, while education, body height and family history had little impact. GDM prevalence was overall 2.4-times higher with the modified IADPSG criteria compared with the WHO criteria. The new criteria identified many subjects with a relatively mild increase in FPG, strongly associated with South Asian origin and prepregnant overweight.

Florida Best Practice Psychotherapeutic Medication Guidelines for Adults With Major Depressive Disorder.

PubMed

McIntyre, Roger S; Suppes, Trisha; Tandon, Rajiv; Ostacher, Michael

2017-06-01

Herein we provide the 2015 update for the Florida Best Practice Psychotherapeutic Medication Guidelines (FPG) for major depressive disorder (MDD). The FPG represent evidence-based decision support for practitioners providing care to adults with MDD. The consensus meeting included representatives from the Florida Agency for Health Care Administration (FAHCA), advocacy members, academic experts in MDD, and multidisciplinary mental health clinicians, as well as health policy experts. The FAHCA provided funding support for the FPG. Evidence was limited to results from adequately powered, randomized, double-blind, placebo-controlled trials; in addition, pooled-, meta-, and network-analyses were included. Recommendations were based on consensus arrived at by the multistakeholder Florida Expert Panel. Articles selected were identified on the electronic search engine PubMed with the dates 2010 to present. The search terms were major depressive disorder, psychopharmacology, antidepressants, psychotherapy, neuromodulation, complementary alternative medicines, pooled-analysis, meta-analysis, and network-analysis. Bibliographies of the identified articles were manually searched for additional citations not identified in the original search. A consensus meeting comprising all representatives took place on September 25-26, 2015, in Tampa, Florida. Guiding principles (eg, emphasis on the most rigorous evidence for efficacy, safety, and tolerability) were discussed, defined, and operationalized prior to review of extant data. As MDD often pursues a recurrent and chronic course, principles of practice, measurement-based care, and comprehensive assessment and management of overall physical and mental health were emphasized. Evidence supporting pretreatment major depressive episode specifiers (eg, mixed features, anxious distress) and the role of pharmacogenomics (and other biological-behavioral markers) in informing treatment selection were comprehensively discussed. Algorithmic priority was assigned to agents with relatively greater therapeutic index (ie, efficacy) and minimal propensity for safety and tolerability disadvantages. The updated 2015 FPG provide concise, pragmatic, evidence-based decision support for treatment selection and sequencing for adults with MDD. Principles of practice include measurement-based care, priority to both psychiatric and medical comorbidity, identification of DSM-5-defined specifiers (eg, mixed features), suicide risk assessment, and evaluation of cognitive symptoms. The FPG have purposefully aimed to minimize emphasis on "expert opinion" and instead differentially emphasized extant evidence for pharmacologic treatments. © Copyright 2017 Physicians Postgraduate Press, Inc.

A global study of the unmet need for glycemic control and predictor factors among patients with type 2 diabetes mellitus who have achieved optimal fasting plasma glucose control on basal insulin.

PubMed

Raccah, Denis; Chou, Engels; Colagiuri, Stephen; Gaàl, Zsolt; Lavalle, Fernando; Mkrtumyan, Ashot; Nikonova, Elena; Tentolouris, Nikolaos; Vidal, Josep; Davies, Melanie

2017-03-01

This study used data from different sources to identify the extent of the unmet need for postprandial glycemic control in patients with type 2 diabetes mellitus (T2DM) after the initiation of basal insulin therapy in Europe, Asia Pacific, the United States, and Latin America. Different levels of evidence were used as available for each country/region, with data extracted from seven randomized controlled trials (RCTs), three clinical trial registries (CTRs), and three electronic medical record (EMR) databases. Glycemic status was categorized as "well controlled" (glycated hemoglobin [HbA 1c ] at target [<7%]), "residual hyperglycemia" (fasting plasma glucose [FPG] but not HbA 1c at target [FPG <7.2/7.8 mmol/L, <130/140 mg/dL, depending on country-specific recommendations]), or "uncontrolled" (both FPG and HbA 1c above target). Predictor factors were identified from the RCT data set using logistic regression analysis. RCT data showed that 16.9% to 28.0%, 42.7% to 54.4%, and 16.9% to 38.1% of patients with T2DM had well-controlled glycemia, residual hyperglycemia, and uncontrolled hyperglycemia, respectively. In CTRs, respective ranges were 21.8% to 33.6%, 31.5% to 35.6%, and 30.7% to 46.8%, and in EMR databases were 4.4% to 21.0%, 23.9% to 31.8%, and 53.6% to 63.8%. Significant predictor factors of residual hyperglycemia identified from RCT data included high baseline HbA 1c (all countries/regions except Brazil), high baseline FPG (United Kingdom/Japan), longer duration of diabetes (Brazil), and female sex (Europe/Latin America). Irrespective of intrinsic differences between data sources, 24% to 54% of patients with T2DM globally had residual hyperglycemia with HbA 1c not at target, despite achieving FPG control, indicating a significant unmet need for postprandial glycemic control. © 2016 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.

Genome-wide copy number variation analysis identified deletions in SFMBT1 associated with fasting plasma glucose in a Han Chinese population.

PubMed

Chung, Ren-Hua; Chiu, Yen-Feng; Hung, Yi-Jen; Lee, Wen-Jane; Wu, Kwan-Dun; Chen, Hui-Ling; Lin, Ming-Wei; Chen, Yii-Der I; Quertermous, Thomas; Hsiung, Chao A

2017-08-08

Fasting glucose and fasting insulin are glycemic traits closely related to diabetes, and understanding the role of genetic factors in these traits can help reveal the etiology of type 2 diabetes. Although single nucleotide polymorphisms (SNPs) in several candidate genes have been found to be associated with fasting glucose and fasting insulin, copy number variations (CNVs), which have been reported to be associated with several complex traits, have not been reported for association with these two traits. We aimed to identify CNVs associated with fasting glucose and fasting insulin. We conducted a genome-wide CNV association analysis for fasting plasma glucose (FPG) and fasting plasma insulin (FPI) using a family-based genome-wide association study sample from a Han Chinese population in Taiwan. A family-based CNV association test was developed in this study to identify common CNVs (i.e., CNVs with frequencies ≥ 5%), and a generalized estimating equation approach was used to test the associations between the traits and counts of global rare CNVs (i.e., CNVs with frequencies <5%). We found a significant genome-wide association for common deletions with a frequency of 5.2% in the Scm-like with four mbt domains 1 (SFMBT1) gene with FPG (association p-value = 2×10 -4 and an adjusted p-value = 0.0478 for multiple testing). No significant association was observed between global rare CNVs and FPG or FPI. The deletions in 20 individuals with DNA samples available were successfully validated using PCR-based amplification. The association of the deletions in SFMBT1 with FPG was further evaluated using an independent population-based replication sample obtained from the Taiwan Biobank. An association p-value of 0.065, which was close to the significance level of 0.05, for FPG was obtained by testing 9 individuals with CNVs in the SFMBT1 gene region and 11,692 individuals with normal copies in the replication cohort. Previous studies have found that SNPs in SFMBT1 are associated with blood pressure and serum urate concentration, suggesting that SFMBT1 may have functional implications in some metabolic-related traits.

Association between serum ferritin, hemoglobin, iron intake, and diabetes in adults in Jiangsu, China.

PubMed

Shi, Zumin; Hu, Xiaoshu; Yuan, Baojun; Pan, Xiaoqun; Meyer, Haakon E; Holmboe-Ottesen, Gerd

2006-08-01

To investigate the association between iron status, iron intake, and diabetes among Chinese adults. This cross-sectional household survey was carried out in 2002 in Jiangsu Province, China. The sample contained 2,849 men and women aged > or =20 years with a response rate of 89.0%. Iron intake was assessed by food weighing plus consecutive individual 3-day food records. Fasting plasma glucose (FPG), serum ferritin, and hemoglobin were measured. The prevalence of anemia was 18.3% in men and 31.5% in women. Mean hemoglobin and serum ferritin increased across groups with increasing FPG. The prevalence of anemia among women was 15.0% in individuals with FPG >7.0 mmol/l compared with 32.6% in individuals with FPG <5.6 mmol/l. There was a similar, however not significant, trend among men. In women, after adjusting for known risk factors, the odds ratio (OR) of diabetes was 2.15 (95% CI 1.03-4.51) for subjects in the upper quartile of hemoglobin compared with the rest, and the corresponding OR for the upper quartile of serum ferritin was 3.79 (1.72-8.36). Iron intake was positively associated with diabetes in women; fourth quartile intake of iron yielded an OR of 5.53 (1.47-20.44) compared with the first quartile in the multivariate analyses. In men, similar trends were suggested, although they were not statistically significant. Iron status and iron intake was independently associated with risk of diabetes in Chinese women but not in men.

Intramyocellular lipid content in subjects with impaired fasting glucose after telmisartan treatment, a randomised cross-over trial.

PubMed

Kratochvílová, Simona; Škoch, Antonín; Wohl, Petr; Švehlíková, Eva; Dezortová, Monika; Hill, Martin; Hájek, Milan; Pelikánová, Terezie

2016-04-01

Ectopic lipid accumulation in skeletal muscle is associated with insulin resistance. Telmisartan improves metabolic parameters in type 2 diabetic patients. The aim of our study was to evaluate the in vivo effect of telmisartan on intramyocellular lipid content (IMCL) in subjects with impaired fasting glucose (IFG) by magnetic resonance spectroscopy (MRS). We enrolled 10 subjects with IFG in a cross-over, placebo-controlled, randomized, double-blind trial, treated with 3 weeks of telmisartan (160 mg daily) or placebo. After completing each treatment, a hyperinsulinaemic euglycaemic clamp (1 mU/kg per min; 5 mmol/l; 120 min) to assess insulin action (metabolic clearance rate of glucose, MCR) and (1)H MRS of the m. tibialis anterior using a MR Scanner Siemens Vision operating at 1.5 T to evaluate IMCL content, were performed. Plasma adipokine levels were determined simultaneously. Telmisartan treatment resulted in a lower fasting plasma glucose (FPG) (p < 0.05), but insulin action was comparable to after placebo. Telmisartan did not affect IMCL content. After placebo, IMCL correlated negatively with total cholesterol (p < 0.001), MCR (p < 0.05) and adiponectin (p < 0.05) and positively with FPG (p < 0.05). After telmisartan treatment there was only a positive correlation between IMCL and TNFα (p < 0.05). IMCL content is related to parameters of glucose metabolism and insulin action in sedentary IFG subjects. A short telmisartan treatment did not affect the IMCL content despite its positive effect on FPG. The improvement in FPG was probably mediated through interference with other metabolic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Improving in the fasting, but not the postprandial, glucose level is associated with reduction of plasma d-ROMs level in patients with type 2 diabetes.

PubMed

Ohara, Makoto; Watanabe, Kentaro; Suzuki, Tatsuya; Sekimizu, Ken-ichi; Motoyama, Masayuki; Ishii, Kazuhito; Sawai, Keisuke; Nakano, Hiroshi; Oba, Kenzo; Mizuno, Kyoichi

2013-01-01

This study aimed to evaluate the relationship between improvement of glucose metabolism and plasma levels of diacron-reactive oxygen metabolites (d-ROMs) in patients with type 2 diabetes. As the first daily profile, the plasma levels of glucose and d-ROMs were determined on admission. Then, after treatment to lower plasma glucose levels, the second daily profile of these levels was evaluated. Fasting plasma glucose (FPG), the total area under the curve (AUC) of the daily plasma glucose profile (AUCDP), the AUC of the postprandial plasma glucose levels (AUCPP), the AUC of the daily plasma d-ROMs profile (AUCd-ROMs), the coefficient of variation (CV) of plasma glucose (CVPG), and the mean amplitude of glycemic excursions (MAGE) were calculated. The relationship between the improvement of glucose metabolism and that of oxidative stress in patients with type 2 diabetes was evaluated. The second determinations of FPG, AUCDP, AUCPP, MAGE, and AUCd-ROMs were significantly lower than those of the first determinations, but no significant difference was observed in CVPG. Linear regression analysis demonstrated significant associations between the changes in AUCd-ROMs and the changes in both FPG and AUCDP, whereas no significant association was observed between the change in AUCd-ROMs and the change in AUCPP, CVPG, or MAGE. This study has demonstrated that improvement of the FPG level, but not of the postprandial glucose level, is associated with a reduction of the plasma level of d-ROMs in patients with type 2 diabetes.

HOMA-IR Values are Associated With Glycemic Control in Japanese Subjects Without Diabetes or Obesity: The KOBE Study

PubMed Central

Hirata, Takumi; Higashiyama, Aya; Kubota, Yoshimi; Nishimura, Kunihiro; Sugiyama, Daisuke; Kadota, Aya; Nishida, Yoko; Imano, Hironori; Nishikawa, Tomofumi; Miyamatsu, Naomi; Miyamoto, Yoshihiro; Okamura, Tomonori

2015-01-01

Background Several studies have reported that insulin resistance was a major risk factor for the onset of type 2 diabetes mellitus in individuals without diabetes or obesity. We aimed to clarify the association between insulin resistance and glycemic control in Japanese subjects without diabetes or obesity. Methods We conducted a community-based cross-sectional study including 1083 healthy subjects (323 men and 760 women) in an urban area. We performed multivariate regression analyses to estimate the association between the homeostasis model assessment of insulin resistance (HOMA-IR) values and markers of glycemic control, including glycated haemoglobin (HbA1c), 1,5-anhydroglucitol (1,5-AG), and fasting plasma glucose (FPG) levels, after adjustment for potential confounders. Results Compared with the lowest tertile of HOMA-IR values, the highest tertile was significantly associated with HbA1c and FPG levels after adjustment for potential confounders, both in men (HbA1c: β = 1.83, P = 0.001; FPG: β = 0.49, P < 0.001) and women (HbA1c: β = 0.82, P = 0.008; FPG: β = 0.39, P < 0.001). The highest tertile of HOMA-IR values was inversely associated with 1,5-AG levels compared with the lowest tertile (β = −18.42, P = 0.009) only in men. Conclusions HOMA-IR values were associated with markers of glycemic control in Japanese subjects without diabetes or obesity. Insulin resistance may influence glycemic control even in a lean, non-diabetic Asian population. PMID:26005064

Comparison of glycated hemoglobin with fasting plasma glucose in definition of glycemic component of the metabolic syndrome in an Iranian population.

PubMed

Janghorbani, Mohsen; Amini, Masoud

2012-01-01

The aim of this study was to compare the utility of glycated hemoglobin (GHb) versus the fasting plasma glucose (FPG) in definition of glycemic component of the metabolic syndrome (MetS) in a non-diabetic Iranian population. A cross-sectional study of first-degree relatives (FDRs) of patients with type 2 diabetes was conducted from 2003 to 2005. A total of 2410 non-diabetic FDRs of consecutive patients with type 2 diabetes 30-60 years old were examined. All subjects underwent a standard 75 g 2-h oral glucose tolerance test and GHb measurement. Consensus criteria in 2009 were used to identify MetS. Glycemic component of MetS was defined as either FPG≥100 mg/dl or GHb≥5.7%. The mean (SD) age of participants was 43.6 (6.5) years. The prevalence of MetS was 33.5% (95% confidence interval (CI): 31.6, 35.4) based on FPG criterion alone and 28.6% (95% CI: 26.8, 30.4) based on GHb criterion alone. Use of combination of both criteria increased the prevalence of MetS (36.7%; 95% CI: 34.8, 38.6). There was 88.7% (95% CI: 87.5, 90.0) agreement between the GHb and FPG when either was used to define MetS (κ coefficient=0.737). These data indicate that using GHb may be an acceptable surrogate of FPG to define glycemic component of MetS. Copyright © 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Association of first-trimester maternal lipid profiles and triglyceride-glucose index with the risk of gestational diabetes mellitus and large for gestational age newborn.

PubMed

Pazhohan, Azar; Rezaee Moradali, Monireh; Pazhohan, Nahideh

2017-11-20

To evaluate the association of maternal first-trimester plasma lipid profiles, fasting plasma glucose (FPG), and triglyceride (TyG) index with the risk of gestational diabetes mellitus (GDM) and large for gestational age (LGA) infant in Iranian mothers. Nine hundred and fifty-four healthy pregnant women were prospectively followed till after delivery. Maternal fasting lipids and glucose concentration were measured at nine-week gestation on average. We used generalized linear models to calculate the relative risks and 95% confidence intervals. The incidence of GDM and LGA infants among our participants was 18.4% and 26.1%, respectively. There was a significant correlation between the increase in FPG, triglyceride, TG/HDL-C ratio, as well as TyG index with the risk of GDM and LGA infant. After adjusting for potential confounders, the relative risk of GDM in women in the top tertile of FPG, triglyceride (TG), triglyceride/high-density lipoprotein-cholesterol (TG/HDL-C) and TyG index was 4.2-, 4.2-, 3.9-, and 4.9-folds of its risk in women in the bottom tertile, respectively. Also after adjusting for GDM, the relative risk of LGA infants in women in the top tertile of FPG, TG, TG/HDL-C ratio and TyG index was 3.9-, 4.3-, 4.8-, and 5.3-folds of its risk in women in the bottom tertile, respectively. Based on our findings, TyG index is more robust early predictors of GDM and LGA in Iranian women.

Effect of Selenium Supplementation on Glycemic Control and Lipid Profiles in Patients with Diabetic Nephropathy.

PubMed

Bahmani, Fereshteh; Kia, Mahsa; Soleimani, Alireza; Asemi, Zatollah; Esmaillzadeh, Ahmad

2016-08-01

To our knowledge, data on the effects of selenium supplementation on glycemic control and lipid concentrations in patients with diabetic nephropathy (DN) are scarce. The current study was done to determine the effects of selenium supplementation on glycemic control and lipid concentrations in patients with DN. This was a randomized double-blind placebo-controlled clinical trial in which 60 patients with DN were randomly allocated into two groups to receive either 200 μg of selenium supplements (n = 30) or placebo (n = 30) daily for 12 weeks. Blood sampling was performed for the quantification of glycemic indicators and lipid profiles at the onset of the study and after 12 weeks of intervention. Selenium supplementation for 12 weeks resulted in a significant decrease in serum insulin levels (P = 0.01), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (P = 0.02), homeostasis model of assessment-estimated B cell function (HOMA-B) (P = 0.009) and a significant rise in plasma glutathione peroxidase (GPx) (P = 0.001) compared with the placebo. Taking selenium supplements had no significant effects on fasting plasma glucose (FPG), quantitative insulin sensitivity check index (QUICKI) and lipid profiles compared with the placebo. Overall, our study demonstrated that selenium supplementation for 12 weeks among patients with DN had beneficial effects on plasma GPx, serum insulin levels, HOMA-IR, and HOMA-B, while it did not affect FPG, QUICKI, and lipid profiles.

Effects of combined physical activity and dietary intervention on obesity and metabolic parameters in adults with abdominal obesity.

PubMed

Soon, Heng Kiang; Saad, Hazizi Abu; Taib, Mohd Nasir Mohd; Rahman, Hejar Abd; Mun, Chan Yoke

2013-03-01

A twelve-week controlled intervention trial was carried out to evaluate the effects of combined physical activity and dietary intervention on obesity and metabolic risk factors among employees of Universiti Putra Malaysia. Participants consisted of adults aged 25-55 years with no reported chronic diseases but with abdominal obesity. They were assigned to either a combined physical activity and dietary intervention group or a control group. The final sample consisted of 56 participants, with an equal number of 28 for each study group. No significant group effect was observed for any variable except for hip circumference (HC) and fasting plasma glucose (FPG). There was a significant increase in HC (p=0.007) and reduction in FPG (p=0.02) in the intervention group compared to the control group. In the intervention group, HC (p=0.002), triglycerides (TG) (p=0.0001), total cholesterol (TC) (p=0.0001), LDL cholesterol (LDLC) (p=0.0001) and FPG (p=0.005) were significantly reduced, while waist circumference (WC) (p=0.025) and the waist-to-hip ratio (WHR) (p=0.027) were significantly reduced in the control group. No significant change in steps/day or calorie intake'was observed in either group. Taken together, these data indicate that the combined physical activity and dietary intervention was not effective at improving diet or physical activity level. However, the intervention was effective in improving FPG among participants with abdominal obesity. The significant increase in HC in the interventions group warrants further study. These findings will be useful to further improve group-based intervention for the prevention and management of obesity.

Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: A meta-analysis of seven clinical trials.

PubMed

Russell-Jones, D; Gall, M-A; Niemeyer, M; Diamant, M; Del Prato, S

2015-10-01

Basal insulin analogues have a reduced risk of hypoglycaemia compared with NPH insulin, but hypoglycaemia still remains a major impediment to achieving recommended fasting plasma glucose (FPG) targets in patients with diabetes. Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after subcutaneous injection resulting in an ultra-long duration of action and stable glucose-lowering effect. The aim of this analysis was to compare the effect of IDeg on FPG and nocturnal confirmed hypoglycaemia as compared to insulin glargine (IGlar). Data were included from seven phase 3a, randomised, open-label, treat-to-target clinical trials in which once-daily IDeg was compared with once-daily IGlar. Two trials included a total of 957 patients with type 1 diabetes (T1D) and five trials included a total of 3360 patients with type 2 diabetes (T2D); all trials were 26 or 52 weeks in duration. Confirmed hypoglycaemia was defined as plasma glucose <3.1 mmol/L or severe episodes requiring assistance, and nocturnal hypoglycaemia occurred between 00:01 and 05:59. In all trials, the mean end-of-trial FPG was lower for IDeg than IGlar, reaching statistical significance in three trials. Similarly, IDeg was associated with a lower rate of nocturnal confirmed hypoglycaemia vs. IGlar, which was statistically significant in three trials, regardless of type of diabetes or background therapy. This analysis shows that the lower rate of nocturnal confirmed hypoglycaemia seen with IDeg relative to IGlar is accompanied by a reduced mean FPG, in particular in patients with T2D. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of lorcaserin on progression of prediabetes to type 2 diabetes and reversion to euglycemia.

PubMed

Nesto, Richard; Fain, Randi; Li, Yuhan; Shanahan, William

2016-05-01

Lorcaserin is a selective 5-HT2C (5-hydroxytryptamine 2C) receptor agonist indicated for weight management. Here, we assess the impact of lorcaserin on progression from prediabetes to type 2 diabetes (T2D) and on reversion from prediabetes to euglycemia. This is a post hoc analysis of pooled data from two Phase 3 studies, BLOOM and BLOSSOM (N = 6136), evaluating the impact of lorcaserin on weight and glycemic parameters over 52 weeks in the subpopulation of obese/overweight subjects with prediabetes, alternately defined by fasting plasma glucose (FPG) 100-125 mg/dl or glycated hemoglobin (HbA1c) 5.7-6.4% at baseline. At Week 52, in the subpopulation with prediabetes, nearly twice as many lorcaserin-treated subjects achieved ≥5% weight loss versus placebo (HbA1c: 55.6% vs. 27.5%, p < 0.001; FPG: 52.8% vs. 28.8%, p < 0.001), and a significantly lower percentage of lorcaserin-treated subjects progressed to T2D versus placebo based on HbA1c (lorcaserin 3.2%, placebo 5.0%, p = 0.032) but not FPG (lorcaserin 1.6%, placebo 2.6%, p = 0.227). A significantly greater proportion of lorcaserin-treated subjects versus placebo also reverted to euglycemia based on both HbA1c (lorcaserin 40%, placebo 29.5%, p < 0.001) and FPG (lorcaserin 52.4%, placebo 46.5%, p = 0.047). In subjects with prediabetes, lorcaserin may contribute to weight loss and improve glycemic parameters, and thus may help with preventing progression to T2D and promoting reversion to euglycemia. www.clinicaltrials.gov identifiers are NCT00395135 (BLOOM) and NCT00603902 (BLOSSOM).

Risk Score for Detecting Dysglycemia: A Cross-Sectional Study of a Working-Age Population in an Oil Field in China.

PubMed

Tian, Xiubiao; Liu, Yan; Han, Ying; Shi, Jieli; Zhu, Tiehong

2017-06-11

BACKGROUND Dysglycemia (pre-diabetes or diabetes) in young adults has increased rapidly. However, the risk scores for detecting dysglycemia in oil field staff and workers in China are limited. This study developed a risk score for the early identification of dysglycemia based on epidemiological and health examination data in an oil field working-age population with increased risk of diabetes. MATERIAL AND METHODS Multivariable logistic regression was used to develop the risk score model in a population-based, cross-sectional study. All subjects completed the questionnaires and underwent physical examination and oral glucose tolerance tests. The performance of the risk score models was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS The study population consisted of 1995 participants, 20-64 years old (49.4% males), with undiagnosed diabetes or pre-diabetes who underwent periodic health examinations from March 2014 to June 2015 in Dagang oil field, Tianjin, China. Age, sex, body mass index, history of high blood glucose, smoking, triglyceride, and fasting plasma glucose (FPG) constituted the Dagang dysglycemia risk score (Dagang DRS) model. The performance of Dagang DRS was superior to m-FINDRISC (AUC: 0.791; 95% confidence interval (CI), 0.773-0.809 vs. 0.633; 95% CI, 0.611-0.654). At the cut-off value of 5.6 mmol/L, the Dagang DRS (AUC: 0.616; 95% CI, 0.592-0.641) was better than the FPG value alone (AUC: 0.571; 95% CI, 0.546-0.596) in participants with FPG <6.1 mmol/L (n=1545, P=0.028). CONCLUSIONS Dagang DRS is a valuable tool for detecting dysglycemia, especially when FPG <6.1 mmol/L, in oil field workers in China.

Impaired glucose metabolism and type 2 diabetes in apparently healthy senior citizens.

PubMed

Medina Escobar, Pedro; Moser, Michel; Risch, Lorenz; Risch, Martin; Nydegger, Urs Ernst; Stanga, Zeno

2015-01-01

To estimate the prevalence of unknown impaired glucose metabolism, also referred to as prediabetes (PreD), and unknown type 2 diabetes mellitus (T2DM) among subjectively healthy Swiss senior citizens. The fasting plasma glucose (FPG) and glycated haemoglobin A(1c) (HbA(1c)) levels were used for screening. A total of 1 362 subjects were included (613 men and 749 women; age range 60-99 years). Subjects with known T2DM were excluded. The FPG was processed immediately for analysis under standardised preanalytical conditions in a cross-sectional cohort study; plasma glucose levels were measured by means of the hexokinase procedure, and HbA(1c) was measured chromatographically and classified using the current American Diabetes Association (ADA) criteria. The crude prevalence of individuals unaware of having prediabetic FPG or HbA(1c) levels, was 64.5% (n = 878). Analogously, unknown T2DM was found in 8.4% (n = 114) On the basis of HbA(1c) criteria alone, significantly more subjects with unknown fasting glucose impairment and laboratory T2DM could be identified than with the FPG. The prevalence of PreD as well as of T2DM increased with age. The mean HOMA indices (homeostasis model assessment) for the different age groups, between 2.12 and 2.59, are consistent with clinically hidden disease and are in agreement with the largely orderly Body Mass Indices found in the normal range. Laboratory evidence of impaired glucose metabolism and, to a lesser extent, unknown T2DM, has a high prevalence among subjectively healthy older Swiss individuals. Laboratory identification of people with unknown out-of-range glucose values and overt diabetic hyperglycaemia might improve the prognosis by delaying the emergence of overt disease.

Glycaemic responses in Asian and non-Asian people with type 2 diabetes initiating insulin glargine 100 units/mL: A patient-level pooled analysis of 16 randomised controlled trials.

PubMed

Chan, Juliana C N; Bunnag, Pongamorn; Chan, Siew P; Tan, Iris T I; Tsai, Shih-Tzer; Gao, Ling; Landgraf, Wolfgang

2018-01-01

To compare outcomes between Asian and non-Asian patients with type 2 diabetes (T2D) inadequately controlled on oral antidiabetic drugs (OADs) initiating insulin glargine 100 units (U)/mL (Gla-100) in randomised controlled clinical trials. Post hoc analysis of patient-level data (Asian n = 235; non-Asian n = 3351) from 16 trials. At baseline, Asian patients were younger with lower body mass index (BMI), fasting C-peptide, and fasting plasma glucose (FPG) than non-Asian patients (all P < .001). Asian patients had a higher mean glycosylated haemoglobin (HbA1c) at Week 24 and less reduction in HbA1c from baseline (7.4% vs. 7.2%; -1.3% vs. -1.6%, respectively; P = .0001), and were less likely to achieve HbA1c <7.0% (40% vs. 47%; P = .002) than non-Asian patients. Reductions in FPG and rates of hypoglycaemia were similar between Asian and non-Asian patients. Asian patients had less weight gain than non-Asian patients (+1.3 vs. +1.9 kg, respectively, P = .013). In our post hoc meta-analysis, Gla-100 effectively lowers HbA1c and FPG in Asian patients with T2D uncontrolled on OADs with similar incidence of hypoglycaemia and less absolute weight gain compared with non-Asian patients. At a similar FPG reduction, fewer Asian patients achieved HbA1c target <7.0%, suggesting that prandial glucose needs to be addressed. Copyright © 2017. Published by Elsevier B.V.

Alcohol consumption reduces HbA1c and glycated albumin concentrations but not 1,5-anhydroglucitol.

PubMed

Inada, Shinya; Koga, Masafumi

2017-11-01

Background The effect of alcohol consumption on glycaemic control indicators is not well known. In this study, we studied the effect of alcohol consumption on the plasma glucose and glycaemic control indicators in non-diabetic men. Methods The study enrolled 300 non-diabetic men who received a complete medical checkup (age: 52.8 ± 6.5 years, body mass index: 24.4 ± 2.8 kg/m 2 ). The subjects were divided into four groups by the amount of alcohol consumed, and the plasma glucose, HbA1c, glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) concentrations of the groups were compared. Results As the level of alcohol consumption increased, significantly high concentrations of fasting plasma glucose (FPG) were observed, and the oral glucose tolerance test 2-h plasma glucose concentrations tended to rise. While no significant effect of alcohol consumption on HbA1c, 1,5-AG, and the 1,5-AG/FPG ratio was observed, the HbA1c/FPG ratio, GA and the GA/FPG ratio exhibited significantly low values as the level of alcohol consumption increased. In stepwise multivariate regression analysis, alcohol consumption was a significant negative independent variable for HbA1c and GA, but not for 1,5-AG. Conclusions As the level of alcohol consumption increased, the plasma glucose concentrations rose, but the HbA1c and GA concentrations were lower compared with the plasma glucose concentrations. These findings suggest that alcohol consumption may reduce HbA1c and GA concentrations, but not 1,5-AG.

Predictors of Abnormal Glucose Tolerance in the Early Postpartum Period in Patients with Gestational Diabetes.

PubMed

Inoue, Shigeru; Shinagawa, Takaaki; Horinouchi, Takashi; Kozuma, Yutaka; Yonemoto, Koji; Hori, Daizo; Ushijima, Kimio

2016-01-01

This study was designed to investigate the clinical predictors of abnormal glucose tolerance 5-7 weeks after delivery. Subjects were 155 women diagnosed with gestational diabetes mellitus (GDM) between October 2005 and September 2013 whose pregnancy and delivery were managed at our center. Subjects were divided into a normal glucose tolerance group (NGT; n = 113), or abnormal glucose tolerance group (AGT; n = 42) with borderline or overt diabetes mellitus, based on 75-g oral glucose tolerance test (75 gOGTT) results 5-7 weeks after delivery. We extracted profiles by which abnormal glucose tolerance levels 5-7 weeks after delivery were predicted using a classification and regression tree (CART) from parameters measured at the time of GDM diagnosis. Logistic regression analysis was used to determine prediction accuracy. Subjects with fasting plasma glucose (FPG) ≥92 mg/dL and immuno-reactive insulin level <100 μU/mL 60 min after load (IRI60min) at time of diagnosis showed a significantly higher risk of developing abnormal glucose tolerance 5-7 weeks after delivery than subjects with FPG <92 mg/dL (p < 0.0001). Subjects with FPG ≥92 mg/dL and IRI60min ≥ 100 μU/mL had the same risk as those with FPG of <92 mg/dL. Patients with gestational diabetes who met the criteria specified above at diagnosis were at a higher risk of developing diabetes mellitus in the future. By explaining this issue to patients, we expect to improve the rate of postpartum follow-up. This should facilitate early detection of diabetes, and help prevent associated complications.

[Association between smoking/smoking cessation and glycemic control in male patients with type 2 diabetes].

PubMed

Su, J; Qin, Y; Shen, C; Gao, Y; Pan, E C; Pan, X Q; Tao, R; Zhang, Y Q; Wu, M

2017-11-10

Objective: To explore the association of smoking and smoking cessation with glycemic control in male patients with type 2 diabetes. Methods: From December 2013 to January 2014, a total of 7 763 male patients with type 2 diabetes, who received national basic public health service in Changshu county of Suzhou city, Huai'an and Qinghe districts of Huai'an city, Jiangsu province, were recruited by cluster sampling. Questionnaire survey and anthropometric measurements were conducted, and fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels were measured. Multiple linear regression model was used to evaluate the association of smoking and smoking cessation with glycemic control. Results: The prevalence of current smoking was 45.5% in male patients with type 2 diabetes. The levels of FPG and HbA1c increased with number of cigarettes smoked per day compared with non-smokers ( P <0.001). Among patients with drug treatment, the average increase of HbA1c level in current smokers with smoking duration ≥30 years and smoking index ≥40 pack-years were 0.27% (95 %CI : 0.05%-0.49%) and 0.38% (95 %CI : 0.23%-0.53%), respectively. FPG and HbA1c level decreased obviously with smoking cessation years among former smokers ( P <0.05). Among the patients receiving no drug treatment, no dose-response relationships were observed between smoking duration, smoking cessation years and levels of FPG and HbA1c. Conclusion: Cigarette smoking was negatively related with glycemic control in male type 2 diabetes patients, especially in patients with drug treatment. Smoking cessation may be beneficial for glycemic control. Smoking cessation should be encouraged for diabetes patients as early as possible.

A mixture of Salacia oblonga extract and IP-PA1 reduces fasting plasma glucose (FPG) and low-density lipoprotein (LDL) cholesterol levels

PubMed Central

Nakata, Kazue; Taniguchi, Yoshie; Yoshioka, Noriko; Yoshida, Aya; Inagawa, Hiroyuki; Nakamoto, Takeru; Yoshimura, Hiroshi; Miyake, Shin-ichiro; Kohchi, Chie; Kuroki, Masahide

2011-01-01

At present, lifestyle-related diseases are one of the most critical health issues worldwide. It has been reported that lipopolysaccharide derived from a Gram-negative bacteria (IP-PA1) symbiotic with wheat exhibited several advantageous biological effects, such as the reduction of plasma glucose levels in NOD mice and low-density lipoprotein (LDL) levels in WHHL rabbits. In this study, the beneficial effects on plasma glucose and lipids of a tea (SI tea) consisting of IP-PA1 and Salacia (which contains an inhibitor of α-glucosidase) were investigated in the KK-Ay/TaJcl type 2 diabetic model mice and in human subjects with premetabolic syndrome in a double-blind, randomized study. SI tea significantly decreased plasma glucose levels in KK-Ay/TaJcl mice. A clinical trial of SI tea was performed with 41 subjects between the ages of 40 and 69, who belonged either to a high plasma glucose group (HG: FPG 100-125 mg/dl) or to a hyperlipidemia group (HL: TG ≥ 150 mg/dl, or LDL ≥ 120 mg/dl, or HDL < 40 mg/dl). These subjects ingested either Salacia without IP-PA1 (the control) or SI tea. Blood samples were collected at 0, 30, and 60 days after initiating SI tea treatment, and were measured for FPG, HbA1c, TG, LDL, and HDL. These results showed that SI tea reduced FPG and HbA1c more rapidly than the control in the HL group, and also significantly improved LDL and HDL levels in the HG group. Thus, SI tea may be helpful in preventing lifestyle-related diseases. PMID:22125681

Association of blood glucose level and hypertension in Elderly Chinese Subjects: a community based study.

PubMed

Yan, Qun; Sun, Dongmei; Li, Xu; Chen, Guoliang; Zheng, Qinghu; Li, Lun; Gu, Chenhong; Feng, Bo

2016-07-13

There is a scarcity of epidemiological researches examining the relationship between blood pressure (BP) and glucose level among older adults. The objective of the current study was to investigate the association of high BP and glucose level in elderly Chinese. A cross-sectional study of a population of 2092 Chinese individuals aged over 65 years was conducted. Multiple logistic analysis was used to explore the association between hypertension and hyperglycemia. Independent risk factors for systolic and diastolic BP were analyzed using stepwise linear regression. Subjects in impaired fasting glucose group (IFG) (n = 144) and diabetes (n = 346), as compared with normal fasting glucose (NFG) (n = 1277), had a significant higher risk for hypertension, with odds ratios (ORs) of 1.81 (95 % CI, 1.39-2.35) (P = 0.000) and 1.40 (95 % CI, 1.09-1.80) (P = 0.009), respectively. Higher fasting plasma glucose (FPG) levels in the normal range were still significantly associated with a higher prevalence of hypertension in both genders, with ORs of 1.24 (95 % CI, 0.85-1.80), R (2) = 0.114, P = 0.023 in men and 1.61 (95 % CI, 1.12-2.30), R (2) = 0.082, P = 0.010 in women, respectively, when compared with lower FPG. Linear regression analysis revealed FPG was an independent factor of systolic and diastolic BP. Our findings suggest that hyperglycemia as well as higher FPG within the normal range is associated with a higher prevalence of hypertension independent of other cardiovascular risk factors in elderly Chinese. Further studies are needed to explore the relationship between hyperglycemia and hypertension in a longitudinal setting.

Photoacoustic Imaging of Epilepsy

DTIC Science & Technology

2012-04-01

fBg ; ð4Þ where the elements of matrix ½K , ½C, and ½M are Kij ¼ Z S ∇ψ i ·∇ψ jdSþ 1 2r I l ψ iψ jdl; Cij ¼ 1 v0 I l ψ iψ jdl; Mij ¼ 1 v20 Z S ψ iψ...jdS; and the column vectors fpg, f _pg, f€pg, and fBg are Bi ¼ β Cp Z S ψ i X k ψkΦk dS · ∂J ∂t fpg ¼ fp1; p2; pNgT ; f _pg ¼ f _p1; _p2

Prediction of exercise-mediated changes in metabolic markers by gene polymorphism.

PubMed

Kahara, Toshio; Takamura, Toshinari; Hayakawa, Tetsuo; Nagai, Yukihiro; Yamaguchi, Hiromi; Katsuki, Tatsuo; Katsuki, Ken-ichi; Katsuki, Michio; Kobayashi, Ken-ichi

2002-08-01

The effects of regular physical exercise on obesity-associated metabolic abnormalities vary for each individual. In this study, we investigated whether genotypes of genes associated with obesity can predict the effects of exercise on changes in metabolic markers in healthy men. Healthy Japanese men (n=106) performed the exercise program at 50% of their maximal heart rate for 20-60 min a day, 2-3 days each week for 3 months. The levels of fasting plasma glucose (FPG) and serum leptin significantly decreased after the exercise program. Polymorphisms of the beta3-adrenergic receptor (beta3AR) and uncoupling protein-1 (UCP-1) genes were analyzed with RFLP methods. In the Trp/Trp genotype of the beta3AR gene, the levels of serum leptin, FPG and fructosamine (FrAm) decreased significantly after the exercise program, but not in the Arg/Arg genotype. In the AG heterozygote and the GG homozygote of the UCP-1 gene, FPG and FrAm levels were significantly reduced, respectively. In conclusion, gene polymorphism of the beta3AR and UCP-1 was found to be associated with the exercise-mediated improvement in glucose tolerance and leptin resistance in healthy Japanese men.

A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients.

PubMed

Derosa, Giuseppe; D'Angelo, Angela; Romano, Davide; Maffioli, Pamela

2016-10-28

The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L -carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG), post-prandial-glucose (PPG), glycated hemoglobin (HbA 1c ), fasting plasma insulin (FPI), HOMA-index (HOMA-IR), lipid profile, high sensitivity C-reactive protein (Hs-CRP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA). There was a reduction of FPG, PPG, and HbA 1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L -carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers.

Evaluation of BAG3 levels in healthy subjects, hypertensive patients, and hypertensive diabetic patients.

PubMed

Derosa, Giuseppe; Maffioli, Pamela; Rosati, Alessandra; M, De Marco; Basile, Anna; D'Angelo, Angela; Romano, Davide; Sahebkar, Amirhossein; Falco, Antonia; Turco, Maria C

2018-03-01

BAG3 is a member of human BAG (Bcl-2-associated athanogene) proteins and plays a role in apoptosis, cell adhesion, cytoskeleton remodeling, and autophagy. The aim of this study was to evaluate BAG3 levels in healthy subjects, hypertensive patients, and hypertensive diabetic patients. We enrolled 209 Caucasian adults, of both sex, 18-75 years of age, 77 were healthy controls, 62 were affected by hypertension, and 70 were affected by hypertension and type 2 diabetes. All patients underwent an assessment that included medical history, physical examination, vital signs, a 12-lead electrocardiogram, measurements of systolic (SBP), and diastolic blood pressure (DBP), heart rate (HR), fasting plasma glucose (FPG), glycated hemoglobin (HbA 1c ), triglycerides (TG), transaminases, high sensitivity C-reactive protein (Hs-CRP), and BAG3. We observed higher blood pressure values in hypertensive, and hypertensive diabetic patients compared to controls. As expected, FPG and HbA 1c were higher in diabetic hypertensive patients, compared to the other two groups. No Tg levels differences were recorded among the three groups. Hs-CRP was higher in diabetic hypertensive patients compared to healthy subjects. Finally, BAG3 levels were higher in hypertensives, and hypertensive diabetic patients compared to controls. We observed higher levels of BAG3 in hypertensive patients compared to healthy controls, and even higher levels in hypertensive diabetic patients compared to healthy subjects. This paper could be the first of a long way to identify potential involvement of deregulated BAG3 levels in cardiometabolic diseases. © 2017 Wiley Periodicals, Inc.

A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients

PubMed Central

Derosa, Giuseppe; D’Angelo, Angela; Romano, Davide; Maffioli, Pamela

2016-01-01

The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L-carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG), post-prandial-glucose (PPG), glycated hemoglobin (HbA1c), fasting plasma insulin (FPI), HOMA-index (HOMA-IR), lipid profile, high sensitivity C-reactive protein (Hs-CRP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA). There was a reduction of FPG, PPG, and HbA1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L-carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers. PMID:27801825

Effects of one year treatment of sibutramine on insulin resistance parameters in type 2 diabetic patients.

PubMed

Derosa, Giuseppe; Maffioli, Pamela; Ferrari, Ilaria; Palumbo, Ilaria; Randazzo, Sabrina; D'Angelo, Angela; Cicero, Arrigo F G

2010-01-01

Comparison of the effects of one year treatment with sibutramine compared to placebo on insulin resistance parameters, body weight, glycemic control, and lipid profile, in type 2 diabetic patients. Two hundred and forty-six patients with uncontrolled type 2 diabetes mellitus in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg or placebo for one year. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: homeostasis model assessment insulin resistance index (HOMA-IR), retinol binding protein-4 (RBP-4), resistin, visfatin, and high sensitivity-C reactive protein (Hs-CRP), body weight, body mass index (BMI), glycated hemoglobin (HbA(₁c)), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and triglycerides (T(g)). A faster decrease of HOMA-IR, resistin, and RBP-4 was recorded with sibutramine compared to the control group. We observed a significant decrease of Hs-CRP in both groups, and a faster improvement of HbA(₁c), FPG and PPG with sibutramine compared to the control group; furthermore we recorded a decrease of FPI, TC, LDL-C, body weight, and BMI in the sibutramine group, but not in the control group. Sibutramine gave a faster improvement of insulin resistance parameters and glycemic control compared to placebo; furthermore sibutramine gave also an improvement of lipid profile, and body weight.

The Influence of Religious Affiliation on Participant Responsiveness to the Complete Health Improvement Program (CHIP) Lifestyle Intervention.

PubMed

Kent, L M; Morton, D P; Ward, E J; Rankin, P M; Ferret, R B; Gobble, J; Diehl, H A

2016-10-01

Seventh-day Adventist (SDA) and non-SDA (21.3 and 78.7 %, respectively) individuals (n = 7172) participating in the Complete Health Improvement Program, a 30-day diet and lifestyle intervention, in North America (241 programs, 2006-2012) were assessed for changes in selected chronic disease risk factors: body mass index (BMI), blood pressure (BP), pulse, lipid profile and fasting plasma glucose (FPG). Reductions were greater among the non-SDA for BMI, pulse and blood lipids. Furthermore, the majority of non-SDA in the highest risk classifications for BP, lipids and FPG, but only some lipids among SDA, were able to show improvement by 20 % or more.

Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin.

PubMed

Chazova, Irina; Almazov, Vladimir A; Shlyakhto, Evgeny

2006-07-01

To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients > or =40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1-35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease.

Joint effects of diabetic-related genomic loci on the therapeutic efficacy of oral anti-diabetic drugs in Chinese type 2 diabetes patients

PubMed Central

Chen, Miao; Zhang, Rong; Jiang, Feng; Wang, Jie; Peng, Danfeng; Yan, Jing; Wang, Shiyun; Wang, Tao; Bao, Yuqian; Hu, Cheng; Jia, Weiping

2016-01-01

Previous pharmacogenomic studies of oral anti-diabetic drugs have primarily focused on the effect of a single site. This study aimed to examine the joint effects of multiple loci on repaglinide or rosiglitazone efficacy in newly diagnosed type 2 diabetes mellitus (T2DM) patients. A total of 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks. The reductions in fasting glucose (ΔFPG), 2h glucose (Δ2hPG) and glycated hemoglobin (ΔHbA1c) levels were significantly associated with genetic score that was constructed using the sum of the effect alleles both in the repaglinide (P = 0.0011, 0.0002 and 0.0067, respectively) and rosiglitazone cohorts (P = 0.0002, 0.0014 and 0.0164, respectively) after adjusting for age, gender, body mass index and dosage. Survival analyses showed a trend towards a greater attainment rate of target HbA1c level in individuals with a high genetic score in the repaglinide cohort and rosiglitazone cohort (Plog-rank = 0.0815 and 0.0867, respectively) when the attainment of treatment targets were defined as more than 20% decrease of FPG, 2hPG, and HbA1c levels after treatment. In conclusion, we identified the joint effects of several T2DM-related loci on the efficacy of oral anti-diabetic drugs; moreover, we built a model to predict the drug efficacy. PMID:26983698

Spectrum of complex DNA damages depends on the incident radiation

NASA Astrophysics Data System (ADS)

Hada, M.; Sutherland, B.

Ionizing radiation induces clustered DNA damages in DNA-two or more abasic sites oxidized bases and strand breaks on opposite DNA strands within a few helical turns Clustered damages are considered to be difficult to repair and therefore potentially lethal and mutagenic damages Although induction of single strand breaks and isolated lesions has been studied extensively little is known of factors affecting induction of clusters other than double strand breaks DSB The aim of the present study was to determine whether the type of incident radiation could affect yield or spectra of specific clusters Genomic T7 DNA a simple 40 kbp linear blunt-ended molecule was irradiated in non-scavenging buffer conditions with Fe 970 MeV n Ti 980 MeV n C 293 MeV n Si 586 MeV n ions or protons 1 GeV n at the NASA Space Radiation Laboratory or with 100 kVp X-rays Irradiated DNA was treated with homogeneous Fpg or Nfo proteins or without enzyme treatment for DSB quantitation then electrophoresed in neutral agarose gels DSB Fpg-OxyPurine clusters and Nfo-Abasic clusters were quantified by number average length analysis The results show that the yields of all these complex damages depend on the incident radiation Although LETs are similar protons induced twice as many DSBs than did X-rays Further the spectrum of damage also depends on the radiation The yield damage Mbp Gy of all damages decreased with increasing linear energy transfer LET of the radiation The relative frequencies of DSBs to Abasic- and OxyBase clusters were higher

Regional body composition changes exhibit opposing effects on coronary heart disease risk factors.

PubMed

Okura, Tomohiro; Nakata, Yoshio; Yamabuki, Keisuke; Tanaka, Kiyoji

2004-05-01

We investigated how regional body composition measured by dual-energy X-ray absorptiometry (DXA) is associated with risk factors for coronary heart disease (CHD) during weight reduction in obese women. Data were gathered from 128 overweight and obese women, aged 34 to 66 years, during a 14-week intervention study with diet and exercise. Regional (arms, legs, and trunk) fat tissue (FT) and lean soft tissue (LST) were measured by DXA. The FT change in legs correlated negatively with changes in diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and the number of CHD risk factors per subject (r=-0.17, P<0.05 to -0.26, P<0.01) in response to weight reduction, whereas truncal FT change had positive correlations with changes in triglycerides, LDL-C, FPG, and the number of CHD risk factors per subject (r=0.17, P<0.05 to 0.25, P<0.01). LST change in legs correlated negatively with changes in systolic blood pressure, FPG, and the number of risk factors (r=-0.20 to -0.21, P<0.05). Regional body composition information is important for evaluating improvement of CHD risk factors during weight-reduction treatment for obesity; differential FTs had opposing effects on CHD risk factors during weight reduction in obese women.

Observational 6-month open-label study of Japanese type 2 diabetes patients switching from NPH insulin to insulin detemir in basal-bolus regimen: 23rd article of the Japan Diabetes Clinical Data Management Study Group (JDDM23).

PubMed

Oishi, M; Abe, N; Yokoyama, H; Kuribayashi, N; Tomonaga, O; Matoba, K; Kobayashi, M

2012-01-01

Glycaemic control is critical to prevent diabetic complications and mortality. This 6-month, open-label, observational study assessed the efficacy and safety of switching Japanese patients with type 2 diabetes from neutral protamine Hagedorn (NPH) insulin to insulin detemir. Patients with type 2 diabetes (n = 126) receiving basal-bolus insulin therapy with NPH insulin plus rapid-acting insulin analogues were recruited. NPH insulin was replaced with insulin detemir for 6 months. Glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), daily glucose levels and hypoglycaemia were monitored. Nocturnal quality of life was assessed by insulin therapy related quality of life at night questionnaire. HbA(1c), FPG and body weight were all significantly reduced after treatment with insulin detemir for 6 months, without increasing severe hypoglycaemia. Insulin dose increased significantly over the same time. There were significant improvements in overall nocturnal quality of life, as well as well-being. Treatment with insulin detemir for 6 months resulted in substantial benefits, including reduced HbA(1c), FPG and body weight, and improvements in nocturnal quality of life, without increasing hypoglycaemia.

Association between HOMA-IR, fasting insulin and fasting glucose with coronary heart disease mortality in nondiabetic men: a 20-year observational study.

PubMed

Kurl, Sudhir; Zaccardi, Francesco; Onaemo, Vivian N; Jae, Sae Young; Kauhanen, Jussi; Ronkainen, Kimmo; Laukkanen, Jari A

2015-02-01

Whether glucose and insulin are differently associated with the risk of coronary heart disease (CHD) mortality is unclear. We aimed to estimate the association between insulin resistance (estimated by the homeostasis model assessment for insulin resistance, HOMA-IR), fasting serum insulin (FI) and fasting plasma glucose (FPG) with incident CHD mortality in a prospective study including middle-aged nondiabetic Finnish men. During an average follow-up of 20 years, 273 (11 %) CHD deaths occurred. In a multivariable Cox regression analysis adjusted for age, body mass index, systolic blood pressure, serum LDL-cholesterol, cigarette smoking, history of CHD, alcohol consumption, blood leukocytes and plasma fibrinogen, the hazard ratios (HRs) for CHD mortality comparing top versus bottom quartiles were as follows: 1.69 (95 % CI: 1.15-2.48; p = 0.008) for HOMA-IR; 1.59 (1.09-2.32; p = 0.016) for FI; and 1.26 (0.90-1.76; p = 0.173) for FPG. These findings suggest that IR and FI, but not FPG, are independent risk factors for CHD mortality. Further studies could help clarify these results in terms of screening and risk stratification, causality of the associations, and therapeutical implications.

Base excision repair: NMR backbone assignments of Escherichia coli formamidopyrimidine-DNA glycosylase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchko, Garry W.; Wallace, Susan S.; Kennedy, Michael A.

2002-03-01

Oxidative damage is emerging as one of the most important mechanisms responsible for mutagenesis, carcinogenesis, aging, and various diseases (Farr and Kogma, 1991). One of the potential targets for oxidation is cellular DNA. While exposure to exogenous agents, such as ionizing radiation and chemicals, contributes to damaging DNA, the most important oxidative agents are endogenous, such as the reactive free radicals produced during normal oxidative metabolism (Adelman et., 1988). To mitigate the potentially deleterious effects of oxidative DNA damage virtually all aerobic organisms have developed complex repair mechanisms (Petit and Sancar, 1999). One repair mechanism, base excision repair (BER), appearsmore » to be responsible for replacing most oxidative DNA damage (David and Williams, 1998). Formamidopyrimidine-DNA glycosylase (Fpg), a 269-residue metalloprotein with a molecular weight of 30.2 kDa, is a key BER enzyme in prokaryotes (Boiteaux et al., 1987). Substrates recognized and released by Fpg include 7,8-dihydro-8-oxoguanine (8-oxoG), 2,6 diamino-4-hydroxy-5-formamido pyrimidine (Fapy-G), the adenine equivalents 8-oxoA and Fapy-A, 5-hydroxycytosine, 5-hydroxyuracil, B ureidoisobutiric acid, and a-R-hydroxy-B-ureidoisobutiric acid (Freidberg et al., 1995). In vitro Fpg bind double-stranded DNA and performs three catalytic activities: (i) DNA glycosylase, (ii) AP lyase, and (iii) deoxyribophosphodiesterase.« less

Screening for gestational diabetes mellitus and its prevalence in Bangladesh.

PubMed

Jesmin, Subrina; Akter, Shamima; Akashi, Hidechika; Al-Mamun, Abdullah; Rahman, Md Arifur; Islam, Md Majedul; Sohael, Farzana; Okazaki, Osamu; Moroi, Masao; Kawano, Satoru; Mizutani, Taro

2014-01-01

The prevalence of gestational diabetes mellitus (GDM) has important health complications for both mother and child and is increasing all over the world. Although prevalence estimates for GDM are not new in developed and many developing countries, data are lacking for many low-income countries like Bangladesh. To evaluate the prevalence of GDM in Bangladesh. This cross-sectional study included 3447 women who consecutively visited the antenatal clinics with an average gestation age of 26 weeks. GDM was defined according to WHO criteria (fasting plasma glucose [FPG] ≥7.0 mmol/L or 2-h ≥7.8 mmol/L) and the new ADA criteria (FPG ≥5.3 mmol/L or 2-h ≥8.6 mmol/L OGTT). We also calculated overt diabetes as FPG ≥7.0 mmol/L. Prevalence of GDM was 9.7% according to the WHO criteria and 12.9% according to the ADA criteria in this study population. Prevalence of overt diabetes was 1.8%. Women with GDM were older, higher educated, had higher household income, higher parity, parental history of diabetes, and more hypertensive, compared with non-GDM women. This study demonstrates a high prevalence of GDM in Bangladesh. These estimates for GDM may help to formulate new policies to prevent and manage diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Decision Tree Analysis of Traditional Risk Factors of Carotid Atherosclerosis and a Cutpoint-Based Prevention Strategy

PubMed Central

Lv, Lihong; Xiao, Yufei; Tu, Jiangfeng; Tao, Lisha; Wu, Jiaqi; Tang, Xiaoxiao; Pan, Wensheng

2014-01-01

Background Reducing the exposure to risk factors for the prevention of cardio-cerebral vascular disease is a crucial issue. Few reports have described practical interventions for preventing cardiovascular disease in different genders and age groups, particularly detailed and specific cutpoint-based prevention strategies. Methods We collected the health examination data of 5822 subjects between 20 and 80 years of age. The administration of medical questionnaires and physical examinations and the measurement of blood pressure, fasting plasma glucose (FPG) and blood lipids [total cholesterol (TC), triglycerides (TG), high density lipoprotein–cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C)] were performed by physicians. Carotid ultrasound was performed to examine the carotid intima-media thickness (CIMT), which was defined as carotid atherosclerosis when CIMT ≥0.9 mm. Decision tree analysis was used to screen for the most important risk factors for carotid atherosclerosis and to identify the relevant cutpoints. Results In the study population, the incidence of carotid atherosclerosis was 12.20% (men: 14.10%, women: 9.20%). The statistical analysis showed significant differences in carotid atherosclerosis incidence between different genders (P<0.0001) and age groups (P<0.001). The decision tree analysis showed that in men, the most important traditional risk factors for carotid atherosclerosis were TC (cutpoint [CP]: 6.31 mmol/L) between the ages of 20–40 and FPG (CP: 5.79 mmol/L) between the ages of 41–59. By comparison, LDL-C (CP: 4.27 mmol/L) became the major risk factor when FPG ≤5.79 mmol/L. FPG (CP: 5.52 mmol/L) and TG (CP: 1.51 mmol/L) were the most important traditional risk factors for women between 20–40 and 41–59 years of age, respectively. Conclusion Traditional risk factors and relevant cutpoints were not identical in different genders and age groups. A specific gender and age group-based cutpoint strategy might contribute to preventing cardiovascular disease. PMID:25398126

Serum 25-hydroxyvitamin D is associated with cognitive executive function in Dutch prefrail and frail elderly: a cross-sectional study exploring the associations of 25-hydroxyvitamin D with glucose metabolism, cognitive performance and depression.

PubMed

Brouwer-Brolsma, Elske M; van de Rest, Ondine; Tieland, Michael; van der Zwaluw, Nikita L; Steegenga, Wilma T; Adam, Jos J; van Loon, Luc J C; Feskens, Edith J M; de Groot, Lisette C P G M

2013-11-01

The primary objective was to explore the possible association of serum 25-hydroxyvitamin D (25[OH]D) and vitamin D intake with markers of glucose metabolism, depression, and cognitive performance. In addition, we examined to what extent the associations between vitamin D and cognitive performance were modified or mediated by fasting plasma glucose (FPG) levels. Cross-sectional study using data of 127 frail or prefrail Dutch elderly, aged 65 years or older. Frailty was defined according to the criteria of Fried and colleagues. A participant was classified prefrail when 1 to 2 criteria were met; frailty was classified as the presence of 3 or more criteria. Associations of 25(OH)D and vitamin D intake with markers of glucose metabolism and domain-specific cognitive performance were examined by multivariable regression analyses. The possible association of vitamin D with depression and global cognitive performance was explored by Poisson regression. No associations were observed for 25(OH)D with FPG, fasting plasma insulin (FPI), Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR), or depression. In contrast, serum 25(OH)D was positively associated with executive functioning (β 0.007, P = .01) and tended to be associated with information-processing speed (β 0.006, P = .06). FPG did not modify or mediate these associations. Vitamin D intake was not associated with cognitive performance, glucose metabolism, or depression. This cross-sectional study suggests an association of serum 25(OH)D with domain-specific cognitive performance, in particular executive functioning and possibly information-processing speed, but not with FPG, FPI, HOMA-IR, or depression. Whether these associations are causal is yet to be demonstrated. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

Efficacy of acarbose and metformin in newly diagnosed type 2 diabetes patients stratified by HbA1c levels.

PubMed

Zhang, Jin-Ping; Wang, Na; Xing, Xiao-Yan; Yang, Zhao-Jun; Wang, Xin; Yang, Wen-Ying

2016-07-01

The aim of the present study was to investigate whether the therapeutic efficacy of acarbose and metformin is correlated with baseline HbA1c levels in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). Data for 711 subjects were retrieved from the MARCH (Metformin and AcaRbose in Chinese as initial Hypoglycemic treatment) trial database and reviewed retrospectively. Patients were grouped according to baseline HbA1c levels (<7%, 7%-8%, and >8%) and the results for these three groups were compared between acarbose and metformin treatments. Acarbose and metformin treatment significantly improved T2DM-associated parameters (weight, fasting plasma glucose [FPG], postprandial glucose [PPG], glucagon-like peptide-1 [GLP-1], HOMA-IR, and total cholesterol) across all HbA1c levels. Acarbose decreased PPG and HOMA-β significantly more than metformin, but only in subjects with lower baseline HbA1c (PPG in the <7% and 7%-8%, HOMA-β in the <7% groups; all P < 0.05). Acarbose decreased triglyceride (TG) levels, and the areas under the curve (AUC) for insulin and glucagon more than metformin at all HbA1c levels (P < 0.05). After 24 weeks treatment, metformin decreased FPG levels significantly more than acarbose for all baseline HbA1c groups (all P < 0.001). With the exception of FPG, PPG, and TG levels, differences between the two treatment groups observed at 24 weeks were not detected at 48 weeks. Acarbose decreased PPG and TG and spared the AUC for insulin more effectively in patients with low-to-moderate baseline HbA1c levels, whereas metformin induced greater reductions in FPG. These results may help guide selection of initial therapy based on baseline HbA1c. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

The product of triglycerides and glucose in comparison with fasting plasma glucose did not improve diabetes prediction.

PubMed

Janghorbani, Mohsen; Almasi, Siedeh Zinab; Amini, Masoud

2015-08-01

Previous study has reported that triglycerides-glucose (TyG) index, a product of triglycerides and fasting plasma glucose (FPG), might be useful in the prediction of incident type 2 diabetes (T2D). We evaluated the ability of the TyG index compared to FPG and OGTT as possible diabetes predictor in nondiabetic first-degree relatives (FDRs) of patients with T2D. A total of 1,488 FDRs without diabetes of consecutive patients with T2D 30-70 years old (361 men and 1,127 women) were examined and followed for a mean (SD) of 6.9 (1.7) years for diabetes incidence. We examined the incidence of diabetes across quartiles of the TyG index and plotted a receiver operating characteristic (ROC) curve to assess discrimination. At baseline and through follow-up, participants underwent a standard 75-g two-hour oral glucose tolerance test. During 10,124 person-years of follow-up, 41 men and 154 women developed T2D. Those in the top quartile of TyG index were 3.4 times more likely to develop T2D than those in the bottom quartile (odds ratio 3.36; 95 % CI 1.83, 6.19). On ROC curve analysis, a higher area under the ROC was found for FPG (76.2; 95 % CI 71.9, 80.6), 1-hPG (81.0, 95 % CI 77.2, 84.9) and 2-hPG (76.5; 95 % CI 72.3, 80.8) than for TyG index (65.1; 95 % CI 60.5, 69.7). TyG index is predicted T2D in high-risk individuals in Iran but FPG, 1-hPG and 2-hPG appeared to be more robust predictor of T2D in our study population.

Development of Risk Score for Predicting 3-Year Incidence of Type 2 Diabetes: Japan Epidemiology Collaboration on Occupational Health Study

PubMed Central

Nanri, Akiko; Nakagawa, Tohru; Kuwahara, Keisuke; Yamamoto, Shuichiro; Honda, Toru; Okazaki, Hiroko; Uehara, Akihiko; Yamamoto, Makoto; Miyamoto, Toshiaki; Kochi, Takeshi; Eguchi, Masafumi; Murakami, Taizo; Shimizu, Chii; Shimizu, Makiko; Tomita, Kentaro; Nagahama, Satsue; Imai, Teppei; Nishihara, Akiko; Sasaki, Naoko; Hori, Ai; Sakamoto, Nobuaki; Nishiura, Chihiro; Totsuzaki, Takafumi; Kato, Noritada; Fukasawa, Kenji; Huanhuan, Hu; Akter, Shamima; Kurotani, Kayo; Kabe, Isamu; Mizoue, Tetsuya; Sone, Tomofumi; Dohi, Seitaro

2015-01-01

Objective Risk models and scores have been developed to predict incidence of type 2 diabetes in Western populations, but their performance may differ when applied to non-Western populations. We developed and validated a risk score for predicting 3-year incidence of type 2 diabetes in a Japanese population. Methods Participants were 37,416 men and women, aged 30 or older, who received periodic health checkup in 2008–2009 in eight companies. Diabetes was defined as fasting plasma glucose (FPG) ≥126 mg/dl, random plasma glucose ≥200 mg/dl, glycated hemoglobin (HbA1c) ≥6.5%, or receiving medical treatment for diabetes. Risk scores on non-invasive and invasive models including FPG and HbA1c were developed using logistic regression in a derivation cohort and validated in the remaining cohort. Results The area under the curve (AUC) for the non-invasive model including age, sex, body mass index, waist circumference, hypertension, and smoking status was 0.717 (95% CI, 0.703–0.731). In the invasive model in which both FPG and HbA1c were added to the non-invasive model, AUC was increased to 0.893 (95% CI, 0.883–0.902). When the risk scores were applied to the validation cohort, AUCs (95% CI) for the non-invasive and invasive model were 0.734 (0.715–0.753) and 0.882 (0.868–0.895), respectively. Participants with a non-invasive score of ≥15 and invasive score of ≥19 were projected to have >20% and >50% risk, respectively, of developing type 2 diabetes within 3 years. Conclusions The simple risk score of the non-invasive model might be useful for predicting incident type 2 diabetes, and its predictive performance may be markedly improved by incorporating FPG and HbA1c. PMID:26558900

The effects of adding group-based lifestyle counselling to individual counselling on changes in plasma glucose levels in a randomized controlled trial: the Inter99 study.

PubMed

Lau, C; Vistisen, D; Toft, U; Tetens, I; Glümer, C; Pedersen, O; Jørgensen, T; Borch-Johnsen, K

2011-12-01

This study aimed to assess whether group-based lifestyle counselling offered to a high-risk population subgroup had any effect beyond individual multifactorial interventions on fasting plasma glucose (FPG) and 2-h plasma glucose (2hPG) changes. In a population-based study of 6784 participants, 4053 were determined to be at high risk based on a risk estimate of ischaemic heart disease or the presence of risk factors (smoking, hypertension, hypercholesterolaemia, obesity, impaired glucose tolerance). Of these subjects, 90% were randomized to high-intensity intervention (group A) and 10% to low-intensity intervention (group B). All participants went through health examinations, risk assessments and individual lifestyle counselling. Participants in group A were further offered group-based lifestyle counselling. The intervention was repeated after 1 and 3 years. A total of 2738 participants free of diabetes at baseline (1999-2001) and with at least one FPG and/or 2hPG measurement during 5 years of follow-up were included in the analyses. Differences in changes of plasma glucose between groups A and B were analyzed using multilevel linear regression. For FPG, crude 5-year changes were significantly different between the two groups (group A: -0.003 mmol/L vs group B: -0.079 mmol/L; P=0.0427). After adjusting for relevant confounders, no differences in FPG changes were observed (P=0.116). Also, no significant differences in the 5-year changes in 2hPG between the two groups were observed (group A: - 0.127 mmol/L vs group B: -0.201 mmol/L; P=0.546). Offering additional group-based intervention to a high-risk population subgroup had no clinical effects on changes in plasma glucose beyond those of individualized multifactorial interventions. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Evaluation of the relationship between subclinical hypothyroidism and metabolic syndrome components among workers.

PubMed

Cheserek, Maureen Jepkorir; Wu, Guirong; Shen, Liye; Shi, Yonghui; Le, Guowei

2014-04-01

Both hyperthyroidism and overt hypothyroidism are associated with increased prevalence of metabolic syndrome and its components, while data on subclinical hypothyroidism is currently limited especially in working populations. The aim of this study was to examine the association between subclinical hypothyroidism and metabolic syndrome components in workers; and to evaluate whether there are differences by sex and occupation. A total of 1150 university employees (male - 792, female - 358) aged 30-60 years who came for an annual medical check-up were studied. Anthropometric measurements were taken, and blood pressure, fasting plasma glucose (FPG), lipid profiles, thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) levels were measured. After adjustment for age and body mass index (BMI), TSH was positively associated with increased triglyceride (TG) levels (β = 0.108, p = 0.020) and FPG (β = 0.130, p = 0.006) in subclinical hypothyroid male workers. However, TSH was not associated (p > 0.05) with any component of metabolic syndrome (MS) in the euthyroid group. In females, TSH was not correlated with MS components in both euthyroid and subclinical hypothyroid groups. Furthermore, comparison by occupation showed higher TSH in subclinical hypothyroid male workers employed in administration (5.23 ± 0.52 mU/l) than those working as academics (5.12 ± 0.52 mU/l), which resulted in elevated systolic and diastolic blood pressure, FPG, total cholesterol, TG and high density lipoprotein cholesterol. In females, BMI, systolic and diastolic blood pressure, TG and FPG were significantly (p < 0.05) higher in subclinical hypothyroid administrators than those in academics. Subclinical hypothyroidism was associated with metabolic syndrome components in male workers and not in females. Administration workers showed increased metabolic risks compared to academics. The findings suggest that the assessment of thyroid function in individuals with metabolic syndrome in the workplace may be favorable especially among men.

Triglyceride-glucose index (TyG index) in comparison with fasting plasma glucose improved diabetes prediction in patients with normal fasting glucose: The Vascular-Metabolic CUN cohort.

PubMed

Navarro-González, David; Sánchez-Íñigo, Laura; Pastrana-Delgado, Juan; Fernández-Montero, Alejandro; Martinez, J Alfredo

2016-05-01

We evaluated the potential role of the triglyceride-glucose index (TyG index) as a predictor of diabetes in a White European cohort, and compared it to fasting plasma glucose (FPG) and triglycerides. 4820 patients of the Vascular-Metabolic CUN cohort (VMCUN cohort) were examined and followed up for 8.84years (±4.39). We performed a Cox proportional hazard ratio with repeated-measures analyses to assess the risk of developing type 2 diabetes across quartiles of FPG, triglycerides and the TyG index (ln[fasting triglycerides (mg/dl)×fasting plasma glucose (mg/dl)/2]), and plotted a receiver operating characteristics (ROC) curve for discrimination. There were 332 incident cases of type 2 diabetes involving 43,197.32person-years of follow-up. We observed a progressively increased risk of diabetes in subjects with TyG index levels of 8.31 or more. Among those with normal fasting glucose at baseline, <100mg/dl, subjects with the TyG index in the fourth quartile were 6.87 times more likely to develop diabetes (95% CI, 2.76-16.85; P for trend<0.001), as compared with the bottom quartile. The areas under the ROC curves (95% CI) were 0.75 (0.70-0.81) for TyG index, 0.66 (0.60-0.72) for FPG and 0.71 (0.65-0.77) for TG, in subjects with normal fasting glucose (p=0.017). Our data suggest that the TyG index is useful for the early identification of individuals at risk of type 2 diabetes. The TyG index seems to be a better predictor than FPG or triglycerides of the potential development of type 2 diabetes in normoglycemic patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of Risk Score for Predicting 3-Year Incidence of Type 2 Diabetes: Japan Epidemiology Collaboration on Occupational Health Study.

PubMed

Nanri, Akiko; Nakagawa, Tohru; Kuwahara, Keisuke; Yamamoto, Shuichiro; Honda, Toru; Okazaki, Hiroko; Uehara, Akihiko; Yamamoto, Makoto; Miyamoto, Toshiaki; Kochi, Takeshi; Eguchi, Masafumi; Murakami, Taizo; Shimizu, Chii; Shimizu, Makiko; Tomita, Kentaro; Nagahama, Satsue; Imai, Teppei; Nishihara, Akiko; Sasaki, Naoko; Hori, Ai; Sakamoto, Nobuaki; Nishiura, Chihiro; Totsuzaki, Takafumi; Kato, Noritada; Fukasawa, Kenji; Huanhuan, Hu; Akter, Shamima; Kurotani, Kayo; Kabe, Isamu; Mizoue, Tetsuya; Sone, Tomofumi; Dohi, Seitaro

2015-01-01

Risk models and scores have been developed to predict incidence of type 2 diabetes in Western populations, but their performance may differ when applied to non-Western populations. We developed and validated a risk score for predicting 3-year incidence of type 2 diabetes in a Japanese population. Participants were 37,416 men and women, aged 30 or older, who received periodic health checkup in 2008-2009 in eight companies. Diabetes was defined as fasting plasma glucose (FPG) ≥ 126 mg/dl, random plasma glucose ≥ 200 mg/dl, glycated hemoglobin (HbA1c) ≥ 6.5%, or receiving medical treatment for diabetes. Risk scores on non-invasive and invasive models including FPG and HbA1c were developed using logistic regression in a derivation cohort and validated in the remaining cohort. The area under the curve (AUC) for the non-invasive model including age, sex, body mass index, waist circumference, hypertension, and smoking status was 0.717 (95% CI, 0.703-0.731). In the invasive model in which both FPG and HbA1c were added to the non-invasive model, AUC was increased to 0.893 (95% CI, 0.883-0.902). When the risk scores were applied to the validation cohort, AUCs (95% CI) for the non-invasive and invasive model were 0.734 (0.715-0.753) and 0.882 (0.868-0.895), respectively. Participants with a non-invasive score of ≥ 15 and invasive score of ≥ 19 were projected to have >20% and >50% risk, respectively, of developing type 2 diabetes within 3 years. The simple risk score of the non-invasive model might be useful for predicting incident type 2 diabetes, and its predictive performance may be markedly improved by incorporating FPG and HbA1c.

Do Cinnamon Supplements Have a Role in Glycemic Control in Type 2 Diabetes? A Narrative Review.

PubMed

Costello, Rebecca B; Dwyer, Johanna T; Saldanha, Leila; Bailey, Regan L; Merkel, Joyce; Wambogo, Edwina

2016-11-01

Cinnamon (Cinnamomum sp) has been suggested to help patients with type 2 diabetes mellitus (T2DM) achieve better glycemic control, although conclusions from meta-analyses are mixed. To evaluate whether the use of cinnamon dietary supplements by adults with T2DM had clinically meaningful effects on glycemic control, as measured by changes in fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c), a comprehensive PubMed literature search was performed. Eleven randomized controlled trials were identified that met our inclusion criteria that enrolled 694 adults with T2DM receiving hypoglycemic medications or not. In 10 of the studies, participants continued to take their hypoglycemic medications during the cinnamon intervention period. Studies ranged from 4 to 16 weeks in duration; seven studies were double-blind. Cinnamon doses ranged from 120 to 6,000 mg/day. The species of cinnamon used varied: seven used Cinnamomum cassia or Cinnamomum aromaticum, one used Cinnamomum zeylanicum, and three did not disclose the species. Because of the heterogeneity of the studies, a meta-analysis was not conducted. All 11 of the studies reported some reductions in FPG during the cinnamon intervention, and of the studies measuring HbA1c very modest decreases were also apparent with cinnamon, whereas changes in the placebo groups were minimal. However, only four studies achieved the American Diabetes Association treatment goals (FPG <7.2 mmol/L [130 mg/dL] and/or HbAlc <7.0). We conclude that cinnamon supplements added to standard hypoglycemic medications and other lifestyle therapies had modest effects on FPG and HbA1c. Until larger and more rigorous studies are available, registered dietitian nutritionists and other health care professionals should recommend that patients continue to follow existing recommendations of authoritative bodies for diet, lifestyle changes, and hypoglycemic drugs. Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Do Cinnamon Supplements Have a Role in Glycemic Control in Type 2 Diabetes – A Narrative Review?

PubMed Central

Costello, Rebecca B.; Dwyer, Johanna T.; Saldanha, Leila; Bailey, Regan L.; Merkel, Joyce; Wambogo, Edwina

2016-01-01

Cinnamon (Cinnamomum sp.) has been suggested to help patients with type 2 diabetes mellitus (T2DM) achieve better glycemic control although conclusions from meta-analyses are mixed. To evaluate whether the use of cinnamon dietary supplements by adults with T2DM had clinically meaningful effects on glycemic control, as measured by changes in fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c), a comprehensive PubMed literature search was performed. Eleven RCTs were identified meeting our inclusion criteria that enrolled 694 adults with T2DM receiving hypoglycemic medications or not. In 10 of the studies participants continued to take their hypoglycemic medications during the cinnamon intervention period. Studies ranged from 4 to 16 weeks in duration; seven studies were double-blinded. Cinnamon doses ranged from 120 to 6000 mg/d. The species of cinnamon used varied; 7 used C. cassia/C. aromaticum; 1 used C. zeylanicum, and 3 did not disclose it. Because of the heterogenity of the studies, a metaanalysis was not conducted. All 11 of the studies reported some reductions in FPG during the cinnamon intervention, and of the studies measuring HbA1c very modest decreases were also apparent with cinnamon, while changes in the placebo groups were minimal. However, only four studies achieved the American Diabetes Association treatment goals (FPG <7.2 mmol/L or 130 mg/dL and/or HbAlc <7.0). We conclude that cinnamon supplements added to standard hypoglycemic medications and other lifestyle therapies had modest effects on FPG and HbA1c. Until larger and more rigorous studies are available, dietitians and other healthcare professionals should recommend that patients continue to follow existing recommendations of authoritative bodies for diet, lifestyle changes, and hypoglycemic drugs. PMID:27618575

Clinical and Metabolic Response to Selenium Supplementation in Pregnant Women at Risk for Intrauterine Growth Restriction: Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Mesdaghinia, Elaheh; Rahavi, Azam; Bahmani, Fereshteh; Sharifi, Nasrin; Asemi, Zatollah

2017-07-01

Data on the effects of selenium supplementation on clinical signs and metabolic profiles in women at risk for intrauterine growth restriction (IUGR) are scarce. This study was designed to assess the effects of selenium supplementation on clinical signs and metabolic status in pregnant women at risk for IUGR. This randomized double-blind placebo-controlled clinical trial was performed among 60 women at risk for IUGR according to abnormal uterine artery Doppler waveform. Participants were randomly assigned to intake either 100 μg selenium supplements as tablet (n = 30) or placebo (n = 30) for 10 weeks between 17 and 27 weeks of gestation. After 10 weeks of selenium administration, a higher percentage of women in the selenium group had pulsatility index (PI) of <1.45) (P = 0.002) than of those in the placebo group. In addition, changes in plasma levels of total antioxidant capacity (TAC) (P < 0.001), glutathione (GSH) (P = 0.008), and high-sensitivity C-reactive protein (hs-CRP) (P = 0.004) in the selenium group were significant compared with the placebo group. Additionally, selenium supplementation significantly decreased serum insulin (P = 0.02), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (P = 0.02), and homeostatic model assessment for B-cell function (HOMA-B) (P = 0.02) and significantly increased quantitative insulin sensitivity check index (QUICKI) (P = 0.04) and HDL-C levels (P = 0.02) compared with the placebo. We did not find any significant effect of selenium administration on malondialdehyde (MDA), nitric oxide (NO), fasting plasma glucose (FPG), and other lipid profiles. Overall, selenium supplementation in pregnant women at risk for IUGR resulted in improved PI, TAC, GSH, hs-CRP, and markers of insulin metabolism and HDL-C levels, but it did not affect MDA, NO, FPG, and other lipid profiles.Clinical trial registration number http://www.irct.ir : IRCT201601045623N64.

The reliability of in-hospital diagnoses of diabetes mellitus in the setting of an acute myocardial infarction.

PubMed

Arnold, Suzanne V; Lipska, Kasia J; Inzucchi, Silvio E; Li, Yan; Jones, Philip G; McGuire, Darren K; Goyal, Abhinav; Stolker, Joshua M; Lind, Marcus; Spertus, John A; Kosiborod, Mikhail

2014-01-01

Incident diabetes mellitus (DM) is important to recognize in patients with acute myocardial infarction (AMI). To develop an efficient screening strategy, we explored the use of random plasma glucose (RPG) at admission and fasting plasma glucose (FPG) to select patients with AMI for glycosylated hemoglobin (HbA1c) testing. Prospective registry of 1574 patients with AMI not taking glucose-lowering medication from 24 US hospitals. All patients had HbA1c measured at a core laboratory and admission RPG and ≥2 FPGs recorded during hospitalization. We examined potential combinations of RPG and FPG and compared these with HbA1c≥6.5%-considered the gold standard for DM diagnosis in these analyses. An RPG>140 mg/dL or FPG≥126 mg/dL had high sensitivity for DM diagnosis. Combining these into a screening protocol (if admission RPG>140, check HbA1c; or if FPG≥126 on a subsequent day, check HbA1c) led to HbA1c testing in 50% of patients and identified 86% with incident DM (number needed to screen (NNS)=3.3 to identify 1 case of DM; vs NNS=5.6 with universal HbA1c screening). Alternatively, using an RPG>180 led to HbA1c testing in 40% of patients with AMI and identified 82% of DM (NNS=2.7). We have established two potential selective screening methods for DM in the setting of AMI that could identify the vast majority of incident DM by targeted screening of 40-50% of patients with AMI with HbA1c testing. Using these methods may efficiently identify patients with AMI with DM so that appropriate education and treatment can be promptly initiated.

Association between cardiac autonomic function, oxidative stress and inflammatory response in impaired fasting glucose subjects: cross-sectional study.

PubMed

Thiyagarajan, Ramkumar; Subramanian, Senthil Kumar; Sampath, Nishanth; Madanmohan Trakroo; Pal, Pravati; Bobby, Zachariah; Paneerselvam, Sankar; Das, Ashok Kumar

2012-01-01

The worldwide burden of diabetes in 2030 is projected around 552 million. Diabetes leads to higher risk for cardiovascular diseases (CVD). Altered cardiac autonomic function (CAF) measured by heart rate variability (HRV) is observed in early stages of diabetes but the relationship between impaired fasting glucose (IFG) and HRV is still debatable. The aim of the study was to evaluate the association between CAF, oxidative stress, insulin resistance (IR), and inflammatory response in IFG subjects. Cross-sectional blinded study. Volunteers recruited from health awareness camps underwent CAF and biochemical tests. Based on fasting plasma glucose (FPG) participants (n = 123) were divided into two groups, normal fasting glucose (n = 76) and IFG (n = 47). The comparison of parameters between the groups was carried out using student t test and Mann-Whitney U test for parametric and non-parametric data respectively. The correlation between the parameters was analyzed by Spearman's rank correlation using SPSS 13.0. The resting cardiovagal modulation parameters, heart rate response to forced timed breathing, and orthostatic stress were reduced in IFG subjects. Fasting plasma lipid profile, coronary atherogenic lipid risk factors, IR, thiobarbituric acid reactive substance (TBARS), high sensitive C-reactive protein, and tumor necrosis factor alpha were increased and total antioxidant capacity (TAC) was decreased significantly in IFG group but no significant alteration was observed in high-density lipoprotein (HDL-c). Cardiovagal modulation parameters were negatively correlated with triglycerides, FPG, insulin, IR, TBARS, and inflammatory markers and positively with TAC. There is a continuous interplay between the altered CAF, hyperinsulinemia, IR, oxidative stress parameters, inflammatory response, and IFG in which one factor perpetuates another leading to the progression of disease.

Evaluation of fasting plasma insulin concentration as an estimate of insulin action in nondiabetic individuals: comparison with the homeostasis model assessment of insulin resistance (HOMA-IR).

PubMed

Abbasi, Fahim; Okeke, QueenDenise; Reaven, Gerald M

2014-04-01

Insulin-mediated glucose disposal varies severalfold in apparently healthy individuals, and approximately one-third of the most insulin resistant of these individuals is at increased risk to develop various adverse clinical syndromes. Since direct measurements of insulin sensitivity are not practical in a clinical setting, several surrogate estimates of insulin action have been proposed, including fasting plasma insulin (FPI) concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) calculated by a formula employing fasting plasma glucose (FPG) and FPI concentrations. The objective of this study was to compare FPI as an estimate of insulin-mediated glucose disposal with values generated by HOMA-IR in 758 apparently healthy nondiabetic individuals. Measurements were made of FPG, FPI, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and insulin-mediated glucose uptake was quantified by determining steady-state plasma glucose (SSPG) concentration during the insulin suppression test. FPI and HOMA-IR were highly correlated (r = 0.98, P < 0.001). The SSPG concentration also correlated to a similar degree (P < 0.001) with FPI (r = 0.60) and HOMA-IR (r = 0.64). Furthermore, the relationship between FPI and TG (r = 0.35) and HDL-C (r = -0.40) was comparable to that between HOMA-IR and TG (r = 0.39) and HDL-C (r = -0.41). In conclusion, FPI and HOMA-IR are highly correlated in nondiabetic individuals, with each estimate accounting for ~40% of the variability (variance) in a direct measure of insulin-mediated glucose disposal. Calculation of HOMA-IR does not provide a better surrogate estimate of insulin action, or of its associated dyslipidemia, than measurement of FPI.

Sibutramine and L-carnitine compared to sibutramine alone on insulin resistance in diabetic patients.

PubMed

Derosa, Giuseppe; Maffioli, Pamela; Salvadeo, Sibilla A T; Ferrari, Ilaria; Gravina, Alessia; Mereu, Roberto; D'Angelo, Angela; Palumbo, Ilaria; Randazzo, Sabrina; Cicero, Arrigo F G

2010-01-01

To evaluate the effects of one year of treatment with sibutramine plus L-carnitine compared to sibutramine on body weight, glycemic control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-four patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) >8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). There was a decrease in body weight, BMI, HbA(1c), FPI, HOMA-IR, and RBP-4 in both groups, even when the values obtained with sibutramine plus L-carnitine were lower than the values obtained in sibutramine group. There was a faster decrease of FPG, PPG, TC, LDL-C, resistin and Hs-CRP with sibutramine plus L-carnitine even when no differences between the two groups were obtained. Furthermore, only sibutramine plus L-carnitine improved Tg, and visfatin. Sibutramine plus L-carnitine gave a faster improvement of lipid profile, insulin resistance parameters, glycemic control, and body weight compared to sibutramine.

Exposure-response modelling for empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes.

PubMed

Riggs, Matthew M; Seman, Leo J; Staab, Alexander; MacGregor, Thomas R; Gillespie, William; Gastonguay, Marc R; Woerle, Hans J; Macha, Sreeraj

2014-12-01

To provide model-based clinical development decision support including dose selection guidance for empagliflozin, an orally administered sodium glucose cotransporter 2 inhibitor, through developed exposure-response (E-R) models for efficacy and tolerability in patients with type 2 diabetes mellitus (T2DM). Five randomized, placebo-controlled, multiple oral dose studies of empagliflozin in patients with T2DM (n = 974; 1-100 mg once daily, duration ≤12 weeks) were used to develop E-R models for efficacy (glycosylated haemoglobin [HbA1c ], fasting plasma glucose [FPG] and urinary glucose excretion). Two studies (n = 748, 12 weeks) were used to evaluate tolerability E-R. The efficacy model predicted maximal decreases in FPG and HbA1c of 16% and 0.6%, respectively, assuming a baseline FPG concentration of 8 mm (144 mg dl(-1) ) and 10-25 mg every day empagliflozin targeted 80-90% of these maximums. Increases in exposure had no effect on incidence rates of hypoglycaemia (n = 4), urinary tract infection (n = 17) or genital/vulvovaginal-related (n = 16) events, although low prevalence rates may have precluded more accurate evaluation. E-R analyses indicated that 10 and 25 mg once daily empagliflozin doses achieved near maximal glucose lowering efficacy. © 2014 The British Pharmacological Society.

Exposure−response modelling for empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes

PubMed Central

Riggs, Matthew M; Seman, Leo J; Staab, Alexander; MacGregor, Thomas R; Gillespie, William; Gastonguay, Marc R; Woerle, Hans J; Macha, Sreeraj

2014-01-01

Aims To provide model-based clinical development decision support including dose selection guidance for empagliflozin, an orally administered sodium glucose cotransporter 2 inhibitor, through developed exposure−response (E−R) models for efficacy and tolerability in patients with type 2 diabetes mellitus (T2DM). Methods Five randomized, placebo-controlled, multiple oral dose studies of empagliflozin in patients with T2DM (n = 974; 1–100 mg once daily, duration ≤12 weeks) were used to develop E−R models for efficacy (glycosylated haemoglobin [HbA1c], fasting plasma glucose [FPG] and urinary glucose excretion). Two studies (n = 748, 12 weeks) were used to evaluate tolerability E−R. Results The efficacy model predicted maximal decreases in FPG and HbA1c of 16% and 0.6%, respectively, assuming a baseline FPG concentration of 8 mm (144 mg dl−1) and 10–25 mg every day empagliflozin targeted 80–90% of these maximums. Increases in exposure had no effect on incidence rates of hypoglycaemia (n = 4), urinary tract infection (n = 17) or genital/vulvovaginal-related (n = 16) events, although low prevalence rates may have precluded more accurate evaluation. Conclusions E−R analyses indicated that 10 and 25 mg once daily empagliflozin doses achieved near maximal glucose lowering efficacy. PMID:24964723

Evaluation of knowledge regarding gestational diabetes mellitus and its association with glycaemic level: A Malaysian study.

PubMed

Hussain, Zahid; Yusoff, Zuraidah Mohd; Sulaiman, Syed Azhar Syed

2015-06-01

The aim of this study was to evaluate the knowledge about GDM and its corresponding relation with glycaemic level in GDM patients. A cross-sectional study was conducted in antenatal clinic of Hospital Pulau Pinang, Malaysia from June 2013 to December 2013 using Gestational Diabetes Mellitus Knowledge Questionnaire (GDMKQ) on the sample of 175 GDM patients. Three most recent fasting plasma glucose (FPG) values (mmol/l) were taken from patients profiles and mean was calculated. A total of 166 patients were included in final analysis. A total mean knowledge score of 166 patients was 10.01±3.63 and total mean FPG value was 5.50±1.13. Knowledge had a significant negative association with FPG (r=- 0.306, P<0.01). Among different knowledge domains, highest mean score was seen for diet/food values domain and lowest for management of GDM. Educational level seems to be the most significant predictor of GDM knowledge and glycaemic control. Highest mean knowledge score and lowest mean glycaemic levels were recorded for patients aged 25-29 years, Malay ethnicity, working women and family history of DM. Higher Knowledge about GDM is related to better glycaemic control. New educational strategies should be developed to improve the lower health literacy. Copyright © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Role of DNA base excision repair in the mutability and virulence of Streptococcus mutans

PubMed Central

Gonzalez, Kaisha; Faustoferri, Roberta C.; Quivey, Robert G.

2012-01-01

Summary The oral pathogen, Streptococcus mutans, possesses inducible DNA repair defenses for protection against pH fluctuations and production of reactive oxygen metabolites such as hydrogen peroxide (H2O2), which are present in the oral cavity. DNA base excision repair (BER) has a critical role in genome maintenance by preventing the accumulation of mutations associated with environmental factors and normal products of cellular metabolism. In this study, we examined the consequences of compromising the DNA glycosylases (Fpg and MutY) and endonucleases (Smx and Smn) of the BER pathway and their relative role in adaptation and virulence. Enzymatic characterization of the BER system showed that it protects the organism against the effects of the highly mutagenic lesion, 7,8-dihydro-8-oxo-2’-deoxyguanine (8-oxo-dG). S. mutans strains lacking a functional Fpg, MutY, or Smn showed elevated spontaneous mutation frequencies; and, these mutator phenotypes correlated with the ability of the strains to survive killing by acid and oxidative agents. In addition, in the G. mellonella virulence model, strains of S. mutans deficient in Fpg, MutY and Smn showed increased virulence as compared to the parent strain. Our results suggest that, for S. mutans, mutator phenotypes, due to loss of BER enzymes, may confer an advantage to virulence of the organism. PMID:22651851

Lixisenatide plus basal insulin in patients with type 2 diabetes mellitus: a meta-analysis.

PubMed

Charbonnel, Bernard; Bertolini, Monica; Tinahones, Francisco J; Domingo, Manuel Puig; Davies, Melanie

2014-01-01

The efficacy of the once-daily prandial GLP-1 receptor agonist lixisenatide plus basal insulin in T2DM was assessed by pooling results of phase III trials. A meta-analysis was performed of results from three trials in the GetGoal clinical program concerning lixisenatide or placebo plus basal insulin with/without OADs. The primary endpoint was change in HbA1c from baseline to week 24. Secondary endpoints were change in PPG, FPG, insulin dose, and weight from baseline to week 24. Hypoglycemia rates and several composite endpoints were assessed. Lixisenatide plus basal insulin was significantly more effective than basal insulin alone at reducing HbA1c at 24 weeks. Composite and secondary endpoints were improved significantly with lixisenatide plus basal insulin, with the exception of FPG, which showed no significant difference between the groups. Lixisenatide plus basal insulin was associated with an increased incidence of hypoglycemia versus basal insulin alone. Lixisenatide plus basal insulin resulted in significant improvement in glycemic control versus basal insulin alone, particularly in terms of controlling PPG. Prandial lixisenatide in combination with basal insulin is a suitable option for treatment intensification in patients with T2DM insufficiently controlled with basal insulin, as these agents have complementary effects on PPG and FPG, respectively. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Chromium supplements for glycemic control in type 2 diabetes: limited evidence of effectiveness

PubMed Central

Dwyer, Johanna T.; Bailey, Regan L.

2016-01-01

Some adults with type 2 diabetes mellitus (T2DM) believe that chromium-containing supplements will help control their disease, but the evidence is mixed. This narrative review examines the efficacy of chromium supplements for improving glycemic control as measured by decreases in fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c). Using systematic search criteria, 20 randomized controlled trials of chromium supplementation in T2DM patients were identified. Clinically meaningful treatment goals were defined as an FPG of ≤7.2 mmol/dL, a decline in HbA1c to ≤7%, or a decrease of ≥0.5% in HbA1c. In only a few randomized controlled trials did FPG (5 of 20), HbA1c (3 of 14), or both (1 of 14) reach the treatment goals with chromium supplementation. HbA1c declined by ≥0.5% in 5 of 14 studies. On the basis of the low strength of existing evidence, chromium supplements have limited effectiveness, and there is little rationale to recommend their use for glycemic control in patients with existing T2DM. Future meta-analyses should include only high-quality studies with similar forms of chromium and comparable inclusion/exclusion criteria to provide scientifically sound recommendations for clinicians. PMID:27261273

Role of DNA repair enzymes in the cellular resistance to oxidative stress.

PubMed

Laval, J

1996-01-01

Oxidative stress occurs in cells when the equilibrium between prooxidant and antioxidant species is broken in favor of the prooxidant state. It is due to reactive oxygen species (ROS) generated either by the cellular metabolism such as phagocytosis, mitochondrial respiration, xenobiotic detoxification, or by exogenous factors such as ionizing radiation or chemical compounds performing red-ox reactions. Some ROS are extremely reactive and interact with all the macromolecules including lipids, nucleic acids and proteins. Cells have numerous defence systems to counteract the deleterious effects of ROS. Proteins and small molecules specifically eliminate ROS when they are formed. There are three species of superoxyde dismutases which transform the superoxyde anion O2- in hydrogen peroxyde H2O2 which in turn will be destroyed by peroxysomal catalase or by various peroxydases. There are numerous small molecules in the cell such as glutathion, alpha-tocopherol, vitamines A and C, melanine, etc. which are antioxydant molecules. ROS escaping destruction generate various lesions in DNA such as base modifications, degradation products of deoxyribose, chain breaks. These various lesions have been characterized and it is possible to quantitate them in the DNA of cells which have been irradiated or treated by free radical generating systems. The biological properties of the bases modified by ROS have been established. For example C8-hydroxyguanine (8-oxoG) is promutagenic since, if present in DNA during replication, it leads to incorporation of dAMP residues, leading to transversion mutation (GC-->TA). Purines whose imidazole ring is opened (Fapy residues) are stops for the DNA polymerase during DNA replication and are therefore potentially lethal lesions for the cell. Oxidized pyrimidines have comparable coding properties. Efficient DNA repair mechanisms remove these oxidized bases. In Escherichia coli cells, endonuclease III (NTH protein) and endonuclease VIII (NEI protein) excise many oxidized pyrimidines, whereas the FPG protein (formamidopyrimidine-DNA-glycosylase) eliminates 8-oxoG and Fapy lesions. Besides its DNA glycosylase activity, the protein FPG has a beta-lyase activity incising DNA at abasic site by a beta-delta elimination mechanism, and a dRPase activity. The FPG protein has a zinc finger motive which is mandatory for the recognition of its substrate. Mammalian cells have similar DNA repair proteins and it should be emphazized that there is conservation of the different functions and in most cases a remarquable homology of the amino acids sequences from E. coli to man.

Association Between the Presence of Iron Deficiency Anemia and Hemoglobin A1c in Korean Adults

PubMed Central

Hong, Jae W.; Ku, Cheol R.; Noh, Jung H.; Ko, Kyung S.; Rhee, Byoung D.; Kim, Dong-Jun

2015-01-01

Abstract Few studies have investigated the clinical effect of iron deficiency anemia (IDA) on the use of the Hemoglobin A1c (HbA1c) as a screening parameter for diabetes or prediabetes. We investigated the association between IDA and HbA1c levels in Korean adults. Among the 11,472 adults (≥19 years of age) who participated in the 2011–2012 Korea National Health and Nutrition Examination Survey (a cross-sectional and nationally representative survey conducted by the Korean Center for Disease Control for Health Statistics), 807 patients with diabetes currently taking anti-diabetes medications were excluded from this study. We compared the weighted HbA1c levels and weighted proportion (%) of HbA1c levels of ≥5.7%, ≥6.1%, and ≥6.5% according to the range of fasting plasma glucose (FPG) levels and the presence of IDA. Among 10,665 participants (weighted n = 35,229,108), the prevalence of anemia and IDA was 7.3% and 4.3%, respectively. The HbA1c levels were higher in participants with IDA (5.70% ± 0.02%) than in normal participants (5.59% ± 0.01%; P < 0.001), whereas there was no significant difference in FPG levels. In participants with an FPG level of <100 mg/dL and 100 to 125 mg/dL, the weighted HbA1c level was higher in those with IDA (5.59% ± 0.02% and 6.00% ± 0.05%) than in normal participants (5.44% ± 0.01% and 5.82% ± 0.01%) after adjusting for confounders such as age, sex, FPG level, heavy alcohol drinking, waist circumference, and smoking status as well as after exclusion of an estimated glomerular filtration rate of <60 mL/min/1.73 m2 (P < 0.001, <0.01). The weighted proportions (%) of an HbA1c level of ≥5.7% and ≥6.1% were also higher in participants with IDA than in normal participants (P < 0.001, <0.05). However, the weighted HbA1c levels in individuals with an FPG level ≥126 mg/dL and a weighted proportion (%) of an HbA1c level of ≥6.5% showed no significant differences according to the presence of IDA. In conclusion, the presence of IDA shifted the HbA1c level upward only in the normoglycemic and prediabetic ranges, not in the diabetic range. Therefore, IDA should be considered before using HbA1c as a screening test for prediabetes. PMID:25997055

Genotoxic and oxidative effects induced on A549 cells by extract of PM10 collected in an electric steel plant.

PubMed

Cavallo, Delia; Ursini, Cinzia L; Maiello, Raffaele; Apostoli, Pietro; Catalani, Simona; Ciervo, Aureliano; Iavicoli, Sergio

2008-01-01

The present study was aimed at assessing the carcinogenic risk of occupational exposure to PM10 in electric steel plants. PM10 was collected on cellulose filter respectively outside (site 1) and inside (site 2) the furnace area, was measured, extracted and its metal content was analysed by ICP-MS. Cells were exposed for 30 min, 2 and 4 hours to extract of filter from each site diluted at 0.004, 0.008 and 0.02%. The direct/oxidative DNA damage caused by PM10 was evaluated on A549 cells by Fpg-modified comet assay, analysing Tail moment (TM) and comet percentage. Air samples contained 1.08 mg/m3 of PM10 in site 1 and 5.54 mg/m3in site 2 and different amounts of metals with higher levels of Zn, Al, Ni, Pb, Cd, Cr, Ba in site 2 and of Fe, Mn, Sb in site 1. In cells exposed for 2h to PM10 from both sites, an oxidative DNA damage was found concentrations of 0.008% and 0.02%. For site 2, a direct DNA damage at 0.02% was also found. After 4h a direct/oxidative DNA damage was detected at 0.02% for site 2 and an oxidative DNA damage for site 1. The results indicate a moderate DNA damage induction by used diluitions of PM10 extracts with higher extent for more polluted site 2. These findings show the suitability of this experimental model to evaluate early DNA damage induced by complex mixtures containing metals on target organ, suggesting its use to study biological effects of occupational exposure to such substances.

[BO's abdominal acupuncture for obese type-2 diabetes mellitus].

PubMed

Yang, Yuan; Liu, Yunxia

2015-04-01

To observe the clinical efficacy of BO's abdominal acupuncture for obese type-2 diabetes mellitus (T2DM). Sixty patients of obese T2DM were randomly divided into an acupuncture group and a medication group, 30 cases in each one. Patients in the medication group were treated with basic treatment combined with oral administration of regular antidiabetics, three weeks as one session. Patients in the acupuncture group, based on the medication group, were treated with abdominal acupuncture at Yinqiguiyuan [Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6), Guanguan (CV 4)], Fusiguan [Huaroumen (ST 24), Wailing (TE 5)], Tianshu (ST 25), Daheng (SP 15), Qixue (KI 13), etc.; the treatment was given three times per week, 3 weeks as one session. The systolic blood pressure (SBP), diastolic blood pressure (DBP), body weight, waist circumference (WC), hip circumference, body mass index (BI) were observed before and after treatment in the two groups, and fasting plasma glucose (FPG), fasting insulin (FINS), 2-hours postprandial blood glucose by oral glucose tolerance test (OGTT) and insulin, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), HOMA-IR of insulin resistance index were calculated and adverge events were recorded. Compared before the treatment, SBP, WC, body weight, BMI, FPG, OG-TT2hBG, FINS, GTT2h insulin, HOMA-IR, TC and LDL-C in the acupuncture group were all significantly reduced (all P <0. 05), while FPG, OGTT2H insulin and TG were increased in the medication group (all P<0. 05)'. The differences of reducing SBP, WC, FPG, OGTT2H insulin, HOMA-IR, TC, TG and LDL-C were statistically significant between the two groups (all P<0. 05). The total effective rate was 93. 3% (28/30) in the acupuncture group, which was significantly superior to 23. 3% (7/30) in the medication group (P<0. 01). BO's abdominal acupuncture has obvious clinical efficacy for obese type-2 diabetes mellitus, featuring in lowering blood pressure, reducing weight, decreasing blood glucose, im- proving insulin resistance and lowering lipid, which has no adverse effects and is worthy of clinical popularization and application.

Patient-level meta-analysis of efficacy and hypoglycaemia in people with type 2 diabetes initiating insulin glargine 100U/mL or neutral protamine Hagedorn insulin analysed according to concomitant oral antidiabetes therapy.

PubMed

Owens, David R; Traylor, Louise; Mullins, Peter; Landgraf, Wolfgang

2017-02-01

Evaluate efficacy and hypoglycaemia according to concomitant oral antidiabetes drug (OAD) in people with type 2 diabetes initiating insulin glargine 100U/mL (Gla-100) or neutral protamine Hagedorn (NPH) insulin once daily. Four studies (target fasting plasma glucose [FPG] ⩽100mg/dL [⩽5.6mmol/L]; duration ⩾24weeks) were included. Standardised data from 2091 subjects (Gla-100, n=1024; NPH insulin, n=1067) were analysed. Endpoints included glycated haemoglobin (HbA1c) and FPG change, glycaemic target achievement, hypoglycaemia, weight change, and insulin dose. Mean HbA1c and FPG reductions were similar with Gla-100 and NPH insulin regardless of concomitant OAD (P=0.184 and P=0.553, respectively) and similar proportions of subjects achieved HbA1c <7.0% (P=0.603). There was a trend for more subjects treated with Gla-100 achieving FPG ⩽100mg/dL versus NPH insulin (relative risk [RR] 1.09 [95% confidence interval (CI) 0.97-1.23]; P=0.135). Plasma glucose confirmed (<70mg/dL) overall and nocturnal hypoglycaemia incidences and rates were lower with Gla-100 versus NPH insulin (overall RR 0.93 [95% CI 0.87-1.00]; P=0.041; nocturnal RR 0.73 [95% CI 0.65-0.83]; P<0.001). After 24weeks, weight gain and insulin doses were higher with Gla-100 versus NPH insulin (2.7kg vs 2.3kg, P=0.009 and 0.42U/kg vs 0.39U/kg; P=0.003, respectively). Insulin doses were higher when either insulin was added to sulfonylurea alone. Pooled results from treat-to-target trials in insulin-naïve people with type 2 diabetes demonstrate a significantly lower overall and nocturnal hypoglycaemia risk across different plasma glucose definitions with Gla-100 versus NPH insulin at similar glycaemic control. OAD therapy co-administered with Gla-100 or NPH insulin impacts glycaemic control and overall nocturnal hypoglycaemia risk. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Repair of 8-oxo-7,8-dihydroguanine in prokaryotic and eukaryotic cells: Properties and biological roles of the Fpg and OGG1 DNA N-glycosylases.

PubMed

Boiteux, Serge; Coste, Franck; Castaing, Bertrand

2017-06-01

Oxidatively damaged DNA results from the attack of sugar and base moieties by reactive oxygen species (ROS), which are formed as byproducts of normal cell metabolism and during exposure to endogenous or exogenous chemical or physical agents. Guanine, having the lowest redox potential, is the DNA base the most susceptible to oxidation, yielding products such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2-6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). In DNA, 8-oxoG was shown to be mutagenic yielding GC to TA transversions upon incorporation of dAMP opposite this lesion by replicative DNA polymerases. In prokaryotic and eukaryotic cells, 8-oxoG is primarily repaired by the base excision repair pathway (BER) initiated by a DNA N-glycosylase, Fpg and OGG1, respectively. In Escherichia coli, Fpg cooperates with MutY and MutT to prevent 8-oxoG-induced mutations, the "GO-repair system". In Saccharomyces cerevisiae, OGG1 cooperates with nucleotide excision repair (NER), mismatch repair (MMR), post-replication repair (PRR) and DNA polymerase η to prevent mutagenesis. Human and mouse cells mobilize all these pathways using OGG1, MUTYH (MutY-homolog also known as MYH), MTH1 (MutT-homolog also known as NUDT1), NER, MMR, NEILs and DNA polymerases η and λ, to prevent 8-oxoG-induced mutations. In fact, mice deficient in both OGG1 and MUTYH develop cancer in different organs at adult age, which points to the critical impact of 8-oxoG repair on genetic stability in mammals. In this review, we will focus on Fpg and OGG1 proteins, their biochemical and structural properties as well as their biological roles. Other DNA N-glycosylases able to release 8-oxoG from damaged DNA in various organisms will be discussed. Finally, we will report on the role of OGG1 in human disease and the possible use of 8-oxoG DNA N-glycosylases as therapeutic targets. Copyright © 2017 Elsevier Inc. All rights reserved.

Differences in Hemoglobin A1c Between Hispanics/Latinos and Non-Hispanic Whites: An Analysis of the Hispanic Community Health Study/Study of Latinos and the 2007–2012 National Health and Nutrition Examination Survey

PubMed Central

Hsu, Lucy L.; Arredondo, Mario; Menke, Andy; Werner, Ellen; Thyagarajan, Bharat; Heiss, Gerardo; Teng, Yanping; Schneiderman, Neil; Giachello, Aida L.; Gallo, Linda C.; Talavera, Gregory A.; Cowie, Catherine C.

2016-01-01

OBJECTIVE To determine whether, after adjustment for glycemia and other selected covariates, hemoglobin A1c (HbA1c) differed among adults from six Hispanic/Latino heritage groups (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American) and between Hispanic/Latino and non-Hispanic white adults without self-reported diabetes. RESEARCH DESIGN AND METHODS We performed a cross-sectional analysis of data from 13,083 individuals without self-reported diabetes from six Hispanic/Latino heritage groups, enrolled from 2008 to 2011 in the Hispanic Community Health Study/Study of Latinos, and 2,242 non-Hispanic white adults enrolled during the 2007–2012 cycles of the National Health and Nutrition Examination Survey. We compared HbA1c levels among Hispanics/Latinos and between Hispanics/Latinos and non-Hispanic whites before and after adjustment for age, sex, fasting (FPG) and 2-h post–oral glucose tolerance test (2hPG) glucose, anthropometric measurements, and selected biochemical and hematologic variables and after stratification by diabetes status: unrecognized diabetes (FPG ≥7.1 mmol/L or 2hPG ≥11.2 mmol/L), prediabetes (FPG 5.6–7.0 mmol/L or 2hPG 7.8–11.1 mmol/L), and normal glucose tolerance (FPG <5.6 mmol/L and 2hPG <7.8 mmol/L). RESULTS Adjusted mean HbA1c differed significantly across all seven groups (P < 0.001). Non-Hispanic whites had significantly lower HbA1c (P < 0.05) than each individual Hispanic/Latino heritage group. Upon stratification by diabetes status, statistically significant differences (P < 0.001) in adjusted mean HbA1c persisted across all seven groups. CONCLUSIONS HbA1c differs among Hispanics/Latinos of diverse heritage groups and between non-Hispanic whites and Hispanics/Latinos after adjustment for glycemia and other covariates. The clinical significance of these differences is unknown. PMID:27208330

FPG Child Development Institute

MedlinePlus

... Development, Teaching, and Learning The Frank Porter Graham Child Development Institute will partner with Zero to Three to ... Center October 6, 2017 More Frank Porter Graham Child Development Institute The University of North Carolina at Chapel ...

Comparison of twelve single-drug regimens for the treatment of type 2 diabetes mellitus

PubMed Central

Wang, Shao-Lian; Dong, Wen-Bin; Dong, Xiao-Lin; Zhu, Wen-Min; Wang, Fang-Fang; Han, Fang; Yan, Xin

2017-01-01

We performed a network meta-analysis to compare the efficacy of 12 single-drug regimens (Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide, Metformin, Sitaglitin, Exenatide, Liraglutide, Acarbose, Benfluorex, and Glipizide) in the treatment of type 2 diabetes mellitus (T2DM). Fifteen relevant randomized controlled trials (RCTs) were included; direct and indirect evidence from these studies was combined, and weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRAs) were examined to evaluate the monotherapies. Liraglutide was more effective than Glimepiride, Pioglitazone, Sitaglitin, Exenatide, and Glipizide at reducing glycated hemoglobin (HbA1c) levels. In contrast, Acarbose was less effective than Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide, Metformin, and Liraglutide at decreasing HbA1c levels. Reductions in fasting plasma glucose (FPG) levels were similar after all treatments. Rosiglitazone was less effective than Glibenclamide and Repaglinide at reducing total cholesterol (TC) levels. High density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride levels did not differ after treatment with any of the monotherapies. HbA1c and FPG SUCRA values were highest for Liraglutide, while HbA1c and FPG values were lowest for Acarbose, and TC and LDL values were lowest for Rosiglitazone. These results suggest that Liraglutide may be most effective, and Acarbose least effective, at reducing blood glucose levels, while Glibenclamide, Repaglinide, and Metformin may be most effective, and Rosiglitazone least effective, at reducing lipoidemia, in T2DM patients. PMID:29069819

Prevalence and risk factors of gestational diabetes in Punjab, North India: results from a population screening program.

PubMed

Arora, Geeti P; Thaman, Richa G; Prasad, Rashmi B; Almgren, Peter; Brøns, Charlotte; Groop, Leif C; Vaag, Allan A

2015-08-01

The World Health Organization (WHO) has in 2013 changed the diagnostic criteria for gestational diabetes mellitus (GDM) to acknowledge the putative effect of mildly elevated fasting plasma glucose (FPG) levels on pregnancy outcomes. We aimed to determine the prevalence and risk factors of GDM comparing the previous WHO 1999 criteria to the WHO 2013 criteria in North India. In a population-based screening programme, 5100 randomly selected North Indian women were studied using a cross-sectional design with a questionnaire, venous FPG and 2-h capillary plasma glucose (PG) after a 75 g oral glucose tolerance test performed between 24 and 28 weeks of pregnancy. The prevalence of GDM was 35% using WHO 2013 criteria vs 9% using WHO 1999 criteria. FPG measurements identified 94% of WHO 2013 GDM cases as opposed to 11% of WHO 1999 GDM cases. In contrast, 2-h PG measurements identified only 13% of WHO 2013 GDM cases compared with 96% of the WHO 1999 GDM cases. Using logistic regression with backward elimination, urban habitat, illiteracy, non-vegetarianism, increased BMI, Hindu religion and low adult height were all independent risk factors of GDM using the 1999 criteria, whereas only urban habitat, low adult height and increased age were independent risk factors of GDM using the 2013 criteria. Intervention studies are needed to justify the WHO 2013 GDM criteria increasing the prevalence four fold to include more than one third of North Indian pregnant women. © 2015 European Society of Endocrinology.

Elevated liver enzymes in women with a family history of diabetes.

PubMed

Inoue, Kazuo; Matsumoto, Masatoshi; Miyoshi, Yuji; Kobayashi, Yasuki

2008-03-01

Both elevated liver enzymes and a family history of diabetes mellitus (FHDM) are independent risk factors for type 2 diabetes. This study evaluates the epidemiological association between elevated liver enzymes and FHDM. Subjects included 3512 women workers without diabetes, hepatitis, a smoking habit, or a history of alcohol intake. Blood samples and personal data were collected from all subjects. Subjects with FHDM had a higher mean body mass index (BMI: 23.9kg/m(2) vs. 23.4kg/m(2); p=0.003). Laboratory testing also revealed higher mean fasting plasma glucose (FPG: 5.67mmol/L vs. 5.22mmol/L; p<0.001), asparate aminotransferase (AST: 20.0IU/L vs. 19.2IU/L; p=0.049), alanine aminotransferase (ALT: 18.4IU/L vs. 16.7IU/L; p=0.004), gamma-glutamyltranspeptidase (GGT: 24.1IU/L vs. 20.5IU/L; p<0.001), and triglycerides (TG: 1.09mmol/L vs. 1.00mmol/L; p=0.011) for FHDM subjects, when adjusted for age and BMI. Multiple linear regression analysis revealed that FHDM, age, BMI, FPG, and TG were correlated with GGT (p=0.004 for FHDM; p<0.001 for age, BMI, FPG, and TG). Elevated liver enzymes were associated with FHDM. In particular, elevated GGT was related to FHDM, independent of the other variables. Elevated liver enzymes, probably due to fat deposition in the liver, may play a role in increasing the risk of diabetes in individuals with FHDM.

A variant of PSMD6 is associated with the therapeutic efficacy of oral antidiabetic drugs in Chinese type 2 diabetes patients.

PubMed

Chen, Miao; Hu, Cheng; Zhang, Rong; Jiang, Feng; Wang, Jie; Peng, Danfeng; Tang, Shanshan; Sun, Xue; Yan, Jing; Wang, Shiyun; Wang, Tao; Bao, Yuqian; Jia, Weiping

2015-05-29

The PSMD6 variant rs831571 has been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of this variant with therapeutic effects of oral antidiabetic drugs in Chinese T2DM patients. 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks, and the therapeutic effects were compared. In the rosiglitazone cohort, rs831571 showed significant associations with fasting plasma glucose (FPG), 2-h glucose and decrement of glycated haemoglobin (HbA1c) levels after 24 weeks of treatment (P = 0.0368, 0.0468 and 0.0247, respectively). The C allele was significantly associated with a better attainment of FPG at 24 and 32 weeks (P = 0.0172 and 0.0257, respectively). Survival analyses showed CC homozygotes were more likely to attain a standard FPG level (P = 0.0654). In the repaglinide cohort, rs831571 was significantly associated with decreased HbA1c levels after 24 weeks of treatment, the homeostatic model assessment of insulin resistance and fasting insulin level after 48 weeks of treatment with repaglinide (P = 0.0096, 0235 and 0.0212, respectively). In conclusion, we observed that the PSMD6 variant rs831571 might be associated with the therapeutic effects of rosiglitazone and repaglinide in Chinese T2DM patients. However, these findings need to be confirmed in the future.

Chromium supplements for glycemic control in type 2 diabetes: limited evidence of effectiveness.

PubMed

Costello, Rebecca B; Dwyer, Johanna T; Bailey, Regan L

2016-07-01

Some adults with type 2 diabetes mellitus (T2DM) believe that chromium-containing supplements will help control their disease, but the evidence is mixed. This narrative review examines the efficacy of chromium supplements for improving glycemic control as measured by decreases in fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c). Using systematic search criteria, 20 randomized controlled trials of chromium supplementation in T2DM patients were identified. Clinically meaningful treatment goals were defined as an FPG of ≤7.2 mmol/dL, a decline in HbA1c to ≤7%, or a decrease of ≥0.5% in HbA1c. In only a few randomized controlled trials did FPG (5 of 20), HbA1c (3 of 14), or both (1 of 14) reach the treatment goals with chromium supplementation. HbA1c declined by ≥0.5% in 5 of 14 studies. On the basis of the low strength of existing evidence, chromium supplements have limited effectiveness, and there is little rationale to recommend their use for glycemic control in patients with existing T2DM. Future meta-analyses should include only high-quality studies with similar forms of chromium and comparable inclusion/exclusion criteria to provide scientifically sound recommendations for clinicians. Published by Oxford University Press on behalf of the International Life Sciences Institute 2016. This work is written by US Government employees and is in the public domain in the United States.

A variant of PSMD6 is associated with the therapeutic efficacy of oral antidiabetic drugs in Chinese type 2 diabetes patients

PubMed Central

Chen, Miao; Hu, Cheng; Zhang, Rong; Jiang, Feng; Wang, Jie; Peng, Danfeng; Tang, Shanshan; Sun, Xue; Yan, Jing; Wang, Shiyun; Wang, Tao; Bao, Yuqian; Jia, Weiping

2015-01-01

The PSMD6 variant rs831571 has been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of this variant with therapeutic effects of oral antidiabetic drugs in Chinese T2DM patients. 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks, and the therapeutic effects were compared. In the rosiglitazone cohort, rs831571 showed significant associations with fasting plasma glucose (FPG), 2-h glucose and decrement of glycated haemoglobin (HbA1c) levels after 24 weeks of treatment (P = 0.0368, 0.0468 and 0.0247, respectively). The C allele was significantly associated with a better attainment of FPG at 24 and 32 weeks (P = 0.0172 and 0.0257, respectively). Survival analyses showed CC homozygotes were more likely to attain a standard FPG level (P = 0.0654). In the repaglinide cohort, rs831571 was significantly associated with decreased HbA1c levels after 24 weeks of treatment, the homeostatic model assessment of insulin resistance and fasting insulin level after 48 weeks of treatment with repaglinide (P = 0.0096, 0235 and 0.0212, respectively). In conclusion, we observed that the PSMD6 variant rs831571 might be associated with the therapeutic effects of rosiglitazone and repaglinide in Chinese T2DM patients. However, these findings need to be confirmed in the future. PMID:26024304

Effect of lorcaserin on glycemic parameters in patients with type 2 diabetes mellitus.

PubMed

Magkos, Faidon; Nikonova, Elena; Fain, Randi; Zhou, Sharon; Ma, Tony; Shanahan, William

2017-05-01

Lorcaserin, a 5-HT 2C receptor agonist approved for chronic weight management, is also associated with improvements in glycemic parameters in patients with/without type 2 diabetes mellitus (T2DM), but the extent to which these effects are mediated by weight loss is unknown. This post hoc analysis further examines glycemic data from the Phase III BLOOM-DM study stratified by weight changes. Patients with T2DM were randomized to lorcaserin 10 mg twice daily or placebo. Glycemic parameters were reported by Week (W) 12 weight loss status ≥5% (Group ≥5%) or <5% (Group <5%). Glycemic parameter changes were analyzed using ANCOVA; the relationship between glycemic parameter changes and percent weight loss was assessed by simple regression modeling. Group ≥5% receiving lorcaserin had greater improvements in fasting plasma glucose (FPG) at W2 (prior to significant weight loss) and greater improvements in glycated hemoglobin (HbA1c) at W12 versus placebo. These improvements were maintained through W52 (FPG, -29.3 mg/dL vs. -24.2 mg/dL; HbA1c, -1.2% vs. -1.1%). Group <5% treated with lorcaserin also had larger decreases in FPG (-28.3 mg/dL vs. -10.0 mg/dL) and HbA1c (-0.8% vs. -0.4%) at W52 versus placebo despite limited weight loss. Lorcaserin may have beneficial effects on glycemic control with or without weight loss. © 2017 The Obesity Society.

Derivation & validation of glycosylated haemoglobin (HbA1c) cut-off value as a diagnostic test for type 2 diabetes in south Indian population

PubMed Central

Mohan, Alladi; Reddy, S. Aparna; Sachan, Alok; Sarma, K.V.S.; Kumar, D. Prabath; Panchagnula, Mahesh V.; Rao, P.V.L.N. Srinivasa; Kumar, B. Siddhartha; Krishnaprasanthi, P.

2016-01-01

Background & Objectives: Glycosylated haemoglobin (HbA1c) has been in use for more than a decade, as a diagnostic test for type 2 diabetes. Validity of HbA1c needs to be established in the ethnic population in which it is intended to be used. The objective of this study was to derive and validate a HbA1c cut-off value for the diagnosis of type 2 diabetes in the ethnic population of Rayalaseema area of south India. Methods: In this cross-sectional study, consecutive patients suspected to have type 2 diabetes underwent fasting plasma glucose (FPG) and 2 h post-load plasma glucose (2 h-PG) measurements after a 75 g glucose load and HbA1c estimation. They were classified as having diabetes as per the American Diabetes Association criteria [(FPG ≥7 mmol/l (≥126 mg/dl) and/or 2 h-PG ≥11.1 mmol/l (≥200 mg/dl)]. In the training data set (n = 342), optimum cut-off value of HbA1c for defining type 2 diabetes was derived by receiver-operator characteristic (ROC) curve method using oral glucose tolerance test results as gold standard. This cut-off was validated in a validation data set (n = 341). Results: On applying HbA1c cut-off value of >6.3 per cent (45 mmol/mol) to the training data set, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing type 2 diabetes were calculated to be 90.6, 85.2, 80.8 and 93.0 per cent, respectively. When the same cut-off value was applied to the validation data set, sensitivity, specificity, PPV and NPV were 88.8, 81.9, 74.0 and 92.7 per cent, respectively, although the latter were consistently smaller than the proportions for the training data set, the differences being not significant. Interpretation & conclusions: HbA1c >6.3 per cent (45 mmol/mol) appears to be the optimal cut-off value for the diagnosis of type 2 diabetes applicable to the ethnic population of Rayalaseema area of Andhra Pradesh state in south India. PMID:27934801

Oxidative Stress Function in Women over 40 Years of Age, Considering Their Lifestyle.

PubMed

Gonçalves Mota, Maria Paula; Santos, Zirlene; Soares, Jorge; Pereira, Ana; Fonseca, Sandra; Peixoto, Francisco; Gaivão, Isabel; Oliveira, Maria

2017-01-01

Aging is dependent on biological processes that determine the aging of the organism at the cellular level. The Oxidative Stress Theory of Aging might explain some of the age-related changes in cell macromolecules. Moreover, exposome and lifestyle may also induce changes in cell damage induced by oxidative stress. The aim of the present study was to analyze the related redox changes in lymphocyte function of healthy women over 40 years old. Three groups: younger (YG: 40-49 years), middle aged (MAG: 50-59 years), and older (OG: ≥60 years) were evaluated on anthropometric variables, blood pressure, cardiovascular fitness, lifestyle habits, perceived stress, DNA damage, malondialdehyde, catalase activity, and total antioxidant capacity. Physical activity and cardiovascular fitness were significantly higher in YG and MAG as compared to the OG. Systolic blood pressure increased significantly with group age. Frequency and total amount of alcohol intake were lower in the OG and higher in the MAG. No significant differences were observed between the three groups in oxidative stress parameters. Only alcohol consumption was associated with the higher DNA FPG-sensitive sites, and only in the YG ( p  < 0.05). Healthy lifestyle is critical to avoiding major ailments associated with aging. This may be inferred from the lack of significant differences in the various oxidative stress parameters measured in the healthy women over the age of 40 who took part in the study. Conscious lifestyle behaviors (decrease in alcohol and smoking habits) could have impaired the expected age-related oxidative stress increase.

The GCKR rs780094 polymorphism is associated with susceptibility of type 2 diabetes, reduced fasting plasma glucose levels, increased triglycerides levels and lower HOMA-IR in Japanese population.

PubMed

Onuma, Hiroshi; Tabara, Yasuharu; Kawamoto, Ryuichi; Shimizu, Ikki; Kawamura, Ryoichi; Takata, Yasunori; Nishida, Wataru; Ohashi, Jun; Miki, Tetsuro; Kohara, Katsuhiko; Makino, Hideichi; Osawa, Haruhiko

2010-09-01

It was recently reported that GCKR rs780094 was associated with fasting plasma glucose (FPG) and triglyceride (TG) levels in various ethnic populations (A allele for low FPG and high TG). An association between GCKR rs780094 and type 2 diabetes mellitus (T2DM) (A allele for low risk) has also been reported. We examined the association between GCKR rs780094 and T2DM in Japanese subjects by analyzing 488 cases and 398 controls. A meta-analysis was performed involving two previous association studies. We also analyzed the association between the single-nucleotide polymorphism and clinical parameters in the general Japanese population (n=1854). In the case-control study, the A allele of GCKR rs780094 was associated with a reduced risk of T2DM (odds ratio=0.711 (95% confidence interval=0.589-0.859), P=4.2 × 10(-4)). A meta-analysis confirmed the association of GCKR rs780094 with T2DM susceptibility. In the general Japanese population, subjects with the A/A genotype had lower levels of FPG, fasting plasma insulin and homeostasis model assessment of insulin resistance than those with the G/G genotype. Conversely, subjects with the A/A genotype had higher levels of TG than those with the G/G genotype. We replicated GCKR rs780094 as a marker of T2DM susceptibility in Japanese subjects. This suggests that GCKR rs780094 is a common variant for T2DM susceptibility in various ethnic groups.

In utero exposure to malaria is associated with metabolic traits in adolescence: The Agogo 2000 birth cohort study.

PubMed

Bedu-Addo, George; Alicke, Marie; Boakye-Appiah, Justice K; Abdul-Jalil, Inusah; van der Giet, Markus; Schulze, Matthias B; Mockenhaupt, Frank P; Danquah, Ina

2017-11-01

Malaria in pregnancy (MiP) contributes to fetal undernutrition and adverse birth outcomes, and may constitute a developmental origin of metabolic diseases in the offspring. In a Ghanaian birth cohort, we examined the relationships between MiP-exposure and metabolic traits in adolescence. MiP at delivery was assessed in 155 mother-child pairs. Among the now teenaged children (mean age, 14.8 years; 53% male), we measured fasting plasma glucose (FPG), body mass index (BMI), and systolic and diastolic blood pressure (BP). Associations of MiP with the adolescents' FPG, BMI, and BP were examined by linear regression. At delivery, 45% were MiP-exposed, which increased FPG in adolescence, adjusted for mother's age at delivery, parity and familial socio-economic status (infected vs. uninfected: mean ΔFPG = 0.20 mmol/L; 95% confidence interval (CI): 0.01, 0.39; p = 0.049). As a trend,this was discernible for BP, particularly for microscopic infections (mean Δsystolic BP = 5.43 mmHg; 95% CI: 0.00, 10.88; p = 0.050; mean Δdiastolic BP = 3.67 mmHg; 95% CI: -0.81, 8.14; p = 0.107). These associations were largely independent of birth weight, gestational age and teenage BMI. Adolescent BMI was not related to MiP. In rural Ghana, exposure to malaria during fetal development contributes to metabolic conditions in young adulthood. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Breast-feeding is associated with reduced postpartum maternal glucose intolerance after gestational diabetes.

PubMed

O'Reilly, M; Avalos, G; Dennedy, M C; O'Sullivan, E P; Dunne, F P

2012-05-01

Gestational diabetes mellitus (GDM) is associated with adverse foetal and maternal outcomes, and identifies women at risk of future Type 2 Diabetes Mellitus (T2DM). Breast-feeding may improve postpartum maternal glucose tolerance. We prospectively examined the prevalence of postpartum dysglycaemia after GDM and examined the effect of lactation on postpartum glucose tolerance. We compared postpartum 75g oral glucose tolerance test (OGTT) results from 300 women with GDM and 220 controls with normal gestational glucose tolerance (NGT). Breast-feeding data was collected at time of OGTT. Postpartum OGTT results were classified as normal [fasting plasma glucose (FPG) < 5.6mmol/l, 2-h < 7.8 mmol/l] and abnormal [impaired fasting glucose (IFG), FPG 5.6-6.9 mmol/l; impaired glucose tolerance (IGT), 2-h glucose 7.8-11 mmol/l; IFG+IGT; T2DM, FPG > or = 7 mmol/l +/- 2h glucose > or = 11.1 mmol/l]. 6 (2.7%) with NGT in pregnancy had postpartum dysglycaemia compared to 57 (19%) with GDM in index pregnancy (p < 0.001). Non-European ethnicity (OR 3.40, 95% CI 1.45-8.02, p = 0.005), family history of T2DM (OR 2.14, 95% CI 1.06-4.32, p = 0.034) and gestational insulin use (OR 2.62, 95% CI 1.17-5.87 p = 0.019) were associated with persistent dysglycaemia. The prevalence of persistent hyperglycaemia was significantly lower in women who breast-fed versus bottle-fed postpartum (8.2% v 18.4%, p < 0.001). Breast-feeding may confer beneficial metabolic effects after GDM and should be encouraged.

Serum uric acid change and modification of blood pressure and fasting plasma glucose in an overall healthy population sample: data from the Brisighella heart study.

PubMed

Cicero, Arrigo F G; Rosticci, Martina; Bove, Marilisa; Fogacci, Federica; Giovannini, Marina; Urso, Riccardo; D'Addato, Sergio; Borghi, Claudio

2017-06-01

Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2 diabetes. It is less clear if changes in SUA are associated to different incidence in these main cardiovascular risk factors. From the cohort of the Brisighella Heart Study, we selected non-diabetic subjects that in 2008 were untreated with SUA-lowering drugs nor antihypertensive ones. Then we divided the subjects in four main groups: the ones that maintained their SUA level unchanged during the next 4 years, the ones that increased it >1 mg/dL without treatment, the ones that reduced it >1 mg/dL without drug treatment and the ones that reduced it >1 mg/dL with the continuous use of allopurinol. Compared with 2008, SBP significantly increased in subjects with worsened (and untreated) SUA level, while improved in subjects treated with allopurinol (p < 0.05). In 2012, subjects with worsened (and untreated) SUA level had a significantly higher SBP compared with subjects with unchanged SUA and those with SUA improved after allopurinol treatment (p < 0.05). An identical trend has been observed as it regards FPG. It seems that SUA improvement could positively influence the age-related worsening of SBP and FPG in general population. Key messages Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2 diabetes. SUA improvement could positively influence the age-related worsening of SBP and FPG in general population.

Insulin resistance during euglycemic clamp studies in chronically undernourished rats with mild streptozocin diabetes.

PubMed

Rao, R H

1995-11-01

Malnutrition has been shown to impair insulin sensitivity, but it is not known whether this effect has any impact on coexisting diabetes. Insulin sensitivity was therefore studied using the glucose clamp technique in rats with chronic nutritional deprivation superimposed on mild streptozocin (STZ) diabetes mellitus. In pair-feeding experiments, 4-week-old littermate rats were either allowed ad libitum access to food or restricted to 50% of ad libitum intake for 8 weeks, and were injected with STZ 40 mg/kg intraperitoneally halfway through the experiment. Fasting plasma glucose (FPG) was similar in both groups of rats, but fasting plasma insulin (FPI) was lower in the undernourished group (P = .016). Undernourished rats were significantly more insulin resistant during euglycemic hyperinsulinemia of the same degree, with glucose disposal rate being impaired by 50% as compared with that in ad libitum-fed diabetic littermates (24.4 +/- 2.8 v 51.5 +/- 4.4 mumol/kg/min, P = .0008). The insulin sensitivity index was significantly lower in the undernourished group (3.03 +/- 0.32 v 5.67 +/- 0.6, P = .0057). The results show that chronic undernutrition markedly reduces insulin sensitivity in rats with mild STZ diabetes. This is further evidence that chronic undernutrition is a deleterious modifying influence on coexisting diabetes mellitus. It suggests that the insulin resistance of malnutrition-related diabetes mellitus (MRDM) could potentially be an acquired defect mediated by the coexistent undernutrition, rather than a "distinctive" feature that is intrinsically unique to this diabetic syndrome.

[An investigation of the statistical power of the effect size in randomized controlled trials for the treatment of patients with type 2 diabetes mellitus using Chinese medicine].

PubMed

Ma, Li-Xin; Liu, Jian-Ping

2012-01-01

To investigate whether the power of the effect size was based on adequate sample size in randomized controlled trials (RCTs) for the treatment of patients with type 2 diabetes mellitus (T2DM) using Chinese medicine. China Knowledge Resource Integrated Database (CNKI), VIP Database for Chinese Technical Periodicals (VIP), Chinese Biomedical Database (CBM), and Wangfang Data were systematically recruited using terms like "Xiaoke" or diabetes, Chinese herbal medicine, patent medicine, traditional Chinese medicine, randomized, controlled, blinded, and placebo-controlled. Limitation was set on the intervention course > or = 3 months in order to identify the information of outcome assessement and the sample size. Data collection forms were made according to the checking lists found in the CONSORT statement. Independent double data extractions were performed on all included trials. The statistical power of the effects size for each RCT study was assessed using sample size calculation equations. (1) A total of 207 RCTs were included, including 111 superiority trials and 96 non-inferiority trials. (2) Among the 111 superiority trials, fasting plasma glucose (FPG) and glycosylated hemoglobin HbA1c (HbA1c) outcome measure were reported in 9% and 12% of the RCTs respectively with the sample size > 150 in each trial. For the outcome of HbA1c, only 10% of the RCTs had more than 80% power. For FPG, 23% of the RCTs had more than 80% power. (3) In the 96 non-inferiority trials, the outcomes FPG and HbA1c were reported as 31% and 36% respectively. These RCTs had a samples size > 150. For HbA1c only 36% of the RCTs had more than 80% power. For FPG, only 27% of the studies had more than 80% power. The sample size for statistical analysis was distressingly low and most RCTs did not achieve 80% power. In order to obtain a sufficient statistic power, it is recommended that clinical trials should establish clear research objective and hypothesis first, and choose scientific and evidence-based study design and outcome measurements. At the same time, calculate required sample size to ensure a precise research conclusion.

Appropriate insulin initiation dosage for insulin-naive type 2 diabetes outpatients receiving insulin monotherapy or in combination with metformin and/or pioglitazone.

PubMed

Liao, Lin; Yang, Ming; Qiu, Lu-Lu; Mou, Ya-Ru; Zhao, Jia-Jun; Dong, Jian-Jun

2010-12-01

Few studies have given suggestions on appropriate initiation insulin dosage when combined with oral antidiabetic drugs (OADs). This research was to investigate appropriate initiation insulin doses for insulin-naive type 2 diabetes patients with different combinations and the relationship between insulin dosage and relevant factors. This was a randomized, open-label, treat to target study. The target was 20% decrease of both fasting plasma glucose (FPG) and 2 hours post-breakfast blood glucose (P2hBG). One hundred and forty-seven insulin-naive Chinese patients recruited were randomly assigned to 3 groups: group A, patients received insulin monotherapy; group B, received insulin plus metformin (0.5 g, tid) and group C, received insulin plus metformin (0.5 g, tid) and pioglitazone (15 mg, qd). Insulin doses were initiated with a dose of 0.3 U×kg(-1)×d(-1) and titrated according to FPG and P2hBG till reached the targets. Both the time of getting 20% reduction of FPG and P2hBG showed significant differences among the three groups. The time was shortest in Group C. The insulin doses needed to achieve glucose reduction of 20% in three treatment groups were (0.40 ± 0.04) U×kg(-1)×d(-1) for Group A, (0.37 ± 0.04) U×kg(-1)×d(-1) for Group B, and (0.35 ± 0.03) U×kg(-1)×d(-1) for Group C, respectively. Multiple linear stepwise regression analysis showed that insulin doses correlated with body weight, FPG, diabetes duration, age and history of sulfonylurea treatment. The standardized regression coefficients were 0.871, 0.322, 0.089, 0.067 and 0.063 (with all P < 0.05). To achieve blood glucose's reduction of 20% within safety context, initial insulin doses were recommended as the following: 0.40 U×kg(-1)×d(-1) for insulin mono-therapy, 0.37 U×kg(-1)×d(-1) for insulin plus metformin treatment, and 0.35 U×kg(-1)×d(-1) for insulin plus metformin and pioglitazone treatment in Chinese type 2 diabetes outpatients. Body weight is found the most closely related factor to the insulin dosage.

The efficacy of repaglinide monotherapy and in combination with metformin in Indonesian type 2 diabetes mellitus patients.

PubMed

Soegondo, Sidartawan; Subekti, Imam; Luthariana, Lies

2004-01-01

To investigate the efficacy and safety of repaglinide alone and in combination with metformin therapy. Seventy-two type 2 diabetes patients who were oral anti-diabetic drugs (OAD)-naive or currently on OAD for 7.0 mmol/L, it appeared that repaglinide alone at doses 0.5 or 1.0 mg achieved FBG <7.0 mmol/L in 67% of patients. The majority of the treatment emergent adverse events were mild and unlikely related to trial product. Episodes of symptomatic hypoglycaemia were low (9.3%) in frequency. The changes in haematology, clinical biochemistry and urinalysis were mostly minor or remained unchanged. Vital signs and the results of physical examination also remained unchanged. Three of the four withdrawals were due to adverse events but were unlikely related to trial product. treatment with repaglinide alone and in combination with metformin was efficacious in glycaemic control in OAD-naive or previous users. Most of the patients appeared to achieve good control with repaglinide alone. The treatment regimens were safe (317 words).

Effect of Aloe vera on glycaemic control in prediabetes and type 2 diabetes: a systematic review and meta-analysis.

PubMed

Suksomboon, N; Poolsup, N; Punthanitisarn, S

2016-04-01

Aloe vera (Aloe vera (L.) Burm.f., Xanthorrhoeaceae family) has long been used in folk or traditional medicine for diabetes. Several studies have been conducted on the effect of Aloe vera on glycaemic control, but the results appear inconsistent. We undertook a systematic review and meta-analysis to assess the effect of Aloe vera on glycaemic control in prediabetes and type 2 diabetes. A comprehensive literature search was conducted through MEDLINE, CENTRAL, CINAHL, Scopus, http://clinicaltrials.gov, Web of Science, Proquest, LILACS, HerbMed, NAPRALERT and CNKI to the end of January 2016 without language restriction. Historical search of relevant articles and personal contact with experts in the area were also undertaken. Studies were included if they were (1) randomized controlled trials of Aloe vera aimed at assessing glycaemic control in prediabetes or type 2 diabetes and (2) reporting fasting plasma glucose (FPG) or haemoglobin A1c (HbA1c ). Treatment effect was estimated with mean difference in the final value of FPG and HbA1c between the treatment and the control groups. Eight trials involving 470 patients (235 each for prediabetes and type 2 diabetes) were included. In prediabetes, Aloe vera significantly improved FPG (mean difference -0·22 mmol/L, 95% CI -0·32 mmol/L to -0·12 mmol/L, P < 0·0001), with no effect on HbA1c (mean difference -2 mmol/mol, 95% CI -5 mmol/mol to 1 mmol/mol). Aloe vera may improve glycaemic control in type 2 diabetes, with a marginal improvement in FPG (mean differences -1·17 mmol/L, 95% CI -2·35 mmol/L to 0·00 mmol/L, P = 0·05) and a significant improvement in HbA1c (mean difference -11 mmol/mol, 95% CI -19 mmol/mol to -2 mmol/mol, P = 0·01). The current evidence suggests some potential benefit of Aloe vera in improving glycaemic control in prediabetes and type 2 diabetes. However, given the limitations of the available evidence and the high heterogeneity in study results, high-quality, well-powered randomized controlled trials using standardized preparations are needed to quantify any beneficial effects of Aloe vera on glycaemic control. © 2016 John Wiley & Sons Ltd.

The reliability of in-hospital diagnoses of diabetes mellitus in the setting of an acute myocardial infarction

PubMed Central

Arnold, Suzanne V; Lipska, Kasia J; Inzucchi, Silvio E; Li, Yan; Jones, Philip G; McGuire, Darren K; Goyal, Abhinav; Stolker, Joshua M; Lind, Marcus; Spertus, John A; Kosiborod, Mikhail

2014-01-01

Objective Incident diabetes mellitus (DM) is important to recognize in patients with acute myocardial infarction (AMI). To develop an efficient screening strategy, we explored the use of random plasma glucose (RPG) at admission and fasting plasma glucose (FPG) to select patients with AMI for glycosylated hemoglobin (HbA1c) testing. Design, setting, andparticipants Prospective registry of 1574 patients with AMI not taking glucose-lowering medication from 24 US hospitals. All patients had HbA1c measured at a core laboratory and admission RPG and ≥2 FPGs recorded during hospitalization. We examined potential combinations of RPG and FPG and compared these with HbA1c≥6.5%—considered the gold standard for DM diagnosis in these analyses. Results An RPG>140 mg/dL or FPG≥126 mg/dL had high sensitivity for DM diagnosis. Combining these into a screening protocol (if admission RPG>140, check HbA1c; or if FPG≥126 on a subsequent day, check HbA1c) led to HbA1c testing in 50% of patients and identified 86% with incident DM (number needed to screen (NNS)=3.3 to identify 1 case of DM; vs NNS=5.6 with universal HbA1c screening). Alternatively, using an RPG>180 led to HbA1c testing in 40% of patients with AMI and identified 82% of DM (NNS=2.7). Conclusions We have established two potential selective screening methods for DM in the setting of AMI that could identify the vast majority of incident DM by targeted screening of 40–50% of patients with AMI with HbA1c testing. Using these methods may efficiently identify patients with AMI with DM so that appropriate education and treatment can be promptly initiated. PMID:25452878

Serum Levels of sRAGE Are Associated with Body Measurements, but Not Glycemic Parameters in Patients with Prediabetes.

PubMed

Guclu, Metin; Ali, Asuman; Eroglu, Derya Ustun; Büyükuysal, Sema Oral; Cander, Soner; Ocak, Nihal

2016-02-01

Our aim was to assess serum levels of the soluble receptor for advanced glycation end products (sRAGE) and to examine their association with anthropometric and metabolic parameters in patients with prediabetes and obese controls. The two study groups were composed of 42 patients with prediabetes and diabetic neuropathy and 42 age-, gender-, body weight (BW)-, and body mass index (BMI)-matched obese adults as the control group. Prediabetes was diagnosed by the following criteria issued by the American Diabetes Association: impaired fasting glucose [fasting plasma glucose (FPG) level of 100-125 mg/dL], impaired glucose tolerance (2 hr plasma glucose level of 140-199 mg/dL after a 75 grams oral glucose challenge), or a glycated hemoglobin (HbA1C) level of 5.7%-6.4%. There were no differences between the groups in terms of age, gender distribution, BW, or BMI. Despite these similarities, patients with prediabetes had higher FPG, HbA1c, and 2-hr postchallenge glucose levels, higher systolic and diastolic blood pressure, and larger waist and hip circumferences compared with the obese controls. Lipid measurements, complete blood counts, kidney and liver function tests, high-sensitivity C-reactive protein, and sRAGE levels were similar between the two groups. We found significant negative correlations between sRAGE levels and BW, BMI, waist and hip circumferences, waist-to-hip ratios, and low-density lipoprotein (LDL) cholesterol levels. There were no significant correlations with other parameters, including demographic, metabolic, and blood pressure measurements. In contrast to glycemic parameters, serum levels of sRAGE were negatively correlated with body measurements indicative of obesity in the prediabetic state. In addition, the negative correlation with LDL cholesterol levels suggests that sRAGE has a more robust association with metabolic syndrome than with prediabetes.

Fasting plasma glucose as initial screening for diabetes and prediabetes in irish adults: The Diabetes Mellitus and Vascular health initiative (DMVhi).

PubMed

Sinnott, Margaret; Kinsley, Brendan T; Jackson, Abaigeal D; Walsh, Cathal; O'Grady, Tony; Nolan, John J; Gaffney, Peter; Boran, Gerard; Kelleher, Cecily; Carr, Bernadette

2015-01-01

Type 2 diabetes has a long pre clinical asymptomatic phase. Early detection may delay or arrest disease progression. The Diabetes Mellitus and Vascular health initiative (DMVhi) was initiated as a prospective longitudinal cohort study on the prevalence of undiagnosed Type 2 diabetes and prediabetes, diabetes risk and cardiovascular risk in a cohort of Irish adults aged 45-75 years. Members of the largest Irish private health insurance provider aged 45 to 75 years were invited to participate in the study. already diagnosed with diabetes or taking oral hypoglycaemic agents. Participants completed a detailed medical questionnaire, had weight, height, waist and hip circumference and blood pressure measured. Fasting blood samples were taken for fasting plasma glucose (FPG). Those with FPG in the impaired fasting glucose (IFG) range had a 75gm oral glucose tolerance test performed. 122,531 subjects were invited to participate. 29,144 (24%) completed the study. The prevalence of undiagnosed diabetes was 1.8%, of impaired fasting glucose (IFG) was 7.1% and of impaired glucose tolerance (IGT) was 2.9%. Dysglycaemia increased among those aged 45-54, 55-64 and 65-75 years in both males (10.6%, 18.5%, 21.7% respectively) and females (4.3%, 8.6%, 10.9% respectively). Undiagnosed T2D, IFG and IGT were all associated with gender, age, blood pressure, BMI, abdominal obesity, family history of diabetes and triglyceride levels. Using FPG as initial screening may underestimate the prevalence of T2D in the study population. This study is the largest screening study for diabetes and prediabetes in the Irish population. Follow up of this cohort will provide data on progression to diabetes and on cardiovascular outcomes.

Randomized Trial of Long-Acting Insulin Glargine Titration Web Tool (LTHome) Versus Enhanced Usual Therapy of Glargine Titration (INNOVATE Trial).

PubMed

Bajaj, Harpreet S; Venn, Karri; Ye, Chenglin; Aronson, Ronnie

2016-10-01

Basal insulin titration in the real world is often unsuccessful. LTHome, a web tool, applies a rules engine-based algorithm providing insulin titration advice directly to the patient. This pilot, randomized trial evaluates basal insulin glargine titration by LTHome compared to enhanced usual therapy ([EUT]-diabetes education program) over 12 weeks. Important inclusion criteria: 18-75 years, type 2 diabetes, computer literacy, and HbA1c >7.0%. Trial protocol was approved by ethics board. We randomized 139 subjects. The achievement of primary composite outcome (four out of seven fasting plasma glucose [FPG] within 5-7.2 mmol/L + mean for three consecutive FPG within 5-7.2 mmol/L + no severe hypoglycemia) was 15% in LTHome versus 41% in EUT (noninferiority not met, P-value = 0.92). Other outcomes were similar between the LTHome and EUT arms: alternate composite outcome achievement (last five FPG mean within the range of 5-7.2 mmol/L + no hypoglycemia, 47% and 51%, P = 0.73); A1c reduction (-1.0% and -1.1%, P = 0.66); proportion achieving A1c ≤7% (14% and 20%, P = 0.36); and hypoglycemia incidence (31% and 37%, P = 0.4), respectively. Patient satisfaction score improvements were greater in LTHome versus EUT (change in fear of hypoglycemia score P = 0.04 and change in diabetes distress score P = 0.04). The mean number of additional healthcare provider visits was 0.13 for LTHome and 1.22 for EUT (P < 0.01). INNOVATE trial suggests clinical utility of LTHome compared to EUT in real-life settings. Further research is needed to evaluate the efficacy and safety of automated insulin titration algorithms.

Prevalence and predictors of postpartum glucose intolerance in Italian women with gestational diabetes mellitus.

PubMed

Capula, Carmelo; Chiefari, Eusebio; Vero, Anna; Foti, Daniela P; Brunetti, Antonio; Vero, Raffaella

2014-08-01

To determine the prevalence of both prediabetes and type 2 diabetes mellitus (T2DM) by postpartum oral glucose tolerance test (ppOGTT) in Italian women diagnosed with gestational diabetes mellitus (GDM), and identify antepartum predictors of glucose intolerance. Retrospective study of 454 Caucasian women that underwent a 75g OGTT between 6 and 12 weeks postpartum in Calabria (Southern Italy) between 2004 and 2012. Prediabetes and T2DM were diagnosed according to the American Diabetes Association (ADA) criteria. Data were examined by univariate analysis and multiple regression analysis. 290 women (63.9%) were normal, 146 (32.1%) had prediabetes (85 impaired fasting glycemia; 61 impaired glucose tolerance), and 18 (4.0%) had T2DM. Of the continuous variables, pre-pregnancy body mass index (BMI), age at pregnancy, fasting plasma glucose (FPG) at gravid OGTT, and week at diagnosis of GDM were associated with prediabetes and T2DM, whereas the parity was associated with T2DM only. For categorical traits, pre-pregnancy BMI ≥ 25 and previous diagnosis of polycystic ovary syndrome (PCOS) emerged as the strongest predictors of prediabetes whereas the strongest predictors of T2DM were FPG ≥ 100 mg/dl (5.6 mmol/l) at GDM diagnosis and pre-pregnancy BMI ≥ 25. Moreover, FPG at GDM screening was a good predictor of T2DM after receiver-operating-characteristic analysis. Our findings confirm the high prevalence of glucose intolerance in the early postpartum period in women with previous GDM. PCOS emerges as a new strong antepartum predictor of prediabetes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Metabolic syndrome: An independent risk factor for erectile dysfunction

PubMed Central

Sanjay, Saran; Bharti, Gupta Sona; Manish, Gutch; Rajeev, Philip; Pankaj, Agrawal; Puspalata, Agroiya; Keshavkumar, Gupta

2015-01-01

Objective: The objective was to determine the role of various components of metabolic syndrome (MetS) as independent risk factor for erectile dysfunction (ED). Materials and Methods: A total of 113 subjects of MetS, as recommended by recent IDF and AHA/NHLBI joint interim statement were selected for study who presented for ED. After doing Anthropometric examination, fasting laboratory assay for fasting plasma glucose (FPG), fasting insulin, hemoglobin A1c, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 2 h oral glucose tolerance test (OGTT) was done. Erectile function was assessed by completing questions one through five of the International Index of Erectile Function (IIEF-5). A multiple linear regression analysis was carried out on 66 subjects with IIEF-5 score as dependent variable and components of MetS FPG, 2 h OGTT, TG, HDL, and waist circumference as independent variables. Results: Using a multiple linear regression analysis, we observed that presence of the various components of MetS was associated with ED and a decrease IIEF-5 score and this effect was greater than the effect associated with any of the individual components. Of the individual components of the MetS, HDL (B = 0.136; P = 0.004) and FPG (B = −0.069; P = 0.007) conferred the strongest effect on IIEF-5 score. However, overall age had most significant effect on IIEF-5 score. Conclusion: It is crucial to formulate strategies and implement them to prevent or control the epidemic of the MetS and its consequences. The early identification and treatment of risk factors might be helpful to prevent ED and secondary cardiovascular disease, including diet and lifestyle interventions. PMID:25729692

Metabolic syndrome: An independent risk factor for erectile dysfunction.

PubMed

Sanjay, Saran; Bharti, Gupta Sona; Manish, Gutch; Rajeev, Philip; Pankaj, Agrawal; Puspalata, Agroiya; Keshavkumar, Gupta

2015-01-01

The objective was to determine the role of various components of metabolic syndrome (MetS) as independent risk factor for erectile dysfunction (ED). A total of 113 subjects of MetS, as recommended by recent IDF and AHA/NHLBI joint interim statement were selected for study who presented for ED. After doing Anthropometric examination, fasting laboratory assay for fasting plasma glucose (FPG), fasting insulin, hemoglobin A1c, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 2 h oral glucose tolerance test (OGTT) was done. Erectile function was assessed by completing questions one through five of the International Index of Erectile Function (IIEF-5). A multiple linear regression analysis was carried out on 66 subjects with IIEF-5 score as dependent variable and components of MetS FPG, 2 h OGTT, TG, HDL, and waist circumference as independent variables. Using a multiple linear regression analysis, we observed that presence of the various components of MetS was associated with ED and a decrease IIEF-5 score and this effect was greater than the effect associated with any of the individual components. Of the individual components of the MetS, HDL (B = 0.136; P = 0.004) and FPG (B = -0.069; P = 0.007) conferred the strongest effect on IIEF-5 score. However, overall age had most significant effect on IIEF-5 score. It is crucial to formulate strategies and implement them to prevent or control the epidemic of the MetS and its consequences. The early identification and treatment of risk factors might be helpful to prevent ED and secondary cardiovascular disease, including diet and lifestyle interventions.

Impact of night sleep duration on glycemic and triglyceride levels in Chinese with different glycemic status.

PubMed

Zheng, Yu; Wang, Anping; Pan, Changyu; Lu, Juming; Dou, Jingtao; Lu, Zhaohui; Ba, Jianming; Wang, Baoan; Mu, Yiming

2015-01-01

The aim of the present study was to assess the relationship between night sleep duration and glycemic and triglyceride (TG) levels among people with different glycemic status. In all, 18,121 subjects aged ≥40 years were enrolled in this cross-sectional study, including 4318 with impaired glucose regulation (IGR), 4225 with diabetes, and 9578 with normal glucose regulation (NGR). The IGR + diabetes and NGR groups were divided into three subgroups according to self-reported night sleep duration as follows: (i) <6 h; (ii) 6-9 h; and (iii) >9 h. The associations of sleep duration with HbA1c, fasting plasma glucose (FPG), 2-h post-load plasma glucose (PPG), and TG levels were examined. Long night sleep duration (>9 h) was associated with higher HbA1c, FPG, PPG, and TG levels compared with sleep duration of 6-9 h (P < 0.01 for all) in the IGR + diabetes group, but not in the NGR group. This association was adjusted for potential confounders, including body mass index and depressive symptoms, and remained significant even after adjusting for snoring. A significant interaction between sleep duration and TG or snoring was observed for HbA1c levels, which attenuated the sleep-HbA1c association in the IGR + diabetes group. However, no significant association was observed between short night sleep duration and HbA1c levels. Long night sleep duration is associated with higher HbA1c, FPG, PPG, and TG levels in IGR and diabetes patients, independent of potential confounders. This may be important in clinical management of IGR and diabetes patients. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Curvilinear associations of sleep patterns during weekdays and weekends with glycemic control in type 2 diabetes: the Hong Kong Diabetes Registry.

PubMed

Kong, Alice P S; Choi, Kai Chow; Zhang, Jihui; Luk, Andrea; Lam, Siu Ping; Chan, Michael H M; Ma, Ronald C W; Chan, Juliana C N; Wing, Yun Kwok

2017-02-01

We aimed to explore the associations of sleep patterns during weekdays and weekends with glycemic control in patients with type 2 diabetes. We examined the association between indices of glycemic control [glycated hemoglobin (HbA 1c ) and fasting plasma glucose (FPG)] and sleep parameters (sleep duration, bedtime, and differences of sleep duration during weekdays and weekends) from adults with type 2 diabetes recruited in a prospective cohort enrolling from hospital medical clinics. Restricted cubic spline regression was used to examine the relationships between the glycemic indices and sleep parameters. Excluding shift workers, a total of 3508 patients enrolled between July 2010 and July 2014 were included in this analysis. Mean age was 53.9 [standard deviation (SD) 8.7] years, and mean disease duration of diabetes was 8.3 (SD 7.1) years. Fifty-nine percentage were men. Mean sleep duration during weekdays and difference of sleep durations between weekdays and weekends were 7.7 (SD 1.3) hours and 0.6 (SD 1.2) hours, respectively. Mean HbA 1c and FPG were 7.6 (1.5) % and 7.6 (2.5) mmol/L, respectively. Using restricted cubic spline regressions with successive adjustments of potential confounders, sleep duration difference between weekdays and weekends remained significantly associated with both HbA 1c and FPG in a curvilinear manner. Sleep duration of about 1 h more during weekends when compared to weekdays was associated with beneficial effect in HbA 1c (-0.13 %, 95 % confidence interval -0.24 to -0.02). In type 2 diabetes, regular sleeping habit with modest sleep compensation during weekends has positive impact on glycemic control.

The effects of a 2 week modified high intensity interval training program on the homeostatic model of insulin resistance (HOMA-IR) in adults with type 2 diabetes.

PubMed

Shaban, N; Kenno, K A; Milne, K J

2014-04-01

High intensity interval training (HIIT) induces similar metabolic adaptations to traditional steady state aerobic exercise training. Until recently, most HIIT studies have examined maximum efforts in healthy populations. The current study aimed to examine the effects of a 2 week modified HIIT program on the homeostatic model of insulin resistance (HOMA-IR) in individuals with type 2 diabetes (T2D). It was hypothesized that HIIT would improve HOMA-IR. Nine individuals with T2D (age=40.2±9.7 y; BMI=33.9±5.3; fasting plasma glucose [FPG]=8.7±2.9 mmol/L; HbA1C=7.3±1.2%; [mean±SD]) performed 6 individualized training sessions of HIIT (4x30 seconds at 100% of estimated maximum workload followed by 4 minutes of active rest) over 2 weeks. HOMA-IR was calculated from FPG and serum insulin and compared against a prior 2 week baseline period. Blood glucose was reduced immediately after each HIIT session (P<0.05). Anthropometrics, FPG, serum insulin, and HOMA-IR were unchanged after training. However, 6 of the 9 individuals exhibited reduced HOMA-IR values after the training period and there was a significant negative correlation between HOMA-IR value prior to training and change in HOMA-IR after HIIT. These observations tend to support the positive health benefits of HITT for individuals with T2D reported in recently published data using a modified HIIT protocol. However, they suggest that the magnitude of the disease should be assessed when examining the effects of exercise interventions in individuals with T2D.

Effect of Guava in Blood Glucose and Lipid Profile in Healthy Human Subjects: A Randomized Controlled Study

PubMed Central

Rakavi, R; Mangaraj, Manaswini

2016-01-01

Introduction The fruit of Psidium guajava (P.guajava) is known to contain free sugars yet the fruit juice showed hypoglycaemic effect. Hypoglycaemic activity of guava leaves has been well documented but not for guava fruit. Aim So we aimed to evaluate the effect of ripe guava (with peel and without peel) fruit supplementation on blood glucose and lipid profile in healthy human subjects. Materials and Methods Randomized Controlled study undertaken in: 1) Baseline; 2) 6 weeks supplementation phase. Forty five healthy MBBS students were included and randomly enrolled into Group A, Group B and Group C. In Baseline phase: Fasting Plasma Glucose (FPG) and serum lipid profile was done in all 3 groups. Group A were supplemented with 400g of ripe guava with peel and group B without peel, for 6 weeks. Rest 15 treated as control i.e., Group C. Result Supplementation of ripe guava fruit with peel reduced BMI as well as blood pressure (p<0.05) in group A, whereas the FPG, Total cholesterol, Triglycerides were found significantly increased (p<0.05). Group B registered a significant fall (p<0.05) in BMI as well as blood pressure. Fall in FPG level after guava pulp supplementation was not significant. Serum Total cholesterol, Triglycerides and Low Density Lipoprotein Cholesterol (LDLc) levels decreased significantly (p<0.05) indicating that guava pulp without peel may have a favourable effect on lipid levels and blood sugar as well. Conclusion Guava fruit without peel is more effective in lowering blood sugar as well as serum total cholesterol, triglycerides and LDLc. It increases HDLc levels also. PMID:27790420

Prevalence of metabolic syndrome in Iran: A 2011 update.

PubMed

Noshad, Sina; Abbasi, Mehrshad; Etemad, Koorosh; Meysamie, Alipasha; Afarideh, Mohsen; Khajeh, Elias; Asgari, Fereshteh; Mousavizadeh, Mostafa; Rafei, Ali; Neishaboury, Mohamadreza; Ghajar, Alireza; Nakhjavani, Manouchehr; Koohpayehzadeh, Jalil; Esteghamati, Alireza

2017-05-01

The aim of the present study was to determine the prevalence of metabolic syndrome and its individual components among the Iranian adult population in 2011 and to investigate changes between 2007 and 2011. Data from two rounds of the Surveillance of Risk Factors of Non-communicable Diseases national surveys conducted in 2007 and 2011 were pooled. Metabolic syndrome was defined according to International Diabetes Federation criteria. In 2007, the prevalence of metabolic syndrome among adults aged 25-64 years was 35.95 (95% confidence interval [CI] 34.27-37.63), which decreased to 32.96 (95% CI 30.73-35.18) in 2011 (P = 0.0108). Despite this overall decline, the prevalence of central obesity (P = 0.1383), raised triglycerides (P = 0.3058), and reduced high-density lipoprotein cholesterol (HDL-C; P = 0.5595) remained constant. There was a trend towards a decline in the proportion of individuals with increased blood pressure (P = 0.0978), and the proportion of adults with increased fasting plasma glucose (FPG) increased (P < 0.0001). In 2011, the prevalence of central obesity, raised triglycerides, reduced HDL-C, increased blood pressure and increased FPG was 51.88 (95% CI 48.97-54.79), 36.99 (95% CI 34.52-39.45), 54.72 (95% CI 50.87-58.57), 38.92 (95% CI 36.19-41.64), and 24.97 (95% CI 22.02-27.93) respectively. Over the period 2007-11, the prevalence of metabolic syndrome has decreased slightly in Iran, although prevalence of increased FPG has increased significantly. One-third of the Iranian adult population is diagnosed with metabolic syndrome. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Psychosocial factors are independent risk factors for the development of Type 2 diabetes in Japanese workers with impaired fasting glucose and/or impaired glucose tolerance1

PubMed Central

Toshihiro, M; Saito, K; Takikawa, S; Takebe, N; Onoda, T; Satoh, J

2008-01-01

Aims We prospectively studied Japanese workers with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and analysed possible risk factors for diabetes, including psychosocial factors such as stress. Methods The participants were 128 male Japanese company employees (mean age, 49.3 ± 5.9 years) with IFG and/or IGT diagnosed by oral glucose tolerance test (OGTT). Participants were prospectively studied for 5 years with annual OGTTs. The Kaplan–Meier method and Cox's proportional hazard model were used to analyse the incidence of diabetes and the factors affecting glucose tolerance, including anthropometric, biochemical and social–psychological factors. Results Of 128 participants, 36 (28.1%) developed diabetes and 39 (30.5%) returned to normal glucose tolerance (NGT) during a mean follow-up of 3.2 years. Independent risk factors for diabetes were night duty [hazard ratio (HR) = 5.48, P = 0.002], higher fasting plasma glucose (FPG) levels within 6.1–6.9 mmol/l (HR = 1.05, P = 0.031), stress (HR = 3.81, P = 0.037) and administrative position (HR = 12.70, P = 0.045), while independent factors associated with recovery were lower FPG levels (HR = 0.94, P = 0.017), being a white-collar worker (HR = 0.34, P = 0.033), non-smoking (HR = 0.31, P = 0.040) and lower serum alanine aminotransferase (ALT) levels (HR = 0.97, P = 0.042). Conclusions In addition to FPG levels at baseline, psychosocial factors (night duty, stress and administrative position) are risk factors for Type 2 diabetes, while being a white-collar worker, a non-smoker and lower serum ALT levels are factors associated with return to NGT in Japanese workers with IFG and/or IGT. PMID:19046200

Propolis Improves Periodontal Status and Glycemic Control in Patients With Type 2 Diabetes Mellitus and Chronic Periodontitis: A Randomized Clinical Trial.

PubMed

El-Sharkawy, Hesham M; Anees, Mohamed M; Van Dyke, Thomas E

2016-12-01

Propolis is a natural resin made by bees from various plant sources and exerts antimicrobial, anti-inflammatory, immunomodulatory, antioxidant, and antidiabetic properties. The purpose of this study is to assess adjunctive benefit of propolis supplementation in individuals with chronic periodontitis (CP) and type 2 diabetes mellitus (DMt2) receiving scaling and root planing (SRP). A 6-month masked, randomized clinical trial comparing SRP with placebo (placebo + SRP group, n = 26) or SRP combined with a 6-month regimen of 400 mg oral propolis once daily (propolis + SRP group, n = 24) was performed in patients with long-standing DMt2 and CP. Treatment outcomes included changes in hemoglobin (Hb) A1c (primary outcome), fasting plasma glucose (FPG), serum N € -(carboxymethyl) lysine (CML), and periodontal parameters (secondary outcomes). After 3 and 6 months, average HbA1c levels in the propolis group decreased significantly by 0.82% and 0.96% units, respectively (P <0.01); however, there were no significant differences in the placebo group. Likewise, FPG and CML levels were significantly reduced in the propolis group, but not in the placebo group. After therapy, periodontal parameters of CP were significantly improved in both groups. The propolis group showed significantly greater probing depth reduction and clinical attachment level gain than the control group after 3 and 6 months. A 6-month regimen of 400 mg propolis once daily is a potentially viable adjunct to SRP that significantly reduces levels of HbA1c, FPG, and CML, and improves periodontal therapy outcome in people with DMt2 and CP.

Metformin does not affect postabsorptive hepatic free fatty acid uptake, oxidation or resecretion in humans: A 3-month placebo-controlled clinical trial in patients with type 2 diabetes and healthy controls.

PubMed

Gormsen, Lars C; Søndergaard, Esben; Christensen, Nana L; Jakobsen, Steen; Nielsen, Erik H T; Munk, Ole L; Tolbod, Lars P; Jessen, Niels; Nielsen, Søren

2018-06-01

To explore whether the pre-clinical findings that metformin improves lipid metabolism, possibly through modulation of intrahepatic partitioning of fatty acids towards oxidation and away from re-esterification and resecretion as triglycerides (TGs), can be translated to a human setting. We performed a 3-month randomized, placebo-controlled, parallel-group clinical trial in patients with type 2 diabetes (T2D; n = 24) and healthy controls (n = 12). Patients with T2D received either placebo (placebo group) or 1000 mg metformin twice daily (metformin group), while healthy subjects were all treated with metformin (control group). Hepatic fatty acid metabolism was measured by [ 11 C]palmitate positron-emission tomography, hepatic TG secretion and peripheral oxidation by ex vivo labelled [1- 14 C]VLDL-TG and VLDL particle size by TG/apolipoprotein B ratio. Body composition was assessed by dual-energy X-ray and whole-body lipid oxidation by indirect calorimetry. Metformin treatment for 3 months produced the anticipated decrease in fasting plasma glucose (FPG) in the metformin group (FPG 7.9 ± 1.8 mM [study day 1] vs 6.4 ± 1.1 mM [study day 2]), whereas patients in the placebo group and healthy controls had similar FPG levels before and after the trial (mixed model group vs time interaction; P = .003); however, contrary to our hypothesis, metformin treatment did not affect hepatic lipid metabolism or peripheral oxidation. The observed beneficial effects on lipid metabolism during metformin treatment in humans appear to be secondary to long-term alterations in body composition or glucose homeostasis. © 2018 John Wiley & Sons Ltd.

Posture Alignment of Adolescent Idiopathic Scoliosis: Photogrammetry in Scoliosis School Screening.

PubMed

Penha, Patrícia Jundi; Penha, Nárima Lívia Jundi; De Carvalho, Bárbarah Kelly Gonçalves; Andrade, Rodrigo Mantelatto; Schmitt, Ana Carolina Basso; João, Sílvia Maria Amado

The objective of this study was to describe the posture patterns of adolescents diagnosed with adolescent idiopathic scoliosis (AIS) in a scoliosis school screening (SSS). Two-dimensional photogrammetry was used to assess the posture of 37 adolescents diagnosed with scoliosis (scoliosis group, SG) (Cobb angle ≥10°) and 76 adolescents with a false positive diagnosis (false positive group, FPG) (Cobb angle <10°, angle of trunk rotation ≥7°). In total, 2562 10- to 14-year-old adolescents were enrolled in the SSS, which was performed in public schools in the cities of Amparo, Pedreira, and Mogi Mirim in the state of São Paulo, Brazil. Their posture was analyzed using Postural Analysis Software. Continuous variables were tested using Student t test, and categorical variables were tested using a χ2 test. The SG, FPG, simple curve group, and double curve group were all compared. Bivariate analysis was used to identify associations between postural deviations and scoliosis. The adopted significance level was α = .05. The SG (2.7 ± 1.9°) had greater shoulder obliquity than the FPG (1.9 ± 1.4°) (P = .010), and this deviation was associated with scoliosis (odds ratio [95% CI] P = 1.4 [1.1-1.8] 0.011). The SG had asymmetry between the right- and left-side lower limb frontal angle, shoulder sagittal alignment, and knee angle. The double curve group (3 ± 1.7°) presented a greater value of the vertical alignment of the torso than the simple curve group did (1.9 ± 1°; P = .032). Adolescents diagnosed with AIS in an SSS had greater shoulder obliquity and asymmetry between the right and left sides. Shoulder obliquity was the only postural deviation associated with AIS. Copyright © 2017. Published by Elsevier Inc.

Zinc and Selenium Co-supplementation Reduces Some Lipid Peroxidation and Angiogenesis Markers in a Rat Model of NAFLD-Fed High Fat Diet.

PubMed

Mousavi, Seyedeh Neda; Faghihi, Amirhosein; Motaghinejad, Majid; Shiasi, Maryam; Imanparast, Fatemeh; Amiri, Hamid Lorvand; Shidfar, Farzad

2018-02-01

Studies have shown that non-alcoholic fatty liver disease (NAFLD) patients are more prone to cardiovascular disease (CVD). Zinc and selenium deficiency are common in NAFLD. But the effects of zinc and selenium co-supplementation before and/or after disease progression on CVD markers are not clear in NAFLD patients. This study aimed to compare the effects of zinc and selenium co-supplementation before and/or after disease progression on some of the CVD markers in an experimental model of NAFLD. Forty male Sprague Dawley rats (197 ± 4 g) were randomly assigned into four dietary groups: control group (C; received 9% of calorie as fat), model group (M; received 82% of calorie as fat), and supplementation before (BS) or after (AS) disease progression. Animals were fed diets for 20 weeks in all groups. Fasting plasma glucose (FPG), insulin, HOMA-IR, ALT, AST, lipid profile, malondialdehyde (MDA) and vascular endothelial growth factor (VEGF) levels were measured as CVD indices. Serum ALT, AST, FPG, insulin, MDA, VEGF and HOMA-IR were significantly higher in the M than C group. Co-supplementation reduced serum ALT and AST levels in the BS and AS groups compared with the M group. FPG, insulin, HOMA-IR, VEGF, MDA, LDL/HDL-c and TC/HDL-c ratio were significantly reduced in the AS compared with the M group. TG/HDL-c ratio was significantly reduced in the BS and AS compared with the M group. Serum MDA, VEGF, Insulin and HOMA-IR were significantly lowered in the AS than BS group (p < 0.05). Zinc and selenium co-supplementation after NAFLD progression reduced CVD risk indices in an experimental model.

Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

PubMed

Kalra, Sanjay; Atkin, Stephen; Cervera, Antonio; Das, Ashok Kumar; Demir, Ozgur; Demir, Tevfik; Fariduddin, Md; Vo, Khoa Tuan; Ku, Bon Jeong; Kumar, Ajay; Latif, Zafar A; Malek, Rachid; Matawaran, Bien J; Mehta, Roopa; Tran, Nam Quang; Panelo, Araceli; Ruder, Sundeep; Saldana, Joel Rodriquez; Shaikh, Khalid A; Shakya, Amit; Shrestha, Dina; Unnikrishnan, A G

2018-05-23

Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.

The antileishmanial drug miltefosine (Impavido(®)) causes oxidation of DNA bases, apoptosis, and necrosis in mammalian cells.

PubMed

Castelo Branco, Patrícia Valéria; Soares, Rossy-Eric Pereira; de Jesus, Luís Cláudio Lima; Moreira, Vanessa Ribeiro; Alves, Hugo José; de Castro Belfort, Marta Regina; Silva, Vera Lucia Maciel; Ferreira Pereira, Silma Regina

2016-08-01

Miltefosine was developed to treat skin cancer; further studies showed that the drug also has activity against Leishmania. Miltefosine is the first oral agent for treating leishmaniasis. However, its mechanism of action is not completely understood. We have evaluated the induction of DNA damage by miltefosine. Cytotoxicity and genotoxicity (comet assay) tests were performed on human leukocytes exposed to the drug in vitro. Apoptosis and necrosis were also evaluated. In vivo tests were conducted in Swiss male mice (Mus musculus) treated orally with miltefosine. Oxidation of DNA bases in peripheral blood cells was measured using the comet assay followed by digestion with formamidopyrimidine glycosylase (FPG), which removes oxidized guanine bases. The micronucleus test was performed on bone marrow erythrocytes. Miltefosine caused DNA damage, apoptosis, and necrosis in vitro. Mice treated with miltefosine showed an increase in the DNA damage score, which was further increased following FPG digestion. The micronucleus test was also positive. Copyright © 2016 Elsevier B.V. All rights reserved.

Repaglinide in type 2 diabetes: a 24-week, fixed-dose efficacy and safety study.

PubMed

Jovanovic, L; Dailey, G; Huang, W C; Strange, P; Goldstein, B J

2000-01-01

In this 24-week multicenter, double-blind, randomized, fixed-dose trial, 361 patients having type 2 diabetes received daily preprandial treatment with placebo (n = 75), repaglinide 1 mg (n = 140), or repaglinide 4 mg (n = 146). By a last-observation carried-forward calculation, repaglinide 1 mg or 4 mg treatment decreased mean fasting plasma glucose (FPG) values (by -47 mg/dL or -49 mg/dL) while the placebo group had increased FPG values (by 19 mg/dL). For the repaglinide treatment groups at the end of the study, changes in HbA1c from baseline values ranged from 1.8 to 1.9 percentage points lower than the placebo group. There were no events of severe hypoglycemia. Nearly all hypoglycemic symptom episodes had blood glucose levels above 45 mg/dL. Repaglinide was well tolerated in a preprandial fixed-dose regimen of 1 mg or 4 mg, assigned without adjustment for clinical parameters.

Reshaping RTI: Building a Better Triangle

ERIC Educational Resources Information Center

Ramaswami, Rama

2010-01-01

Response to intervention (RTI), the controversial three-tiered, triangular instructional model is getting stretched in new directions by educators who favor holistic, proactive support strategies over formal remediation. A senior scientist at the FPG Child Development Institute at the University of North Carolina at Chapel Hill, Virginia Buysse…

Population PKPD modelling of the long-term hypoglycaemic effect of gliclazide given as a once-a-day modified release (MR) formulation

PubMed Central

Frey, N; Laveille, C; Paraire, M; Francillard, M; Holford, N H G; Jochemsen, Roeline

2003-01-01

Aims To study the relationship between the pharmacokinetics (PK) of gliclazide and its long-term pharmacodynamic (PD) effect in a large population of Type 2 diabetic patients and to identify factors predicting intersubject variability. Methods A PKPD database of 634 Type 2 diabetic patients with a total of 5258 fasting plasma glucose (FPG) samples was built up from the data collected during the clinical development of a modified release formulation of gliclazide (gliclazide MR). The PKPD analysis used a nonlinear mixed effect modelling approach. A mixture model was used to identify patients with a FPG response to treatment. In patients identified as responders, the decrease in FPG was related to gliclazide exposure (AUC) by an Emax relationship. An effect compartment was used to describe the link between PK and PD. A linear disease-progression model was used to assess the glycaemic deterioration observable over several months of treatment. Simulations were performed to evaluate the predictive performance of the PKPD model and to illustrate the time course of the antidiabetic effect of gliclazide MR. Results Disease state was found to be the main explanatory factor for intersubject variability in response to gliclazide. The percentage of responders to gliclazide, used as monotherapy, increased inversely to the number of classes of antidiabetic agents received prior to entry in the studies. In responders, the initial dose (30 mg) of the gliclazide MR dosing regimen induced half of the maximum hypoglycaemic effect. The equilibration half-life between the PK and PD steady states was 3 weeks (intersubject variability of 84%). The rate of disease progression was 0.84 mmol l−1 year−1 (intersubject variability 143%). The PKPD model adequately predicted the FPG profiles of 234 patients who received the current formulation of gliclazide. Simulation of a 1-year parallel dose ranging clinical trial illustrated the influence of dose, time and type of previous antidiabetic treatment on the percentage of patients with clinically significant improvement of blood glucose control. Conclusions This population PKPD analysis has characterized the relationship between the exposure to gliclazide and its long-term hypoglycaemic effect, and has established that the intersubject variability in response is mostly related to disease state. These results underline the clinical interest of quickly increasing the dose of gliclazide MR according to the response to treatment in order to achieve effective blood glucose control. PMID:12580986

[Endonuclease modified comet assay for oxidative DNA damage induced by detection of genetic toxicants].

PubMed

Zhao, Jian; Li, Hongli; Zhai, Qingfeng; Qiu, Yugang; Niu, Yong; Dai, Yufei; Zheng, Yuxin; Duan, Huawei

2014-03-01

The aim of this study was to investigate the use of the lesion-specific endonucleases-modified comet assay for analysis of DNA oxidation in cell lines. DNA breaks and oxidative damage were evaluated by normal alkaline and formamidopyrimidine-DNA-glycosylase (FPG) modified comet assays. Cytotoxicity were assessed by MTT method. The human bronchial epithelial cell (16HBE) were treated with benzo (a) pyrene (B(a)P), methyl methanesulfonate (MMS), colchicine (COL) and vincristine (VCR) respectively, and the dose is 20 µmol/L, 25 mg/ml, 5 mg/L and 0.5 mg/L for 24 h, respectively. Oxidative damage was also detected by levels of reactive oxygen species in treated cells. Four genotoxicants give higher cytotoxicity and no significant changes on parameters of comet assay treated by enzyme buffer. Cell survival rate were (59.69 ± 2.60) %, (54.33 ± 2.81) %, (53.11 ± 4.00) %, (51.43 ± 3.92) % in four groups, respectively. There was the direct DNA damage induced by test genotoxicants presented by tail length, Olive tail moment (TM) and tail DNA (%) in the comet assay. The presence of FPG in the assays increased DNA migration in treated groups when compared to those without it, and the difference was statistically significant which indicated that the clastogen and aneugen could induce oxidative damage in DNA strand. In the three parameters, the Olive TM was changed most obviously after genotoxicants treatment. In the contrast group, the Olive TM of B(a) P,MMS, COL,VCR in the contrast groups were 22.99 ± 17.33, 31.65 ± 18.86, 19.86 ± 9.56 and 17.02 ± 9.39, respectively, after dealing with the FPG, the Olive TM were 34.50 ± 17.29, 43.80 ± 10.06, 33.10 ± 12.38, 28.60 ± 10.53, increased by 58.94%, 38.48%, 66.86% and 68.21%, respectively (t value was 3.91, 3.89, 6.66 and 3.87, respectively, and all P < 0.05), and the correlation between Olive TM and reactive oxygen species was better than other parameters (r = 0.77, P < 0.05). This study indicates that FPG-comet assay appears more specific for detecting oxidative DNA damage induced by genotoxicants exposure, and the application of comet assay will be expanded. The endonuclease modified comet assay will be used widely in the toxicology and molecular epidemiology study.

Patterns of glycemic control using glycosylated hemoglobin in diabetics.

PubMed

Kahlon, Arunpreet Singh; Pathak, Rambha

2011-07-01

Till now estimation of blood glucose is the highly effective method for diagnosing diabetes mellitus but it provides a short-term picture of control. More evidence is required to prove that plasma glucose and glycosylated hemoglobin levels together gives a better estimate of glycemic control and compliance with treatment. Indian diabetes risk score (IDRS) is a simplified screening tool for identifying undiagnosed diabetic subjects, requires minimum time, and effort and can help to considerably reduce the costs of screening. To study patterns of glycemic control using glycosylated hemoglobin in diabetic patients. To find out correlation between levels of plasma glucose and glycosylated hemoglobin in diabetics and to calculate IDRS of the study population. A cross sectional study was conducted among 300 known diabetic patients attending outpatient department of a rural medical college in Haryana, India. Following standard procedures and protocols FPG and glycosylated hemoglobin were measured to find out a pattern of glycemic control in them after taking their written and informed consent. A correlation between the levels of glycosylated hemoglobin and fasting blood glucose was also calculated. These patients were made to fill a performa and their demographic and clinical risk factors were noted and based on this, their IDRS was calculated. This was done to validate the IDRS in Indian rural population. Fifty-two percent of the population had fasting plasma glucose level between 125-150 mg/dl, 21% had this level between 151-175 mg/dl. Thirteen percent of the study subjects had HbA1C between 6.5-7.5, more than half (57.3%) had this value between 7.5-8.5, 12% and 18% had values between 8.5-9.5 and 9.5-10.5, respectively. Twelve percent of the participants had HbA1C level higher than 10.5. Correlation of fasting plasma glucose level and HbA1C was also studied and found that correlation coefficient came out to be .311. This correlation was found to be statistically significant (P = .007). Sixty-five percent of the case had IDRS higher than 60. Glycaemic control in diabetics can be better assessed with glycosylated hemoglobin and FPG together. A positive correlation between FPG and HbA1c allows for the use of HbA1c along with FPG in diagnosing type 2 DM but the two should not be used interchangeably. IDRS can be used as a screening tool for diabetes.

[A health promotion campaign to improve flu vaccination adherence among medical residents in an Italian Teaching Hospital].

PubMed

Barbara, Andrea; Poscia, Andrea; De Meo, Concetta; De Waure, Chiara; Anzelmo, Vincenza; Santoro, Paolo Emilio; Maruccia, Antonio; Giubbini, Gabriele; Corsaro, Alice; Berloco, Filippo; Damiani, Gianfranco; Ricciardi, Walter; Laurenti, Patrizia

2017-01-01

In Italy annual flu vaccination for health care workers is recommended but coverage is usually unsatisfying. The compliance is even worse among medical residents (MRs) both in literature, both in our experience: in the flu season 2014/ 15 only 0.6% of MRs enrolled at the Università Cattolica del Sacro Cuore (UCSC) were vaccinated. For this reason, during the influenza season 2015/16, the Institute of Public Health of the UCSC, in collaboration with the Health Management of the "Agostino Gemelli" Teaching Hospital (FPG) and with the directive board of the Medical Specialization Schools (SSM) present at the University has tested several strategies to improve awareness and adherence to flu vaccination campaign by its staff. This study aims to analyze the impact of the strategies used during the 2015/16 campaign on flu vaccination coverage among MRs of an important Italian Teaching Hospital. The study was conducted among MRs enrolled at the UCSC - FPG in 2015/16. The data was collected by the Occupational Medicine which, during the influenza seasons, immunize MRs against influenza free of charge. For each variable - vaccination, area of specialization (surgical, medical, clinical services), typology of SSM - was measured the absolute and percentage frequency. In order to compare the flu vaccination coverage between seasons 2014/15 and 2015/16 and between areas of specialization in 2015/16 chi-square test was used (statistical significance level of 0.05). The data were analyzed using STATA Software. Were included in the analysis 42 SSM with a total of 1041 MRs. During the vaccination campaign 2015/16, flu vaccine was administered to 99 MRs (9.5%), 8.9% more than in the previous season (p<0.001). There is also a significant difference in vaccine coverage between surgical, medical and clinical services areas in 2015/16 (p <0.001). The highest vaccination coverage was recorded among MRs of Hematology and Urology (54.5%). However, no one MRs had undergone flu vaccination in about 40% of SSM. Seasonal flu vaccination among HCWs is important to protect patients as well as them self and their family members. Considering that MRs represent the next generation of HCWs, they should be sensitized about the importance of preventing the spread of influenza in hospital population, becoming an active part of the necessary cultural change. This study highlights a first and promising, although insufficient, increase in flu vaccination coverage among MRs enrolled at the UCSC - FPG after introducing simple strategies to promote vaccination itself and, more generally, positive and proactive behaviors. The study summarizes the results in the short term, but it is well known that cultural changes require time and constancy. Therefore, it will be useful to monitor the improvement over time and extend the assessment to all health care professionals.

The single-strand DNA binding activity of human PC4 preventsmutagenesis and killing by oxidative DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jen-Yeu; Sarker, Altaf Hossain; Cooper, Priscilla K.

Human positive cofactor 4 (PC4) is a transcriptional coactivator with a highly conserved single-strand DNA (ssDNA) binding domain of unknown function. We identified PC4 as a suppressor of the oxidative mutator phenotype of the Escherichia coli fpg mutY mutant and demonstrate that this suppression requires its ssDNA binding activity. Yeast mutants lacking their PC4 ortholog Sub1 are sensitive to hydrogen peroxide and exhibit spontaneous and peroxide induced hypermutability. PC4 expression suppresses the peroxide sensitivity of the yeast sub l{Delta} mutant, suggesting that the human protein has a similar function. A role for yeast and human proteins in DNA repair ismore » suggested by the demonstration that Sub1 acts in a peroxide-resistance pathway involving Rad2 and by the physical interaction of PC4 with the human Rad2 homolog XPG. We show XPG recruits PC4 to a bubble-containing DNA substrate with resulting displacement of XPG and formation of a PC4-DNA complex. We discuss the possible requirement for PC4 in either global or transcription-coupled repair of oxidative DNA damage to mediate the release of XPG bound to its substrate.« less

Effect of bromocriptine-QR therapy on glycemic control in subjects with type 2 diabetes mellitus whose dysglycemia is inadequately controlled on insulin.

PubMed

Chamarthi, Bindu; Cincotta, Anthony H

2017-05-01

The concurrent use of an insulin sensitizer in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control on basal-bolus insulin may help improve glycemic control while limiting further insulin requirement. Bromocriptine-QR (B-QR), a quick release, sympatholytic, dopamine D2 receptor agonist therapy for T2DM, is a postprandial insulin sensitizer. This study evaluated the effect of B-QR on dysglycemia in T2DM subjects with suboptimal glycemic control on basal-bolus insulin plus metformin. The effect of once-daily morning administration of B-QR on dysglycemia was evaluated in 60 T2DM subjects derived from the Cycloset Safety Trial, with HbA1c >7% on basal-bolus insulin plus metformin at baseline, randomized to B-QR (N = 44) versus placebo (N = 16) and completed 12 weeks of study drug treatment. The analyses also included a subset of subjects on high-dose insulin (total daily insulin dose (TDID) ≥70 units; N = 36: 27 B-QR; 9 placebo). Subjects were well matched at baseline. After 12 weeks of B-QR treatment, mean % HbA1c decreased by -0.73% relative to baseline (p < 0.001) and by -1.13 relative to placebo (p < 0.001). In the high-dose insulin subset, B-QR therapy resulted in % HbA1c reductions of -0.95 and -1.49 relative to baseline (p < 0.001) and placebo (p = 0.001) respectively. Secondary analyses of treatment effect at 24 and 52 weeks demonstrated similar influences of B-QR on HbA1c. The fasting plasma glucose (FPG) and TDID changes within each treatment group were not significant. More subjects achieved HbA1c ≤7 at 12 weeks with B-QR relative to placebo (36.4% B-QR vs 0% placebo, Fisher's exact 2-sided p = 0.003 in the entire cohort and 37% vs 0%, 2-sided p = 0.039 in the high-dose insulin subset). B-QR therapy improves glycemic control in T2DM subjects whose glycemia is poorly controlled on metformin plus basal-bolus insulin, including individuals on high-dose basal-bolus insulin. This glycemic impact occurred without significant change in FPG, suggesting a postprandial glucose lowering mechanism of action. Cycloset Safety Trial registration: ClinicalTrials.gov Identifier: NCT00377676.

Incision of trivalent chromium [Cr(III)]-induced DNA damage by Bacillus caldotenax UvrABC endonuclease.

PubMed

O'Brien, Travis J; Jiang, Guohui; Chun, Gina; Mandel, H George; Westphal, Craig S; Kahen, Kaveh; Montaser, Akbar; States, J Christopher; Patierno, Steven R

2006-11-07

Some hexavalent chromium [Cr(VI)]-containing compounds are lung carcinogens. Once within cells, Cr(VI) is reduced to trivalent chromium [Cr(III)] which displays an affinity for both DNA bases and the phosphate backbone. A diverse array of genetic lesions is produced by Cr including Cr-DNA monoadducts, DNA interstrand crosslinks (ICLs), DNA-Cr-protein crosslinks (DPCs), abasic sites, DNA strand breaks and oxidized bases. Despite the large amount of information available on the genotoxicity of Cr, little is known regarding the molecular mechanisms involved in the removal of these lesions from damaged DNA. Recent work indicates that nucleotide excision repair (NER) is involved in the processing of Cr-DNA adducts in human and rodent cells. In order to better understand this process at the molecular level and begin to identify the Cr-DNA adducts processed by NER, the incision of CrCl(3) [Cr(III)]-damaged plasmid DNA was studied using a thermal-resistant UvrABC NER endonuclease from Bacillus caldotenax (Bca). Treatment of plasmid DNA with Cr(III) (as CrCl(3)) increased DNA binding as a function of dose. For example, at a Cr(III) concentration of 1 microM we observed approximately 2 Cr(III)-DNA adducts per plasmid. At this same concentration of Cr(III) we found that approximately 17% of the plasmid DNA contained ICLs ( approximately 0.2 ICLs/plasmid). When plasmid DNA treated with Cr(III) (1 microM) was incubated with Bca UvrABC we observed approximately 0.8 incisions/plasmid. The formation of endonuclease IV-sensitive abasic lesions or Fpg-sensitive oxidized DNA bases was not detected suggesting that the incision of Cr(III)-damaged plasmid DNA by UvrABC was not related to the generation of oxidized DNA damage. Taken together, our data suggest that a sub-fraction of Cr(III)-DNA adducts is recognized and processed by the prokaryotic NER machinery and that ICLs are not necessarily the sole lesions generated by Cr(III) that are substrates for NER.

Why Young Children Enter Early Intervention Services. FPG Snapshot. #38

ERIC Educational Resources Information Center

FPG Child Development Institute, 2007

2007-01-01

Part C of the Individuals with Disabilities Education Act (IDEA) provides funding to states to provide services for children from birth to three years of age with developmental delays and disabilities. States have flexibility--and therefore variation--in determining the criteria for eligibility. A study published in the Journal of Policy and…

Evidence-Based Practice Empowers Early Childhood Professionals and Families. FPG Snapshot #33

ERIC Educational Resources Information Center

FPG Child Development Institute, 2006

2006-01-01

Evidence-based practice emerged as a result of the gap often seen between research and practice and gained momentum with the standards and accountability movement. Yet it originates in medicine. Healthcare professionals using evidence-based medicine determine a patient's treatment based on an assessment of evidence from the literature and current…

Recognition & Response: Findings from the First Implementation Study

ERIC Educational Resources Information Center

FPG Child Development Institute, 2009

2009-01-01

Researchers at the FPG (Frank Porter Graham) Child Development Institute recently completed a study on a new approach to teaching pre-kindergartners called Recognition & Response (R&R). Designed specifically for use in pre-k, R&R is based on Response to Intervention (RTI), an approach that is gaining widespread acceptance in schools…

How Does Fragile X Syndrome Affect Speech and Language Skills? FPG Snapshot. Number 51. January 2008

ERIC Educational Resources Information Center

FPG Child Development Institute, 2008

2008-01-01

Children with fragile X syndrome (FXS), the most common known inherited cause of intellectual disability, typically experience communication difficulties. Children with other intellectual disabilities such as Down syndrome also experience communication difficulties. Further, many boys with FXS (some estimates are as high as 35 percent) also are…

77 FR 36510 - Applications for New Awards: Personnel Development To Improve Services and Results for Children...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-19

... of the institutions of higher education (IHEs) surveyed reported receiving assistance from the... discrete, self-contained units of instruction designed to increase educators' knowledge or skills that can...://community.fpg.unc.edu . User survey results from both of these centers show that college and graduate...

DNA damage in blood cells exposed to low-level lasers.

PubMed

Sergio, Luiz Philippe da Silva; Silva, Ana Paula Almeida da; Amorim, Philipi Freitas; Campos, Vera Maria Araújo; Magalhães, Luis Alexandre Gonçalves; de Paoli, Flavia; de Souza da Fonseca, Adenilson

2015-04-01

In regenerative medicine, there are increasing applications of low-level lasers in therapeutic protocols for treatment of diseases in soft and in bone tissues. However, there are doubts about effects on DNA, and an adequate dosimetry could improve the safety of clinical applications of these lasers. This work aimed to evaluate DNA damage in peripheral blood cells of Wistar rats induced by low-level red and infrared lasers at different fluences, powers, and emission modes according to therapeutic protocols. Peripheral blood samples were exposed to lasers and DNA damage was accessed by comet assay. In other experiments, DNA damage was accessed in blood cells by modified comet assay using formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III enzymes. Data show that exposure to low-level red and infrared lasers induce DNA damage depending on fluence, power and emission mode, which are targeted by Fpg and endonuclease III. Oxidative DNA damage should be considered for therapeutic efficacy and patient safety in clinical applications based on low-level red and infrared lasers. © 2015 Wiley Periodicals, Inc.

The effect of vitamin D on insulin resistance in patients with type 2 diabetes

PubMed Central

2013-01-01

Introduction Over the past decade, numerous non-skeletal diseases have been reported to be associated with vitamin D deficiency including type2 diabetes mellitus (T2DM). Different studies provide evidence that vitamin D may play a functional role in glucose tolerance through its effects on insulin secretion and insulin sensitivity. This study evaluates the effects of vitamin D supplementation on insulin resistance in T2DM. Method Through a before-after study, 100 patients with T2DM, 30–70 years old, were recruited from an Arak diabetes clinic as consecutive attenders. Participants were assessed for clinical and biochemistry. Serum insulin and, 25(OH)D concentration, and HOMA-IR was calculated. All measurements were performed at the beginning and the end of the study. Patients received 50,000 unit of vitamin D3 orally per week for eight weeks, Statistical analysis was made using SPSS17. The results were analyzed by descriptive tests, and a comparison between variables were made using paired T-tests or Wilcoxon tests, as appropriate. Results 100 participants including 70 women (70%) and 30 men (30%) took part in the study. All results were presented as Mean±SD, or medians of non-normally distributed. 24% of the participants were Vitamin D deficient {serum 25(OH)D ≤ 20 ng/ml(50 nmol/l)}. Mean serum 25 (OH) D concentration was 43.03± 19.28 ng/ml (107.5±48.2 nmol/l). The results at baseline and at the end, for FPG were 138.48±36.74 and 131.02±39 mg/dl (P=0.05), for insulin, 10.76±9.46 and 8.6±8.25 μIu/ml (P=0.028) and for HOMA-IR, 3.57±3.18 and 2.89±3.28 (P=0.008) respectively. Conclusion Our data showed significant improvements in serum FPG, insulin and in HOMA-IR after treatment with vitamin D, suggested that vitamin D supplementation could reduce insulin resistance in T2DM. PMID:23443033

Soy Protein Supplementation Reduces Clinical Indices in Type 2 Diabetes and Metabolic Syndrome.

PubMed

Zhang, Xi-Mei; Zhang, Yun-Bo; Chi, Mei-Hua

2016-05-01

Clinical trials have studied the use of soy protein for treating type 2 diabetes (T2D) and metabolic syndrome (MS). The purpose of this study was to outline evidence on the effects of soy protein supplementation on clinical indices in T2D and MS subjects by performing a meta-analysis of randomized controlled trials (RCTs). We searched PubMed, EMBASE, and Cochrane databases up to March 2015 for RCTs. Pooled estimates and 95% confidence intervals (CIs) were calculated by the fixed-and-random-effects model. A total of eleven studies with eleven clinical variables met the inclusion criteria. The meta-analysis showed that fasting plasma glucose (FPG) [weighted mean difference (WMD), -0.207; 95% CI, -0.374 to -0.040; p=0.015], fasting serum insulin (FSI) (WMD, -0.292; 95% CI, -0.496 to -0.088; p=0.005), homeostasis model of assessment for insulin resistance index (HOMA-IR) (WMD, -0.346; 95% CI, -0.570 to -0.123; p=0.002), diastolic blood pressure (DBP) (WMD, -0.230; 95% CI, -0.441 to -0.019; p=0.033), low-density lipoprotein cholesterol (LDL-C) (WMD, -0.304; 95% CI, -0.461 to -0.148; p=0.000), total cholesterol (TC) (WMD, -0.386; 95% CI, -0.548 to -0.225; p=0.000), and C-reactive protein (CRP) (WMD, -0.510; 95% CI, -0.722 to -0.299; p=0.000) are significant reduced with soy protein supplementation, compared with a placebo control group, in T2D and MS patients. Furthermore, soy protein supplementation for longer duration (≥6 mo) significantly reduced FPG, LDL-C, and CRP, while that for a shorter duration (<6 mo) significantly reduced FSI and HOMA-IR. Soy protein supplementation could be beneficial for FPG, FSI, HOMA-IR, DBP, LDL-C, TC, and CRP control in plasma.

Hemoglobin glycation index as a useful predictor of therapeutic responses to dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes

PubMed Central

Chen, Yu-Wei; Wang, Jun-Sing; Sheu, Wayne H-H; Lin, Shih-Yi; Lee, I-Te; Song, Yuh-Min; Fu, Chia-Po; Lee, Chia-Lin

2017-01-01

Introduction A high hemoglobin glycation index (HGI) and glycated hemoglobin (HbA1c) level are associated with greater inflammatory status, and dipeptidyl peptidase-4 (DPP-4) inhibitors can suppress inflammation. We aimed to evaluate the relationship between HGI and the therapeutic effect of DPP-4 inhibitors. Methods This retrospective cohort study followed 468 patients with type 2 diabetes receiving DPP-4 inhibitor treatment for 1 year. Estimated HbA1c was calculated using a linear regression equation derived from another 2969 randomly extracted patients with type 2 diabetes based on fasting plasma glucose (FPG) level. The subjects were divided into two groups based on HGI (HGI = observed HbA1c - estimated HbA1c). Mixed model repeated measures were used to compare the treatment efficacy after 1 year in patients with a low (HGI<0, n = 199) and high HGI (HGI≧0, n = 269). Results There were no significant group differences in mean changes of FPG after 1 year (-12.8 and -13.4 mg/dL in the low and high HGI groups, respectively). However, the patients with a high HGI had a significantly greater reduction in HbA1c from baseline compared to those with a low HGI (-1.9 versus -0.3% [-20.8 versus -3.3 mmol/mol]). Improvements in glycemic control were statistically significantly associated with the tested DPP-4 inhibitors in the high HGI group (-2.4, -1.4, -1.2 and -2.2% [-26.2, -15.3, -13.1 and -24.0 mmol/mol] for vildagliptin, linagliptin, saxagliptin and sitagliptin, respectively) but not in the low HGI group. Conclusions The HGI index derived from FPG and HbA1c may be able to identify who will have a better response to DPP-4 inhibitors. PMID:28182722

Efficacy and safety of luseogliflozin monotherapy in Japanese patients with type 2 diabetes mellitus: a 12-week, randomized, placebo-controlled, phase II study.

PubMed

Seino, Yutaka; Sasaki, Takashi; Fukatsu, Atsushi; Sakai, Soichi; Samukawa, Yoshishige

2014-07-01

Luseogliflozin is a novel sodium glucose cotransporter 2 inhibitor for type 2 diabetes mellitus (T2DM) treatment. An exploratory Phase II study was conducted to assess the efficacy and safety of several doses of luseogliflozin in Japanese T2DM patients. Japanese T2DM patients aged 20-74 years with hemoglobin A1c (HbA1c) of 6.9-10.5%, fasting plasma glucose (FPG) ≥126 mg/dL and on diet therapy were randomized in a double-blind manner to receive luseogliflozin (0.5, 2.5, or 5 mg) or placebo once daily for 12 weeks (n = 61, 61, 61, and 56, respectively). The primary endpoint was the change in HbA1c from baseline to end of treatment. Other endpoints included FPG, 2 h postprandial plasma glucose (PPG) in a meal tolerance test (MTT), and body weight. Drug safety was also assessed. Japan Pharmaceutical Information Center (identifier: JapicCTI-090908). Changes in HbA1c from baseline to end of treatment were -0.36, -0.62, and -0.75% in the 0.5, 2.5, and 5 mg luseogliflozin groups, respectively, versus +0.06% in the placebo group (all P < 0.001). The reductions in FPG and 2 h-PPG in the MTT were also significantly greater in the luseogliflozin groups (all P < 0.01) without increases in insulin levels from baseline. Luseogliflozin reduced body weight at all doses. There were no significant differences in the incidences of adverse events among groups. Most adverse events were mild in severity. There were no serious adverse events. Although this was a small-scale study with a short duration, all tested doses of luseogliflozin significantly improved glycemic control, reduced body weight, and were well tolerated in Japanese T2DM patients over the 12-week treatment period.

Medication use and disease management of type 2 diabetes in Belgium.

PubMed

Mehuys, Els; De Bolle, Leen; Van Bortel, Luc; Annemans, Lieven; Van Tongelen, Inge; Remon, Jean-Paul; Giri, Mimi

2008-01-01

The aim of this study was (International Diabetes Federation. Diabetes Atlas Second Edition Executive Summary. Brussels: International Diabetes Federation; 2003) to describe the current status of medication use and disease management of type 2 diabetic patients in Flanders (Belgium), (World Health Organization. Prevention of diabetes mellitus. Technical report series no. 844. Geneva: World Health Organization; 1994) to identify the aspects of type 2 diabetes care a community pharmacist could provide additional educational services for, and (American Diabetes Association. Diabetes Care 2006;29:S4-42) to propose these services as a pharmacist intervention. We recruited 338 patients in 77 community pharmacies in Flanders (Belgium). Each patient completed a questionnaire collecting personal data, information on duration of diabetes, medication, diabetes symptoms and self-management. At inclusion, patients measured their fasting plasma glucose (FPG) on three consecutive days. Prescription drugs (antidiabetic and other) purchased by each patient during the 12 months prior to inclusion in the study were reviewed from anonymized computerized pharmacy records. Degree of self-management, glycaemic control and medication use. The mean FPG of the sample was 150.7+/-43.0 mg/dl. Controlled glycaemia (FPG between 90 and 130 mg/dl (5.0-7.2 mmol/l)) was achieved in only 34.9% of the patients. Mainstay of hypoglycemic treatment consisted of metformin monotherapy (29.6%) and metformin combined with sulfonylurea (29.0%). Regarding co-medication, 76.9% of the patients used antihypertensive drugs whereas only 33.1% and 39.9% were on aspirin and statin therapy, respectively. ADA recommendations for annual eye and foot examination were not followed in 38.8% (eye) and 39.2% (feet) of the patients. The current management of type 2 diabetic Flemish patients falls short of recommended treatment goals. Community pharmacists may play a role in enhancing the awareness of glycaemic control and in stimulating self-management in diabetic patients by motivating patients towards correct medication use, better medication adherence, healthy lifestyle and smoking cessation.

Prevalence of hypovitaminosis D, and its association with hypoadiponectinemia and hyperfollistatinemia, in Saudi women with naïve polycystic ovary syndrome.

PubMed

Kensara, Osama Adnan

2018-06-01

The association between vitamin D and polycystic ovary syndrome (PCOS) is an active area of growing research. However, data in Saudi Arabia are scarce. This study aimed to define serum 25-hydroxyvitamin D (25(OH)D) levels among Saudi women with naïve PCOS, and to investigate the associations of their 25(OH)D status with their serum adiponectin and follistatin levels, along with indices of insulin resistance and hormonal deteriorations. In this case-control observational study, 63 women with PCOS and 65 age-and body mass index (BMI)-matched control women were assessed. PCOS was diagnosed based on the revised criteria of Rotterdam. Fasting serum levels of 25(OH)D, adiponectin, follistatin, insulin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), androgen (Δ 4 -androstenedione), estradiol, progesterone, along with fasting plasma glucose (FPG), homeostasis model assessment-insulin resistance (HOMA-IR) index and lipid profile were measured in both groups. The prevalence of hypovitaminosis D (serum 25(OH)D <30 ng/ml) was higher in PCOS group than control group (77.8% vs. 12.3%). Serum adiponectin and FSH concentrations were significantly lower, while serum follistatin, LH, TT, Δ 4 -androstenedione and insulin levels, as well as FPG and HOMA-IR were significantly higher in PCOS group than control group. In addition, 25(OH)D levels of PCOS women were significantly correlated positively with adiponectin and FSH levels, but negatively with follistatin, HOMA-IR, FPG, LH, testosterone, and Δ 4 -androstenedione levels. Hypovitaminosis D, coexisted and correlated with hypoadiponectinemia and hyperfollistatinemia, is being an alarming risk factor in Saudi women with PCOS. Further investigational and explanatory studies in large size samples are warranted to realize these findings and to improve both diagnostic and treatment tools in Saudi women with PCOS.

Altered fructosamine and lipid fractions in subclinical hypothyroidism.

PubMed

Udupa, Sridevi V; Manjrekar, Poornima A; Udupa, Vinit A; Vivian, D'Souza

2013-01-01

Thyroid function disorders lead to changes in the lipoprotein metabolism. To study the lipid and the glycaemic abnormalities in the subclinical hypothyroidism cases and to compare the same with the euthyroid, overt hypothyroid and the hyperthyroid subjects. Four groups, euthyroid (Group-I), hypothyroid (Group-II), subclinical hypothyroid (Group-III) and hyperthyroid (Group-IV), which consisted of 30 subjects each, of either sex, who were aged 25-55 years, underwent Fasting Plasma Glucose (FPG), fructosamine, lipid profile and total T3, T4 and TSH estimations. The subjects who were on lipid lowering or thyroid disorder drugs and known diabetics were excluded from the study. In Group-III, all the lipid fractions were comparable to those of Group-II and they were significantly deranged, as compared to those of Group-I. The fructosamine levels were significantly higher in Group-II and Group-III (p<0.05), but the subclinical hypothyroid pool had statistically lower levels than the hypothyroid pool (376.63±54.73, 587.80±65.10). In the Group-IV patients, the LDL-C levels were significantly higher as compared to those in the euthyroid pool. The fructosamine levels were significantly lower in comparison with both the euthyroid and the hypothyroid pools (both in Groups-II and III). The FPG levels were higher in all the classes of the thyroid abnormalities (subclinical hypothyroidnot significant) but within the reference range of 70-100mg/dl. Since the lipid derangement in subclinical hypothyroidism is on par with that in overt hypothyrodism, the subclinical hypothyroid cases also need to be treated similarly. The fructosamine values which are largely in excess of the FPG values, indicate a higher propensity to glycation and a decreased turnover of the proteins in the hypothyroid and the subclinical hypothyroid pools. Vice versa is true of the hyperthyroid pool. Fructosamine can be included in the thyroid work up of the patients to assess the metabolic function and the subsequent response after the initiation of the therapy.

Long‐term safety and efficacy of canagliflozin as add‐on therapy to teneligliptin in Japanese patients with type 2 diabetes

PubMed Central

Kadowaki, Takashi; Inagaki, Nobuya; Kondo, Kazuoki; Nishimura, Kenichi; Kaneko, Genki; Maruyama, Nobuko; Nakanishi, Nobuhiro; Watanabe, Yumi; Gouda, Maki

2017-01-01

Aim To evaluate the long‐term safety and efficacy of canagliflozin as add‐on therapy in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control with teneligliptin monotherapy. Methods This open‐label 52‐week study was conducted in Japan. Patients received canagliflozin 100 mg added to teneligliptin 20 mg orally once daily for 52 weeks. The safety endpoint was the incidence of adverse events (AEs). The efficacy endpoints included changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and body weight from baseline to week 52 (with last observation carried forward). Results Overall, 153 patients entered the treatment period and 142 completed the study. The overall incidence rates of AEs and drug‐related AEs were 69.9% and 22.9%, respectively. Most AEs and drug‐related AEs were mild or moderate in severity. There were no previously undescribed safety signals. The mean changes in HbA1c, FPG and body weight were −0.99% (95% confidence interval [CI] −1.12 to −0.85), −38.6 mg/dL (95% CI −43.4 to −33.9) and −3.92% (95% CI −4.53 to −3.31), respectively. These effects were maintained for 52 weeks without attenuation. HbA1c and body weight were both decreased in 82.24% of patients at the end of the treatment period. Reductions in postprandial glucose were observed at weeks 24 and 52. Conclusions No new safety risks with this combination were identified, and sustained improvements in HbA1c, FPG and body weight were observed. The findings suggest that long‐term co‐administration of canagliflozin with teneligliptin is well tolerated and effective in Japanese patients with T2DM who have inadequate glycaemic control on teneligliptin alone. PMID:28608617

The co-formulation of insulin degludec and insulin aspart lowers fasting plasma glucose and rates of confirmed and nocturnal hypoglycaemia, independent of baseline glycated haemoglobin levels, disease duration or body mass index: A pooled meta-analysis of phase III studies in patients with type 2 diabetes.

PubMed

Haluzík, Martin; Fulcher, Greg; Pieber, Thomas R; Bardtrum, Lars; Tutkunkardas, Deniz; Rodbard, Helena W

2018-02-16

To investigate whether the proven benefits of insulin degludec (IDeg) combined with insulin aspart (IAsp), known as IDegAsp, given twice daily, extend across a wide spectrum of patients with diabetes. This was a post hoc pooled analysis of 5 phase III randomized, 26-week, open-label, treat-to-target trials comparing IDegAsp twice daily (n = 1111) with one of two comparators: premixed insulin (biphasic insulin aspart 30 [BIAsp 30]) twice daily (n = 561) or IDeg once daily + IAsp (n = 136). Patient data were stratified according to baseline glycated haemoglobin (HbA1c) or fasting plasma glucose (FPG) categories, as well as by baseline duration of diabetes or body mass index (BMI) categories. We conducted a meta-analysis of 5 clinical trials: NCT01513590, NCT01009580, NCT01059812, NCT01680341 and NCT01713530. End-of-trial results were broadly consistent, with differences between IDegAsp and comparators observed in phase III trials. HbA1c results were similar for IDegAsp and the comparators in all baseline characteristic (HbA1c, duration of diabetes or BMI) and category groups (number ranges). Significantly lower FPG level was observed with IDegAsp vs comparators in all baseline characteristic and most category groups (excluding FPG <5.5 mmol/L). Significantly lower insulin doses were observed with IDegAsp vs comparators in all baseline characteristic and half of the category groups, and significantly lower rates of confirmed and nocturnal confirmed hypoglycaemia were observed with IDegAsp vs comparators in all baseline variable and category groups. IDegAsp retains a consistent safety and efficacy profile in patients with different baseline characteristics. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Associations of circulating calcium and 25-hydroxyvitamin D with glucose metabolism in pregnancy: a cross-sectional study in European and South Asian women.

PubMed

Whitelaw, Donald C; Scally, Andrew J; Tuffnell, Derek J; Davies, T Jeffrey; Fraser, William D; Bhopal, Raj S; Wright, John; Lawlor, Debbie A

2014-03-01

Vitamin D deficiency is thought to impair insulin action and glucose metabolism; however, previous studies have not examined ethnic differences or the influence of calcium and parathyroid hormone. We investigated this in a cohort of predominantly white European and south Asian women during pregnancy. In this cross-sectional study from an urban population in northern England (53.8°N), 1467 women were recruited when undergoing glucose tolerance testing (75 g oral glucose tolerance test) at 26 weeks' gestation. Gestational diabetes mellitus (GDM) was diagnosed in 137 women (9.3%). Median 25-hydroxyvitamin D concentration for the study population was 9.3 ng/mL (interquartile range 5.2, 16.9) and was higher in European [15.2 ng/mL (10.7, 23.5)] than in south Asian women [5.9 ng/mL (3.9, 9.4), P < .001]. After appropriate adjustment for confounders, 25-hydroxyvitamin D showed a weak inverse association with fasting plasma glucose (FPG; mean difference 1.0% per 1 SD; the ratio of geometric means (RGM) 0.99, 95% confidence interval (CI) 0.98, 1.00), and PTH was weakly associated with FPG (RGM 1.01, 95% CI 1.00, 1.02), but neither was associated with fasting insulin, postchallenge glucose, or GDM. Serum calcium (albumin adjusted) was strongly associated with fasting insulin (RGM 1.06; 95% CI 1.03, 1.08), postchallenge glucose (RGM 1.03, 95% CI 1.01, 1.04), and GDM (odds ratio 1.33, 95% CI 1.06, 1.66) but not with FPG. Associations were similar in European and south Asian women. These findings do not indicate any important association between vitamin D status and glucose tolerance in pregnancy. Relationships between circulating calcium and glucose metabolism warrant further investigation.

Serum Uric Acid Levels were Dynamically Coupled with Hemoglobin A1c in the Development of Type 2 Diabetes

NASA Astrophysics Data System (ADS)

Wei, Fengjiang; Chang, Baocheng; Yang, Xilin; Wang, Yaogang; Chen, Liming; Li, Wei-Dong

2016-06-01

The aim of the study was to decipher the relationship between serum uric acid (SUA) and glycated hemoglobin A1c (HbA1c) or fasting plasma glucose (FPG) in both type 2 diabetes mellitus (T2DM) patients and normal subjects. A total of 2,250 unrelated T2DM patients and 4,420 Han Chinese subjects from a physical examination population were recruited for this study. In T2DM patients SUA levels were negatively correlated with HbA1c (rs = -0.109, P = 0.000) and 2 h plasma glucose levels (rs = -0.178, P = 0.000). In the physical examination population, SUA levels were inversely correlated with HbA1c (rs = -0.175, P = 0.000) and FPG (rs = -0.131, P = 0.009) in T2DM patients but positively correlated with HbA1c (rs = 0.040, P = 0.012) and FPG (rs = 0.084, P = 0.000) in normal-glucose subjects. Multivariate analyses showed that HbA1c was significantly negatively associated with HUA both in T2DM patients (OR = 0.872, 95% CI: 0.790~0.963) and in the physical examination T2DM patients (OR = 0.722, 95% CI: 0.539~0.968). Genetic association studies in T2DM patients showed that alleles of two glucose-uric acid transporter genes, ABCG2 and SLC2A9 were significantly associated with SUA levels (P < 0.05). SUA level is inversely correlated with HbA1c in T2DM patients but positively correlated with HbA1c in normal-glucose subjects. The reverse transporting of uric acid and glucose in renal tubules might be accounted for these associations.

Synergistic potential of Zingiber officinale and Curcuma longa to ameliorate diabetic-dyslipidemia.

PubMed

Hussain, Naveed; Hashmi, Abu-Saeed; Wasim, Muhammad; Akhtar, Tauqeer; Saeed, Shagufta; Ahmad, Toheed

2018-03-01

To find the cure of world's one of the leading morbid and mortal disorders; diabetes mellitus and its most prevalent complication, 'diabetic-dyslipidemia', is one of the leading health challenges of 21st century. The use of phytomedicine is a glimmer of hope in this scenario. Studies of current decade have shown that methanolic extracts of Zingiber officinale and Curcuma longa have highly effective therapeutic potentials against the aforesaid disorders, however, which of the extracts has more potential is still unclear. Furthermore, synergistic effect of the extracts has never been studied. Forty-eight Albino adult rats of either sex were randomly divided into eight groups. A-D groups were containing healthy rats while E-H groups were of induced diabetic-dyslipidemic rats. For forty-two days, rats of each group were given either distilled water or Zingiber officinale methanolic extract (ZOME) or Curcuma longa methanolic extract (CLME) or ZOME+CLME therapies at dose rate of 300mg/100 mL dist. H 2 O/kg body wt/day. FPG and lipid profiles were estimated before and after the trial, and were statistically analyzed by one-way ANOVA along with Post-hoc Tukey's multiple comparison tests. Although, ZOME and CLME significantly (P<0.05) lowered fasting plasma glucose (FPG) levels and controlled lipid profiles in diabetic-dyslipidemic rats; yet, synergistic therapy of both extracts (ZOME+CLME) most significantly (P<0.05) controlled all parameters of diabetic-dyslipidemia (78.00±1.06mg/dL FPG, 62.00±0.58mg/dL TG, 66.50±0.76mg/dL cholesterol, 32.00±0.36mg/dL HDL, 22.43±0.64 mg/dL LDL, and 12.40±0.12mg/dL VLDL). Our findings may be useful to formulate new medicines having multiple potentials to control diabetes mellitus, dyslipidemia, and diabetic-dyslipidemia.

The Individuals with Disabilities Education Act: State Achievements, Challenges, and Implications. FPG Snapshot #65

ERIC Educational Resources Information Center

FPG Child Development Institute, 2012

2012-01-01

The goal of Individuals with Disabilities Education Act (IDEA) is no longer simply to make services available to young children with disabilities and their families, but also to ensure that those services lead to enhanced outcomes for participating children and families. To that end, IDEA 2004 requires states to submit State Performance Plans…

Parent Involvement: A New Question for Head Start. FPG Snapshot. #24

ERIC Educational Resources Information Center

FPG Child Development Institute, 2005

2005-01-01

Parent involvement in Head Start has been key since its inception in 1965. In contrast to other early childhood intervention programs in the early 1960s, the program broke ground by viewing parental participation as essential to both children's and families' growth and development. Research has demonstrated that greater parent involvement links to…

Lack of Consensus on How to Evaluate Programs for Preschool Children with Disabilities Leaves States Floundering. FPG Snapshot #32

ERIC Educational Resources Information Center

FPG Child Development Institute, 2006

2006-01-01

With no single definition of how publicly-funded programs for preschool children with disabilities should define or measure success, states are struggling to develop accountability systems that demonstrate results and understand how to best serve children and families. This report summarizes a new paper, "Issues in Designing State…

Otitis Media in Young Children with Disabilities--Practical Strategies. FPG Snapshot #16

ERIC Educational Resources Information Center

FPG Child Development Institute, University of North Carolina, 2004

2004-01-01

Studies have shown that some children are at higher risk for otitis media. Those at risk may include children with some developmental disorders such as Down syndrome, Williams syndrome, Apert syndrome, fragile X syndrome, Turner syndrome, cleft palate, and autism; as well as all children attending childcare. It has been hypothesized that the link…

Poverty and Early Childhood Intervention. FPG Snapshot #42

ERIC Educational Resources Information Center

FPG Child Development Institute, 2007

2007-01-01

In the spring of 2006, the University of North Carolina's (UNC) Center on Poverty, Work and Opportunity hosted a competitive process to support original research by UNC faculty members in the form of policy briefs. Each brief was authored by a UNC faculty member and was reviewed by an academic and a practitioner in the field that the brief…

Music Therapy Engages Children with Autism in Outdoor Play. FPG Snapshot. Number 39, February 2007

ERIC Educational Resources Information Center

FPG Child Development Institute, 2007

2007-01-01

The unstructured space, running, climbing, sliding, and loud nature of playground time can be overwhelming for children with autism who thrive on predictable and structured routines. As a result, these preschoolers often do not experience the learning and social development benefits from outdoor play seen in their typically developing classmates.…

Using Music to Improve Task Learning. FPG Snapshot #43

ERIC Educational Resources Information Center

FPG Child Development Institute, 2007

2007-01-01

Learning to wash hands, go to the bathroom and other self-care skills are significant steps toward independence for young children. Each step toward independent self-care is a milestone that is expected and valued. However, for young children with autism such steps may not occur naturally. Research shows that songs can assist children with…

Diversity, Child Care Quality and Developmental Outcomes. FPG Snapshot, #21

ERIC Educational Resources Information Center

FPG Child Development Institute, University of North Carolina, 2004

2004-01-01

It is widely accepted that high quality child care enhances children's cognitive and social development, but some people question if what constitutes quality care depends on the child's ethnic and cultural background. To examine this issue, secondary analysis of the two largest U.S. studies of child care--the Cost, Quality, and Outcomes Study and…

The tryptophan-derived endogenous arylhydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole (FICZ) is a nanomolar UVA-photosensitizer in epidermal keratinocytes

PubMed Central

Williams, Joshua D.; Cabello, Christopher M.; Qiao, Shuxi; Wondrak, Georg T.

2014-01-01

Endogenous UVA-chromophores may act as sensitizers of oxidative stress underlying cutaneous photoaging and photocarcinogenesis, but the molecular identity of non-DNA key chromophores displaying UVA-driven photodyamic activity in human skin remains largely undefined. Here we report that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct and endogenous high affinity aryl hydrocarbon receptor (AhR) agonist, acts as a nanomolar photosensitizer potentiating UVA-induced oxidative stress irrespective of AhR ligand activity. In human HaCaT and primary epidermal keratinocytes, photodynamic induction of apoptosis was elicited by the combined action of solar simulated UVA and FICZ, whereas exposure to the isolated action of UVA or FICZ did not impair viability. In a human epidermal tissue reconstruct, FICZ/UVA-cotreatment caused pronounced phototoxicity inducing keratinocyte cell death, and FICZ photodynamic activity was also substantiated in a murine skin exposure model. Array analysis revealed pronounced potentiation of cellular heat shock, ER stress, and oxidative stress response gene expression observed only upon FICZ/UVA-cotreatment. FICZ photosensitization caused intracellular oxidative stress, and comet analysis revealed introduction of formamidopyrimidine-DNA glycosylase (FPG)-sensitive oxidative DNA lesions suppressible by antioxidant cotreatment. Taken together, our data demonstrate that the endogenous AhR ligand FICZ displays nanomolar photodynamic activity representing a molecular mechanism of UVA-induced photooxidative stress potentially operative in human skin. PMID:25431849

Effects of electroacupuncture and Chinese kidney-nourishing medicine on polycystic ovary syndrome in obese patients.

PubMed

Yu, Liqing; Liao, Yanjun; Wu, Huangan; Zhao, Jimeng; Wu, Luyi; Shi, Yin; Fang, Jianqiao

2013-06-01

To explore the effect of electroacupuncture and Chinese kidney-nourishing medicine on insulin (INS), adiponectin (APN), leptin (LEP), and glucolipid metabolism of obese patients with polycystic ovary syndrome (PCOS). Sixty-seven obese PCOS patients were randomly divided into two groups. Thirty-three patients in the acupuncture-medicine group were treated three times a week with electroacupuncture at the Tianshu (ST 25), Zhongwan (CV 12), Qi-hai (CV 6), Sanyinjiao (SP 6), Geshu (BL 17), and Ciliao (BL 32) acupoints. They also took the Chinese drug, Tiankui capsule, for 3 months as a course of treatment. Point-taking and treatment in the electroacupuncture group of 34 patients was the same as those in the acupuncture-medicine group. We observed and compared the changes in the obesity-related indexes of body weight (BW), body mass index (BMI), and waist-hip ratio (WHR), as well as fasting plasma glucose (FPG), fasting insulin (FINS), APN, and LEP. BW, BMI, WHR, and FINS decreased and insulin sensitivity index (ISI) and APN were higher in the acupuncture-medicine group than in the electroacupuncture group (P < 0.01). There was no obvious difference in LEP between the two groups (P > 0.05). Acupuncture combined with medicine is better than just electroacupuncture for obese PCOS patients by improving obesity-related indexes, insulin sensitivity, and APN level. This indicates that acupuncture-medicine therapy is worth clinical popularization.

Evaluation of the effects of roselle (Hibiscus sabdariffa L.) on oxidative stress and serum levels of lipids, insulin and hs-CRP in adult patients with metabolic syndrome: a double-blind placebo-controlled clinical trial.

PubMed

Asgary, Sedigheh; Soltani, Rasool; Zolghadr, Mohsen; Keshvari, Mahtab; Sarrafzadegan, Nizal

2016-06-01

Roselle (Hibiscus sabdariffa L.) is a plant with antihyperlipidemic and antihypertensive effects. This study aimed to evaluate the effects of roselle calyces on the serum levels of lipids and insulin, inflammation, and oxidative stress in patients with metabolic syndrome (MetS). Forty adult patients with MetS were randomly assigned to receive either 500 mg of H. sabdariffa calyx powder or placebo once daily for 4 weeks. Systolic and diastolic blood pressures (SBP and DBP) and BMI (body mass index) as well as fasting serum levels of glucose (FPG; fasting plasma glucose), insulin, lipoproteins, triglycerides (TG), high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde (MDA) were determined pre- and post-intervention and compared. H. sabdariffa significantly reduced serum TG (p=0.044) and SBP (p=0.049) compared to placebo. All other variables were not significantly affected by the interventions. Daily consumption of 500 mg of H. sabdariffa L. calyx powder can decrease SBP and serum TG in MetS patients.

Parents' Decisions to Screen Their Newborn for Fragile X Syndrome. FPG Snapshot #63

ERIC Educational Resources Information Center

FPG Child Development Institute, 2011

2011-01-01

State newborn screening (NBS) programs have expanded in recent years, and more tests may be added in the future. The expansion of neonatal screening raises ethical, legal, and social questions. The questions surrounding NBS for fragile X syndrome (FXS) typify these concerns. FXS is an X-linked genetic condition that is the most common inherited…

Celebrating 40 Years. Early Developments. Volume 10, Number 1, Spring 2006

ERIC Educational Resources Information Center

Winton, Pam, Ed.; Buyssee, Virginia, Ed.; Hambrick, Catherine, Ed.

2006-01-01

Although the FPG Child Development Institute's primary mission is to generate new knowledge, this research is in the service of a higher goal: child and family well being. This goal is distilled in their tag line: "Advancing knowledge, enhancing lives." This phrase is not just a tag line--it encapsulates 40 years of striving to be an…

Moringa Oleifera leaf extract increases plasma antioxidant status associated with reduced plasma malondialdehyde concentration without hypoglycemia in fasting healthy volunteers.

PubMed

Ngamukote, Sathaporn; Khannongpho, Teerawat; Siriwatanapaiboon, Marent; Sirikwanpong, Sukrit; Dahlan, Winai; Adisakwattana, Sirichai

2016-12-29

To investigate the effect of Moringa Oleifera leaf extract (MOLE) on plasma glucose concentration and antioxidant status in healthy volunteers. A randomized crossover design was used in this study. Healthy volunteers were randomly assigned to receive either 200 mL of warm water (10 cases) or 200 mL of MOLE (500 mg dried extract, 10 cases). Blood samples were drawn at 0, 30, 60, 90, and 120 min for measuring fasting plasma glucose (FPG), ferric reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC) and malondialdehyde (MDA). FPG concentration was not signifificantly different between warm water and MOLE. The consumption of MOLE acutely improved both FRAP and TEAC, with increases after 30 min of 30 μmol/L FeSO 4 equivalents and 0.18 μmol/L Trolox equivalents, respectively. The change in MDA level from baseline was signifificantly lowered after the ingestion of MOLE at 30, 60, and 90 min. In addition, FRAP level was negatively correlated with plasma MDA level after an intake of MOLE. MOLE increased plasma antioxidant capacity without hypoglycemia in human. The consumption of MOLE may reduce the risk factors associated with chronic degenerative diseases.

Can rs3767140 SNP of the perlecan (HSPG2) gene affect the diabetes mellitus through the dyslipidemia?

PubMed

Kurnaz-Gömleksiz, Ö; Tokat, B; Aslan, E I; Yanar, F; Ermiş-Karaali, Z; Öztürk, O; Yilmaz-Aydoğan, H

2016-07-31

Perlecan (HSPG2) play an important role in the lipoprotein metabolisms. The G allele of the HSPG2-rs3767140 may affect the binding of heparan sulfate (HS) chains and hence cause loss of HS from the basement membrane. HSPG2-rs3767140 was studied in 60 T2DM patients and 109 healthy controls. In diabetic patients HSPG2-rs3767140 T variant allele carriers (TT+GT) have decreased fasting plasma glucose (FPG) and serum LDL-C levels (p=0.071 and p=0.060, respectively) versus GG genotype carriers. Moreover, in both of the two groups in which the T allele carriers HDL-cholesterol levels tend to be high. We investigated that the HSPG2-rs3767140 promoted to the dyslipidemic phenotype in the type 2 diabetes mellitus (T2DM) patients. We suggest that the HSPG2-rs3767140 might be associated with the decreased FPG and LDL-C and with the increased HDL-C in diabetics. Therefore, the HSPG2-rs3767140 might be a protective for the diabetes mellitus due to its ameliorating effect on the dyslipidemic phenotype.

High Prevalence of Diabetes and Prediabetes and Their Coexistence with Cardiovascular Risk Factors in a Hispanic Community.

PubMed

Pérez, Cynthia M; Soto-Salgado, Marievelisse; Suárez, Erick; Guzmán, Manuel; Ortiz, Ana Patricia

2015-08-01

This study examined the prevalence and association of diabetes mellitus (DM) and prediabetes with cardiovascular risk factors among Puerto Ricans adults. Data from a household survey of 857 adults aged 21-79 years who underwent interviews, physical exams, and blood draws were analyzed. Prevalence of total DM and prediabetes was estimated using American Diabetes Association diagnostic criteria of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Poisson regression models were used to estimate the prevalence ratio for each cardiovascular risk factor under study. Age-standardized prevalence of total DM and prediabetes, detected by FPG and/or HbA1c, was 25.5 and 47.4 %, respectively. Compared with participants with normoglycemia, those with previously diagnosed DM, undiagnosed DM, and prediabetes had more adverse cardiovascular risk factor profiles, characterized by a higher prevalence of general and abdominal obesity, hypertension, low HDL cholesterol, elevated LDL cholesterol, elevated triglycerides, and elevated plasminogen activator inhibitor 1 (p < 0.05). The high prevalence of DM and prediabetes calls for public health actions to plan and implement lifestyle interventions to prevent or delay the onset of DM and cardiovascular disease.

High Prevalence of Diabetes and Prediabetes and Their Coexistence with Cardiovascular Risk Factors in a Hispanic Community

PubMed Central

Soto-Salgado, Marievelisse; Suárez, Erick; Guzmán, Manuel; Ortiz, Ana Patricia

2014-01-01

This study examined the prevalence and association of diabetes mellitus (DM) and prediabetes with cardiovascular risk factors among Puerto Ricans adults. Data from a household survey of 857 adults aged 21–79 years who underwent interviews, physical exams, and blood draws were analyzed. Prevalence of total DM and prediabetes was estimated using American Diabetes Association diagnostic criteria of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Poisson regression models were used to estimate the prevalence ratio for each cardiovascular risk factor under study. Age-standardized prevalence of total DM and prediabetes, detected by FPG and/or HbA1c, was 25.5 and 47.4 %, respectively. Compared with participants with normoglycemia, those with previously diagnosed DM, undiagnosed DM, and prediabetes had more adverse cardiovascular risk factor profiles, characterized by a higher prevalence of general and abdominal obesity, hypertension, low HDL cholesterol, elevated LDL cholesterol, elevated triglycerides, and elevated plasminogen activator inhibitor 1 (p < 0.05). The high prevalence of DM and prediabetes calls for public health actions to plan and implement lifestyle interventions to prevent or delay the onset of DM and cardiovascular disease. PMID:24781780

[Role of visfatin in the pathogenesis of gestational diabetes mellitus and its relationship with insulin resistance].

PubMed

Huo, Yan; Liu, Suxin; Feng, Jing; Li, Hongyan; Fan, Yanli; Jin, Ying; Li, Li

2014-08-01

To investigate the role of visfatin in the pathogenesis of gestational diabetes mellitus (GDM) and its correlation with insulin resistance. The study recruited 58 pregnant women of 24 to 28 gestational weeks in People's Hospital of Hebei Province from January to June 2013. Among them, 30 were patients with GDM (GDM group), 28 had normal oral glucose tolerance test and was referred as healthy pregnancy group (NGT group). Fourteen age-matched female who were first-degree relatives (FDR1) of type 2 diabetes mellitus patients, and 27 healthy nonpregnant women with normal oral glucose tolerance test were referred as high-risk group and normal controls (NC), respectively. The fasting plasma glucose (FPG), 1 hour and 2 hours postprandial glucose levels were measured by glucose oxidase method. The fasting insulin (FIN) levels were measured by radioimmunoassay and the homeostatic model assessment-insulin resistance index (HOMA- IR) was calculated. The levels of total cholesterol (TC), triglycerdes (TG), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) were determined. The visfatin levels were measured by ELISA. (1)The levels of FPG were significantly higher in GDM, FDR1 and NC group [(5.5 ± 0.7), (5.1 ±0.6), (5.2 ± 0.4)mmol/L] than that in NGT group [(4.5 ± 0.3) mmol/L], respectively (P < 0.05). (2) The levels of INS [(14 ± 6)mU/L], HOMA- IR (4.0 ± 2.0), 1 hour [(10.9 ± 1.8) mmol/L] and 2 hours [(8.6 ± 1.8) mmol/L] postprandial glucose levels of GDM group were significantly higher than those in NGT group [(12 ± 4) mU/L, 2.0 ± 1.0, (7. 4 ± 1.3) and (6.2 ± 0.9) mmol/L], respectively (P < 0.05). (3) The levels of TC, TG, HDL and LDL levels in GDM group were (5.5 ± 0.9), (2.8 ± 0.8), (1.8 ± 0.4) and (3.3 ± 0.8) mmol/L, and were(5.9 ± 0.8), (2.5 ± 0.7), (1.9 ± 0.4) and (3.4 ± 0.6) mmol/L in NGT group. The levels of lipid in the two groups were significantly higher than those in FDR1 or NC group, respectively(P < 0.05).(4)The levels of visfatin in GDM group and NGT group [(43 ± 10), (45 ± 12) µg/L] were significantly higher than that in FDR1 or NC group [(29 ± 9), (36 ± 7) µg/L], respectively (P < 0.05), but the visfatin levels in FDR1 group were significantly lower than that in NC group (P < 0.05). The visfatin levels in GDM group were slightly lower than that in NGT group, but the difference was not statistically significant (P > 0.05). (5)The visfatin levels in NGT group were negatively correlated to the levels of FPG, HOMA-IR and TC (r = -0.38, -0.44, -0.47, respectively, P < 0.05). But the visfatin levels in GDM group were not correlated with the levels of FPG, HOMA-IR, TC (r = -0.16, -0.01, 0.33, respectively, P > 0.05). While in NC group, the levels of visfatin were negatively correlated with FPG and 2 hours postprandial glucose(r = -0.48, -0.42, respectively, P < 0.05). Visfatin may be an important adipokine that involved in the carbohydrate and lipid metabolism in GDM, and is related to the pathogensis of GDM and insulin resistance.

[Effect of Qingre Yangyin Recipe on Endocrine and Metabolism of Polycystic Ovary Syndrome Patients].

PubMed

Zhang, Ting

2015-10-01

To observe the effect of Qingre Yangyin Recipe (QRYYR) on sex hormones and insulin resistance (IR) in polycystic ovary syndrome (PCOS) patients. Totally 90 PCOS patients were randomly assigned to the Chinese herbs group,the Western medicine group, the combined group, 30 in each group. Patients in the Chinese herbs group took QRYYR, one dose per day in two portions, once in the morning and once in the evening. Patients in the Western medicine group took Metformin 500 mg, twice per day for 3 consecutive months. Patients in the combined group took QRYYR and Metformin (the same as the former said two groups) in the 1st month, and took QRYYR for the following two months. Fasting blood glucose (FPG) and postprandial 2 h blood glucose (2 h GLU) were determined using hexokinase method before and after treatment. Fasting insulin (FINS), postprandial 2 h insulin (2 h INS), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), progesterone (P), prolactin (PRL), and testosterone (T) were detected using chemiluminescent method. Leptin and adiponectin (APN) were determined using ELISA. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Body weight and height were measured once before treatment and once after treatment to calculate body mass index (BMI). The total two-phase basal body temperature (BBT) actually obtained within 3 months was statistically collected to calculate the two-phase BBT rate. Scores for Chinese medical syndromes were compared between the two groups before and after treatment. Compared with before treatment in the same group, BMI, FINS, 2 h INS, HOMA-IR, leptin, LH, PRL, T, and scores for Chinese medical syndromes obviously decreased, and APN levels increased (P < 0.05). FPG and 2 h FPG obviously decreased in the Western medicine group and the combined group (P < 0.05). E2 levels obviously decreased in the combined group with statistical difference (P < 0.05). Compared with the Chinese herbs group, the difference of BMI between pre-treatment and post-treatment was more in the combined group (P < 0.05). The difference of FPG,2 h GLU, 2 h INS, HOMA-IR, and APN between pre-treatment and post-treatment was more in the Chinese herbs group and the combined group (P < 0.05). Compared with the Western medicine group, the difference of PRL, T, and scores for Chinese medical syndromes was more in the Western medicine group and the combined group (P < 0.05); the difference of E2 and LH was even more in the combined group (P < 0.05). Compared with the combined group, the biphasic rate was obviously lowered in the Western medicine group (P < 0.05). QRYYR could improve IR but with weaker power to that of Metformin. It also could decrease serum levels of LH, T, PRL, and scores for Chinese medical syndromes, with superior effect to that of Metformin. The effect in the combined group was better.

Early Learning Visual Impairment Services Training and Advancement (EL VISTA) Project: Leading the Way for a New Profession within a Profession

ERIC Educational Resources Information Center

Landa-Vialard, Olaya; Ely, Mindy S.; Lartz, Maribeth Nelson

2018-01-01

The Frank Porter Graham (FPG) Child Development Institute, Early Intervention Training Center for Infants and Toddlers with Visual Impairments and Their Families, University of North Carolina at Chapel Hill, was a national project that developed resources with the goal of building the capacity of colleges and universities to prepare personnel to…

Recognition & Response: Developing and Evaluating a Model of RTI for Pre-K

ERIC Educational Resources Information Center

Buysse, Virginia; Peisner-Feinberg, Ellen; Burchinal, Margaret

2012-01-01

The Recognition & Response (R&R) model was developed and is being validated by a research team at the FPG Child Development Institute at the University of North Carolina at Chapel Hill. R&R has generated widespread attention in the early childhood field as a promising RTI model for pre-k (see entire issue of NHSA Dialog, Volume 12[3],…

The Impact of Early Childhood Teacher Education: How to Answer the Unanswerable Question. FPG Snapshot #68

ERIC Educational Resources Information Center

FPG Child Development Institute, 2013

2013-01-01

Public awareness of the value of a high quality early childhood education has never been stronger with Nobel-prize winning economist James J. Heckman declaring that it is the key to the nation's future. Higher education's role in preparing teachers to deliver on that promise is significant and continues to grow. A special issue of the "Journal of…

Technology Stereotypes Broken when Children's Health Involved. FPG Snapshot. Number 52. March 2008

ERIC Educational Resources Information Center

FPG Child Development Institute, 2008

2008-01-01

When it comes to people's perceptions of internet usage, stereotypes prevail. There is the assumption that people living in poverty and those with less education do not log on. It is true that their numbers are lower than those of individuals with higher education and incomes, but these statistics may not paint the whole picture. In some…

Efficacy and tolerability of vildagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes mellitus.

PubMed

Pan, C; Xing, X; Han, P; Zheng, S; Ma, J; Liu, J; Lv, X; Lu, J; Bader, G

2012-08-01

To investigate the efficacy and tolerability of vildagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. This was a 24-week, randomized, double-blind, placebo-controlled study. Patients with T2DM (N = 438) with haemoglobin A1c (HbA1c) of 7.0-10.0% and fasting plasma glucose (FPG) <15 mmol/l (<270 mg/dl) were randomized (1 : 1 : 1) to vildagliptin 50 mg bid, vildagliptin 50 mg qd or placebo in addition to metformin. The treatment groups were well balanced at baseline [mean HbA1c, 8.0%, FPG, 8.8 mmol/l (158 mg/dl); body mass index, 25.5 kg/m(2) ]. The adjusted mean change (AMΔ) in HbA1c at endpoint was -1.05 ± 0.08%, -0.92 ± 0.08% and -0.54 ± 0.08% in patients receiving vildagliptin 50 mg bid, 50 mg qd and placebo, respectively. The between-treatment difference (vildagliptin 50 mg bid-placebo) was -0.51 ± 0.11%, p < 0.001. A greater proportion of vildagliptin-treated patients met at least one responder criterion (82.1 and 70.7%) compared to placebo-treated patients (60.4%). The AMΔ at endpoint for FPG with vildagliptin 50 mg bid, -0.95 mmol/l (-17.1 mg/dl); 50 mg qd, -0.84 mmol/l (-15.1 mg/dl) was significantly different compared with the placebo -0.26 mmol/l (-4.68 mg/dl) (p ≤ 0.001). Adverse events (AEs) were reported as 34.2, 36.5 and 37.5% for patients receiving vildagliptin 50 mg bid, 50 mg qd or placebo, respectively. Two patients in the vildagliptin 50 mg qd and one in the placebo group reported serious AEs, which were not considered to be related to the study drug; one incidence of hypoglycaemic event was reported in the vildagliptin 50 mg bid group. Vildagliptin as add-on therapy to metformin improved glycaemic control and was well tolerated in Chinese patients who were inadequately controlled by metformin only. © 2012 Blackwell Publishing Ltd.

Earlier triple therapy with pioglitazone in patients with type 2 diabetes.

PubMed

Charpentier, G; Halimi, S

2009-09-01

This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA(1c)) 6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA(1c) (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-B) were calculated. Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA(1c) and -2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA(1c) level of <8.5% achieved the HbA(1c) target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA(1c) level was >or= 8.5%, 13% achieved the HbA(1c) target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA(1c), FPG and surrogate measures of beta-cell function. Patients were more likely to reach target HbA(1c) levels (< 7.0%) with pioglitazone treatment if their baseline HbA(1c) levels were < 8.5%, highlighting the importance of early triple therapy.

Effect of dragon fruit on glycemic control in prediabetes and type 2 diabetes: A systematic review and meta-analysis

PubMed Central

Poolsup, Nalinee; Paw, Naw Juna

2017-01-01

Objective The purpose of this study was to systematically determine the effect of dragon fruit on glycemic control in prediabetes and type 2 diabetes. Methods Electronic databases including MEDLINE, CENTRAL, CINAHL, Scopus, ScienceDirect®, Proquest, Web of Science®, LILACS, NAPRALERT, SciFinder, Clinicalkey, Herbmed, NCCIH and Google Scholar were searched from their earliest inception up to March 2017 for relevant randomized controlled trials (RCTs) which compared dragon fruit with placebo or no treatment in prediabetes or type 2 diabetes. Clinicaltrials.gov, clinicaltrialresults.org, and ISRCTN registry were also searched. Personal contact with experts and historical search of related articles was undertaken. Outcome of interest were fasting plasma glucose (FPG) and 2 hours post-prandial glucose (2HPP). Study selection, data extraction and study quality assessment were performed independently by two investigators. Disagreements were resolved by a third reviewer. Treatment effect was estimated with mean difference (MD). Effect estimates were pooled using inverse-variance weighted method. Heterogeneity was assessed with the Q statistic and quantified with the I2 statistic. DerSimonian and Laird random-effects model was used when the Q-statistic was significant at the level of 0.1, otherwise a fixed-effects model was used. Results Among 401 studies identified from literature search, 4 RCTs involving 36 prediabetes subjects and 109 type 2 diabetes patients were included in the analysis. In prediabetes, FPG reduction was significant with MD of -15.1 mg/dL (95% CI: -23.8 to -6.5 mg/dL, P-value = 0.0006). Meta-analysis in type 2 diabetes showed no effect of dragon fruit on FPG (MD -26.5 mg/dL, 95% CI: -72.6 mg/dL to 19.6 mg/dL) and in 2HPP (MD -30.5 mg/dL, 95% CI: -80.9 mg/dL to 19.9 mg/dL). Conclusion The available evidence in prediabetes is interesting. This will shed some light on diabetes prevention. The effect in T2DM was not significant. However, a trend towards greater blood glucose reduction with higher dose was observed. PMID:28886195

[Correlation between self-management behaviors and blood glucose control in patients with type 2 diabetes mellitus in community].

PubMed

Yu, Pingping; Xiao, Xiangcheng; Wang, Linyun; Wang, Lei

2013-04-01

To investigate the self-management behaviors of patients with type 2 diabetes mellitus (DM) in a community and to explore the relationship between self-management behaviors and the glycemic control. A total of 211 type 2 DM patients in a community were selected by stratified random sampling. Patients were grouped according to the scores of self-management behaviors. The fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2hPG) and glycated hemoglobin (HbA1C) level were tested. The differences between groups and relationship between self-management behaviors and glycemic control were analyzed. Self-management behaviors of most patients were not effective, and 2hPG and HbA1C were affected by different levels of the self-management behaviors (P<0.05). The self-management behaviors were negatively related to FPG (r=-0.277, P=0.015), 2hPG (r=-0.453, P=0.001), and HbA1C (r=-0.435, P=0.001). Glycemic control of the patients whose course of disease was over 5 years was significantly different due to different self-management behaviors. FPG level of the patients was positively related to alimentary control. The 2hPG level of the patients was positively related to alimentary control, medication persistence, and blood glucose self-monitoring. The HbA1C level of the patients was positively related to alimentary control and medication persistence. The times the patients received DM education, the way to use insulin, and the disease course of the patients were important factors to affect self-management behaviors of type 2 DM in the community. Self-management behaviors of type 2 DM patients in the community are not effective. Satisfactory self-management behaviors, specially the control of 2hPG and HbA1C are beneficial to glycemic control. We can improve the self-management behaviors in type 2 DM patients by paying attention to the disease course, the treatment method, and the contents and effect of DM education.

Effect of dragon fruit on glycemic control in prediabetes and type 2 diabetes: A systematic review and meta-analysis.

PubMed

Poolsup, Nalinee; Suksomboon, Naeti; Paw, Naw Juna

2017-01-01

The purpose of this study was to systematically determine the effect of dragon fruit on glycemic control in prediabetes and type 2 diabetes. Electronic databases including MEDLINE, CENTRAL, CINAHL, Scopus, ScienceDirect®, Proquest, Web of Science®, LILACS, NAPRALERT, SciFinder, Clinicalkey, Herbmed, NCCIH and Google Scholar were searched from their earliest inception up to March 2017 for relevant randomized controlled trials (RCTs) which compared dragon fruit with placebo or no treatment in prediabetes or type 2 diabetes. Clinicaltrials.gov, clinicaltrialresults.org, and ISRCTN registry were also searched. Personal contact with experts and historical search of related articles was undertaken. Outcome of interest were fasting plasma glucose (FPG) and 2 hours post-prandial glucose (2HPP). Study selection, data extraction and study quality assessment were performed independently by two investigators. Disagreements were resolved by a third reviewer. Treatment effect was estimated with mean difference (MD). Effect estimates were pooled using inverse-variance weighted method. Heterogeneity was assessed with the Q statistic and quantified with the I2 statistic. DerSimonian and Laird random-effects model was used when the Q-statistic was significant at the level of 0.1, otherwise a fixed-effects model was used. Among 401 studies identified from literature search, 4 RCTs involving 36 prediabetes subjects and 109 type 2 diabetes patients were included in the analysis. In prediabetes, FPG reduction was significant with MD of -15.1 mg/dL (95% CI: -23.8 to -6.5 mg/dL, P-value = 0.0006). Meta-analysis in type 2 diabetes showed no effect of dragon fruit on FPG (MD -26.5 mg/dL, 95% CI: -72.6 mg/dL to 19.6 mg/dL) and in 2HPP (MD -30.5 mg/dL, 95% CI: -80.9 mg/dL to 19.9 mg/dL). The available evidence in prediabetes is interesting. This will shed some light on diabetes prevention. The effect in T2DM was not significant. However, a trend towards greater blood glucose reduction with higher dose was observed.

Genoprotective effects of green tea (Camellia sinensis) in human subjects: results of a controlled supplementation trial.

PubMed

Han, K C; Wong, W C; Benzie, Iris F F

2011-01-01

Green tea is rich in polyphenolic antioxidants and has widely reported but largely unsubstantiated health benefits. In the present study, genoprotective effects of two types of green tea were studied both in an in vitro and in a human supplementation trial. For the in vitro study, human lymphocytes were pre-incubated in tea (0·005-0·1 %, w/v), washed and subjected to oxidant challenge induced by H2O2. In a placebo-controlled, cross-over supplementation study, eighteen healthy volunteers took 2 x 150 ml/d of 1% (w/v) green tea ('Longjing' green tea or 'screw-shaped' green tea) or water (control) for 4 weeks (n 6). Subjects took all the three treatments in a random order, with 6 weeks' washout between each treatment. Fasting blood and urine were collected before and after each treatment. The comet assay was used to measure the resistance of lymphocytic DNA to H2O2-induced challenge. Basal oxidation-induced DNA damage was measured using the formamidopyrimidine glycosylase (Fpg) enzyme-assisted comet assay. Urine 7,8-dihydro-2-deoxyguanosine (8-oxodG, mol/mmol creatinine), a biomarker of whole-body oxidative stress, was measured by liquid chromatography with tandem MS. In vitro testing results of tea-treated cells showed increased (P < 0·05) resistance of DNA to the challenge. In the supplementation trial, a significant (P < 0·05) increase in resistance was also observed. Furthermore, the FPg comet data showed .20% decrease in DNA damage with tea supplementation: mean and standard deviation changes in %DNA in comet tail in the Fpg-assisted comet assay were: -5·96 (SD 3·83) % after Longjing tea; -6·22 (SD 3·34) % after screw-shaped tea; +0·91 (SD 5·79) % after water (P < 0·05). No significant changes in urine 8-oxodG were seen. The results indicate that green tea has significant genoprotective effects and provide evidence for green tea as a 'functional food'.

Altered Fructosamine and Lipid Fractions in Subclinical Hypothyroidism

PubMed Central

Udupa, Sridevi V.; Manjrekar, Poornima A.; Udupa, Vinit A.; Vivian, D’Souza

2013-01-01

Background: Thyroid function disorders lead to changes in the lipoprotein metabolism. Objectives: To study the lipid and the glycaemic abnormalities in the subclinical hypothyroidism cases and to compare the same with the euthyroid, overt hypothyroid and the hyperthyroid subjects. Methodology: Four groups, euthyroid (Group-I), hypothyroid (Group-II), subclinical hypothyroid (Group-III) and hyperthyroid (Group-IV), which consisted of 30 subjects each, of either sex, who were aged 25-55 years, underwent Fasting Plasma Glucose (FPG), fructosamine, lipid profile and total T3, T4 and TSH estimations. The subjects who were on lipid lowering or thyroid disorder drugs and known diabetics were excluded from the study. Results: In Group-III, all the lipid fractions were comparable to those of Group-II and they were significantly deranged, as compared to those of Group-I. The fructosamine levels were significantly higher in Group-II and Group-III (p<0.05), but the subclinical hypothyroid pool had statistically lower levels than the hypothyroid pool (376.63±54.73, 587.80±65.10). In the Group-IV patients, the LDL-C levels were significantly higher as compared to those in the euthyroid pool. The fructosamine levels were significantly lower in comparison with both the euthyroid and the hypothyroid pools (both in Groups-II and III). The FPG levels were higher in all the classes of the thyroid abnormalities (subclinical hypothyroidnot significant) but within the reference range of 70-100mg/dl. Conclusion: Since the lipid derangement in subclinical hypothyroidism is on par with that in overt hypothyrodism, the subclinical hypothyroid cases also need to be treated similarly. The fructosamine values which are largely in excess of the FPG values, indicate a higher propensity to glycation and a decreased turnover of the proteins in the hypothyroid and the subclinical hypothyroid pools. Vice versa is true of the hyperthyroid pool. Fructosamine can be included in the thyroid work up of the patients to assess the metabolic function and the subsequent response after the initiation of the therapy. PMID:23449765

Correlation of blood glucose, serum chemerin and insulin resistance with NAFLD in patients with type 2 diabetes mellitus.

PubMed

Zhang, Zhengjun; Wang, Jijun; Wang, Hongmei

2018-03-01

Non-alcoholic fatty liver disease (NAFLD) is a form of clinical syndrome characterized by the fatty degeneration in liver histology and should be further investigated. The aim of the study was to investigate the effects of blood glucose, serum chemerin and insulin resistance on non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus to provide a basis for the prevention and treatment thereof. In total, 300 patients with type 2 diabetes mellitus treated and admitted into the Endocrinology Department of our hospital from June 2015 to June 2017 were enrolled and divided into the simple type 2 diabetes mellitus (group A) and concurrent NAFLD (group B) groups. The sex, age, body mass index (BMI), blood pressure, blood biochemical indexes and chemerin level were compared between the two groups. The patients in group B were further divided into the mild fatty liver (group B1), moderate fatty liver (group B2) and severe fatty liver (group B3) groups. The sex, age, BMI blood pressure, blood biochemical indexes and chemerin level were also compared among the three groups. Finally, the risk factors of type 2 diabetes mellitus complicated by NAFLD were analyzed via logistic regression. The BMI, fasting plasma glucose (FPG), 2 h post-prandial plasma glucose (2hPG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), alanine aminotransferase (ALT), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and HOMA-β indexes and serum chemerin level in group B were significantly higher than those in group A (P<0.05 or P<0.01). Notably, the aggravation of NAFLD, the aforementioned indexes were obviously increased (P<0.05 or P<0.01). The regression analysis revealed that BMI, FPG, TC, LDL-c, FINS, HOMA-IR and chemerin were risk factors of concurrent NAFLD. Thus, type 2 diabetes mellitus complicated by NAFLD is closely associated with severe glucose-lipid metabolism disorder and insulin resistance, and BMI, FPG, TC, LDL-c, FINS, HOMA-IR and chemerin constitute risk factors of concurrent NAFLD.

Effects of NOS1AP rs12742393 polymorphism on repaglinide response in Chinese patients with type 2 diabetes mellitus.

PubMed

Wang, Tao; Wang, Yan; Lv, Dong-Mei; Song, Jin-Fang; Lu, Qian; Gao, Xing; Zhang, Fan; Guo, Hao; Li, Wei; Yin, Xiao-Xing

2014-02-01

To investigate the associations of NOS1AP rs12742393 polymorphism with the risk of type 2 diabetes mellitus (T2DM) and repaglinide therapeutic efficacy in Chinese patients with T2DM. Prospective case-control study. Academic medical center. A total of 300 patients with T2DM and 200 healthy volunteers were enrolled to identify NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay. Eighty-four patients with various genotypes were randomly selected to receive oral repaglinide as a single-agent therapy (3 mg/day) for 8 weeks. Anthropometric measurements and fasting plasma glucose (FPG), postprandial plasma glucose, hemoglobin A1c , fasting serum insulin (FINS), postprandial serum insulin, homeostasis model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol tests were obtained before and after repaglinide treatment. The risk C allelic frequency of NOS1AP rs12742393 was higher in patients with T2DM than in healthy volunteers (p<0.001). Patients with T2DM and genotypes AA and AC at NOS1AP rs12742393 had a significant reduction in FPG (mmol/l) compared with those with genotype CC (p<0.01). Patients with CC homozygotes and AC heterozygotes had a greater increase in FINS (mU/l) than those with wild-type AA (p<0.05). In addition, the carriers of genotype CC at NOS1AP rs12742393 had higher differential values of HOMA-IR compared with genotypes AC and AA carriers (p<0.001). The effects of repaglinide treatment on FPG (p<0.01), FINS (p<0.05) and HOMA-IR (p<0.001) were reduced in patients with T2DM carrying the NOS1AP rs12742393 risk C allele compared with the AA genotype carriers. The NOS1AP rs12742393 polymorphism is associated with therapeutic efficacy of repaglinide in Chinese T2DM patients. © 2013 Pharmacotherapy Publications, Inc.

Repaglinide versus nateglinide monotherapy: a randomized, multicenter study.

PubMed

Rosenstock, Julio; Hassman, David R; Madder, Robert D; Brazinsky, Shari A; Farrell, James; Khutoryansky, Naum; Hale, Paula M

2004-06-01

A randomized, parallel-group, open-label, multicenter 16-week clinical trial compared efficacy and safety of repaglinide monotherapy and nateglinide monotherapy in type 2 diabetic patients previously treated with diet and exercise. Enrolled patients (n = 150) had received treatment with diet and exercise in the previous 3 months with HbA(1c) >7 and < or =12%. Patients were randomized to receive monotherapy with repaglinide (n = 76) (0.5 mg/meal, maximum dose 4 mg/meal) or nateglinide (n = 74) (60 mg/meal, maximum dose 120 mg/meal) for 16 weeks. Primary and secondary efficacy end points were changes in HbA(1c) and fasting plasma glucose (FPG) values from baseline, respectively. Postprandial glucose, insulin, and glucagon were assessed after a liquid test meal (baseline, week 16). Safety was assessed by incidence of adverse events or hypoglycemia. Mean baseline HbA(1c) values were similar in both groups (8.9%). Final HbA(1c) values were lower for repaglinide monotherapy than nateglinide monotherapy (7.3 vs. 7.9%). Mean final reductions of HbA(1c) were significantly greater for repaglinide monotherapy than nateglinide monotherapy (-1.57 vs. -1.04%; P = 0.002). Mean changes in FPG also demonstrated significantly greater efficacy for repaglinide than nateglinide (-57 vs. -18 mg/dl; P < 0.001). HbA(1c) values <7% were achieved by 54% of repaglinide-treated patients versus 42% for nateglinide. Median final doses were 6.0 mg/day for repaglinide and 360 mg/day for nateglinide. There were 7% of subjects treated with repaglinide (five subjects with one episode each) who had minor hypoglycemic episodes (blood glucose <50 mg/dl) versus 0 patients for nateglinide. Mean weight gain at the end of the study was 1.8 kg in the repaglinide group as compared with 0.7 kg for the nateglinide group. In patients previously treated with diet and exercise, repaglinide and nateglinide had similar postprandial glycemic effects, but repaglinide monotherapy was significantly more effective than nateglinide monotherapy in reducing HbA(1c) and FPG values after 16 weeks of therapy.

Atlantic DIP: high prevalence of abnormal glucose tolerance post partum is reduced by breast-feeding in women with prior gestational diabetes mellitus.

PubMed

O'Reilly, Michael W; Avalos, Gloria; Dennedy, Michael C; O'Sullivan, Eoin P; Dunne, Fidelma

2011-12-01

Gestational diabetes (GDM) is associated with adverse fetal and maternal outcomes, and identifies women at risk of future type 2 diabetes mellitus (T2DM). Breast-feeding may improve post partum maternal glucose tolerance. Our objective was to identify the prevalence of post partum dysglycemia after GDM, to delineate associated factors and to examine the effect of lactation on post partum glucose tolerance. We compared post partum 75 g oral glucose tolerance test (OGTT) results from 300 women with GDM and 220 controls with normal gestational glucose tolerance (NGT) in five regional centers. Breast-feeding data was collected at time of OGTT. Methods Post partum OGTT results were classified as normal (fasting plasma glucose (FPG) <5.6 mmol/l, 2 h <7.8 mmol/l) and abnormal (impaired fasting glucose (IFG), FPG 5.6-6.9 mmol/l; impaired glucose tolerance (IGT), 2 h glucose 7.8-11 mmol/l; IFG+IGT; T2DM, FPG ≥7 mmol/l±2 h glucose ≥11.1 mmol/l). Binary logistic regression was used to identify factors predictive of persistent hyperglycemia. Five hundred and twenty women were tested; six (2.7%) with NGT in pregnancy had post partum dysglycemia compared with 57 (19%) with GDM in index pregnancy (P<0.001). Non-European ethnicity (odds ratio (OR) 3.40; 95% confidence interval (CI) 1.45-8.02, P=0.005), family history of T2DM (OR 2.14; 95% CI 1.06-4.32, P=0.034), and gestational insulin use (OR 2.62; 95% CI 1.17-5.87, P=0.019) were associated with persistent dysglycemia. The prevalence of persistent hyperglycemia was significantly lower in women who breast-fed vs bottle-fed post partum (8.2 vs 18.4%, P<0.001). Non-European ethnicity, gestational insulin use, family history of T2DM, and elevated body mass index were associated with persistent dysglycemia after GDM. Breast-feeding may confer beneficial metabolic effects after GDM and should be encouraged.

A 20-Year Prospective Study of Childbearing and Incidence of Diabetes in Young Women, Controlling for Glycemia Before Conception

PubMed Central

Gunderson, Erica P.; Lewis, Cora E.; Tsai, Ai-Lin; Chiang, Vicky; Carnethon, Mercedes; Quesenberry, Charles P.; Sidney, Stephen

2010-01-01

OBJECTIVE We sought to determine whether childbearing increases incidence of type 2 diabetes after accounting for preconception glycemia and gestational glucose intolerance. RESEARCH DESIGN AND METHODS A prospective, biracial cohort was examined up to five times during 1985–2006 in the multicenter, U.S. population–based Coronary Artery Risk Development in Young Adults Study. The analysis included 2,408 women (1,226 black and 1,182 white) aged 18–30 years who were free of diabetes and had a fasting plasma glucose (FPG) <126 mg/dl at baseline. Incident diabetes was diagnosed by self-report, diabetes medication use, FPG ≥126 mg/dl, and/or plasma glucose ≥200 mg/dl after a 2-h oral glucose load. Time-dependent interim birth groups were those with zero and those with one or more births with or without gestational diabetes mellitus (GDM), stratified by baseline parity. Complementary log-log models estimated relative hazards of incident diabetes by interim births adjusted for age, race, family history of diabetes, and baseline covariates (FPG, BMI, education, smoking, and physical activity). RESULTS Of 193 incident diabetes cases in 42,782 person-years (4.5 cases/1,000 person-years), 84 (44%) had one or more interim births. Among nulliparas at baseline, incident rates per 1,000 person-years were 3.2 (95% CI 2.4–4.1) for those with no births, 2.9 (1.8 –3.9) for one or more births without GDM, and 18.4 (10.9 –25.9) for one or more births with GDM; adjusted relative hazards (95% CI) were 0.9 (0.6 –1.4) for one or more births without GDM and 3.8 (2.2– 6.6) for one or more births with GDM versus no births. CONCLUSIONS Childbearing did not elevate diabetes incidence among those with normal glucose tolerance during pregnancy (without GDM). GDM conferred the highest risk of developing diabetes independent of family history of diabetes and preconception glycemia and obesity. PMID:17898128

High burden of prediabetes and diabetes in three large cities in South Asia: The Center for Cardio-metabolic Risk Reduction in South Asia (CARRS) Study

PubMed Central

Deepa, Mohan; Grace, Mundu; Binukumar, Bhaskarapillai; Pradeepa, Rajendra; Roopa, Shivashankar; Khan, Hassan M; Fatmi, Zafar; Kadir, Muhammad M.; Naeem, Imran; Ajay, Vamadevan S; Anjana, Ranjit Mohan; Ali, Mohammed K; Prabhakaran, Dorairaj; Tandon, Nikhil; Mohan, Viswanathan; Venkat Narayan, KM

2016-01-01

Aim To estimate the prevalence of, and assess factors associated with, diabetes and prediabetes in three South Asian cities. Methods Using a multi-stage cluster random sample representative of each city, 16,288 subjects aged ≥20 years (Chennai: 6906, Delhi: 5365 and Karachi: 4017) were recruited to the Centre for cArdiometabolic Risk Reduction in South-Asia (CARRS) Study. Fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) were measured in 13720 subjects. Prediabetes was defined as FPG 100-125mg/dl (5.6-6.9 mmol/l) and/or HbA1c 5.7-6.4% (39-46mmol/mol) and diabetes as self-report and/or drug treatment for diabetes and/or FPG ≥126 mg/dl (≥7.0mmol/l) and/or HbA1c ≥6.5% (48mmol/mol). We assessed factors associated with diabetes and prediabetes using polytomous logistic regression models. Results Overall 47.3-73.1% of the population had either diabetes or prediabetes: Chennai 60.7% [95%CI: 59.0-62.4%] (diabetes-22.8% [21.5-24.1%], prediabetes-37.9% [36.1-39.7%]); Delhi 72.7% [70.6-74.9%] (diabetes-25.2% [23.6-26.8%], prediabetes-47.6% [45.6-49.5%]); and Karachi 47.4% [45.7-49.1%]; (diabetes-16.3% [15.2-17.3%], prediabetes-31.1% [29.5-32.8%], respectively). Proportions of self-reported diabetes were 55.1%, 39.0%, and 48.0% in Chennai, Delhi, and Karachi, respectively. City, age, family history of diabetes, generalized obesity, abdominal obesity, body fat, high cholesterol, high triglyceride, and low HDL cholesterol levels were each independently associated with prediabetes, while the same factors plus waist-to-height ratio and hypertension were associated with diabetes. Conclusion Six in ten adults in large South Asian cities have either diabetes or prediabetes. These data call for urgent action to prevent diabetes in South Asia. PMID:26432412

Evaluation of a 12-week lifestyle education intervention with or without partial meal replacement in Thai adults with obesity and metabolic syndrome: a randomised trial.

PubMed

Chaiyasoot, Kusuma; Sarasak, Rungnapha; Pheungruang, Banchamaphon; Dawilai, Suwitcha; Pramyothin, Pornpoj; Boonyasiri, Adhiratha; Supapueng, Orawan; Jassil, Friedrich C; Yamwong, Preyanuj; Batterham, Rachel L

2018-04-25

There have been no studies examining the efficacy of meal replacement (MR) on weight loss and metabolic syndrome (MS) improvement in Southeast Asians. Thus, we undertook a 12-week randomised trial to evaluate the effect of a lifestyle education intervention alone (LEI) or with partial MR (LEI + MR) in obese Thai adults with MS. A total of 110 patients were randomised to receive either LEI or LEI + MR. Both groups received LEI to achieve weight loss. LEI + MR group additionally received two MR daily to replace either breakfast, lunch or dinner. Mean ± SE body mass index of all participants was 34.6 ± 0.6 kg/m 2 , mean ± SE age was 42.5 ± 1.1 years and 83% of patients were female. Both groups were compared for anthropometric and cardiometabolic indices at 12-week. Body weight was also compared at weeks 38 and 64. At 12 weeks, both groups exhibited statistically significant percentage weight loss (%WL) compared to initial weight but greater %WL was observed in LEI + MR compared to LEI, 2.9% vs. 1.5%, respectively (p < 0.05). MS criteria such as waist circumference and blood pressure improved significantly in both groups compared to baseline. However, improvement in fasting plasma glucose (FPG) was only significant in LEI + MR, and more participants with impaired FPG at baseline in LEI + MR (42.9%) than LEI (19%) returned to normal FPG at 12 weeks (p < 0.05). HbA 1c , fasting insulin and HOMA-IR in LEI + MR were significantly lower than with LEI. At the end of the 12-week intervention period, 16% of participants no longer fulfilled MS criteria. A statistically significant weight loss from baseline persisted until 38 weeks but no longer reached statistically significant difference between groups CONCLUSIONS: LEI and LEI + MR were acceptable and led to improvement in weight and MS. LEI + MR group exhibited additional weight reduction and glycemic benefits at 12 weeks.

Combined intervention of swimming plus metformin ameliorates the insulin resistance and impaired lipid metabolism in murine gestational diabetes mellitus

PubMed Central

Wu, Xuefei; Yu, Ting; Wang, Yang; Zhou, Ji; Kong, Derun

2018-01-01

Gestational diabetes mellitus (GDM) has short- and long- term influence on pregnant women and fetus. Swimming, as an aerobic exercise, can effectively improve the blood glucose level in GDM, but the effect of mild swimming alone was not very substantial. Metformin, as an oral antidiabetic drug, has obvious hypoglycemic effect, and is economic also, but the long-term effect on pregnant women and fetus has not been completely clear. We hypothesize that combined intervention of mild swimming and low dose of metformin, may effectively reduce blood glucose, improve the pregnancy outcomes in GDM dams, but simultaneously avoiding the adverse effects caused by overdose of drug and impotence of mild swimming. The streptozotocin was used to stimulate C57BL/6J mice to develop GDM, by which serum glucose, TC, TG, LDL-C were increased significantly, meanwhile HDL-C was decreased significantly in the GDM control (DC) group compared with the normal control group. Swimming or metformin intervention slightly or moderately improves hyperglycemia, insulin sensitivity and lipid metabolism both in liver and skeletal muscle from GDM mice, while combined therapy of swimming plus metformin markedly ameliorated hyperglycemia (FPG, decreased by 22.2–59.5% from G10 to G18 versus DC group), insulin sensitivity (2.1 and 2.8 fold increase, respectively, in AKT activity versus DC group) and de novo lipogenesis (3.2 and 7.0 fold decrease, respectively, in ACC activity, and 1.94 and 5.1 fold decrease, respectively, in SREBP2 level, versus DC group) both in liver and skeletal muscle from GDM mice. We conclude that the combined intervention by metformin plus swimming may be more effective than single action to ameliorate glucose and lipid metabolism via improving insulin sensitivity in GDM mice. PMID:29677194

The favorable effects of garlic intake on metabolic profiles, hs-CRP, biomarkers of oxidative stress and pregnancy outcomes in pregnant women at risk for pre-eclampsia: randomized, double-blind, placebo-controlled trial.

PubMed

Aalami-Harandi, Rezvan; Karamali, Maryam; Asemi, Zatollah

2015-01-01

This study was performed to determine the favorable effects of garlic on metabolic status and pregnancy outcomes among pregnant women at risk for pre-eclampsia. This randomized, double-blind, placebo-controlled trial was conducted among 44 pregnant women, primigravida, aged 18-40 years old at 27 weeks' gestation with positive roll-over test. Participants were randomly assigned to receive either one garlic tablet (equal to 400 mg garlic and 1 mg allicin) (n = 22) or placebo (n = 22) once daily for 9 weeks. Fasting blood samples were taken at baseline and after 9 weeks' intervention to measure metabolic profiles and biomarkers of oxidative stress. Administration of garlic compared with the placebo resulted in decreased levels of serum high sensitivity C-reactive protein (hs-CRP) (-1425.90 versus 1360.50 ng/mL, p = 0.01) and increased plasma glutathione (GSH) (+98.10 versus. -49.87 µmol/l, p = 0.03). A trend toward a significant effect of garlic intake on reducing fasting plasma glucose (FPG) (p = 0.07), insulin (p = 0.09) and increasing quantitative insulin sensitivity check (QUICKI) (p = 0.05) was also observed. Consumption of garlic for 9 weeks among pregnant women at risk for pre-eclampsia led to decreased hs-CRP and increased GSH, but did not affect lipid profiles, total antioxidant capacity (TAC) and pregnancy outcomes.

Comparison of repaglinide and metformin monotherapy as an initial therapy in Chinese patients with newly diagnosed type 2 diabetes mellitus.

PubMed

Fang, Fu-Sheng; Gong, Yan-Ping; Li, Chun-Lin; Li, Jian; Tian, Hui; Huang, Wei; Wang, Liang-Chen; Li, Lin

2014-06-01

We aimed to compare the effect of repaglinide and metformin monotherapy as an initial therapy in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). In this 15-week, open-labelled, parallel-controlled, randomised study, 60 Chinese drug-naive patients with newly diagnosed T2DM were randomised (2:1) to receive repaglinide or metformin monotherapy. Primary endpoint was change in HbA1c from baseline to the end of the trial. Secondary endpoints included changes in glycaemic variability, insulin sensitivity and β-cell function. Patients in both repaglinide and metformin groups achieved significant reductions in HbA1c (-1.8 ± 1.5 vs -1.6 ± 1.5%), FPG (fasting blood glucose) (-1.7 ± 1.7 vs -2.1 ± 1.7  mmol/l) and 2-h PPG (post-prandial glucose) (-3.8 ± 3.1 vs -3.8 ± 3.6  mmol/l), with no statistical differences between the groups. Glycaemic variability, glucose infusion rate and β-cell function were all significantly improved from baseline in the two groups (all P<0.05), without any statistical differences in the improvement between the groups. Repaglinide and metformin achieved comparable efficacy in improving glycaemic control, reducing glycaemic variability, enhancing insulin sensitivity and ameliorating β-cell function. Therefore, repaglinide is an optional agent for initial therapy in Chinese patients with newly diagnosed T2DM. © 2014 European Society of Endocrinology.

[Mechanisms and efficacy of SGLT2 inhibitors].

PubMed

Shiba, Teruo

2015-03-01

SGLT2 is a low affinity, high capacity glucose co-transporter, almost exclusively expressed in the kidney cortex. Inhibition of SGLT2 has been shown to increase the daily 50g or more urinary glucose excretion, as compared to placebo, leading to a reduction in blood glucose levels and indicated only for the treatment of type 2 diabetes. In Japan 6 species of SGLT2 inhibitors have already been sold and reported to results in a decrease of FPG by 14.4 to 45.8 (mg/dL), in a reduction of HbA1c by 0.35 to 1.24% and in loss of body weight by 1.29 to 2.50(kg). There is less effect of the SGLT2 inhibitor in diabetic subjects with renal impairment and the reduction in HbA1c and FPG will be approximately half of the average in those with 30 ≤ eGFR ≤ 59. The position of SGLT2 inhibitors would be considered as the drug administered in combination or add-on therapy when the young obese type 2 diabetics without renal impairment has not yet reached to the glycemic target with other drugs although in AACE consensus statement of 2013, it has been shelved for inexperienced use with respect to the positioning of the SGLT2 inhibitors.

Metabolic Derangement in Acute and Chronic Liver Disorders.

PubMed

Bajaj, Sarita; Kashyap, Richi; Srivastava, Anubha; Singh, Smriti

2017-01-01

This study aims to assess glycemic and lipid derangement in acute and chronic liver disorders. A cross-sectional study was conducted on 104 patients diagnosed with acute or chronic liver disorder. Acute liver disease (ALD) patients were 40 and chronic liver disease (CLD) patients were 64. The mean value of fasting plasma glucose (FPG) in patients with ALD was 91.8 ± 5.4 mg/dl and in CLD was 115.7 ± 17.9 mg/dl, the difference was significant. The mean value of A1c was 4.3 ± 0.6 in ALD and 6.1 ± 0.8 in CLD, the difference was significant. In patients with CLD mean cholesterol was higher 177.4 ± 28.8 mg/dl when compared to ALD 140 ± 35.1 mg/dl, but the difference was not significant. ALD patients' high-density lipoprotein (HDL) was 50.4 ± 5.1 mg/dl, and in CLD patients, HDL was 44.4 ± 6.1 mg/dl. In CLD mean triglyceride (T) was 148.9 ± 6.4 mg/dl while in ALD T was 134.8 ± 14.2 mg/dl, the difference was significant. CLD is associated with glycemic derangement demonstrated by deranged FPG and A1c. In patients of ALD, no metabolic derangement was observed.

Evaluation of imazethapyr-induced DNA oxidative damage by alkaline Endo III- and Fpg-modified single-cell gel electrophoresis assay in Hypsiboas pulchellus tadpoles (Anura, Hylidae).

PubMed

Pérez-Iglesias, Juan Manuel; Ruiz de Arcaute, Celeste; Natale, Guillermo S; Soloneski, S; Larramendy, Marcelo L

2017-08-01

Imazethapyr (IMZT) is a selective postemergent herbicide with residual action. Available data analyzing its effects in aquatic vertebrates are scarce. In previous studies, we demonstrated that IMZT induces lesions into the DNA of Hypsiboas pulchellus tadpoles using the single-cell gel electrophoresis (SCGE) assay as a biomarker for genotoxicity. Currently, this assay can be modified by including incubation with lesion-specific endonucleases, e.g., endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg), which detect oxidized pyrimidine and purine bases, respectively. The aim of this study was to evaluate the role of oxidative stress in the genotoxic damage in circulating blood cells of H. pulchellus tadpoles exposed to the IMZT-based Pivot H ® formulation (10.59% IMZT) at a concentration equivalent to 25% of the LC 50 (96h) value (0.39mg/L IMZT) during 48 and 96h. Our results demonstrate that the herbicide induces oxidative DNA damage on H. pulchellus tadpoles at purines bases but not at pyrimidines. Our findings represent the first evidence of oxidative damage caused by IMZT on anuran DNA using the alkaline restriction enzyme-modified SCGE assay. Copyright © 2017 Elsevier Inc. All rights reserved.

Body mass index, metabolic factors, and striatal activation during stressful and neutral-relaxing states: an FMRI study.

PubMed

Jastreboff, Ania M; Potenza, Marc N; Lacadie, Cheryl; Hong, Kwangik A; Sherwin, Robert S; Sinha, Rajita

2011-02-01

Stress is associated with alterations in neural motivational-reward pathways in the ventral striatum (VS), hormonal/metabolic changes, and weight increases. The relationship between these different factors is not well understood. We hypothesized that body mass index (BMI) status and hormonal/metabolic factors would be associated with VS activation. We used functional magnetic resonance imaging (fMRI) to compare brain responses of overweight and obese (OW/OB: BMI ≥ 25 kg/m(2): N=27) individuals with normal weight (NW: BMI<18.5-24.9 kg/m(2): N=21) individuals during exposure to personalized stress, alcohol cue, and neutral-relaxing situations using a validated, autobiographical, script-driven, guided-imagery paradigm. Metabolic factors, including fasting plasma glucose (FPG), insulin, and leptin, were examined for their association with VS activation. Consistent with previous studies, stress and alcohol cue exposure each increased activity in cortico-limbic regions. Compared with NW individuals, OW/OB individuals showed greater VS activation in the neutral-relaxing and stress conditions. FPG was correlated with VS activation. Significant associations between VS activation and metabolic factors during stress and relaxation suggest the involvement of metabolic factors in striatal dysfunction in OW/OB individuals. This relationship may contribute to non-homeostatic feeding in obesity.

Body Mass Index, Metabolic Factors, and Striatal Activation During Stressful and Neutral-Relaxing States: An fMRI Study

PubMed Central

Jastreboff, Ania M; Potenza, Marc N; Lacadie, Cheryl; Hong, Kwangik A; Sherwin, Robert S; Sinha, Rajita

2011-01-01

Stress is associated with alterations in neural motivational-reward pathways in the ventral striatum (VS), hormonal/metabolic changes, and weight increases. The relationship between these different factors is not well understood. We hypothesized that body mass index (BMI) status and hormonal/metabolic factors would be associated with VS activation. We used functional magnetic resonance imaging (fMRI) to compare brain responses of overweight and obese (OW/OB: BMI ⩾25 kg/m2: N=27) individuals with normal weight (NW: BMI<18.5–24.9 kg/m2: N=21) individuals during exposure to personalized stress, alcohol cue, and neutral-relaxing situations using a validated, autobiographical, script-driven, guided-imagery paradigm. Metabolic factors, including fasting plasma glucose (FPG), insulin, and leptin, were examined for their association with VS activation. Consistent with previous studies, stress and alcohol cue exposure each increased activity in cortico-limbic regions. Compared with NW individuals, OW/OB individuals showed greater VS activation in the neutral-relaxing and stress conditions. FPG was correlated with VS activation. Significant associations between VS activation and metabolic factors during stress and relaxation suggest the involvement of metabolic factors in striatal dysfunction in OW/OB individuals. This relationship may contribute to non-homeostatic feeding in obesity. PMID:21048702

Hypoglycemic and antioxidant effects of honey supplementation in streptozotocin-induced diabetic rats.

PubMed

Erejuwa, O O; Omotayo, Erejuwa O; Gurtu, Sunil; Sulaiman, Siti Amrah; Ab Wahab, Mohd Suhaimi; Sirajudeen, K N S; Salleh, Md Salzihan Md

2010-01-01

Oxidative stress plays a crucial role in the development of diabetic complications. The aims of this study were to investigate whether honey could reduce hyperglycemia and ameliorate oxidative stress in kidneys of streptozotocin-induced diabetic rats. Diabetes was induced by a single dose of STZ (60 mg/kg; i. p.). Diabetic rats were randomly grouped and administered distilled water (0.5 mL/day) and honey (0.2 g/kg/day, 1.2 g/kg/day and 2.4 g/kg/day) by oral gavage for four weeks. Each group consisted of six rats. Total antioxidant status (TAS), activities of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST) were significantly reduced, while superoxide dismutase (SOD) activity was up-regulated in kidneys of diabetic rats. Lipid peroxidation (TBARS) and fasting plasma glucose (FPG) were significantly elevated while body weight was reduced in diabetic rats. Honey significantly increased body weight, TAS, activities of CAT, GPx, GR, and GST in diabetic rats. It significantly restored SOD activity, and reduced FPG and TBARS levels in diabetic rats. Histopathological examinations of the kidneys revealed that mesangial matrix expansion and thickening of glomerular basement membrane were reduced in the honey-treated diabetic rats. Honey exerts a hypoglycemic effect and ameliorates oxidative stress in kidneys of streptozotocin-induced diabetic rats.

Psoralen-induced DNA adducts are substrates for the base excision repair pathway in human cells

PubMed Central

Couvé-Privat, Sophie; Macé, Gaëtane; Saparbaev, Murat K.

2007-01-01

Interstrand cross-link (ICL) is a covalent modification of both strands of DNA, which prevents DNA strand separation during transcription and replication. Upon photoactivation 8-methoxypsoralen (8-MOP+UVA) alkylates both strands of DNA duplex at the 5,6-double bond of thymidines, generating monoadducts (MAs) and ICLs. It was thought that bulky DNA lesions such as MAs are eliminated only in the nucleotide excision repair pathway. Instead, non-bulky DNA lesions are substrates for DNA glycosylases and AP endonucleases which initiate the base excision repair (BER) pathway. Here we examined whether BER might be involved in the removal of psoralen–DNA photoadducts. The results show that in human cells DNA glycosylase NEIL1 excises the MAs in duplex DNA, subsequently the apurinic/apyrimidinic endonuclease 1, APE1, removes the 3′-phosphate residue at single-strand break generated by NEIL1. The apparent kinetic parameters suggest that NEIL1 excises MAs with high efficiency. Consistent with these results HeLa cells lacking APE1 and/or NEIL1 become hypersensitive to 8-MOP+UVA exposure. Furthermore, we demonstrate that bacterial homologues of NEIL1, the Fpg and Nei proteins, also excise MAs. New substrate specificity of the Fpg/Nei protein family provides an alternative repair pathway for ICLs and bulky DNA damage. PMID:17715144

Task shifting to non-physician clinicians for integrated management of hypertension and diabetes in rural Cameroon: a programme assessment at two years

PubMed Central

2010-01-01

Background The burden of non-communicable chronic diseases, such as hypertension and diabetes, increases in sub-Saharan Africa. However, the majority of the rural population does still not have access to adequate care. The objective of this study is to examine the effectiveness of integrating care for hypertension and type 2 diabetes by task shifting to non-physician clinician (NPC) facilities in eight rural health districts in Cameroon. Methods Of the 75 NPC facilities in the area, 69 (87%) received basic equipment and training in hypertension and diabetes care. Effectiveness was assessed after two years on status of equipment, knowledge among trained NPCs, number of newly detected patients, retention of patients under care, treatment cost to patients and changes in blood pressure (BP) and fasting plasma glucose (FPG) among treated patients. Results Two years into the programme, of 54 facilities (78%) available for re-assessment, all possessed a functional sphygmomanometer and stethoscope (65% at baseline); 96% stocked antihypertensive drugs (27% at baseline); 70% possessed a functional glucose meter and 72% stocked oral anti-diabetics (15% and 12% at baseline). NPCs' performance on multiple-choice questions of the knowledge-test was significantly improved. During a period of two years, trained NPCs initiated treatment for 796 patients with hypertension and/or diabetes. The retention of treated patients at one year was 18.1%. Hypertensive and diabetic patients paid a median monthly amount of 1.4 and 0.7 Euro respectively for their medication. Among hypertensive patients with ≥ 2 documented visits (n = 493), systolic BP decreased by 22.8 mmHg (95% CI: -20.6 to -24.9; p < 0.0001) and diastolic BP by 12.4 mmHg (-10.9 to -13.9; p < 0.0001). Among diabetic patients (n = 79) FPG decreased by 3.4 mmol/l (-2.3 to -4.5; p < 0.001). Conclusions The integration of hypertension and diabetes into primary health care of NPC facilities in rural Cameroon was feasible in terms of equipment and training, accessible in terms of treatment cost and showed promising BP- and FPG-trends. However, low case-detection rates per NPC and a very high attrition among patients enrolled into care, limited the effectiveness of the programme. PMID:21144064

Difference between observed and predicted glycated hemoglobin at baseline and treatment response to vildagliptin-based dual oral therapy in patients with type 2 diabetes.

PubMed

Wang, Jun-Sing; Hung, Yi-Jen; Lu, Yung-Chuan; Tsai, Cheng-Lin; Yang, Wei-Shiung; Lee, Ting-I; Hsiao, Ya-Chun; Sheu, Wayne Huey-Herng

2018-04-01

We aimed to investigate the association of difference between observed and predicted glycated hemoglobin (dopHbA1c) and HbA1c reduction after vildagliptin-based oral therapy in patients with type 2 diabetes (T2D). This was a prospective observational study. Adults ≥ 20 years old with T2D and HbA1c ≧7% treated with oral anti-diabetic drugs (OADs) were eligible if their OADs were shifted to vildagliptin-based dual oral therapy. Fasting plasma glucose (FPG) and HbA1c were recorded at baseline, week 12, and week 24. To determine baseline dopHbA1c, a predicted HbA1c was calculated by inserting baseline FPG into a regression equation (HbA1c = FPG ∗ 0.0225 + 4.3806) developed from linear relationship between HbA1c and FPG in an independent cohort of 3239 outpatients with T2D (dopHbA1c = observed HbA1c - predicted HbA1c). Patients were assigned to low (≦0) or high (>0) dopHbA1c group according to their baseline dopHbA1c levels. The study endpoint was changes from baseline to week 24 in HbA1c levels. A total of 1224 patients were enrolled. Patients with a dopHbA1c >0 had a greater HbA1c reduction after vildagliptin-based dual oral therapy than those with a dopHbA1c ≦0 (-1.5 ± 2.0 vs. -0.4 ± 1.0%, p < 0.001). Baseline dopHbA1c was positively associated with HbA1c reduction from baseline to week 24 (β coefficient 0.883, 95% CI 0.811 to 0.955, p < 0.001), and the association remained significant after adjustment for confounders. In T2D patients with an HbA1c ≧7%, a higher baseline dopHbA1c was associated with a greater HbA1c reduction after shifting to vildagliptin-based dual oral therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Improvement of Insulin Secretion and Pancreatic β-cell Function in Streptozotocin-induced Diabetic Rats Treated with Aloe vera Extract

PubMed Central

Noor, Ayesha; Gunasekaran, S.; Vijayalakshmi, M. A.

2017-01-01

Background: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. Plant extracts and their products are being used as an alternative system of medicine for the treatment of diabetes. Aloe vera has been traditionally used to treat several diseases and it exhibits antioxidant, anti-inflammatory, and wound-healing effects. Streptozotocin (STZ)-induced Wistar diabetic rats were used in this study to understand the potential protective effect of A. vera extract on the pancreatic islets. Objective: The aim of the present study was to evaluate the A. vera extract on improvement of insulin secretion and pancreatic β-cell function by morphometric analysis of pancreatic islets in STZ-induced diabetic Wistar rats. Materials and Methods: After acclimatization, male Wistar rats, maintained as per the Committee for the Purpose of Control and Supervision of Experiments on Animals guidelines, were randomly divided into four groups of six rats each. Fasting plasma glucose and insulin levels were assessed. The effect of A. vera extract in STZ-induced diabetic rats on the pancreatic islets by morphometric analysis was evaluated. Results: Oral administration of A. vera extract (300 mg/kg) daily to diabetic rats for 3 weeks showed restoration of blood glucose levels to normal levels with a concomitant increase in insulin levels upon feeding with A. vera extract in STZ-induced diabetic rats. Morphometric analysis of pancreatic sections revealed quantitative and qualitative gain in terms of number, diameter, volume, and area of the pancreatic islets of diabetic rats treated with A. vera extract when compared to the untreated diabetic rats. Conclusion: A. vera extract exerts antidiabetic effects by improving insulin secretion and pancreatic β-cell function by restoring pancreatic islet mass in STZ-induced diabetic Wistar rats. SUMMARY Fasting plasma glucose (FPG) and insulin levels were restored to normal levels in diabetic rats treated with Aloe vera extractIslets of pancreas were qualitatively and quantitatively restored to normalcy leading to restoration of FPG and insulin levels of diabetic rats treated with Aloe vera extractMorphometric analysis of pancreatic sections revealed quantitative and qualitative gain in terms of number, diameter, volume, and area of the pancreatic islets of diabetic rats treated with Aloe vera extract when compared to the untreated diabetic rats. Abbreviations Used: A. vera, FPG: Fasting plasma glucose, STZ: Streptozotocin, BW: Body weight PMID:29333050

Development of a Smartphone-Enabled Hypertension and Diabetes Mellitus Management Package to Facilitate Evidence-Based Care Delivery in Primary Healthcare Facilities in India: The mPower Heart Project.

PubMed

Ajay, Vamadevan S; Jindal, Devraj; Roy, Ambuj; Venugopal, Vidya; Sharma, Rakshit; Pawar, Abha; Kinra, Sanjay; Tandon, Nikhil; Prabhakaran, Dorairaj

2016-12-21

The high burden of undetected and undertreated hypertension and diabetes mellitus is a major health challenge worldwide. The mPower Heart Project aimed to develop and test a feasible and scalable intervention for hypertension and diabetes mellitus by task-sharing with the use of a mobile phone-based clinical decision support system at Community Health Centers in Himachal Pradesh, India. The development of the intervention and mobile phone-based clinical decision support system was carried out using mixed methods in five Community Health Centers. The intervention was subsequently evaluated using pre-post evaluation design. During intervention, a nurse care coordinator screened, examined, and entered patient parameters into mobile phone-based clinical decision support system to generate a prescription, which was vetted by a physician. The change in systolic blood pressure, diastolic blood pressure, and fasting plasma glucose (FPG) over 18 months of intervention was quantified using generalized estimating equations models. During intervention, 6797 participants were enrolled. Six thousand sixteen participants had hypertension (mean systolic blood pressure: 146.1 mm Hg, 95% CI: 145.7, 146.5; diastolic blood pressure: 89.52 mm Hg, 95% CI: 89.33, 89.72), of which 3152 (52%) subjects were newly detected. Similarly, 1516 participants had diabetes mellitus (mean FPG: 177.9 mg/dL, 95% CI: 175.8, 180.0), of which 450 (30%) subjects were newly detected. The changes in systolic blood pressure, diastolic blood pressure, and FPG observed at 18 months of follow-up were -14.6 mm Hg (95% CI: -15.3, -13.8), -7.6 mm Hg (CI: -8.0, -7.2), and -50.0 mg/dL (95% CI: -54.6, -45.5), respectively, and were statistically significant even after adjusting for age, sex, and Community Health Center. A nurse-facilitated, mobile phone-based clinical decision support system-enabled intervention in primary care was associated with improvements in blood pressure and blood glucose control and has the potential to scale-up in resource poor settings. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01794052. Clinical Trial Registry-India: CTRI/2013/02/003412. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Task shifting to non-physician clinicians for integrated management of hypertension and diabetes in rural Cameroon: a programme assessment at two years.

PubMed

Labhardt, Niklaus D; Balo, Jean-Richard; Ndam, Mama; Grimm, Jean-Jacques; Manga, Engelbert

2010-12-14

The burden of non-communicable chronic diseases, such as hypertension and diabetes, increases in sub-Saharan Africa. However, the majority of the rural population does still not have access to adequate care. The objective of this study is to examine the effectiveness of integrating care for hypertension and type 2 diabetes by task shifting to non-physician clinician (NPC) facilities in eight rural health districts in Cameroon. Of the 75 NPC facilities in the area, 69 (87%) received basic equipment and training in hypertension and diabetes care. Effectiveness was assessed after two years on status of equipment, knowledge among trained NPCs, number of newly detected patients, retention of patients under care, treatment cost to patients and changes in blood pressure (BP) and fasting plasma glucose (FPG) among treated patients. Two years into the programme, of 54 facilities (78%) available for re-assessment, all possessed a functional sphygmomanometer and stethoscope (65% at baseline); 96% stocked antihypertensive drugs (27% at baseline); 70% possessed a functional glucose meter and 72% stocked oral anti-diabetics (15% and 12% at baseline). NPCs' performance on multiple-choice questions of the knowledge-test was significantly improved. During a period of two years, trained NPCs initiated treatment for 796 patients with hypertension and/or diabetes. The retention of treated patients at one year was 18.1%. Hypertensive and diabetic patients paid a median monthly amount of 1.4 and 0.7 Euro respectively for their medication. Among hypertensive patients with ≥ 2 documented visits (n = 493), systolic BP decreased by 22.8 mmHg (95% CI: -20.6 to -24.9; p < 0.0001) and diastolic BP by 12.4 mmHg (-10.9 to -13.9; p < 0.0001). Among diabetic patients (n = 79) FPG decreased by 3.4 mmol/l (-2.3 to -4.5; p < 0.001). The integration of hypertension and diabetes into primary health care of NPC facilities in rural Cameroon was feasible in terms of equipment and training, accessible in terms of treatment cost and showed promising BP- and FPG-trends. However, low case-detection rates per NPC and a very high attrition among patients enrolled into care, limited the effectiveness of the programme.

Comparison of the effects of Roux-en-Y gastrojejunostomy and LRYGB with small stomach pouch on type 2 diabetes mellitus in patients with BMI<35 kg/m(2).

PubMed

Yi, Bo; Jiang, Juan; Zhu, Liyong; Li, Pengzhou; Im, Ibrahim; Zhu, Shaihong

2015-01-01

Based on distinct epidemiologic features of Chinese type 2 diabetes mellitus (T2DM) patients, who tend to have abdominal fat deposition, but with normal or mildly overweight epidemiologic features, our center initially had treated T2DM with body mass index (BMI)<35 kg/m² by performing laparoscopic Roux-en-Y gastrojejunostomy since 2008. This procedure is successful in treating abnormal glucose metabolism but not in improving abdominal visceral obesity. However, since 2011, laparoscopic Roux-Y gastric bypass (LRYGB) with a small stomach pouch has been performed at our center, with prominent resolution of abdominal visceral obesity and lower incidences of postoperative complications. The purpose of the present study was to formally compare these different procedures. From 2011 to 2013, 60 patients who met the NIH criteria were recruited and randomly assigned to undergo either laparoscopic Roux-en-Y gastrojejunostomy (n = 30) or LRYGB with a small stomach pouch (n = 30). All of the patients were followed for 12 months, and pre- and postoperative changes in BMI, waist circumference, fasting plasma glucose (FPG), postprandial plasma glucose (PBG), glycated hemoglobin (HbA1c), homoeostatic model assessment (HOMA-IR), the body fat rate and major complications were recorded. Both procedures were successful in reducing HbA1c, FPG, and PBG levels and HOMA-IR scores. However, LRYGB with a small stomach pouch resulted in a greater reduction in FPG, PBG, and HbA1c levels, and HOMA-IR scores compared with Roux-en-Y gastrojejunostomy. In addition, the reductions in BMI, body fat content, waist circumference, and the incidence of postoperative marginal ulcers in the small-stomach-pouch LRYGB were significant. Both procedures are effective treatments for T2DM patients with BMI<35 kg/m². However, the advantages of resolved abnormal glucose metabolism and abdominal visceral obesity and decreased incidences of surgical complications are more obvious for LRYGB with a small gastric pouch. Potentially, LRYGB with a small gastric pouch is more suitable for Chinese diabetic patients with BMI <35 kg/m². Copyright © 2015 American Society for Bariatric Surgery. All rights reserved.

[Comparative study on oral candidal infection in individuals with diabetes mellitus and impaired glucose regulation].

PubMed

Huang, Jing-hua; Liu, Yang; Liu, Hong-wei

2012-06-01

To investigate the positive rate, infection rate and bearing rate of salivary candida in patients with type 2 diabetes mellitus (DM), individuals with impaired glucose regulation (IGR) and individuals with normal glucose tolerance (NGT) and their predisposing factors. Questionnaire was given to 145 patients with DM, 142 individuals with IGR and 149 NGT individuals. Oral examination was carried out, and fasting plasma glucose (FPG) level and plasma glucose level of 2 hours post glucose-load (PG2h), resting salivary flow, salivary pH value were tested. Salivary candida was cultured. In DM, IGR and NGT groups, the positive rates of salivary candida were 21.4% (31/145), 7.0% (10/142), 4.7% (7/149) respectively, the infection rates were 7.6% (11/145), 1.4% (2/142), 1.3% (2/149) respectively, and the bearing rates of salivary candida were 13.8% (20/145), 5.6% (8/142), 3.4% (5/149) respectively. The candida positive rate, candida infection rate in DM group were higher than those of IGR and NGT groups respectively (P < 0.05). There were no significant differences in the candida positive rate, infection rate and bearing rate between IGR and NGT groups (P > 0.05). Resting salivary flow in DM [(1.30 ± 1.20) ml/10 min] and IGR [(1.40 ± 1.17) ml/10 min]groups were lower than that in NGT group [(1.93 ± 1.66) ml/10 min], salivary pH values in DM (7.11 ± 0.56) and IGR (7.05 ± 0.48) groups were lower than that in NGT group (7.38 ± 0.48) (P < 0.05), while FPG value in DM [(7.68 ± 2.75) mmol/L] and IGR [(5.67 ± 0.73) mmol/L] groups were respectively higher tham that in NGT group [(4.99 ± 0.44) mmol/L], P < 0.05. The infection rate of salivary candida was influenced to some degree by age, FPG level and bearing denture (OR value = 1.106, 1.258, 3.166). The patients with DM were more subjected to bearing or infection of candida than individuals with IGR and NGT. To control the plasma glucose level will help to decrease the positive rate and infection rate of oral candida.

Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients.

PubMed

Anan, Futoshi; Masaki, Takayuki; Umeno, Yoshikazu; Iwao, Tetsu; Yonemochi, Hidetoshi; Eshima, Nobuoki; Saikawa, Tetsunori; Yoshimatsu, Hironobu

2007-09-01

The elevated level of high-sensitivity C-reactive protein (HSCRP) and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the HSCRP correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 46 Japanese patients with type 2 diabetes and high HSCRP group (0.3-1.0 mg/dl, age: 57+/-5 years, mean+/-s.d.) and a control group of 55 age-matched patients with low HSCRP group (<0.3 mg/dl, 57+/-6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method and was used as an index of atherosclerosis. The body mass index (BMI) values (P<0.05) and waist circumferences (P<0.0005) and the waist-to-hip ratios (P<0.05) were higher in the high HSCRP group than in the low HSCRP group. The BaPWV was higher in the high HSCRP group than in the low HSCRP group (P<0.0001). Fasting plasma glucose (FPG; P<0.005) and insulin concentrations (P<0.0001), and the homeostasis model assessment (HOMA) index (P<0.0001), were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by BaPWV and HOMA index. Our results indicate that the elevated level of HSCRP in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and HOMA index are independent predictors of HSCRP.

Efficacy and safety of triple therapy with dapagliflozin add-on to saxagliptin plus metformin over 52 weeks in patients with type 2 diabetes.

PubMed

Mathieu, C; Herrera Marmolejo, M; González González, J G; Hansen, L; Chen, H; Johnsson, E; Garcia-Sanchez, R; Iqbal, N

2016-11-01

We previously reported that dapagliflozin versus placebo as add-on to saxagliptin plus metformin resulted in greater reductions in glycated haemoglobin (A1C), fasting plasma glucose (FPG) and body weight (BW) after 24 weeks of treatment in patients with type 2 diabetes (T2D). Here we report results after 52 weeks of treatment. Patients stabilized on open-label metformin and saxagliptin 5 mg/day for 8-16 weeks were randomized to placebo or dapagliflozin 10 mg/day plus open-label saxagliptin plus metformin for 52 weeks. Changes from baseline to week 52 were greater with dapagliflozin versus placebo in A1C (-0.74% vs. 0.07%), FPG (-27 vs. 10 mg/dL) and BW (-2.1 vs. -0.4 kg). More patients achieved A1C <7% with dapagliflozin (29.4%) versus placebo (12.6%). Adverse events were similar with dapagliflozin (66%) and placebo (71%), and hypoglycaemia was rare (≤2%). Genital infections occurred more often with dapagliflozin (6%) than with placebo (1%); frequency of urinary tract infections was similar between the two groups (9% vs. 10%). Triple therapy with dapagliflozin add-on to saxagliptin plus metformin is a durable, effective and well-tolerated intervention for the treatment of T2D. © 2016 John Wiley & Sons Ltd.

The logarithmic and power law behaviors of the accelerating, turbulent thermal boundary layer

NASA Astrophysics Data System (ADS)

Castillo, Luciano; Hussain, Fazle

2017-02-01

Direct numerical simulation of spatially evolving thermal turbulent boundary layers with strong favorable pressure gradient (FPG) shows that the thermal fluctuation intensity, θ' + and the Reynolds shear stress, u'v'¯+ exhibit a logarithmic behavior spanning the meso-layer (e.g., 50 ≤y+≤170 ). However, the mean thermal profile is not logarithmic even in the zero pressure gradient (ZPG) region; instead, it follows a power law. The maxima of u' 2 ¯+ and v'θ'¯+ change little with the strength of acceleration, while v'+, w'+, and u'v'¯+ continue to decay in the flow direction. Furthermore, θ'+ and u'θ'¯+ surprisingly experience changes from constants in ZPG to sharp rises in the FPG region. Such behavior appears to be due to squashing of the streaks which decreases the streak flank angle below the critical value for "transient growth" generation of streamwise vortices, shutting down production [W. Schoppa and F. Hussain, "Coherent structure generation near-wall turbulence," J. Fluid Mech. 453, 57-108 (2002)]. The streamwise vortices near the wall, although shrink because of stretching, simultaneously, also become weaker as the structures are progressively pushed farther down to the more viscous region near the wall. While the vortical structures decay rapidly in accelerating flows, the thermal field does not—nullifying the myth that both the thermal and velocity fields are similar.

Socioeconomic Status, Energy Cost, and Nutrient Content of Supermarket Food Purchases

PubMed Central

Appelhans, Bradley M.; Milliron, Brandy-Joe; Woolf, Kathleen; Johnson, Tricia J.; Pagoto, Sherry L.; Schneider, Kristin L.; Whited, Matthew C.; Ventrelle, Jennifer C.

2013-01-01

Background The relative affordability of energy-dense versus nutrient-rich foods may promote socioeconomic disparities in dietary quality and obesity. Although supermarkets are the largest food source in the American diet, the associations between SES and the cost and nutrient content of freely chosen food purchases have not been described. Purpose To investigate relationships of SES with the energy cost ($/1000 kcal) and nutrient content of freely chosen supermarket purchases. Methods Supermarket shoppers (n=69) were recruited at a Phoenix AZ supermarket in 2009. The energy cost and nutrient content of participants’ purchases were calculated from photographs of food packaging and nutrition labels using dietary analysis software. Data were analyzed in 2010–2011. Results Two SES indicators, education and household income as a percentage of the federal poverty guideline (FPG), were associated with the energy cost of purchased foods. Adjusting for covariates, the amount spent on 1000 kcal of food was $0.26 greater for every multiple of the FPG, and those with a baccalaureate or postbaccalaureate degree spent an additional $1.05 for every 1000 kcal of food compared to those with no college education. Lower energy cost was associated with higher total fat and less protein, dietary fiber, and vegetables per 1000 kcal purchased. Conclusions Low-SES supermarket shoppers purchase calories in inexpensive forms that are higher in fat and less nutrient-rich. PMID:22424253

Socioeconomic status, energy cost, and nutrient content of supermarket food purchases.

PubMed

Appelhans, Bradley M; Milliron, Brandy-Joe; Woolf, Kathleen; Johnson, Tricia J; Pagoto, Sherry L; Schneider, Kristin L; Whited, Matthew C; Ventrelle, Jennifer C

2012-04-01

The relative affordability of energy-dense versus nutrient-rich foods may promote socioeconomic disparities in dietary quality and obesity. Although supermarkets are the largest food source in the American diet, the associations between SES and the cost and nutrient content of freely chosen food purchases have not been described. To investigate relationships of SES with the energy cost ($/1000 kcal) and nutrient content of freely chosen supermarket purchases. Supermarket shoppers (n=69) were recruited at a Phoenix AZ supermarket in 2009. The energy cost and nutrient content of participants' purchases were calculated from photographs of food packaging and nutrition labels using dietary analysis software. Data were analyzed in 2010-2011. Two SES indicators, education and household income as a percentage of the federal poverty guideline (FPG), were associated with the energy cost of purchased foods. Adjusting for covariates, the amount spent on 1000 kcal of food was $0.26 greater for every multiple of the FPG, and those with a baccalaureate or postbaccalaureate degree spent an additional $1.05 for every 1000 kcal of food compared to those with no college education. Lower energy cost was associated with higher total fat and less protein, dietary fiber, and vegetables per 1000 kcal purchased. Low-SES supermarket shoppers purchase calories in inexpensive forms that are higher in fat and less nutrient-rich. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Effects of Urtica dioica supplementation on blood lipids, hepatic enzymes and nitric oxide levels in type 2 diabetic patients: A double blind, randomized clinical trial.

PubMed

Amiri Behzadi, Alidad; Kalalian-Moghaddam, Hamid; Ahmadi, Amir Hossein

2016-01-01

Oxidative stress plays an important role in the development of diabetic complications including metabolic abnormality-induced diabetic micro-vascular and macro-vascular complications. Urtica dioica L. ( U. dioica ) has been traditionally used in Iranian medicine as an herbal remedy for hypoglycemic or due to its anti-inflammatory properties. The aim of the present study was to evaluate the effects of hydro-alcoholic extract of U. dioica on blood lipids, hepatic enzymes and nitric oxide levels in patients with type 2 diabetes mellitus. 50 women with type 2 diabetes participated in this study and were randomly divided into two groups namely, control and intervention groups. Control group received placebo and intervention group received hydro-alcoholic extract of U. dioica . Before and after 8 weeks of continuous treatment, some biochemical serum levels including FPG, TG, SGPT, SGOT, HDL, LDL, SOD and NO were measured. The results indicated that after 8 weeks, in the intervention group, FPG, TG, and SGPT levels significantly decreased and HDL, NO and SOD levels significantly increased as compared to the control group. Our results encourage the use of hydro-alcoholic extract of U. dioica as an antioxidant agent for additional therapy of diabetes as hydro-alcoholic extract of U. dioica may decrease risk factors of cardiovascular incidence and other complications in patients with diabetes mellitus.

Prediction of functional profiles of gut microbiota from 16S rRNA metagenomic data provides a more robust evaluation of gut dysbiosis occurring in Japanese type 2 diabetic patients.

PubMed

Inoue, Ryo; Ohue-Kitano, Ryuji; Tsukahara, Takamitsu; Tanaka, Masashi; Masuda, Shinya; Inoue, Takayuki; Yamakage, Hajime; Kusakabe, Toru; Hasegawa, Koji; Shimatsu, Akira; Satoh-Asahara, Noriko

2017-11-01

We assessed whether gut microbial functional profiles predicted from 16S rRNA metagenomics differed in Japanese type 2 diabetic patients. A total of 22 Japanese subjects were recruited from our outpatient clinic in an observational study. Fecal samples were obtained from 12 control and 10 type 2 diabetic subjects. 16S rRNA metagenomic data were generated and functional profiles predicted using "Phylogenetic Investigation of Communities by Reconstruction of Unobserved States" software. We measured the parameters of glucose metabolism, gut bacterial taxonomy and functional profile, and examined the associations in a cross-sectional manner. Eleven of 288 "Kyoto Encyclopedia of Genes and Genomes" pathways were significantly enriched in diabetic patients compared with control subjects ( p <0.05, q<0.1). The relative abundance of almost all pathways, including the Insulin signaling pathway and Glycolysis/Gluconeogenesis , showed strong, positive correlations with hemoglobin A 1c (HbA 1c ) and fasting plasma glucose (FPG) levels. Bacterial taxonomic analysis showed that genus Blautia significantly differed between groups and had negative correlations with HbA 1c and FPG levels. Our findings suggest a novel pathophysiological relationship between gut microbial communities and diabetes, further highlighting the significance and utility of combining prediction of functional profiles with ordinal bacterial taxonomic analysis (UMIN Clinical Trails Registry number: UMIN000026592).

Total Antioxidant Status in Type 2 Diabetic Patients in Palestine.

PubMed

Kharroubi, Akram T; Darwish, Hisham M; Akkawi, Mutaz A; Ashareef, Abdelkareem A; Almasri, Zaher A; Bader, Khaldoun A; Khammash, Umaiyeh M

2015-01-01

The objective of this study was to compare the level of total antioxidant status (TAS) in type 2 diabetic and normal Palestinian subjects as well as the major factors influencing TAS levels. A sample of convenience composed of 212 type 2 diabetic and 208 normal subjects above the age of 40 were recruited. Only 9.8% of the subjects had normal body mass index (BMI) levels (<25), 29% were overweight (≥25 to <30), and 61.2% were obese (≥30). The mean levels of TAS were significantly higher in diabetic compared to control subjects (2.18 versus 1.84 mM Trolox, P = 0.001) and in hypertensive subjects compared to subjects with normal blood pressure (BP). Mean TAS levels were higher in obese compared to nonobese subjects (2.12 versus 1.85 mM Trolox, P = 0.001). Mean TAS levels were similarly higher in subjects with high fasting plasma glucose (FPG) compared to normal FPG (2.19 versus 1.90 mM Trolox) and high HbA1c (≥6.5%) compared to HbA1c < 6.5% (2.14 versus 1.91 mM Trolox). Multivariate analysis revealed that only diabetic status (P = 0.032) and the level of education (P = 0.036) were significantly associated with TAS. In conclusion diabetic patients had 18.5% increase in TAS levels compared to control subjects.

Isolated post-challenge hyperglycaemia and risk of cardiovascular events: Tehran Lipid and Glucose Study.

PubMed

Barzin, Maryam; Hosseinpanah, Farhad; Malboosbaf, Ramin; Hajsheikholeslami, Farhad; Azizi, Fereidoun

2013-07-01

To evaluate the risk of cardiovascular events in diabetes defined by isolated post-challenge hyperglycaemia (IPH). We followed 3794 subjects aged ≥40 years without known history of diabetes or cardiovascular disease (CVD) at baseline for CVD events. Participants were categorized as subjects without diabetes [fasting plasma glucose (FPG) < 126 mg/dL and 2-h post-challenge plasma glucose (2-hPG) < 200 mg/dL], IPH (FPG < 126 mg/dL and 2-h PG ≥ 200 mg/dL) and fasting hyperglycaemia (fasting blood glucose (FBS) ≥ 126 mg/dL). Hazard ratios (HRs) were calculated with the use of Cox proportional-hazards regression models to evaluate the risk of CVD events. At baseline, of 486 subjects with newly diagnosed diabetes, 190 (39%) had IPH. Over the next 8 years, age and sex-adjusted HR for incident CVD was 1.77 (95% confidence interval (CI): 1.19-2.64; p = 0.005) in subjects with IPH compared with subjects without diabetes. After further adjustment for potential confounders, the HR for CVD was not significant [1.32 (95% CI: 0.88-1.99; p = 0.2)]. IPH in middle-aged adults adds nothing for identifying CVD risks when other risk factors are taken into account. Associated metabolic risk factors seem to be more important than hyperglycaemia per se.

Exercise training with weight loss and either a high or low glycemic diet reduces metabolic syndrome severity in older adults

PubMed Central

Malin, Steven K.; Niemi, Nicole; Solomon, Thomas P.J.; Haus, Jacob M.; Kelly, Karen R.; Filion, Julianne; Rocco, Michael; Kashyap, Sangeeta R.; Barkoukis, Hope; Kirwan, John P.

2012-01-01

Background The efficacy of combining carbohydrate quality with exercise on metabolic syndrome risk is unclear. Thus, we determined the effects of exercise training with a low or high glycemic diet on metabolic syndrome severity (Z-score). Methods Twenty-one adults (66.2 ± 1.1 yr; BMI = 35.3 ± 0.9 kg/m2) with metabolic syndrome were randomized to 12 weeks of exercise (60 minutes/d for 5 d/week at ~85% HRmax) and provided a low-glycemic (n=11; LoGIx) or high glycemic (n=10; HiGIx) diet. Z-scores were determined from: blood pressure, triglycerides (TG), high-density lipoproteins (HDL), fasting plasma glucose (FPG), and waist circumference (WC) before and after the intervention. Body composition, aerobic fitness, insulin resistance, and non-esterfied fatty acid (NEFA) suppression were also assessed. Results LoGIx and HiGIx decreased body mass and insulin resistance and increased aerobic fitness comparably (p < 0.05). LoGIx and HiGIx decreased the Z-score similarly, as each intervention decreased blood pressure, TG, FPG, and WC (p < 0.05). HiGIx tended to suppress NEFA during insulin stimulation compared to LoGIx (p = 0.06). Conclusions Our findings highlight that exercise with weight loss reduces metabolic syndrome severity whether individuals were randomized to a high or low glycemic index diet. PMID:23036993

Unravelling the effects of age, period and cohort on metabolic syndrome components in a Taiwanese population using partial least squares regression

PubMed Central

2011-01-01

Background We investigate whether the changing environment caused by rapid economic growth yielded differential effects for successive Taiwanese generations on 8 components of metabolic syndrome (MetS): body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TG), high-density lipoprotein (HDL), Low-density lipoproteins (LDL) and uric acid (UA). Methods To assess the impact of age, birth year and year of examination on MetS components, we used partial least squares regression to analyze data collected by Mei-Jaw clinics in Taiwan in years 1996 and 2006. Confounders, such as the number of years in formal education, alcohol intake, smoking history status, and betel-nut chewing were adjusted for. Results As the age of individuals increased, the values of components generally increased except for UA. Men born after 1970 had lower FPG, lower BMI, lower DBP, lower TG, Lower LDL and greater HDL; women born after 1970 had lower BMI, lower DBP, lower TG, Lower LDL and greater HDL and UA. There is a similar pattern between the trend in levels of metabolic syndrome components against birth year of birth and economic growth in Taiwan. Conclusions We found cohort effects in some MetS components, suggesting associations between the changing environment and health outcomes in later life. This ecological association is worthy of further investigation. PMID:21619595

Sustaining Effect of Intensive Nutritional Intervention Combined with Health Education on Dietary Behavior and Plasma Glucose in Type 2 Diabetes Mellitus Patients.

PubMed

Fan, Rui; Xu, Meihong; Wang, Junbo; Zhang, Zhaofeng; Chen, Qihe; Li, Ye; Gu, Jiaojiao; Cai, Xiaxia; Guo, Qianying; Bao, Lei; Li, Yong

2016-09-13

Diabetes mellitus is very common in elderly Chinese individuals. Although nutritional intervention can provide a balanced diet, the sustaining effect on at-home dietary behavior and long-term plasma glucose control is not clear. Consequently, we conducted a long-term survey following one month of experiential nutritional intervention combined with health education. Based on the Dietary Guidelines for a Chinese Resident, we found that the food items met the recommended values, the percentages of energy provided from fat, protein, and carbohydrate were more reasonable after one year. The newly formed dietary patterns were "Healthy", "Monotonous", "Vegetarian", "Japanese", "Low energy", and "Traditional" diets. The 2h-PG of female participants as well as those favoring the "Japanese diet" decreased above 12 mmol/L. Participants who selected "Japanese" and "Healthy" diets showed an obvious reduction in FPG while the FPG of participants from Group A declined slightly. "Japanese" and "Healthy" diets also obtained the highest DDP scores, and thus can be considered suitable for T2DM treatment in China. The results of the newly formed dietary patterns, "Japanese" and "Healthy" diets, confirmed the profound efficacy of nutritional intervention combined with health education for improving dietary behavior and glycemic control although health education played a more important role. The present study is encouraging with regard to further exploration of comprehensive diabetes care.

Guar sprinkled on food: effect on glycaemic control, plasma lipids and gut hormones in non-insulin dependent diabetic patients.

PubMed

Fuessl, H S; Williams, G; Adrian, T E; Bloom, S R

1987-01-01

The effects of guar granules sprinkled over food on carbohydrate and lipid metabolism were studied in a double-blind cross-over trial in 18 patients with non-insulin-dependent diabetes mellitus (mean +/- SEM age 61.3 +/- 2.5 years). Five-gram guar granules (Guarem, Rybar Laboratories, Amersham, Bucks) were sprinkled over food at each main meal for 4 weeks, and during a 4-week placebo period (separated by a 2-week 'wash-out' period), 5 g wheat bran was taken in the same way. Diabetic treatment was not changed during the study. Mean fasting plasma glucose (FPG) concentration and glycosylated haemoglobin (HbA1) concentration after treatment were significantly lower than after the placebo period (FPG 8.29 +/- 0.47 vs 8.78 +/- 0.53 mmol/l, p less than 0.05; HbA1: 8.70 +/- 0.39 vs 9.09 +/- 0.39%, p less than 0.05). There was a 50% reduction in the incremental area under the postprandial glycaemic curve when guar was eaten with a standardized test meal. Total plasma cholesterol decreased from 5.79 +/- 0.29 to 5.19 +/- 0.22 mmol/l (p less than 0.05) after the guar treatment period. Guar ingestion reduced postprandial insulin and enteroglucagon responses, the latter significantly so, but had no apparent effect on gastric inhibitory polypeptide, pancreatic glucagon, gastrin, and pancreatic polypeptide.

Cinnamon in glycaemic control: Systematic review and meta analysis.

PubMed

Akilen, Rajadurai; Tsiami, Amalia; Devendra, Devasenan; Robinson, Nicola

2012-10-01

Cinnamon seems to be highly bioactive, appearing to mimic the effect of insulin through increased glucose uptake in adipocytes and skeletal muscles. This systematic review and Meta analysis examined the effect of cinnamon on glycaemic control in patients with Type 2 Diabetes mellitus. A systematic literature search was conducted from the earliest possible date through to 01 August 2011. Search terms included free text terms, MeSH and Medline medical index terms such as: "cinnamon", "cinnamomum", "cinnamomum cassia", "cinnamomum zeylanicum", "type 2 diabetes mellitus". Each was crossed with the term "diabetes mellitus". In addition, references of key articles were hand searched. A total of 6 clinical trials met the strict inclusion criteria and considered a total of 435 patients; follow up between 40 days-4 months, doses ranging from 1 g to 6 g per day. Meta-analysis of RCTs showed a significant decrease in mean HbA1c [0.09%; 95% CI was 0.04-0.14] and mean FPG [0.84 mmol/l; 95% CI was 0.66-1.02]. Use of cinnamon showed a beneficial effect on glycaemic control (both HbA1c and FPG) and the short term (<4 months) effects of the use of cinnamon on glycaemic control looks promising. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Unsatisfactory Glucose Management and Adverse Pregnancy Outcomes of Gestational Diabetes Mellitus in the Real World of Clinical Practice: A Retrospective Study.

PubMed

Feng, Ru; Liu, Lu; Zhang, Yuan-Yuan; Yuan, Zhong-Shang; Gao, Ling; Zuo, Chang-Ting

2018-05-05

Facing the increasing prevalence of gestational diabetes mellitus (GDM), this study aimed to evaluate the management of GDM and its association with adverse pregnancy outcomes. The data of 996 inpatients with GDM who terminated pregnancies in our hospital from January 2011 to December 2015 were collected. Treatments during pregnancy and the last hospital admission before delivery were analyzed. Pregnancy outcomes of the GDM patients were compared with 996 nondiabetic subjects matched by delivery year and gestational age. The association between fasting plasma glucose (FPG) and adverse pregnancy outcomes was examined by logistic regression analyses. The average prevalence of GDM over the 5 years was 4.4% (1330/30,191). Within the GDM patients, 42.8% (426/996) received dietary intervention, whereas 19.1% (190/996) received insulin treatment. Adverse outcomes were more likely to occur in patients with unsatisfactory control of blood glucose such as respiratory distress syndrome (RDS, χ 2 = 13.373, P < 0.01). Elevated FPG was identified as an independent risk factor for premature birth (odds ratio [OR] = 1.460, P < 0.001), neonatal care unit admission (OR = 1.284, P < 0.001), RDS (OR = 1.322, P = 0.001), and stillbirth (OR = 1.427, P < 0.001). Management of GDM in the real world of clinical practice was unsatisfactory, which might have contributed to adverse pregnancy outcomes.

Metabolic effect of repaglinide or acarbose when added to a double oral antidiabetic treatment with sulphonylureas and metformin: a double-blind, cross-over, clinical trial.

PubMed

Derosa, Giuseppe; Salvadeo, Sibilla A T; D'Angelo, Angela; Ferrari, Ilaria; Mereu, Roberto; Palumbo, Ilaria; Maffioli, Pamela; Randazzo, Sabrina; Cicero, Arrigo F G

2009-03-01

To compare the metabolic effects of acarbose and repaglinide in type 2 diabetic patients who are being treated with a sulphonylurea-metformin combination therapy. The primary endpoint of the study was to evaluate which add-on treatment between acarbose and repaglinide is more efficacious in reducing PPG. The second endpoint was to evaluate which of these two treatment is more efficacious in the global management of glucose homeostasis in the enrolled patients. After a 4-week run-in period with a sulphonylurea-metformin combination, 103 patients were randomised to receive in addition either repaglinide, up to 6 mg/day (2 mg three times a day) or acarbose, up to 300 mg/day (100 mg three times a day) with forced titration (independently of their glycaemic control, unless side-effects developed due to the drug dosage) for 15 weeks. The treatment was then crossed-over for further 12 weeks until the 27th week. We assessed body mass index (BMI), glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), homeostatic model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (Tg), at baseline and at 1, 2, 15 and 27 weeks of treatment. Seven patients did not complete the study, comprising one patient who was lost to follow-up and a further six through side-effects (two in week 1, one in week 15 and three after cross-over) Side-effects were classified as nausea (one in acarbose group), gastrointestinal events (four in acarbose group), and hypoglycaemia (one in repaglinide group). After 15 weeks of therapy, the repaglinide-treated patients experienced a significant decrease in HbA(1c) (-1.1%, p < 0.05), FPG (-9.5%, p < 0.05), and PPG (-14.9%, p < 0.05), when compared to the baseline values. However, the same treatment was associated with a significant increase in body weight (+2.3%, p < 0.05), BMI (+3.3%, p < 0.05) and FPI (+22.5%, p < 0.05); The increase was reversed during the cross-over phase. After 15 weeks of therapy, the acarbose-treated patients experienced a significant decrease in body weight (-1.9%, p < 0.05), BMI (-4.1%, p < 0.05), HbA(1c) (-1.4%, p < 0.05), FPG (-10.7%, p < 0.05), PPG (-16.2%, p < 0.05), FPI (-16.1%, p < 0.05), PPI (-26.9%, p < 0.05), HOMA index (-30.1%, p < 0.05), when compared to the baseline values. All these changes were reversed during the cross-over study phase, except those relating to HbA(1c), FPG and PPG. The only changes that significantly differed when directly comparing acarbose- and repaglinide-treated patients were those relating to FPI (-16.1% vs. +22.5%, respectively, p < 0.05) and HOMA index (-30.1% vs. +2.7%, p < 0.05). In addition from having a similar effect to repaglinide on PPG, acarbose appeared to have a more comprehensive positive effect on glucose metabolism compared to repaglinide in this relatively small sample of type 2 diabetic patients when used as add-on therapy to sulphonylureas and metformin.

Plasma lipid profile in Nigerians with high--normal blood pressure.

PubMed

Saidu, Hadiza; Karaye, Kamilu Musa; Okeahialam, Basil N

2014-12-18

High blood pressure levels have been associated with elevated atherogenic blood lipid fraction, but epidemiological surveys often give inconsistent results across population sub-groups. To determine the extent to which there are differences in lipid profile based on blood pressure levels, we assessed lipid profile of subjects with high-normal blood pressure and compared with those of hypertensives and optimally normal blood pressure. The study was a cross-sectional comparative study conducted at Aminu Kano Teaching Hospital, Kano, Nigeria. Fasting lipid levels were examined among randomly selected patients with optimally normal blood pressure (group 1), high-normal blood pressure (group 2) and those with hypertension (group 3). Optimal blood pressure was defined as systolic blood pressure (SBP) of <120 mmHg/or diastolic blood pressure (DBP) of <80 mmHg; and high-normal blood pressure as SBP of 130-139 mmHg and/or DBP of 85-89 mmHg. A total of 300 subjects were studied, 100 in each group. The mean age of subjects in group 1 was 27.32±8.20 years and 60% were female, while that of group 2 was 34.04±6.25 years, and 53% were female, and that for group 3 was 52.81±13.3 years and 56% were female. The mean total cholesterol (TC) for subjects in group1 (3.96±0.40 mmol/L) was significantly lower than levels in group2 (4.55±1.01 mmol/L); P=<0.001. Subjects in group 3 (5.20±1.88 mmol/L), however had statistically significant higher mean TC when compared with group 2; (P=0.03). The difference between the groups for low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) followed the same pattern as that of TC, with statistically significant increasing trend across the blood pressure categories. Levels of high density lipoprotein cholesterol (HDL-C) were however similar across the three groups (group 2 versus group 1; P=0.49, group 2 versus group 3; P=0.9). Increased TC (>5.2 mmol/L) was absent in group1, but found among 11% of group2 subjects and 40% of those in group 3 (P-value for trend<0.001). Mean fasting plasma glucose (FPG) was 3.8±0.4 mmol/L, 4.7±1.1 mmol/L, 5.1±1.9 mmol/L and for subjects in groups 1, 2 and 3 respectively (p>0.05 for groups 2 Vs 1 and p<0.001 for groups 2 Vs 3). The differences in mean body mass index (BMI) between the groups followed a similar trend as that of FPG. Multivariate logistic regression analysis showed that FPG, TG and BMI were the strongest predictors of prehypertension [odds ratio (OR) 10.14, 95% CI (confidence interval) 3.63-28.33, P=0.000; OR 5.75, 95% CI 2.20-15.05, P=0.000; and OR 2.03, 95% CI 1.57-2.62, P=0.000 respectively]. The study has shown a significant increase in plasma TC, LDL-C and TG values as blood pressure levels increased from optimally normal, across high-normal to hypertensive levels. There was a similar trend for FPG and BMI, demonstrating the central role that blood pressure plays in these metabolic disorders in Nigerians. These findings are relevant in terms of both prevention and treatment of cardiovascular morbidities and mortality.

Omitting late-night eating may cause hypoglycemia in "well controlled" basal insulin-treated type 2 diabetes.

PubMed

King, Allen B; Clark, Dawn

2015-03-01

To assess hypoglycemia caused by eating the last meal of the day earlier or its omission in "well controlled" type 2 diabetes mellitus patients treated with once-nightly basal insulin. Previously basal insulin-titrated subjects (n = 20) (fasting plasma glucose, FPG, <110 mg/dL and no self-reported hypoglycemia) underwent continuous glucose monitoring (CGM) during 3 consecutive eating conditions of 3 days each; (1) usual eating, (2) the last meal restricted to 18:00, and (3) 1 sequential meal omitted/day thereby creating a fasting day after transposing the 4-hour period after a meal with that when the meal was omitted. One 24-hour (00:00 to 00:00) period within each eating condition was selected for comparison. The mean duration in all hypoglycemic ranges doubled (P = .0584 or greater) when the last meal was omitted or eaten at 18:09 ± 0:39 instead of 19:43 ± 1:01, the usual time for the subjects' undisturbed eating. The mean duration of hypoglycemia was greatest between 00:00 to 06:00 compared to the 3 other 6-hour periods of the day. Increased hypoglycemia occurs when the subject's last meal is eaten earlier or omitted and may not be recognized because it occurs predominately during sleep. When titrating basal insulin from the morning FPG, considerations should be given to the effect of the last meal of the day and possible hypoglycemia between 00:00 and 06:00 to avoid excessive basal insulin treatment.

Amelioration of fatty liver index in patients with type 2 diabetes on ipragliflozin: an association with glucose-lowering effects.

PubMed

Takase, Takahiro; Nakamura, Akinobu; Miyoshi, Hideaki; Yamamoto, Chiho; Atsumi, Tatsuya

2017-03-31

In this study, we investigated the ameliorating effects of ipragliflozin on fatty liver in patients with type 2 diabetes. The factors that influenced the amelioration of fatty liver were also examined. Analysis included data of 21 Japanese patients with type 2 diabetes obtained from our prospective observational study. After obtaining patients' informed consent, once-daily ipragliflozin (50 mg/day) was given for 16 weeks. In addition to several clinical parameters, body composition was also compared before and after 16 weeks of treatment. The extent of fatty liver was estimated using a fatty liver index (FLI). After 16 weeks, FLI significantly decreased, from 70.1 ± 19.4 to 60.3 ± 25.5 (p = 0.0009) as well as levels of fasting plasma glucose (FPG), HbA1c, body weight, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and fat mass. To reveal the factors influencing the FLI changes observed on ipragliflozin treatment, correlations between changes in FLI and several other measured parameters were examined. Changes in FPG (correlation coefficient = 0.4683, p = 0.0323) and HbA1c (correlation coefficient = 0.4383, p = 0.0469) showed significant positive correlations with changes in FLI. On the other hand, no correlations of changes in FLI were observed with body weight, VAT, SAT nor fat mass. In conclusion, ipragliflozin ameliorated FLI in Japanese patients with type 2 diabetes. Improvement in FLI was associated with that of glucose intolerance.

Significant but weak spousal concordance of metabolic syndrome components in Japanese couples.

PubMed

Okuda, Tomoko; Miyazaki, Tadayoshi; Sakuragi, Sonoko; Moriguchi, Jiro; Tachibana, Hiroshi; Ohashi, Fumiko; Ikeda, Masayuki

2014-03-01

This study was initiated to investigate if spousal concordance in metabolic syndrome (MS) components exist in Japan. In all, 756 couples (mean age: 48.9 and 47.3 years for husbands and wives, respectively) were identified. Each subject was classified as an MS, MS reserves (MSRES) or no risk of MS (NonMS) case after Japanese Ministry of Health, Labour and Welfare (JMHLW) criteria. Criteria of the National Cholesterol Education Program and of the Joint Interim Statement were also applied. With Japanese Ministry of Health, Labor and Welfare (JMHLW) criteria, MS, MSRES and NonMS cases accounted for 11.9, 14.7 and 73.4 % in husbands and 1.6, 3.7 and 94.7 % in wives. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SBP) and hemoglobin A1c (HbA1c) showed significant correlation (p < 0.01). Correlation was also significant (p < 0.05) for mean blood pressure (MBP) and fasting plasma glucose (FPG). When adjusted for age, correlations were significant only for WC, BMI and HbA1c. Furthermore, none of the correlation coefficients were greater than 0.2. Logistic regression analyses did not suggest significant mutual influence in MS status between the couples. Spousal concordance in MS components was detected for WC, BMI, SBP, MBP, FPG and HbA1c, but the correlation was generally weak and modest in Japanese couples.

In Vitro Fluorogenic Real-time Assay of the Repair of Oxidative DNA Damage

PubMed Central

Edwards, Sarah K.; Ono, Toshikazu; Wang, Shenliang; Jiang, Wei; Franzini, Raphael M.; Jung, Jong Wha; Chan, Ke Min; Kool, Eric T.

2015-01-01

The repair of oxidative damage to DNA is essential to avoidance of mutations that lead to cancer. Oxidized DNA bases, such as 8-oxoguanine, are a chief source of these mutations, and the enzyme 8-oxoguanine glycosylase 1 (OGG1) is the chief human enzyme that excises 8-oxoguanine from DNA. The activity of OGG1 has been linked to human inflammation responses and to cancer, and researchers are beginning to search for inhibitors of the enzyme. However, measuring the activity of the enzyme typically requires laborious gel-based measurements of radiolabeled DNAs. Here we report on the design and properties of fluorogenic probes that directly report on OGG1 (and bacterial homologue Fpg) activity in real time as the oxidized base is excised. The probes are short modified DNA oligomers containing fluorescent DNA bases and are designed to utilize the damaged DNA base itself as a fluorescence quencher. Screening of combinations of fluorophores and 8-oxoguanine revealed two fluorophores, pyrene and tCo, that are strongly quenched by the damaged base. We tested 42 potential probe designs containing these fluorophores, and we found an optimized probe OGR1 that yields a 60-fold light-up signal in vitro with OGG1 and Fpg, and can report on oxidative repair activity in mammalian cell lysate and with bacterial cells overexpressing a repair enzyme. Such probes may be useful in quantifying enzyme activity and performing competitive inhibition assays. PMID:26073452

The effect of educational status on the relationship between obesity and risk of type 2 diabetes.

PubMed

Madjid, I S; Backholer, K; Williams, E D; Magliano, D J; Shaw, J E; Peeters, A

2014-01-01

Obesity trends are likely to increase social disparities in diabetes. The magnitude of this effect depends on the strength of the relationship between obesity and diabetes across categories of disadvantage. This study aims to test the hypothesis that education level moderates the association between obesity and fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), HbA1c level, and diabetes prevalence. We used the baseline data from the Australian Obesity, Diabetes, and Lifestyle study in 2000 (n = 8646). We performed multiple linear regression analysis adjusted for confounding factors and stratified by education level. Body mass index (BMI) and waist circumference (WC) were positively associated with FPG, 2hPG, HbA1c and prevalence of diabetes. No moderating effect of education on these relationships was observed in the total population. In never smokers free of diagnosed diabetes at baseline the association of WC with 2hPG and HbA1c and of BMI with HbA1c was stronger in those with a lower level of education. Overall, these results suggest that the association between obesity and diabetes risk is independent of educational status. However, inconsistent results suggest that further analyses of an adequately powered longitudinal study of never smokers free of diabetes would be useful to further explore this hypothesis. © 2014 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

A 4-week study assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of the glucagon receptor antagonist PF-06291874 administered as monotherapy in subjects with type 2 diabetes mellitus.

PubMed

Bergman, Arthur; Tan, Beesan; Somayaji, Veena R; Calle, Roberto A; Kazierad, David J

2017-04-01

The glucagon receptor antagonist PF-06291874 has demonstrated robust glucose reductions in subjects with type 2 diabetes mellitus (T2DM) on background metformin. This study assessed the pharmacokinetics, pharmacodynamics, safety, and tolerability of PF-06291874 administered as monotherapy in subjects with T2DM. After a ≥4-week antidiabetic therapy washout period, 172 subjects were randomized to placebo or PF-06291874 15, 35, 75, or 150mg once daily for 28days. Mean daily glucose (MDG), fasting plasma glucose (FPG), and predefined safety endpoints were assessed at baseline and day 28. Dose-dependent reductions (placebo-adjusted) from baseline in MDG ranged from 40.3 to 68.8mg/dL and in FPG from 27.1 to 57.2mg/dL after 28days of dosing with PF-06291874. There were no significant changes in low-density lipoprotein cholesterol at doses ≤75mg relative to placebo. Small, dose-dependent increases in alanine aminotransferase and aspartate aminotransferase were observed; however, the incidence of these values >3×upper limit of normal was similar across doses. PF-06291874 exposures were consistent with previous studies and PF-06291874 was well tolerated, with minimal incidence of hypoglycemia. PF-06291874 as monotherapy was well tolerated and produced robust reductions in plasma glucose following 4weeks of dosing in subjects with T2DM. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevention of Insulin Resistance by Dietary Intervention among Pregnant Mothers: A Randomized Controlled Trial.

PubMed

Goodarzi-Khoigani, Masoomeh; Mazloomy Mahmoodabad, Seyed Saeed; Baghiani Moghadam, Mohammad Hossein; Nadjarzadeh, Azadeh; Mardanian, Farahnaz; Fallahzadeh, Hossein; Dadkhah-Tirani, Azam

2017-01-01

Chronic insulin resistance (IR) is a basic part of the pathophysiology of gestational diabetes mellitus. Nutrition significantly impacts IR and weight loss reduces insulin levels, whereas weight gain increases the concentrations. Therefore, we surveyed the effect of nutrition intervention on IR in pregnant women and whether this effect is irrespective of weight gaining in accordance with Institute of Medicine limits. This prospective, randomized clinical trial was carried out among 150 primiparous pregnant mothers in fifteen health centers, five hospitals, and 15 private obstetrical offices in Isfahan. The nutrition intervention included education of healthy diet with emphasize on 50%-55% of total energy intake from carbohydrate (especially complex carbohydrates), 25%-30% from fat (to increase mono unsaturated fatty acids and decrease saturated and trans-fatty acids), and 15%-20% from protein during pregnancy for experimental group. The controls received the usual prenatal care by their health-care providers. This trial decreased pregnancy-induced insulin increases ( P = 0.01) and IR marginally ( P = 0.05). ANCOVA demonstrated that control of gestational weight gaining was more effective to decrease IR ( P = 0.02) while insulin values decreased by nutrition intervention and irrespective of weight control ( P = 0.06). Fasting plasma glucose (FPG) concentrations did not decrease by intervention ( P = 0.56) or weight management ( P = 0.15). The current intervention was effective to decrease pregnancy-induced insulin increases and IR. Considering study results on FPG levels and incidence of GDM, we suggest repeat of study design in a larger sample.

Exercise training with weight loss and either a high- or low-glycemic index diet reduces metabolic syndrome severity in older adults.

PubMed

Malin, Steven K; Niemi, Nicole; Solomon, Thomas P J; Haus, Jacob M; Kelly, Karen R; Filion, Julianne; Rocco, Michael; Kashyap, Sangeeta R; Barkoukis, Hope; Kirwan, John P

2012-01-01

The efficacy of combining carbohydrate quality with exercise on metabolic syndrome risk is unclear. Thus, we determined the effects of exercise training with a low (LoGIx)- or high (HiGIx)-glycemic index diet on the severity of the metabolic syndrome (Z-score). Twenty-one adults (66.2±1.1 years; BMI=35.3±0.9 kg/m2) with the metabolic syndrome were randomized to 12 weeks of exercise (60 min/day for 5 days/week at about 85% HRmax) and provided a LoGIx (n=11) or HiGIx (n=10) diet. Z-scores were determined from: blood pressure, triglycerides (TGs), high-density lipoproteins (HDLs), fasting plasma glucose (FPG), and waist circumference (WC) before and after the intervention. Body composition, aerobic fitness, insulin resistance, and nonesterfied fatty acid (NEFA) suppression were also assessed. LoGIx and HiGIx diets decreased body mass and insulin resistance and increased aerobic fitness comparably (p<0.05). LoGIx and HiGIx diets decreased the Z-score similarly as each intervention decreased blood pressure, TGs, FPG and WC (p<0.05). The HiGIx diet tended to suppress NEFA during insulin stimulation compared with the LoGIx diet (p=0.06). Our findings highlight that exercise with weight loss reduces the severity of the metabolic syndrome whether individuals were randomized to a HiGIx or a LoGIx diet.

KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) polymorphisms affect therapeutic efficacy of repaglinide in Chinese patients with type 2 diabetes.

PubMed

Yu, M; Xu, X-J; Yin, J-Y; Wu, J; Chen, X; Gong, Z-C; Ren, H-Y; Huang, Q; Sheng, F-F; Zhou, H-H; Liu, Z-Q

2010-03-01

This study showed that the polymorphisms KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) are associated with a heightened risk of developing type 2 diabetes mellitus (T2DM). We also explored the effects of these polymorphisms on the efficacy of repaglinide therapy in Chinese patients with T2DM. A total of 259 patients with T2DM and 188 healthy controls were genotyped. Forty patients with various genotypes were randomly selected to undergo an 8-week repaglinide treatment regimen. Patients with the G allele of the KCNJ11 Lys23Glu polymorphism showed higher levels of fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) (P < 0.05). After repaglinide treatment, patients with the GA or AA genotype showed higher levels of FPG, PPG, and glycated hemoglobin (HbA(1c)) compared with patients with the GG genotype (P < 0.05). Patients with the C allele of TCF7L2 rs290487(C/T) had higher total cholesterol levels and lower body mass index (BMI) (P < 0.05). In patients with the TT genotype, the drug showed better efficacy with respect to levels of fasting insulin, triglycerides, and low-density lipoprotein cholesterol (LDL-c) than in patients with the CC or CT genotype (P < 0.05). The KCNJ11 and TCF7L2 polymorphisms were associated with repaglinide efficacy.

Effects of Urtica dioica supplementation on blood lipids, hepatic enzymes and nitric oxide levels in type 2 diabetic patients: A double blind, randomized clinical trial

PubMed Central

Amiri Behzadi, Alidad; Kalalian-Moghaddam, Hamid; Ahmadi, Amir Hossein

2016-01-01

Objective: Oxidative stress plays an important role in the development of diabetic complications including metabolic abnormality-induced diabetic micro-vascular and macro-vascular complications. Urtica dioica L. (U. dioica) has been traditionally used in Iranian medicine as an herbal remedy for hypoglycemic or due to its anti-inflammatory properties. The aim of the present study was to evaluate the effects of hydro-alcoholic extract of U. dioica on blood lipids, hepatic enzymes and nitric oxide levels in patients with type 2 diabetes mellitus. Materials and Methods: 50 women with type 2 diabetes participated in this study and were randomly divided into two groups namely, control and intervention groups. Control group received placebo and intervention group received hydro-alcoholic extract of U. dioica. Before and after 8 weeks of continuous treatment, some biochemical serum levels including FPG, TG, SGPT, SGOT, HDL, LDL, SOD and NO were measured. Results: The results indicated that after 8 weeks, in the intervention group, FPG, TG, and SGPT levels significantly decreased and HDL, NO and SOD levels significantly increased as compared to the control group. Conclusion: Our results encourage the use of hydro-alcoholic extract of U. dioica as an antioxidant agent for additional therapy of diabetes as hydro-alcoholic extract of U. dioica may decrease risk factors of cardiovascular incidence and other complications in patients with diabetes mellitus. PMID:28078249

Comparison of the Sensitivity of Surface Downward Longwave Radiation to Changes in Water Vapor at Two High Elevation Sites

NASA Technical Reports Server (NTRS)

Chen, Yonghua; Naud, Catherine M.; Rangwala, Imtiaz; Landry, Christopher C.; Miller, James R.

2014-01-01

Among the potential reasons for enhanced warming rates in many high elevation regions is the nonlinear relationship between surface downward longwave radiation (DLR) and specific humidity (q). In this study we use ground-based observations at two neighboring high elevation sites in Southwestern Colorado that have different local topography and are 1.3 kilometers apart horizontally and 348 meters vertically. We examine the spatial consistency of the sensitivities (partial derivatives) of DLR with respect to changes in q, and the sensitivities are obtained from the Jacobian matrix of a neural network analysis. Although the relationship between DLR and q is the same at both sites, the sensitivities are higher when q is smaller, which occurs more frequently at the higher elevation site. There is a distinct hourly distribution in the sensitivities at both sites especially for high sensitivity cases, although the range is greater at the lower elevation site. The hourly distribution of the sensitivities relates to that of q. Under clear skies during daytime, q is similar between the two sites, however under cloudy skies or at night, it is not. This means that the DLR-q sensitivities are similar at the two sites during daytime but not at night, and care must be exercised when using data from one site to infer the impact of water vapor feedbacks at another site, particularly at night. Our analysis suggests that care should be exercised when using the lapse rate adjustment to infill high frequency data in a complex topographical region, particularly when one of the stations is subject to cold air pooling as found here.

EFFECTS OF LIRAGLUTIDE 3.0 MG ON WEIGHT AND RISK FACTORS IN HISPANIC VERSUS NON-HIPANIC POPULATIONS: SUBGROUP ANALYSIS FROM SCALE RANDOMIZED TRIALS.

PubMed

O'Neil, Patrick M; Garvey, W Timothy; Gonzalez-Campoy, J Michael; Mora, Pablo; Ortiz, Rafael Violante; Guerrero, German; Claudius, Birgitte; Pi-Sunyer, Xavier

2016-11-01

Scarce data exist on pharmacotherapy for obesity in Hispanic individuals. This post hoc analysis of pooled data from 4 phase 3a trials compared the efficacy and safety of liraglutide 3.0 mg versus placebo, as adjunct to a reduced-calorie diet and physical activity, in Hispanic versus non-Hispanic subgroups. We conducted the double-blind randomized, placebo-controlled trials in adults with a minimum body mass index (BMI) of 27 kg/m 2 with at least 1 comorbidity, or a minimum BMI of 30 kg/m 2 , at clinical research sites worldwide. In this analysis, we investigated possible differences in treatment effects between 534 Hispanics (10.4% of the population) and 4,597 non-Hispanics (89.6%) through statistical tests of interaction between subgroups and treatment. Variables examined included mean and categorical weight change, cardiovascular risk markers, and safety data. Both subgroups achieved clinically significant mean weight loss at end-of-treatment with liraglutide 3.0 mg versus placebo: Hispanics 7.0% versus 1.5%, treatment difference -5.1% (95% CI, -6.2 to -4.0); non-Hispanics 7.5% versus 2.3%, -5.2% (95% CI, -5.5 to -4.8). More individuals in both subgroups lost ≥5%, >10%, and >15% of their baseline weight with liraglutide 3.0 mg than with placebo. Efficacy endpoints generally did not vary with ethnicity (P>.05). Adverse events were comparable between ethnic subgroups, with more gastrointestinal disorders reported with liraglutide 3.0 mg than placebo. Efficacy and safety were largely similar between Hispanic and non-Hispanic subgroups. Results support that liraglutide 3.0 mg, used with a reduced-calorie diet and physical activity, can facilitate weight loss in Hispanic individuals. A1c = glycated hemoglobin BMI = body mass index CI = confidence interval FPG = fasting plasma glucose GLP-1 = glucagon-like peptide-1 hsCRP = high-sensitivity C-reactive protein SCALE = Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes T2DM = type 2 diabetes mellitus.

Genotoxicity of TiO2 nanoparticles assessed by mini-gel comet assay and micronucleus scoring with flow cytometry.

PubMed

Di Bucchianico, Sebastiano; Cappellini, Francesca; Le Bihanic, Florane; Zhang, Yuning; Dreij, Kristian; Karlsson, Hanna L

2017-01-01

The widespread production and use of nanoparticles calls for faster and more reliable methods to assess their safety. The main aim of this study was to investigate the genotoxicity of three reference TiO 2 nanomaterials (NM) within the frame of the FP7-NANoREG project, with a particular focus on testing the applicability of mini-gel comet assay and micronucleus (MN) scoring by flow cytometry. BEAS-2B cells cultured under serum-free conditions were exposed to NM100 (anatase, 50-150nm), NM101 (anatase, 5-8nm) and NM103 (rutile, 20-28nm) for 3, 24 or 48h mainly at concentrations 1-30 μg/ml. In the mini-gel comet assay (eight gels per slide), we included analysis of (i) DNA strand breaks, (ii) oxidised bases (Fpg-sensitive sites) and (iii) light-induced DNA damage due to photocatalytic activity. Furthermore, MN assays were used and we compared the results of more high-throughput MN scoring with flow cytometry to that of cytokinesis-block MN cytome assay scored manually using a microscope. Various methods were used to assess cytotoxic effects and the results showed in general no or low effects at the doses tested. A weak genotoxic effect of the tested TiO 2 materials was observed with an induction of oxidised bases for all three materials of which NM100 was the most potent. When the comet slides were briefly exposed to lab light, a clear induction of DNA strand breaks was observed for the anatase materials, but not for the rutile. This highlights the risk of false positives when testing photocatalytically active materials if light is not properly avoided. A slight increase in MN formation for NM103 was observed in the different MN assays at the lower doses tested (1 and 5 μg/ml). We conclude that mini-gel comet assay and MN scoring using flow cytometry successfully can be used to efficiently study cytotoxic and genotoxic properties of nanoparticles. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.

Genotoxicity of TiO2 nanoparticles assessed by mini-gel comet assay and micronucleus scoring with flow cytometry

PubMed Central

Di Bucchianico, Sebastiano; Cappellini, Francesca; Le Bihanic, Florane; Zhang, Yuning; Dreij, Kristian; Karlsson, Hanna L.

2017-01-01

The widespread production and use of nanoparticles calls for faster and more reliable methods to assess their safety. The main aim of this study was to investigate the genotoxicity of three reference TiO2 nanomaterials (NM) within the frame of the FP7-NANoREG project, with a particular focus on testing the applicability of mini-gel comet assay and micronucleus (MN) scoring by flow cytometry. BEAS-2B cells cultured under serum-free conditions were exposed to NM100 (anatase, 50–150nm), NM101 (anatase, 5–8nm) and NM103 (rutile, 20–28nm) for 3, 24 or 48h mainly at concentrations 1–30 μg/ml. In the mini-gel comet assay (eight gels per slide), we included analysis of (i) DNA strand breaks, (ii) oxidised bases (Fpg-sensitive sites) and (iii) light-induced DNA damage due to photocatalytic activity. Furthermore, MN assays were used and we compared the results of more high-throughput MN scoring with flow cytometry to that of cytokinesis-block MN cytome assay scored manually using a microscope. Various methods were used to assess cytotoxic effects and the results showed in general no or low effects at the doses tested. A weak genotoxic effect of the tested TiO2 materials was observed with an induction of oxidised bases for all three materials of which NM100 was the most potent. When the comet slides were briefly exposed to lab light, a clear induction of DNA strand breaks was observed for the anatase materials, but not for the rutile. This highlights the risk of false positives when testing photocatalytically active materials if light is not properly avoided. A slight increase in MN formation for NM103 was observed in the different MN assays at the lower doses tested (1 and 5 μg/ml). We conclude that mini-gel comet assay and MN scoring using flow cytometry successfully can be used to efficiently study cytotoxic and genotoxic properties of nanoparticles. PMID:27382040

Accumulation of lipids and oxidatively damaged DNA in hepatocytes exposed to particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vesterdal, Lise K.; Danielsen, Pernille H.; Folkmann, Janne K.

Exposure to particles has been suggested to generate hepatosteatosis by oxidative stress mechanisms. We investigated lipid accumulation in cultured human hepatocytes (HepG2) and rat liver after exposure to four different carbon-based particles. HepG2 cells were exposed to particles for 3 h and subsequently incubated for another 18 h to manifest lipid accumulation. In an animal model of metabolic syndrome we investigated the association between intake of carbon black (CB, 14 nm) particles and hepatic lipid accumulation, inflammation and gene expression of Srebp-1, Fasn and Scd-1 involved in lipid synthesis. There was a concentration-dependent increase in intracellular lipid content after exposuremore » to CB in HepG2 cells, which was only observed after co-exposure to oleic/palmitic acid. Similar results were observed in HepG2 cells after exposure to diesel exhaust particles, fullerenes C{sub 60} or pristine single-walled carbon nanotubes. All four types of particles also generated oxidatively damaged DNA, assessed as formamidopyrimidine DNA glycosylase (FPG) sensitive sites, in HepG2 cells after 3 h exposure. The animal model of metabolic syndrome showed increased lipid load in the liver after one oral exposure to 6.4 mg/kg of CB in lean Zucker rats. This was not associated with increased iNOS staining in the liver, indicating that the oral CB exposure was associated with hepatic steatosis rather than steatohepatitis. The lipid accumulation did not seem to be related to increased lipogenesis because there were unaltered gene expression levels in both the HepG2 cells and rat livers. Collectively, exposure to particles is associated with oxidative stress and steatosis in hepatocytes. - Highlights: • Oral exposure to nanosized carbon black was associated with hepatosteatosis in rats. • In vitro studies included carbon black, C{sub 60}, diesel exhaust particles and SWCNTs. • Exposure to particles and free fatty acids increased lipid load in HepG2 cells. • Unaltered expression of lipogenesis genes despite oxidative stress in hepatocytes • Particles evoke hepatosteatosis by increased uptake rather than synthesis of lipids.« less

Free to be me: The relationship between the true self, rejection sensitivity, and use of online dating sites.

PubMed

Hance, Margaret A; Blackhart, Ginette; Dew, Megan

2018-01-01

Prior research (Blackhart et al., 2014) found that rejection-sensitive individuals are more likely to use online dating sites. The purpose of the current research was to explain the relationship between rejection sensitivity and online dating site usage. Study 1 examined whether true self mediated the relation between rejection sensitivity and online dating. Study 2 sought to replicate the findings of Study 1 and to examine whether self-disclosure moderated the relationship between true self and online dating in the mediation model. Results replicated those found by Blackhart et al. and also found that true self mediated the relationship between rejection sensitivity and online dating site usage. These findings suggest that rejection-sensitive individuals feel they can more easily represent their "true" selves in online environments, such as online dating sites, which partially explains why they are more likely to engage in online dating.

The Sensitivity of Genetic Connectivity Measures to Unsampled and Under-Sampled Sites

PubMed Central

Koen, Erin L.; Bowman, Jeff; Garroway, Colin J.; Wilson, Paul J.

2013-01-01

Landscape genetic analyses assess the influence of landscape structure on genetic differentiation. It is rarely possible to collect genetic samples from all individuals on the landscape and thus it is important to assess the sensitivity of landscape genetic analyses to the effects of unsampled and under-sampled sites. Network-based measures of genetic distance, such as conditional genetic distance (cGD), might be particularly sensitive to sampling intensity because pairwise estimates are relative to the entire network. We addressed this question by subsampling microsatellite data from two empirical datasets. We found that pairwise estimates of cGD were sensitive to both unsampled and under-sampled sites, and FST, Dest, and deucl were more sensitive to under-sampled than unsampled sites. We found that the rank order of cGD was also sensitive to unsampled and under-sampled sites, but not enough to affect the outcome of Mantel tests for isolation by distance. We simulated isolation by resistance and found that although cGD estimates were sensitive to unsampled sites, by increasing the number of sites sampled the accuracy of conclusions drawn from landscape genetic analyses increased, a feature that is not possible with pairwise estimates of genetic differentiation such as FST, Dest, and deucl. We suggest that users of cGD assess the sensitivity of this measure by subsampling within their own network and use caution when making extrapolations beyond their sampled network. PMID:23409155

Early gene-diet interaction between glucokinase regulatory protein (GCKR) polymorphism, vegetable and fish intakes in modulating triglyceride levels in healthy adolescents.

PubMed

Tam, C H T; Wang, Y; Lee, H M; Luk, A O Y; Tong, P C Y; Chan, M H M; Ozaki, R; Kong, A P S; So, W Y; Chan, J C N; Ma, R C W

2015-10-01

The benefits of dietary vegetable and fish consumptions on improving glucose and lipid metabolism have been well established. Recently, the T-allele of a common genetic variant rs780094 at glucokinase regulatory protein (GCKR) was reported to be associated with elevated triglyceride (TG) levels but reduced fasting plasma glucose (FPG) and type 2 diabetes risk. However, the dietary modulation on genetic risk is not clearly understood. A cohort of 2095 Chinese adolescents (mean age 15.6 ± 2.0 years, 45.3% male) recruited from a population-based school survey for cardiovascular risk factor assessment, with dietary data including weekly vegetable and fish consumptions as well as clinical data were genotyped for the GCKR rs780094 polymorphism. In the linear regression analysis with adjustment for sex, age, body mass index, and socioeconomic status (school banding, paternal and maternal education levels), the frequency of vegetable intake per week was inversely associated with FPG (P = 0.044). Individuals with low fish intake generally had elevated TG levels but reduced TC, HDL-C and LDL-C (0.006 < P < 0.029). We also observed significant associations of the minor T-allele of GCKR rs780094 with decreased FPG (P = 0.013) and increased TG levels (P = 2.7 × 10(-8)). There were significant gene-diet interactions between rs780094 and vegetable consumption (P(interaction) = 0.009), and between rs780094 and fish consumption (P(interaction) = 0.031) in modulating TG levels. The T-allele of GCKR locus was associated with higher TG levels amongst individuals with ≥7 vegetable meals per week (P = 6.4 × 10(-9)), and among individuals with <7 fish meals per week (P = 0.020 and 7.0 × 10(-7) for 4-6 and ≤3 meals per week, respectively). High intake of vegetable exerted a reduction in TG levels only among CC genotype carriers (Ptrend = 0.020), while high intake of fish was associated with reduced TG levels only among TT genotype carriers (Ptrend = 0.026). In summary, our data indicated that the favorable associations of higher vegetable and fish intakes on TG levels are dependent on the genetic background of an individual. In particular, at-risk TT- genotype carriers of the GCKR variant may derive more benefits from a high fish intake, while the CC-genotype carriers may find further benefits from a high consumption of vegetable. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of a combination of rhGH and metformin on adiponectin levels in patients with metabolic syndrome.

PubMed

Herrmann, B L; Saller, B; Stratmann, M; Berg, C; Mann, K; Janssen, O E

2005-01-01

Adiponectin is a recently discovered adipocytokine that correlates negatively with body mass index and body fat. In patients with GH deficiency, treatment with recombinant human growth hormone (rhGH) reduces body fat mass and thus may also have a favorable effect in patients with metabolic syndrome, and would also be expected to increase adiponectin levels. However, due to its diabetogenic effect, rhGH treatment also bears an increased risk for the development of type 2 diabetes mellitus. We conducted a 18-month randomized, double-blind, placebo-controlled study to assess the effect of rhGH in combination with metformin (MGH) in 14 obese men (7 MGH; 7 Metformin+Placebo, 54 +/- 2 years, BMI 33.0 +/- 1.2 kg/m(2)) with mildly elevated fasting plasma glucose (FPG) at screening (6.1-8.0 mmol/l). All patients received metformin (850 mg twice daily) for treatment of type 2 diabetes mellitus/impaired glucose tolerance, either alone or in combination with rhGH (daily dose 9.5 mug/kg body weight). Glucose disposal rate (GDR) was measured using the euglycemic hyperinsulinemic clamp technique, and body composition was measured by DEXA at 0 and 18 months. After 18 months, the mean adiponectin concentration increased by 32 +/- 11 % (p = 0.018) in the MGH group and did not change in the MP group (- 10 +/- 13 %; p = n. s.). The difference in relative changes in adiponectin levels between the two groups after 18 months was statistically significant (p = 0.026). Improvement in insulin sensitivity (GDR) correlated positively with adiponectin levels (r = 0.73; p = 0.004). In conclusion, the additional administration of rhGH increased adiponectin levels in patients with metabolic syndrome, indicating its potential role in adiponectin-associated insulin sensitivity alterations.

Effect of lipoprotein-associated phospholipase A2 inhibitor on insulin resistance in streptozotocin-induced diabetic pregnant rats.

PubMed

Wang, Guo-Hua; Jin, Jun; Sun, Li-Zhou

2018-06-21

This paper aims to investigate the influence of lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, darapladib, on insulin resistance (IR) in streptozotocin (STZ)-induced diabetic pregnant rats. The rat models were divided into Control (normal pregnancy), STZ + saline (STZ-induced diabetic pregnant rats), STZ + Low-dose and STZ + High-dose darapladib (STZ-induced diabetic pregnant rats treated with low-/high-dose darapladib) groups. Pathological changes were observed by Hematoxylin-eosin (HE) and Immunohistochemistry staining. Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). An automatic biochemical analyzer was used to measure the serum levels of biochemical indicators, and homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated. Western blot was applied to determine levels of inflammatory cytokines. Compared with Control group, rats in the STZ + saline group were significantly decreased in body weight, the number of embryo implantation, the number of insulin positive cells and pancreatic islet size as well as the islet endocrine cells, and high-density lipoprotein (HDL-C) level, but substantially increased in Lp-PLA2, low-density lipoprotein (LDL-C), fatty acids (FFA), serum total cholesterol (TC), triglyceride (TG) levels. Moreover, the increased fasting plasma glucose (FPG) and HOMA-IR and inflammatory cytokines but decreased fasting insulin (FINS) and ISI were also found in diabetic pregnant rats. On the contrary, rats in the darapladib-treated groups were just opposite to the STZ + saline group, and STZ + High-dose group improved better than STZ + Low-dose group. Thus, darapladib can improve lipid metabolism, and enhance insulin sensitivity of diabetic pregnant rats by regulating inflammatory cytokines.

Selection on Inversion Breakpoints Favors Proximity to Pairing Sensitive Sites in Drosophila melanogaster.

PubMed

Corbett-Detig, Russell B

2016-09-01

Chromosomal inversions are widespread among taxa, and have been implicated in a number of biological processes including adaptation, sex chromosome evolution, and segregation distortion. Consistent with selection favoring linkage between loci, it is well established that length is a selected trait of inversions. However, the factors that affect the distribution of inversion breakpoints remain poorly understood. "Sensitive sites" have been mapped on all euchromatic chromosome arms in Drosophila melanogaster, and may be a source of natural selection on inversion breakpoint positions. Briefly, sensitive sites are genomic regions wherein proximal structural rearrangements result in large reductions in local recombination rates in heterozygotes. Here, I show that breakpoints of common inversions are significantly more likely to lie within a cytological band containing a sensitive site than are breakpoints of rare inversions. Furthermore, common inversions for which neither breakpoint intersects a sensitive site are significantly longer than rare inversions, but common inversions whose breakpoints intersect a sensitive site show no evidence for increased length. I interpret these results to mean that selection favors inversions whose breakpoints disrupt synteny near to sensitive sites, possibly because these inversions suppress recombination in large genomic regions. To my knowledge this is the first evidence consistent with positive selection acting on inversion breakpoint positions. Copyright © 2016 by the Genetics Society of America.

Cost consideration as a factor affecting recreation site decisions

Treesearch

Allan Marsinko; John Dwyer; Herb Schroeder

2001-01-01

Because they are charged with providing opportunities for all potential site users, it is important that managers at public sites understand the characteristics and behaviors of different user groups. Recreationists who are sensitive to cost may be more sensitive to certain changes in policies, such as fees and other charges, than those who are not sensitive to costs....

Report of the Committee on the classification and diagnostic criteria of diabetes mellitus.

PubMed

Kuzuya, Takeshi; Nakagawa, Shoichi; Satoh, Jo; Kanazawa, Yasunori; Iwamoto, Yasuhiko; Kobayashi, Masashi; Nanjo, Kisihio; Sasaki, Akira; Seino, Yutaka; Ito, Chikako; Shima, Kenji; Nonaka, Kyohei; Kadowaki, Takashi

2002-01-01

In 1995, the Japan Diabetes Society (JDS) appointed the Committee for the Classification and Diagnosis of Diabetes Mellitus. The Committee presented a final report in May 1999 in Japanese. This is the English version with minor modifications for readers outside Japan. Diabetes mellitus represents a group of diseases of heterogeneous etiology, characterized by chronic hyperglycemia and other metabolic abnormalities, which are due to deficiency of insulin effect. After a long duration of metabolic derangement, specific complications of diabetes (retinopathy, nephropathy, and neuropathy) may occur. Arteriosclerosis is also accelerated. Depending on the severity of the metabolic abnormality, diabetes may be asymptomatic, or may be associated with symptoms (thirst, polyuria, and weight loss), or may progress to ketoacidosis and coma. Both etiological classification and staging of pathophysiology by the degree of deficiency of insulin effect need to be considered. The etiological classification of diabetes and related disorders of glycemia includes, (1) type 1; (2) type 2; (3) those due to specific mechanisms and diseases; and (4) gestational diabetes mellitus. Type 1 is characterized by destructive lesions of pancreatic beta cells either by an autoimmune mechanism or of unknown cause. Type 2 diabetes is characterized by combinations of decreased insulin secretion and decreased insulin sensitivity (insulin resistance). Category (3) includes two subgroups; subgroup A is diabetes in which specific mutations have been identified as a cause of genetic susceptibility, while subgroup B is diabetes associated with other pathologic conditions or diseases. The staging of glucose metabolism includes normal, borderline and diabetic stages. The diabetic stage is further classified into three substages; non-insulin requiring, insulin-requiring for glycemic control, and insulin-dependent (ID) for survival. In each individual, these stages may vary according to the deterioration or the improvement of the metabolic state, either spontaneously or by treatment. The confirmation of chronic hyperglycemia is a prerequisite for the diagnosis of diabetes mellitus. The state of glycemia may be classified within three categories, diabetic type; borderline type; and normal type. Diabetic type is defined when fasting plasma glucose (FPG) is 7.0 mmol/l (126 mg/dl) or higher, and/or plasma glucose 2 h after 75 g glucose load (2hPG) is 11.1 mmol/l (200 mg/dl) or higher. A casual plasma glucose (PG) > or =11.1 mmol/l (200 mg/dl) also indicates diabetic type. Normal type is defined when FPG is below 6.1 mmol/l (110 mg/dl) and 2hPG below 7.8 mmol/l (140 mg/dl). Borderline type includes those who are neither diabetic nor normal types. These cutoff values are for venous PG measurements. The persistence of 'diabetic type' in a subject indicates that he or she has diabetes. For children, a dose of 1.75 g/kg (maximum, 75 g) is used for oral glucose tolerance test (OGTT). The procedure for clinical diagnosis is as follows. Diabetes mellitus is diagnosed when hyperglycemia meeting the criteria for 'diabetic type' is shown on two or more occasions examined on separate days. Diabetes can be diagnosed by a single PG test of 'diabetic type' if one of the following three conditions co-exists, (1) typical symptoms of diabetes mellitus; (2) HbA1c > or =6.5% by a standardized method; or (3) unequivocal diabetic retinopathy. If the above conditions ((1) or (2)) have been present in the past and well documented, the subject is diagnosed either to have diabetes or to be suspected of diabetes, even if the present level of glycemia does not reach that of 'diabetic type'. If the diagnosis of diabetes cannot be established by these procedures, re-testing of PG is recommended after an appropriate interval. The physician should assess not only the presence or absence of diabetes, but also its etiology and glycemic stage, and the presence and absence of diabetic complications or associated conditions. In order to determine the prevalence of diabetes in a population, 'diabetic type' may be regarded as 'diabetes'. The use of 2hPG cutoff level of > or =11.1 mmol/l (200 mg/dl) is recommended. If this is difficult, the FPG cutoff level of > or =7.0 mmol/l (126 mg/dl) can be used, but is likely to lead to under-ascertainment. For screening, the most important point is not to overlook 'diabetes'. In addition to parameters of hyperglycemia, clinical information such as family history, obesity etc., should be regarded as indications for further testing. Only FPG and 2hPG are adopted as cutoff values, but in clinical situations, it is recommended to measure PG also at 30 and 60 min during 75 g OGTT. Among people with normal type, those with 1hPG higher than 10.0 mmol/l (180 mg/dl) are at higher risk to develop diabetes than those with lower 1hPG. When OGTT is performed, the borderline type corresponds to the sum of impaired fasting glycemia (IFG) plus impaired glucose tolerance (IGT) according to the new WHO report. Subjects in this category are at higher risk of developing diabetes than those with 'normal type'. Those with low insulinogenic index (the ratio of increment of plasma insulin to that of PG at 30 min during OGTT) are at particularly high risk to develop diabetes. Microvascular complications are rare but arteriosclerotic complications are fairly frequent in this category. The current definition of GDM is ' any glucose intolerance developed or detected during pregnancy'. We adopt the proposal of the Japan Society of Gynecology and Obstetrics for the diagnosis of GDM (1984). GDM is defined when two or more values during a 75 g OGTT are higher than the following cutoff levels; FPG > or =5.5 mmol/l (100 mg/dl), 1hPG > or =10.0 mmol/l (180 mg/dl) and 2hPG > or =8.3 mmol/l (150 mg/dl). As a screening test, subjects with casual PG > or =5.5 mmol/l (100 mg/dl) are recommended for further testing. Patients who have had documented glucose intolerance before pregnancy, and who present as 'diabetic type' should be under closer supervision than those who develop GDM during pregnancy for the first time. HbA1c: There is a large overlap in the distribution of HbA1c between groups with 'normal type' and 'borderline type' and mild 'diabetic type'. Therefore, HbA1c is not a suitable parameter to detect mild glucose intolerance. HbA1c higher than 6.5% suggests diabetes, but HbA1c below 6.5% alone should not be taken as evidence against the diagnosis of diabetes. COMPARISON WITH REPORTS OF AMERICAN DIABETES ASSOCIATION (ADA) IN 1997 AND WHO IN 1999: The present report is unique in the following points when compared with those of the ADA 'Diabetes Care 20 (1997) 1183' and WHO 'Report of a WHO Consultation (1999)'. (1) Diabetes due to specific mechanisms and diseases is divided into two subgroups; diabetes in which genetic susceptibility is clarified at the DNA level and diabetes associated with other diseases or conditions. (2) Cutoff PG levels are the same as those of ADA and WHO, but a term 'type' is added to each glycemic category, because a single coding of 'diabetic type' hyperglycemia does not define diabetes. Diabetes is diagnosed when 'diabetic type' hyperglycemia is shown on two or more occasions. (3) A single 'diabetic type' hyperglycemia is considered sufficient for the diagnosis of diabetes, if the patient has typical symptoms, HbA1c > or =6.5%, or diabetic retinopathy. (4) OGTT is recommended for those with mild hyperglycemia, because FPG criteria alone would overlook many subjects with 'diabetic type' in Japan. High 1hPG without elevation of FPG and 2hPG is also considered to be a risk factor for future diabetes. (5) Borderline type in the present report corresponds to the sum of IFG and IGT by WHO when OGTT is performed. (6) New criteria for GDM by OGTT are proposed.

Selection on Inversion Breakpoints Favors Proximity to Pairing Sensitive Sites in Drosophila melanogaster

PubMed Central

Corbett-Detig, Russell B.

2016-01-01

Chromosomal inversions are widespread among taxa, and have been implicated in a number of biological processes including adaptation, sex chromosome evolution, and segregation distortion. Consistent with selection favoring linkage between loci, it is well established that length is a selected trait of inversions. However, the factors that affect the distribution of inversion breakpoints remain poorly understood. “Sensitive sites” have been mapped on all euchromatic chromosome arms in Drosophila melanogaster, and may be a source of natural selection on inversion breakpoint positions. Briefly, sensitive sites are genomic regions wherein proximal structural rearrangements result in large reductions in local recombination rates in heterozygotes. Here, I show that breakpoints of common inversions are significantly more likely to lie within a cytological band containing a sensitive site than are breakpoints of rare inversions. Furthermore, common inversions for which neither breakpoint intersects a sensitive site are significantly longer than rare inversions, but common inversions whose breakpoints intersect a sensitive site show no evidence for increased length. I interpret these results to mean that selection favors inversions whose breakpoints disrupt synteny near to sensitive sites, possibly because these inversions suppress recombination in large genomic regions. To my knowledge this is the first evidence consistent with positive selection acting on inversion breakpoint positions. PMID:27343234

Biomarkers of oxidative damage and antioxidant defense capacity in Caiman latirostris blood.

PubMed

Poletta, Gisela L; Simoniello, María Fernanda; Mudry, Marta D

2016-01-01

Several xenobiotics, and among them pesticides, can produce oxidative stress, providing a mechanistic basis for their observed toxicity. Chronic oxidative stress induces deleterious modifications to DNA, lipids and proteins that are used as effective biomarkers to study pollutant-mediated oxidative stress. No previous report existed on the application of oxidative damage and antioxidant defense biomarkers in Caiman latirostris blood, while few studies reported in other crocodilians were done in organs or muscles of dead animals. The aim of this study was to characterize a new set of oxidative stress biomarkers in C. latirostris blood, through the modification of conventional techniques: 1) damage to lipids by thiobarbituric acid reactive substances (TBARS), 2) damage to DNA by comet assay modified with the enzymes FPG and Endo III, and 3) antioxidant defenses: catalase, superoxide dismutase and glutathione; in order to apply them in future biomonitoring studies. We successfully adapted standard procedures for CAT, SOD, GSH and TBARS determination in C. latirostris blood. Calibration curves for FPG and Endo III showed that the three dilutions tested were appropriate to conduct the modified comet assay for the detection of oxidized bases in C. latirostris erythrocytes. One hour of incubation allowed a complete repair of the damage generated. The incorporation of these biomarkers in biomonitoring studies of caiman populations exposed to xenobiotics is highly important considering that this species has recovered from a serious endangered state through the implementation of sustainable use programs in Argentina, and represents nowadays a relevant economic resource for many human communities. Copyright © 2015 Elsevier Inc. All rights reserved.

Assessing the Effect of High Performance Inulin Supplementation via KLF5 mRNA Expression in Adults with Type 2 Diabetes: A Randomized Placebo Controlled Clinical Trail.

PubMed

Ghavami, Abed; Roshanravan, Neda; Alipour, Shahriar; Barati, Meisam; Mansoori, Behzad; Ghalichi, Faezeh; Nattagh-Eshtivan, Elyas; Ostadrahimi, Alireza

2018-03-01

Purpose: The worldwide prevalence of metabolic disorders such as diabetes is increasing rapidly. Currently, the complications of diabetes are the major health concern. The aim of this study was to investigate the effect of high performance (HP) inulin supplementation on glucose homeostasis via KLF5 mRNA expression in adults with type 2 diabetes. Methods: In the present clinical trial conducted for a duration of 6 weeks, 46 volunteers diabetic patients referring to diabetes clinic in Tabriz, Iran, were randomly assigned into intervention (n= 23, consuming 10 gr/d HP inulin) and control groups (n= 23, consuming 10 gr/ d starch). We assessed glycemic and anthropometric indices, blood lipids and plasmatic level of miR-375 as well as KLF5 mRNA expression before and after the intervention. Results: Findings indicated that inulin supplementation significantly decreased fasting plasma glucose (FPG) in comparison to the placebo group (P<0.001). Also Intra-group and between group results showed that inulin supplementation resulted in significant decrease in KLF5 mRNA expression in peripheral blood mononuclear cells (PBMCs) (Fold change: 0.61± 0.11; P-value= 0.001) and significant increase in plasmatic level of miR-375 (Fold change: 3.75± 0.70; P-value=0.004). Conclusion: Considering the improvements of FPG level in diabetic patients, it seems that HP inulin supplementation may be beneficial in controlling diabetes via the expression of some genes. However, further studies are needed to achieve concise conclusions.

Assessing the Effect of High Performance Inulin Supplementation via KLF5 mRNA Expression in Adults with Type 2 Diabetes: A Randomized Placebo Controlled Clinical Trail

PubMed Central

Ghavami, Abed; Roshanravan, Neda; Alipour, Shahriar; Barati, Meisam; Mansoori, Behzad; Ghalichi, Faezeh; Nattagh- Eshtivan, Elyas; Ostadrahimi, Alireza

2018-01-01

Purpose: The worldwide prevalence of metabolic disorders such as diabetes is increasing rapidly. Currently, the complications of diabetes are the major health concern. The aim of this study was to investigate the effect of high performance (HP) inulin supplementation on glucose homeostasis via KLF5 mRNA expression in adults with type 2 diabetes. Methods: In the present clinical trial conducted for a duration of 6 weeks, 46 volunteers diabetic patients referring to diabetes clinic in Tabriz, Iran, were randomly assigned into intervention (n= 23, consuming 10 gr/d HP inulin) and control groups (n= 23, consuming 10 gr/ d starch). We assessed glycemic and anthropometric indices, blood lipids and plasmatic level of miR-375 as well as KLF5 mRNA expression before and after the intervention. Results: Findings indicated that inulin supplementation significantly decreased fasting plasma glucose (FPG) in comparison to the placebo group (P<0.001). Also Intra-group and between group results showed that inulin supplementation resulted in significant decrease in KLF5 mRNA expression in peripheral blood mononuclear cells (PBMCs) (Fold change: 0.61± 0.11; P-value= 0.001) and significant increase in plasmatic level of miR-375 (Fold change: 3.75± 0.70; P-value=0.004). Conclusion: Considering the improvements of FPG level in diabetic patients, it seems that HP inulin supplementation may be beneficial in controlling diabetes via the expression of some genes. However, further studies are needed to achieve concise conclusions. PMID:29670837

Acarbose plus metformin fixed-dose combination outperforms acarbose monotherapy for type 2 diabetes.

PubMed

Wang, Jun-Sing; Huang, Chien-Ning; Hung, Yi-Jen; Kwok, Ching-Fai; Sun, Jui-Hung; Pei, Dee; Yang, Chwen-Yi; Chen, Ching-Chu; Lin, Ching-Ling; Sheu, Wayne Huey-Herng

2013-10-01

To compare the efficacy and safety of acarbose plus metformin fixed-dose combination (FDC) versus acarbose monotherapy for type 2 diabetes (T2D). Eligible T2D patients undergoing treatment with diet control only or oral antidiabetic medications were run-in on acarbose 50mg thrice-daily for 4 weeks, then randomised either to continue this monotherapy, or to acarbose 50mg plus metformin hydrochloride 500mg FDC (acarbose/metformin FDC), each thrice-daily for 16 weeks. Acarbose/metformin FDC therapy significantly reduced HbA1c, fasting plasma glucose (FPG), and postprandial plasma glucose (PPG) from baseline (all p<0.0001) with superior efficacy compared with acarbose monotherapy (between-group differences; HbA1c -1.35%; FPG -29.5mg/dl; PPG -41.6mg/dl; all p<0.0001). Proportionally more patients treated with acarbose/metformin FDC achieved HbA1c <7.0% (47.8% vs. 10.7%, p<0.0001). Both treatments reduced bodyweight (p<0.0001), with a significant between-group difference (-0.6kg, p<0.01) favouring acarbose/metformin FDC. Hypoglycaemia was not reported with either treatment, and the incidence of other adverse events did not differ significantly between the groups. Compared with acarbose monotherapy, acarbose/metformin FDC has superior antihyperglycaemic efficacy, brings proportionally more T2D patients to HbA1c goal, and further reduces bodyweight. Acarbose/metformin FDC is well-tolerated without significant risk of hypoglycaemia and is a potentially advantageous therapy for T2D. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Global Cardiovascular Risk Transition: Associations of Four Metabolic Risk Factors with Macroeconomic Variables in 1980 and 2008

PubMed Central

Danaei, Goodarz; Singh, Gitanjali M; Paciorek, Christopher J; Lin, John K; Cowan, Melanie J; Finucane, Mariel M; Farzadfar, Farshad; Stevens, Gretchen A; Riley, Leanne M; Lu, Yuan; Rao, Mayuree; Ezzati, Majid

2014-01-01

Background It is commonly assumed that globally CVD risk factors are associated with affluence and Westernization. We investigated the associations of body mass index (BMI), fasting plasma glucose (FPG), systolic blood pressure (SBP), and serum total cholesterol (TC) with national income, Western diet, and (for BMI) urbanization in 1980 and 2008. Methods and Results Country-level risk factor estimates for 199 countries between 1980 and 2008 were from a previous systematic analysis of population-based data. We analyzed the associations between risk factors and natural logarithm of per-capita GDP [Ln(GDP)], a measure of Western diet, and (for BMI) percent population living in urban areas. In 1980, there was a positive association between national income and population mean BMI, SBP, and TC. By 2008, the slope of the association between Ln(GDP) and SBP became negative for women and zero for men. TC was associated with national income and Western diet throughout the period. In 1980, BMI rose with per-capita GDP and then flattened at about Int$7000; by 2008, the relationship resembled an inverted-U for women, peaking at middle income levels. BMI had a positive relationship with percent urban population in both 1980 and 2008. FPG had weaker associations with these country macro characteristics, but was positively associated with BMI. Conclusions The changing associations of metabolic risk factors with macroeconomic variables indicate that there will be a global pandemic of hyperglycemia and diabetes, together with high blood pressure in low income countries, unless effective lifestyle, and pharmacological interventions are implemented. PMID:23481623

Dietary patterns predict changes in two-hour post-oral glucose tolerance test plasma glucose concentrations in middle-aged adults.

PubMed

Lau, Cathrine; Toft, Ulla; Tetens, Inge; Carstensen, Bendix; Jørgensen, Torben; Pedersen, Oluf; Borch-Johnsen, Knut

2009-03-01

We examined whether the adherence to major dietary patterns at baseline of 5824 nondiabetic Danes (30-60 y) enrolled in the nonpharmacological Inter99 intervention predicted changes in fasting plasma glucose (FPG) and postchallenge 2-h plasma glucose (2h-PG) concentrations during a 5 y period and whether a potential association was dependent on baseline glucose tolerance status. Through principal component analysis, a score for a traditional dietary pattern (characterized by higher intakes of high-fat sandwich spreads, red meat, potatoes, butter and lard, low-fat fish, sandwich meat, and sauces) and a score for a modern dietary pattern (characterized by higher intakes of vegetables, fruit, vegetable oil/vinegar dressing, poultry, pasta, rice, and cereals) were estimated for each person at baseline. Random effect models adjusting for relevant confounders were used to estimate changes in repetitive measures of FPG and 2h-PG. A higher modern score (of 1 SD) predicted an annual decrease in 2h-PG of 0.015 mmol/L (P < 0.01) regardless of glucose tolerance status. For individuals with isolated impaired glucose tolerance, a higher traditional score (of 1 SD) predicted an annual increase in 2h-PG of 0.083 mmol/L (P < 0.0001). In conclusion, glucose tolerance status did not, in general, affect the predictive effect of the dietary patterns. The study suggests that the risk of worsening 2h-PG concentrations may be smaller for individuals with a high modern dietary pattern score characterized by high intakes of vegetables, fruit, vegetable oil/vinegar dressing, poultry, pasta, rice, and cereals.

Effect of genetic polymorphism of UCP2-866 G/A on repaglinide response in Chinese patients with type 2 diabetes.

PubMed

Wang, Shan; Se, Yan-Mei; Liu, Zhao-Qian; Lei, Ming-Xiang; Hao-BoYang; Sun, Zhi-Xiang; Nie, Sheng-Dan; Zeng, Xiao-min; Wu, Jing

2012-01-01

The aim of the present study was to evaluate the impact of the UCP2-866 G/A polymorphism on the efficacy of repaglinide in treating patients with diabetes mellitus type 2 (T2DM). 370 patients with T2DM and 166 healthy volunteers were enrolled to identify UCP2-866 G/A genotypes. 16 patients with GG genotype, 14 with GA genotype and 11 with AA genotype of UCP2-866 G/A underwent an 8-week repaglinide treatment regimen. There were no differences in allele frequency of UCP2-866 G/A between T2DM patients and control subjects. The patient with AA genotype of UCP2-866 G/A had higher levels of fasting plasma glucose (FPG), 30-min and 2-h postload plasma glucose, glycated haemoglobin (HbA1c), and lower concentrations of 30-min and 2-h postload plasma insulin, homeostasis model assessment of beta cell function (HOMA-beta), deltaI30/deltaG30 compared with GG genotype. After repaglinide treatment for 8 consecutive weeks, we found that A allele carriers of UCP2 in the T2DM patients had smaller decrease in FPG (P < 0.05) and HbA1c (P < 0.05), and smaller increase in 30-min postload plasma insulin (P < 0.01) compared with GG genotypes. We demonstrated that UCP2-866 G/A polymorphism is associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.

Beta-cell response during a meal test: a comparative study of incremental doses of repaglinide in type 2 diabetic patients.

PubMed

Cozma, Lawrence S; Luzio, Stephen D; Dunseath, Gareth J; Underwood, Paul M; Owens, David R

2005-05-01

To assess the effects of incremental doses of repaglinide on postprandial insulin and glucose profiles after a standard 500-kcal test meal. Sixteen diet-treated Caucasians with type 2 diabetes (mean HbA(1c) 8.4%) were enrolled in this randomized, open-label, crossover trial. Subjects received 0.5, 1, 2, and 4 mg repaglinide or placebo in a random fashion, followed by a standard 500-kcal test meal on 5 separate study days, 1 week apart. The insulinogenic index (DeltaI30/DeltaG30) and insulin area under the curve (AUC) from 0 to 30 min (AUC(0-30)) were higher with the 4-mg drug dose compared with the two lower doses and with 2 mg compared with 0.5 mg. On subgroup analysis, the incremental insulin responses were apparent only in the fasting plasma glucose (FPG) < 9-mmol/l subgroup of subjects and not in the FPG >9-mmol/l subgroup. There was a significant dose-related increase in the late postprandial insulin secretion (insulin AUC(120-240)), which resulted in hypoglycemia in four subjects. Proinsulin-to-insulin ratios at 30 and 60 min improved with increasing doses of repaglinide; higher drug doses (2 and 4 mg) were more effective than the 0.5- and 1-mg doses. Significant dose-related increases in early insulin secretion were found only in less advanced diabetic subjects. In advanced diabetic patients, only the maximum dose (4 mg) was significant compared with placebo. Better proinsulin-to-insulin processing was noted with increasing drug doses.

Diagnosis and follow-up of type 2 diabetes in women with PCOS. A role of OGTT?

PubMed

Andersen, Marianne Skovsager; Glintborg, Dorte

2018-06-19

Polycystic ovary syndrome (PCOS) is common in premenopausal women. The majority of women with PCOS have insulin resistance and the risk of type 2 diabetes mellitus (T2D) is higher in women with PCOS compared to controls. In non-pregnant women with PCOS, glycemic status may be assessed by oral glucose tolerance test (OGTT), fasting plasma glucose (FPG), or HbA1c. OGTT has been reckoned gold standard test for diagnosing T2D, but OGTT is rarely used for diagnostic purpose in other non-pregnant individuals at risk of T2D, apart from PCOS. OGTT has questionable reproducibility, and the high sensitivity of the 2 hour glucose value is at the expense of relatively low specificity, especially regarding impaired glucose tolerance (IGT). Furthermore, lean women with PCOS are rarely diagnosed with T2D and only few percent of normal-weight women have prediabetes. Glycemic status is necessary at diagnosis and during follow-up of PCOS, especially in women with high risk of T2D (obesity, previous gestational diabetes (GDM)). We suggest that OGTT should be used in the same situations in PCOS as in other patient groups at risk of T2D. OGTT is indicated for diagnosing GDM, however, OGTT during pregnancy may not be indicated in lean women with PCOS without other risk factors for GDM.

The Effect of Cumin cyminum L. Plus Lime Administration on Weight Loss and Metabolic Status in Overweight Subjects: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

PubMed

Taghizadeh, Mohsen; Memarzadeh, Mohammad Reza; Abedi, Fatemeh; Sharifi, Nasrin; Karamali, Fatemeh; Fakhrieh Kashan, Zohreh; Asemi, Zatollah

2016-08-01

Limited data are available regarding the effects of combined administration of Cumin cyminum L. and lime on weight loss and metabolic profiles among subjects with overweight subjects. The current study aimed to assess the effects of combined administration of Cumin cyminum L. and lime on weight loss and metabolic profiles among subjects with overweight. This randomized double-blind placebo-controlled clinical trial was conducted on 72 subjects with overweight, aged 18 - 50 years old. Participants were randomly divided into three groups: Group A received high-dose Cumin cyminum L. and lime capsules (75 mg each, n = 24), group B low-dose Cumin cyminum L. and lime capsules (25 mg each, n = 24) and group C placebos (n = 24) twice daily for eight weeks. After eight weeks of intervention, compared with low-dose C. cyminum L. plus lime and placebo, taking high-dose C. cyminum L. plus lime resulted in significant weight loss (in the high-dose group: -2.1 ± 1.7 vs. in the low-dose group: -1.2 ± 1.5 and in the placebo group: + 0.2 ± 1.3 kg, respectively; P < 0.001) and body mass index (-0.8 ± 0.6 vs. -0.5 ± 0.5 and +0.1 ± 0.5 kg/m 2 , respectively; P < 0.001). In addition, administration of high-dose C. cyminum L. plus lime compared with low-dose C. cyminum L. plus lime and placebo, led to a significant reduction in fasting plasma glucose (FPG) (P < 0.001) and a significant rise in quantitative insulin sensitivity check index (QUICKI) (+ 0.02 ± 0.02 vs. + 0.01 ± 0.02 and 0.01 ± 0.01, respectively; P = 0.01). Moreover, a significant decrease in serum triglycerides (-14.1 ± 56.2 vs. +13.9 ± 36.8 and + 10.6 ± 25.1 mg/dL; respectively; P = 0.03), total-cholesterol (-18.4 ± 28.6 vs. +8.6 ± 28.5 and -1.0 ± 24.8 mg/dL; respectively; P = 0.004) and low density lipoproteins- (LDL)-cholesterol levels (-11.8 ± 20.7 vs. +6.5 ± 23.2 and -2.9 ± 20.4 mg/dL, respectively; P = 0.01) was observed following the consumption of high-dose C. cyminum L. plus lime compared with low-dose C. cyminum L. plus lime and placebo. Results of the current study indicated that taking high-dose C. cyminum L. plus lime for eight weeks among subjects with overweight had beneficial effects on weight, BMI, FPG, QUICKI, triglycerides, total-cholesterol and LDL-cholesterol levels.

The Effect of Cumin cyminum L. Plus Lime Administration on Weight Loss and Metabolic Status in Overweight Subjects: A Randomized Double-Blind Placebo-Controlled Clinical Trial

PubMed Central

Taghizadeh, Mohsen; Memarzadeh, Mohammad Reza; Abedi, Fatemeh; Sharifi, Nasrin; Karamali, Fatemeh; Fakhrieh Kashan, Zohreh; Asemi, Zatollah

2016-01-01

Background Limited data are available regarding the effects of combined administration of Cumin cyminum L. and lime on weight loss and metabolic profiles among subjects with overweight subjects. Objectives The current study aimed to assess the effects of combined administration of Cumin cyminum L. and lime on weight loss and metabolic profiles among subjects with overweight. Patients and Methods This randomized double-blind placebo-controlled clinical trial was conducted on 72 subjects with overweight, aged 18 - 50 years old. Participants were randomly divided into three groups: Group A received high-dose Cumin cyminum L. and lime capsules (75 mg each, n = 24), group B low-dose Cumin cyminum L. and lime capsules (25 mg each, n = 24) and group C placebos (n = 24) twice daily for eight weeks. Results After eight weeks of intervention, compared with low-dose C. cyminum L. plus lime and placebo, taking high-dose C. cyminum L. plus lime resulted in significant weight loss (in the high-dose group: -2.1 ± 1.7 vs. in the low-dose group: -1.2 ± 1.5 and in the placebo group: + 0.2 ± 1.3 kg, respectively; P < 0.001) and body mass index (-0.8 ± 0.6 vs. -0.5 ± 0.5 and +0.1 ± 0.5 kg/m2, respectively; P < 0.001). In addition, administration of high-dose C. cyminum L. plus lime compared with low-dose C. cyminum L. plus lime and placebo, led to a significant reduction in fasting plasma glucose (FPG) (P < 0.001) and a significant rise in quantitative insulin sensitivity check index (QUICKI) (+ 0.02 ± 0.02 vs. + 0.01 ± 0.02 and 0.01 ± 0.01, respectively; P = 0.01). Moreover, a significant decrease in serum triglycerides (-14.1 ± 56.2 vs. +13.9 ± 36.8 and + 10.6 ± 25.1 mg/dL; respectively; P = 0.03), total-cholesterol (-18.4 ± 28.6 vs. +8.6 ± 28.5 and -1.0 ± 24.8 mg/dL; respectively; P = 0.004) and low density lipoproteins- (LDL)-cholesterol levels (-11.8 ± 20.7 vs. +6.5 ± 23.2 and -2.9 ± 20.4 mg/dL, respectively; P = 0.01) was observed following the consumption of high-dose C. cyminum L. plus lime compared with low-dose C. cyminum L. plus lime and placebo. Conclusions Results of the current study indicated that taking high-dose C. cyminum L. plus lime for eight weeks among subjects with overweight had beneficial effects on weight, BMI, FPG, QUICKI, triglycerides, total-cholesterol and LDL-cholesterol levels. PMID:27781121

A randomized controlled clinical trial investigating the effect of calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress and insulin resistance in pregnant women at risk for pre-eclampsia.

PubMed

Asemi, Z; Samimi, M; Heidarzadeh, Z; Khorrammian, H; Tabassi, Z

2012-05-15

Increased levels of pro-inflammatory factors, markers of oxidative stress and insulin resistance during pregnancy have been associated with the development of pre-eclampsia. There is some evidence to suggest that calcium supplement and aspirin can reduce the risk of the disorder. To our knowledge, no reports are available indicating the effects of consumed calcium supplement plus aspirin on high sensitivity C-reactive protein (hs-CRP), oxidative stress parameters and insulin resistance in pregnant women at risk for pre-eclampsia. This study was designed to investigate the effects of consumed calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress parameters and insulin resistance among Iranian pregnant women at risk for pre-eclampsia. This randomized single-blind controlled clinical trial was carried out among 42 pregnant women at risk for pre-eclampsia, primigravida, aged 18-40 year old who were carrying singleton pregnancy at their third trimester. Subjects were randomly assigned to received either the placebo (n = 22) or calcium supplement plus low-dose aspirin (n = 20) for 9 weeks. Calcium supplement plus low-dose aspirin were containing 500 mg carbonate calcium plus 80 mg aspirin. Fasting blood samples were taken at baseline and after 9 weeks intervention to measure serum hs-CRP, oxidative stress parameters including plasma Total Antioxidant Capacity (TAC) and Total Glutathione (GSH), Fasting Plasma Glucose (FPG), serum insulin and HOMA-IR score. Consumption of calcium supplement plus low-dose aspirin resulted in a significant difference serum hs-CRP levels as compared to the placebo (102.87 vs. 3227.75 ng mL(-1), p = 0.01). Also, mean changes for plasma TAC (68.96 vs. -74.46 mmol L(-1), p = 0.04) and total GSH levels (304.33 vs. -39.33 micromol L(-1), p = 0.03) were significantly different between the two groups. No significant differences were found comparing calcium supplement plus low-dose aspirin and placebo in terms of their effects on FPG, serum insulin levels and HOMA-IR. Within-group differences in the placebo group revealed a significant increase in serum hs-CRP levels (3227.75 ng mL(-1), p = 0.008) and marginally significant increase in plasma total GSH levels (304.33 micromol L(-1), p = 0.07). In conclusion, consumption calcium supplement plus low-dose aspirin during pregnancy for 9 weeks in pregnant women at risk for pre-eclampsia resulted in a significant difference serum hs-CRP and increased levels of plasma TAC and total GSH as compared to the placebo group, but could not affect serum insulin levels and HOMA-IR score.

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages

PubMed Central

Greinert, R.; Volkmer, B.; Henning, S.; Breitbart, E. W.; Greulich, K. O.; Cardoso, M. C.; Rapp, Alexander

2012-01-01

UVA (320–400 nm) represents the main spectral component of solar UV radiation, induces pre-mutagenic DNA lesions and is classified as Class I carcinogen. Recently, discussion arose whether UVA induces DNA double-strand breaks (dsbs). Only few reports link the induction of dsbs to UVA exposure and the underlying mechanisms are poorly understood. Using the Comet-assay and γH2AX as markers for dsb formation, we demonstrate the dose-dependent dsb induction by UVA in G1-synchronized human keratinocytes (HaCaT) and primary human skin fibroblasts. The number of γH2AX foci increases when a UVA dose is applied in fractions (split dose), with a 2-h recovery period between fractions. The presence of the anti-oxidant Naringin reduces dsb formation significantly. Using an FPG-modified Comet-assay as well as warm and cold repair incubation, we show that dsbs arise partially during repair of bi-stranded, oxidative, clustered DNA lesions. We also demonstrate that on stretched chromatin fibres, 8-oxo-G and abasic sites occur in clusters. This suggests a replication-independent formation of UVA-induced dsbs through clustered single-strand breaks via locally generated reactive oxygen species. Since UVA is the main component of solar UV exposure and is used for artificial UV exposure, our results shine new light on the aetiology of skin cancer. PMID:22941639

Effect of gender on treatment outcomes in type 2 diabetes mellitus.

PubMed

McGill, J B; Vlajnic, A; Knutsen, P G; Recklein, C; Rimler, M; Fisher, S J

2013-12-01

To evaluate the effect of gender on clinical outcomes in people with type 2 diabetes mellitus (T2DM) receiving antidiabetes therapy. This is a pooled analysis from nine similarly designed phase 3 and 4 randomized, controlled studies evaluating insulin glargine and an active comparator (NPH insulin, insulin lispro, premixed insulin, oral antidiabetes drugs, dietary intervention) in adults with T2DM. Impact of gender on outcomes including HbA1c, fasting plasma glucose (FPG), weight-adjusted insulin dose, and hypoglycemia incidence was evaluated after 24 weeks of treatment. Overall, 1651 male and 1287 female individuals were included; 49.8% and 50.2% were treated with insulin glargine or comparators, respectively. Females receiving insulin glargine were less likely than males to achieve a glycemic target of HbA1c≤7.0% (53mmol/mol) (54.3% vs 60.8%, respectively, p=0.0162); there was no difference between females and males receiving comparators (52.7% vs 51.3%, respectively, p=0.4625). Females had significantly greater reductions in FPG (3.1mg/dL, p=0.0458), required significantly higher insulin doses (0.03IU/kg, p=0.0071), and had significantly higher annual rates of symptomatic (p<0.0001), glucose-confirmed (<50 and <70mg/dL) symptomatic (p=0.0005 and p<0.0001), and severe hypoglycemia (p=0.0020) than males. Females in this analysis had smaller reductions in HbA1c and were less likely to reach glycemic goals despite higher insulin doses and more hypoglycemic events than males. Differences in gender responses to therapy should be considered when individualizing treatment for people with T2DM. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Dose-ranging study with the glucokinase activator AZD1656 as monotherapy in Japanese patients with type 2 diabetes mellitus.

PubMed

Kiyosue, A; Hayashi, N; Komori, H; Leonsson-Zachrisson, M; Johnsson, E

2013-10-01

To assess the glucose-lowering effects of monotherapy with the glucokinase activator AZD1656 in Japanese patients with type 2 diabetes mellitus. This was a randomized, double-blind, placebo-controlled study performed in Japan (NCT01152385). Patients (n = 224) were randomized to AZD1656 (40-200, 20-140 or 10-80 mg titrated doses) or placebo. The primary variable was the placebo-corrected change from baseline to 4 months in glycated haemoglobin (HbA1c). Effects on fasting plasma glucose (FPG) and safety were also assessed. HbA1c was reduced numerically from baseline by 0.3-0.8% with AZD1656 and by 0.1% with placebo over the first 2 months of treatment, after which effects of AZD1656 started to decline. The changes from baseline to 4 months in HbA1c were not significant for the AZD1656 40-200 mg group versus placebo [mean (95% CI) placebo-corrected change: -0.22 (-0.65, 0.20)%; p = 0.30]. Formal significance testing was not carried out for the other two AZD1656 dose groups. A higher percentage of patients on AZD1656 achieved HbA1c ≤ 7% after 4 months versus placebo, but responder rates were low. Results for FPG reflected those for HbA1c. Cases of hypoglycaemia were rare with AZD1656 (one patient) and no safety concerns were raised. Although initially favourable plasma glucose reductions were observed, there was a loss of effect over time with sustained AZD1656 treatment. The study design did not allow an evaluation of the reasons for this lack of long-term efficacy. © 2013 John Wiley & Sons Ltd.

[An evaluation of clinical characteristics and prognosis of brain-stem infarction in diabetics].

PubMed

Lu, Zheng-qi; Li, Hai-yan; Hu, Xue-qiang; Zhang, Bing-jun

2011-01-01

To analyze the relationship between diabetics and the onset, clinical outcomes and prognosis of brainstem infarction, and to evaluate the impact of diabetes on brainstem infarction. Compare 172 cases of acute brainstem infarction in patients with or without diabetes. Analyze the associated risk factors of patients with brain-stem infarction in diabetics by multi-variate logistic regression analysis. Compare the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin scale (mRS) Score, pathogenetic condition and the outcome of the two groups in different times. The systolic blood pressure (SBP), TG, LDL-C, apolipoprotein B (Apo B), glutamyl transpeptidase (γ-GT), fibrinogen (Fb), fasting blood glucose (FPG) and glycosylated hemoglobin(HbA1c)in diabetic group were higher than those in non-diabetic group, which was statistically significant (P < 0.05). From multi-variate logistic regression analysis, γ-GT, Apo B and FPG were the risk predictors of diabetes with brainstem infarction(OR = 1.017, 4.667 and 3.173, respectively), while HDL-C was protective (OR = 0.288). HbA1c was a risk predictor of severity for acute brainstem infarction (OR = 1.299), while Apo A was beneficial (OR = 0.212). Compared with brain-stem infarction in non-diabetic group, NIHSS score and intensive care therapy of diabetic groups on the admission had no statistically significance, while the NIHSS score on discharge and the outcome at 6 months' of follow-up were statistically significant. Diabetes is closely associated with brainstem infarction. Brainstem infarction with diabetes cause more rapid progression, poorer prognosis, higher rates of mortality as well as disability and higher recurrence rate of cerebral infarction.

[Correlation study between obesity and dawn phenomenon in patients with type 2 diabetes].

PubMed

Guo, Zhenhong; Xu, Jie; Wang, Jingyu; Han, Fei; Zhang, Yi; Yang, X iaoyun; Yang, Shaohua; Chang, Bai; Yang, Juhong; Shan, Chunyan; Chen, Liming; Chang, Baocheng; Xu, Yanguang

2016-01-01

To investigate the correlation between the frequency of dawn phenomenon and obesity in patients with type 2 diabetes. This study was conducted in 98 patients with type 2 diabetes admitted to the Metabolic Disease Hospital of Tianjin Medical University from 2011 to 2014. The subjects were divided into 3 groups according to BMI: the normal weight (BMI 18.5-23.9 kg/m(2), n = 30), the overweight(BMI 24-27.9 kg/m(2), n = 33)and the obesity (BMI ≥ 28.0 kg/m(2), n = 35). All participants underwent continuous glucose monitoring for 72 h. Fasting plasma glucose(FPG), insulin and C-peptide were tested. Frequency of dawn phenomenon among the 3 groups was calculated, and the correlations between dawn phenomenon and its related factors were analyzed. The frequency of dawn phenomenon in type 2 diabetes increased with the increase of BMI in the 3 groups (P < 0.05) with 33.3% in the normal weight, 78.8% in the overweight and 88.6% in the obesity groups, respectively. The dawn phenomenon was positively correlated with BMI (r = 0.424, P < 0.05), Homeostasis model assessment of insulin resistance(HOMA-IR) (r = 0.781, P < 0.05), waist circumference (r = 0.394, P < 0.05), fasting C-peptide (r = 0.254, P < 0.05)and TG (r = 0.220, P < 0.05). It was negatively correlated with the course of diabetes mellitus (r = -0.278, P<0.05) and HDL-C (r = -0.268, P < 0.05). No correlation could be viewed between the dawn phenomenon and age, LDL-C, glycosylated hemoglobin A1c(HbA1c), TC and FPG (P > 0.05). The dawn phenomenon is closely associated with obesity and insulin resistance. The frequency of dawn phenomenon increases with BMI.

The role of a fixed Berberis aristata/Silybum marianum combination in the treatment of type 1 diabetes mellitus.

PubMed

Derosa, Giuseppe; D'Angelo, Angela; Maffioli, Pamela

2016-10-01

To evaluate if the addition of Berberis aristata/Silybum marianum (Berberol(®)) leads to a reduction of insulin dose and to an improvement of glycemic control in patients with type 1 diabetes mellitus. 85 type 1 diabetic patients were enrolled and randomized to take placebo or B. aristata/S. marianum 588/105 mg, 1 tablet at lunch and 1 tablet at dinner, for six months. We evaluated if there was a reduction of insulin dose necessary to reach an adequate glycemic control. We also evaluated at the study start, and after 6 months: body mass index (BMI), glycated hemoglobin, fasting plasma glucose (FPG), post-prandial glucose (PPG), lipid profile. We observed a reduction of total insulin consumption in B. aristata/S. marianum, both compared to baseline and to placebo. Regarding insulin administration at meals, we recorded that the group treated with B. aristata/S. marianum used less insulin at meals, and at bedtime. Glycated hemoglobin decreased with B. aristata/S. marianum compared to baseline, but not compared to placebo. There was a decrease of FPG, and PPG with B. aristata/S. marianum both compared to baseline and to placebo. Regarding lipid profile, we recorded a decrease of total cholesterol, triglycerides, and LDL-cholesterol and an increase of HDL-cholesterol with B. aristata/S. marianum, both compared to baseline and to placebo. The addition of B. aristata/S. marianum to insulin therapy in patients with type 1 diabetes mellitus leads to a reduction of the insulin dose necessary to have an adequate glycemic control. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Predicting the development of diabetes using the product of triglycerides and glucose: the Chungju Metabolic Disease Cohort (CMC) study.

PubMed

Lee, Seung-Hwan; Kwon, Hyuk-Sang; Park, Yong-Moon; Ha, Hee-Sung; Jeong, Seung Hee; Yang, Hae Kyung; Lee, Jin-Hee; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Yoon, Kun-Ho

2014-01-01

To determine whether the TyG index, a product of the levels of triglycerides and fasting plasma glucose (FPG) might be a valuable marker for predicting future diabetes. A total of 5,354 nondiabetic subjects who had completed their follow-up visit for evaluating diabetes status were selected from a large cohort of middle-aged Koreans in the Chungju Metabolic Disease Cohort study. The risk of diabetes was assessed according to the baseline TyG index, calculated as ln[fasting triglycerides (mg/dL) × FPG (mg/dL)/2]. The median follow-up period was 4.6 years. During the follow-up period, 420 subjects (7.8%) developed diabetes. The baseline values of the TyG index were significantly higher in these subjects compared with nondiabetic subjects (8.9 ± 0.6 vs. 8.6 ± 0.6; P<0.0001) and the incidence of diabetes increased in proportion to TyG index quartiles. After adjusting for age, gender, body mass index, waist circumference, systolic blood pressure, high-density lipoprotein (HDL)-cholesterol level, a family history of diabetes, smoking, alcohol drinking, education level and serum insulin level, the risk of diabetes onset was more than fourfold higher in the highest vs. the lowest quartile of the TyG index (relative risk, 4.095; 95% CI, 2.701-6.207). The predictive power of the TyG index was better than the triglyceride/HDL-cholesterol ratio or the homeostasis model assessment of insulin resistance. The TyG index, a simple measure reflecting insulin resistance, might be useful in identifying individuals at high risk of developing diabetes.

Predicting the Development of Diabetes Using the Product of Triglycerides and Glucose: The Chungju Metabolic Disease Cohort (CMC) Study

PubMed Central

Lee, Seung-Hwan; Kwon, Hyuk-Sang; Park, Yong-Moon; Ha, Hee-Sung; Jeong, Seung Hee; Yang, Hae Kyung; Lee, Jin-Hee; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Yoon, Kun-Ho

2014-01-01

Background To determine whether the TyG index, a product of the levels of triglycerides and fasting plasma glucose (FPG) might be a valuable marker for predicting future diabetes. Methods A total of 5,354 nondiabetic subjects who had completed their follow-up visit for evaluating diabetes status were selected from a large cohort of middle-aged Koreans in the Chungju Metabolic Disease Cohort study. The risk of diabetes was assessed according to the baseline TyG index, calculated as ln[fasting triglycerides (mg/dL) × FPG (mg/dL)/2]. The median follow-up period was 4.6 years. Results During the follow-up period, 420 subjects (7.8%) developed diabetes. The baseline values of the TyG index were significantly higher in these subjects compared with nondiabetic subjects (8.9±0.6 vs. 8.6±0.6; P<0.0001) and the incidence of diabetes increased in proportion to TyG index quartiles. After adjusting for age, gender, body mass index, waist circumference, systolic blood pressure, high-density lipoprotein (HDL)-cholesterol level, a family history of diabetes, smoking, alcohol drinking, education level and serum insulin level, the risk of diabetes onset was more than fourfold higher in the highest vs. the lowest quartile of the TyG index (relative risk, 4.095; 95% CI, 2.701–6.207). The predictive power of the TyG index was better than the triglyceride/HDL-cholesterol ratio or the homeostasis model assessment of insulin resistance. Conclusions The TyG index, a simple measure reflecting insulin resistance, might be useful in identifying individuals at high risk of developing diabetes. PMID:24587359

Serum calcium changes and risk of type 2 diabetes mellitus in Asian population.

PubMed

Suh, Sunghwan; Bae, Ji Cheol; Jin, Sang-Man; Jee, Jae Hwan; Park, Mi Kyoung; Kim, Duk Kyu; Kim, Jae Hyeon

2017-11-01

We examined the association between changes in serum calcium levels with the incidence of type 2 diabetes mellitus (T2DM) in apparently healthy South Korean subjects. A retrospective longitudinal analysis was conducted with subjects who had participated in comprehensive health check-ups at least four times over a 7-year period (between 2006 and 2012). In total, 23,121 subjects were categorized into tertiles based on changes in their albumin-adjusted serum calcium levels. Multivariate Cox regression models were fitted to assess the association between changes in serum calcium levels during follow-up and the relative risk of diabetes incidence. After a median follow-up of 57.4months, 1,929 (8.3%) new cases of T2DM occurred. Simple linear regression analysis showed serum calcium level changes correlated positively with changes in HbA1c and fasting plasma glucose (FPG) levels (B=5.72, p<0.001 for FPG; B=0.13, p<0.001 for HbA1c). An increase in albumin-adjusted serum calcium levels during follow-up was related to an increased risk of T2DM. After adjustment for potential confounders, the risk of T2DM was 1.6 times greater for subjects whose albumin-adjusted serum calcium levels were in the highest change tertile during follow-up than for subjects whose levels were in the lowest tertile (HR 1.65, 95% CI 1.44-1.88, P<0.001). The elevation of albumin-adjusted serum calcium levels was associated with an increased risk of T2DM, independent of baseline glycemic status. Copyright © 2017 Elsevier B.V. All rights reserved.

Progression from impaired glucose tolerance to type 2 diabetes in obese children and adolescents: a 3-6-year cohort study in southern Thailand.

PubMed

Jaruratanasirikul, Somchit; Thammaratchuchai, Sudarat; Puwanant, Maneerat; Mo-Suwan, Ladda; Sriplung, Hutcha

2016-11-01

Childhood obesity is associated with abnormal glucose metabolism and type 2 diabetes mellitus (T2DM). This study evaluated the prevalence of abnormal glucose metabolism in asymptomatic obese children and adolescents, and determined the percentage of T2DM development after 3-6 years of follow-up. During 2007-2013, 177 obese children and adolescents who had normal fasting plasma glucose (FPG<100 mg/dL) were given an oral glucose tolerance test (OGTT). The participants were classified into four groups: normal glucose tolerance (NGT), NGT-hyperinsulinemia (NGT-HI), impaired glucose tolerance (IGT), and diabetes mellitus (DM). Blood chemistries, including FPG, glycated hemoglobin, and lipid profiles, and liver function test were performed every 6-12 months or when the patient developed any symptom or sign indicative of diabetes. Glucose metabolism alterations were detected in 81.4% of the participants: 63.8% with NGT-HI, 15.3% with IGT, and 2.3% with T2DM. The median levels of homeostasis model assessment-insulin resistance (HOMA-IR) in patients with IGT (8.63) were significantly greater than those in the patients with NGT (4.04) (p<0.01). During the follow-up, 22 patients (14.4%) developed T2DM significantly more from the IGT group (nine of 33 cases, 27.3%) than the NGT-HI group (12 of 108 cases, 11.1%) (p=0.022). The predicting parameters for T2DM conversion were weight status, body mass index (BMI), FBG, fasting insulin, alanine transaminase (ALT) levels, and HOMA-IR. Glucose metabolism alteration was commonly found among obese adolescents. Factors associated with T2DM development were greater weight status and the severity of insulin resistance as shown by higher HOMA-IR levels.

Dietary Fiber Intake Is Associated with HbA1c Level among Prevalent Patients with Type 2 Diabetes in Pudong New Area of Shanghai, China

PubMed Central

Jiang, Junyi; Qiu, Hua; Zhao, Genming; Zhou, Yi; Zhang, Zhijie; Zhang, Hong; Jiang, Qingwu; Sun, Qiao; Wu, Hongyan; Yang, Liming; Ruan, Xiaonan; Xu, Wang-Hong

2012-01-01

Background Dietary factors play an important role in glycemic control in diabetic patients. However, little is known about their effects among Chinese diabetic patients, whose diets are typically abundant in fiber and high in glycemic index (GI) values. Methodology/Principal Findings 934 patients with type 2 diabetes and 918 healthy volunteers from Pudong New Area, Shanghai, China, were interviewed during the period of Oct-Dec, 2006 to elicit demographic characteristics and lifestyle factors. Dietary habits were assessed using a validated food frequency questionnaire. Anthropometric measurements, bio-specimen collection and biochemical assays were conducted at the interview according to a standard protocol. In this population, diabetic patients consumed lower levels of energy and macronutrients but had higher levels of fasting plasma glucose (FPG), glycolated hemoglobin A1c (HbA1c), triglyceride and body mass index than healthy adults. While the average consumption levels of the nutrients among diabetic patients did not vary along duration of the disease, the average levels of FPG and HbA1c increased with increasing duration. Regardless of diabetes duration, HbA1c level was observed lower in patients having a higher fiber or lower GI intake. Compared with those with the lowest tertile intake of fiber, the adjusted odds ratios (ORs) for poor glycemic control reduced from 0.75 (95%CI: 0.54–1.06) to 0.51 (95%CI: 0.34–0.75) with increasing tertile intake (P for trend <0.001). Conclusions Dietary fiber may play an important role in reducing HbA1c level. Increasing fiber intake may be an effective approach to improve glycemic control among Chinese diabetic patients. PMID:23077514

Prevalence of prediabetes in patients with acute coronary syndrome: impact on in-hospital outcomes.

PubMed

AbuShady, M M; Mohamady, Y; Enany, B; Nammas, W

2015-02-01

Prediabetes is a serious condition that is associated with an increase in cardiovascular morbidity and mortality. We sought to explore the prevalence of prediabetes in patients admitted with acute coronary syndrome (ACS) who were not known to have diabetes and to determine the impact of prediabetes on in-hospital clinical outcomes versus non-diabetic patients. Prospectively, we enrolled 200 patients not known to have diabetes or prediabetes, admitted with ACS. Laboratory tests included fasting plasma glucose (FPG), 2-h plasma glucose (2hPG) after 75 g glucose, HbA1c and lipid profile. Electrocardiogram and echocardiography were done. The primary end-point was in-hospital major adverse cardiovascular events (MACE). Mean age was 50.9 ± 6.8 years (70.5% males). The prevalence of patients with diabetes and patients with prediabetes was 24.5% and 20% respectively. Newly discovered diabetic patients were excluded. Compared with patients without diabetes, prediabetic patients had a higher body mass index (BMI) (P = 0.002) and a longer hospital stay (P = 0.09). In-hospital MACE occurred in 10 (25%) patients with prediabetes versus six (5.4%) in patients without diabetes (P = 0.001). In-hospital MACE correlated with prediabetes (r = 0.28, P < 0.001), BMI (r = 0.14, P = 0.093), FPG (r = 0.19, P = 0.014), 2hPG (r = 0.19, P = 0.017) and HbA1c (r = 0.19, P = 0.019). Multivariate regression analysis identified prediabetes as the only independent predictor of in-hospital MACE. Prediabetes is common in patients presenting with ACS who are not previously known to have diabetes. Prediabetic patients had worse in-hospital clinical outcomes compared with patients without diabetes. © 2014 Royal Australasian College of Physicians.

Consensus on Insulin Dose and Titration Algorithms in Ambulatory Care of Type 2 Diabetes in India.

PubMed

Kovil, Rajiv; Chawla, Manoj; Rajput, Rajesh; Singh, A K; Sinha, Binayak; Ghosal, Samit; Ballani, Piya; Gupta, Sunil; Tanna, Snehal; Bandukwala, S M; Shah, Tejas; Negalur, Vijay; Bhoraskar, Anil; Aravind, S R; Zargar, Abdul H; Kesavadev, Jothydev; Das, Ashok Kumar

2017-02-01

Insulin is the oldest of the currently available treatment options in Type 2 diabetes mellitus (T2DM) and is considered as the most effective glucose lowering agent. Despite this, decision on starting insulin therapy is often delayed in India as well as worldwide due to various barriers at both patient and physician levels. Appropriate insulin dosing and titration is also critical to the successful achievement of tight glycaemic control. To provide simple and easily implementable guidelines to primary care physicians on appropriate insulin dosing and titration of various insulin regimens for both initiation and intensification. Each insulin regimen (once daily [OD] basal, OD, twice daily and thrice daily premixed, basal-plus and basal-bolus) was presented and evaluated for dosing and titration based on established guidelines, data from approved pack inserts, and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives patient-physician experience in their clinical practice and common therapeutic practices followed in India. Recommendations for dosing and titration of basal, basal-plus, premixed and basal-bolus insulins were developed. The key recommendations are that insulin doses can be adjusted once or twice weekly; adjustment can be based on lowest/mean of three recent self-monitoring of plasma glucose pre-meal/fasting plasma glucose (FPG) values. The titration should be based on FPG or pre-meal value of 80-130 mg/dL and the dose should be reduced by 10-20% for patients reporting hypoglycaemia(<70mg/dL). The consensus based recommendations mentioned in this paper will be a useful reference tool for health care practitioners, to initiate, optimise and intensify insulin therapy and to successfully achieve optimal glucose control.

Methanol seed extract of Citrus paradisi Macfad lowers blood glucose, lipids and cardiovascular disease risk indices in normal Wistar rats.

PubMed

Adeneye, Adejuwon A

2008-01-01

Alcoholic decoction of Citrus paradisi Macfad (Rutaceae) seed is traditionally used for the management of diabetes mellitus and obesity by the natives of South-West Nigeria. Despite its ancestral use, scientific validations of its therapeutic uses in the management of these conditions are lacking. The present preliminary study was undertaken to evaluate blood glucose and lipid lowering effects as well as cardiovascular disease risk factor-reducing effect of Citrus paradisi Macfad (100% methanol seed extract) in male Wistar rats. Rats, divided into groups I - V, with 6 rats in each group, were gavaged at the dose levels of 10 ml/kg/day of distilled water, 10 ml/kg of body weight/day of dimethyl sulphoxide (DMSO), 100, 300, and 600 mg/kg of body weight/ day of the extract dissolved in 10 ml/kg DMSO, respectively, for 30 days. On day 31, blood samples obtained were assayed for fasting plasma glucose (FPG), total cholesterol (TC), high density lipoprotein (HDL-c), low density lipoprotein (LDL-c), and very low density lipoprotein (VLDL-c) using standard procedures. Cardiovascular disease risk assessing factors such as obesity or body mass index (BMI), atherogenic index (AI), coronary risk index (CRI) were calculated. Results showed significant (p < 0.05, p < 0.001) dose related lowering effects of the extract on FPG, cardiovascular disease risk assessing indices and lipid parameters except HDL-c fraction which was significantly (p < 0.05, p < 0.001) elevated. The extract also induced significant (p < 0.05) dose related weight loss in the treated rats in the latter 15 days of their treatment. These results, therefore, lend support to its therapeutic potentials in the management of suspected type 2 diabetic patients.

Effects of pomegranate juice consumption on inflammatory markers in patients with type 2 diabetes: A randomized, placebo-controlled trial.

PubMed

Sohrab, Golbon; Nasrollahzadeh, Javad; Zand, Hamid; Amiri, Zohreh; Tohidi, Maryam; Kimiagar, Masoud

2014-03-01

Diabetes causes the increased concentration of circulatory cytokines as a result of inflammation. Considering that pomegranate juice (PJ) is known to have antioxidant and anti-inflammatory properties, the purpose of this study was to determine the effects of PJ consumption on markers of inflammation in patients with type 2 diabetes (T2D). In a randomized, double-blind clinical trial study, 50 patients with T2D (40-65 years old) were randomly assigned to one of two groups. Participants in each group received either 250 mL/day PJ or a control beverage for 12 weeks. Biochemical markers including fasting plasma glucose (FPG), insulin and inflammatory markers were assayed on the baseline and follow-up blood samples. In all, 44 patients in two groups were included in the analysis: PJ (n = 22) and placebo (n = 22). After 12 weeks of intervention, in the PJ group, there were 32% and 30% significant decreases in plasma C-reactive protein (hs-CRP) and Interlukin-6, respectively (P < 0.05). The mean ± SD plasma interlukin-6 (7.1 ± 5.6 vs. 11.9 ± 14.4 mg/L) and hs-CRP (1791 ± 1657 and 1953 ± 1561 ng/mL) concentrations in the PJ group were significantly lower than the placebo group after intervention (P < 0.05). PJ consumption by patients with T2D does not affect FPG or the insulin resistance index (HOMA-IR), whereas it does reduce Interlukin-6 and hs-CRP concentrations in plasma. Therefore, PJ consumption may have an anti-inflammatory effect in patients with T2D.

Effects of pomegranate juice consumption on inflammatory markers in patients with type 2 diabetes: A randomized, placebo-controlled trial

PubMed Central

Sohrab, Golbon; Nasrollahzadeh, Javad; Zand, Hamid; Amiri, Zohreh; Tohidi, Maryam; Kimiagar, Masoud

2014-01-01

Background: Diabetes causes the increased concentration of circulatory cytokines as a result of inflammation. Considering that pomegranate juice (PJ) is known to have antioxidant and anti-inflammatory properties, the purpose of this study was to determine the effects of PJ consumption on markers of inflammation in patients with type 2 diabetes (T2D). Materials and Methods: In a randomized, double-blind clinical trial study, 50 patients with T2D (40-65 years old) were randomly assigned to one of two groups. Participants in each group received either 250 mL/day PJ or a control beverage for 12 weeks. Biochemical markers including fasting plasma glucose (FPG), insulin and inflammatory markers were assayed on the baseline and follow-up blood samples. Results: In all, 44 patients in two groups were included in the analysis: PJ (n = 22) and placebo (n = 22). After 12 weeks of intervention, in the PJ group, there were 32% and 30% significant decreases in plasma C-reactive protein (hs-CRP) and Interlukin-6, respectively (P < 0.05). The mean ± SD plasma interlukin-6 (7.1 ± 5.6 vs. 11.9 ± 14.4 mg/L) and hs-CRP (1791 ± 1657 and 1953 ± 1561 ng/mL) concentrations in the PJ group were significantly lower than the placebo group after intervention (P < 0.05). Conclusion: PJ consumption by patients with T2D does not affect FPG or the insulin resistance index (HOMA-IR), whereas it does reduce Interlukin-6 and hs-CRP concentrations in plasma. Therefore, PJ consumption may have an anti-inflammatory effect in patients with T2D. PMID:24949028

Antidiabetic and antihyperlipidemic effects of the stem of Musa sapientum Linn. in streptozotocin-induced diabetic rats.

PubMed

Dikshit, Piyush; Shukla, Kirtikar; Tyagi, Mool Kumar; Garg, Piyush; Gambhir, Jasvindar K; Shukla, Rimi

2012-12-01

Musa sapientum Linn. is a herbaceous plant of the Musaceae family. It has been used in India for the treatment of gastric ulcer, hypertension, diarrhea, dysentery, and diabetes. The antidiabetic effect of the fruit, root, and flower has been demonstrated. The aim of the present study was to assess the antidiabetic and antihyperlipidemic effects of the stem of M. sapientum Linn. Diabetes was induced in rats by streptozotocin injection (45 mg/kg, i.p.). Diabetic rats were treated for 2 weeks with different doses of lyophilized stem juice of M. sapientum Linn. (25, 50, and 100 mg/kg) to select the most effective dose. The effects of 4 weeks treatment with this dose (50 mg/kg) on fasting and postprandial plasma glucose (FPG, PPG) levels, body weight, lipid profile, HbA1c, insulin, liver enzymes (i.e. glucokinase, glucose-6-phosphatase and 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase) and muscle and liver glycogen were evaluated. The most effective dose of lyophilized stem juice of M. sapientum Linn. was 50 mg/kg. Four weeks treatment with this dose resulted in significant decreases in FPG and PPG (P < 0.05). Serum insulin increased (P < 0.05) whereas HbA1c decreased (P < 0.05). Diabetes-induced changes to the lipid profile, muscle and liver glycogen, and enzyme activity (i.e. glucokinase, glucose-6-phosphatase, and HMG-CoA reductase) were restored near to normal levels (P < 0.05). Diabetic rats responded favorably to treatment with lyophilized stem juice of M. sapientum Linn., which exhibits antidiabetic and antihyperlipidemic effects. © 2012 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Disparities in undiagnosed diabetes among United States-Mexico border populations.

PubMed

Stoddard, Pamela; He, Guozhong; Vijayaraghavan, Maya; Schillinger, Dean

2010-09-01

To compare the prevalence of undiagnosed diabetes among populations with diabetes living on the United States (U.S.)-Mexico border, examine explanations for differences between groups, and investigate differences in metabolic outcomes by diagnosis status. Data come from the U.S.-Mexico Border Diabetes Prevention and Control Project survey (2001-2002), which used a stratified, multistage design. The sample included 603 adults (18 years or older) with diabetes. Undiagnosed diabetes was defined as a fasting plasma glucose (FPG) value of ≥ 126 mg/dL and no report of diagnosis. Logistic regression was used to compare the odds of being undiagnosed among border populations with diabetes. Metabolic outcomes included FPG, glycosylated hemoglobin, and mean arterial blood pressure. One in four adults with diabetes (25.9%) living on the U.S.-Mexico border was undiagnosed. Mexicans (43.8%) and Mexican immigrants (39.0%) with diabetes were significantly more likely to be undiagnosed than were U.S.-born Hispanics (15.0%; P < 0.05 for either comparison) or non-Hispanic whites (6.6%; P < 0.001 for either comparison). Mexicans were more likely to be undiagnosed than were all U.S. adults (14.7%; P < 0.001) with diabetes. Significant differences in the likelihood of being undiagnosed remained between all groups with diabetes after adjustment for sociodemographic and healthcare-related covariates, with the exception of that between Mexicans and U.S.-born Hispanics. Worse metabolic control and potentially greater benefits of diagnosis for control were observed for Mexicans in particular compared with U.S. groups with undiagnosed diabetes. Efforts to improve diabetes diagnosis should concentrate on Mexican and Mexican immigrant populations on the U.S.-Mexico border.

Glycemic effects of vildagliptin and metformin combination therapy in Indian patients with type 2 diabetes: an observational study.

PubMed

Chatterjee, Sanjay; Chatterjee, Sudip

2014-05-01

To analyze the glycemic response of Indian patients with type2 diabetes mellitus (T2DM) to combination therapy with vildagliptin and metformin and compare our data with those of clinical trials. In a retrospective study of the hospital database, the glycemic control of 280 patients with T2DM who were either on a once- or twice-daily regimen of combination therapy with vildagliptin 50 mg and metformin 500 mg was analyzed. The mean duration of follow-up of the patients was 16.8 months. There was a reduction in fasting plasma glucose (FPG) of 1.52 ± 0.79 and 1.88 ± 0.87 mmol/L in the once- and twice-daily groups, respectively (both P < 0.0001) from baseline to last visit. The reduction in postprandial plasma glucose (PPPG) in the once- and twice-daily groups was 3.98 ± 1.72 and 4.33 ± 1.88 mmol/L, respectively (both P < 0.0001), whereas the reduction in HbA1c was 1.41 ± 1.39% and 1.90 ± 1.49%, respectively (both P < 0.0001). The differences in the reductions achieved in FPG and HbA1c with the two dosing regimens were significant. Although the present retrospective study shows a robust response to the combination of vildagliptin and metformin in Indian patients, more multicenter studies from India with a greater number patients are necessary to confirm this finding. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Comparison of tofogliflozin 20 mg and ipragliflozin 50 mg used together with insulin glargine 300 U/mL using continuous glucose monitoring (CGM): A randomized crossover study.

PubMed

Takeishi, Soichi; Tsuboi, Hiroki; Takekoshi, Shodo

2017-10-28

To investigate whether sodium glucose co-transporter 2 inhibitors (SGLT2i), tofogliflozin or ipragliflozin, achieve optimal glycemic variability, when used together with insulin glargine 300 U/mL (Glargine 300). Thirty patients with type 2 diabetes were randomly allocated to 2 groups. For the first group: After admission, tofogliflozin 20 mg was administered; Fasting plasma glucose (FPG) levels were titrated using an algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using continuous glucose monitoring (CGM); Tofogliflozin was then washed out over 5 days; Subsequently, ipragliflozin 50 mg was administered; FPG levels were titrated using the same algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using CGM. For the second group, ipragliflozin was administered prior to tofogliflozin, and the same regimen was maintained. Glargine 300 and SGLT2i were administered at 8:00 AM. Data collected on the second day of measurement (mean amplitude of glycemic excursion [MAGE], average daily risk range [ADRR]; on all days of measurement) were analyzed. Area over the glucose curve (<70 mg/dL; 0:00 to 6:00, 24-h), M value, standard deviation, MAGE, ADRR, and mean glucose levels (24-h, 8:00 to 24:00) were significantly lower in patients on tofogliflozin than in those on ipragliflozin. Tofogliflozin, which reduces glycemic variability by preventing nocturnal hypoglycemia and decreasing postprandial glucose levels, is an ideal SGLT2i when used together with Glargine 300 during basal insulin therapy.

Role of APN and TNF-α in type 2 diabetes mellitus complicated by nonalcoholic fatty liver disease.

PubMed

Lin, X; Zhang, Z; Chen, J M; Xu, Y Y; Ye, H R; Cui, J; Fang, Y; Jin, Y; Zhu, D R; Yuan, L

2015-04-10

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by non-excessive alcohol consumption and is the most common cause of elevated levels of serum liver enzymes. We examined changes in adiponectin (APN) and tumor necrosis factor-α (TNF-α) in type 2 diabetes mellitus (T2DM) complicated by NAFLD and their relationships with insulin resistance (IR). Forty-two T2DM, 39 NAFLD, and 45 T2DM complicated with NAFLD (complicated group) patients were enrolled in this study. Body mass index, fasting blood plasma glucose (FPG), fasting insulin, triglyceride (TG), alanine aminotransferase, gamma-glutamyl transpeptidase, APN, TNF-α, and homeostasis model of assessment (HOMA)-IR were determined. The degree of fatty liver was graded according to liver/spleen computed tomography ratio and intrahepatic vessel manifestations. Compared with the T2DM and NAFLD groups, fasting blood plasma glucose, alanine aminotransferase, gamma-glutamyl transpeptidase, TG, TNF-α, and HOMA-IR in the complicated group were significantly increased, while APN was significantly reduced. Body mass index in the complicated group was significantly higher than in the T2DM group. The complicated group was prone to severe fatty liver compared with the NAFLD group. APN was negatively correlated with body mass index, fasting blood plasma glucose, TG, TNF-α, and HOMA-IR. TNF-α was negatively correlated with APN, but positively correlated with FPG, fasting insulin, TG, and HOMA-IR. The complicated group had clear IR. A more severe degree of fatty liver was associated with higher HOMA-IR and TNF-α and lower APN. APN was an important factor for antagonizing inflammation and mitigating IR.

Maternal Efficacy and Safety Outcomes in a Randomized, Controlled Trial Comparing Insulin Detemir With NPH Insulin in 310 Pregnant Women With Type 1 Diabetes

PubMed Central

Mathiesen, Elisabeth R.; Hod, Moshe; Ivanisevic, Marina; Duran Garcia, Santiago; Brøndsted, Lise; Jovanovič, Lois; Damm, Peter; McCance, David R.

2012-01-01

OBJECTIVE This randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS Patients were randomized and exposed to IDet or NPH up to 12 months before pregnancy or at 8–12 weeks gestation. The primary analysis aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear regression, taking several baseline factors and covariates into account. RESULTS A total of 310 type 1 diabetic women were randomized and exposed to IDet (n = 152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy at 8–12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, –0.06% [95% CI –0.21 to 0.08]; per protocol, –0.15% [–0.34 to 0.04]). Fasting plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017). Major and minor hypoglycemia rates during pregnancy were similar between groups. CONCLUSIONS Treatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable. PMID:22851598

Association between fried food consumption and hypertension in Korean adults.

PubMed

Kang, Yunjin; Kim, Jihye

2016-01-14

The present study explored the relationships between fried food consumption and metabolic risk factors and hypertension in Korean adults. The study was based on the fifth Korean National Health and Nutrition Examination Survey between 2010 and 2011. A total of 9221 Korean adults aged ≥19 years were studied. Fried food consumption was assessed using a validated FFQ. Metabolic risk factors such as waist circumference, fasting plasma glucose (FPG), TAG, HDL-cholesterol and systolic and diastolic blood pressure (SBP and DBP) were measured. Hypertension was defined as SBP≥140 mmHg, DBP≥90 mmHg or current use of antihypertensive medication. Adjusted OR for elevated blood pressure significantly increased in men (OR 1·62; 95% CI 1·11, 2·37; P(trend)=0·0447) and women (OR 2·20; 95% CI 1·21, 4·00; P(trend)=0·0403) with a greater than twice a week consumption of fried food compared with those who rarely consumed fried food. However, fried food consumption was not associated with other metabolic risk factors (abdominal obesity, high FPG, hypertriacylglycerolaemia, low HDL-cholesterol and the metabolic syndrome). The adjusted OR for hypertension increased by 2·4-fold in women (OR 2·37; 95% CI 1·19, 4·72; P(trend)=0·0272) with a greater than twice a week fried food consumption compared with those who rarely consumed it. No significant association was found between fried food consumption and hypertension in men. This study suggests that frequent fried food consumption is associated with hypertension in Korean women. Further studies are needed to investigate the effect of different types of fried foods on hypertension.

Association analysis of SLC30A8 rs13266634 and rs16889462 polymorphisms with type 2 diabetes mellitus and repaglinide response in Chinese patients.

PubMed

Huang, Qiong; Yin, Ji-Ye; Dai, Xing-Ping; Wu, Jing; Chen, Xiang; Deng, Cai-Shu; Yu, Min; Gong, Zhi-Cheng; Zhou, Hong-Hao; Liu, Zhao-Qian

2010-12-01

Genome-wide association studies (GWASs) identified that SLC30A8 genetic polymorphism was a risk of type 2 diabetes mellitus (T2DM) in several populations. This study aimed to investigate whether the SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with T2DM susceptibility and repaglinide therapeutic efficacy in Chinese T2DM patients. We conducted a case-control study of 443 T2DM patients and 229 healthy volunteers to identify SLC30A8 rs13266634 and rs16889462 genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-eight patients were randomly selected and underwent an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c) and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment. SLC30A8 rs13266634 risk C allele frequency was higher in T2DM patients than in healthy controls (P < 0.05). There was a better repaglinide response on FINS (P < 0.05) and PINS (P < 0.01) in patients with rs13266634 CT+TT genotypes compared with CC genotype carriers. Patients with rs16889462 GA genotype showed an enhanced repaglinide efficacy on FPG (P < 0.01), PPG (P < 0.01) and HbAlc (P < 0.05) compared with GG genotype individuals. SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with repaglinide therapeutic efficacy in Chinese T2DM patients.

Management of endocrine disease. Effects of telecare intervention on glycemic control in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Huang, Zhenru; Tao, Hong; Meng, Qingdong; Jing, Long

2015-03-01

To review the published literature on the effects of telecare intervention in patients with type 2 diabetes and inadequate glycemic control. A review of randomized controlled trials on telecare intervention in patients with type 2 diabetes, and a search of electronic databases such as The Cochrane Library, PubMed, EBSCO, CINAHL, Science Direct, Journal of Telemedicine and Telecare, and China National Knowledge Infrastructure (CNKI), were conducted from December 8 to 16, 2013. Two evaluators independently selected and reviewed the eligible studies. Changes in HbA1c, fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), BMI, and body weight were analyzed. An analysis of 18 studies with 3798 subjects revealed that telecare significantly improved the management of diabetes. Mean HbA1c values were reduced by -0.54 (95% CI, -0.75 to -0.34; P<0.05), mean FPG levels by -9.00 mg/dl (95% CI, -17.36 to -0.64; P=0.03), and mean PPG levels reduced by -52.86 mg/dl (95% CI, -77.13 to -28.58; P<0.05) when compared with the group receiving standard care. Meta-regression and subgroup analyses indicated that study location, sample size, and treatment-monitoring techniques were the sources of heterogeneity. Patients monitored by telecare showed significant improvement in glycemic control in type 2 diabetes when compared with those monitored by routine follow-up. Significant reduction in HbA1c levels was associated with Asian populations, small sample size, and telecare, and with those patients with baseline HbA1c greater than 8.0%. © 2015 European Society of Endocrinology.

Efficacy and safety of combination therapy: repaglinide plus metformin versus nateglinide plus metformin.

PubMed

Raskin, Philip; Klaff, Leslie; McGill, Janet; South, Stephen A; Hollander, Priscilla; Khutoryansky, Naum; Hale, Paula M

2003-07-01

An open-label, parallel-group, randomized, multicenter trial was conducted to compare efficacy and safety of repaglinide versus nateglinide, when used in a combination regimen with metformin for treatment of type 2 diabetes. Enrolled patients (n = 192) had HbA(1c) >7% and < or =12% during previous treatment with a sulfonylurea, metformin, or low-dose Glucovance (glyburide < or =2.5 mg, metformin < or =500 mg). After a 4-week metformin run-in therapy period (doses escalated to 1,000 mg b.i.d.), patients were randomized to addition of repaglinide (n = 96) (1 mg/meal, maximum 4 mg/meal) or nateglinide (n = 96) (120 mg/meal, reduced to 60 mg if needed) to the regimen for 16 weeks. Glucose, insulin, and glucagon were assessed after a liquid test meal at baseline and week 16. Final HbA(1c) values were lower for repaglinide/metformin treatment than for nateglinide/metformin (7.1 vs. 7.5%). Repaglinide/metformin therapy showed significantly greater mean reductions of HbA(1c) (-1.28 vs. -0.67%; P < 0.001) and of fasting plasma glucose (FPG) (-39 vs. -21 mg/dl; P = 0.002). Self-monitoring of blood glucose profiles were significantly lower for repaglinide/metformin before breakfast, before lunch, and at 2:00 A.M. Changes in the area under the curve of postprandial glucose, insulin, or glucagon peaks after a test meal were not significantly different for the two treatment groups during this study. Median final doses were 5.0 mg/day for repaglinide and 360 mg/day for nateglinide. Safety assessments were comparable for the two regimens. The addition of repaglinide to metformin therapy resulted in reductions of HbA(1c) and FPG values that were significantly greater than the reductions observed for addition of nateglinide.

Repaglinide/troglitazone combination therapy: improved glycemic control in type 2 diabetes.

PubMed

Raskin, P; Jovanovic, L; Berger, S; Schwartz, S; Woo, V; Ratner, R

2000-07-01

This multicenter open-label clinical trial compared the efficacy and safety of repaglinide/troglitazone combination therapy, repaglinide monotherapy, and troglitazone monotherapy in type 2 diabetes that had been inadequately controlled by sulfonylureas, acarbose, or metformin alone. Patients with type 2 diabetes (n = 256) who had inadequate glycemic control (HbA1c > or =7.0%) during previous monotherapy were randomly assigned to receive repaglinide (0.5-4.0 mg at meals), troglitazone (200-600 mg once daily), or a combination of repaglinide (1-4 mg at meals) and troglitazone (200-600 mg once daily). After a 4-6 week washout period, the trial assessed 22 weeks of treatment: 3 weeks (weeks 0-2) of forced titration, 11 weeks of fixed-dose treatment (weeks 3-13), and 8 weeks (weeks 14-21) of titration to maximum dose. Changes in HbA1c and fasting plasma glucose (FPG) values were measured. The combination therapy showed a significant reduction in mean HbA1c values (-1.7%) that was greater than with either type of monotherapy Repaglinide monotherapy resulted in a reduction of HbA1c values that was significantly greater than troglitazone (-0.8 vs. -0.4%) (P < 0.05). Combination therapy was more effective in reducing FPG values (-80 mg/dl) than either repaglinide (-43 mg/dl) or troglitazone (-46 mg/dl) monotherapies. Adverse events were similar in all groups. Combination therapy with repaglinide and troglitazone leads to better glycemic control than monotherapy with either agent alone. Repaglinide monotherapy was more effective in lowering HbA1c levels than troglitazone monotherapy Repaglinide/troglitazone combination therapy was effective and did not show unexpected adverse events.

Waist-hip ratio related genetic loci are associated with risk of impaired fasting glucose in Chinese children: a case control study.

PubMed

Song, Qi-Ying; Meng, Xiang-Rui; Hinney, Anke; Song, Jie-Yun; Huang, Tao; Ma, Jun; Wang, Hai-Jun

2018-01-01

The meta-analyses of genome-wide association studies identified several waist-hip ratio (WHR) related loci in individuals of European ancestry. Since the pattern of fat distribution and the relationship between fat distribution and glucose metabolism disturbance in Chinese are different from those in Europeans, the present study aimed to explore the individual and cumulative effects of WHR-related loci on glycemic phenotypes in Chinese children. A total of 2030 children were recruited from two independent studies. Eleven single nucleotide polymorphisms (SNPs) were selected and genotyped using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Logistic regression and linear regression model were used to examine the association of 11 SNPs and genetic risk score (GRS) with impaired fasting glucose (IFG) and fasting plasma glucose (FPG), respectively. Three SNPs (rs6795735, rs984222 and rs1011731) were nominally associated with IFG (all P  < 0.05). Each WHR-increasing (C) allele of rs6795735 ( ADAMTS9 ) was associated with a 40.1% increased risk of IFG (OR = 1.401, 95% CI = 1.131-1.735, P  = 0.002), which remained significant after Bonferroni correction. We observed no association of both weighted and unweighted GRS with FPG and IFG (all P  > 0.05). We identified individual effects of rs6795735 ( ADAMTS9 ), rs984222 ( TBX15-WARS2 ), and rs1011731 ( DNM3-PIGC ) on glycemic phenotypes in Chinese children for the first time. The study suggests that genetic predisposition to central obesity is associated with impaired fasting glucose, providing more evidence for the pathogenesis of diabetes.

Basal insulin treatment intensification in patients with type 2 diabetes mellitus: A comprehensive systematic review of current options.

PubMed

Raccah, D

2017-04-01

As type 2 diabetes mellitus progresses, most patients require treatment with basal insulin in combination with another agent to achieve recommended glycaemic targets. The purpose of this systematic review was to examine the evidence supporting the use of the available add-on treatments [rapid-acting insulin (RAI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors] to basal insulin. MEDLINE, EMBASE and EBSCOhost were searched for English-language articles, and all those captured were original articles (case studies and narrative reviews were omitted). Data on study design, population demographics, interventions and outcomes were tabulated. The extracted outcome data included changes in glycated haemoglobin (HbA 1c ), fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), as well as body weight and safety data. A total of 88 publications were deemed relevant. All treatments reduced HbA 1c and FPG. The most pronounced reductions in PPG, an unmet need in patients not controlled by basal insulin, were seen following administration of RAIs and short-acting GLP-1 RAs, although data for this outcome are generally lacking. Body weight benefits were observed with GLP-1 RAs and SGLT-2 inhibitors. However, as only articles in English were included, the result was a possible publication bias, while the diversity of study designs and drug combinations limited comparisons between studies. The evidence supports effectiveness of the available add-on treatments to basal insulin. However, other factors, such as potential body-weight increases, convenience/compliance and adverse events, particularly hypoglycaemia, should be considered on a patient-by-patient basis to optimalize treatment outcomes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials.

PubMed

Yao, Kecheng; Zeng, Linghai; He, Qian; Wang, Wei; Lei, Jiao; Zou, Xiulan

2017-06-22

BACKGROUND It has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. This meta-analysis aimed to summarize the effect of probiotics on glucose and lipid metabolism and C-reactive protein (CRP) from 12 randomized controlled trials (RCTs). MATERIAL AND METHODS An up-to-date search was performed for all relevant RCTs up to April 2016 from PubMed, Embase, and Cochrane Library. Standardized mean difference (SMD) and weighted mean difference (WMD) were calculated for a fixed-effect and random-effect meta-analysis to assess the impact of supplemental probiotics on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, and CRP level. RESULTS A total of 12 studies (684 patients) were entered into the final analysis. The effect of probiotics was significant on reducing HbA1c level (standardized mean difference [SMD], -0.38; confidence interval [CI], -0.62 to -0.14, P=0.002; I²=0%, P=0.72 for heterogeneity), fasting insulin level (SMD, -0.38; CI -0.59 to -0.18, P=0.0003; I²=0%, P=0.81 for heterogeneity), and HOMA-IR (SMD, -0.99; CI -1.52 to -0.47, P=0.0002; I²=86%, P<0.00001 for heterogeneity). Pooled results on effects of probiotics on FPG, CRP, or lipid profile were either non-significant or highly heterogeneous. CONCLUSIONS This meta-analysis demonstrated that probiotics supplementation was associated with significant improvement in HbA1c and fasting insulin in type 2 diabetes patients. More randomized placebo-controlled trials with large sample sizes are warranted to confirm our conclusions.

Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials

PubMed Central

Yao, Kecheng; Zeng, Linghai; He, Qian; Wang, Wei; Lei, Jiao; Zou, Xiulan

2017-01-01

Background It has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. This meta-analysis aimed to summarize the effect of probiotics on glucose and lipid metabolism and C-reactive protein (CRP) from 12 randomized controlled trials (RCTs). Material/Methods An up-to-date search was performed for all relevant RCTs up to April 2016 from PubMed, Embase, and Cochrane Library. Standardized mean difference (SMD) and weighted mean difference (WMD) were calculated for a fixed-effect and random-effect meta-analysis to assess the impact of supplemental probiotics on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, and CRP level. Results A total of 12 studies (684 patients) were entered into the final analysis. The effect of probiotics was significant on reducing HbA1c level (standardized mean difference [SMD], −0.38; confidence interval [CI], −0.62 to −0.14, P=0.002; I2=0%, P=0.72 for heterogeneity), fasting insulin level (SMD, −0.38; CI −0.59 to −0.18, P=0.0003; I2=0%, P=0.81 for heterogeneity), and HOMA-IR (SMD, −0.99; CI −1.52 to −0.47, P=0.0002; I2=86%, P<0.00001 for heterogeneity). Pooled results on effects of probiotics on FPG, CRP, or lipid profile were either non-significant or highly heterogeneous. Conclusions This meta-analysis demonstrated that probiotics supplementation was associated with significant improvement in HbA1c and fasting insulin in type 2 diabetes patients. More randomized placebo-controlled trials with large sample sizes are warranted to confirm our conclusions. PMID:28638006

[Risk factors analysis of nonalcoholic fatty liver disease in Chinese men].

PubMed

Zheng, Rui-Dan; Zhuang, Qun-Ying; Chen, Jian-Neng; Chen, Jie; Lu, Yan-Hui

2013-01-01

To explore risk factors of nonalcoholic fatty liver disease (NAFLD) in men in order to provide a theoretical basis for developing more effective NAFLD prevention and control strategies. One-hundred-and-two male patients (37.3+/-11.4 years old) hospitalized with NAFLD at the Dongnan Affiliated Hospital of Xiamen University between January 2009 and December 2010 were enrolled in the study, along with 23 age-matched healthy men (34.4+/-16.7 years old) to serve as the control group. The correlation(s) of body mass index (BMI; overweight defined as more than or equal to 22.717 kg/m2), waist circumference (WC), waist-to-hip ratio (WHR; central obesity defined as more than or equal to 0.866), fasting plasma glucose (FPG), triglyceride (TG), and total cholesterol (TC) with NAFLD was analyzed by univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were used to select proper thresholds for classification. BMI, WC, WHR, FPG, TG, and TC were significantly different between the cases and controls (P less than 0.01). BMI, WC, WHR, TG and TC were identified as risk factors of NAFLD in these male cases (P less than 0.01). Relative to WC, TG and TC, both BMI and WHR had significant predictive value for NAFLD (odds ratio (OR) = 10.819 and 10.588, respectively). In addition, BMI had the highest diagnostic value for the prediction of NAFLD (area under the curve (AUC) = 0.931) followed by WHR (AUC = 0.879). BMI, WC, WHR, TG, and TC are risk factors of NAFLD in Chinese men. BMI and WHR are effective anthroposomatology indices of NAFLD and may be useful factors on which to base future prevention and early diagnosis strategies for NAFLD in males.

Obesity measures, metabolic profiles and dietary fatty acids in lean and obese postmenopausal diabetic Asian Indian women.

PubMed

Ghosh, Arnab

2009-03-01

The present investigation was aimed to compare anthropometric, metabolic and dietary fatty acids profiles in lean and obese postmenopausal diabetic Asian Indian women. A total of 125 postmenopausal Asian Indian women (Group I: lean postmenopausal control, n = 50; Group II: lean postmenopausal diabetic, n = 40 and Group III: obese postmenopausal diabetic, n = 35) aged 40 years and above were studied. Anthropometric [height, weight, waist (WC) and hip circumference] metabolic [total cholesterol (TC), triglyceride (TG), high (HDL), low density lipoprotein (LDL) and fasting plasma glucose (FPG)] and dietary profiles were collected from each participant. Body mass index (BMI), waist-hip ratio (WHR) and conicity index (CI) were subsequently computed. Obesity was defined as women having a BMI > or = 25 kg/m2. An open-ended 24 h food recall schedule was used to collect nutrient information from each participant. Daily intake of nutrients including saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) were also estimated on weekly and monthly basis. Group I had significantly lower mean than both Group II and Group III for WC, WHR, CI, TC, TG, LDL, FPG and total carbohydrates. On the other hand, Group I had significantly greater mean than both Group II and Group III for UFA/SFA, MUFA/SFA and PUFA/SFA. Discriminant analysis had revealed that overall 88% of all cases were correctly (positively) classified in three groups using fatty acids and their ratios. It seems reasonable to argue that while dealing with postmenopausal diabetic women, clinicians should consider obesity measures, lipids and dietary fatty acids simultaneously to better comprehend clinical assessments and risk stratification.

Triglyceride Glucose-Body Mass Index Is a Simple and Clinically Useful Surrogate Marker for Insulin Resistance in Nondiabetic Individuals.

PubMed

Er, Leay-Kiaw; Wu, Semon; Chou, Hsin-Hua; Hsu, Lung-An; Teng, Ming-Sheng; Sun, Yu-Chen; Ko, Yu-Lin

2016-01-01

Insulin resistance (IR) and the consequences of compensatory hyperinsulinemia are pathogenic factors for a set of metabolic abnormalities, which contribute to the development of diabetes mellitus and cardiovascular diseases. We compared traditional lipid levels and ratios and combined them with fasting plasma glucose (FPG) levels or adiposity status for determining their efficiency as independent risk factors for IR. We enrolled 511 Taiwanese individuals for the analysis. The clinical usefulness of various parameters--such as traditional lipid levels and ratios; visceral adiposity indicators, visceral adiposity index (VAI), and lipid accumulation product (LAP); the product of triglyceride (TG) and FPG (the TyG index); TyG with adiposity status (TyG-body mass index [BMI]) and TyG-waist circumference index [WC]); and adipokine levels and ratios--was analyzed to identify IR. For all lipid ratios, the TG/high-density lipoprotein cholesterol (HDL-C) ratio had the highest additional percentage of variation in the homeostasis model assessment of insulin resistance (HOMA-IR; 7.0% in total); for all variables of interest, TyG-BMI and leptin-adiponectin ratio (LAR) were strongly associated with HOMA-IR, with 16.6% and 23.2% of variability, respectively. A logistic regression analysis revealed similar patterns. A receiver operating characteristic (ROC) curve analysis indicated that TG/HDL-C was a more efficient IR discriminator than other lipid variables or ratios. The area under the ROC curve (AUC) for VAI (0.734) and TyG (0.708) was larger than that for TG/HDL-C (0.707). TyG-BMI and LAR had the largest AUC (0.801 and 0.801, respectively). TyG-BMI is a simple, powerful, and clinically useful surrogate marker for early identification of IR.

Triglyceride Glucose-Body Mass Index Is a Simple and Clinically Useful Surrogate Marker for Insulin Resistance in Nondiabetic Individuals

PubMed Central

Er, Leay-Kiaw; Wu, Semon; Chou, Hsin-Hua; Hsu, Lung-An; Teng, Ming-Sheng; Sun, Yu-Chen; Ko, Yu-Lin

2016-01-01

Background Insulin resistance (IR) and the consequences of compensatory hyperinsulinemia are pathogenic factors for a set of metabolic abnormalities, which contribute to the development of diabetes mellitus and cardiovascular diseases. We compared traditional lipid levels and ratios and combined them with fasting plasma glucose (FPG) levels or adiposity status for determining their efficiency as independent risk factors for IR. Methods We enrolled 511 Taiwanese individuals for the analysis. The clinical usefulness of various parameters—such as traditional lipid levels and ratios; visceral adiposity indicators, visceral adiposity index (VAI), and lipid accumulation product (LAP); the product of triglyceride (TG) and FPG (the TyG index); TyG with adiposity status (TyG-body mass index [BMI]) and TyG-waist circumference index [WC]); and adipokine levels and ratios—was analyzed to identify IR. Results For all lipid ratios, the TG/high-density lipoprotein cholesterol (HDL-C) ratio had the highest additional percentage of variation in the homeostasis model assessment of insulin resistance (HOMA-IR; 7.0% in total); for all variables of interest, TyG-BMI and leptin-adiponectin ratio (LAR) were strongly associated with HOMA-IR, with 16.6% and 23.2% of variability, respectively. A logistic regression analysis revealed similar patterns. A receiver operating characteristic (ROC) curve analysis indicated that TG/HDL-C was a more efficient IR discriminator than other lipid variables or ratios. The area under the ROC curve (AUC) for VAI (0.734) and TyG (0.708) was larger than that for TG/HDL-C (0.707). TyG-BMI and LAR had the largest AUC (0.801 and 0.801, respectively). Conclusion TyG-BMI is a simple, powerful, and clinically useful surrogate marker for early identification of IR. PMID:26930652

Serum vaspin levels and vaspin mRNA expression in subcutaneous adipose tissue in women with gestational diabetes mellitus.

PubMed

Mm, Wei Qian; Fan, Jianxia; Khor, Shuzin; Song, Mengfan; Hong, Wei; Dai, Xiaobei

2014-11-01

To compare serum vaspin level and mRNA and protein levels of vaspin in adipose tissue in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGR), along with the correlation between serum vaspin level with fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and birth-weight. Thirty-seven women with GDM and 36 with NGR were enrolled. Total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), FINS and vaspin levels were measured. The mRNA and protein levels were detected using RT-PCR and Western blot. Pearson correlation analysis (PCA) was performed to reveal the correlation between serum vaspin level and FINS, HOMA-IR. Spearman correlation analysis (SCA) was conducted to examine the association between serum vaspin level and birth-weight. HDL-C level in GDM was lower than NGR group (P<0.05), and there were no statistical differences in TC, TG, LDL-C, FPG, FINS and HOMA-IR between the two groups. Serum vaspin level, mRNA and protein expression levels of vaspin in GDM were higher than NGR group (P<0.05). Serum vaspin level was not significantly correlated with FINS and HOMA-IR, but had a positive correlation with birth-weight (P=0.023). Serum vaspin level cannot serve as an independent predictor of IR. The increased serum vaspin level and increased vaspin mRNA and protein expression in adipose tissues in GDM women indicate that vaspin may be involved in the pathogenesis of GDM, but its exact mechanism needs further study. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Missed opportunities for diabetes prevention: post-pregnancy follow-up of women with gestational diabetes mellitus in England

PubMed Central

Pierce, Mary; Modder, Jo; Mortagy, Iman; Springett, Anna; Hughes, Heather; Baldeweg, Stephanie

2011-01-01

Background Women with gestational diabetes mellitus (GDM) should be followed-up to exclude ongoing diabetes and for prevention of type 2 diabetes. The National Institute for Health and Clinical Excellence (NICE) diabetes in pregnancy guideline recommends checking fasting plasma glucose (FPG) at 6 weeks postpartum (short term), and annually thereafter (long term). Aim To examine the reported practice regarding GDM follow-up. Design and setting Nationwide postal survey in England 2008-2009. Method Questionnaires were distributed to a consultant diabetologist and obstetrician in all maternity units, and to a random sample of general practices (approximately 1 in 5). Results Response rates were: 60% (915/1532) GPs, 93% (342/368) specialists; 80% of GPs and 98% of specialists reported women with GDM had short-term follow-up. More GPs (55%) than specialists (13%) used a FPG test to exclude ongoing diabetes; 26% of GPs versus 89% of specialists thought the hospital was responsible for ordering the test. Twenty per cent of GPs had difficulty in discovering women had been diagnosed with GDM in secondary care. Seventy-three per cent of specialists recommended long-term follow-up; only 39% of GPs recalled women with GDM for this. A minority of GPs and specialists had joint follow-up protocols Conclusion Follow-up of GDM in England diverged from national guidance. Despite consensus that short-term follow-up occurred, primary and secondary care doctors disagreed about the tests and responsibility for follow-up. There was lack of long-term follow-up. Agreement about the NICE guideline, its promotion and effective implementation by primary and secondary care, and the systematic recall of women with GDM for long-term follow-up is required. PMID:22152832

High risk of progression to NIDDM in South-African Indians with impaired glucose tolerance.

PubMed

Motala, A A; Omar, M A; Gouws, E

1993-04-01

A four-yr prospective study was undertaken to examine the natural history of IGT in 128 South-African Indians classified as such at year 0 of the study, based on WHO criteria. Subjects were reexamined at year 1 and year 4. Of the 113 subjects who completed the study, 50.4% progressed to NIDDM (rate of progression 12.6%/yr), 24.8% persisted with IGT, and 24.8%, reverted to NGT. The majority (72%) who progressed to NIDDM did so in year 1. At year 1, 47 subjects were still classified as IGT; of the 40 subjects completing the study, 16 subjects (40%) progressed to NIDDM, 17 subjects (42.5%) persisted with IGT, and 7 subjects (17.5%) reverted to NGT. Examination of risk factors predictive of subsequent progression to NIDDM was undertaken by analysis of baseline variables in two ways: When year 0 was used as baseline (in 113 IGT0 subjects), significant predictive risk factors were the FPG and 2-h plasma glucose concentrations. All subjects who at year 0 had 2-h plasma glucose > or = 10.2 and < 11.1 mM or FPG > or = 7.3 but < 7.8 mM, subsequently progressed to NIDDM. When year 1 was used as baseline (40 IGT1 subjects), 90-min plasma glucose concentration (midtest level) was found to be a significant risk factor for development of NIDDM. In conclusion, this study has demonstrated that in South-African Indians with IGT, the majority (50.4%) progress to NIDDM within 4 yr; significant predictors of subsequent diabetes are the baseline fasting and 2-h plasma glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum glycerophosphate levels are increased in Japanese men with type 2 diabetes.

PubMed

Daimon, Makoto; Soga, Tomoyoshi; Hozawa, Atsushi; Oizumi, Toshihide; Kaino, Wataru; Takase, Kaoru; Karasawa, Shigeru; Jimbu, Yumi; Wada, Kiriko; Kameda, Wataru; Susa, Shinji; Kayama, Takamasa; Saito, Kaori; Tomita, Masaru; Kato, Takeo

2012-01-01

To identify metabolites showing changes in serum levels among Japanese male with diabetes. We performed metabolite profiling by coupling capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry using fasting serum samples from Japanese male subjects with diabetes (n=17), impaired glucose tolerance (IGT; n=5) and normal glucose tolerance (NGT; n=14). Other than the expected differences in characteristics related to abnormal glucose metabolism, the percent body fat was significantly different among subjects with diabetes, IGT and NGT (27.3±6.2, 22.2±4.5 and 19.2±6.0%, respectively, p=0.0022). Therefore, percent body fat was considered as a possible confounding factor in subsequent analyses. Of 560 metabolites detected using our platform, the levels of 74 metabolites were quantified in all of the serum samples. Significant differences between diabetes and NGT were observed for 24 metabolites. The top-ranked metabolite was glycerol-3-phophate (glycerophosphate), which was significantly higher in subjects with diabetes than in those with NGT, even after Bonferroni correction for multiple testing (11.7±3.6 vs. 6.4±1.9 µM, respectively; corrected p=0.0222). Stepwise multiple regression analyses revealed that serum glycerophosphate levels were significantly correlated with 2-h plasma glucose after a 75-g oral glucose tolerance test (r=0.553, p=0.0005), independently of other characteristics, including FPG and HbA1c. Serum glycerophosphate levels were found to be elevated in Japanese men with diabetes, and correlated with 2-h PG, independent of FPG and HbA1c. Namely, serum glycerophosphate level at fasting condition can be a marker for predicting glucose intolerance. These results warrant further studies to evaluate the relevance of glycerophosphate in the pathophysiology of diabetes.

Global Assessment of the Impact of Type 2 Diabetes on Sleep through Specific Questionnaires. A Case-Control Study.

PubMed

Lecube, Albert; Sánchez, Enric; Gómez-Peralta, Fernando; Abreu, Cristina; Valls, Joan; Mestre, Olga; Romero, Odile; Martínez, María Dolores; Sampol, Gabriel; Ciudin, Andreea; Hernández, Cristina; Simó, Rafael

2016-01-01

Type 2 diabetes (T2D) is an independent risk factor for sleep breathing disorders. However, it is unknown whether T2D affects daily somnolence and quality of sleep independently of the impairment of polysomnographic parameters. A case-control study including 413 patients with T2D and 413 non-diabetic subjects, matched by age, gender, BMI, and waist and neck circumferences. A polysomnography was performed and daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). In addition, 135 subjects with T2D and 45 controls matched by the same previous parameters were also evaluated through the Pittsburgh Sleep Quality Index (PSQI) to calculate sleep quality. Daytime sleepiness was higher in T2D than in control subjects (p = 0.003), with 23.9% of subjects presenting an excessive daytime sleepiness (ESS>10). Patients with fasting plasma glucose (FPG ≥13.1 mmol/l) were identified as the group with a higher risk associated with an ESS>10 (OR 3.9, 95% CI 1.8-7.9, p = 0.0003). A stepwise regression analyses showed that the presence of T2D, baseline glucose levels and gender but not polysomnographic parameters (i.e apnea-hyoapnea index or sleeping time spent with oxigen saturation lower than 90%) independently predicted the ESS score. In addition, subjects with T2D showed higher sleep disturbances [PSQI: 7.0 (1.0-18.0) vs. 4 (0.0-12.0), p<0.001]. The presence of T2D and high levels of FPG are independent risk factors for daytime sleepiness and adversely affect sleep quality. Prospective studies addressed to demonstrate whether glycemia optimization could improve the sleep quality in T2D patients seem warranted.

Interstitial telomeric sequences in human chromosomes cluster with common fragile sites, mutagen sensitive sites, viral integration sites, cancer breakpoints, proto-oncogenes and breakpoints involved in primate evolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adekunle, S.S.A.; Wyandt, H.; Mark, H.F.L.

1994-09-01

Recently we mapped the telomeric repeat sequences to 111 interstitial sites in the human genome and to sites of gaps and breaks induced by aphidicolin and sister chromatid exchange sites detected by BrdU. Many of these sites correspond to conserved fragile sites in man, gorilla and chimpazee, to sites of conserved sister chromatid exchange in the mammalian X chromosome, to mutagenic sensitive sites, mapped locations of proto-oncogenes, breakpoints implicated in primate evolution and to breakpoints indicated as the sole anomaly in neoplasia. This observation prompted us to investigate if the interstitial telomeric sites cluster with these sites. An extensive literaturemore » search was carried out to find all the available published sites mentioned above. For comparison, we also carried out a statistical analysis of the clustering of the sites of the telomeric repeats with the gene locations where only nucleotide mutations have been observed as the only chromosomal abnormality. Our results indicate that the telomeric repeats cluster most with fragile sites, mutagenic sensitive sites and breakpoints implicated in primate evolution and least with cancer breakpoints, mapped locations of proto-oncogenes and other genes with nucleotide mutations.« less

Acid-Sensitive Sheddable PEGylated, Mannose-Modified Nanoparticles Increase the Delivery of Betamethasone to Chronic Inflammation Sites in a Mouse Model.

PubMed

O'Mary, Hannah L; Aldayel, Abdulaziz M; Valdes, Solange A; Naguib, Youssef W; Li, Xu; Salvady, Karun; Cui, Zhengrong

2017-06-05

Inflammation is implicated in a host of chronic illnesses. Within these inflamed tissues, the pH of the microenvironment is decreased and immune cells, particularly macrophages, infiltrate the area. Additionally, the vascular integrity of these sites is altered with increased fenestrations between endothelial cells. These distinctive properties may be exploited to enhance targeted delivery of anti-inflammatory therapies. Using a mouse model of chronic inflammation, we previously showed that acid-sensitive sheddable PEGylation increases the distribution and retention of nanoparticles in chronic inflammation sites. Here we demonstrated that surface modification of the acid-sensitive sheddable PEGylated nanoparticles with mannose, a ligand to mannose receptors present in chronic inflammation sites, significantly increases the targeted delivery of the nanoparticles to these areas. Furthermore, we showed that the acid-sensitive sheddable PEGylated, mannose-modified nanoparticles are able to significantly increase the delivery of betamethasone-21-acetate (BA), a model anti-inflammatory compound, to chronic inflammation sites as compared to free BA. These results highlight the ability to engineer formulations to target chronic inflammation sites by exploiting the microenvironment of these regions.

Enhanced yield of chromosome aberrations after CT examinations in paediatric patients.

PubMed

Stephan, G; Schneider, K; Panzer, W; Walsh, L; Oestreicher, U

2007-05-01

To determine whether computed tomography (CT) could enhance the chromosome aberration yields in paediatric patients. Blood samples were taken before and after CT scans from 10 children for whom the medical justifications for CT examinations were accidental injuries and not diseases as investigated in earlier studies. Chromosome analysis was carried out in lymphocytes by fluorescence plus Giemsa (FPG) staining exclusively in metaphases of the first cell cycle in vitro. The mean blood dose of the 10 children was about 12.9 mGy which was determined by a newly developed dose estimation. Based on more than 20,000 analyzed cells it was found that after CT examination the frequencies of dicentrics (dic) and excess acentric fragments (ace) in lymphocytes were significantly increased. By subdividing the children into two age groups, those with an age from 0.4 years to 9 years and from 10 - 15 years, it became obvious that the observed increase in chromosome aberrations was mainly contributed by the younger age group. In this group the frequency of dicentrics was significantly increased whereas in the older group the observed increase was not significant. Our results demonstrate that CT examinations enhance the dicentrics yields in peripheral lymphocytes of children aged up to 15 years. Since in particular significantly increased dicentric yields could be observed in children with an age from 0.4 - 9 years, it can be assumed that children younger than 10 years may be more radiation sensitive than older subjects.

Barnidipine compared to lercanidipine in addition to losartan on endothelial damage and oxidative stress parameters in patients with hypertension and type 2 diabetes mellitus.

PubMed

Derosa, Giuseppe; Mugellini, Amedeo; Pesce, Rosa Maria; D'Angelo, Angela; Maffioli, Pamela

2016-04-12

Essential hypertension has been extensively reported to cause endothelial dysfunction. The aim of this study was to evaluate the effects of barnidipine or lercanidipine, in addition to losartan, on some parameters indicative of endothelial damage and oxidative stress in hypertensive, type 2 diabetic patients. One hundred and fifty one patients were randomised to barnidipine, 20 mg/day, or lercanidipine, 20 mg/day, both in addition to losartan, 100 mg/day, for 6 months. We assessed BP every month, in addition, patients underwent ambulatory blood pressure monitoring (ABPM). We also assessed: fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), some markers such as high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α), metalloproteinase-2 (MMP-2) and -9 (MMP-9), soluble vascular adhesion protein-1 (sVCAM-1), soluble intercellular adhesion protein-1 (sICAM-1), isoprostanes and paraoxonase-1 (PON-1). Both barnidipine and lercanidipine resulted in a significant reduction in blood pressure, even if the reduction obtained with barnidipine + losartan was greater than that obtained with lercanidipine + losartan. Data recorded with ABPM also showed a similar trend. Barnidipine + losartan reduced the levels of Hs-CRP, TNF-α, sVCAM-1, sICAM-1, and isoprostanes both compared to baseline and to lercanidipine + losartan. Barnidipine + losartan gave an improvement of some parameters indicative of endothelial damage and oxidative stress in diabetic and hypertensive patients. NCT02064218 , ClinicalTrials.gov.

Performance of the Finnish Diabetes Risk Score and a Simplified Finnish Diabetes Risk Score in a Community-Based, Cross-Sectional Programme for Screening of Undiagnosed Type 2 Diabetes Mellitus and Dysglycaemia in Madrid, Spain: The SPREDIA-2 Study.

PubMed

Salinero-Fort, M A; Burgos-Lunar, C; Lahoz, C; Mostaza, J M; Abánades-Herranz, J C; Laguna-Cuesta, F; Estirado-de Cabo, E; García-Iglesias, F; González-Alegre, T; Fernández-Puntero, B; Montesano-Sánchez, L; Vicent-López, D; Cornejo-Del Río, V; Fernández-García, P J; Sánchez-Arroyo, V; Sabín-Rodríguez, C; López-López, S; Patrón-Barandio, P; Gómez-Campelo, P

2016-01-01

To evaluate the performance of the Finnish Diabetes Risk Score (FINDRISC) and a simplified FINDRISC score (MADRISC) in screening for undiagnosed type 2 diabetes mellitus (UT2DM) and dysglycaemia. A population-based, cross-sectional, descriptive study was carried out with participants with UT2DM, ranged between 45-74 years and lived in two districts in the north of metropolitan Madrid (Spain). The FINDRISC and MADRISC scores were evaluated using the area under the receiver operating characteristic curve method (ROC-AUC). Four different gold standards were used for UT2DM and any dysglycaemia, as follows: fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), HbA1c, and OGTT or HbA1c. Dysglycaemia and UT2DM were defined according to American Diabetes Association criteria. The study population comprised 1,426 participants (832 females and 594 males) with a mean age of 62 years (SD = 6.1). When HbA1c or OGTT criteria were used, the prevalence of UT2DM was 7.4% (10.4% in men and 5.2% in women; p<0.01) and the FINDRISC ROC-AUC for UT2DM was 0.72 (95% CI, 0.69-0.74). The optimal cut-off point was ≥13 (sensitivity = 63.8%, specificity = 65.1%). The ROC-AUC of MADRISC was 0.76 (95% CI, 0.72-0.81) with ≥13 as the optimal cut-off point (sensitivity = 84.8%, specificity = 54.6%). FINDRISC score ≥12 for detecting any dysglycaemia offered the best cut-off point when HbA1c alone or OGTT and HbA1c were the criteria used. FINDRISC proved to be a useful instrument in screening for dysglycaemia and UT2DM. In the screening of UT2DM, the simplified MADRISC performed as well as FINDRISC.

Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects.

PubMed

Mathew, Manoj; Tay, Eric; Cusi, Kenneth

2010-02-16

CVD in obesity and T2DM are associated with endothelial activation, elevated plasma vascular inflammation markers and a prothrombotic state. We examined the contribution of FFA to these abnormalities following a 48-hour physiological increase in plasma FFA to levels of obesity and diabetes in a group of healthy subjects. 40 non-diabetic subjects (age = 38 +/- 3 yr, BMI = 28 +/- 1 kg/m2, FPG = 95 +/- 1 mg/dl, HbA1c = 5.3 +/- 0.1%) were admitted twice and received a 48-hour infusion of normal saline or low-dose lipid. Plasma was drawn for intracellular (ICAM-1) and vascular (VCAM-1) adhesion molecules-1, E-selectin (sE-S), myeloperoxidase (MPO) and total plasminogen inhibitor-1 (tPAI-1). Insulin sensitivity was measured by a hyperglycemic clamp (M/I). Lipid infusion increased plasma FFA to levels observed in obesity and T2DM and reduced insulin sensitivity by 27% (p = 0.01). Elevated plasma FFA increased plasma markers of endothelial activation ICAM-1 (138 +/- 10 vs. 186 +/- 25 ng/ml), VCAM-1 (1066 +/- 67 vs. 1204 +/- 65 ng/ml) and sE-S (20 +/- 1 vs. 24 +/- 1 ng/ml) between 13-35% and by > or = 2-fold plasma levels of myeloperoxidase (7.5 +/- 0.9 to 15 +/- 25 ng/ml), an inflammatory marker of future CVD, and tPAI-1 (9.7 +/- 0.6 to 22.5 +/- 1.5 ng/ml), an indicator of a prothrombotic state (all p < or = 0.01). The FFA-induced increase was independent from the degree of adiposity, being of similar magnitude in lean, overweight and obese subjects. An increase in plasma FFA within the physiological range observed in obesity and T2DM induces markers of endothelial activation, vascular inflammation and thrombosis in healthy subjects. This suggests that even transient (48-hour) and modest increases in plasma FFA may initiate early vascular abnormalities that promote atherosclerosis and CVD.

Obese First-Degree Relatives of Patients with Type 2 Diabetes with Elevated Triglyceride Levels Exhibit Increased β-Cell Function

PubMed Central

Torres-Rasgado, Enrique; Porchia, Leonardo M.; Ruiz-Vivanco, Guadalupe; Gonzalez-Mejia, M. Elba; Báez-Duarte, Blanca G.; Pulido-Pérez, Patricia; Rivera, Alicia; Romero, Jose R.

2015-01-01

Abstract Background: Type 2 diabetes mellitus (T2DM) is characterized as a disease continuum that is marked by metabolic changes that are present for several years, sometimes well before frank diagnosis of T2DM. Genetic predisposition, ethnicity, geography, alterations in BMI, and lipid profile are considered important markers for the pathogenesis of T2DM through mechanisms that remain unresolved and controversial. The aim of this study was to investigate the relationship between triglycerides (TGs) and β-cell function, insulin resistance (IR), and insulin sensitivity (IS) in obese first-degree relatives of patients with T2DM (FDR-T2DM) among subjects from central Mexico with normal glucose tolerance (NGT). Methods: We studied 372 FDR-T2DM subjects (ages,18–65) and determined body mass index (BMI), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), insulin, and TGs levels. Subjects were categorized based on glycemic control [NGT, prediabetes (PT2DM), or T2DM]. NGT subjects were further categorized by BMI [normal weight (Ob−) or obese (Ob+)] and TGs levels (TG−, <150 mg/dL, or TG+, ≥150 mg/dL). β-cell function, IR, and IS were determined by the homeostasis model assessment of β-cell function (HOMA2-β), homeostasis model assessment of insulin resistance (HOMA2-IR), and Quantitative Insulin Sensitivity Check Index (QUICKI) indices, respectively. Results: The obese subjects with elevated TGs levels had 21%–60% increased β-cell function when compared to all groups (P<0.05). In addition, this group had insulin levels, IS, and IR similar to PT2DM. Furthermore, only in obese subjects did TGs correlate with β-cell function (ρ=0.502, P<0.001). Conclusion: We characterized FDR-T2DM subjects from central Mexico with NGT and revealed a class of obese subjects with elevated TGs and β-cell function, which may precede PT2DM. PMID:25423015

Cost Effective, Ultra Sensitive Groundwater Monitoring for Site Remediation and Management: Standard Operating Procedures with QA/QC

DTIC Science & Technology

2015-05-01

in consultation with the site management . 4.0 DATA TYPES AND QUALITY CONTROL A sampling plan must account for the collection, handling, and...GUIDANCE DOCUMENT Cost-Effective, Ultra-Sensitive Groundwater Monitoring for Site Remediation and Management : Standard Operating Procedures...Groundwater Monitoring for Site Remediation and Management 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Halden, R.U., Roll, I.B. 5d

Acid-sensitive sheddable PEGylated, mannose-modified nanoparticles increase the delivery of betamethasone to chronic inflammation sites in a mouse model

PubMed Central

O’Mary, Hannah L.; Aldayel, Abdulaziz M.; Valdes, Solange A.; Naguib, Youssef W.; Li, Xu; Salvady, Karun; Cui, Zhengrong

2017-01-01

Inflammation is implicated in a host of chronic illnesses. Within these inflamed tissues, the pH of the microenvironment is decreased and immune cells, particularly macrophages, infiltrate the area. Additionally, the vascular integrity of these sites is altered with increased fenestrations between endothelial cells. These distinctive properties may be exploited to enhance targeted delivery of anti-inflammatory therapies. Using a mouse model of chronic inflammation, we previously showed that acid-sensitive sheddable PEGylation increases the distribution and retention of nanoparticles in chronic inflammation sites. Here we demonstrated that surface modification of the acid-sensitive sheddable PEGylated nanoparticles with mannose, a ligand to mannose receptors present in chronic inflammation sites, significantly increases the targeted delivery of the nanoparticles to these areas. Furthermore, we showed that the acid-sensitive sheddable PEGylated, mannose-modified nanoparticles are able to significantly increase the delivery of betamethasone-21-acetate (BA), a model anti-inflammatory compound, to chronic inflammation sites as compared to free BA. These results highlight the ability to engineer formulations to target chronic inflammation sites by exploiting the microenvironment of these regions. PMID:28463518

High frequency electrical stimulation concurrently induces central sensitization and ipsilateral inhibitory pain modulation.

PubMed

Vo, L; Drummond, P D

2013-03-01

In healthy humans, analgesia to blunt pressure develops in the ipsilateral forehead during various forms of limb pain. The aim of the current study was to determine whether this analgesic response is induced by ultraviolet B radiation (UVB), which evokes signs of peripheral sensitization, or by high-frequency electrical stimulation (HFS), which triggers signs of central sensitization. Before and after HFS and UVB conditioning, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the treated site in the forearm. In addition, sensitivity to blunt pressure was measured bilaterally in the forehead. The effect of ipsilateral versus contralateral temple cooling on electrically evoked pain in the forearm was then examined, to determine whether HFS or UVB conditioning altered inhibitory pain modulation. UVB conditioning triggered signs of peripheral sensitization, whereas HFS conditioning triggered signs of central sensitization. Importantly, ipsilateral forehead analgesia developed after HFS but not UVB conditioning. In addition, decreases in electrically evoked pain at the HFS-treated site were greater during ipsilateral than contralateral temple cooling, whereas decreases at the UVB-treated site were similar during both procedures. HFS conditioning induced signs of central sensitization in the forearm and analgesia both in the ipsilateral forehead and the HFS-treated site. This ipsilateral analgesia was not due to peripheral sensitization or other non-specific effects, as it failed to develop after UVB conditioning. Thus, the supra-spinal mechanisms that evoke central sensitization might also trigger a hemilateral inhibitory pain modulation process. This inhibitory process could sharpen the boundaries of central sensitization or limit its spread. © 2012 European Federation of International Association for the Study of Pain Chapters.

Interannual and Seasonal Patterns of Carbon Dioxide, Water, and Energy Fluxes From Ecotonal and Thermokarst-Impacted Ecosystems on Carbon-Rich Permafrost Soils in Northeastern Siberia

NASA Astrophysics Data System (ADS)

Euskirchen, Eugénie S.; Edgar, Colin W.; Syndonia Bret-Harte, M.; Kade, Anja; Zimov, Nikita; Zimov, Sergey

2017-10-01

Eastern Siberia Russia is currently experiencing a distinct and unprecedented rate of warming. This change is particularly important given the large amounts of carbon stored in the yedoma permafrost soils that become vulnerable to thaw and release under warming. Data from this region pertaining to year-round carbon, water, and energy fluxes are scarce, particularly in sensitive ecotonal ecosystems near latitudinal treeline, as well as those already impacted by permafrost thaw. Here we investigated the interannual and seasonal carbon dioxide, water, and energy dynamics at an ecotonal forested site and a disturbed thermokarst-impacted site. The ecotonal site was approximately neutral in terms of CO2 uptake/release, while the disturbed site was either a source or neutral. Our data suggest that high rates of plant productivity during the growing season at the disturbed site may, in part, counterbalance higher rates of respiration during the cold season compared to the ecotonal site. We also found that the ecotonal site was sensitive to the timing of the freezeup of the soil active layer in fall, releasing more CO2 when freezeup occurred later. Both sites showed a negative water balance, although the ecotonal site appeared more sensitive to dry conditions. Water use efficiency at the ecotonal site was lower during warmer summers. Overall, these Siberian measurements indicate ecosystem sensitivity to warmer conditions during the fall and to drier conditions during the growing season and provide a better understanding of ecosystem response to climate in a part of the circumpolar Arctic where current knowledge is weakest.

Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial.

PubMed

Sabatine, Marc S; Leiter, Lawrence A; Wiviott, Stephen D; Giugliano, Robert P; Deedwania, Prakash; De Ferrari, Gaetano M; Murphy, Sabina A; Kuder, Julia F; Gouni-Berthold, Ioanna; Lewis, Basil S; Handelsman, Yehuda; Pineda, Armando Lira; Honarpour, Narimon; Keech, Anthony C; Sever, Peter S; Pedersen, Terje R

2017-12-01

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab reduced LDL cholesterol and cardiovascular events in the FOURIER trial. In this prespecified analysis of FOURIER, we investigated the efficacy and safety of evolocumab by diabetes status and the effect of evolocumab on glycaemia and risk of developing diabetes. FOURIER was a randomised trial of evolocumab (140 mg every 2 weeks or 420 mg once per month) versus placebo in 27 564 patients with atherosclerotic disease who were on statin therapy, followed up for a median of 2·2 years. In this prespecified analysis, we investigated the effect of evolocumab on cardiovascular events by diabetes status at baseline, defined on the basis of patient history, clinical events committee review of medical records, or baseline HbA 1c of 6·5% (48 mmol/mol) or greater or fasting plasma glucose (FPG) of 7·0 mmol/L or greater. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina, or coronary revascularisation. The key secondary endpoint was a composite of cardiovascular death, myocardial infarction, or stroke. We also assessed the effect of evolocumab on glycaemia, and on the risk of new-onset diabetes among patients without diabetes at baseline. HbA 1c was measured at baseline then every 24 weeks and FPG was measured at baseline, week 12, week 24, and every 24 weeks thereafter, and potential cases of new-onset diabetes were adjudicated centrally. In a post-hoc analysis, we also investigated the effects on glycaemia and diabetes risk in patients with prediabetes (HbA 1c 5·7-6·4% [39-46 mmol/mol] or FPG 5·6-6·9 mmol/L) at baseline. FOURIER is registered with ClinicalTrials.gov, number NCT01764633. At study baseline, 11 031 patients (40%) had diabetes and 16 533 (60%) did not have diabetes (of whom 10 344 had prediabetes and 6189 had normoglycaemia). Evolocumab significantly reduced cardiovascular outcomes consistently in patients with and without diabetes at baseline. For the primary composite endpoint, the hazard ratios (HRs) were 0·83 (95% CI 0·75-0·93; p=0·0008) for patients with diabetes and 0·87 (0·79-0·96; p=0·0052) for patients without diabetes (p interaction =0·60). For the key secondary endpoint, the HRs were 0·82 (0·72-0·93; p=0·0021) for those with diabetes and 0·78 (0·69-0·89; p=0·0002) for those without diabetes (p interaction =0·65). Evolocumab did not increase the risk of new-onset diabetes in patients without diabetes at baseline (HR 1·05, 0·94-1·17), including in those with prediabetes (HR 1·00, 0·89-1·13). Levels of HbA 1c and FPG were similar between the evolocumab and placebo groups over time in patients with diabetes, prediabetes, or normoglycaemia. Among patients with diabetes at baseline, the proportions of patients with adverse events were 78·5% (4327 of 5513 patients) in the evolocumab group and 78·3% (4307 of 5502 patients) in the placebo group; among patients without diabetes at baseline, the proportions with adverse events were 76·8% (6337 of 8256 patients) in the evolocumab group and 76·8% (6337 of 8254 patients) in the placebo group. PCSK9 inhibition with evolocumab significantly reduced cardiovascular risk in patients with and without diabetes. Evolocumab did not increase the risk of new-onset diabetes, nor did it worsen glycaemia. These data suggest evolocumab use in patients with atherosclerotic disease is efficacious and safe in patients with and without diabetes. Amgen. Copyright © 2017 Elsevier Ltd. All rights reserved.

The identification of hydrophobic sites on the surface of proteins using absorption difference spectroscopy of bromophenol blue.

PubMed

Bertsch, M; Mayburd, A L; Kassner, R J

2003-02-15

Hydrophobic sites on the surface of protein molecules are thought to have important functional roles. The identification of such sites can provide information about the function and mode of interaction with other cellular components. While the fluorescence enhancement of polarity-sensitive dyes has been useful in identifying hydrophobic sites on a number of targets, strong intrinsic quenching of Nile red and ANSA dye fluorescence is observed on binding to a cytochrome c('). Fluorescence quenching is also observed to take place in the presence of a variety of other biologically important molecules which can compromise the quantitative determination of binding constants. Absorption difference spectroscopy is shown not to be sensitive to the presence of fluorescence quenchers but sensitive enough to measure binding constants. The dye BPB is shown to bind to the same hydrophobic sites on proteins as polarity-sensitive fluorescence probes. The absorption spectrum of BPB is also observed to be polarity sensitive. A binding constant of 3x10(6)M(-1) for BPB to BSA has been measured by absorption difference spectroscopy. An empirical correlation is observed between the shape of the absorption difference spectrum of BPB and the polarity of the environment. The results indicate that absorption difference spectroscopy of BPB provides a valuable supplement to fluorescence for determining the presence of hydrophobic sites on the surface of proteins as well as a method for measuring binding constants.

Hunted Woolly Monkeys (Lagothrix poeppigii) Show Threat-Sensitive Responses to Human Presence

PubMed Central

Papworth, Sarah; Milner-Gulland, E. J.; Slocombe, Katie

2013-01-01

Responding only to individuals of a predator species which display threatening behaviour allows prey species to minimise energy expenditure and other costs of predator avoidance, such as disruption of feeding. The threat sensitivity hypothesis predicts such behaviour in prey species. If hunted animals are unable to distinguish dangerous humans from non-dangerous humans, human hunting is likely to have a greater effect on prey populations as all human encounters should lead to predator avoidance, increasing stress and creating opportunity costs for exploited populations. We test the threat sensitivity hypothesis in wild Poeppigi's woolly monkeys (Lagothrix poeppigii) in Yasuní National Park, Ecuador, by presenting human models engaging in one of three behaviours “hunting”, “gathering” or “researching”. These experiments were conducted at two sites with differing hunting pressures. Visibility, movement and vocalisations were recorded and results from two sites showed that groups changed their behaviours after being exposed to humans, and did so in different ways depending on the behaviour of the human model. Results at the site with higher hunting pressure were consistent with predictions based on the threat sensitivity hypothesis. Although results at the site with lower hunting pressure were not consistent with the results at the site with higher hunting pressure, groups at this site also showed differential responses to different human behaviours. These results provide evidence of threat-sensitive predator avoidance in hunted primates, which may allow them to conserve both time and energy when encountering humans which pose no threat. PMID:23614003

Projected shell model study of odd-odd f-p-g shell proton-rich nuclei

NASA Astrophysics Data System (ADS)

Palit, R.; Sheikh, J. A.; Sun, Y.; Jain, H. C.

2003-01-01

A systematic study of two-quasiparticle bands of the proton-rich odd-odd nuclei in the mass A˜70 80 region is performed using the projected shell model approach. The study includes Br, Rb, and Y isotopes with N=Z+2 and Z+4. We describe the energy spectra and electromagnetic transition strengths in terms of the configuration mixing of the angular-momentum projected multi-quasiparticle states. Signature splitting and signature inversion in the rotational bands are discussed and are shown to be well described. A preliminary study of the odd-odd N=Z nucleus 74Rb, using the concept of spontaneous symmetry breaking is also presented.

A magnetotelluric study of the sensitivity of an area to seismoelectric signals

USGS Publications Warehouse

Balasis, G.; Bedrosian, P.A.; Eftaxias, K.

2005-01-01

During recent years, efforts at better understanding the physical properties of precursory ultra-low frequency pre-seismic electric signals (SES) have been intensified. Experiments show that SES cannot be observed at all points of the Earth's surface but only at certain so-called sensitive sites. Moreover, a sensitive site is capable of collecting SES from only a restricted number of seismic areas (selectivity effect). Tberefore the installation of a permanent station appropriate for SES collection should necessarily be preceded by a pilot study over a broad area and for a long duration. In short, a number of temporary stations are installed and, after the occurrence of several significant earthquakes (EQs) from a given seismic area, the most appropriate (if any) of these temporary stations, in the sense that they happen to collect SES, can be selected as permanent. Such a long experiment constitutes a serious disadvantage in identifying a site as SES sensitive. However, the SES sensitivity of a site should be related to the geoelectric structure of the area that hosts the site as well as the regional geoelectric structure between the station and the seismic focal area. Thus, knowledge of the local and regional geoelectric structure can dramatically reduce the time involved in identifying SES sites. hi this paper the magnetotelluric method is used to investigate the conductivity structure of an area where a permanent SES station is in operation. Although general conclusions cannot be drawn, the area surrounding an SES site near Ioannina, Greece is characterized by: (1) major faults in the vicinity; (2) highly resistive structure flanked by abrupt conductivity contrasts associated with large-scale geologic contacts, and (3) local inhomogeneities in conductivity structure. The above results are consistent with the fact that electric field amplitudes from remotely-generated signals should be appreciably stronger at such sites when compared to neighboring sites. European Geosciences Union ?? 2005 Author(s). This work is licensed under a Creative Commons License.

Glucocorticoid effects on contact hypersensitivity and on the cutaneous response to ultraviolet light in the mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ross, P.M.; Walberg, J.A.; Bradlow, H.L.

1988-03-01

A single exposure to 254 nm ultraviolet irradiation (UV) can systemically suppress experimental sensitization to the simple allergen 2,4-dinitro, 1-chlorobenzene (DNCB) in the mouse. We show here that topical application at the site of irradiation of the 21-oic acid methyl ester derivative of the synthetic glucocorticoid triamcinolone acetonide (TAme) prevents UV suppression of sensitization. That is, mice painted with TAme at the site of UV exposure developed normal contact hypersensitivity (CH); mice exposed to UV only, like mice treated with the parent compound triamcinolone acetonide (TA), failed to be sensitized by DNCB applied to a distal site. TAme is inactivatedmore » rapidly by plasma esterases, so its effect is thought to be confined to the skin. Apparently, TAme blocked the cutaneous signal(s) for systemic suppression of CH. Histologically, irradiated skin exhibited mild inflammation and hyperproliferation, but these effects were greatly exaggerated and prolonged in the UV + TAme-treated skin, independent of sensitization at the distal site. The infiltrate consisted mostly of neutrophils and lacked the round cells characteristic of cell-mediated immunity. Apparently, normal immune suppression by UV prevented this vigorous reaction to irradiated skin. Applied together with DNCB. TAme blocked sensitization. It also prevented response to challenge by DNCB in previously sensitized animals. However, unlike the parent compound triamcinolone acetonide (TA), Budesonide or Beclomethasone diproprionate, each of which can penetrate the epidermis in active form, TAme had no effect on sensitization when applied at a distal site. Likewise, TAme did not affect plasma B (17-desoxycortisol) levels, whereas the other three compounds reduced plasma B tenfold, as expected of compounds causing adrenal-pituitary suppression.« less

Drought sensitivity changes over the last century at the North American savanna-forest boundary

NASA Astrophysics Data System (ADS)

Heilman, K.; McLachlan, J. S.

2017-12-01

Future environmental changes can affect the sensitivity of tree growth to climate. Theses changes are of particular concern at biome boundaries where tree distribution could shift as a result of changes in both drought and drought sensitivity. One such region is the North American savanna-forest boundary, where increased CO2 and droughts could alter savanna and forest ecosystem distributions in two contrasting ways: 1). More severe droughts may increase drought sensitivity, favoring open savanna ecosystems or, 2). Increases in water use efficiency resulting from higher atmospheric CO2 may decrease drought sensitivity, promoting forest expansion. This study sought to understand whether the past 100 years of climate and CO2 changes have impacted regional tree growth-climate sensitivity. To test for these climate sensitivity changes, we measured the sensitivity of Quercus spp. radial growth to Palmer Drought Severity Index (PDSI). Tree growth sensitivity to climate can vary according to many factors, including: stand structure, available moisture, and tree age. To control for these factors, we sampled tree growth-climate responses at sites in both open and closed forests, and at both low and high annual precipitation. Within each site, we compared growth responses to climate between trees established under high CO2 conditions after 1950 (high CO2 young), and tree established before 1950 under low CO2 levels (low CO2 young). At most sites, low CO2 young have a higher drought sensitivity than higher CO2 young. These changes in the sensitivity to drought are consistent with CO2 enhancement of water use efficiency. Furthermore, these differences in drought sensitivity are higher at sites with high temperature and low precipitation, suggesting that the alleviation of drought is more likely in hot and dry regions. Thus, if CO2 enhancement is indeed occurring in these systems, lower growth sensitivity to drought in hot and dry regions could favor increased forest growth. If changes in drought sensitivity scale to ecosystem level, decreased drought sensitivity may have helped promote regional forest expansion.

Sensitized luminescence from water-soluble LaF3:Eu nanocrystals via partially-capped 1,10-phenanthroline: time-gated emission and multiple lifetimes.

PubMed

Irfanullah, Mir; Bhardwaj, Navneet; Chowdhury, Arindam

2016-08-02

Water dispersible citrate-capped LaF3:Eu(5%) nanocrystals (NCs) have been partially surface-functionalized by 1,10-phenanthroline (phen) via a ligand exchange method to produce novel water dispersed citrate/phen-capped LaF3:Eu(5%) NCs in which citrate ligands preserve the water dispersibility of the NCs and phen ligands act as sensitizers of surface Eu(3+)-dopant sites. The partial ligand exchange and the formation of water dispersed NCs have been monitored by (1)H NMR spectroscopy, as well as luminescence measurements at different time intervals during the reaction. These NCs display a distinct phen-sensitized Eu(3+)-emission profile with enhanced intensity in water as compared to the emission profile and intensity obtained upon direct excitation. Time-resolved (or time-gated) emission spectroscopy (TRES) has been used to probe PL dynamics of Eu(3+)-sites of LaF3:Eu(5%) NCs by taking advantage of selectively sensitizing surface Eu(3+)-dopant sites by phen ligands as well as by exciting all the Eu(3+)-sites in the NCs upon direct excitation. TRES upon direct excitation of the citrate-capped LaF3:Eu(5%) NCs reveals that Eu(3+)-dopants occupy at least three different sites, each with a different emission profile and lifetime, and emission from purely interior Eu(3+)-sites has been resolved due to their long lifetime as compared to the lifetime of purely surface and near surface Eu(3+)-sites. In contrast, the phen-sensitized emission from citrate/phen-capped LaF3:Eu(5%) NCs displays similar emission profiles and lifetimes in TRES measurements, which reveal that phen truly sensitizes purely surface dopant sites of the NCs in water, all of which have nearly the same local environment. The phen-sensitized Eu(3+)-emission of the NCs in water remains stable even upon addition of various buffer solutions at physiological pH, as well as upon addition of water-miscible organic solvents. Furthermore, the two-photon excitation (λex. = 720 nm) of these water-soluble phen-capped NCs produces bright red Eu(3+) emission, which reveals that these NCs are promising for potential applications in biological imaging.

INVESTIGATING UNCERTAINTY AND SENSITIVITY IN INTEGRATED, MULTIMEDIA ENVIRONMENTAL MODELS: TOOLS FOR FRAMES-3MRA

EPA Science Inventory

Elucidating uncertainty and sensitivity structures in environmental models can be a difficult task, even for low-order, single-medium constructs driven by a unique set of site-specific data. Quantitative assessment of integrated, multimedia models that simulate hundreds of sites...

Comparative effectiveness of light-microscopic techniques and PCR in detecting Thelohania solenopsae (Microsporidia) infections in red imported fire ants (Solenopsis invicta).

PubMed

Milks, Maynard L; Sokolova, Yuliya Y; Isakova, Irina A; Fuxa, James R; Mitchell, Forrest; Snowden, Karen F; Vinson, S Bradleigh

2004-01-01

The main goal of this study was to compare the effectiveness of three staining techniques (calcofluor white M2R, Giemsa and modified trichrome), and the polymerase chain reaction (PCR) in detecting the microsporidium Thelohania solenopsae in red imported fire ants (Solenopsis invicta). The effect of the number of ants in a sample on the sensitivity of the staining techniques and the PCR, and the effect of three DNA extraction protocols on the sensitivity of PCR were also examined. In the first protocol, the ants were macerated and the crude homogenate was used immediately in the PCR. In the second protocol, the homogenate was placed on a special membrane (FTA card) that traps DNA, which is subsequently used in the PCR. In the third protocol, the DNA was purified from the homogenate by traditional phenol-chloroform extraction. Except for PCR using FTA cards, the sensitivity (number of samples positive for T. solenopsae) of all detection techniques increased with the number of ants in the sample. Overall, Giemsa was the least sensitive of all detection techniques. Calcofluor was more sensitive than modified trichrome with ants from one site and was equally as sensitive as PCR with crude DNA or a FTA card with ants from both sites. Trichrome staining was equally as sensitive as PCR with a FTA card at both sites, but it was less sensitive than PCR with crude DNA at one site. PCR on FTA cards was less sensitive than PCR with crude DNA for ants from one site but not the other. There was no difference whether crude or phenol-chloroform purified DNA was used as template. In summary, the results of this study show that PCR based on a crude DNA solution is equal to or more sensitive in detecting T. solenopsae than the other detection techniques investigated, and that it can be used as a reliable diagnostic tool for screening field samples of S. invicta for T. solenopsae. Nevertheless, ant smear stained with calcofluor or modified trichrome should be used to buttress findings from PCR.

Sites of ozone sensitivity in diverse maize inbred lines

USDA-ARS?s Scientific Manuscript database

Tropospheric ozone (O3) is an air pollutant that costs ~$14-26 billion in global crop losses and is projected to worsen in the future. Potential sites of O3 sensitivity in maize were tested by growing 200 inbred lines, including the nested association mapping population founder lines, under ambient...

Differential sensitivity to regional-scale drought in six central US grasslands.

PubMed

Knapp, Alan K; Carroll, Charles J W; Denton, Elsie M; La Pierre, Kimberly J; Collins, Scott L; Smith, Melinda D

2015-04-01

Terrestrial ecosystems often vary dramatically in their responses to drought, but the reasons for this are unclear. With climate change forecasts for more frequent and extensive drought in the future, a more complete understanding of the mechanisms that determine differential ecosystem sensitivity to drought is needed. In 2012, the Central US experienced the fourth largest drought in a century, with a regional-scale 40% reduction in growing season precipitation affecting ecosystems ranging from desert grassland to mesic tallgrass prairie. This provided an opportunity to assess ecosystem sensitivity to a drought of common magnitude in six native grasslands. We tested the prediction that drought sensitivity is inversely related to mean annual precipitation (MAP) by quantifying reductions in aboveground net primary production (ANPP). Long-term ANPP data available for each site (mean length = 16 years) were used as a baseline for calculating reductions in ANPP, and drought sensitivity was estimated as the reduction in ANPP per millimeter reduction in precipitation. Arid grasslands were the most sensitive to drought, but drought responses and sensitivity varied by more than twofold among the six grasslands, despite all sites experiencing 40% reductions in growing season precipitation. Although drought sensitivity generally decreased with increasing MAP as predicted, there was evidence that the identity and traits of the dominant species, as well as plant functional diversity, influenced sensitivity. A more comprehensive understanding of the mechanisms leading to differences in drought sensitivity will require multi-site manipulative experiments designed to assess both biotic and abiotic determinants of ecosystem sensitivity.

Efficacy and safety of ipragliflozin as add-on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): a multi-centre, randomized, placebo-controlled, double-blind study.

PubMed

Ishihara, Hisamitsu; Yamaguchi, Susumu; Nakao, Ikko; Okitsu, Akira; Asahina, Seitaro

2016-12-01

To examine the efficacy and safety of add-on ipragliflozin in Japanese patients with type 2 diabetes in the early stage of insulin therapy. Patients treated with insulin (bolus component <30% of total daily dose) with/without a dipeptidyl peptidase-4 (DPP-4) inhibitor were randomized to receive placebo (n = 87) or ipragliflozin (n = 175) for 16 weeks. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline. Secondary endpoints included changes in fasting plasma glucose (FPG) and metabolic hormones. Safety endpoints were also examined. The changes in HbA1c were 0.27% and -0.79% (2.9 and -8.7 mmol/mol) in the placebo and ipragliflozin groups, respectively (baseline: 8.62% vs 8.67% [70.8 vs 71.2 mmol/mol]), corresponding to an adjusted mean difference of -1.07% (95% confidence interval -1.24, -0.91) or -11.7 mmol/mol (-13.5, -9.9), p < .001. Ipragliflozin reduced FPG and serum C-peptide levels and body weight (all p < .001), and increased serum adiponectin levels (p = .022). There was a statistically significant interaction for use/non-use of a DPP-4 inhibitor × treatment group for the change in HbA1c (p = .042). Hypoglycaemia was the only treatment-related adverse event reported in >5% of patients (14.9% vs 29.1%). Events consistent with urinary tract infection (placebo 1.1% vs ipragliflozin 2.3%) or genital infection (0.0% and 4.0%, respectively) occurred in <5% of patients. Ipragliflozin was well tolerated and effective in insulin-treated patients, especially when used with a DPP-4 inhibitor. © 2016 John Wiley & Sons Ltd.

Extent of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation and glycated hemoglobin of 5.6-6.4.

PubMed

Iwahashi, Hiromi; Noguchi, Midori; Okauchi, Yukiyoshi; Morita, Sachiko; Imagawa, Akihisa; Shimomura, Iichiro

2015-09-01

Weight reduction improves glycemic control in obese men with glycated hemoglobin (HbA1c) of 5.6-6.4%, suggesting that it can prevent the development of diabetes in these patients. The aim of the present study was to quantify the amount of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation. The study participants were 482 men with an estimated visceral fat area of ≥100 cm(2), HbA1c of 5.6-6.4%, fasting plasma glucose (FPG) of <126 mg/dL or casual plasma glucose <200 mg/dL. They were divided into two groups based on weight change at the end of the 3-year follow-up period (weight gain and weight loss groups). The weight loss group was classified into quartile subgroups (lowest group, 0 to <1.2%: second lowest group, ≥1.2 to <2.5%: second highest group, ≥2.5 to <4.3%: highest group, ≥4.3% weight loss). The development of diabetes at the end-point represented a rise in HbA1c to ≥6.5% or FPG ≥126 mg/dL, or casual plasma glucose ≥200 mg/dL. The cumulative incidence of diabetes at the end of the 3-year follow-up period was 16.2% in the weight gain group and 10.1% in the weight loss group (P not significant). The incidence of diabetes was significantly lower in the highest weight loss group (3.1%), but not in the second highest, the second lowest and the lowest weight loss groups (9.7, 10.1 and 18.3%), compared with the weight gain group. Minimization of the risk of diabetes in Japanese men with visceral fat accumulation requires a minimum of 4-5% weight loss in those with HbA1c of 5.6-6.4%.

Association of the relative change in weight and body mass index with lung function in teenagers and adults with cystic fibrosis: Influence of gender and diabetes.

PubMed

Cano Megías, Marta; Guisado Vasco, Pablo; González Albarrán, Olga; Lamas Ferreiro, Adelaida; Máiz Carro, Luis

2015-11-01

Nutritional status is a prognostic factor in cystic fibrosis. Prevention of nutritional impairment and weigh loss are major clinical objectives because they are associated with worsening of lung function and increased mortality. To identify a potential relationship of clinical nutrition parameters, and their relative changes, with lung function (FEV1%) in a cohort of adolescent and adult patients with CF. A retrospective analysis of 64 patients older than 14years. Weight, height, BMI, and lung function data were collected at a period of disease stability, both in the year of the first abnormal oral glucose tolerance test (OGTT) and in the previous year. Relative changes in weight and BMI, and their relationship with FEV1%, were determined by linear regression and ANOVA tests; influence of gender and diabetes was also assessed. Mean age of the series (28 females and 36 males) was 26.8years. Normal glucose tolerance (NGT) was found in 26.7%, while 18.3% had diabetes without impaired fasting glucose (CFRD without FPG). Mean BMI was 20.32, with a mean weight of 53.53kg; 32.8% had BMI<18.5, and only 4.7% were overweight. Overall, a positive relative change in weight (≥6%) was associated with an increase in FEV1% (9.31%), as compared to those with a greater weight loss (at least 2%), who had a 12.09% fall in FEV1. Patients with CFRD without FPG had poorer lung function if they had a negative relative change in weight by at least 2% as compared to NGT. In patients with CF, a relative weight gain is positively associated to FEV1%, while a relative weight loss of at least 2% has a significant negative impact on lung function. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

The impact of fasting during Ramadan on the glycemic control of patients with type 2 diabetes mellitus.

PubMed

Sahin, S B; Ayaz, T; Ozyurt, N; Ilkkilic, K; Kirvar, A; Sezgin, H

2013-10-01

Millions of Muslims fast from dawn until dusk during the annual Islamic holy month of Ramadan. Most of the studies evaluating biochemical changes in diabetic patients during Ramadan showed little changes in the glycemic control. In this study, our aim was to assess the impact of fasting during Ramadan on glycemic control in patients with type 2 diabetes. We examined 122 patients with type 2 diabetes (82 female, 40 male, age 56.93 ± 9.57 years) before and after the Ramadan. 66.4% of the patients were treated with oral antidiabetic (OAD) alone, 6.5% with a combination of insulin plus OAD and 19.7% with insulin alone. 88 of 122 patients fasted during Ramadan (26.98 ± 5.93 days). Weight, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), postprandial glucose (PPG), fructosamine, HbA1c, fasting insulin and lipid parameters were measured. The frequencies of both severe hyperglycemia and hypoglycemia were higher in the fasting group, but the difference was not significant (p=0.18). Weight, BMI, waist circumference, blood pressure, FPG (143.38 ± 52.04 vs. 139.31 ± 43.47 mg/dl) PPG (213.40 ± 98.56 vs. 215.66+109.31 mg/dl), fructosamine (314.18 ± 75.40 vs. 314.49 ± 68.36 µmol/l), HbA1c (6.33 ± 0.98 vs. 6.22 ± 0.92%) and fasting insulin (12.61 ± 8.94 vs. 10.51 ± 6.26 µU/ml) were unchanged in patients who fasted during Ramadan. Microalbuminuria significantly decreased during Ramadan (132.85 ± 197.11 vs. 45.03 ± 73.11 mg/dl). In this study, we concluded that fasting during Ramadan did not worsen the glycemic control of patients with type 2 diabetes. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

The Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately Controlled Type 2 Diabetes With Metformin Alone

PubMed Central

DeFronzo, Ralph A.; Hissa, Miguel N.; Garber, Alan J.; Luiz Gross, Jorge; Yuyan Duan, Raina; Ravichandran, Shoba; Chen, Roland S.

2009-01-01

OBJECTIVE This 24-week trial assessed the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes with inadequate glycemic control with metformin alone. RESEARCH DESIGN AND METHODS This was a randomized, double-blind, placebo-controlled study of saxagliptin (2.5, 5, or 10 mg once daily) or placebo plus a stable dose of metformin (1,500–2,500 mg) in 743 patients (A1C ≥7.0 and ≤10.0%). Efficacy analyses were performed using an ANCOVA model using last observation carried forward methodology on primary (A1C) and secondary (fasting plasma glucose [FPG] and postprandial glucose [PPG] area under the curve [AUC]) end points. RESULTS Saxagliptin (2.5, 5, and 10 mg) plus metformin demonstrated statistically significant adjusted mean decreases from baseline to week 24 versus placebo in A1C (−0.59, −0.69, and −0.58 vs. +0.13%; all P < 0.0001), FPG (−14.31, −22.03, and −20.50 vs. +1.24 mg/dl; all P < 0.0001), and PPG AUC (−8,891, −9,586, and −8,137 vs. −3,291 mg · min/dl; all P < 0.0001). More than twice as many patients achieved A1C <7.0% with 2.5, 5, and 10 mg saxagliptin versus placebo (37, 44, and 44 vs. 17%; all P < 0.0001). β-Cell function and postprandial C-peptide, insulin, and glucagon AUCs improved in all saxagliptin treatment groups at week 24. Incidence of hypoglycemic adverse events and weight reductions were similar to those with placebo. CONCLUSIONS Saxagliptin once daily added to metformin therapy was generally well tolerated and led to statistically significant improvements in glycemic indexes versus placebo added to metformin in patients with type 2 diabetes inadequately controlled with metformin alone. PMID:19478198

A post hoc analysis of saxagliptin efficacy and safety in patients with type 2 diabetes stratified by UKPDS 10-year cardiovascular risk score.

PubMed

Bonora, E; Bryzinski, B; Hirshberg, B; Cook, W

2016-05-01

To assess the efficacy and safety of saxagliptin 2.5 and 5 mg/d in patients with type 2 diabetes mellitus (T2DM) and high risk of coronary heart disease (CHD) or stroke as estimated by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Post hoc analysis of data pooled from 5 previously reported phase 3, randomized, placebo-controlled, 24-week studies was conducted. Patients were stratified into subgroups by UKPDS 10-year CHD and/or stroke risk ≥20% and CHD and stroke risk <20%. End points were adjusted mean change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), 120-min postprandial glucose (PPG), and body weight and the proportion of patients achieving HbA1c <7% and ≤8% at week 24. Pooled safety data were analyzed for adverse events (AEs) and hypoglycemia. Both doses of saxagliptin reduced HbA1c, FPG, and PPG to a greater extent than placebo regardless of UKPDS risk score. The proportions of patients achieving HbA1c <7% and ≤8% were greater with saxagliptin than placebo and consistent across risk score groups. AE profile and hypoglycemia incidence were similar for saxagliptin and placebo across UKPDS risk score groups. Saxagliptin was well tolerated and improved glycemic control in patients with T2DM regardless of their CHD and stroke UKPDS risk score. Clinical trial registration numbers: Clinicaltrials.gov NCT00121641, NCT00316082, NCT00121667, NCT00313313, and NCT00295633. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Comparative Evaluation of Safety and Efficacy of Glimepiride and Sitagliptin in Combination with Metformin in Patients with Type 2 Diabetes Mellitus: Indian Multicentric Randomized Trial - START Study.

PubMed

Devarajan, T V; Venkataraman, S; Kandasamy, Narayanan; Oomman, Abraham; Boorugu, Hari Kishan; Karuppiah, S K P; Balat, Dushyant

2017-01-01

Modern sulfonylureas like glimepiride offer effective glycemic control with extrapancreatic benefits and good tolerability. The objective of the present study was to evaluate and compare safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus (T2DM). In this open-label, randomized, comparative, multicenter study, a total of 305 T2DM patients who were either drug naïve or uncontrolled on metformin were randomized to glimepiride 1 or 2 mg/sustained-release metformin 1000 mg once daily (glimepiride group, n = 202) or sitagliptin 50 mg/metformin 500 mg twice daily (sitagliptin group, n = 103) for 12 weeks. Primary endpoint was change in glycosylated hemoglobin (HbA1c). Secondary endpoints were change in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), body mass index (BMI) and to assess overall safety profile. At 12 weeks, there was a statistically significant difference in the mean HbA1c reduction in glimepiride group (0.42%) as compared to sitagliptin group (0.30%) ( P = 0.001). Mean reduction in FPG and PPG was also statistically significant in the glimepiride group as compared to the sitagliptin group ( P = 0.008). There was no significant difference in terms of change in BMI (0.07 ± 0.39 kg/m 2 vs. 0.08 ± 0.31 kg/m 2 ) in glimepiride and sitagliptin groups, respectively, ( P = 0.644) between both the groups. The incidences of hypoglycemic events were also comparable among both the groups. In T2DM patients, glimepiride/metformin combination exhibited significant reduction in glycemic parameters as compared to sitagliptin/metformin combination. Moreover, there was no significant difference between both the groups in terms of change in BMI and incidence of hypoglycemia.

Hepatic steatosis and steatohepatitis in human immunodeficiency virus/hepatitis C virus-coinfected patients.

PubMed

Macías, Juan; Berenguer, Juan; Japón, Miguel A; Girón-González, José A; Rivero, Antonio; López-Cortés, Luis F; Moreno, Ana; Márquez, Manuel; Iribarren, José A; Ortega, Enrique; Miralles, Pilar; Merchante, Nicolás; Pineda, Juan A

2012-10-01

Hepatic steatosis (HS) is frequent in human immunodeficiency virus (HIV)- and hepatitis C virus (HCV)-coinfected patients. Antiretroviral therapy (ART) and metabolic alterations could induce HS. However, a protective effect of ART has been reported in a paired biopsy study. Thus, our aim was to examine the changes and predictors of HS progression among HIV/HCV-coinfected patients with sequential biopsies. We also evaluated the rates of steatohepatitis and factors associated thereof. HIV-infected patients with detectable serum HCV RNA, who underwent two biopsies, separated at least by 1 year, were included in this retrospective study. HS progression was defined as increase in one or more HS grades. The median (interquartile range) time between biopsies was 3.3 (2.0-5.2) years. Among 146 individuals, HS at baseline was observed in 86 (60%) patients and in 113 (77%) in the follow-up biopsy (P < 0.001). Progression of HS was observed in 60 (40%) patients. HS regressed in 11 (8%) patients. Factors associated with HS progression were changes in fasting plasma glucose (FPG) between biopsies (per 10 mg/dL increase; odds ratio [OR] [95% confidence interval; CI] = 1.4 [1.04-1.8]; P = 0.024) and cumulative use of dideoxynucleoside analogs (per year; OR [95% CI] = 1.5 [1.2-1.8]; P = 0.001). Persistent steatohepatitis or progression to steatohepatitis between biopsies was observed in 27 (18%) patients. Persistence of or progression to steatohepatitis was associated with progression ≥ 1 fibrosis stages between biopsies (OR [95% CI] = 2.4 [1.01-5.7]; P = 0.047). HS progresses frequently and regression is rarely observed in HIV/HCV-coinfected patients, including in those on ART. Cumulative exposure to dideoxynucleoside analogs and increases in FPG are related with HS progression. Stetatohepatitis is frequently observed in these patients and is linked to fibrosis progression. Copyright © 2012 American Association for the Study of Liver Diseases.

Insulin 70/30 mix plus metformin versus triple oral therapy in the treatment of type 2 diabetes after failure of two oral drugs: efficacy, safety, and cost analysis.

PubMed

Schwartz, Sherwyn; Sievers, Richard; Strange, Poul; Lyness, William H; Hollander, Priscilla

2003-08-01

Subjects (n = 188) with type 2 diabetes and inadequate response to two oral medications (A1C >8.0%) were randomly assigned to treatment with either a third oral medication or an insulin 70/30 mix b.i.d. plus metformin for a comparison of efficacy, safety, and cost. The protocol called for aggressive dose titration to achieve target values of fasting blood glucose (80-120 mg/dl), postprandial glucose (<160 mg/dl), and A1C (<7%). These efficacy parameters were evaluated at weeks 2, 6, 12, and 24 of therapy. If dose adjustments failed to achieve targeted glycemic control, subjects were switched to an alternate therapy. At the end of study (week 24 of therapy), A1C and fasting plasma glucose (FPG) values showed comparable decreases in the two treatment groups. Only 31% (oral therapy) and 32% (insulin plus metformin) of subjects achieved target values of A1C (<7%). A total of 10 of the 98 subjects randomized to triple oral therapy (10.2%) who failed to improve sufficiently were switched to insulin therapy. An additional four subjects dropped out of the oral treatment group due to adverse events felt to be potentially drug related. Only two of the subjects randomized to insulin plus metformin had to be switched to basal-bolus regimens (regular insulin and NPH insulin). Cost analysis determined that insulin plus metformin (mean cost 3.20 dollars/day) provided efficacy equal to that of a triple oral drug regimen (10.40 dollars/day). Insulin 70/30 mix plus metformin was as effective as triple oral therapy in lowering A1C and FPG values. The triple oral regimen was not as cost effective, and a high percentage of subjects (total of 16.3%) did not complete this regimen due to lack of efficacy or side effects.

Genetic damage induced by organic extract of coke oven emissions on human bronchial epithelial cells.

PubMed

Zhai, Qingfeng; Duan, Huawei; Wang, Yadong; Huang, Chuanfeng; Niu, Yong; Dai, Yufei; Bin, Ping; Liu, Qingjun; Chen, Wen; Ma, Junxiang; Zheng, Yuxin

2012-08-01

Coke oven emissions are known as human carcinogen, which is a complex mixture of polycyclic aromatic hydrocarbon. In this study, we aimed to clarify the mechanism of action of coke oven emissions induced carcinogenesis and to identify biomarkers of early biological effects in a human bronchial epithelial cell line with CYP1A1 activity (HBE-CYP1A1). Particulate matter was collected in the oven area on glass filter, extracted and analyzed by GC/MS. DNA breaks and oxidative damage were evaluated by alkaline and endonucleases (FPG, hOGG1 and ENDO III)-modified comet assays. Cytotoxicity and chromosomal damage were assessed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The cells were treated with organic extract of coke oven emissions (OE-COE) representing 5, 10, 20, 40μg/mL extract for 24h. We found that there was a dose-effect relationship between the OE-COE and the direct DNA damage presented by tail length, tail intensity and Olive tail moment in the comet assay. The presence of lesion-specific endonucleases in the assays increased DNA migration after OE-COE treatment when compared to those without enzymes, which indicated that OE-COE produced oxidative damage at the level of pyrimidine and purine bases. The dose-dependent increase of micronuclei, nucleoplasmic bridges and nuclear buds in exposed cells was significant, indicating chromosomal and genomic damage induced by OE-COE. Based on the cytotoxic biomarkers in CBMN-Cyt assay, OE-COE may inhibit nuclear division, interfere with apoptosis, or induce cell necrosis. This study indicates that OE-COE exposure can induce DNA breaks/oxidative damage and genomic instability in HBE-CYP1A1 cells. The FPG-comet assay appears more specific for detecting oxidative DNA damage induced by complex mixtures of genotoxic substances. Copyright © 2012 Elsevier Ltd. All rights reserved.

A randomized clinical trial of the safety and efficacy of sitagliptin in patients with type 2 diabetes mellitus inadequately controlled by acarbose alone.

PubMed

Wang, Weiqing; Ning, Guang; Ma, Jianhua; Liu, Xiaomin; Zheng, Shaoxiong; Wu, Fan; Xu, Lei; O'Neill, Edward A; Fujita, Kenji P; Engel, Samuel S; Kaufman, Keith D; Shankar, R Ravi

2017-04-01

To evaluate the safety and efficacy of sitagliptin when added to the treatment of patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on acarbose monotherapy. This was a multicenter, randomized, placebo-controlled, double-blind clinical trial. Patients (N = 381) with T2DM and inadequate glycemic control (glycated hemoglobin [HbA1c] ≥ 7.0% and ≤10.0%) on acarbose monotherapy (at least 50 mg three times daily) were randomized in a 1:1 ratio to receive the addition of sitagliptin 100 mg or matching placebo once daily for 24 weeks. Changes from baseline in HbA1c and fasting plasma glucose (FPG) at Week 24. The mean baseline HbA1c in randomized patients was 8.1%. At Week 24, the placebo-controlled, least squares mean changes from baseline (95% confidence interval) in HbA1c and FPG in the sitagliptin group were -0.62% and -0.8 mmol/L (p < .001), respectively. At Week 24, 37.8% of patients in the sitagliptin group were at HbA1c goal of <7% compared with 17.2% in the placebo group (p < .001). Sitagliptin was generally well tolerated, and there were no significant between-group differences in prespecified safety parameters (symptomatic hypoglycemia, diarrhea, abdominal pain, nausea, vomiting). A higher incidence of serious adverse events was observed in the sitagliptin group (5.2%) relative to placebo (0.5%); all but one, in the sitagliptin group, were not considered related to drug. Sitagliptin was generally well tolerated and provided statistically superior and clinically meaningful improvements in glycemic control after 24 weeks of treatment compared to placebo when added to treatment of patients with inadequate glycemic control on acarbose monotherapy. Clinicaltrials.gov: NCT01177384.

Dose-finding study of luseogliflozin in Japanese patients with type 2 diabetes mellitus: a 12-week, randomized, double-blind, placebo-controlled, phase II study.

PubMed

Seino, Yutaka; Sasaki, Takashi; Fukatsu, Atsushi; Ubukata, Michito; Sakai, Soichi; Samukawa, Yoshishige

2014-07-01

Luseogliflozin is a selective sodium glucose cotransporter 2 inhibitor under development for the treatment of type 2 diabetes mellitus (T2DM). This phase II study was conducted to confirm the efficacy and safety of luseogliflozin monotherapy at doses of up to 10 mg in Japanese patients with T2DM. Patients with hemoglobin A1c (HbA1c) of 6.9-10.5% on diet therapy were randomized in a double-blind manner to treatment with 1, 2.5, 5, or 10 mg luseogliflozin or placebo for 12 weeks (n = 56, 56, 54, 58, and 58, respectively). Japan Pharmaceutical Information Center (identifier: Japic CTI-101191). The primary endpoint was the change in HbA1c from baseline to the end of treatment. Other endpoints included fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and body weight. Adverse events were recorded throughout the study. HbA1c decreased significantly at the end of treatment in the 1, 2.5, 5, and 10 mg luseogliflozin groups compared with placebo (-0.29, -0.39, -0.46, and -0.43%, respectively, versus +0.22%; all P < 0.001), as did FPG and PPG (all P < 0.001). Body weight also decreased significantly in all luseogliflozin groups compared with placebo (all P < 0.001). The incidence rates of adverse events (40.0-50.0%) were not significantly different among the five groups. The overall incidence of hypoglycemia was low. Limitations of this study include the short study duration and the relatively small sample size. In Japanese patients with T2DM, luseogliflozin was well tolerated, improved glycemic control, and reduced body weight over 12 weeks of treatment at all tested doses. Doses of ≥2.5 mg achieved similar improvements in glycemic control.

The effect of vitamin D supplementation on insulin resistance, visceral fat and adiponectin in vitamin D deficient women with polycystic ovary syndrome: a randomized placebo-controlled trial.

PubMed

Seyyed Abootorabi, Maryam; Ayremlou, Parvin; Behroozi-Lak, Tahereh; Nourisaeidlou, Sakineh

2018-06-01

Low plasma 25-hydroxy-vitamin D (25OHD) is associated with polycystic ovary syndrome (PCOS). Vitamin D deficiency may contribute to the development of insulin resistance, visceral fat and low level of adiponectin which are common feature in PCOS women. This study aimed to evaluate the effect of vitamin D supplementation on insulin resistance, visceral fat, and adiponectin in hypovitaminosis D women with polycystic ovary syndrome. In this randomized, placebo-controlled clinical trial, 44 PCOS women aged 20-38 years with plasma 25OHD <20 ng/mL were randomized in the intervention or placebo groups and followed for 8 weeks. Participants received 50,000 IU of oral vitamin D3 once weekly in the intervention group or placebo. The visceral adipose tissue, Insulin resistance (HOMA-IR), HOMA-B, QUICKI, and circulating adiponectin were compared before and after the intervention within groups using paired tests and the mean changes were analyzed between two groups by independent t-test. Of 44 eligible participates, 36 patients (81.8%) completed the study. After 8 week intervention, vitamin D supplementation compared to the placebo group significantly decreased fasting plasma glucose (FPG) (7.67 ± 7.66 versus 1.71 ± 7.50 mg/dL, p = .001) and significantly increased homeostasis model of assessment-estimated B cell function (HOMA-B) (129.76 ± 121.02 versus 48.32 ± 128.35, p = .014), Adiponectin (5.17 ± 8.09 versus -5.29 ± 8.64 mg/dL, p = .001), and serum vitamin D level (28.24 ± 6.47 versus 3.55 ± 4.25 ng/mL, p = .001). Vitamin D supplementation in vitamin D deficient women with PCOS, improved the FPG, HOMA-B, Adiponectin, and serum vitamin D level.

Comparison of vildagliptin as an add-on therapy and sulfonylurea dose-increasing therapy in patients with inadequately controlled type 2 diabetes using metformin and sulfonylurea (VISUAL study): A randomized trial.

PubMed

Hong, A Ram; Lee, Jeun; Ku, Eu Jeong; Hwangbo, Yul; Kim, Kyoung Min; Moon, Jae Hoon; Choi, Sung Hee; Jang, Hak Chul; Lim, Soo

2015-07-01

The aim of present study is to compare the efficacy and safety of adding vildagliptin with sulfonylurea dose-increasing as an active comparator in patients who had inadequately controlled type 2 diabetes mellitus (T2DM) using metformin plus sulfonylurea in real clinical practice. Patients using metformin plus sulfonylurea were assigned to either vildagliptin add-on (50 mg twice a day, n=172) or sulfonylurea dose-increasing by 50% (n=172) treatment groups. The primary endpoint was a change in HbA(1c) after 24 weeks. The secondary endpoints were patients achieving HbA(1c)≤7.0% (53 mmol/mol) and changes in the fasting plasma glucose (FPG), 2-h postprandial glucose (2pp), lipid profiles, and urine albumin-to-creatinine ratio. Body weight and hypoglycemia were also investigated. The mean HbA(1c) at baseline was 8.6% (70 mmol/mol) in both groups. At week 24, the adjusted mean HbA(1c) levels decreased by -1.19% (-13.09 mmol/mol) with vildagliptin add-on and -0.46% (-5.06 mmol/mol) with sulfonylurea (P<0.001). Significantly more vildagliptin add-on patients achieved HbA(1c)≤7.0% (53 mmol/mol) than did sulfonylurea patients (40.1% vs. 7.9%; P<0.001). Greater reductions in FPG and 2pp were observed with vildagliptin add-on than with sulfonylurea (P<0.001). The vildagliptin add-on group exhibited no clinically relevant weight gain and had a lower incidence of hypoglycemia compared with the sulfonylurea group. Vildagliptin add-on therapy might be a suitable option for patients with T2DM that is controlled inadequately by metformin and sulfonylurea, based on its greater glucose control and better safety profile (ClinicalTrial.gov: NCT01099137). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prevalence of diabetes complications in people with type 2 diabetes mellitus and its association with baseline characteristics in the multinational A1chieve study.

PubMed

Litwak, Leon; Goh, Su-Yen; Hussein, Zanariah; Malek, Rachid; Prusty, Vinay; Khamseh, Mohammad E

2013-10-24

Current International Diabetes Federation guidelines recommend a target HbA1c <7.0%, but many people with diabetes worldwide find this difficult to achieve, increasing their risk of developing complications. This publication examines the prevalence of diabetes complications and its association with baseline characteristics in people with type 2 diabetes who participated in the A1chieve study. A1chieve was a 24-week, multinational, open-label, observational study of 66,726 people with type 2 diabetes who had begun using biphasic insulin aspart 30, insulin aspart, or insulin detemir in routine clinical care. Participants were enrolled from 28 countries across four continents (Asia, Africa, Europe and South America). Baseline measurements of disease characteristics included: glycated haemoglobin (HbA1c), fasting (FPG) and post-prandial plasma glucose (PPG), high- and low-density lipoprotein cholesterol (H- or LDL-C), systolic blood pressure (SBP), and body mass index (BMI). Data on complications and use of vascular disease preventative drugs were collected. Complication rates were high (27.2% had macrovascular complications and 53.5% had microvascular complications), particularly in Russia, and use of vascular disease preventative drugs was lower than expected. Age, BMI, diabetes duration, LDL-C, and SBP were positively associated, and HDL-C negatively associated, with macro- and microvascular complications (all p < 0.05). HbA1c and FPG were negatively associated with macrovascular complications (both p < 0.05), which may be linked to the cross-sectional study design. These results suggest a worldwide failure to achieve glycaemic targets. Better diabetes management with earlier initiation and optimisation of insulin regimens (e.g., with insulin analogues in the A1chieve population) may reduce the prevalence of vascular complications, improve the lives of people with diabetes and reduce the burden on healthcare systems.

Active vitamin D3, 1,25-(OH)2D3, protects against macrovasculopathy in a rat model of type 2 diabetes mellitus.

PubMed

Ma, R; Deng, X L; Du, G L; Li, C; Xiao, S; Aibibai, Y; Zhu, J

2016-06-03

To investigate the protective effect of the active form of vitamin D3, 1,25-(OH)2D3, on macrovasculopathy in rats with type 2 diabetes mellitus (T2DM), 8-week-old male Sprague-Dawley rats were randomly divided into control group, T2DM group, and treatment group. The T2DM model was established after 6 weeks by administering an intraperitoneal injection of streptozotocin (30 mg/kg). 1,25-(OH)2D3 was administered by gavage to rats in the treatment group, and an equal volume of peanut oil was administered to rats in the T2DM group. Fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterols were measured in all rats. The morphology of the thoracic aorta was examined, and the expression of tumor necrosis factor alpha (TNF-α), endothelin (ET), endothelial nitric oxide synthase (eNOS), CD54, and CD106 in the thoracic aorta was determined by immunohistochemistry. The expression of FPG, TG, TC, and LDL-C in rats from the T2DM and treatment groups was significantly elevated compared with rats from the control group (P < 0.05). Compared with that in control group, the expression of TNF-α, ET, eNOS, and CD106 was significantly upregulated in the T2DM group and the treatment group, while the expression of CD54 was increased only in the T2DM group (P < 0.05). Moreover, the levels of TNF-α, CD54, and CD106 in rats from the treatment group were lower than those in the T2DM group (P < 0.05). These data suggest that 1,25-(OH)2D3 may protect the macrovessels from injury in T2DM rats by inhibiting the expression of TNF-α, CD54, and CD106.

Efficacy and Safety of Multiple Doses of Exenatide Once-Monthly Suspension in Patients With Type 2 Diabetes: A Phase II Randomized Clinical Trial.

PubMed

Wysham, Carol H; MacConell, Leigh; Hardy, Elise

2016-10-01

This study investigated the efficacy and safety of multiple exenatide once-monthly suspension (QMS) doses of exenatide-containing microspheres in Miglyol referenced against the clinical dose of exenatide once-weekly (QW) microspheres in aqueous solution. In this phase II, randomized, controlled, single-blind study, 121 adults (∼30/arm) with type 2 diabetes and HbA1c 7.1-11.0% (54-97 mmol/mol) were randomized 1:1:1:1 to subcutaneous exenatide QW 2 mg (self-administered) or exenatide QMS 5, 8, or 11 mg (caregiver-administered) for 20 weeks. The primary end point was change in HbA1c. At baseline, mean age was 50 years, HbA1c was 8.5% (69 mmol/mol), fasting plasma glucose (FPG) was 184 mg/dL, and body weight was 98 kg. At week 20, mean ± SD HbA1c reductions were -1.54% ± 1.26% with exenatide QW and -1.29% ± 1.07%, -1.31% ± 1.66%, and -1.45% ± 0.93% with exenatide QMS 5, 8, and 11 mg, respectively (evaluable population: n = 110). There were no significant differences in HbA1c reductions among the exenatide QMS doses. FPG reductions were -34 ± 48 mg/dL with exenatide QW and -25 ± 43, -30 ± 52, and -49 ± 49 mg/dL with exenatide QMS 5, 8, and 11 mg, respectively. Weight decreased with all treatments. For exenatide QMS, nausea (16.7-23.3%) and headache (16.7-26.7%) were the most common adverse events. No major or minor hypoglycemia occurred. All doses of exenatide QMS resulted in efficacy and tolerability profiles consistent with exenatide QW. These results combined with pharmacokinetic and pharmacodynamic modeling could inform dose selection for further development. © 2016 by the American Diabetes Association.

The Impact of Vitamin D Supplementation on Post-Partum Glucose Tolerance and Insulin Resistance in Gestational Diabetes: A Randomized Controlled Trial

PubMed Central

Valizadeh, Majid; Piri, Zahra; Mohammadian, Farnaz; Kamali, Koorosh; Amir Moghadami, Hamid Reza

2016-01-01

Background Hypovitaminosis D has been associated with the development of gestational diabetes mellitus (GDM) in many observational studies. Objectives We report the first study of the impact of prenatal vitamin D supplementation on postpartum dysglycemia in GDM patients in a randomized clinical trial. Patients and Methods Women with GDM at 12 - 32 weeks of gestation were assigned randomly to either the intervention group (in which serum 25-hydroxy vitamin D [25OHD] levels were measured immediately, n = 48) or the control group (in which the serum was stored and assayed at 6 - 12 weeks post-partum, n = 48). Participants with initial serum 25OHD < 30 ng/mL in the intervention group were instructed to take a total of 700,000 IU vitamin D3 during pregnancy. The primary outcomes were fasting plasma glucose (FPG), insulin, 2-h post 75 g glucose load plasma glucose (2-hPLG), homeostasis model assessment of insulin resistance (HOMA-IR), HbA1C, and 25 OHD at 6 - 12 weeks after delivery. Results The mean ± SD of serum 25OHD in the intervention group raised dramatically from 14.6 ± 6.3 to 32.4 ± 14.4 ng/mL, whereas no significant change occurred in the control group (from 17.7 ± 6.1 to 19.3 ± 9.6 ng/mL, P < 0.001). Thirteen participants developed dysglycemia in each group. Mean FPG, 2-hPLG, and HOMA-IR were not significantly different between the groups. There was no significant difference between the groups for maternal and neonatal outcomes. Conclusions Although the high vitamin D supplementation dose in the present study (compared to the 400 IU/day dose usually recommended for pregnancy) safely increases the serum 25OHD, in GDM cases, the higher dose does not affect the plasma glucose level or insulin resistance at short term follow-up after delivery. PMID:27679649

A randomized controlled trial to evaluate the effects of high Protein Complete (lActo) VEgetaRian (PACER) diet in non-diabetic obese Asian Indians in North India.

PubMed

Bhardwaj, Swati; Misra, Anoop; Gulati, Seema; Anoop, Shajith; Kamal, Vineet Kumar; Pandey, Ravindra Mohan

2017-12-01

In view of the increasing prevalence of obesity in largely vegetarian Asian Indians, it is important to research a high protein, low carbohydrate vegetarian diet. The present study was designed to evaluate the effects of a "High P rotein C omplete (lacto) V E geta R ian Diet (Acronym; 'PACER diet'), on weight, body composition and metabolic profiles in non-diabetic obese Asian Indians living in north India. In this 8-week randomized control trial, 102 vegetarian subjects with body mass index (BMI) >25 kg/m 2 were randomized to either a test diet (PACER diet; high protein, high fat and moderately low carbohydrate, lacto-vegetarian diet) or control diet (standard vegetarian diet formulated as the dietary guidelines for Asian Indians) after 4 weeks of diet and exercise run-in period. A standard exercise protocol was followed for both groups. Body weight, BMI, waist circumference (WC), blood pressure, fasting plasma glucose (FPG), fasting serum insulin and lipid profile were assessed before and after the intervention. There was significant weight loss along with improvements in cardio-metabolic risk factors among both the groups post intervention. Percent reductions in the intervention group for weight (6.1± 2.9; p < 0.001), WC (3.9 ± 1.7; p < 0.001), FPG (5.9 ± 3.2; p < 0.001), total cholesterol (10.2 ± 6.3: p < 0.001), serum triacylglycerol (13.6 ± 10.6; p < 0.001) and low-density lipoprotein cholesterol (11.9 ± 7.1; p < 0.001]) were significantly greater than the control diet group. In summary, intervention with a PACER diet (high protein, high fat and moderately low carbohydrate, lacto-vegetarian diet) showed significant improvement in weight loss, body composition and cardio-metabolic profile as compared to a standard vegetarian diet among obese Asian Indians in north India.

Efficacy and Safety of the Glucagon Receptor Antagonist PF-06291874: A 12-Week, Randomized, Dose-Response Study in Patients With Type 2 Diabetes Mellitus on Background Metformin Therapy.

PubMed

Kazierad, David J; Chidsey, Kristin; Somayaji, Veena R; Bergman, Arthur J; Calle, Roberto A

2018-06-19

To conduct a dose-response assessment of the efficacy and safety of the glucagon receptor antagonist PF-06291874 in adults with type 2 diabetes (T2DM) receiving stable doses of metformin. This randomized, double-blind, statin-stratified, placebo-controlled, 4-arm, parallel-group study was conducted in patients with T2DM receiving background metformin. After an 8-week, non-metformin oral antidiabetic agent washout period, 206 patients were randomized to placebo or PF-06291874 (30, 60, or 100 mg once daily) for 12 weeks. Glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and safety endpoints were assessed at baseline and postbaseline. Dose-dependent mean reductions from baseline in HbA1c for PF-06291874 ranged from -0.67% (-7.29 mmol/mol) to -0.93% (-10.13 mmol/mol); and in FPG from -16.6 to -33.3 mg/dL after 12 weeks of dosing. The incidence of hypoglycemia was low and similar between groups receiving PF-06291874. Small, non-dose-dependent increases in LDL cholesterol (<10%) and blood pressure (BP; systolic BP>2 mmHg, diastolic BP>1 mmHg) were observed with PF-06291874. Modest non-dose-dependent median increases were observed across PF-06291874 groups at 12 weeks for alanine aminotransferase (range, 37.6-48.7 U/L versus placebo) and aspartate aminotransferase (range, 33.3-36.6 U/L versus placebo) that were not associated with bilirubin changes. Small increases were observed for body weight (<0.5 kg) in each PF-06291874 group versus placebo. In patients with T2DM, PF-06291874 significantly lowered HbA1c and glucose, was well tolerated, and had low risk of hypoglycemia. Small, non-dose-related increases in BP, lipids, and hepatic transaminases were observed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Haplotype Structure of the ENPP1 Gene and Nominal Association of the K121Q Missense Single Nucleotide Polymorphism With Glycemic Traits in the Framingham Heart Study

PubMed Central

Stolerman, Elliot S.; Manning, Alisa K.; McAteer, Jarred B.; Dupuis, Josée; Fox, Caroline S.; Cupples, L. Adrienne; Meigs, James B.; Florez, Jose C.

2008-01-01

OBJECTIVE—A recent meta-analysis demonstrated a nominal association of the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K→Q missense single nucleotide polymorphism (SNP) at position 121 with type 2 diabetes. We set out to confirm the association of ENPP1 K121Q with hyperglycemia, expand this association to insulin resistance traits, and determine whether the association stems from K121Q or another variant in linkage disequilibrium with it. RESEARCH DESIGN AND METHODS—We characterized the haplotype structure of ENPP1 and selected 39 tag SNPs that captured 96% of common variation in the region (minor allele frequency ≥5%) with an r2 value ≥0.80. We genotyped the SNPs in 2,511 Framingham Heart Study participants and used age- and sex-adjusted linear mixed effects (LME) models to test for association with quantitative metabolic traits. We also examined whether interaction between K121Q and BMI affected glycemic trait levels. RESULTS—The Q allele of K121Q (rs1044498) was associated with increased fasting plasma glucose (FPG), A1C, fasting insulin, and insulin resistance by homeostasis model assessment (HOMA-IR; all P = 0.01–0.006). Two noncoding SNPs (rs7775386 and rs7773477) demonstrated similar associations, but LME models indicated that their effects were not independent from K121Q. We found no association of K121Q with obesity, but interaction models suggested that the effect of the Q allele on FPG and HOMA-IR was stronger in those with a higher BMI (P = 0.008 and 0.01 for interaction, respectively). CONCLUSIONS—The Q allele of ENPP1 K121Q is associated with hyperglycemia and insulin resistance in whites. We found an adiposity-SNP interaction, with a stronger association of K121Q with diabetes-related quantitative traits in people with a higher BMI. PMID:18426862

HbA1c as a Predictor of Diabetes and as an Outcome in the Diabetes Prevention Program: A Randomized Clinical Trial

PubMed Central

2015-01-01

OBJECTIVE Glycated hemoglobin (HbA1c), a standard measure of chronic glycemia for managing diabetes, has been proposed to diagnose diabetes and identify people at risk. The Diabetes Prevention Program (DPP) was a 3.2-year randomized clinical trial of preventing type 2 diabetes with a 10-year follow-up study, the DPP Outcomes Study (DPPOS). We evaluated baseline HbA1c as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA1c ≥6.5% (48 mmol/mol). RESEARCH DESIGN AND METHODS We randomized 3,234 nondiabetic adults at high risk of diabetes to placebo, metformin, or intensive lifestyle intervention and followed them for the development of diabetes as diagnosed by fasting plasma glucose (FPG) and 2-h postload glucose (2hPG) concentrations (1997 American Diabetes Association [ADA] criteria). HbA1c was measured but not used for study eligibility or outcomes. We now evaluate treatment effects in the 2,765 participants who did not have diabetes at baseline according to FPG, 2hPG, or HbA1c (2010 ADA criteria). RESULTS Baseline HbA1c predicted incident diabetes in all treatment groups. Diabetes incidence defined by HbA1c ≥6.5% was reduced by 44% by metformin and 49% by lifestyle during the DPP and by 38% by metformin and 29% by lifestyle throughout follow-up. Unlike the primary DPP and DPPOS findings based on glucose criteria, metformin and lifestyle were similarly effective in preventing diabetes defined by HbA1c. CONCLUSIONS HbA1c predicted incident diabetes. In contrast to the superiority of the lifestyle intervention on glucose-defined diabetes, metformin and lifestyle interventions had similar effects in preventing HbA1c-defined diabetes. The long-term implications for other health outcomes remain to be determined. PMID:25336746

[Clinical laboratory examination of diabetic patients in conjunction with metabolic syndrome].

PubMed

Kishitani, Yuzuru

2009-11-01

Diabetic patients tend to show a reduced QOL because of macrovascular complications such as cerebral and myocardial infarction, as well as marked microvascular complications. It is important for the prevention and amelioration of these complications to diagnose diabetes mellitus (DM) early and effectively control glycemia, the blood pressure, lipids, and body weight. We examine fasting plasma glucose (FPG) and HbA1c for a diagnosis of diabetes at any time, but examine 75gOGTT for impaired glucose tolerance or DM. Examination to be necessary for a pathologic classification of DM is islet-associated antibody, namely, GAD antibody, IA-2 antibody and the measurement of IRI, blood/urinary C-peptide to evaluate insulin secretory ability. HOMA-R is an index of insulin resistance, and HOMA-beta is an index of insulin secretory ability which can be calculated from FPG and IRI, but we need to be aware that the insulin secretory ability of the patient may have decreased already. HbA1c is a standard index of glycemic control, but glycoalbumin measurement is suitable for disease states such as anemia and liver cirrhosis, and 1,5-anhydroglucitol is suitable for detecting changes in levels of urinary glucose. Examinations necessary for the evaluation of diabetic nephropathy are microalbumin and 24hr Ccr in the urine, but eGFR has been recently recommended instead of 24hr Ccr. We measure small dense LDL-C, RLP-C, and Lp (a) as well as conduct conventional lipid analyses for dislipidemia combined with DM for qualitative as well as quantitative data. Metabolic syndrome is caused by the life habits of overeating and lack of exercise, leading to atherosclerotic disease, because insulin resistance advances from visceral fat accumulation. TNF-alpha and leptin levels as insulin resistance advances and adiponectin levels as insulin resistance improves are measured as adipocytokines secreted by visceral fat tissue.

The characteristics of impaired fasting glucose associated with obesity and dyslipidaemia in a Chinese population.

PubMed

Qian, Yun; Lin, Yudi; Zhang, Tiemei; Bai, Jianling; Chen, Feng; Zhang, Yi; Luo, Senlin; Shen, Hongbing

2010-03-17

Different populations have diverse patterns of relationships between Impaired Fasting Glucose (IFG) and obesity and lipid markers, it is important to investigate the characteristics of associations between IFG and other related risk factors including body mass index (BMI), waist circumstance (WC), serum lipids and blood pressure (BP) in a Chinese population. This was a case-control study of 648 IFG subjects and 1,296 controls derived from a large-scale, community-based, cross-sectional survey of 10,867 participants. Each subject received a face-to-face interview, physical examination, and blood tests, including fasting blood glucose and lipids. Student's t-test, Chi-square test, Spearman correlation and multiple logistic regressions were used for the statistical analyses. Fasting plasma glucose (FPG) was positively correlated with BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), and total cholesterol (TC), and was negatively correlated with high density lipoprotein-cholesterol (HDL-C) (all p < 0.05). BMI was more strongly correlated with IFG than with WC. The correlation coefficient of FPG was remarkably higher with TG (0.244) than with TC (0.134) and HDL-C (-0.192). TG was an important predictor of IFG, with odds ratios of 1.76 (95%CI: 1.31-2.36) for subjects with borderline high TG level (1.70 mmol/l < or = TG < 2.26 mmol/l) and 3.13 (95% CI: 2.50-3.91) for those with higher TG level (TG > or = 2.26 mmol/l), when comparing to subjects with TG < 1.70 mmol/l. There was a significant dose-response relationship between the number of abnormal variables and increased risk of IFG. In this Chinese population, both BMI and WC were important predictors of IFG. Abnormal TG as a lipid marker was more strongly associated with IFG than were TC and HDL-C. These factors should be taken into consideration simultaneously for prevention of IFG.

Trends in the prevalence of diabetes and impaired fasting glucose in association with obesity in Iran: 2005-2011.

PubMed

Esteghamati, Alireza; Etemad, Koorosh; Koohpayehzadeh, Jalil; Abbasi, Mehrshad; Meysamie, Alipasha; Noshad, Sina; Asgari, Fereshteh; Mousavizadeh, Mostafa; Rafei, Ali; Khajeh, Elias; Neishaboury, Mohamadreza; Sheikhbahaei, Sara; Nakhjavani, Manouchehr

2014-02-01

To estimate the prevalence and trends of diabetes mellitus (DM) and impaired fasting glucose (IFG), 2005-2011, and to determine the contribution of obesity to DM prevalence. Data from Surveillance of Risk Factors of Non-communicable Diseases (SuRFNCD) conducted in 2005, 2007, and 2011 were gathered. DM was defined as presence of self-reported previous diagnosis or a fasting plasma glucose (FPG)≥7 mmol/L. IFG was diagnosed with FPG levels between 5.6 and 6.9 mmol/L. Prevalence rates for 2011 and trends for 2005-2011 were determined by extrapolating survey results to Iran's adult population. Population attributable fraction (PAF) of obesity was also calculated. In 2011, IFG and total DM prevalence rates were 14.60% (95%CI: 12.41-16.78) and 11.37% (95%CI: 9.86-12.89) among 25-70 years, respectively. DM was more common in older age (p < 0.0001), in women (p = 0.0216), and in urban-dwellers (p = 0.0001). In 2005-2011, trend analysis revealed a 35.1% increase in DM prevalence (OR: 1.04, 95%CI: 1.01-1.07, p = 0.011); albeit, IFG prevalence remained relatively unchanged (OR: 0.98, 95%CI: 0.95-1.00, p = 0.167). In this period, DM awareness improved; undiagnosed DM prevalence decreased from 45.7% to 24.7% (p < 0.001). PAF analysis demonstrated that 33.78%, 10.25%, and 30.56% of the prevalent DM can be attributed to overweight (BMI≥25kg/m(2)), general obesity (BMI≥30 kg/m(2)), and central obesity (waist circumference≥90 cm), respectively. Additionally, the DM increase rate in 2005-2011, was 20 times higher in morbidly obese compared with lean individuals. More than four million Iranian adults have DM which has increased by 35% over the past seven years, owing in large part, to expanding obesity epidemic. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population.

PubMed

Huang, Qiong; Yin, Ji-ye; Dai, Xing-ping; Pei, Qi; Dong, Min; Zhou, Zhi-guang; Huang, Xi; Yu, Min; Zhou, Hong-hao; Liu, Zhao-qian

2010-06-01

To investigate whether the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs1470579 and rs4402960 polymorphisms are associated with the development of type 2 diabetes mellitus (T2DM) and the repaglinide therapeutic efficacy in Chinese T2DM patients. A case-control study of a total of 350 patients with T2DM and 207 healthy volunteers was conducted to identify their genotypes for the IGF2BP2 rs1470579 and rs4402960 polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two patients were randomly selected to undergo an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment. The frequencies of the IGF2BP2 rs1470579 C allele and the rs4402960 T allele were higher in T2DM patients than in healthy controls (P<0.05 and P<0.001, respectively). The effects of the repaglinide treatment on FPG (P<0.05) and PPG (P<0.05) were reduced in patients with the rs1470579 AC+CC genotypes compared with AA genotype carriers. Patients with the rs4402960 GT+TT genotypes exhibited an enhanced effect of repaglinide treatment on PINS (P<0.01) compared with GG genotype subjects. The IGF2BP2 rs1470579 and rs4402960 polymorphisms may be associated with the development of T2DM, and these polymorphisms may affect the therapeutic efficacy of repaglinide in Chinese T2DM patients.

Randomized study of repaglinide alone and in combination with metformin in Chinese subjects with type 2 diabetes naive to oral antidiabetes therapy.

PubMed

Wang, Weiqing; Bu, Ruifang; Su, Qing; Liu, Jianying; Ning, Guang

2011-12-01

The aim of this research is to determine efficacy and safety of repaglinide alone and in combination with metformin in Chinese subjects with type 2 diabetes naive to oral antidiabetes therapy. A 16-week, open-label, randomized, active-controlled, parallel-group trial was carried out. Subjects were randomized (1:1) to repaglinide 1 mg t.i.d. (maximum dose, 4 mg t.i.d.) or repaglinide plus metformin 1 mg/500 mg t.i.d. (maximum dose, 4 mg/500 mg t.i.d.). Eligible subjects (18 - 75 years old) had type 2 diabetes, A1C > 8.5%, BMI ≤ 35 kg/m(2), and were naive to oral antidiabetes agents. The primary outcome was A1C reduction. Secondary end points included fasting plasma glucose (FPG), 2-h postprandial glucose (PPG), and 7-point plasma glucose. Baseline characteristics (repaglinide/metformin, n = 218; repaglinide-only, n = 214) were similar between groups. Mean A1C reduction (± SD) was 4.51 ± 1.64% (combination) and 4.05 ± 1.59% (monotherapy). Estimated mean treatment difference for repaglinide/metformin versus repaglinide-only was -0.30% (95% CI -0.49 to -0.11; p < 0.01). Combination treatment demonstrated significant improvements versus monotherapy in FPG, 7-point plasma glucose, and lunchtime and dinnertime 2-h PPG (all p < 0.05). Hypoglycemia rates were 2.04 (combination) versus 1.35 (monotherapy) events/subject-year (p = 0.058). Adverse events were comparable between groups. Repaglinide plus metformin and repaglinide alone provided significant improvements in glycemic control and were well tolerated in Chinese patients naive to treatment with oral antidiabetes agents. Combination therapy with repaglinide plus metformin showed superiority to repaglinide monotherapy in this population. Limitations of this study are that subjects were newly diagnosed and had high mean baseline A1C, which may affect generalizability of results.

IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population

PubMed Central

Huang, Qiong; Yin, Ji-ye; Dai, Xing-ping; Pei, Qi; Dong, Min; Zhou, Zhi-guang; Huang, Xi; Yu, Min; Zhou, Hong-hao; Liu, Zhao-qian

2010-01-01

Aim: To investigate whether the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs1470579 and rs4402960 polymorphisms are associated with the development of type 2 diabetes mellitus (T2DM) and the repaglinide therapeutic efficacy in Chinese T2DM patients. Methods: A case-control study of a total of 350 patients with T2DM and 207 healthy volunteers was conducted to identify their genotypes for the IGF2BP2 rs1470579 and rs4402960 polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two patients were randomly selected to undergo an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment. Results: The frequencies of the IGF2BP2 rs1470579 C allele and the rs4402960 T allele were higher in T2DM patients than in healthy controls (P<0.05 and P<0.001, respectively). The effects of the repaglinide treatment on FPG (P<0.05) and PPG (P<0.05) were reduced in patients with the rs1470579 AC+CC genotypes compared with AA genotype carriers. Patients with the rs4402960 GT+TT genotypes exhibited an enhanced effect of repaglinide treatment on PINS (P<0.01) compared with GG genotype subjects. Conclusion: The IGF2BP2 rs1470579 and rs4402960 polymorphisms may be associated with the development of T2DM, and these polymorphisms may affect the therapeutic efficacy of repaglinide in Chinese T2DM patients. PMID:20523342

'Change means sacrificing a good life': perceptions about severity of type 2 diabetes and preventive lifestyles among people afflicted or at high risk of type 2 diabetes in Iganga Uganda.

PubMed

Mayega, Roy W; Etajak, Samuel; Rutebemberwa, Elizeus; Tomson, Goran; Kiguli, Juliet

2014-08-21

Interventions for prevention of type 2 diabetes ought to be acceptable to target communities. We assessed perceptions about type 2 diabetes and lifestyle change among people afflicted or at high risk of this disease in a low income setting in Iganga Uganda. Twelve focus group discussions (FGDs) of eight participants each were conducted, balancing rural and peri-urban (near the Municipality) residence and gender. The FGDs involved people with suspected type 2 diabetes (based on fasting plasma glucose (FPG), people with suspected pre-diabetes and obese people with normal FPG. Content analysis was conducted. Diabetes was perceived to be a very severe disease. Its severity was attributed to its incurability and its numerous health effects. Men were also concerned about reduced sexual performance. However, participants' strong concerns about the severity of diabetes were not reflected in their perceptions about the risk factors and lifestyles associated with it. While people with diabetes perceive obesity as 'sickness', those without diabetes perceive it as a sign of 'success'. Although participants are willing to change their diet, they mention numerous barriers including poverty, family size, and access to some foods. Because of their good taste, reduction of high risk foods like sugar and fried food is perceived as 'sacrificing a good life'. Increments in physical activity were said to be feasible, but only in familiar forms like domestic work. An over-arching theme emerged that 'lifestyle changes are viewed as sacrificing a good life'. Health promotion should target both community norms and individual awareness regarding obesity, physical activity and diet, and should address the notion that obesity and unhealthy foods represent a good life. Health educators should plan with clients on how to overcome barriers and misconceptions to lifestyle change, leveraging the pervasive perception of type 2 diabetes as a severe disease to motivate change.