Fasting hyperglycaemia blunts the reversal of impaired glucose tolerance after exercise training in obese older adults.

PubMed

Malin, S K; Kirwan, J P

2012-09-01

Lifestyle modification, consisting of exercise and weight loss, delays the progression from prediabetes to type 2 diabetes (T2D). However, no study has determined the efficacy of exercise training on glucose metabolism in the different prediabetes subtypes. Seventy-six older (65.1 ± 0.6 years) obese adults with impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 9) and combined glucose intolerance (IFG + IGT = CGI; n = 22) were compared with normal glucose tolerant (NGT; n = 15) and T2D (n = 18) groups after 12 weeks of exercise training (60 min/day for 5 days/week at ~85% HR(max)). An oral glucose tolerance test was used to assess glucose levels. Insulin sensitivity (IS; euglycaemic hyperinsulinaemic clamp at 40 mU/m(2)/min), β-cell function (glucose-stimulated insulin secretion corrected for IS), body composition (hydrostatic weighing/computed tomography scan) and cardiovascular fitness (treadmill VO(2) max) were also assessed. Exercise training reduced weight and increased cardiovascular fitness (p < 0.05). Exercise training lowered fasting glucose levels in IFG, CGI and T2D (p < 0.05) and 2-h glucose levels in IGT, CGI and T2D (p < 0.05). However, 2-h glucose levels were not normalized in adults with CGI compared with IGT (p < 0.05). β-Cell function improved similarly across groups (p < 0.05). Although not statistically significant, IS increased approximately 40% in IFG and IGT, but only 17% in CGI. The magnitude of improvement in glucose metabolism after 12 weeks of exercise training is not uniform across the prediabetes subtypes. Given the high risk of progressing to T2D, adults with CGI may require more aggressive therapies to prevent diabetes. © 2012 Blackwell Publishing Ltd.

Impaired glucose tolerance and impaired fasting glucose--a review of diagnosis, clinical implications and management.

PubMed

Petersen, John L; McGuire, Darren K

2005-02-01

The diagnostic categories of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were stablished in an effort to identify populations at risk for developing type 2 diabetes mellitus (T2DM). Both IGT and IFG are associated with increased risk of developing T2DM, but recent analyses found that the thresholds of risk vary among different populations and an even lower diagnostic threshold of IFG may be appropriate. IGT has been linked with an increased risk of cardiovascular events and some analyses have demonstrated an increased mortality risk compared with patients with normal glucose tolerance. In contrast, a continuum of increased risk of microvascular manifestations of T2DM has been demonstrated with IFG but an association of IFG with cardiovascular events has not been well established. Although both IGT and IFG are associated with resistance to insulin and increased insulin secretion, they do not identify the identical patient populations and are not equivalent in predicting development of T2DM or cardiovascular events. IFG and IGT have been associated with other features of insulin resistance, including dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of inflammation and hypercoagulability, traits collectively referred to as the metabolic syndrome. Analyses of combinations of these components have also been associated with progression to T2DM, cardiovascular disease and increased mortality. The foundation of treatment for IGT, IFG, and the metabolic syndrome is lifestyle modification, including both dietary change and routine exercise. To date, several clinical trials have found that lifestyle modification is the most efficacious strategy to prevent progression to T2DM. Alternative treatments include pharmacotherapy with metformin or acarbose, both of which have been demonstrated to decrease the development of T2DM. Ongoing clinical trials are evaluating newer pharmacotherapies, including

Associations of Green Tea and Rock Tea Consumption with Risk of Impaired Fasting Glucose and Impaired Glucose Tolerance in Chinese Men and Women

PubMed Central

Huang, Huibin; Guo, Qiuxuan; Qiu, Changsheng; Huang, Baoying; Fu, Xianguo; Yao, Jin; Liang, Jixing; Li, Liantao; Chen, Ling; Tang, Kaka; Lin, Lixiang; Lu, Jieli; Bi, Yufang; Ning, Guang; Wen, Junping; Lin, Caijing; Chen, Gang

2013-01-01

Objective To explore the associations of green tea and rock tea consumption with risk of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Methods A multistage, stratified, cluster, random-sampling method was used to select a representative sample from Fujian Province in China. In total, 4808 subjects without cardiovascular disease, hypertension, cancer, or pancreatic, liver, kidney, or gastrointestinal diseases were enrolled in the study. A standard questionnaire was used to gather data on tea (green, rock, and black) consumption and other relevant factors. The assessment of impaired glucose regulation (IGR) was using 75-g oral glucose tolerance test (OGTT), the diagnostic criteria of normal glucose tolerance was according to American Diabetes Association. Results Green tea consumption was associated with a lower risk of IFG, while rock tea consumption was associated with a lower risk of IGT. The adjusted odds ratios for IFG for green tea consumption of <1, 1–15, 16–30, and >30 cups per week were 1.0 (reference), 0.42 (95% confidence intervals (CI) 0.27–0.65), 0.23 (95% CI, 0.12–0.46), and 0.41 (95% CI, 0.17–0.93), respectively. The adjusted odds ratios for IGT for rock tea consumption of <1, 1–15, 16–30, and >30 cups per week were 1.0 (reference), 0.69 (95% CI, 0.48–0.98), 0.59 (95% CI, 0.39–0.90), and 0.64 (95% CI, 0.43–0.97), respectively. A U-shaped association was observed, subjects who consumed 16–30 cups of green or rock tea per week having the lowest odds ratios for IFG or IGT. Conclusions Consumption of green or rock tea may protect against the development of type 2 diabetes mellitus in Chinese men and women, particularly in those who drink 16–30 cups per week. PMID:24260170

Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study.

PubMed

Bone, Henry G; Lindsay, Robert; McClung, Michael R; Perez, Alfonso T; Raanan, Marsha G; Spanheimer, Robert G

2013-12-01

Meta-analyses of clinical studies have suggested an increased incidence of peripheral fractures in postmenopausal women with type 2 diabetes mellitus taking pioglitazone. The mechanism behind this apparent increase is unknown. The objective of the study was to examine the effects of pioglitazone on bone mineral density (BMD) and turnover. Twenty-five sites (in the United States) enrolled participants in this randomized, double-blind, placebo-controlled study. Postmenopausal women (n = 156) with impaired fasting glucose or impaired glucose tolerance participated in the study. The intervention consisted of pioglitazone 30 mg/d (n = 78) or placebo (n = 78), increased to 45 mg/d after 1 month, for 12 months of treatment total, followed by 6 months of washout/follow-up. Percentage changes from baseline to month 12 and from month 12 to month18 in BMD in total proximal femur (primary end point), total body, femoral neck, lumbar spine, and radius were measured. Least squares mean changes from baseline to month 12 in total proximal femur BMD were -0.69% for pioglitazone and -0.14% for placebo (P = .170). No statistically significant between-group differences were observed for any BMD or bone remodeling marker end point. We observed improved glycemic control and insulin sensitivity with pioglitazone treatment. In addition, pioglitazone appeared to increase body fat, which may affect bone density measurements, especially in the lumbar spine. One pioglitazone-treated and three placebo-treated women experienced confirmed fractures. Over 18 months, one pioglitazone-treated (1.3%) and eight placebo-treated women (10.3%) developed overt type 2 diabetes mellitus. The pattern and incidence of adverse events with pioglitazone were consistent with clinical experience with thiazolidinediones. Maximal-dose pioglitazone had no effects on BMD or bone turnover, while improving glycemic control as expected, in postmenopausal women with impaired fasting glucose or impaired glucose tolerance.

Ceylon cinnamon does not affect postprandial plasma glucose or insulin in subjects with impaired glucose tolerance.

PubMed

Wickenberg, Jennie; Lindstedt, Sandra; Berntorp, Kerstin; Nilsson, Jan; Hlebowicz, Joanna

2012-06-01

Previous studies on healthy subjects have shown that the intake of 6 g Cinnamomum cassia reduces postprandial glucose and that the intake of 3 g C. cassia reduces insulin response, without affecting postprandial glucose concentrations. Coumarin, which may damage the liver, is present in C. cassia, but not in Cinnamomum zeylanicum. The aim of the present study was to study the effect of C. zeylanicum on postprandial concentrations of plasma glucose, insulin, glycaemic index (GI) and insulinaemic index (GII) in subjects with impaired glucose tolerance (IGT). A total of ten subjects with IGT were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with placebo or C. zeylanicum capsules. Finger-prick capillary blood samples were taken for glucose measurements and venous blood for insulin measurements, before and at 15, 30, 45, 60, 90, 120, 150 and 180 min after the start of the OGTT. The ingestion of 6 g C. zeylanicum had no significant effect on glucose level, insulin response, GI or GII. Ingestion of C. zeylanicum does not affect postprandial plasma glucose or insulin levels in human subjects. The Federal Institute for Risk Assessment in Europe has suggested the replacement of C. cassia by C. zeylanicum or the use of aqueous extracts of C. cassia to lower coumarin exposure. However, the positive effects seen with C. cassia in subjects with poor glycaemic control would then be lost.

Effect of impaired glucose tolerance on atherosclerotic lesion formation: an evaluation in selectively bred mice with different susceptibilities to glucose intolerance.

PubMed

Asai, Akira; Nagao, Mototsugu; Kawahara, Momoyo; Shuto, Yuki; Sugihara, Hitoshi; Oikawa, Shinichi

2013-12-01

Impaired glucose tolerance (IGT) is an independent risk factor for atherosclerotic cardiovascular disease. However, due to the lack of appropriate animal models, the underlying mechanisms for IGT-induced atherosclerosis remain to be elucidated in vivo. We recently used selective breeding to establish 2 mouse lines with distinctively different susceptibilities to diet-induced glucose intolerance, designated selectively bred diet-induced glucose intolerance-resistant (SDG-R) and SDG-prone (SDG-P), respectively. Here, we assessed atherosclerotic lesion formation in these mice. Female SDG-R and SDG-P mice were fed an atherogenic diet (AD; 1.25% cholesterol, 0.5% sodium cholate, and 36% energy as fat) for 20 weeks (8-28 weeks of age). Oral glucose tolerance tests were performed during the AD-feeding period. Atherosclerotic lesion formation was quantitatively analyzed in serial aortic sinus sections by oil red O staining. Plasma lipids were measured after the AD-feeding period. Glucose tolerance was impaired in SDG-P mice as compared to SDG-R mice over the 20-week AD-feeding period. No significant differences were observed in any plasma lipid measurement between the 2 mouse lines. Aortic sinus atherosclerotic lesion formation in SDG-P mice was approximately 4-fold greater than that in SDG-R mice. In 2 mouse lines with different susceptibilities to diet-induced glucose intolerance, IGT accelerated atherosclerotic lesion formation. These mice may therefore serve as useful in vivo models for investigating the causal role of IGT in the pathogenesis of atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Value of the intravenous and oral glucose tolerance tests for detecting subtle impairments in insulin sensitivity and beta-cell function in former gestational diabetes.

PubMed

Tura, A; Mari, A; Prikoszovich, T; Pacini, G; Kautzky-Willer, A

2008-08-01

Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta-cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta-cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance. A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT). Measurements Insulin sensitivity and beta-cell function were assessed by both the IVGTT and the OGTT. Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 4.2 +/- 0.3 vs. 5.4 +/- 0.4 10(-4) min(-1) (microU/ml)(-1); OGTT: 440 +/- 7 vs. 472 +/- 9 ml min(-1) m(-2)). Conversely, no difference was found in beta-cell function from the IVGTT. However, some parameters of beta-cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 +/- 5 vs. 124 +/- 7 pmol min(-1) m(-2) mm(-1), P = 0.0407) and insulin secretion at 5 mm glucose (168 +/- 9 vs. 206 +/- 10 pmol min(-1) m(-2), P = 0.003). Both insulin sensitivity and beta-cell function are impaired in normotolerant fGDM but the subtle defect in beta-cell function is disclosed only by OGTT modelling analysis.

Effects of coffee consumption on glucose tolerance, serum glucose and insulin levels--a cross-sectional analysis.

PubMed

Bidel, S; Hu, G; Sundvall, J; Kaprio, J; Tuomilehto, J

2006-01-01

Coffee has several metabolic effects that could reduce the risk of type 2 diabetes. Our objective was to examine the effects of coffee consumption on glucose tolerance, glucose and insulin levels. A subsample of subjects aged 45 to 64 years in 1987 and in 1992 from the population-based FINRISK study (12,287 individuals) was invited to receive the standard oral glucose tolerance test at baseline. Plasma samples were taken after an overnight fast, and a two-hour oral glucose tolerance test was administered. Fasting and two-hour plasma glucose and insulin were measured in 2434 subjects with data on coffee use and potential confounders. After adjustment for potential confounding factors (age, body mass index, systolic blood pressure, occupational, commuting and leisure time physical activity, alcohol and tea drinking, smoking), coffee consumption was significantly and inversely associated with fasting glucose, two-hour plasma glucose, and fasting insulin in both men and women. Coffee consumption was significantly and inversely associated with impaired fasting glucose, impaired glucose regulation, and hyperinsulinemia among both men and women and with isolated impaired glucose tolerance among women. In this cross-sectional analysis, coffee showed positive effects on several glycemia markers.

Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood.

PubMed

Taskinen, M; Saarinen-Pihkala, U M; Hovi, L; Lipsanen-Nyman, M

2000-09-16

This follow-up study aimed to assess the frequency of late effects on glucose and lipid metabolism after bone-marrow transplantation in childhood. 23 long-term survivors (median age 20 years) were studied 3-18 years after bone-marrow transplantation and compared with 23 healthy controls matched for age and sex and with 13 patients in remission from leukaemia. 12 (52%) of the 23 bone-marrow transplantation patients had insulin resistance, including impaired glucose tolerance in six and type 2 diabetes in four. The core signs of the metabolic syndrome (hyperinsulinaemia and hypertriglyceridaemia combined), were found in nine (39%) of the bone-marrow transplantation patients compared with one (8%) of the 13 leukaemia patients and none of the healthy controls (p=0.0015). The frequency of insulin resistance increased with the time since bone-marrow transplantation. Abdominal obesity, but not overweight, was common among the patients with insulin resistance. Long-term survivors of bone-marrow transplantation are at substantial risk of insulin resistance, impaired glucose tolerance, and type 2 diabetes even at normal weight and young age. They also develop typical signs of the metabolic syndrome. We advocate measurement of serum lipids, fasting blood glucose, and serum insulin for the follow-up of all patients who undergo transplants in childhood, to be continued regularly and possibly life-long.

Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance.

PubMed

Yang, Sae Jeong; Kim, Tae Nyun; Baik, Sei Hyun; Kim, Tae Sun; Lee, Kwan Woo; Nam, Moonsuk; Park, Yong Soo; Woo, Jeong-Teak; Kim, Young Seol; Kim, Sung-Hoon

2013-05-01

The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose ≥ 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index β-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p ≤ 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p < 0.001 for all). Among the GIGT subjects, the 1-hour plasma glucose abnormal levels group showed significantly greater weight gain during pregnancy and higher values in the 50-g OGCT than the other two groups. Moreover, the 1-hour and 2-hour abnormal levels groups had poorer insulin secretion status than the 3-hour abnormal levels group. Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both β-cell dysfunction and insulin resistance.

Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired Glucose Tolerance, or New Onset Diabetes After Transplantation.

PubMed

Rosettenstein, Kerri; Viecelli, Andrea; Yong, Kenneth; Nguyen, Hung Do; Chakera, Aron; Chan, Doris; Dogra, Gursharan; Lim, Ee Mun; Wong, Germaine; Lim, Wai H

2016-07-01

New onset diabetes after transplantation (NODAT) is associated with a 3-fold greater risk of cardiovascular disease events, with early identification and treatment potentially attenuating this risk. The optimal screening test to identify those with NODAT remains unclear, and the aim of this study was to examine the diagnostic accuracies of 4 screening tests in identifying impaired fasting glucose, impaired glucose tolerance (IGT), and NODAT. This is a single-center prospective cohort study of 83 nondiabetic kidney transplant recipients between 2008 and 2011. Oral glucose tolerance test was considered the gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using the area under the receiver operating characteristic curve. Forty (48%) recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66), fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95% CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of 0.88 (95% CI, 0.76-0.96). Although HBA1c is an acceptable and widely used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more accurate diagnostic test but this needs to be further examined in larger cohorts.

Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study.

PubMed

Bianchi, Cristina; Miccoli, Roberto; Trombetta, Maddalena; Giorgino, Francesco; Frontoni, Simona; Faloia, Emanuela; Marchesini, Giulio; Dolci, Maria A; Cavalot, Franco; Cavallo, Gisella; Leonetti, Frida; Bonadonna, Riccardo C; Del Prato, Stefano

2013-05-01

In subjects with normal glucose tolerance (NGT) 1-hour postload plasma glucose (1-h oral glucose tolerance test [OGTT]) of >155 mg/dL predicts type 2 diabetes (T2DM) and is associated with subclinical atherosclerosis. The purpose of this study was to evaluate β-cell function, insulin resistance, and cardiovascular risk profile in subjects with NGT with a 1-h OGTT glucose of >155 mg/dL. The GENFIEV (Genetics, PHYsiopathology, and Evolution of Type 2 diabetes) study is a multicenter study recruiting individuals at high risk of T2DM. A total of 926 subjects underwent a 75-g OGTT for assessment of plasma glucose and C-peptide for mathematical modeling of β-cell function (derivative and proportional control). Fasting insulin, lipid profile, and clinical parameters were determined as well. A 1-hour OGTT glucose of >155 mg/dL was found in 39% of subjects with NGT, 76% with impaired fasting glucose (IFG), 90% with impaired glucose tolerance (IGT), and 99% and 98% with IFG + IGT or newly diagnosed T2DM, respectively. Among subjects with NGT (n = 474), those with 1-hour OGTT glucose of >155 mg/dL were more insulin-resistant and had worse β-cell function than those with 1-hour OGTT glucose of ≤155 mg/dL. Moreover, glycosylated hemoglobin, blood pressure, low-density lipoprotein cholesterol, and triglycerides were higher in subjects with NGT with 1-hour OGTT glucose of >155 mg/dL, whereas high-density lipoprotein cholesterol was lower compared with that in subjects with NGT with 1-hour OGTT glucose of ≤155 mg/dL. Compared with subjects with IGT, those with NGT with 1-hour OGTT glucose of >155 mg/dL had comparable cardiovascular risk profile and insulin resistance but slightly better β-cell function. Among subjects with NGT, those with 1-hour OGTT glucose of >155 mg/dL showed lower insulin sensitivity, impaired β-cell function, and worse cardiovascular risk profile and therefore are at greater risk of developing T2DM and cardiovascular disease.

Effect of N. sativa oil on impaired glucose tolerance and insulin insensitivity induced by high-fat-diet and turpentine-induced trauma.

PubMed

Alsaif, Mohammed A

2008-04-15

The aim of this study was to investigate the effect of N. sativa oil on impaired glucose tolerance and insulin insensitivity induced by high-fat diet and trauma. Three dietary groups were used in this study; Rat-Chow (RC), N. sativa oil diet (Combination 4% N. sativa oil and 16% butter oil) (NSOD) and 20% Butter Oil Diet (BOD). Each group was subdivided in two groups; control and trauma. Diets were supplemented for five consecutive weeks body weight increase per week was calculated. At end of the dietary treatments, single dose (2 mL kg(-1) body weight) of turpentine was injected in the dorso-lumber region. Intravenous glucose tolerance test (i.v. GTT) was performed, insulinogenic index and insulin sensitivity was measured. The results showed butter oil diet significantly increased the body weights and visceral fats compared other two groups, respectively. Fasting glucose levels did not change in trauma induced rats while insulin levels increased significantly and it found highest in butter oil diet fed animals. Impaired glucose tolerance was found sever in BOD fed traumatized rats. N. sativa oil diet protected impaired glucose tolerance and insulin insensitivity induced either via saturated fatty acids or injury. In conclusion, N. sativa oil may be used in post surgery diabetic patients to prevent the long going adverse effects from surgical trauma.

Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance

PubMed Central

Yang, Sae Jeong; Kim, Tae Nyun; Baik, Sei Hyun; Kim, Tae Sun; Lee, Kwan Woo; Nam, Moonsuk; Park, Yong Soo; Woo, Jeong-Teak; Kim, Young Seol

2013-01-01

Background/Aims The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). Methods A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose ≥ 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). Results The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index β-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p ≤ 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p < 0.001 for all). Among the GIGT subjects, the 1-hour plasma glucose abnormal levels group showed significantly greater weight gain during pregnancy and higher values in the 50-g OGCT than the other two groups. Moreover, the 1-hour and 2-hour abnormal levels groups had poorer insulin secretion status than the 3-hour abnormal levels group. Conclusions Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both β-cell dysfunction and insulin resistance. PMID:23682224

Retrospective study on the efficacy of a low-carbohydrate diet for impaired glucose tolerance

PubMed Central

Maekawa, Satoshi; Kawahara, Tetsuya; Nomura, Ryosuke; Murase, Takayuki; Ann, Yasuyoshi; Oeholm, Masayuki; Harada, Masaru

2014-01-01

Background In recent years, the number of people with impaired glucose tolerance (IGT) has increased steadily worldwide. It is clear that the prevention of diabetes is important from the perspective of public health, medical care, and economics. It was recently reported that a low-carbohydrate diet (LCD) is useful for achieving weight loss and glycemic control, but there is no information about the effects of the LCD on IGT. We designed a 7-day in-hospital educational program focused on the LCD for IGT. Methods The subjects were 72 patients with IGT (36 in the LCD group and 36 in the control group) who were enrolled from April 2007–March 2012 and followed for 12 months. We retrospectively compared the LCD group with the control group. Results In 69.4% of the LCD group, blood glucose was normalized at 12 months and the 2-hour plasma glucose level in the oral glucose tolerance test (OGTT) was reduced by 33 mg/dL. In addition, the incidence of diabetes was significantly lower in the LCD group than in the control group at 12 months (0% versus 13.9%, P=0.02). The LCD group showed a significant decrease in fasting plasma glucose, hemoglobin A1c, the homeostasis model of assessment of insulin resistance value, body weight and serum triglycerides (TGs) at 12 months, while there was a significant increase of the serum high-density lipoprotein (HDL) cholesterol level. Conclusion The LCD is effective for normalizing blood glucose and preventing progression to type 2 diabetes in patients with IGT. PMID:24966689

Long-term feeding of red algae (Gelidium amansii) ameliorates glucose and lipid metabolism in a high fructose diet-impaired glucose tolerance rat model.

PubMed

Liu, Hshuan-Chen; Chang, Chun-Ju; Yang, Tsung-Han; Chiang, Meng-Tsan

2017-07-01

This study was designed to investigate the effect of Gelidium amansii (GA) on carbohydrate and lipid metabolism in rats with high fructose (HF) diet (57.1% w/w). Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1) control diet group (Con); (2) HF diet group (HF); and (3) HF with GA diet group (HF + 5% GA). The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation of GA caused a decrease in plasma glucose, insulin, tumor necrosis factor-α, and leptin. HF diet increased hepatic lipid content. However, intake of GA reduced the accumulation of hepatic lipids including total cholesterol (TC) and triglyceride contents. GA elevated the excretion of fecal lipids and bile acid in HF diet-fed rats. Furthermore, GA significantly decreased plasma TC, triglyceride, low density lipoprotein plus very low density lipoprotein cholesterol, and TC/high density lipoprotein cholesterol ratio in HF diet-fed rats. HF diet induced an in plasma glucose and an impaired glucose tolerance, but GA supplementation decreased homeostasis model assessment equation-insulin resistance and improved impairment of glucose tolerance. Taken together, these results indicate that supplementation of GA can improve the impairment of glucose and lipid metabolism in an HF diet-fed rat model. Copyright © 2016. Published by Elsevier B.V.

Impaired glucose tolerance in first-episode drug-naïve patients with schizophrenia: relationships with clinical phenotypes and cognitive deficits.

PubMed

Chen, D C; Du, X D; Yin, G Z; Yang, K B; Nie, Y; Wang, N; Li, Y L; Xiu, M H; He, S C; Yang, F D; Cho, R Y; Kosten, T R; Soares, J C; Zhao, J P; Zhang, X Y

2016-11-01

Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia. A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB. IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.

Changes in glucose-elicited blood metabolite responses following weight loss and long term weight maintenance in obese individuals with impaired glucose tolerance.

PubMed

Geidenstam, Nina; Danielsson, Anders P H; Spégel, Peter; Ridderstråle, Martin

2016-03-01

Weight loss improves insulin sensitivity and glucose tolerance in obese subjects with impaired glucose tolerance (IGT), but the long term dynamic effects on blood metabolites other than glucose during an oral glucose tolerance test (OGTT), are largely unknown. Here, we studied changes in OGTT-elicited metabolite patterns in obese subjects during a diet-induced weight loss study. Blood samples from 14 obese individuals with IGT were collected at 0, 30 and 120 min during a standard 75 g OGTT at baseline (BMI 44 ± 2 kg/m(2)), after weight loss (BMI 36 ± 2 kg/m(2)) and after weight maintenance (BMI 35 ± 2 kg/m(2)). Serum metabolite levels were analyzed by gas chromatography/mass spectrometry and compared to a lean glucose tolerant group. Changes in the OGTT-elicited metabolite patterns occurred differentially during weight loss and weight maintenance. Enhanced suppression of aromatic amino acids were associated with decreased insulinogenic index observed after weight loss (tyrosine: r=0.72, p=0.013; phenylalanine: r=0.63, p=0.039). The OGTT-elicited suppression and/or lack of increase in levels of glutamate, glutamine, isoleucine, leucine, and the fatty acids laurate, oleate and palmitate, improved towards the lean profile after weight maintenance, paralleling an improvement in glucose tolerance. The greater heterogeneity in the response before and after weight loss in the obese, compared to lean subjects, was markedly reduced after weight maintenance. Diet-induced weight loss followed by weight maintenance results in changes in metabolite profiles associated with either hepatic insulin sensitivity or peripheral glucose tolerance. Our results highlight the importance of evaluating the effects of weight loss and weight maintenance separately. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke (MAAS): study protocol for a randomized controlled trial.

PubMed

Osei, Elizabeth; Fonville, Susanne; Zandbergen, Adrienne A M; Brouwers, Paul J A M; Mulder, Laus J M M; Lingsma, Hester F; Dippel, Diederik W J; Koudstaal, Peter J; den Hertog, Heleen M

2015-08-05

Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients. The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (<6 months) TIA, amaurosis fugax or minor ischemic stroke (modified Rankin scale ≤ 3) and impaired glucose tolerance, defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated standard oral glucose tolerance test, will be included. Patients with renal or liver impairment, heart failure, chronic hypoxic lung disease stage III-IV, history of lactate acidosis or diabetic ketoacidosis, pregnancy or breastfeeding, pancreatitis and use of digoxin will be excluded. The patients will be randomly assigned in a 1:1:2 ratio to metformin, sitagliptin or "no treatment." Patients allocated to metformin will start with 500 mg twice daily, which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg. Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg. The study has been registered as NTR 3196 in The Netherlands Trial Register. Primary outcomes include percentage still on treatment, percentage of (serious) adverse events, and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months. This study will give

Altered walking strategy and increased unsteadiness in participants with impaired glucose tolerance and Type 2 diabetes relates to small-fibre neuropathy but not vitamin D deficiency.

PubMed

Almurdhi, M M; Brown, S J; Bowling, F L; Boulton, A J M; Jeziorska, M; Malik, R A; Reeves, N D

2017-06-01

To investigate alterations in walking strategy and dynamic sway (unsteadiness) in people with impaired glucose tolerance and people with Type 2 diabetes in relation to severity of neuropathy and vitamin D levels. A total of 20 people with Type 2 diabetes, 20 people with impaired glucose tolerance and 20 people without either Type 2 diabetes or impaired glucose tolerance (control group) underwent gait analysis using a motion analysis system and force platforms, and detailed assessment of neuropathy and serum 25 hydroxy-vitamin D levels. Ankle strength (P = 0.01) and power (P = 0.003) during walking and walking speed (P = 0.008) were preserved in participants with impaired glucose tolerance but significantly lower in participants with Type 2 diabetes compared with control participants; however, step width (P = 0.005) and dynamic medio-lateral sway (P = 0.007) were significantly higher and posterior maximal movement (P = 0.000) was lower in participants with impaired glucose tolerance, but preserved in those with Type 2 diabetes compared with the control group. Dynamic medio-lateral sway correlated with corneal nerve fibre length (P = 0.001) and corneal nerve branch density (P = 0.001), but not with vibration perception threshold (P = 0.19). Serum 25 hydroxy-vitamin D levels did not differ significantly among the groups (P = 0.10) and did not correlate with any walking variables or measures of dynamic sway. Early abnormalities in walking strategy and dynamic sway were evident in participants with impaired glucose tolerance, whilst there was a reduction in ankle strength, power and walking speed in participants with Type 2 diabetes. Unsteadiness correlated with small-, but not large-fibre neuropathy and there was no relationship between vitamin D levels and walking variables. © 2017 Diabetes UK.

Effect of Linagliptin Versus Metformin on Glycemic Variability in Patients with Impaired Glucose Tolerance.

PubMed

González-Heredia, Tonatiuh; Hernández-Corona, Diana M; González-Ortiz, Manuel; Martínez-Abundis, Esperanza

2017-08-01

Impaired glucose tolerance (IGT) and glycemic variability may be associated with increased risk of micro- and macrovascular complications. The aim of this study was to assess the effect of linagliptin versus metformin on glycemic variability in patients with IGT. A randomized, double-blind clinical trial with parallel groups was carried out in 16 adult patients with IGT, overweight or obesity. All patients signed an informed consent. The therapies were randomly assigned: (a) metformin 500 mg bid (n = 8) or (b) linagliptin 5 mg a.m. and placebo p.m. (n = 8), both for 90 days. At the beginning of the trial and 3 months later, fasting glucose, glycated hemoglobin A1c, oral glucose tolerance test (OGTT), and glycemic variability [area under the curve (AUC) of glucose, mean amplitude of glycemic excursion (MAGE), standard deviation (SD) of glucose, coefficient of variation (CV) of glucose, and mean blood glucose (MBG)] were measured. Mann-Whitney U, Wilcoxon, and Fisher exact tests were used for statistical analyses. Both groups were similar in basal characteristics. After linagliptin administration, a significant decrease in glucose levels at 120 min of OGTT (9.0 ± 0.9 vs. 6.9 ± 2.2 mmol/L, P = 0.012) was observed. Glycemic variability showed a similar behavior and there were no significant differences in the AUC, MAGE, SD of glucose, CV of glucose, and MBG between groups. Linagliptin administration resulted in better glycemic control according to the decrease of glucose levels by the OGTT at 120 min in patients with IGT. Meanwhile, glycemic variability was not modified in any of the study groups.

Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation

PubMed Central

Reno, Candace M.; Puente, Erwin C.; Sheng, Zhenyu; Daphna-Iken, Dorit; Bree, Adam J.; Routh, Vanessa H.; Kahn, Barbara B.

2017-01-01

GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. PMID:27797912

Testosterone is protective against impaired glucose metabolism in male intrauterine growth-restricted offspring

PubMed Central

Dasinger, John Henry; Fahling, Joel M.; Backstrom, Miles A.; Alexander, Barbara T.

2017-01-01

Placental insufficiency alters the intrauterine environment leading to increased risk for chronic disease including impaired glucose metabolism in low birth weight infants. Using a rat model of low birth weight, we previously reported that placental insufficiency induces a significant increase in circulating testosterone in male intrauterine growth-restricted offspring (mIUGR) in early adulthood that is lost by 12 months of age. Numerous studies indicate testosterone has a positive effect on glucose metabolism in men. Female growth-restricted littermates exhibit glucose intolerance at 6 months of age. Thus, the aim of this paper was to determine whether mIUGR develop impaired glucose metabolism, and whether a decrease in elevated testosterone levels plays a role in its onset. Male growth-restricted offspring were studied at 6 and 12 months of age. No impairment in glucose tolerance was observed at 6 months of age when mIUGR exhibited a 2-fold higher testosterone level compared to age-matched control. Fasting blood glucose was significantly higher and glucose tolerance was impaired with a significant decrease in circulating testosterone in mIUGR at 12 compared with 6 months of age. Castration did not additionally impair fasting blood glucose or glucose tolerance in mIUGR at 12 months of age, but fasting blood glucose was significantly elevated in castrated controls. Restoration of elevated testosterone levels significantly reduced fasting blood glucose and improved glucose tolerance in mIUGR. Thus, our findings suggest that the endogenous increase in circulating testosterone in mIUGR is protective against impaired glucose homeostasis. PMID:29145418

Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation.

PubMed

Reno, Candace M; Puente, Erwin C; Sheng, Zhenyu; Daphna-Iken, Dorit; Bree, Adam J; Routh, Vanessa H; Kahn, Barbara B; Fisher, Simon J

2017-03-01

GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. © 2017 by the American Diabetes Association.

Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study.

PubMed

Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John J V; Califf, Robert M; Krum, Henry

2013-12-09

To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. NAVIGATOR trial. Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. ClinicalTrials.gov NCT00097786.

Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study

PubMed Central

Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John JV; Califf, Robert M

2013-01-01

Objective To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Design Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Setting NAVIGATOR trial. Participants Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Main outcome measures Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. Results During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Conclusions Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. Trial registration ClinicalTrials.gov NCT00097786. PMID:24322398

Impact of exercise on diurnal and nocturnal markers of glycaemic variability and oxidative stress in obese individuals with type 2 diabetes or impaired glucose tolerance.

PubMed

Farabi, Sarah S; Carley, David W; Smith, Donald; Quinn, Lauretta

2015-09-01

We measured the effects of a single bout of exercise on diurnal and nocturnal oxidative stress and glycaemic variability in obese subjects with type 2 diabetes mellitus or impaired glucose tolerance versus obese healthy controls. Subjects (in random order) performed either a single 30-min bout of moderate-intensity exercise or remained sedentary for 30 min at two separate visits. To quantify glycaemic variability, standard deviation of glucose (measured by continuous glucose monitoring system) and continuous overlapping net glycaemic action of 1-h intervals (CONGA-1) were calculated for three 12-h intervals during each visit. Oxidative stress was measured by 15-isoprostane F(2t) levels in urine collections for matching 12-h intervals. Exercise reduced daytime glycaemic variability (ΔCONGA-1 = -12.62 ± 5.31 mg/dL, p = 0.04) and urinary isoprostanes (ΔCONGA-1 = -0.26 ± 0.12 ng/mg, p = 0.04) in the type 2 diabetes mellitus/impaired glucose tolerance group. Daytime exercise-induced change in urinary 15-isoprostane F(2t) was significantly correlated with both daytime standard deviation (r = 0.68, p = 0.03) and with subsequent overnight standard deviation (r = 0.73, p = 0.027) in the type 2 diabetes mellitus/impaired glucose tolerance group. Exercise significantly impacts the relationship between diurnal oxidative stress and nocturnal glycaemic variability in individuals with type 2 diabetes mellitus/impaired glucose tolerance. © The Author(s) 2015.

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 influence of physical training on metabolic indices in men with myocardial infarction and impaired glucose tolerance].

PubMed

Stochmal, Anna; Jasiak-Tyrkalska, Bozena; Stochmal, Ewa; Huszno, Bohdan; Kawecka-Jaszcz, Kalina

2007-01-01

Body mass reduction and regular physical training form part of a strategy to treat disorders of carbohydrate metabolism associated with obesity. Evidence shows that even a slight reduction in body mass may improve carbohydrate tolerance, lipid profile and insulin resistance, reduce insulin levels and finally delay or reduce risk of diabetes mellitus. Multiple studies, including prospective studies confirm the independent protective effects of physical training against future development of type 2 diabetes mellitus. Myocardial infarction is a severe complication of atherosclerosis. Patients with glucose intolerance have a 2-fold higher risk of dying. Impaired glucose tolerance is negatively associated with prognosis in patients after myocardial infarction. Glucose intolerance accompanies hyperinsulinemia, a major indicator of insulin resistance. The aim of the study was to analyze the effect of physical training on hyperinsulinemia/ insulin resistance in patients after myocardial infarction (MI) with impaired glucose tolerance (IGT). 31 men aged 37-69 years (mean 51 +/- 7.4) with IGT 3.5 years after MI, in NYHA class I and II participated in the study. Group A (n=16 men) underwent supervised physical training and group B (n=15) received standard information on physical training. Tissue glucose disposal using normoglycemic glucose clamp technique, fasting insulinemia, glycemia during OGTT, lipid profile, BMI and body mass composition were obtained in all patients. The groups were matched for age. There were no differences in BMI, percent fat content, blood pressure, diet, smoking status and pharmacotherapy. Glycemia during baseline OGTT did not differentiate the groups, either. Analysis of insulinemia and glycemia during OGTT at baseline and at 12 weeks after regular physical training showed lower levels of insulinemia and glycemia compared with baseline levels in group A (fasting glycemia 6.41+/-0.46 vs. 4.8+/-0.32 mmol/l, p<0.001; fasting insulinemia 59

Significant association of serum creatinine with HbA1C in impaired glucose tolerant Pakistani subjects

PubMed Central

Farasat, Tasnim; Sharif, Saima; Naz, Shagufta; Fazal, Sabiha

2015-01-01

Objective: The present study was conducted to assess the serum concentration of creatinine and determine its relationship with potential risk factors of diabetes in Impaired Glucose tolerance subjects. Methods: This cross sectional study was conducted on 100 IGT patients who attended Amin Hayat diabetic center in Lahore from January 2011- June 2011. Patients with age group 34-67 years, (both sexes) were included in the study. Different demographic parameters as age, BMI, WHR, B.P, personal history and socioeconomic status were recorded. Oral Glucose Tolerance Test was performed. The biochemical parameters including HbA1c, lipid profile, urea, uric acid, creatinine and bilirubin level were measured by chemistry analyzer. Results: A strong correlation between creatinine and HbA1c was observed. The level of creatinine was also significantly associated with age in IGT subjects. Creatinine is non-significantly correlated with Cholesterol, LDL-Chol and TG while negatively significantly associated with BMI, fasting blood glucose and HDL-Chol. Conclusion: The present study concluded significant association of serum creatinine with HbA1c, BMI and HDL cholesterol. PMID:26430445

Significant association of serum creatinine with HbA1C in impaired glucose tolerant Pakistani subjects.

PubMed

Farasat, Tasnim; Sharif, Saima; Naz, Shagufta; Fazal, Sabiha

2015-01-01

The present study was conducted to assess the serum concentration of creatinine and determine its relationship with potential risk factors of diabetes in Impaired Glucose tolerance subjects. This cross sectional study was conducted on 100 IGT patients who attended Amin Hayat diabetic center in Lahore from January 2011- June 2011. Patients with age group 34-67 years, (both sexes) were included in the study. Different demographic parameters as age, BMI, WHR, B.P, personal history and socioeconomic status were recorded. Oral Glucose Tolerance Test was performed. The biochemical parameters including HbA1c, lipid profile, urea, uric acid, creatinine and bilirubin level were measured by chemistry analyzer. A strong correlation between creatinine and HbA1c was observed. The level of creatinine was also significantly associated with age in IGT subjects. Creatinine is non-significantly correlated with Cholesterol, LDL-Chol and TG while negatively significantly associated with BMI, fasting blood glucose and HDL-Chol. The present study concluded significant association of serum creatinine with HbA1c, BMI and HDL cholesterol.

Dipeptidyl peptidase IV inhibitors for the treatment of impaired glucose tolerance and type 2 diabetes.

PubMed

Wiedeman, Paul E; Trevillyan, James M

2003-04-01

Glucagon-like peptide-1 (GLP-1 (7-36) amide) is a gut hormone released from L-cells in the small intestine in response to the ingestion of nutrients and enhances the glucose-dependent secretion of insulin from pancreatic beta-cells. In type 2 diabetic patients, the continuous infusion of GLP-1 (7-36) amide decreases plasma glucose and hemoglobin A1c concentrations and improves beta-cell function. Hormone action is rapidly terminated by the N-terminal cleavage of GLP-1 at Ala2 by the aminopeptidase, dipeptidyl peptidase IV (DPPIV). The short in vivo half-life of GLP-1 (< 3 min) poses challenges to the development of exogenous GLP-1-based therapy. The inhibition of endogenous GLP-1 degradation by reducing DPPIV activity is an alternative strategy for improving the incretin action of GLP-1 in vivo. This review summarizes recent advances in the design of potent and selective small molecule inhibitors of DPPIV and the potential challenges to the development of DPPIV inhibitors for the treatment of impaired glucose tolerance and type 2 diabetes.

Associations of lipid profiles with insulin resistance and β cell function in adults with normal glucose tolerance and different categories of impaired glucose regulation.

PubMed

Zheng, Shuang; Xu, Hua; Zhou, Huan; Ren, Xingxing; Han, Tingting; Chen, Yawen; Qiu, Huiying; Wu, Peihong; Zheng, Jun; Wang, Lihua; Liu, Wei; Hu, Yaomin

2017-01-01

To investigate the associations of dyslipidemia with insulin resistance and β cell function in individuals with normal glucose tolerance (NGT) and different categories of impaired glucose regulation (IGR). 544 subjects (365 with dyslipidemia and/or IGR and 179 with normal lipid and glucose tolerance) were enrolled in the study. All subjects underwent oral glucose tolerance test (OGTT). HOMA-IR was used to evaluate insulin sensitivity. Disposition index (DI) was used to evaluate β cell function. Multiple linear regression analysis was performed to assess correlations among lipid profiles, insulin resistance and β cell function. Among subjects with NGT, those with dyslipidemia had higher level of HOMA-IR but lower level of DI. While among subjects with different categories of IGR, those with dyslipidemia and CGI had significantly decreased DI. No obvious differences of insulin resistance or β cell function were found in IFG or IGT subjects with or without dyslipidemia. TG and HDL-C were correlated with HOMA-IR (β = 0.79, p <0.001; β = -0.38, p = 0.027, respectively, compared with subjects in the low level groups). Moreover, TG and TC were negatively correlated with DI (β = -2.17, p = 0.013; β = -2.01, p = 0.034 respectively, compared with subjects in the low level groups) after adjusting for confounding parameters. Dyslipidemia induces insulin resistance and impaired β cell response to insulin resistance in individuals with NGT. Furthermore, dyslipidemia diminishes β cell function in subjects with CGI. TG and HDL-C were correlated with insulin resistance, and TG, TC were negatively correlated with β cell response to insulin resistance in non-diabetic individuals.

Associations of lipid profiles with insulin resistance and β cell function in adults with normal glucose tolerance and different categories of impaired glucose regulation

PubMed Central

Ren, Xingxing; Han, Tingting; Chen, Yawen; Qiu, Huiying; Wu, Peihong; Zheng, Jun; Wang, Lihua; Liu, Wei; Hu, Yaomin

2017-01-01

Aims To investigate the associations of dyslipidemia with insulin resistance and β cell function in individuals with normal glucose tolerance (NGT) and different categories of impaired glucose regulation (IGR). Methods 544 subjects (365 with dyslipidemia and/or IGR and 179 with normal lipid and glucose tolerance) were enrolled in the study. All subjects underwent oral glucose tolerance test (OGTT). HOMA-IR was used to evaluate insulin sensitivity. Disposition index (DI) was used to evaluate β cell function. Multiple linear regression analysis was performed to assess correlations among lipid profiles, insulin resistance and β cell function. Results Among subjects with NGT, those with dyslipidemia had higher level of HOMA-IR but lower level of DI. While among subjects with different categories of IGR, those with dyslipidemia and CGI had significantly decreased DI. No obvious differences of insulin resistance or β cell function were found in IFG or IGT subjects with or without dyslipidemia. TG and HDL-C were correlated with HOMA-IR (β = 0.79, p <0.001; β = -0.38, p = 0.027, respectively, compared with subjects in the low level groups). Moreover, TG and TC were negatively correlated with DI (β = -2.17, p = 0.013; β = -2.01, p = 0.034 respectively, compared with subjects in the low level groups) after adjusting for confounding parameters. Conclusions Dyslipidemia induces insulin resistance and impaired β cell response to insulin resistance in individuals with NGT. Furthermore, dyslipidemia diminishes β cell function in subjects with CGI. TG and HDL-C were correlated with insulin resistance, and TG, TC were negatively correlated with β cell response to insulin resistance in non-diabetic individuals. PMID:28199386

Association between ghrelin gene variations and blood pressure in subjects with impaired glucose tolerance.

PubMed

Mager, Ursula; Kolehmainen, Marjukka; Lindström, Jaana; Eriksson, Johan G; Valle, Timo T; Hämäläinen, Helena; Ilanne-Parikka, Pirjo; Keinänen-Kiukaanniemi, Sirkka; Tuomilehto, Jaakko O; Pulkkinen, Leena; Uusitupa, Matti I

2006-09-01

Ghrelin is a gut-brain hormone, which stimulates food intake and controls energy balance. Recently, it has been shown that ghrelin may also play a role in the regulation of blood pressure (BP) by acting at the sympathetic nervous system. In the present study we genotyped six variants of the ghrelin gene and its promoter, and tested whether these single nucleotide polymorphisms (SNPs) were associated with BP levels in participants of the Finnish Diabetes Prevention Study. The Finnish Diabetes Prevention Study was a longitudinal study where 522 subjects with impaired glucose tolerance were randomized into either an intervention or control group. DNA was available from 507 subjects (mean body mass index [BMI] 31.2+/-4.5 kg/m2, age 55+/-7 years). All six SNPs were screened by the restriction fragment length polymorphism method. Subjects with the most common genotype combination of the following four SNPs, -604G/A, -501A/C, Leu72Met, and Gln90Leu, had the lowest systolic (131+/-11 v 137+/-13 mm Hg, P=.003) and diastolic BP levels (79+/-7 v 83+/-7 mm Hg, P=.004) at the baseline of the study and during 3 years of follow-up compared to all other genotypes. Adjustments for age, gender, antihypertensive medication, BMI, waist circumference, and alcohol intake did not change this association. Several ghrelin gene variations were associated with BP levels in subjects with impaired glucose tolerance.

Relationship between major dietary patterns and metabolic syndrome among individuals with impaired glucose tolerance.

PubMed

Amini, Massoud; Esmaillzadeh, Ahmad; Shafaeizadeh, Shila; Behrooz, Jhila; Zare, Maryam

2010-10-01

Dietary habits have been associated with the prevalence of the metabolic syndrome and limited data are available in this field for individuals with impaired glucose tolerance. This study focused on the association between major dietary patterns and prevalence of the metabolic syndrome in individuals with impaired glucose tolerance. This cross-sectional study was done in 425 subjects 35 to 55 y of age. Dietary data were collected using a food-frequency questionnaire. Blood pressure, waist circumference, glucose, triacylglycerols, and high-density lipoprotein cholesterol were measured and metabolic syndrome was defined based on Adult Treatment Panel III guidelines. Five major dietary patterns were found: a western pattern (high in sweets, butter, soda, mayonnaise, sugar, cookies, tail of a lamb, hydrogenated fat, and eggs), a prudent pattern (high in fish, peas, honey, nuts, juice, dry fruits, vegetable oil, liver and organic meat, and coconuts and low in hydrogenated fat and non-leafy vegetables), a vegetarian pattern (high in potatoes, legumes, fruits rich in vitamin C, rice, green leafy vegetables, and fruits rich in vitamin A), a high-fat dairy pattern (high in high-fat yogurt and high-fat milk and low in low-fat yogurt, peas, and bread), and a chicken and plant pattern (high in chicken, fruits rich in vitamin A, green leafy vegetables, and mayonnaise and low in beef, liver, and organic meat). After adjusting for confounding variables, the western pattern was associated with greater odds of having increased triacylglycerol (odds ratio 1.76, 95% confidence interval 1.01-3.07) and blood pressure (odds ratio 2.62, 95% confidence interval 1.32-5.23). The prudent pattern was positively associated with a prevalence of low high-density lipoprotein cholesterol levels (odds ratio 0.55, 95% confidence interval 0.31-0.96). The vegetarian dietary pattern was inversely associated with a risk of an abnormal fasting blood glucose level (odds ratio 2.26, 95% confidence interval

Effects of indigestible dextrin on glucose tolerance in rats.

PubMed

Wakabayashi, S; Kishimoto, Y; Matsuoka, A

1995-03-01

A recently developed indigestible dextrin (IDex) was studied for its effects on glucose tolerance in male Sprague-Dawley rats. IDex is a low viscosity, water-soluble dietary fibre obtained by heating and enzyme treatment of potato starch. It has an average molecular weight of 1600. An oral glucose tolerance test was conducted with 8-week-old rats to evaluate the effects of IDex on the increase in plasma glucose and insulin levels after a single administration of various sugars (1.5 g/kg body weight). The increase in both plasma glucose and insulin levels following sucrose, maltose and maltodextrin loading was significantly reduced by IDex (0.15 g/kg body weight). This effect was not noted following glucose, high fructose syrup and lactose loading. To evaluate the effects of continual IDex ingestion on glucose tolerance, 5-week-old rats were kept for 8 weeks on a stock diet, a high sucrose diet or an IDex-supplemented high sucrose diet. An oral glucose (1.5 g/kg body weight) tolerance test was conducted in week 8. Increases in both plasma glucose and insulin levels following glucose loading were higher in the rats given a high sucrose diet than in the rats fed a stock diet. However, when IDex was included in the high sucrose diet, the impairment of glucose tolerance was alleviated. Moreover, IDex feeding also significantly reduced accumulation of body fat, regardless of changes in body weight. These findings suggest that IDex not only improves glucose tolerance following sucrose, maltose and maltodextrin loading but also stops progressive decrease in glucose tolerance by preventing a high sucrose diet from causing obesity.

Pioglitazone decreases coronary artery inflammation in impaired glucose tolerance and diabetes mellitus: evaluation by FDG-PET/CT imaging.

PubMed

Nitta, Yoshikazu; Tahara, Nobuhiro; Tahara, Atsuko; Honda, Akihiro; Kodama, Norihiro; Mizoguchi, Minori; Kaida, Hayato; Ishibashi, Masatoshi; Hayabuchi, Naofumi; Ikeda, Hisao; Yamagishi, Sho-ichi; Imaizumi, Tsutomu

2013-11-01

The aim of this study was to compare the effect of pioglitazone with glimepiride on coronary arterial inflammation with serial (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT) angiography. Recent studies have shown that FDG-PET combined with CT is a reliable tool to visualize and quantify vascular inflammation. Although pioglitazone significantly prevented the progression of coronary atherosclerosis and reduced the recurrence of myocardial infarction in patients with type 2 diabetes mellitus (DM), it remains unclear whether pioglitazone could attenuate coronary artery inflammation. Fifty atherosclerotic patients with impaired glucose tolerance or type 2 DM underwent determination of blood chemistries, anthropometric and inflammatory variables, and FDG-PET/CT angiography, and then were randomized to receive either pioglitazone or glimepiride for 16 weeks. Effects of the treatments on vascular inflammation of the left main trunk were evaluated by FDG-PET/CT angiography at baseline and end of the study. Vascular inflammation of the left main trunk was measured by blood-normalized standardized uptake value, known as a target-to-background ratio. Three patients dropped out of the study during the assessment or treatment. Finally, 25 pioglitazone-treated patients and 22 glimepiride-treated patients (37 men; mean age: 68.1 ± 8.3 years; glycosylated hemoglobin: 6.72 ± 0.70%) completed the study. After 16-week treatments, fasting plasma glucose and glycosylated hemoglobin values were comparably reduced in both groups. Changes in target-to-background ratio values from baseline were significantly greater in the pioglitazone group than in the glimepiride group (-0.12 ± 0.06 vs. 0.09 ± 0.07, p = 0.032), as well as changes in high-sensitivity C-reactive protein (pioglitazone vs. glimepiride group: median: -0.24 [interquartile range (IQR): -1.58 to -0.04] mg/l vs. 0.08 [IQR: -0.07 to 0.79] mg/l, p = 0.031). Our study

Effect of zinc supplementation on insulin resistance, energy and macronutrients intakes in pregnant women with impaired glucose tolerance.

PubMed

Roshanravan, Neda; Alizadeh, Mohammad; Hedayati, Mehdi; Asghari-Jafarabadi, Mohammad; Mesri Alamdari, Naimeh; Anari, Farideh; Tarighat-Esfanjani, Ali

2015-02-01

Hyperglycemia and gestational diabetes mellitus are complications of pregnancy. Both mothers and newborns are typically at increased risk for complications. This study sought to determine effect of zinc supplementation on serum glucose levels, insulin resistance, energy and macronutrients intakes in pregnant women with impaired glucose tolerance. In this clinical trial 44 pregnant women with impaired glucose tolerance, from December 2012 -April 2013 were randomly divided into zinc (n=22) and placebo (n=22) groups and recived 30mg/day zinc gluconate and (n=22), and placebo for eight consecutive weeks respectively. Dietary food intake was estimated from 3-days diet records. Serum levels of zinc, fasting blood sugar, and insulin were measured by conventional methods. Also homeostatic model assessment of insulin resistance was calculated. Serumlevels of fasting blood sugar, insulin and homeostatic model assessment of insulin resistance slightly decreased in zinc group, but these changes were not statistically significant. Serum zinc levels (P =0.012), energy (P=0.037), protein (P=0.019) and fat (P=0.017) intakes increased statistically significant in the zinc group after intervention but not in the placebo group. Oral supplementation with zinc could be effective in increasing serum zinc levels and energy intake with no effects on fasting blood sugar, homeostatic model assessment of insulin resistance and insulin levels.

Effect of Chinese Herbal Medicine Jinlida Granule in Treatment of Patients with Impaired Glucose Tolerance

PubMed Central

Shi, Ya-Lin; Liu, Wen-Juan; Zhang, Xiao-Fang; Su, Wei-Juan; Chen, Ning-Ning; Lu, Shu-Hua; Wang, Li-Ying; Shi, Xiu-Lin; Li, Zhi-Bin; Yang, Shu-Yu

2016-01-01

Background: Diabetes mellitus (DM) remains a major health problem worldwide. Several clinical trials have shown the superiority of the Traditional Chinese Medicine in delaying or reversing the development and progression of DM. This study aimed to evaluate the efficacy of Jinlida (JLD) granule, a Chinese herbal recipe, in the treatment of impaired glucose tolerance (IGT) and its effect on the prevention of DM. Methods: Sixty-five IGT patients were randomized to receive one bag of JLD granules three times daily (JLD group, n = 34) or no drug intervention (control group, n = 31) for 12 weeks. Oral glucose tolerance test, glycated hemoglobin A1c (HbA1c), body mass index, blood lipids levels, fasting insulin, and insulin resistance calculated using homeostatic model assessment (HOMA-IR) of all the patients were observed and compared before and after the treatment. Results: Sixty-one participants completed the trial (32 in JLD group and 29 in the control group). There were statistically significant decreases in HbA1c (P < 0.001), 2-h plasma glucose (P < 0.001), and HOMA-IR (P = 0.029) in JLD group compared with the control group after 12 weeks of treatment. After 12 weeks of treatment, two (6.9%) patients returned to normal blood glucose, and five (17.2%) patients turned into DM in control group, while in the JLD group, 14 (43.8%) returned to normal blood glucose and 2 (6.2%) turned into DM. There was a significant difference in the number of subjects who had normal glucose at the end of the study between two groups (P = 0.001). Conclusions: JLD granule effectively improved glucose control, increased the conversion of IGT to normal glucose, and improved the insulin resistance in patients with IGT. This Chinese herbal medicine may have a clinical value for IGT. PMID:27647185

Effect of Chinese Herbal Medicine Jinlida Granule in Treatment of Patients with Impaired Glucose Tolerance.

PubMed

Shi, Ya-Lin; Liu, Wen-Juan; Zhang, Xiao-Fang; Su, Wei-Juan; Chen, Ning-Ning; Lu, Shu-Hua; Wang, Li-Ying; Shi, Xiu-Lin; Li, Zhi-Bin; Yang, Shu-Yu

2016-10-05

Diabetes mellitus (DM) remains a major health problem worldwide. Several clinical trials have shown the superiority of the Traditional Chinese Medicine in delaying or reversing the development and progression of DM. This study aimed to evaluate the efficacy of Jinlida (JLD) granule, a Chinese herbal recipe, in the treatment of impaired glucose tolerance (IGT) and its effect on the prevention of DM. Sixty-five IGT patients were randomized to receive one bag of JLD granules three times daily (JLD group, n = 34) or no drug intervention (control group, n = 31) for 12 weeks. Oral glucose tolerance test, glycated hemoglobin A1c (HbA1c), body mass index, blood lipids levels, fasting insulin, and insulin resistance calculated using homeostatic model assessment (HOMA-IR) of all the patients were observed and compared before and after the treatment. Sixty-one participants completed the trial (32 in JLD group and 29 in the control group). There were statistically significant decreases in HbA1c (P < 0.001), 2-h plasma glucose (P < 0.001), and HOMA-IR (P = 0.029) in JLD group compared with the control group after 12 weeks of treatment. After 12 weeks of treatment, two (6.9%) patients returned to normal blood glucose, and five (17.2%) patients turned into DM in control group, while in the JLD group, 14 (43.8%) returned to normal blood glucose and 2 (6.2%) turned into DM. There was a significant difference in the number of subjects who had normal glucose at the end of the study between two groups (P = 0.001). JLD granule effectively improved glucose control, increased the conversion of IGT to normal glucose, and improved the insulin resistance in patients with IGT. This Chinese herbal medicine may have a clinical value for IGT.

Continuous glucose monitoring, oral glucose tolerance, and insulin - glucose parameters in adolescents with simple obesity.

PubMed

El Awwa, A; Soliman, A; Al-Ali, M; Yassin, M; De Sanctis, V

2012-09-01

In obese adolescents pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type2 diabetes (T2DM To assess oral glucose tolerance, 72-h continuous blood glucose concentrations (CGM) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in 13 adolescents with simple obesity (BMI SDS=4 ± 1.06). OGTT performed in 13 obese adolescents (13.47 ± 3 years) revealed 3 cases (23%) with impaired fasting glucose (IFG: fasting glucose >5.6 mmol/L), 4 cases (30%) with impaired glucose tolerance (IGT: 2h blood glucose >7.8 <11.1 mmol/L), and none with diabetes. Using the continuous glucose monitoring system ( CGMS), IFG was detected in 4 cases, the maximum serum blood glucose (BG : 2h or more after meal) was >7.8 and <11.1 mmol/L (IGT) in 9 children (69%) and >11.1 mmol/L (diabetes) in one case (7.6%). Five cases had a minimum BG recorded of <2.7 mmol/L (hypoglycemia). No glycemic abnormality was detected using HbA1C (5.7 ± 0.3%). 11/13 patients had HOMA values >2.6 and QUICKI values <0.35 denoting insulin resistance. Beta cell mass percent (B %) = 200 ± 94.8% and insulin sensitivity values (IS)=50.4 ± 45.5% denoted insulin resistance with hyper-insulinaemia and preserved beta cell mass. In obese adolescents, CGMS is superior to OGTT and HbA1C in detecting glycemic abnormalities, which appears to be secondary to insulin resistance.

Glucose tolerance test - non-pregnant

MedlinePlus

Oral glucose tolerance test - non-pregnant; OGTT - non-pregnant; Diabetes - glucose tolerance test; Diabetic - glucose tolerance test ... The most common glucose tolerance test is the oral glucose ... the test begins, a sample of blood will be taken. You will then ...

Dosakaya Juice Assuages Development of Sucrose Induced Impaired Glucose Tolerance and Imbalance in Antioxidant Defense

PubMed Central

Kumar, Dommati Anand; Sweeya, Pisupati S. R.; Shukla, Srishti; Anusha, Sanga Venkata; Akshara, Dasari; Madhusudana, Kuncha; Tiwari, Ashok Kumar

2015-01-01

Objective: The objective was to explore the effect of Dosakaya (DK) (Cucumis melo var. chito) juice on sucrose induced dysglycemia and disturbances in antioxidant defense in rats. Materials and Methods: Rats were preconditioned with DK juice before administration of sucrose beverage continuously for 1-month. Blood glucose tolerance test and glutathione (GSH) homeostasis pathways in kidney were analyzed in different group of animals at the end of the study. Results: DK juice diffused (P < 0.001) hypertriglyceridemia inducing effect of sucrose and arrested sucrose induced weight gain. It improved glucose tolerance ability by significantly reducing (P < 0.05) first-hour glycemic excursion and decreasing 2 h glycemic load (P < 0.05) following oral glucose tolerance test in sucrose fed animals. Furthermore, disturbances in antioxidant defense mechanisms in terms of GSH homeostasis in kidney were restored due to juice feeding. DK juice administration checked reduction in GSH-S-transferase and glyoxalase-I activity, thus, significantly mitigated lipid peroxidation (P < 0.05), and formation of advanced glycation end-products (P < 0.001) in kidney and serum (P < 0.01). Quantitative analysis of juice found it a rich source of protein and polyphenols. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed the presence of multiple protein bands in whole fruit juice. Therefore, SDS-PAGE protein fingerprint of DK juice may serve as a quality control tool for standardization of juice. Conclusion: The whole fruit juice of DK may become cost-effective, affordable health beverage in extenuating ill-health effects of sugar consumption. This is the first report identifying DK juice in preventing development dysglycemia, dyslipidemia, and oxidative stress induced due to chronic sucrose feeding in rats. SUMMARY Chronic sucrose consumption induced development of dysglycemia and also impaired antioxidant defense mechanism in rats. The oral administration of

Feeding butter with elevated content of trans-10, cis-12 conjugated linoleic acid to obese-prone rats impairs glucose and insulin tolerance.

PubMed

Hamilton, Melissa; Hopkins, Loren E; AlZahal, Ousama; MacDonald, Tara L; Cervone, Daniel T; Wright, David C; McBride, Brian W; Dyck, David J

2015-09-28

We recently demonstrated that feeding a natural CLAt10,c12-enriched butter to lean female rats resulted in small, but significant increases in fasting glucose and insulin concentrations, and impaired insulin tolerance. Our goal was to extend these findings by utilizing the diabetes-prone female fatty Zucker rat. Rats were fed custom diets containing 45 % kcal of fat derived from control and CLAt10,c12-enriched butter for 8 weeks. CLA t10,c12-enriched butter was prepared from milk collected from cows fed a high fermentable carbohydrate diet to create subacute rumen acidosis (SARA); control (non-SARA) butter was collected from cows fed a low grain diet. Female fatty Zucker rats (10 weeks old) were randomly assigned to one of four diet treatments: i) low fat (10 % kcal), ii) 45 % kcal lard, iii) 45 % kcal SARA butter, or iv) 45 % kcal non-SARA butter. A low fat fed lean Zucker group was used as a control group. After 8 weeks, i) glucose and insulin tolerance tests, ii) insulin signaling in muscle, adipose and liver, and iii) metabolic caging measurements were performed. Glucose and insulin tolerance were significantly impaired in all fatty Zucker groups, but to the greatest extent in the LARD and SARA conditions. Insulin signaling (AKT phosphorylation) was impaired in muscle, visceral (perigonadal) adipose tissue and liver in fatty Zucker rats, but was generally similar across dietary groups. Physical activity, oxygen consumption, food intake and weight gain were also similar amongst the various fatty Zucker groups. Increasing the consumption of a food naturally enriched with CLAt10,c12 significantly worsens glucose and insulin tolerance in a diabetes-prone rodent model. This outcome is not explained by changes in tissue insulin signaling, physical activity, energy expenditure, food intake or body mass.

Comparable Attenuation of Sympathetic Nervous System Activity in Obese Subjects with Normal Glucose Tolerance, Impaired Glucose Tolerance, and Treatment Naïve Type 2 Diabetes following Equivalent Weight Loss

PubMed Central

Straznicky, Nora E.; Grima, Mariee T.; Sari, Carolina I.; Lambert, Elisabeth A.; Phillips, Sarah E.; Eikelis, Nina; Mariani, Justin A.; Kobayashi, Daisuke; Hering, Dagmara; Dixon, John B.; Lambert, Gavin W.

2016-01-01

Background and Purpose: Elevated sympathetic nervous system (SNS) activity is a characteristic of obesity and type 2 diabetes (T2D) that contributes to target organ damage and cardiovascular risk. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss. Methods: Un-medicated obese individuals categorized as normal glucose tolerant (NGT, n = 15), impaired glucose tolerant (IGT, n = 24), and newly-diagnosed T2D (n = 15) consumed a hypocaloric diet (29% fat, 23% protein, 45% carbohydrate) for 4-months. The three groups were matched for baseline age (56 ± 1 years), body mass index (BMI, 32.9 ± 0.7 kg/m2), and gender. Clinical measurements included whole-body norepinephrine kinetics, muscle sympathetic nerve activity (MSNA, by microneurography), spontaneous cardiac baroreflex sensitivity (BRS), and oral glucose tolerance test. Results: Weight loss averaged −7.5 ± 0.8, −8.1 ± 0.5, and −8.0 ± 0.9% of body weight in NGT, IGT, and T2D groups, respectively. T2D subjects had significantly greater reductions in fasting glucose, 2-h glucose and glucose area under the curve (AUC0−120) compared to NGT and IGT (group effect, P <0.001). Insulinogenic index decreased in IGT and NGT groups and increased in T2D (group × time, P = 0.04). The magnitude of reduction in MSNA (−7 ± 3, −8 ± 4, −15 ± 4 burst/100 hb, respectively) and whole-body norepinephrine spillover rate (−28 ± 8, −18 ± 6, and −25 ± 7%, respectively), time effect both P <0.001, did not differ between groups. After adjustment for age and change in body weight, Δ insulin AUC0−120 was independently associated with reduction in arterial norepinephrine concentration, whilst Δ LDL-cholesterol and improvement in BRS were independently associated with decrease in MSNA. Conclusions: Equivalent weight loss through hypocaloric diet is accompanied by similar sympathoinhibition in matched obese subjects

Treatments for gestational diabetes and impaired glucose tolerance in pregnancy.

PubMed

Tuffnell, D J; West, J; Walkinshaw, S A

2003-01-01

Gestational diabetes and impaired glucose tolerance (IGT) in pregnancy affects between 3 and 6% of all pregnancies and both have been associated with pregnancy complications. A lack of conclusive evidence has led clinicians to equate the risk of adverse perinatal outcome with pre-existing diabetes. Consequently, women are often intensively managed with increased obstetric monitoring, dietary regulation, and in some cases insulin therapy. However, there has been no sound evidence base to support intensive treatment. The key issue for clinicians and consumers is whether treatment of gestational diabetes and IGT will improve perinatal outcome. The objective of this review was to compare alternative policies of care for women with gestational diabetes and IGT in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group trials register (12 September 2002) and the bibliographies of relevant papers. The Cochrane Central Register of Controlled Trials was also searched (The Cochrane Library, Issue 3, 2002). Randomised controlled trials comparing alternative management strategies for women with gestational diabetes and IGT in pregnancy. Quality was assessed according to the criteria defined by the Cochrane Reviewers' Handbook. Data were extracted and checked independently by two reviewers. Any disagreements were resolved through discussion with the third reviewer. Three studies with a total of 223 women were included. All three included studies involved women with IGT. No trials reporting treatments for gestational diabetes met the criteria. There are insufficient data for any reliable conclusions about the effect of treatments for IGT on perinatal outcome. The difference in abdominal operative delivery rates is not statistically significant (relative risk (RR) 0.86, 95% confidence interval 0.51 to 1.45) and the effect on special care baby unit admission is also not significant (RR 0.49, 95% confidence interval (CI) 0.19 to 1.24). Reduction in birthweight greater

A Controlled Trial of CPAP Therapy on Metabolic Control in Individuals with Impaired Glucose Tolerance and Sleep Apnea

PubMed Central

Weinstock, Tanya G.; Wang, Xuelei; Rueschman, Michael; Ismail-Beigi, Faramarz; Aylor, Joan; Babineau, Denise C.; Mehra, Reena; Redline, Susan

2012-01-01

Study Objectives: To address whether treatment of sleep apnea improves glucose tolerance. Design: Randomized, double-blind crossover study. Setting: Sleep clinic referrals. Patients: 50 subjects with moderate to severe sleep apnea (AHI > 15) and impaired glucose tolerance. Interventions: Subjects were randomized to 8 weeks of CPAP or sham CPAP, followed by the alternate therapy after a one-month washout. After each treatment, subjects underwent 2-hour OGTT, polysomnography, actigraphy, and measurements of indices of glucose control. Measurements and Results: The primary outcome was normalization of the mean 2-h OGTT; a secondary outcome was improvement in the Insulin Sensitivity Index (ISI (0,120). Subjects were 42% men, mean age of 54 (10), BMI of 39 (8), and AHI of 44 (27). Baseline fasting glucose was 104 (12), and mean 2-h OGTT was 110 (57) mg/dL. Seven subjects normalized their mean 2-h OGTT after CPAP but not after sham CPAP, while 5 subjects normalized after sham CPAP but not after CPAP. Overall, there was no improvement in ISI (0,120) between CPAP and sham CPAP (3.6%; 95% CI: [-2.2%, 9.7%]; P = 0.22). However, in those subjects with baseline AHI ≥ 30 (n = 25), there was a 13.3% (95% CI: [5.2%, 22.1%]; P < 0.001) improvement in ISI (0,120) and a 28.7% (95%CI: [-46.5%, −10.9%], P = 0.002) reduction in the 2-h insulin level after CPAP compared to sham CPAP. Conclusions: This study did not show that IGT normalizes after CPAP in subjects with moderate sleep apnea and obesity. However, insulin sensitivity improved in those with AHI ≥ 30, suggesting beneficial metabolic effects of CPAP in severe sleep apnea. Clinical Trials Information: ClinicalTrials.gov Identifier: NCT01385995. Citation: Weinstock TG; Wang X; Rueschman M; Ismail-Beigi F; Aylor J; Babineau DC; Mehra R; Redline S. A controlled trial of CPAP therapy on metabolic control in individuals with impaired glucose tolerance and sleep apnea. SLEEP 2012;35(5):617-625. PMID:22547887

Feeding butter with elevated content of trans-10, cis-12 conjugated linoleic acid to lean rats does not impair glucose tolerance or muscle insulin response

PubMed Central

2014-01-01

Background Numerous studies have investigated the effects of isolated CLA supplementation on glucose homeostasis in humans and rodents. However, both the amount and relative abundance of CLA isomers in supplemental form are not representative of what is consumed from natural sources. No study to date has examined the effects of altered CLA isomer content within a natural food source. Our goal was to increase the content of the insulin desensitizing CLAt10,c12 isomer relative to the CLAc9,t11 isomer in cow’s milk by inducing subacute rumenal acidosis (SARA), and subsequently investigate the effects of this milk fat on parameters related to glucose and insulin tolerance in rats. Methods We fed female rats (~2.5 to 3 months of age) CLA t10,c12 –enriched (SARA) butter or non-SARA butter based diets for 4 weeks in either low (10% of kcal from fat; 0.18% total CLA by weight) or high (60% of kcal from fat; 0.55% total CLA by weight) amounts. In an effort to extend these findings, we then fed rats high (60% kcal) amounts of SARA or non-SARA butter for a longer duration (8 weeks) and assessed changes in whole body glucose, insulin and pyruvate tolerance in comparison to low fat and 60% lard conditions. Results There was a main effect for increased fasting blood glucose and insulin in SARA vs. non-SARA butter groups after 4 weeks of feeding (p < 0.05). However, blood glucose and insulin concentration, and maximal insulin-stimulated glucose uptake in skeletal muscle were similar in all groups. Following 8 weeks of feeding, insulin tolerance was impaired by the SARA butter, but not glucose or pyruvate tolerance. The non-SARA butter did not impair tolerance to glucose, insulin or pyruvate. Conclusions This study suggests that increasing the consumption of a naturally enriched CLAt10,c12 source, at least in rats, has minimal impact on whole body glucose tolerance or muscle specific insulin response. PMID:24956949

Feeding butter with elevated content of trans-10, cis-12 conjugated linoleic acid to lean rats does not impair glucose tolerance or muscle insulin response.

PubMed

Stefanson, Amanda; Hopkins, Loren E; AlZahal, Ousama; Ritchie, Ian R; MacDonald, Tara; Wright, David C; McBride, Brian W; Dyck, David J

2014-06-23

Numerous studies have investigated the effects of isolated CLA supplementation on glucose homeostasis in humans and rodents. However, both the amount and relative abundance of CLA isomers in supplemental form are not representative of what is consumed from natural sources. No study to date has examined the effects of altered CLA isomer content within a natural food source. Our goal was to increase the content of the insulin desensitizing CLAt10,c12 isomer relative to the CLAc9,t11 isomer in cow's milk by inducing subacute rumenal acidosis (SARA), and subsequently investigate the effects of this milk fat on parameters related to glucose and insulin tolerance in rats. We fed female rats (~2.5 to 3 months of age) CLA t10,c12 -enriched (SARA) butter or non-SARA butter based diets for 4 weeks in either low (10% of kcal from fat; 0.18% total CLA by weight) or high (60% of kcal from fat; 0.55% total CLA by weight) amounts. In an effort to extend these findings, we then fed rats high (60% kcal) amounts of SARA or non-SARA butter for a longer duration (8 weeks) and assessed changes in whole body glucose, insulin and pyruvate tolerance in comparison to low fat and 60% lard conditions. There was a main effect for increased fasting blood glucose and insulin in SARA vs. non-SARA butter groups after 4 weeks of feeding (p < 0.05). However, blood glucose and insulin concentration, and maximal insulin-stimulated glucose uptake in skeletal muscle were similar in all groups. Following 8 weeks of feeding, insulin tolerance was impaired by the SARA butter, but not glucose or pyruvate tolerance. The non-SARA butter did not impair tolerance to glucose, insulin or pyruvate. This study suggests that increasing the consumption of a naturally enriched CLAt10,c12 source, at least in rats, has minimal impact on whole body glucose tolerance or muscle specific insulin response.

FFA2 Contribution to Gestational Glucose Tolerance Is Not Disrupted by Antibiotics.

PubMed

Fuller, Miles; Li, Xiaoran; Fisch, Robert; Bughara, Moneb; Wicksteed, Barton; Kovatcheva-Datchary, Petia; Layden, Brian T

2016-01-01

During the insulin resistant phase of pregnancy, the mRNA expression of free fatty acid 2 receptor (Ffar2) is upregulated and as we recently reported, this receptor contributes to insulin secretion and pancreatic beta cell mass expansion in order to maintain normal glucose homeostasis during pregnancy. As impaired gestational glucose levels can affect metabolic health of offspring, we aimed to explore the role of maternal Ffar2 expression during pregnancy on the metabolic health of offspring and also the effects of antibiotics, which have been shown to disrupt gut microbiota fermentative activity (the source of the FFA2 ligands) on gestational glucose homeostasis. We found that maternal Ffar2 expression and impaired glucose tolerance during pregnancy had no effect on the growth rates, ad lib glucose and glucose tolerance in the offspring between 3 and 6 weeks of age. To disrupt short chain fatty acid production, we chronically treated WT mice and Ffar2-/- mice with broad range antibiotics and further compared their glucose tolerance prior to pregnancy and at gestational day 15, and also quantified cecum and plasma SCFAs. We found that during pregnancy antibiotic treatment reduced the levels of SCFAs in the cecum of the mice, but resulted in elevated levels of plasma SCFAs and altered concentrations of individual SCFAs. Along with these changes, gestational glucose tolerance in WT mice, but not Ffar2-/- mice improved while on antibiotics. Additional data showed that gestational glucose tolerance worsened in Ffar2-/- mice during a second pregnancy. Together, these results indicate that antibiotic treatment alone is inadequate to deplete plasma SCFA concentrations, and that modulation of gut microbiota by antibiotics does not disrupt the contribution of FFA2 to gestational glucose tolerance.

The impact of low and no-caloric sweeteners on glucose absorption, incretin secretion, and glucose tolerance.

PubMed

Chan, Catherine B; Hashemi, Zohre; Subhan, Fatheema B

2017-08-01

The consumption of non-nutritive, low, or no-calorie sweeteners (LCS) is increasing globally. Previously thought to be physiologically inert, there is a growing body of evidence that LCS not only provide a sweet taste but may also elicit metabolic effects in the gastrointestinal tract. This review provides a brief overview of the chemical and receptor-binding properties and effects on chemosensation of different LCS but focuses on the extent to which LCS stimulates glucose transport, incretin and insulin secretion, and effects on glucose tolerance. Aspartame and sucralose both bind to a similar region of the sweet receptor. For sucralose, the data are contradictory regarding effects on glucose tolerance in humans and may depend on the food or beverage matrix and the duration of administration, as suggested by longer term rodent studies. For aspartame, there are fewer data. On the other hand, acesulfame-potassium (Ace-K) and saccharin have similar binding characteristics to each other but, while Ace-K may increase incretin secretion and glucose responses in humans, there are no data on saccharin except in rats, which show impaired glucose tolerance after chronic administration. Additional research, particularly of the effects of chronic consumption, is needed to provide concrete evidence for beneficial or detrimental effects of LCS on blood glucose regulation in humans.

Risk of chronic kidney disease in young adults with impaired glucose tolerance/impaired fasting glucose: a retrospective cohort study using electronic primary care records.

PubMed

Jadhakhan, Ferozkhan; Marshall, Tom; Ryan, Ronan; Gill, Paramjit

2018-02-26

The risk of chronic kidney disease (CKD) is known to be elevated in patients with diabetes mellitus but the risk of young adults aged 18 to 40 years with impaired glucose tolerance/impaired fasting glucose (IGT/IFG) developing CKD is not well characterised. Furthermore, progression of IGT/IFG to diabetes and subsequent CKD development is not well understood. A retrospective cohort study was undertaken using The Health Improvement Network (THIN) database, a large dataset of electronic patient records. THIN database is jointly managed by IMS Health Real World Evidence Solution ( http://www.epic-uk.org/index.html ) and In Practice System (InPs). Cases were aged 18 to 40, with a diagnosis of IGT/IFG and registered at a practice contributing to THIN between 2000 and 2015. The study population consisted of 40,092 patients, including 21,454 (53.5%) female and 18,638 (46.5%) male. The median follow-up was approximately 2 years. The outcome was a diagnosis of CKD determined from either clinical coding or laboratory results. For the primary analysis the unadjusted and adjusted relative risk of CKD in IGT/IFG was compared to age, sex and practice matched controls with normoglycaemia. For the secondary analysis we compared the incidence of CKD before to after a diagnosis of type 2 diabetes (T2DM) in the IGT/IFG study cohort. The Incidence Rate Ratio (IRR) for CKD for IGT/IFG compared to normoglycaemia was 4.0 [95% confidence interval (CI), 3.2 to 5.1, P < 0.001]. The adjusted IRR was 2.6 [95% CI, 2.0 to 3.4, P < 0.001]. The unadjusted IRR was 8.8 [95% CI, 7.7 to 10.0, P < 0.001] after IGT/IFG patients had developed T2DM and the adjusted IRR was 6.3 [95% CI, 5.5 to 7.2, P < 0.001]. Our results show that young IGT/IFG subjects are also at higher risk of developing CKD. This risk is modulated by the degree of baseline renal function and glucose tolerance, being higher in those developing T2DM.

Prevalence of diabetes, impaired fasting glucose and impaired glucose tolerance in patients with thalassemia major in Iran: A meta-analysis study

PubMed Central

Azami, Milad; Sharifi, Ali; Norozi, Siros; Mansouri, Akram; Sayehmiri, Kourosh

2017-01-01

Background: This study aimed to investigate the prevalence of diabetes, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in Iranian patients with thalassemia major. Methods: The current study has been conducted based on PRISMA guideline. To obtain the documents, Persian and English scientific databases such as Magiran, Iranmedex, SID, Medlib, IranDoc, Scopus, PubMed, ScienceDirect, Cochrane, Web of Science, Springer, Wiley Online Library as well as Google Scholar were searched until December 2015. All steps of the study were conducted by two authors independently. To the high heterogeneity of the studies, the random effect model was used to combine studies. Data were analyzed using STATA Version 11.1 software. Results: Thirty-two studies involving 3959 major thalassemia patients with mean age of 16.83 years were included in the meta-analysis. The prevalence of diabetes in Iranian patients with thalassemia major was estimated as 9% (95% CI: 6.8-10.5) and estimated rate was 12.6% (95% CI: 6.1-19.1) for males and 10.8% (95% CI: 8.2-14.5) for females. The prevalence of IFG and IGT were 12.9% (95% CI: 7-18.8) and 9.6% (95% CI: 6.6-12.5) respectively. No relationship between serum ferritin and development of diabetes was noted. Conclusion: The prevalence of diabetes, IFG, and IGT in patients with thalassemia major in Iran is high and accordingly requires new management strategies and policies to minimize endocrine disorders in Iranian patients with thalassemia major. Screening of patients for the early diagnosis of endocrine disorders particularly diabetes, IFG, and IGT is recommended. PMID:28503277

Assessment of Insulin Resistance and Impaired Glucose Tolerance in Lean Women with Polycystic Ovary Syndrome

PubMed Central

Bailey, Amelia Purser; Pastore, Lisa M.

2011-01-01

Abstract Objective To analyze insulin resistance (IR) and determine the need for a 2-hour oral glucose tolerance test (OGTT) for the identification of IR and impaired glucose tolerance (IGT) in lean nondiabetic women with polycystic ovary syndrome (PCOS). Methods This was a cross-sectional analysis of treatment-naive women with PCOS who enrolled in a university-based clinical trial. Nondiabetic women with PCOS based on the Eunice Kennedy Shriven National Institute of Child Health and Human Development (NICHD) definition, aged 18–43 years and weighing ≤113 kg, were evaluated. Glucose and insulin levels were assessed at times 0, 30, 60, 90, and 120 minutes after a 75-g glucose load. Lean was defined as body mass index (BMI) <25 kg/m2. Multiple linear regression was performed. Results A cohort of 78 women was studied. The prevalence of IR was 0% among lean women vs. 21% among nonlean subjects based on fasting insulin I0 and 40%–68% based on two different homeostatic model assessment (HOMA) cutoff points (p < 0.005). All women with IR had a BMI ≥ 28. Controlling for age and race, BMI explained over 57% of the variation in insulin fasting (Io), glucose fasting/Io (Go/Io), the qualitative insulin sensitivity check index (QUICKI), and HOMA and was a highly significant predictor of these outcomes (p < 0.0001). Only 1 of 31 (3%) of the lean PCOS women had IGT based on a 2-hour OGTT, and no lean subjects had IGT based on their fasting blood glucose. Conclusions Diabetes mellitus, IGT, and IR are far less common in young lean women with PCOS compared with obese women with PCOS. These data imply that it is unnecessary to routinely perform either IR testing or 2-hour OGTT in lean women with PCOS; however, greater subject accumulation is needed to determine if OGTT is necessary in lean women with PCOS. BMI is highly predictive of both insulin and glucose levels in women with PCOS. PMID:21194310

Assessment of insulin resistance and impaired glucose tolerance in lean women with polycystic ovary syndrome.

PubMed

Stovall, Dale William; Bailey, Amelia Purser; Pastore, Lisa M

2011-01-01

To analyze insulin resistance (IR) and determine the need for a 2-hour oral glucose tolerance test (OGTT) for the identification of IR and impaired glucose tolerance (IGT) in lean nondiabetic women with polycystic ovary syndrome (PCOS). This was a cross-sectional analysis of treatment-naive women with PCOS who enrolled in a university-based clinical trial. Nondiabetic women with PCOS based on the Eunice Kennedy Shriven National Institute of Child Health and Human Development (NICHD) definition, aged 18-43 years and weighing ≤113 kg, were evaluated. Glucose and insulin levels were assessed at times 0, 30, 60, 90, and 120 minutes after a 75-g glucose load. Lean was defined as body mass index (BMI) <25 kg/m(2). Multiple linear regression was performed. A cohort of 78 women was studied. The prevalence of IR was 0% among lean women vs. 21% among nonlean subjects based on fasting insulin I(0) and 40%-68% based on two different homeostatic model assessment (HOMA) cutoff points (p < 0.005). All women with IR had a BMI ≥ 28. Controlling for age and race, BMI explained over 57% of the variation in insulin fasting (I(o)), glucose fasting/Io (G(o)/I(o)), the qualitative insulin sensitivity check index (QUICKI), and HOMA and was a highly significant predictor of these outcomes (p < 0.0001). Only 1 of 31 (3%) of the lean PCOS women had IGT based on a 2-hour OGTT, and no lean subjects had IGT based on their fasting blood glucose. Diabetes mellitus, IGT, and IR are far less common in young lean women with PCOS compared with obese women with PCOS. These data imply that it is unnecessary to routinely perform either IR testing or 2-hour OGTT in lean women with PCOS; however, greater subject accumulation is needed to determine if OGTT is necessary in lean women with PCOS. BMI is highly predictive of both insulin and glucose levels in women with PCOS.

Clinical Neuropathy Scales in Neuropathy Associated with Impaired Glucose Tolerance

PubMed Central

Zilliox, Lindsay A.; Ruby, Sandra K.; Singh, Sujal; Zhan, Min; Russell, James W.

2015-01-01

AIMS Disagreement exists on effective and sensitive outcome measures in neuropathy associated with impaired glucose tolerance (IGT). Nerve conduction studies and skin biopsies are costly, invasive and may have their problems with reproducibility and clinical applicability. A clinical measure of neuropathy that has sufficient sensitivity and correlates to invasive measures would enable significant future research. METHODS Data was collected prospectively on patients with IGT and symptomatic early neuropathy (neuropathy symptoms < 2 years) and normal controls. The seven scales that were examined were the Neuropathy Impairment Score of the Lower Limb (NIS-LL), Michigan Diabetic Neuropathy Score (MNDS), modified Toronto Clinical Neuropathy Scale (mTCNS), Total Neuropathy Score (Clinical) (TNSc), The Utah Early Neuropathy Scale (UENS), the Early Neuropathy Score (ENS), and the Neuropathy Disability Score (NDS). RESULTS All seven clinical scales were determined to be excellent in discriminating between patients with neuropathy from controls without neuropathy. The strongest discrimination was seen with the mTCNS. The best sensitivity and specificity for the range of scores obtained, as determined by using receiver operating characteristic curves, was seen for the mTCNS followed by the TNSc. Most scales show a stronger correlation with measures of large than small fiber neuropathy. CONCULSIONS All seven scales identify patients with neuropathy. For the purpose of screening potential patients for a clinical study, the mTCNS followed by the TNSc would be most helpful to select patients with neuropathy. PMID:25690405

Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study.

PubMed

Huang, Feng; Dong, Jianxun; Kong, Jian; Wang, Hongcai; Meng, Hong; Spaeth, Rosa B; Camhi, Stephanie; Liao, Xing; Li, Xia; Zhai, Xu; Li, Shaoyuan; Zhu, Bing; Rong, Peijing

2014-06-26

Impaired glucose tolerance (IGT) is a pre-diabetic state of hyperglycemia that is associated with insulin resistance, increased risk of type II diabetes, and cardiovascular pathology. Recently, investigators hypothesized that decreased vagus nerve activity may be the underlying mechanism of metabolic syndrome including obesity, elevated glucose levels, and high blood pressure. In this pilot randomized clinical trial, we compared the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) and sham taVNS on patients with IGT. 72 participants with IGT were single-blinded and were randomly allocated by computer-generated envelope to either taVNS or sham taVNS treatment groups. In addition, 30 IGT adults were recruited as a control population and not assigned treatment so as to monitor the natural fluctuation of glucose tolerance in IGT patients. All treatments were self-administered by the patients at home after training at the hospital. Patients were instructed to fill in a patient diary booklet each day to describe any side effects after each treatment. The treatment period was 12 weeks in duration. Baseline comparison between treatment and control group showed no difference in weight, BMI, or measures of systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), or glycosylated hemoglobin (HbAlc). 100 participants completed the study and were included in data analysis. Two female patients (one in the taVNS group, one in the sham taVNS group) dropped out of the study due to stimulation-evoked dizziness. The symptoms were relieved after stopping treatment. Compared with sham taVNS, taVNS significantly reduced the two-hour glucose tolerance (F(2) = 5.79, p = 0.004). In addition, we found that taVNS significantly decreased (F(1) = 4.21, p = 0.044) systolic blood pressure over time compared with sham taVNS. Compared with the no-treatment control group, patients receiving taVNS significantly

Chromium effects on glucose tolerance and insulin sensitivity in persons at risk for diabetes mellitus.

PubMed

Ali, Ather; Ma, Yingying; Reynolds, Jesse; Wise, John Pierce; Inzucchi, Silvio E; Katz, David L

2011-01-01

To investigate the effects of daily chromium picolinate supplementation on serum measures of glucose tolerance and insulin sensitivity in patients at high risk for type 2 diabetes mellitus. We conducted a randomized, double-blind, placebo-controlled, modified cross-over clinical trial with 6-month sequences of intervention and placebo followed by a 6-month postintervention assessment. Adult patients with impaired fasting glucose, impaired glucose tolerance, or metabolic syndrome were enrolled. Participants received 6-month sequences of chromium picolinate or placebo at 1 of 2 dosages (500 or 1000 mcg daily). Primary outcome measures were change in fasting plasma glucose, 2-hour plasma glucose during oral glucose tolerance testing, fasting and 2-hour insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes included anthropometric measures, blood pressure, endothelial function, hemoglobin A1c, lipids, and urinary microalbumin. Fifty-nine participants were enrolled. No changes were seen in glucose level, insulin level, or HOMA-IR (all P>.05) after 6 months of chromium at either dosage level (500 mcg or 1000 mcg daily) when compared with placebo. None of the secondary outcomes improved with either chromium dosage compared with placebo (P>.05). Chromium supplementation does not appear to ameliorate insulin resistance or impaired glucose metabolism in patients at risk for type 2 diabetes and thus is unlikely to attenuate diabetes risk.

Abnormal glucose tolerance post-gestational diabetes mellitus as defined by the International Association of Diabetes and Pregnancy Study Groups criteria.

PubMed

Noctor, Eoin; Crowe, Catherine; Carmody, Louise A; Saunders, Jean A; Kirwan, Breda; O'Dea, Angela; Gillespie, Paddy; Glynn, Liam G; McGuire, Brian E; O'Neill, Ciarán; O'Shea, P M; Dunne, F P

2016-10-01

An increase in gestational diabetes mellitus (GDM) prevalence has been demonstrated across many countries with adoption of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria. Here, we determine the cumulative incidence of abnormal glucose tolerance among women with previous GDM, and identify clinical risk factors predicting this. Two hundred and seventy women with previous IADPSG-defined GDM were prospectively followed up for 5years (mean 2.6) post-index pregnancy, and compared with 388 women with normal glucose tolerance (NGT) in pregnancy. Cumulative incidence of abnormal glucose tolerance (using American Diabetes Association criteria for impaired fasting glucose, impaired glucose tolerance and diabetes) was determined using the Kaplan-Meier method of survival analysis. Cox regression models were constructed to test for factors predicting abnormal glucose tolerance. Twenty-six percent of women with previous GDM had abnormal glucose tolerance vs 4% with NGT, with the log-rank test demonstrating significantly different survival curves (P<0.001). Women meeting IADPSG, but not the World Health Organization (WHO) 1999 criteria, had a lower cumulative incidence than women meeting both sets of criteria, both in the early post-partum period (4.2% vs 21.7%, P<0.001) and at longer-term follow-up (13.7% vs 32.6%, P<0.001). Predictive factors were glucose levels on the pregnancy oral glucose tolerance test, family history of diabetes, gestational week at testing, and BMI at follow-up. The proportion of women developing abnormal glucose tolerance remains high among those with IADPSG-defined GDM. This demonstrates the need for continued close follow-up, although the optimal frequency and method needs further study. © 2016 European Society of Endocrinology.

Identical anthropometric characteristics of impaired fasting glucose combined with impaired glucose tolerance and newly diagnosed type 2 diabetes: anthropometric indicators to predict hyperglycaemia in a community-based prospective cohort study in southwest China

PubMed Central

Zhang, Fang; Wan, Qin; Cao, Hongyi; Tang, Lizhi; Li, Daigang; Lü, Qingguo; Yan, Zhe; Li, Jing; Yang, Qiu; Zhang, Yuwei; Tong, Nanwei

2018-01-01

Objectives To assess the anthropometric characteristics of normoglycaemic individuals who subsequently developed hyperglycaemia, and to evaluate the validity of these measures to predict prediabetes and diabetes. Design A community-based prospective cohort study. Participants In total, 1885 residents with euglycaemia at baseline from six communities were enrolled. Setting Sichuan, southwest China. Primary outcome measures The incidences of prediabetes and diabetes were the primary outcomes. Methods The waist-to-height ratio (WHtR), body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) of all participants were measured at baseline and during follow-up. A 75 g glucose oral glucose tolerance test was conducted at each survey. Results During a median of 3.00 (IQR: 2.92–4.17) years follow-up, the cumulative incidence of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), IFG combined with IGT (IFG+IGT), and newly diagnosed diabetes mellitus (NDDM) were 8.44%, 18.14%, 8.06% and 13.79%, respectively. WHtR, BMI, WC and WHR were significantly different among subjects who subsequently progressed to isolated IFG or IGT, IFG+IGT or NDDM (p<0.05). The anthropometric characteristics of IFG+IGT subjects were similar to those of the NDDM population (p>0.005). All the baseline anthropometric measurements were useful for the prediction of future prediabetes and NDDM (p<0.05). The optimal thresholds for the four measurements were calculated for the prediction of hyperglycaemia, with a WHtR value of 0.52 performing best to identify isolated IFG or IGT, IFG+IGT and NDDM. Conclusions Anthropometric measures, especially WHtR, could be used to predict hyperglycaemia 3 years in advance. Distinct from isolated IFG and IGT, the individuals who developed combined IFG+IGT had identical anthropometric profiles to those who progressed to NDDM. PMID:29743321

Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance

PubMed Central

Eriksson, Maria J.; Fritz, Tomas; Nyberg, Gunnar; Östenson, Claes Göran; Krook, Anna; Zierath, Juleen R.; Caidahl, Kenneth

2015-01-01

To determine whether Nordic walking improves cardiovascular function in middle-aged women and men, we included 121 with normal glucose tolerance, 33 with impaired glucose tolerance and 47 with Type 2 diabetes mellitus in a randomized controlled study. The intervention group added Nordic walking 5 h/week for 4 months to their ordinary activities. Aortic pulse wave velocity, aortic augmentation index, stiffness index, reflection index, intima–media thickness in the radial and carotid arteries, echogenicity of the carotid intima–media and systemic vascular resistance were measured. While baseline blood pressure did not differ by gender or diagnosis, aortic augmentation index was found to be higher in women in all groups. Vascular function was unchanged with intervention, without differences by gender or diagnosis. In conclusion, 4 months of Nordic walking is an insufficient stimulus to improve vascular function. Future studies should consider hard endpoints in addition to measures of vascular health, as well as larger population groups, long-term follow-up and documented compliance to exercise training. PMID:26092821

Detection of impaired glucose tolerance and undiagnosed type 2 diabetes in UK South Asians: an effective screening strategy.

PubMed

Hanif, M W; Valsamakis, G; Dixon, A; Boutsiadis, A; Jones, A F; Barnett, A H; Kumar, S

2008-09-01

We tested a stepwise, community-based screening strategy for glucose intolerance in South Asians using a health questionnaire in conjunction with body mass index (BMI). Anthropometric measurements (waist and hip circumference, sagittal diameter and percentage body fat) were then conducted in a hospital setting followed by an oral glucose tolerance test (OGTT) to identify subjects at the highest risk and analyse the factors predicting that risk. A health questionnaire was administered to 435 subjects in a community setting and BMI was measured. Subjects were graded by a risk score based on the health questionnaire as high, medium and low. Subjects with high and medium risk scores and a representative sample of those with low scores had anthropometric measurements in hospital followed by an OGTT. In total, 205 (47%) of the subjects had an OGTT performed. In total, 48.7% of the subjects tested with an OGTT had evidence of glucose dysregulation: 20% had diabetes and 28.7% had impaired glucose tolerance (IGT). Logistic regression model explained 49.1% of the total variability. The significant predictors of diabetes and IGT were Blood Glucose Monitoring Strips (BMI), random blood glucose (BM), sibling with diabetes and presence of diagnosed hypertension or ischaemic disease. Most of these predictors along with other heredity diabetes factors create a composite score, with high predictability, as the receiver operating curve analysis shows. We describe a simple, stepwise strategy in a community setting, based on a health questionnaire and anthropometric measurements, to explain about 50% of cases with IGT and diabetes and diagnose about 50% of cases from the population screened. We have also identified factors that predict the risk.

Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism

PubMed Central

van der Zijl, Nynke J.; Moors, Chantalle C.M.; Goossens, Gijs H.; Hermans, Marc M.H.; Blaak, Ellen E.; Diamant, Michaela

2011-01-01

OBJECTIVE Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex. RESULTS Valsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P < 0.001). BMI remained unchanged in both treatment groups (P = 0.89). CONCLUSIONS Twenty-six weeks of valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of

Reduction in reactive oxygen species production by mitochondria from elderly subjects with normal and impaired glucose tolerance.

PubMed

Ghosh, Sangeeta; Lertwattanarak, Raweewan; Lefort, Natalie; Molina-Carrion, Marjorie; Joya-Galeana, Joaquin; Bowen, Benjamin P; Garduno-Garcia, Jose de Jesus; Abdul-Ghani, Muhammad; Richardson, Arlan; DeFronzo, Ralph A; Mandarino, Lawrence; Van Remmen, Holly; Musi, Nicolas

2011-08-01

Aging increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes. It has been proposed that increased reactive oxygen species (ROS) generation by dysfunctional mitochondria could play a role in the pathogenesis of these metabolic abnormalities. We examined whether aging per se (in subjects with normal glucose tolerance [NGT]) impairs mitochondrial function and how this relates to ROS generation, whether older subjects with IGT have a further worsening of mitochondrial function (lower ATP production and elevated ROS generation), and whether exercise reverses age-related changes in mitochondrial function. Mitochondrial ATP and ROS production were measured in muscle from younger individuals with NGT, older individuals with NGT, and older individuals with IGT. Measurements were performed before and after 16 weeks of aerobic exercise. ATP synthesis was lower in older subjects with NGT and older subjects with IGT versus younger subjects. Notably, mitochondria from older subjects (with NGT and IGT) displayed reduced ROS production versus the younger group. ATP and ROS production were similar between older groups. Exercise increased ATP synthesis in the three groups. Mitochondrial ROS production also increased after training. Proteomic analysis revealed downregulation of several electron transport chain proteins with aging, and this was reversed by exercise. Old mitochondria from subjects with NGT and IGT display mitochondrial dysfunction as manifested by reduced ATP production but not with respect to increased ROS production. When adjusted to age, the development of IGT in elderly individuals does not involve changes in mitochondrial ATP and ROS production. Lastly, exercise reverses the mitochondrial phenotype (proteome and function) of old mitochondria.

Variation of glucose tolerance in adult patients with cystic fibrosis: What is the potential contribution of insulin sensitivity?

PubMed

Boudreau, Valérie; Coriati, Adèle; Hammana, Imane; Ziai, Sophie; Desjardins, Katherine; Berthiaume, Yves; Rabasa-Lhoret, Rémi

2016-11-01

Reduced insulin secretion is a key factor to explain high prevalence of glucose intolerance in patients with cystic fibrosis (CF). However, the role of insulin sensitivity remains unclear. The aim of this study is to investigate the association of insulin secretion and sensitivity with the evolution of glucose tolerance. A total of 152 patients without known diabetes from the Montreal CF cohort underwent two 2-h oral glucose tolerance tests (OGTT) at baseline and again after 21.2±5.5months. Pulmonary function and anthropometric measurements were also collected at each visit. At both visits, based on their OGTT results, patients were categorized in glucose tolerance groups (normal glucose tolerance, impaired glucose tolerance or CF-related diabetes) and stratified in 3 groups according to the variation of their glucose tolerance: stable, improved or deteriorated. At baseline, patients in the deteriorated group had a better sensitivity to insulin than those in the improved group (P=0.029). At follow-up glucose tolerance remained stable in 55.3%, improved in 14.5% and deteriorated in 30.3% of patients. During follow-up, insulin secretion remained stable in all 3 groups. While insulin sensitivity remained stable in patients without changes in glucose tolerance it worsened in patients who deteriorated glucose tolerance (P<0.001) and improved in patients who improved their glucose tolerance (P=0.003). In a context of significantly reduced insulin secretion, variations of insulin sensitivity are associated with variations of glucose tolerance in adult patients with CF. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Circulating Betatrophin Correlates with Triglycerides and Postprandial Glucose among Different Glucose Tolerance Statuses--A Case-Control Study.

PubMed

Gao, Ting; Jin, Kairui; Chen, Peihong; Jin, Hua; Yang, Lili; Xie, Xinmiao; Yang, Meili; Hu, Cheng; Yu, Xuemei

2015-01-01

Previous researches of betatrophin on glucose and lipids metabolism under insulin-resistant condition have reached controversial conclusions. To further identify the possible impact of betatrophin, we measured the circulating betatrophin levels in newly diagnosed type 2 diabetes (T2DM) patients, and in subjects with both impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) and investigated the relationship between serum betatrophin and other clinical parameters in these patients with different glucose tolerance statuses. A total of 460 permanent residents of the Fengxian District, aged 40-60 years, were enrolled. Based on the results of a 75 g oral glucose tolerance test, we selected newly diagnosed T2DM (n = 50) patients and subjects with IGT (n = 51) and NGT (n = 50) according to their age, gender and body mass index (18-28 kg/m2). Anthropometric parameters, glycosylated haemoglobin, blood lipids and fasting insulin were measured. Serum betatrophin concentrations were determined via ELISA. Serum betatrophin levels in T2DM patients were increased significantly compared with IGT and NGT groups, and decreased in subjects with better islet beta cell function. Serum betatrophin was positively correlated with triglyceride, 2-hour postprandial glucose, alanine aminotransferase and aspartate transaminase after adjusting for age, sex and body mass index in all subjects. Multiple regression analysis showed that 2-hour postprandial glucose was independently associated with serum betatrophin significantly. Circulating betatrophin is increased in newly-diagnosed T2DM patients and positively correlated with the triglycerides and postprandial glucose levels. The results suggest that betatrophin may participate in glucose and triglycerides metabolism.

β-Cell secretory defects are present in pancreatic insufficient cystic fibrosis with 1-hour oral glucose tolerance test glucose ≥155 mg/dL.

PubMed

Nyirjesy, Sarah C; Sheikh, Saba; Hadjiliadis, Denis; De Leon, Diva D; Peleckis, Amy J; Eiel, Jack N; Kubrak, Christina; Stefanovski, Darko; Rubenstein, Ronald C; Rickels, Michael R; Kelly, Andrea

2018-06-08

Patients with pancreatic insufficient cystic fibrosis (PI-CF) meeting standard criteria for normal glucose tolerance display impaired β-cell secretory capacity and early-phase insulin secretion defects. We sought evidence of impaired β-cell secretory capacity, a measure of functional β-cell mass, among those with early glucose intolerance (EGI), defined as 1-hour oral glucose tolerance test (OGTT) glucose ≥155 mg/dL (8.6 mmol/L). A cross-sectional study was conducted in the Penn and CHOP Clinical & Translational Research Centers. PI-CF categorized by OGTT as normal (PI-NGT: 1-hour glucose <155 mg/dL and 2-hour <140 mg/dL [7.8 mmol/L]; n = 13), PI-EGI (1-hour ≥155 mg/dL and 2-hour <140 mg/dL; n = 13), impaired (PI-IGT: 2-hour ≥140 and <200 mg/dL [11.1 mmol/L]; n = 8), and diabetic (cystic fibrosis-related diabetes, CFRD: 2-hour ≥200 mg/dL; n = 8) participated. Post-prandial glucose tolerance and insulin secretion, and β-cell secretory capacity and demand were derived from mixed-meal tolerance tests (MMTTs), and glucose-potentiated arginine (GPA) tests, respectively. PI-EGI had elevated post-prandial glucose with reduced early-phase insulin secretion during MMTT compared to PI-NGT (P < .05). PI-EGI also exhibited impaired acute insulin and C-peptide responses to GPA (P < .01 vs PI-NGT), measures of β-cell secretory capacity. Proinsulin secretory ratios were higher under hyperglycemic clamp conditions in PI-IGT and CFRD (P < .05 vs PI-NGT), and correlated with 1-hour glucose in PI-CF (P < .01). PI-CF patients with 1-hour OGTT glucose ≥155 mg/dL already manifest impaired β-cell secretory capacity with associated early-phase insulin secretion defects. Avoiding hyperglycemia in patients with EGI may be important for preventing excessive insulin demand indicated by disproportionately increased proinsulin secretion. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oral glucose tolerance test significantly impacts the prevalence of abnormal glucose tolerance among Indian women with polycystic ovary syndrome: lessons from a large database of two tertiary care centers on the Indian subcontinent.

PubMed

Ganie, Mohd Ashraf; Dhingra, Atul; Nisar, Sobia; Sreenivas, Vishnubhatla; Shah, Zaffar Amin; Rashid, Aafia; Masoodi, Shariq; Gupta, Nandita

2016-01-01

To estimate the prevalence of abnormal glucose tolerance (AGT) among Indian women with polycystic ovary syndrome (PCOS) and analyze the role of oral glucose tolerance (OGTT) test on its estimation. Cross-sectional clinical study. Tertiary care center. A total of 2,014 women with PCOS diagnosed on the basis of the Rotterdam 2003 criteria were enrolled, and the data of 1,746 subjects were analyzed. In addition to recording clinical, biochemical, and hormone parameters, a 75 g OGTT was administered. Prevalence of AGT and impact of age, body mass index (BMI), family history, and OGTT on its prevalence. The mean age of subjects was 23.8 ± 5.3 years, with a mean BMI of 24.9 ± 4.4 kg/m(2). The overall prevalence of AGT was 36.3% (6.3% diabetes and 30% impaired fasting plasma glucose/impaired glucose tolerance) using American Diabetes Association criteria. The glucose intolerance showed a rising trend with advancing age (30.3%, 35.4%, 51%, and 58.8% in the second, third, fourth, and fifth decades, respectively) and increasing BMI. Family history of diabetes mellitus was present in 54.6% (953/1,746) subjects, and it did not correlate with any of the studied parameters except waist circumference and BMI. Sensitivity was better with 2-hour post-OGTT glucose values as compared with fasting plasma glucose, since using fasting plasma glucose alone would have missed the diagnosis in 107 (6.1%) subjects. We conclude that AGT is high among young Indian women with PCOS and that it is not predicted by family history of type 2 DM. OGTT significantly improves the detection rate of AGT among Indian women with PCOS. Copyright © 2016. Published by Elsevier Inc.

Clinical usefulness of the thickness of preperitoneal and subcutaneous fat layer in the abdomen estimated by ultrasonography for diagnosing abdominal obesity in each type of impaired glucose tolerance in man.

PubMed

Soyama, Akiko; Nishikawa, Tetsuo; Ishizuka, Toshiharu; Ito, Hiroko; Saito, Jun; Yagi, Kazuo; Saito, Yasushi

2005-04-01

For this study we enrolled 1,615 males who were admitted to our hospital for a general health check-up. Plasma glucose (PG) and insulin were measured during 75 g OGTT, and abdominal obesity was assessed by ultrasonography in all subjects. We divided them into several groups: normal glucose tolerance (NGT), high-normal glucose tolerance (h-NGT) who showed >10.0 nmol/l at 1 hr PG among those with NGT, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and DM, according to the results of 75 g OGTT. The aim of the present study was to clarify the clinical characteristics of pre-diabetic disorders relating to metabolic syndrome by comparing various parameters including body mass index (BMI), blood levels of various lipids and abdominal wall fat index (AFI) calculated from the thickness of preperitoneal (Pmax) and subcutaneous (Smin) fat layer in the abdomen estimated by ultrasonography with insulin sensitivity determined by homeostatic model assessment (HOMA-IR) in each type of abnormal glucose regulation as classified by PG changes in 75 g OGTT. We also investigated the relationship between insulin secretion capability and insulin sensitivity to delineate the characteristics of each type of abnormal glucose regulation, and compared the area under the insulin curve (AUCins) and the time axis, and the ability of early insulin secretion by glucose loading (insulinogenic index: I.I.) in each type of abnormal glucose regulation. There was a significant positive correlation between HOMA-IR and Smin or Pmax, suggesting that Smin and Pmax may reflect insulin sensitivity. Abdominal obesity, which was diagnosed from the data of AFI, was present in the h-NGT and IFG + IGT groups, suggesting that those groups belong to the clinical entity of metabolic syndrome. HOMA-IR was higher in IFG than in IGT, although I.I. was reduced and AUCins was increased in IFG as well as in IGT. h-NGT demonstrated a slightly lower I.I. and higher AUCins, compared with IGT

The Fruiting Bodies, Submerged Culture Biomass, and Acidic Polysaccharide Glucuronoxylomannan of Yellow Brain Mushroom Tremella mesenterica Modulate the Immunity of Peripheral Blood Leukocytes and Splenocytes in Rats with Impaired Glucose Tolerance

PubMed Central

Hsu, Tai-Hao; Lee, Chien-Hsing; Lin, Fang-Yi; Wasser, Solomon P.; Lo, Hui-Chen

2014-01-01

The prevalence of diabetes mellitus (DM), a chronic disease with hyperglycemia and impaired immune function, is increasing worldwide. Progression from impaired glucose tolerance (IGT) to type 2 DM has recently become a target for early intervention. The fruiting bodies (FB) and submerged culture mycelium (CM) of Tremella mesenterica, an edible and medicinal mushroom, have been demonstrated to have antihyperglycemic and immunomodulatory activities in type 1 DM rats. Herein, we investigated the effects of acidic polysaccharide glucuronoxylomannan (GX) extracted from CM on the immunocyte responses. Male Wistar rats were injected with streptozotocin (65 mg/kg) plus nicotinamide (200 mg/kg) for the induction of IGT, and gavaged daily with vehicle, FB, CM, or GX (1 g/kg/day). Rats injected with saline and gavaged vehicle were used as controls. Two weeks later, peripheral blood leukocytes (PBLs) and splenocytes were collected. Ingestion of FB, CM, and GX significantly decreased blood glucose levels in the postprandial period and in oral glucose tolerance test, and partially reversed T-splenocytic proliferation in IGT rats. CM significantly decreased T-helper lymphocytes in the PBLs and B-splenocytes. In addition, FB, CM, and GX significantly reversed the IGT-induced decreases in tumor necrosis factor-α production; GX significantly increased interleukin-6 production in T-lymphocytes in the PBLs and splenocytes; and CM and GX significantly reversed IGT-induced decrease in interferon-γ production in T-lymphocytes in the spleen. In conclusion, FB, CM, and acidic polysaccharide GX of T. mesenterica may increase T-cell immunity via the elevation of proinflammatory and T-helper cytokine production in rats with impaired glucose tolerance. PMID:24872934

Altered microRNA expression during Impaired Glucose Tolerance and High-fat Diet Feeding.

PubMed

Pheiffer, Carmen; Dias, Stephanie; Willmer, Tarryn; Pace, Ryan; Aagaard, Kjersti; Louw, Johan

2018-06-11

MicroRNAs (miRNAs) play a critical role in metabolic regulation. Recently, we identified novel miRNAs in the whole blood of South African women of mixed ethnic ancestry. The aim of this study was to investigate whether five of these novel miRNAs are expressed in serum and whether their expression is altered during metabolic dysregulation. Expression levels of the five novel miRNAs (MYN08, MYNO22, MYN059, MYNO66 and MYNO95) were measured in the serum of women with Impaired Glucose Tolerance (IGT) and Normoglycemia (NGT) (n=24), and in the whole blood of vervet monkeys fed a high-fat or standard diet (n=16) using quantitative real-time PCR. Only three of the selected novel miRNAs (MYNO8, MYNO22 and MYNO66) were expressed in serum. The expression of MYN08 and MYNO22 were associated with fasting glucose and insulin concentrations, decreased during IGT and able to predict IGT. The expression of these miRNAs were similarly decreased in vervet monkeys fed a high-fat diet. In silico analysis identified a total of 291 putative messenger RNA targets for MYNO8 and MYNO22, including genes involved in gluconeogenesis, carbohydrate metabolism, glucose homeostasis and lipid transport. Two novel miRNAs, MYNO8 and MYNO22, are associated with metabolic dysregulation in South African women of mixed ethnic ancestry and with high-fat diet feeding in vervet monkeys. Furthermore, putative gene targets were enriched in biological processes involved in key aspects of glucose regulation, which strengthens the candidacy of these miRNAs as biomarkers for dysglycemia, and warranting further studies to assess their clinical applicability. © Georg Thieme Verlag KG Stuttgart · New York.

Prevalence of abnormal glucose tolerance and risk factors in urban and rural Malaysia.

PubMed

Mustafa, Norlaila; Kamarudin, Nor Azmi; Ismail, Ab Aziz; Khir, Amir Sharifuddin; Ismail, Ikram Shah; Musa, Kamarul Imran; Kadir, Khalid Abdul; Yaacob, Nor Azwany; Ali, Osman; Isa, Siti Harnida Md; Wan Bebakar, Wan Mohamad; wan Mohamud, Wan Nazaimoon

2011-06-01

To determine the prevalence of prediabetes and diabetes among rural and urban Malaysians. This cross-sectional survey was conducted among 3,879 Malaysian adults (1,335 men and 2,544 women). All subjects underwent the 75-g oral glucose tolerance test (OGTT). The overall prevalence of prediabetes was 22.1% (30.2% in men and 69.8% in women). Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were found in 3.4 and 16.1% of the study population, respectively, whereas 2.6% of the subjects had both IFG and IGT. Based on an OGTT, the prevalence of newly diagnosed type 2 diabetes was 12.6% (31.0% in men and 69.0% in women). The prediabetic subjects also had an increased prevalence of cardiovascular disease risk factors. The large proportion of undiagnosed cases of prediabetes and diabetes reflects the lack of public awareness of the disease.

Intermittent Hypoxia Impairs Glucose Homeostasis in C57BL6/J Mice: Partial Improvement with Cessation of the Exposure

PubMed Central

Polak, Jan; Shimoda, Larissa A.; Drager, Luciano F.; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y.; Punjabi, Naresh M.

2013-01-01

Objectives: Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. Interventions: C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Results: Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Conclusions: Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism. Citation: Polak J; Shimoda LA; Drager LF; Undem C; McHugh H; Polotsky VY; Punjabi NM

Effect of valsartan on kidney outcomes in people with impaired glucose tolerance.

PubMed

Currie, Gemma; Bethel, M Angelyn; Holzhauer, Björn; Haffner, Steven M; Holman, Rury R; McMurray, John J V

2017-06-01

To examine the effect of valsartan on kidney outcomes in patients with impaired glucose tolerance (IGT). In a double-blind randomized trial, 9306 patients with IGT were assigned to valsartan (160 mg daily) or placebo. The co-primary endpoints were the development of diabetes and two composite cardiovascular outcomes. Prespecified renal endpoints included: the composite of renal death, end-stage renal disease (ESRD) or doubling of serum creatinine; estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m 2 ; hospitalization for renal failure; and progression from normoalbuminuria to microalbuminuria, microalbuminuria to macroalbuminuria, and normoalbuminuria to macroalbuminuria. The median follow-up was 6.2 years. Valsartan reduced the incidence of diabetes but not cardiovascular events. In the valsartan group, 25/4631 patients (0.5%), vs 26/4675 (0.6%) patients in the placebo group, developed ESRD or experienced doubling of serum creatinine (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.55-1.66; P  = .87). Few patients in either group developed an eGFR of ≤30 mL/min/1.73 m 2 or had a renal hospitalization. Fewer patients on valsartan (237/4084 [5.8%]) than on placebo (342/4092 [8.4%]) developed microalbuminuria (HR 0.68, 95% CI 0.57-0.80; P  < .0001), and fewer valsartan-treated patients developed macroalbuminuria. Overall, urinary albumin-to-creatinine ratio (UACR) was 11% lower with valsartan (95% CI 8-13; P  < .0001) and 9% lower (95% CI 6-11; P  < .0001) after adjusting for both glucose and blood pressure. The effect of valsartan on UACR was not wholly explained by change in blood pressure or glucose. Valsartan reduced the incidence of microalbuminuria in IGT without increasing the incidence of hyperkalaemia or renal dysfunction compared with placebo. © 2017 John Wiley & Sons Ltd.

Experience with the high-intensity sweetener saccharin impairs glucose homeostasis and GLP-1 release in rats

PubMed Central

Swithers, Susan E.; Laboy, Alycia F.; Clark, Kiely; Cooper, Stephanie; Davidson, T.L.

2012-01-01

Previous work from our lab has demonstrated that experience with high-intensity sweeteners in rats leads to increased food intake, body weight gain and adiposity, along with diminished caloric compensation and decreased thermic effect of food. These changes may occur as a result of interfering with learned relations between the sweet taste of food and the caloric or nutritive consequences of consuming those foods. The present experiments determined whether experience with the high-intensity sweetener saccharin versus the caloric sweetener glucose affected blood glucose homeostasis. The results demonstrated that during oral glucose tolerance tests, blood glucose levels were more elevated in animals that had previously consumed the saccharin-sweetened supplements. In contrast, during glucose tolerance tests when a glucose solution was delivered directly into the stomach, no differences in blood glucose levels between the groups were observed. Differences in oral glucose tolerance responses were not accompanied by differences in insulin release; insulin release was similar in animals previously exposed to saccharin and those previously exposed to glucose. However, release of GLP-1 in response to an oral glucose tolerance test, but not to glucose tolerance tests delivered by gavage, was significantly lower in saccharin-exposed animals compared to glucose-exposed animals. Differences in both blood glucose and GLP-1 release in saccharin animals were rapid and transient, and suggest that one mechanism by which exposure to high-intensity sweeteners that interfere with a predictive relation between sweet tastes and calories may impair energy balance is by suppressing GLP-1 release, which could alter glucose homeostasis and reduce satiety. PMID:22561130

Circulating Betatrophin Correlates with Triglycerides and Postprandial Glucose among Different Glucose Tolerance Statuses—A Case-Control Study

PubMed Central

Chen, Peihong; Jin, Hua; Yang, Lili; Xie, Xinmiao; Yang, Meili; Hu, Cheng; Yu, Xuemei

2015-01-01

Purpose Previous researches of betatrophin on glucose and lipids metabolism under insulin-resistant condition have reached controversial conclusions. To further identify the possible impact of betatrophin, we measured the circulating betatrophin levels in newly diagnosed type 2 diabetes (T2DM) patients, and in subjects with both impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) and investigated the relationship between serum betatrophin and other clinical parameters in these patients with different glucose tolerance statuses. Methods A total of 460 permanent residents of the Fengxian District, aged 40–60 years, were enrolled. Based on the results of a 75 g oral glucose tolerance test, we selected newly diagnosed T2DM (n = 50) patients and subjects with IGT (n = 51) and NGT (n = 50) according to their age, gender and body mass index (18–28 kg/m2). Anthropometric parameters, glycosylated haemoglobin, blood lipids and fasting insulin were measured. Serum betatrophin concentrations were determined via ELISA. Results Serum betatrophin levels in T2DM patients were increased significantly compared with IGT and NGT groups, and decreased in subjects with better islet beta cell function. Serum betatrophin was positively correlated with triglyceride, 2-hour postprandial glucose, alanine aminotransferase and aspartate transaminase after adjusting for age, sex and body mass index in all subjects. Multiple regression analysis showed that 2-hour postprandial glucose was independently associated with serum betatrophin significantly. Conclusions Circulating betatrophin is increased in newly-diagnosed T2DM patients and positively correlated with the triglycerides and postprandial glucose levels. The results suggest that betatrophin may participate in glucose and triglycerides metabolism. PMID:26247824

Reduction in Reactive Oxygen Species Production by Mitochondria From Elderly Subjects With Normal and Impaired Glucose Tolerance

PubMed Central

Ghosh, Sangeeta; Lertwattanarak, Raweewan; Lefort, Natalie; Molina-Carrion, Marjorie; Joya-Galeana, Joaquin; Bowen, Benjamin P.; de Jesus Garduno-Garcia, Jose; Abdul-Ghani, Muhammad; Richardson, Arlan; DeFronzo, Ralph A.; Mandarino, Lawrence; Van Remmen, Holly; Musi, Nicolas

2011-01-01

OBJECTIVE Aging increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes. It has been proposed that increased reactive oxygen species (ROS) generation by dysfunctional mitochondria could play a role in the pathogenesis of these metabolic abnormalities. We examined whether aging per se (in subjects with normal glucose tolerance [NGT]) impairs mitochondrial function and how this relates to ROS generation, whether older subjects with IGT have a further worsening of mitochondrial function (lower ATP production and elevated ROS generation), and whether exercise reverses age-related changes in mitochondrial function. RESEARCH DESIGN AND METHODS Mitochondrial ATP and ROS production were measured in muscle from younger individuals with NGT, older individuals with NGT, and older individuals with IGT. Measurements were performed before and after 16 weeks of aerobic exercise. RESULTS ATP synthesis was lower in older subjects with NGT and older subjects with IGT versus younger subjects. Notably, mitochondria from older subjects (with NGT and IGT) displayed reduced ROS production versus the younger group. ATP and ROS production were similar between older groups. Exercise increased ATP synthesis in the three groups. Mitochondrial ROS production also increased after training. Proteomic analysis revealed downregulation of several electron transport chain proteins with aging, and this was reversed by exercise. CONCLUSIONS Old mitochondria from subjects with NGT and IGT display mitochondrial dysfunction as manifested by reduced ATP production but not with respect to increased ROS production. When adjusted to age, the development of IGT in elderly individuals does not involve changes in mitochondrial ATP and ROS production. Lastly, exercise reverses the mitochondrial phenotype (proteome and function) of old mitochondria. PMID:21677280

Ethnic differences in the prevalence of new and known diabetes mellitus, impaired glucose tolerance, and impaired fasting glucose. Diabetes Heart and Health Survey (DHAH) 2002-2003, Auckland New Zealand.

PubMed

Sundborn, Gerhard; Metcalf, Patricia; Scragg, Robert; Schaaf, David; Dyall, Lorna; Gentles, Dudley; Black, Peter; Jackson, Rodney

2007-06-29

To estimate the prevalence of new and known diabetes mellitus, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) by ethnic group in Auckland. The Diabetes Heart and Health Survey (DHAH) was a cross-sectional population based survey and was carried out in Auckland between January 2002 and December 2003, inclusive. Participants answered a self-administered questionnaire to assess whether they had previously diagnosed diabetes. Those participants who were not previously diagnosed with diabetes were then given a glucose tolerance test (GTT) to determine diabetes status. Of the total sample 6.7% were previously diagnosed (known) with type 2 diabetes, and a further 2.6% were newly diagnosed. Within the ethnic groups Europeans had the lowest level of both new and known diabetes followed by Maori and then Pacific people (mostly of Samoan, Tongan, Niuean, or Cook Islands origin). The proportions of new/known diabetes by ethnicity were 1.8%/3.9% for Europeans, 3.8%/12.0% for Maori, and 4.0%/19.5% for Pacific. Only Pacific were found to have a significantly greater relative risk (RR) than Europeans of being newly diagnosed with diabetes, particularly in the <45 (RR 11.6), and 45-54 year (RR 4.2) age groups. Compared to Europeans, Maori had a significantly greater risk of known diabetes in the 45-54 (RR 6.4) and 55-64 (RR 4.1) year age groups, while Pacific had a significantly greater risk in all age groups which ranged from RR 2.5 in those aged 65+ to RR 9.3 in the 55-64 year age group. For Europeans and Maori, the greatest proportions of diabetes occurred in the 65+ year age group, however for Pacific this occurred in the 55-64 year age group. IFG levels were only found to be significantly different from Europeans in Maori aged 45-54, and Pacific aged 45-54 and <45 years. IGT levels were only found to be significantly different from Europeans in Pacific aged 45-54 years. The prevalence of diabetes was 2.8 times greater for Maori, and 4.1 times greater for

Impaired glucose regulation is associated with poorer performance on the Stroop Task.

PubMed

Gluck, Marci E; Ziker, Cindy; Schwegler, Matthew; Thearle, Marie; Votruba, Susanne B; Krakoff, Jonathan

2013-10-02

Type 2 diabetes is a risk factor for development of cognitive dysfunction. Impairments in glucose regulation have been associated with poorer performance on tests of executive function and information processing speed. We administered the Stroop Color Word Task, where higher interference scores are indicative of decreased selective attention, to 98 non-diabetic volunteers (64 m; %fat=37 ± 12; age=36 ± 9 yrs, race=41 NA/30 C/13 H/14 AA) on our inpatient unit. After 3d on a weight maintaining diet, % body fat was measured by DXA and a 75 g oral glucose tolerance test (OGTT) was administered. Impaired glucose regulation (IGR) was defined as: fasting plasma glucose ≥ 100 and ≤ 125 mg/dL and/or 2h plasma glucose between ≥ 140 and ≤ 199 mg/dL (IGR; n=48; NGR; n=50). Total and incremental area under the curve (AUC) for insulin and glucose were calculated. Stroop interference scores were not significantly associated with any measure of adiposity or insulin concentrations. Individuals with IGR had significantly higher interference scores than those with normal glucose regulation (NGR; p=0.003). Higher interference scores were significantly correlated with fasting plasma glucose concentrations (r=0.26, p=0.007) and total glucose AUC (r=0.30, p=0.02) and only trending so for iAUC and 2h plasma glucose (r=0.18, p=0.08; r=0.17, p=0.09 respectively). In separate multivariate linear models, fasting plasma glucose (p=0.002) and total glucose AUC (p=0.0005) remained significant predictors of Stroop interference scores, even after adjustment for age, sex, race, education and %fat. Individuals with IGR had decreased performance on a test of selective attention. Fasting plasma glucose was more strongly associated with lower performance scores than 2h plasma glucose. Our results indicate that even mild hyperglycemia in the non-diabetic range is associated with attentional processing difficulties in a sample of younger adults. Whether these impairments precede or are induced

Low osteocalcin level is a risk factor for impaired glucose metabolism in a Chinese male population.

PubMed

Liang, Yaojie; Tan, Aihua; Liang, Danyan; Yang, Xiaobo; Liao, Ming; Gao, Yong; Jiang, Yonghua; Yao, Ziting; Lin, Xinggu; Lu, Zheng; Wu, Chunlei; Zhang, Shijun; Hu, Yanlin; Qin, Xue; Mo, Zengnan; Li, Hong; Zhang, Haiying

2016-07-01

This study was to assess the association between serum osteocalcin level and glucose metabolism in a Chinese male population. We carried out a cross-sectional study with a cohort of participants from the Fangchenggang Area Male Health and Examination Survey. The cross-sectional study was carried out among 2,353 men, including 2,139 participants with normal glucose tolerance, 148 with impaired fasting glucose and 66 with type 2 diabetes. A subsample of 1,109 men with measurement of osteocalcin was observed in the cohort. After a 4-year follow-up period, 1,049 non-diabetic and 983 participants with normal glucose tolerance who submitted the available information were enrolled in the cohort. Participants were divided into group-H (≥23.33 ng/mL) and group-L (<23.33 ng/mL) by osteocalcin level. In the cross-sectional study, osteocalcin levels were highest in participants with normal glucose tolerance, followed by those with impaired fasting glucose and type 2 diabetes (P < 0.001). In partial correlation analysis adjusted for age, serum osteocalcin level was related to glucose level (r = -0.082, P < 0.001), insulin level (r = -0.079, P < 0.001) and insulin resistance (r = -0.065, P = 0.002). Compared with group-H, group-L was associated with an increased risk of type 2 diabetes (odds ratio 2.107, 95% confidence interval 1.123-3.955), impaired fasting glucose (odds ratio 2.106; 95% CI 1.528-2.902), and insulin resistance (odds ratio 1.359, 95% confidence interval 1.080-1.710) adjusted for age, education levels, cigarette smoking and lipid profiles. In the cohort study, the increased risk of impaired fasting glucose was significant in group-L vs group-H (3.3% vs 1.2%, P = 0.026). Low serum osteocalcin level was a risk factor for impaired glucose metabolism and subsequent type 2 diabetes. © 2015 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Methods for Measuring Risk for Type 2 Diabetes in Youth: the Oral Glucose Tolerance Test (OGTT).

PubMed

Chen, Melinda E; Aguirre, Rebecca S; Hannon, Tamara S

2018-06-16

The oral glucose tolerance test (OGTT) is used both in clinical practice and research to assess glucose tolerance. In addition, the OGTT is utilized for surrogate measures of insulin sensitivity and the insulin response to enteral glucose and has been widely applied in the evaluation of β-cell dysfunction in obesity, prediabetes, and type 2 diabetes. Here we review the use of the OGTT and the OGTT-derived indices for measurement of risk markers for type 2 diabetes in youth. Advantages of using the OGTT for measures of diabetes risk include its accessibility and the incorporation of physiological contributions of the gut-pancreas axis in the measures of insulin response to glucose. Mathematical modeling expands the potential gains from the OGTT in physiology and clinical research. Disadvantages include individual differences in the rate of glucose absorption that modify insulin responses, imperfect control of the glycemic stimulus, and poor intraindividual reproducibility. Available research suggests the OGTT provides valuable information about the development of impaired glycemic control and β-cell function in obese youth along the spectrum of glucose tolerance.

A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance

PubMed Central

Goldfine, A. B.; Conlin, P. R.; Halperin, F.; Koska, J.; Permana, P.; Schwenke, D.; Shoelson, S. E.

2016-01-01

Aims/hypothesis Chronic sub-acute inflammation contributes to the pathogenesis of type 2 diabetes mellitus and cardiovascular disease. High doses of salicylate reduce inflammation, glucose and triacylglycerols, and may improve insulin sensitivity, suggesting therapeutic potential in impaired fasting glucose and/or impaired glucose tolerance. This trial aimed to evaluate the effect of salsalate vs placebo on insulin resistance and glycaemia in impaired fasting glucose and/or impaired glucose tolerance. Methods We conducted a 12 week, two-centre, randomised, placebo-controlled study to evaluate the effect of salsalate (up to 4 g/day) vs placebo on systemic glucose disposal. Secondary objectives included treatment effects on glycaemia, inflammation and cardiovascular risk factors. Seventy-eight participants with impaired fasting glucose and/or impaired glucose tolerance from two VA healthcare systems were enrolled. Randomisation assignment was provided by the coordinating center directly to site pharmacists, and participants and research staff were blinded to treatment assignment. Results Seventy-one individuals were randomised to placebo (n = 36) or salsalate (n = 35). Glucose disposal did not change in either group (salsalate 1% [95% CI −39%, 56%]; placebo 6% [95% CI −20%, 61%], p = 0.3 for placebo vs salsalate). Fasting glucose was reduced by 6% during the study by salsalate (p = 0.006) but did not change with placebo. Declines in glucose were accompanied by declines in fasting C-peptide with salsalate. Insulin clearance was reduced with salsalate. In the salsalate group, triacylglycerol levels were lower by 25% (p = 0.01) and adiponectin increased by 53% (p = 0.02) at the end of the study. Blood pressure, endothelial function and other inflammation markers did not differ between groups. Adipose tissue nuclear factor κB (NF-κB) activity declined in the salsalate group compared with placebo (−16% vs 42%, p = 0.005), but was not correlated with metabolic

Impaired fasting blood glucose is associated to cognitive impairment and cerebral atrophy in middle-aged non-human primates

PubMed Central

Djelti, Fathia; Dhenain, Marc; Terrien, Jérémy; Picq, Jean-Luc; Hardy, Isabelle; Champeval, Delphine; Perret, Martine; Schenker, Esther; Epelbaum, Jacques; Aujard, Fabienne

2017-01-01

Age-associated cognitive impairment is a major health and social issue because of increasing aged population. Cognitive decline is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. In middle-aged healthy humans, fasting blood glucose levels in the upper normal range are associated with memory impairment and cerebral atrophy. Due to a close evolutional similarity to Man, non-human primates may be useful to investigate the relationships between glucose homeostasis, cognitive deficits and structural brain alterations. In the grey mouse lemur, Microcebus murinus, spatial memory deficits have been associated with age and cerebral atrophy but the origin of these alterations have not been clearly identified. Herein, we showed that, on 28 female grey mouse lemurs (age range 2.4-6.1 years-old), age correlated with impaired fasting blood glucose (rs=0.37) but not with impaired glucose tolerance or insulin resistance. In middle-aged animals (4.1-6.1 years-old), fasting blood glucose was inversely and closely linked with spatial memory performance (rs=0.56) and hippocampus (rs=−0.62) or septum (rs=−0.55) volumes. These findings corroborate observations in humans and further support the grey mouse lemur as a natural model to unravel mechanisms which link impaired glucose homeostasis, brain atrophy and cognitive processes. PMID:28039490

Impaired fasting blood glucose is associated to cognitive impairment and cerebral atrophy in middle-aged non-human primates.

PubMed

Djelti, Fathia; Dhenain, Marc; Terrien, Jérémy; Picq, Jean-Luc; Hardy, Isabelle; Champeval, Delphine; Perret, Martine; Schenker, Esther; Epelbaum, Jacques; Aujard, Fabienne

2016-12-28

Age-associated cognitive impairment is a major health and social issue because of increasing aged population. Cognitive decline is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. In middle-aged healthy humans, fasting blood glucose levels in the upper normal range are associated with memory impairment and cerebral atrophy. Due to a close evolutional similarity to Man, non-human primates may be useful to investigate the relationships between glucose homeostasis, cognitive deficits and structural brain alterations. In the grey mouse lemur, Microcebus murinus , spatial memory deficits have been associated with age and cerebral atrophy but the origin of these alterations have not been clearly identified. Herein, we showed that, on 28 female grey mouse lemurs (age range 2.4-6.1 years-old), age correlated with impaired fasting blood glucose (r s =0.37) but not with impaired glucose tolerance or insulin resistance. In middle-aged animals (4.1-6.1 years-old), fasting blood glucose was inversely and closely linked with spatial memory performance (r s =0.56) and hippocampus (r s =-0.62) or septum (r s =-0.55) volumes. These findings corroborate observations in humans and further support the grey mouse lemur as a natural model to unravel mechanisms which link impaired glucose homeostasis, brain atrophy and cognitive processes.

Effect of hypothyroidism on insulin sensitivity and glucose tolerance in dogs.

PubMed

Hofer-Inteeworn, Natalie; Panciera, David L; Monroe, William E; Saker, Korinn E; Davies, Rebecca Hegstad; Refsal, Kent R; Kemnitz, Joseph W

2012-04-01

To determine the effects of hypothyroidism on insulin sensitivity, glucose tolerance, and concentrations of hormones counter-regulatory to insulin in dogs. 8 anestrous mixed-breed bitches with experimentally induced hypothyroidism and 8 euthyroid control dogs. The insulin-modified frequently sampled IV glucose tolerance test and minimal model analysis were used to determine basal plasma insulin and glucose concentrations, acute insulin response to glucose, insulin sensitivity, glucose effectiveness, and disposition index. Growth hormone response was assessed by stimulation and suppression tests. Additionally, basal serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentrations and urine cortisol-to-creatinine concentration ratios were measured and dual energy x-ray absorptiometry was performed to evaluate body composition. Insulin sensitivity was lower in the hypothyroid group than in the euthyroid group, whereas acute insulin response to glucose was higher. Glucose effectiveness and disposition index were not different between groups. Basal serum GH and IGF-1 concentrations as well as abdominal fat content were high in hypothyroid dogs, but urine cortisol-to-creatinine concentration ratios were unchanged. Hypothyroidism appeared to negatively affect glucose homeostasis by inducing insulin resistance, but overall glucose tolerance was maintained by increased insulin secretion in hypothyroid dogs. Possible factors affecting insulin sensitivity are high serum GH and IGF-1 concentrations and an increase in abdominal fat. In dogs with diseases involving impaired insulin secretion such as diabetes mellitus, concurrent hypothyroidism can have important clinical implications.

Evaluation of a Standardized Extract from Morus alba against α-Glucosidase Inhibitory Effect and Postprandial Antihyperglycemic in Patients with Impaired Glucose Tolerance: A Randomized Double-Blind Clinical Trial

PubMed Central

Hwang, Seung Hwan; Li, Hong Mei; Wang, Zhiqiang

2016-01-01

To evaluate the antihyperglycemic effect of a standardized extract of the leaves of Morus alba (SEMA), the present study was designed to investigate the α-glucosidase inhibitory effect and acute single oral toxicity as well as evaluate blood glucose reduction in animals and in patients with impaired glucose tolerance in a randomized double-blind clinical trial. SEMA was found to inhibit α-glucosidase at a fourfold higher level than the positive control (acarbose), in a concentration-dependent manner. Moreover, blood glucose concentration was suppressed by SEMA in vivo. Clinical signs and weight changes were observed when conducting an evaluation of the acute toxicity of SEMA through a single-time administration, with clinical observation conducted more than once each day. After administration of the SEMA, observation was for 14 days; all of the animals did not die and did not show any abnormal symptoms. In addition, the inhibitory effects of rice coated with SEMA were evaluated in a group of impaired glucose tolerance patients on postprandial glucose and a group of normal persons, and results showed that SEMA had a clear inhibitory effect on postprandial hyperglycemia in both groups. Overall, SEMA showed excellent potential in the present study as a material for improving postprandial hyperglycemia. PMID:27974904

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.

Impaired Glucose Regulation is Associated with Poorer Performance on the Stroop Task

PubMed Central

Gluck, Marci E.; Ziker, Cindy; Schwegler, Matthew; Thearle, Marie; Votruba, Susanne B.; Krakoff, Jonathan

2013-01-01

Background Type 2 diabetes is a risk factor for development of cognitive dysfunction. Impairments in glucose regulation have been associated with poorer performance on tests of executive function and information processing speed. Methods We administered the Stroop Color Word Task, where higher interference scores are indicative of decreased selective attention, to 98 non-diabetic volunteers (64m; %fat=37±12; age=36±9 y, race=41 NA/30 C/13 H/14 AA) on our inpatient unit. After 3d on a weight maintaining diet, % body fat was measured by DXA and a 75g oral glucose tolerance test (OGTT) was administered. Impaired glucose regulation (IGR) was defined as: fasting plasma glucose ≥100 and ≤125 mg/dL and/or 2h plasma glucose between ≥140 and ≤199 mg/dL (IGR; n = 48; NGR; n = 50). Total and incremental area under the curve (AUC) for insulin and glucose were calculated. Results Stroop interference scores were not significantly associated with any measure of adiposity or insulin concentrations. Individuals with IGR had significantly higher interference scores than those with normal glucose regulation (NGR; p=0.003). Higher interference scores were significantly correlated with fasting plasma glucose concentrations (r=0.26, p = 0.007) and total glucose AUC (r=0.30, p = 0.02) and only trending so for iAUC and 2h plasma glucose (r=0.18, p=0.08; r=0.17, p=0.09 respectively). In separate multivariate linear models, fasting plasma glucose (p = 0.002) and total glucose AUC (p = 0.0005) remained significant predictors of Stroop interference scores, even after adjustment for age, sex, race, education and %fat. Conclusions Individuals with IGR had decreased performance on a test of selective attention. Fasting plasma glucose was more strongly associated with lower performance scores than 2h plasma glucose. Our results indicate that even mild hyperglycemia in the non-diabetic range is associated with attentional processing difficulties in a sample of younger adults. Whether

[Effects of barley flake on metabolism of glucose and lipids in the patients with impaired fasting glucose].

PubMed

Bi, Mingxin; Niu, Yucun; Li, Xue; Li, Ying; Sun, Changhao

2013-09-01

To investigate the effects of barley flake (BF) on the glucose-lipid metabolism in patients with impaired fasting glucose (IFG). 100 patients with IFG were divided into the oat meal (OM) control group and barley flake experimental group for three months intervention according to randomized controlled trail (RCT). Biochemical indicators, glucose-lipid metabolism related enzymes, the area under curve (AUC) of blood glucose and insulin after oral glucose tolerance test (OGTT) were assessed before and after intervention. In addition, the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated by FBG (mmol/L) x INS (microU/L)/ 22.5. At the end of the three month active intervention, the mean fasting blood glucose (FBG) and insulin (INS) in the patients with BF treatment decreased by 9.26% (P < 0.001) and 13.37% (P = 0.001) separately compared with that in patients with OM treatment; meanwhile, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in patients with BF treatment also decreased by 7.20% (P < 0.001) and 9.42% (P = 0. 002), respectively. Glycosylated hemoglobin (HbA1c), HOMA-IR, total glyceride (TG), Apo-B, the AUC of blood glucose and insulin after OGTT were also significantly decreased separately (P < 0.01 or < 0.05 ). However, statistically significant differences failed to be found in HDL-C, Apo-A, ALP and SOD between these two groups. BF had favorable effect on improvement of glucose-lipid metabolism in the patients with impaired fasting glucose.

[Characteristics of the stages of change in physical behavior of male workers suffering from impaired glucose tolerance].

PubMed

Takahashi, Hirokazu; Yamamoto, Naoki; Shinoda, Jyunji; Iwata, Masamitsu; Watanabe, Takemasa

2011-01-01

The purpose of this study was to describe the characteristics of the stages of change in physical behavior of workers with diabetes and impaired glucose tolerance according to their dietary behavior, BMI, FBS, and HbA1c. The annual health checkup records of 15,317 male employees of an automobile corporation were examined. The stages of change in physical behavior were assessed through a self-reported questionnaire about "regular exercise" related to the five transformation stages and the date were used to analyze analyzes its relationship to dietary behavior, BMI, FBS, and HbA1c. The older age groups reported that the time spent on the "Action" and the "Maintenance" stages increased gradually over time. From the results we deduced that activity in the 30-39-year-old age group is low, which may be due lifestyle influence. The groups with advanced HbA1c levels reported that the time spent on the "Action" and the "Maintenance" stages increased. This may reflect the effects of present health management and continued research on its effects is needed. Significant correlations between the stages of change for physical and dietary behavior were observed in every age group and in every HbA1c level group. Developing regular exercise habits was closely related to developing adequate dietary habits in every age group and in every HbA1c level group. The correlation between exercise and dietary habits is so strong that future research into the causes inhibiting individuals from developing regular exercise habits is needed for workers with diabetes and impaired glucose tolerance. Developing regular exercise habits did not have a significant relation to FBS disorders in the 30-39 yr old age group or obesity in any age group. The results suggest that the effect and the limit of the physical behavior can be appropriately guided, and the offer of that encourages and supports the maintenance of the education physical behavior established is important. Health management systems for

Should living kidney donor candidates with impaired fasting glucose donate?

PubMed

Vigneault, Christine Buchek; Asch, William Stuart; Dahl, Neera Kanhouwa; Bia, Margaret Johnson

2011-08-01

As the kidney transplant waiting list grows, the willingness of transplant centers to accept complex donors increases. Guidelines for the evaluation of living kidney donors exist but do not provide clear guidance when evaluating the complex donor. Although few transplant centers will approve donor candidates with impaired glucose tolerance and most, if not all, will deny candidates with diabetes, many will approve candidates with impaired fasting glucose (IFG). Furthermore, the demographic of living donors has changed in the past 10 years to increasingly include more nonwhite and Hispanic individuals who are at greater risk for future diabetes and hypertension. IFG may be more of a concern in potential donors whose nonwhite and Hispanic ethnicity already places them at greater risk. We review the definition of diabetes, diabetes prediction tools, and transplant guidelines for donor screening and exclusion as it pertains to impaired glucose metabolism, and additional ethnic and nonethnic factors to consider. We offer an algorithm to aid in evaluation of potential living donors with IFG in which ethnicity, age, and features of the metabolic syndrome play a role in the decision making.

Improvement of Glucose Metabolism in Patients with Impaired Glucose Tolerance or Diabetes by Long-Term Administration of a Palatinose-Based Liquid Formula as a Part of Breakfast

PubMed Central

Sakuma, Masae; Arai, Hidekazu; Mizuno, Akira; Fukaya, Makiko; Matsuura, Motoi; Sasaki, Hajime; Yamanaka-Okumura, Hisami; Yamamoto, Hironori; Taketani, Yutaka; Doi, Toshio; Takeda, Eiji

2009-01-01

A palatinose-based liquid formula (palatinose-formula), suppresses postprandial plasma glucose and insulin levels in healthy men. The objective of this study was to investigate the effects of long-term palatinose-formula ingestion on glucose metabolism in patients with impaired glucose tolerance (IGT) or type 2 diabetes. Two patients with IGT and 7 patients with type 2 diabetes participated in the palatinose-formula and dextrin-based liquid formula (dextrin-formula) loading test and long-term palatinose-formula administration study. After a 3-month control period, palatinose-formula (1046 kJ) was ingested daily by patients as a part of breakfast for 5 months. In the loading test, palatinose-formula suppressed postprandial plasma glucose and insulin levels and areas under the curve compared with those after dextrin-formula ingestion. In the long-term study, glycated hemoglobin levels (after 3 months and 5 months of treatment) and serum 8-hydroxydeoxyguanosine levels (after 5 months of treatment) were markedly decreased comparing with those at baseline. Intake of 1046 kJ palatinose-formula as a part of breakfast over a long-term period may be effective for improvement of glucose metabolism in patients with IGT or type 2 diabetes. PMID:19794923

Beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to Type 2 diabetes

USDA-ARS?s Scientific Manuscript database

Using the hyperglycemic and euglycemic clamp, we demonstrated impaired Beta-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled Beta-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. Bet...

Deletion of Rab GAP AS160 modifies glucose uptake and GLUT4 translocation in primary skeletal muscles and adipocytes and impairs glucose homeostasis.

PubMed

Lansey, Melissa N; Walker, Natalie N; Hargett, Stefan R; Stevens, Joseph R; Keller, Susanna R

2012-11-15

Tight control of glucose uptake in skeletal muscles and adipocytes is crucial to glucose homeostasis and is mediated by regulating glucose transporter GLUT4 subcellular distribution. In cultured cells, Rab GAP AS160 controls GLUT4 intracellular retention and release to the cell surface and consequently regulates glucose uptake into cells. To determine AS160 function in GLUT4 trafficking in primary skeletal muscles and adipocytes and investigate its role in glucose homeostasis, we characterized AS160 knockout (AS160(-/-)) mice. We observed increased and normal basal glucose uptake in isolated AS160(-/-) adipocytes and soleus, respectively, while insulin-stimulated glucose uptake was impaired and GLUT4 expression decreased in both. No such abnormalities were found in isolated AS160(-/-) extensor digitorum longus muscles. In plasma membranes isolated from AS160(-/-) adipose tissue and gastrocnemius/quadriceps, relative GLUT4 levels were increased under basal conditions and remained the same after insulin treatment. Concomitantly, relative levels of cell surface-exposed GLUT4, determined with a glucose transporter photoaffinity label, were increased in AS160(-/-) adipocytes and normal in AS160(-/-) soleus under basal conditions. Insulin augmented cell surface-exposed GLUT4 in both. These observations suggest that AS160 is essential for GLUT4 intracellular retention and regulation of glucose uptake in adipocytes and skeletal muscles in which it is normally expressed. In vivo studies revealed impaired insulin tolerance in the presence of normal (male) and impaired (female) glucose tolerance. Concurrently, insulin-elicited increases in glucose disposal were abolished in all AS160(-/-) skeletal muscles and liver but not in AS160(-/-) adipose tissues. This suggests AS160 as a target for differential manipulation of glucose homeostasis.

Metabolism and Energy Expenditure, But Not Feeding or Glucose Tolerance, Are Impaired in Young Kiss1r KO Female Mice.

PubMed

Tolson, Kristen P; Garcia, Christian; Delgado, Iris; Marooki, Nuha; Kauffman, Alexander S

2016-11-01

Kisspeptin regulates reproduction via signaling through the receptor, Kiss1r, in GnRH neurons. However, both kisspeptin and Kiss1r are produced in several peripheral tissues, and recent studies have highlighted a role for kisspeptin signaling in metabolism and glucose homeostasis. We recently reported that Kiss1r knockout (KO) mice display a sexually dimorphic metabolic phenotype, with KO females displaying obesity, impaired metabolism, and glucose intolerance at 4-5 months of age. However, it remains unclear when this metabolic phenotype first emerges in development, or which aspects of the pleiotropic phenotype underlie the metabolic defects and which are secondary to the obesity. Here, we studied Kiss1r KO females at different ages, including several weeks before the emergence of body weight (BW) differences and later when obesity is present. We determined that at young adult ages (6 wk old), KO females already exhibit altered adiposity, leptin levels, metabolism, and energy expenditure, despite having normal BWs at this time. In contrast, food intake, water intake, and glucose tolerance are normal at young ages and only show impairments at older adult ages, suggesting that these impairments may be secondary to earlier alterations in metabolism and adiposity. We also demonstrate that, in addition to BW, all other facets of the adult metabolic phenotype persist even when gonadal sex steroids are similar between genotypes. Collectively, these data highlight the developmental emergence of a metabolic phenotype induced by disrupted kisspeptin signaling and reveal that multiple, but not all, aspects of this phenotype are already disrupted before detectable changes in BW.

Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy.

PubMed

Brufani, Claudia; Ciampalini, Paolo; Grossi, Armando; Fiori, Rossana; Fintini, Danilo; Tozzi, Alberto; Cappa, Marco; Barbetti, Fabrizio

2010-02-01

Childhood obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM). Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy. The study group included 510 overweight/obese subjects (3-18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta-cell function was estimated by insulinogenic index. Fat mass was measured by dual-energy x-ray absorptiometry. Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA-IR and glucose-stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA-IR = 4.4 +/- 2.5 vs. 3.4 +/- 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT. Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents.

Low sensitivity of the metabolic syndrome to identify adolescents with impaired glucose tolerance: an analysis of NHANES 1999-2010.

PubMed

DeBoer, Mark D; Gurka, Matthew J

2014-04-23

The presence of impaired glucose tolerance (IGT) and metabolic syndrome (MetS) are two risk factors for Type 2 diabetes. The inter-relatedness of these factors among adolescents is unclear. We evaluated the sensitivity and specificity of MetS for identifying IGT in an unselected group of adolescents undergoing oral glucose tolerance tests (OGTT) in the National Health and Nutrition Evaluation Survey 1999-2010. We characterized IGT as a 2-hour glucose ≥140 mg/dL and MetS using ATP-III-based criteria and a continuous sex- and race/ethnicity-specific MetS Z-score at cut-offs of +1.0 and +0.75 standard deviations (SD) above the mean. Among 1513 adolescents, IGT was present in 4.8%, while ATP-III-MetS was present in 7.9%. MetS performed poorly in identifying adolescents with IGT with a sensitivity/specificity of 23.7%/92.9% for ATP-III-MetS, 23.6%/90.8% for the MetS Z-score at +1.0 SD and 35.8%/85.0 for the MetS Z-score at +0.75 SD. Sensitivity was higher (and specificity lower) but was still overall poor among overweight/obese adolescents: 44.7%/83.0% for ATP-III-MetS, 43.1%/77.1% for the MetS Z-score at +1.0 SD and 64.3%/64.3% for MetS Z-score at +0.75 SD. This lack of overlap between MetS and IGT may indicate that assessment of MetS is not likely to be a good indicator of which adolescents to screen using OGTT. These data further underscore the importance of other potential contributors to IGT, including Type 1 diabetes and genetic causes of poor beta-cell function. Practitioners should keep these potential causes of IGT in mind, even when evaluating obese adolescents with IGT.

Impaired glucose metabolism in subjects with the Williams-Beuren syndrome: A five-year follow-up cohort study

PubMed Central

Lunati, Maria Elena; Bedeschi, Maria Francesca; Resi, Veronica; Grancini, Valeria; Palmieri, Eva; Salera, Simona; Lalatta, Faustina; Pugliese, Giuseppe

2017-01-01

Objective The Williams-Beuren syndrome (WS) is associated with impaired glucose metabolism (IGM) early in adulthood. However, the pathophysiology of IGM remains poorly defined, due to the lack of longitudinal studies investigating the contribution of β-cell dysfunction and impaired insulin sensitivity. This study aimed at assessing incidence of IGM and the underlying mechanisms in WS adults. Methods This observational, longitudinal (5-year), cohort study enrolled thirty-one consecutive WS subjects attending a tertiary referral center. An oral glucose tolerance test (OGTT) was performed yearly and used to classify patients as normal or IGM, including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and diabetes mellitus (DM), and to calculate surrogate measures of insulin secretion and/or sensitivity. Results IGM patients were 18 (58.1%, three DM) at baseline and 19 (61.3%, five DM) at end-of-follow-up. However, 13 individuals changed category of glucose homeostasis in both directions during follow-up (8 progressors, 5 regressors) and 18 did not (8 non-progressors, 10 non-regressors). New cases of IGM and DM were 11.1 and 2.53 per 100 persons-year, respectively, and were treated non-pharmacologically. In the whole cohort and, to a higher extent, in progressors, indices of early-phase insulin secretion and insulin sensitivity decreased significantly from baseline to end-of-follow-up, with concurrent reduction of the oral disposition index and insulin secretion-sensitivity index-2 (ISSI-2), compensating insulin secretion for the level of insulin resistance. No baseline measure independently predicted progression, which correlated with change from baseline in ISSI-2. Compared with patients with normal glucose homeostasis, IGT subjects had impaired insulin sensitivity, whereas insulin secretion was reduced only in those with IFG+IGT or DM. Conclusions IGM incidence is high in young adults with WS, suggesting the need of early screening and timed

Ethnic differences in cross-sectional associations between impaired glucose regulation, identified by oral glucose tolerance test or HbA1c values, and cardiovascular disease in a cohort of European and South Asian origin.

PubMed

Eastwood, S V; Tillin, T; Mayet, J; Shibata, D K; Wright, A; Heasman, J; Beauchamp, N; Forouhi, N G; Hughes, A D; Chaturvedi, N

2016-03-01

We contrasted impaired glucose regulation (prediabetes) prevalence, defined according to oral glucose tolerance test or HbA1c values, and studied cross-sectional associations between prediabetes and subclinical/clinical cardiovascular disease (CVD) in a cohort of European and South Asian origin. For 682 European and 520 South Asian men and women, aged 58-85 years, glycaemic status was determined by oral glucose tolerance test or HbA1c thresholds. Questionnaires, record review, coronary artery calcification scores and cerebral magnetic resonance imaging established clinical plus subclinical coronary heart and cerebrovascular disease. Prediabetes was more prevalent in South Asian participants when defined by HbA1c rather than by oral glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood pressure, triglycerides and waist-hip ratio, prediabetes was associated with coronary heart disease and cerebrovascular disease in European participants, most obviously when defined by HbA1c rather than by oral glucose tolerance test [odds ratios for HbA1c -defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast, non-significant associations were present between oral glucose tolerance test-defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI 0.84, 2.36)] and HbA1c -defined prediabetes only and cerebrovascular disease [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes defined by HbA1c or oral glucose tolerance test criteria was associated with cardiovascular disease (defined as coronary heart and/or cerebrovascular disease) in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria] but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66); ethnicity interaction P = 0.04]. Prediabetes appeared to be less associated with cardiovascular disease in the South Asian than in the European

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.

Combined use of fasting plasma glucose and glycated hemoglobin A1c in the screening of diabetes and impaired glucose tolerance.

PubMed

Hu, Yaomin; Liu, Wei; Chen, Yawen; Zhang, Ming; Wang, Lihua; Zhou, Huan; Wu, Peihong; Teng, Xiangyu; Dong, Ying; Zhou, Jia wen; Xu, Hua; Zheng, Jun; Li, Shengxian; Tao, Tao; Hu, Yumei; Jia, Yun

2010-09-01

The aim of this study is to assess the validity of combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) as screening tests for diabetes and impaired glucose tolerance (IGT) in high-risk subjects. A total of 2,298 subjects were included. All subjects underwent a 75-g oral glucose tolerance test (OGTT) and HbA1c measurement. Receiver operating characteristic curve (ROC curve) analysis was used to examine the sensitivity and specificity of FPG and HbA1c for detecting diabetes and IGT, which was defined according to the 1999 World Health Organization (WHO) criteria. (1) Based on the ROC curve, the optimal cut point of FPG related to diabetes diagnosed by OGTT was 6.1 mmol/l that was associated with a sensitivity and specificity of 81.5 and 81.0%, respectively; The optimal cut point of HbA1c related to diabetes diagnosed by OGTT was 6.1%, which was associated with a sensitivity and specificity of 81.0 and 81.0%, respectively; The screening model using FPG > or = 6.1 mmol/l or HbA1c > or = 6.1% had sensitivity of 96.5% for detecting undiagnosed diabetes; the screening model using FPG > or = 6.1 mmol/l and HbA1c > or = 6.1% had specificity of 96.3% for detecting undiagnosed diabetes. (2) Based on the ROC curve, the optimal cut point of FPG related to IGT diagnosed by OGTT was 5.6 mmol/l that was associated with a sensitivity and specificity of 64.1 and 65.4%, respectively; The optimal cut point of HbA1c related to IGT diagnosed by OGTT was 5.6%, which was associated with a sensitivity and specificity of 66.2 and 51.0%, respectively; The screening model using FPG > or = 5.6 mmol/l or HbA1c > or = 5.6% had sensitivity of 87.9% for detecting undiagnosed IGT; The screening model using FPG > or = 5.6 mmol/l and HbA1c > or = 5.6% had specificity of 82.4% for detecting undiagnosed IGT. Compared with FPG or HbA1c alone, the simultaneous measurement of FPG and HbA1c (FPG and/or HbA1C) might be a more sensitive and specific screening tool for identifying

Lysophosphatidic acid impairs glucose homeostasis and inhibits insulin secretion in high-fat diet obese mice.

PubMed

Rancoule, C; Attané, C; Grès, S; Fournel, A; Dusaulcy, R; Bertrand, C; Vinel, C; Tréguer, K; Prentki, M; Valet, P; Saulnier-Blache, J S

2013-06-01

Lysophosphatidic acid (LPA) is a lipid mediator produced by adipocytes that acts via specific G-protein-coupled receptors; its synthesis is modulated in obesity. We previously reported that reducing adipocyte LPA production in high-fat diet (HFD)-fed obese mice is associated with improved glucose tolerance, suggesting a negative impact of LPA on glucose homeostasis. Here, our aim was to test this hypothesis. First, glucose tolerance and plasma insulin were assessed after acute (30 min) injection of LPA (50 mg/kg) or of the LPA1/LPA3 receptor antagonist Ki16425 (5 mg kg(-1) day(-1), i.p.) in non-obese mice fed a normal diet (ND) and in obese/prediabetic (defined as glucose-intolerant) HFD mice. Glucose and insulin tolerance, pancreas morphology, glycogen storage, glucose oxidation and glucose transport were then studied after chronic treatment (3 weeks) of HFD mice with Ki16425. In ND and HFD mice, LPA acutely impaired glucose tolerance by inhibiting glucose-induced insulin secretion. These effects were blocked by pre-injection of Ki16425 (5 mg/kg, i.p.). Inhibition of glucose-induced insulin secretion by LPA also occurred in isolated mouse islets. Plasma LPA was higher in HFD mice than in ND mice and Ki16425 transiently improved glucose tolerance. The beneficial effect of Ki16425 became permanent after chronic treatment and was associated with increased pancreatic islet mass and higher fasting insulinaemia. Chronic treatment with Ki16425 also improved insulin tolerance and increased liver glycogen storage and basal glucose use in skeletal muscle. Exogenous and endogenous LPA exerts a deleterious effect on glucose disposal through a reduction of plasma insulin; pharmacological blockade of LPA receptors improves glucose homeostasis in obese/prediabetic mice.

Calculation of Glucose Dose for Intraperitoneal Glucose Tolerance Tests in Lean and Obese Mice.

PubMed

Jørgensen, Mikkel S; Tornqvist, Kristina S; Hvid, Henning

2017-01-01

Glucose tolerance tests are used frequently in nonclinical research with laboratory animals, for example during characterization of obese phenotypes. Despite published standard operating procedures for glucose tolerance tests in rodents, how glucose doses should be calculated when obese and lean animals are compared is not well documented. Typically the glucose dose is calculated as 2 g/kg body weight, regardless of body composition. With this approach, obese mice receive larger glucose doses than do lean animals, potentially leading to overestimation of glucose intolerance in obese animals. In this study, we performed intraperitoneal glucose tolerance tests in mice with diet-induced obesity and their lean controls, with glucose doses based on either the total body weight or the lean body mass of the animals. To determine glucose tolerance, we determined the blood glucose AUC during the glucose tolerance test. We found that the blood glucose AUC was increased significantly in obese mice compared with lean mice by 75% on average when glucose was dosed according to the lean body mass and by 87% when the glucose dose was calculated according to total body weight. Therefore, mice with diet-induced obesity were approximately equally glucose intolerant between the 2 dose-calculation protocols. However, we recommend calculating the glucose dose according to the lean body mass of the mice, because doing so eliminates the concern regarding overdosing of obese animals.

Body Composition Is Altered in Pre-Diabetic Patients With Impaired Fasting Glucose Tolerance: Results From the NHANES Survey.

PubMed

Julian, Valerie; Blondel, Romain; Pereira, Bruno; Thivel, David; Boirie, Yves; Duclos, Martine

2017-11-01

Previous studies suggest that type 2 diabetes mellitus (T2DM) is associated with a loss of muscle mass but the impact of fasting blood glucose (FBG) on body composition remains underappreciated in pre-diabetic subjects. The aim of this study was to determine the influence of FBG on lean mass (LM), fat mass (FM) and their distribution (trunk vs. appendicular), separately in middle-aged men and women. One thousand nine hundred and eleven (1,911) men (63.9 ± 11.7 years) and 1,977 women (63.7 ± 12.1 years) from the National Health and Nutrition Examination Survey (1999 - 2004) were divided into four groups: normal glucose tolerance (NGT), low impaired fasting glucose (IFG), high IFG and T2DM. Body composition was obtained from dual X-ray absorptiometry (DXA). Of the patients, 68.7% had NGT, 16.1% low IFG, 9.4% high IFG and 5.8% T2DM. After adjustment for age, body mass index, ethnicity, smoking, alcohol and physical activity (PA), no change in appendicular LM was observed between groups, but significant increases in trunk FM (in both gender) and trunk LM (in women) were found with increased glucose intolerance (T2DM > IFG > NGT), as well as significant decreases in trunk and total LM/FM ratios (T2DM < IFG < NGT) and a significant increase in trunk/appendicular FM ratio (T2DM > IFG > NGT). Elevated FBG within the normal range is not associated with a significant loss of appendicular LM, but modifications in LM and FM trunk and total distribution with IFG suggest that nutritional and physical lifestyle strategies should be implemented in the pre-diabetic state.

Triglycerides to High-Density Lipoprotein Cholesterol Ratio Can Predict Impaired Glucose Tolerance in Young Women with Polycystic Ovary Syndrome.

PubMed

Song, Do Kyeong; Lee, Hyejin; Sung, Yeon Ah; Oh, Jee Young

2016-11-01

The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio could be related to insulin resistance (IR). We previously reported that Korean women with polycystic ovary syndrome (PCOS) had a high prevalence of impaired glucose tolerance (IGT). We aimed to determine the cutoff value of the TG/HDL-C ratio for predicting IR and to examine whether the TG/HDL-C ratio is useful for identifying individuals at risk of IGT in young Korean women with PCOS. We recruited 450 women with PCOS (24±5 yrs) and performed a 75-g oral glucose tolerance test (OGTT). IR was assessed by a homeostasis model assessment index over that of the 95th percentile of regular-cycling women who served as the controls (n=450, 24±4 yrs). The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in women with PCOS. Among the women with PCOS who had normal fasting glucose (NFG), the prevalence of IGT was significantly higher in the women with PCOS who had a high TG/HDL-C ratio compared with those with a low TG/HDL-C ratio (15.6% vs. 5.6%, p<0.05). The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in young Korean women with PCOS, and women with NFG and a high TG/HDL-C ratio had a higher prevalence of IGT. Therefore, Korean women with PCOS with a TG/HDL-C ratio >2.5 are recommended to be administered an OGTT to detect IGT even if they have NFG.

The dietary flavonoids naringenin and quercetin acutely impair glucose metabolism in rodents possibly via inhibition of hypothalamic insulin signalling.

PubMed

Koch, Christiane E; Ganjam, Goutham K; Steger, Juliane; Legler, Karen; Stöhr, Sigrid; Schumacher, Daniela; Hoggard, Nigel; Heldmaier, Gerhard; Tups, Alexander

2013-03-28

Secondary metabolites of herbs and spices are widely used as an alternative strategy in the therapy of various diseases. The polyphenols naringenin, quercetin and curcumin have been characterised as anti-diabetic agents. Conversely, in vitro, naringenin and quercetin are described to inhibit phosphoinositide-3-kinase (PI3K), an enzyme that is essential for the neuronal control of whole body glucose homoeostasis. Using both in vitro and in vivo experiments, we tested whether the inhibitory effect on PI3K occurs in neurons and if it might affect whole body glucose homoeostasis. Quercetin was found to inhibit basal and insulin-induced phosphorylation of Akt (Ser473), a downstream target of PI3K, in HT-22 cells, whereas naringenin and curcumin had no effect. In Djungarian hamsters (Phodopus sungorus) naringenin and quercetin (10 mg/kg administered orally) diminished insulin-induced phosphorylation of Akt (Ser473) in the arcuate nucleus, indicating a reduction in hypothalamic PI3K activity. In agreement with this finding, glucose tolerance in naringenin-treated hamsters (oral) and mice (oral and intracerebroventricular) was reduced compared with controls. Dietary quercetin also impaired glucose tolerance, whereas curcumin was ineffective. Circulating levels of insulin and insulin-like growth factor-binding protein were not affected by the polyphenols. Oral quercetin reduced the respiratory quotient, suggesting that glucose utilisation was impaired after treatment. These data demonstrate that low doses of naringenin and quercetin acutely and potently impair glucose homoeostasis. This effect may be mediated by inhibition of hypothalamic PI3K signalling. Whether chronic impairments in glucose homoeostasis occur after long-term application remains to be identified.

Type 2 diabetes mellitus and impaired glucose regulation in overweight and obese children and adolescents living in Serbia.

PubMed

Vukovic, R; Mitrovic, K; Milenkovic, T; Todorovic, S; Zdravkovic, D

2012-11-01

An increase in the prevalence of pediatric type 2 diabetes mellitus (T2DM) has been reported by numerous studies in the United States during the past two decades. Available data from Europe are scarce, but also suggest the rising prevalence of this disease in overweight children. The aim of this study was to determine the prevalence of previously undiagnosed T2DM, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a clinic cohort of otherwise healthy overweight and obese Caucasian children and adolescents living in Serbia. The study group consisted of 301 subjects (176 girls, 125 boys) aged 5.2-18.9 years, with body mass index >90th percentile. Oral glucose tolerance test was performed in all subjects. Previously undiagnosed T2DM was discovered in 0.3% (n=1) and impaired glucose regulation in 15.9% (n=48) of the subjects. Isolated IFG was detected in 4.3% (n=13), isolated IGT in 8.3% (n=25) and combined IFG and IGT in 3.3% (n=10) of the subjects. Disturbances of glucose metabolism were present in a substantial number of the subjects, which emphasizes the need for prevention and treatment of childhood obesity.

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.

Standing Balance and Trunk Position Sense in Impaired Glucose Tolerance (IGT)-Related Peripheral Neuropathy

PubMed Central

Goldberg, Allon; Russell, James William; Alexander, Neil Burton

2009-01-01

Type 2 diabetes mellitus (T2DM) and pre-diabetes or impaired glucose tolerance (IGT) affects a large segment of the population. Peripheral neuropathy (PN) is a common complication of T2DM, leading to sensory and motor deficits. While T2DM-related PN often results in balance- and mobility-related dysfunction which manifests as gait instability and falls, little is known about balance capabilities in patients who have evidence of PN related to IGT (IGT-PN). We evaluated patients with IGT-PN on commonly-used clinical balance and mobility tests as well as a new test of trunk position sense and balance impairment, trunk repositioning errors (TREs). Eight participants aged 50–72 years with IGT-PN, and eight age and gender matched controls underwent balance, mobility and trunk repositioning accuracy tests at a university neurology clinic and mobility research laboratory. Compared to controls, IGT-PN participants had as much as twice the magnitude of TREs and stood approximately half as long on the single leg balance test. People with IGT-PN exhibit deficits in standing balance and trunk position sense. Furthermore, there was a significant association between performance on commonly-used clinical balance and mobility tests, and electrophysiological and clinical measures of neuropathy in IGT-PN participants. Because IGT-related neuropathy represents the earliest stage of diabetic neuropathy, deficits in IGT-PN participants highlights the importance of early screening in the dysglycemic process for neuropathy and associated balance deficits. PMID:18439624

Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high-density lipoprotein of adult men.

PubMed

Riales, R; Albrink, M J

1981-12-01

Chromium deficiency may cause insulin resistance, hyperinsulinemia, impaired glucose tolerance, and hyperlipidemia, recovered by chromium supplementation. The effect of chromium supplementation on serum lipids and glucose tolerance was tested in a double-blind 12-wk study of 23 healthy adult men aged 31 to 60 yr. Either 200 micrograms trivalent chromium in 5 ml water (Cr) or 5 ml plain water (W) was ingested daily 5 days each week. Half the subjects volunteered for glucose tolerance tests with insulin levels. At 12 wk high-density lipoprotein cholesterol increased in the Cr group from 35 to 39 mg/dl (p less than 0.05) but did not change in the water group (34 mg/dl). The largest increase in high-density lipoprotein cholesterol and decreases in insulin and glucose were found in those subjects having normal glucose levels together with elevated insulin levels at base-line. The data are thus consistent with the hypothesis that Cr supplementation raises high-density lipoprotein cholesterol and improves insulin sensitivity in those with evidence of insulin resistance but normal glucose tolerance.

Differential effects of early-life NMDA receptor antagonism on aspartame-impaired insulin tolerance and behavior.

PubMed

Collison, Kate S; Inglis, Angela; Shibin, Sherin; Andres, Bernard; Ubungen, Rosario; Thiam, Jennifer; Mata, Princess; Al-Mohanna, Futwan A

2016-12-01

We have previously showed that lifetime exposure to aspartame, commencing in utero via the mother's diet, may impair insulin tolerance and cause behavioral deficits in adulthood via mechanisms which are incompletely understood. The role of the CNS in regulating glucose homeostasis has been highlighted by recent delineation of the gut-brain axis, in which N-methyl-d-aspartic acid receptors (NMDARs) are important in maintaining glucose homeostasis, in addition to regulating certain aspects of behavior. Since the gut-brain axis can be modulated by fetal programming, we hypothesized that early-life NMDAR antagonism may affect aspartame-induced glucose deregulation in adulthood, and may alter the aspartame behavioral phenotype. Accordingly, C57Bl/6J mice were chronically exposed to aspartame commencing in utero, in the presence and absence of maternal administration of the competitive NMDAR antagonist CGP 39551, from conception until weaning. Drug/diet interactions in adulthood glucocentric and behavioral parameters were assessed. Aspartame exposure elevated blood glucose and impaired insulin-induced glucose disposal during an insulin tolerance test, which could be normalized by NMDAR antagonism. The same effects were not observed in control diet mice, suggesting an early-life drug/diet interaction. Behavioral analysis of adult offspring indicated that NMDAR antagonism of control diet mice caused hyperlocomotion and impaired spatial navigation. Conversely hypolocomotion, reduced exploratory activity and increased anxiety-related behavior were apparent in aspartame diet mice with early-life NMDAR antagonism. significant drug/diet interactions in glucocentric and behavioral parameters were identified in aspartame-exposed mice with early-life NMDAR antagonism. This suggests a possible involvement of early NMDAR interactions in aspartame-impaired glucose homeostasis and behavioral deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

Modest Salt Reduction Lowers Blood Pressure and Albumin Excretion in Impaired Glucose Tolerance and Type 2 Diabetes Mellitus: A Randomized Double-Blind Trial.

PubMed

Suckling, Rebecca J; He, Feng J; Markandu, Nirmala D; MacGregor, Graham A

2016-06-01

The role of salt restriction in patients with impaired glucose tolerance and diabetes mellitus is controversial, with a lack of well controlled, longer term, modest salt reduction trials in this group of patients, in spite of the marked increase in cardiovascular risk. We carried out a 12-week randomized double-blind, crossover trial of salt restriction with salt or placebo tablets, each for 6 weeks, in 46 individuals with diet-controlled type 2 diabetes mellitus or impaired glucose tolerance and untreated normal or high normal blood pressure (BP). From salt to placebo, 24-hour urinary sodium was reduced by 49±9 mmol (2.9 g salt). This reduction in salt intake led to fall in clinic BP from 136/81±2/1 mm Hg to 131/80±2/1 mm Hg, (systolic BP; P<0.01). Mean ambulatory 24-hour BP was reduced by 3/2±1/1 mm Hg (systolic BP, P<0.01 and diastolic BP, P<0.05), and albumin/creatinine ratio was reduced from 0.73 mg/mmol (0.5-1.5) to 0.64 mg/mmol (0.3-1.1; P<0.05). There was no significant change in fasting glucose, hemoglobin A1c, or insulin sensitivity. These results demonstrate that a modest reduction in salt intake, to approximately the amount recommended in public health guidelines, leads to significant and clinically relevant falls in BP in individuals who are early on in the progression of diabetes mellitus with normal or mildly raised BP. The reduction in urinary albumin excretion may carry additional benefits in reducing cardiovascular disease above the effects on BP. © 2016 American Heart Association, Inc.

Association of late-night carbohydrate intake with glucose tolerance among pregnant African American women.

PubMed

Chandler-Laney, Paula C; Schneider, Camille R; Gower, Barbara A; Granger, Wesley M; Mancuso, Melissa S; Biggio, Joseph R

2016-10-01

Obesity and late-night food consumption are associated with impaired glucose tolerance. Late-night carbohydrate consumption may be particularly detrimental during late pregnancy because insulin sensitivity declines as pregnancy progresses. Further, women who were obese (Ob) prior to pregnancy have lower insulin sensitivity than do women of normal weight (NW). The aim of this study is to test the hypothesis that night-time carbohydrate consumption is associated with poorer glucose tolerance in late pregnancy and that this association would be exacerbated among Ob women. Forty non-diabetic African American women were recruited based upon early pregnancy body mass index (NW, <25 kg m(-2) ; Ob, ≥30 kg m(-2) ). Third trimester free-living dietary intake was assessed by food diary, and indices of glucose tolerance and insulin action were assessed during a 75-g oral glucose tolerance test. Women in the Ob group reported greater average 24-h energy intake (3055 kcal vs. 2415 kcal, P < 0.05). Across the whole cohort, night-time, but not day-time, carbohydrate intake was positively associated with glucose concentrations after the glucose load and inversely associated with early phase insulin secretion (P < 0.05). Multiple linear regression modelling within each weight group showed that the associations among late-night carbohydrate intake, glucose concentrations and insulin secretion were present only in the Ob group. This is the first study to report an association of night-time carbohydrate intake specifically on glucose tolerance and insulin action during pregnancy. If replicated, these results suggest that late-night carbohydrate intake may be a potential target for intervention to improve metabolic health of Ob women in late pregnancy. © 2015 John Wiley & Sons Ltd.

Triglycerides to High-Density Lipoprotein Cholesterol Ratio Can Predict Impaired Glucose Tolerance in Young Women with Polycystic Ovary Syndrome

PubMed Central

Song, Do Kyeong; Lee, Hyejin; Sung, Yeon-Ah

2016-01-01

Purpose The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio could be related to insulin resistance (IR). We previously reported that Korean women with polycystic ovary syndrome (PCOS) had a high prevalence of impaired glucose tolerance (IGT). We aimed to determine the cutoff value of the TG/HDL-C ratio for predicting IR and to examine whether the TG/HDL-C ratio is useful for identifying individuals at risk of IGT in young Korean women with PCOS. Materials and Methods We recruited 450 women with PCOS (24±5 yrs) and performed a 75-g oral glucose tolerance test (OGTT). IR was assessed by a homeostasis model assessment index over that of the 95th percentile of regular-cycling women who served as the controls (n=450, 24±4 yrs). Results The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in women with PCOS. Among the women with PCOS who had normal fasting glucose (NFG), the prevalence of IGT was significantly higher in the women with PCOS who had a high TG/HDL-C ratio compared with those with a low TG/HDL-C ratio (15.6% vs. 5.6%, p<0.05). Conclusion The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in young Korean women with PCOS, and women with NFG and a high TG/HDL-C ratio had a higher prevalence of IGT. Therefore, Korean women with PCOS with a TG/HDL-C ratio >2.5 are recommended to be administered an OGTT to detect IGT even if they have NFG. PMID:27593868

Relationship between serum secreted frizzled-related protein 4 levels and the first-phase of glucose-stimulated insulin secretion in individuals with different glucose tolerance.

PubMed

Liu, Fang; Qu, Hua; Li, Yingjie; Tang, Qian; Yang, Zesong; Wang, Hang; Deng, Huacong

2015-01-01

Recent evidence suggests that serum secreted frizzled-related protein (SFRP) 4 may affect β-cell function. In a cross-sectional clinical study, 56 subjects with type 2 diabetes mellitus (T2DM), 52 subjects with impaired glucose tolerance (IGT) and 42 normal glucose tolerance (NGT) subjects were enrolled to investigate the relationship between SFRP4 levels and the first-phase of glucose-stimulated insulin secretion, glucose metabolism and inflammation. Intravenous glucose tolerance tests were conducted, and acute insulin response (AIR), the area under the curve of the first-phase (0-10 min) insulin secretion (AUC), and the glucose disposition index (GDI) were calculated. The serum levels of SFRP4, IL-1β, plasma glucose, serum lipid, and glycated hemoglobin (HbA1c) were measured. Levels of serum SFRP4 and IL-1β in the T2DM group and IGT group were significantly higher than those in the NGT group (P < 0.01). The AIR, AUC and GDI between the three groups showed a progressive decrease from the NGT to IGT groups with the lowest value in the T2DM groups (P < 0.01). The serum SFRP4 levels were negatively correlated with AIR, AUC, GDI and HOMA-β (P < 0.01) and were positively correlated with fasting plasma glucose, HbA1c, hs-CRP, and IL-1β (P < 0.01). Our study provides evidence that the concentrations of serum SFRP4 in T2DM and IGT subjects were increased and were correlated closely with glycose metabolic disorder, the first-phase of glucose-stimulated insulin secretion and chronic low-grade inflammation. SFRP4 may participate in the development of type 2 diabetes mellitus.

Hepatitis C virus eradication by direct antiviral agents improves glucose tolerance and reduces post-load insulin resistance in nondiabetic patients with genotype 1.

PubMed

Salomone, Federico; Catania, Maurizio; Montineri, Arturo; Bertino, Gaetano; Godos, Justyna; Rizzo, Leonardo; Magrì, Giovanni; Li Volti, Giovanni

2017-12-19

Genotype 1 chronic hepatitis C is associated with an impairment of glucose homoeostasis, especially in the advanced stages of the disease. Glucose tolerance is an independent predictor of liver-related mortality in patients with cirrhosis because of chronic hepatitis C. However, no study has demonstrated so far weather hepatitis C virus clearance affects glucose tolerance. To this aim, we performed a prospective study assessing the effects of direct antiviral agents treatment in nondiabetic cirrhotic patients with genotypes 1a/1b and impaired glucose tolerance based on a 75-g oral glucose tolerance test. Impaired glucose tolerance was diagnosed by a 2-hour plasma glucose between 140 and 199 mg/dL. Insulin resistance was estimated by the oral glucose insulin sensitivity index, an oral glucose tolerance test-derived measure. After meeting the inclusion criteria, the study population included 32 outpatients (26/6 genotypes 1b/1a; age 62 ± 7.4 years; 18 males) with compensated Child-A cirrhosis. All patients achieved a sustained virological response following direct antiviral agents treatment. After viral eradication, we did not observe change in fasting plasma glucose (103.5 ± 7.1 vs 102.8 ± 7.2 mg/dL, P = .15) but 2-hour plasma glucose was reduced (165.2 ± 22.7 vs 138.5 ± 21.3 mg/dL, P < .001). Hepatitis C virus eradication led also to a significant reduction in HbA1c (6.1 ± 0.2% vs 5.7 ± 0.3%, P < .001) and post-load insulin resistance as assessed by the oral glucose insulin sensitivity index (6.92 ± 1.56 vs 9.52 ± 1.39 mg/kg/min, P < .001). These effects were observed despite no change in body mass index from baseline to follow-up (25.6 ± 4.3 vs 25.8 ± 4.4, P > .5). Our results indicate that hepatitis C virus eradication may early improve glucose tolerance in patients with hepatitis C virus-related cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Triglycerides-to-HDL cholesterol ratio as screening tool for impaired glucose tolerance in obese children and adolescents.

PubMed

Manco, Melania; Grugni, Graziano; Di Pietro, Mario; Balsamo, Antonio; Di Candia, Stefania; Morino, Giuseppe Stefano; Franzese, Adriana; Di Bonito, Procolo; Maffeis, Claudio; Valerio, Giuliana

2016-06-01

To identify metabolic phenotypes at increased risk of impaired glucose tolerance (IGT) in Italian overweight/obese children (n = 148, age 5-10 years) and adolescents (n = 531, age 10-17.9 year). Phenotypes were defined as follows: obesity by the 95th cut-points of the Center for Disease Control body mass index reference standards, impaired fasting glucose (fasting plasma glucose ≥100 mg/dl), high circulating triglycerides (TG), TG/HDL cholesterol ≥2.2, waist-to-height ratio (WTHR) >0.6, and combination of the latter with high TG or TG/HDL cholesterol ≥2.2. In the 148 obese children, TG/HDL-C ≥ 2.2 (OR 20.19; 95 % CI 2.50-163.28, p = 0.005) and the combination of TG/HDL-C ≥ 2.2 and WTHR > 0.60 (OR 14.97; 95 % CI 2.18-102.76, p = 0.006) were significantly associated with IGT. In the 531 adolescents, TG/HDL-C ≥ 2.2 (OR 1.991; 95 % CI 1.243-3.191, p = 0.004) and the combination with WTHR > 0.60 (OR 2.24; 95 % CI 1.29-3.87, p = 0.004) were associated with significantly increased risk of IGT. In the whole sample, having high TG levels according to the NIH National Heart, Lung and Blood Institute Expert Panel was not associated with an increased risk of presenting IGT. TG/HDL-C ratio can be useful, particularly in children, to identify obese young patients at risk of IGT. Its accuracy as screening tool in a general population needs to be verified. The combination of TG/HDL-C ratio and WTHR > 0.6 did not improve prediction. Having high TG according to the NIH definition was not associated with increased risk of developing IGT.

Regulation of liver glucokinase activity in rats with fructose-induced insulin resistance and impaired glucose and lipid metabolism.

PubMed

Francini, Flavio; Castro, María C; Gagliardino, Juan J; Massa, María L

2009-09-01

We evaluated the relative role of different regulatory mechanisms, particularly 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFK2/FBPase-2), in liver glucokinase (GK) activity in intact animals with fructose-induced insulin resistance and impaired glucose and lipid metabolism. We measured blood glucose, triglyceride and insulin concentration, glucose tolerance, liver triglyceride content, GK activity, and GK and PFK2 protein and gene expression in fructose-rich diet (FRD) and control rats. After 3 weeks, FRD rats had significantly higher blood glucose, insulin and triglyceride levels, and liver triglyceride content, insulin resistance, and impaired glucose tolerance. FRD rats also had significantly higher GK activity in the cytosolic fraction (18.3 +/- 0.35 vs. 11.27 +/- 0.34 mU/mg protein). Differences in GK protein concentration (116% and 100%) were not significant, suggesting a potentially impaired GK translocation in FRD rats. Although GK transcription level was similar, PFK2 gene expression and protein concentration were 4- and 5-fold higher in the cytosolic fraction of FRD animals. PFK2 immunological blockage significantly decreased GK activity in control and FRD rats; in the latter, this blockage decreased GK activity to control levels. Results suggest that increased liver GK activity might participate in the adaptative response to fructose overload to maintain glucose/triglyceride homeostasis in intact animals. Under these conditions, PFK2 increase would be the main enhancer of GK activity.

Beyond the morphology of the glucose curve following an oral glucose tolerance test in obese youth.

PubMed

Nolfe, Giuseppe; Spreghini, Maria Rita; Sforza, Rita Wietrzycowska; Morino, Giuseppe; Manco, Melania

2012-01-01

To describe the morphology of glucose curve during the oral glucose tolerance test (OGTT) and any association with glucose tolerance, insulin action and secretion in obese youth. Cross-sectional. OGTT data of 553 patients were analysed. Subjects were divided in groups based on the morphology (i.e. monophasic, biphasic, triphasic and upward monotonous) of glucose curve. Insulin action was estimated by the homeostasis model assessment of insulin resistance, the insulin sensitivity, the muscle insulin sensitivity and the hepatic insulin resistance indexes (HIRI), and the oral glucose insulin sensitivity (OGIS). Insulin secretion was estimated by the insulinogenic index (IGI). Disposition index, including the insulin secretion-sensitivity index-2, and areas under glucose (AUC(G)) and insulin (AUC(I)) curves were computed. In patients with normal glucose tolerance (n=522), prevalent morphology of the glucose curve was monophasic (n=285, 54%). Monophasic morphology was associated with the highest concentration of 1 h plasma glucose (P<0.0001) and AUC(G) (P<0.0001); biphasic morphology with better insulin sensitivity as estimated by OGIS (P<0.03) and lower AUC(I) (P<0.0001); triphasic morphology with the highest values of HIRI (P<0.02) and IGI (P<0.007). By combining morphologies of glucose and insulin curves or time of the glucose peak, a deeper characterisation of different phenotypes of glucose metabolism emerged. Morphologies of the glucose curve seem reflecting different metabolic phenotypes of insulin action and secretion, particularly when combined with morphologies of insulin curve or time of glucose peak. Such findings may deserve validation in cohort study, in which glucose metabolism would be estimated by using gold standard techniques.

Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues

PubMed Central

Baena, Miguel; Sangüesa, Gemma; Dávalos, Alberto; Latasa, María-Jesús; Sala-Vila, Aleix; Sánchez, Rosa María; Roglans, Núria; Laguna, Juan Carlos; Alegret, Marta

2016-01-01

Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months’ supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake. PMID:27194405

Changing the definition of impaired fasting glucose: impact on the classification of individuals and risk definition.

PubMed

Vaccaro, Olga; Riccardi, Gabriele

2005-07-01

This study evaluates the impact of lowering the diagnostic threshold for impaired fasting glucose (IFG) from 6.1 to 5.6 mmol/l as proposed by the American Diabetes Association (ADA) on the prevalence of the condition, classification of individuals, and risk definition. A total of 1,285 employees of the Italian Telephone Company aged 35-59 years without known diabetes underwent an oral glucose tolerance test (OGTT). BMI, serum cholesterol, triglycerides, and blood pressure were measured. Medication use was recorded. With the new ADA criterion, the proportion of people diagnosed with IFG increased from 3.2 to 9.7%. The newly proposed IFG category identified 41% of all subjects with impaired glucose tolerance (IGT) compared with 16.2% identified with the use of the World Health Organization criterion for IFG; the improvement in accuracy has been achieved at the cost of classifying more previously "normal" subjects as having IFG (from 2.3 to 7.3%). Both IFG and IGT were associated with an unfavorable risk profile for diabetes and cardiovascular disease, with a higher estimated risk for IGT than IFG. Even with the revised diagnostic criterion, IFG and IGT identify distinct groups that have a different background risk. The cost/benefit of preventive measures tested in people with IGT may not apply to the new IFG category.

Effects of ramipril and rosiglitazone on cardiovascular and renal outcomes in people with impaired glucose tolerance or impaired fasting glucose: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial.

PubMed

Dagenais, G R; Gerstein, H C; Holman, R; Budaj, A; Escalante, A; Hedner, T; Keltai, M; Lonn, E; McFarlane, S; McQueen, M; Teo, K; Sheridan, P; Bosch, J; Pogue, J; Yusuf, S

2008-05-01

Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) are risk factors for diabetes, cardiovascular disease (CVD), and kidney disease. We determined the effects of ramipril and rosiglitazone on combined and individual CVD and renal outcomes in people with IGT and/or IFG in the Diabetes REduction Assessment With ramipril and rosiglitazone Medication (DREAM) trial. A total of 5,269 people aged >or=30 years, with IGT and/or IFG without known CVD or renal insufficiency, were randomized to 15 mg/day ramipril versus placebo and 8 mg/day rosiglitazone versus placebo. A composite cardiorenal outcome and its CVD and renal components were assessed during the 3-year follow-up. Compared with placebo, neither ramipril (15.7% [412 of 2,623] vs. 16.0% [424 of 2,646]; hazard ratio [HR] 0.98 [95% CI 0.84-1.13]; P = 0.75) nor rosiglitazone (15.0% [394 of 2,635] vs. 16.8% [442 of 2,634]; 0.87 [0.75-1.01]; P = 0.07) reduced the risk of the cardiorenal composite outcome. Ramipril had no impact on the CVD and renal components. Rosiglitazone increased heart failure (0.53 vs. 0.08%; HR 7.04 [95% CI 1.60-31.0]; P = 0.01) but reduced the risk of the renal component (0.80 [0.68-0.93]; P = 0.005); prevention of diabetes was independently associated with prevention of the renal component (P < 0.001). Ramipril did not alter the cardiorenal outcome or its components. Rosiglitazone, which reduced diabetes, also reduced the development of renal disease but not the cardiorenal outcome and increased the risk of heart failure.

Insulin resistance, β-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis.

PubMed

Cano Megías, Marta; González Albarrán, Olga; Guisado Vasco, Pablo; Lamas Ferreiro, Adelaida; Máiz Carro, Luis

2015-02-01

diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis. To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic β-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes. It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA- IR), and pancreatic β-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC0-120) were also measured. Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse β cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC0-120). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC0-120 being higher in the different diagnostic categories as compared to NGT. In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that β-cell dysfunction is the main pathogenetic

C-Reactive Protein Concentrations and Level of Physical Activity in Men and Women With Normal and Impaired Glucose Tolerance. A Cross-Sectional Population-Based Study in Sweden.

PubMed

Hellgren, Margareta I; Larsson, Charlotte A; Daka, Bledar; Petzold, Max; Jansson, Per-Anders; Lindblad, Ulf

2016-06-01

We aimed to explore the association between self-reported leisure time physical activity (LTPA) and C-reactive protein (CRP) concentrations in men and women with and without impaired glucose tolerance (IGT). In a cross-sectional study, a random sample (n = 2,816) was examined with an oral glucose tolerance test, CRP and information about LTPA. Those with IGT or normal glucose tolerance (NGT) and CRP value ≤10 mg/L were selected (n = 2,367) for the study. An inverse association between LTPA and CRP concentrations was observed in the population (P < .001), though, only in men with IGT (P = .023) and in women with NGT. Men with IGT, reporting slight physical activity up to 4 hours a week presented significantly higher CRP concentrations than normoglycemic men (Δ0.6 mg/L, P = .004). However, this difference could not be found in men with IGT reporting more intense physical activity (Δ0.01 mg/L, P = .944). Physical inactivity seems to have greater inflammatory consequences for men (vs. women) with IGT. More importantly, although 4 hours of physical activity per week is more than the usual minimum recommendation, an even greater intensity of LTPA appears to be required to limit subclinical inflammation in men with IGT.

Ameliorating effect and potential mechanism of Rehmannia glutinosa oligosaccharides on the impaired glucose metabolism in chronic stress rats fed with high-fat diet.

PubMed

Zhang, Ruxue; Zhou, Jun; Li, Maoxing; Ma, Haigang; Qiu, Jianguo; Luo, Xiaohong; Jia, Zhengping

2014-04-15

The aim of this study was to determine whether the Rehmannia glutinosa oligosaccharides (ROS) ameliorate the impaired glucose metabolism and the potential mechanism in chronic stress rats fed with high-fat diet. The rats were fed by a high-fat diet and simultaneously stimulated by chronic stress over 5 weeks. Body weight, fasting plasma glucose, intraperitoneal glucose tolerance test (IPGTT), plasma lipids, gluconeogenesis test (GGT), glycogen content, and corticosterone, insulin and leptin levels were measured. The results showed that ROS administration (100, 200 mg/kg, i.g.) for 5 weeks exerted the effects of increasing the organ weights of thymus and spleen, lowering the fasting plasma glucose level, improving impaired glucose tolerance, increasing the contents of liver and muscle glycogen, decreasing the gluconeogenesis ability, plasma-free fatty acid's level, as well as plasma triglyceride and total cholesterol levels in chronic stress and high-fat fed rats, especially in the group of 200mg/kg; while the plasma corticosterone level was decreased, and plasma leptin level was increased. These results suggest that ROS exert an ameliorating effect of impaired glucose metabolism in chronic stress rats fed with high-fat diet, and the potential mechanism may be mediated through rebuilding the glucose homeostasis in the neuroendocrine immuno-modulation (NIM) network through multilinks and multitargets. Copyright © 2013 Elsevier GmbH. All rights reserved.

The C57BL/6J Niemann-Pick C1 mouse model with decreased gene dosage has impaired glucose tolerance independent of body weight.

PubMed

Jelinek, David; Castillo, Joseph J; Garver, William S

2013-09-15

The human Niemann-Pick C1 (NPC1) gene has been found to be associated with extreme (early-onset and morbid-adult) obesity and type 2 diabetes independent of body weight. We previously performed growth studies using BALB/cJ Npc1 normal (Npc1+/+) and Npc1 heterozygous (Npc1+/-) mice and determined that decreased Npc1 gene dosage interacts with a high-fat diet to promote weight gain and adiposity. The present study was performed using both BALB/cJ and C57BL/6J Npc1+/+ and Npc1+/- mice to determine if decreased Npc1 gene dosage predisposes to metabolic features associated with type 2 diabetes. The results indicated that C57BL/6J Npc1+/- mice, but not BALB/cJ Npc1+/- mice, have impaired glucose tolerance when fed a low-fat diet and independent of body weight. The results also suggest that an accumulation of liver free fatty acids and hepatic lipotoxicity marked by an elevation in the amount of plasma alanine aminotransferase (ALT) may be responsible for hepatic insulin resistance and impaired glucose tolerance. Finally, the peroxisome-proliferator activated receptor α (PPARα) and sterol regulatory element-binding protein-1 (SREBP-1) pathways known to have a central role in regulating free fatty acid metabolism were downregulated in the livers, but not in the adipose or muscle, of C57BL/6J Npc1+/- mice compared to C57BL/6J Npc1+/+ mice. Therefore, decreased Npc1 gene dosage among two different mouse strains interacts with undefined modifying genes to manifest disparate yet often related metabolic diseases. Published by Elsevier B.V.

The role of α1-adrenergic receptors in regulating metabolism: increased glucose tolerance, leptin secretion and lipid oxidation.

PubMed

Shi, Ting; Papay, Robert S; Perez, Dianne M

2017-04-01

The role of α 1 -adrenergic receptors (α 1 -ARs) and their subtypes in metabolism is not well known. Most previous studies were performed before the advent of transgenic mouse models and utilized transformed cell lines and poorly selective antagonists. We have now studied the metabolic regulation of the α 1A - and α 1B -AR subtypes in vivo using knock-out (KO) and transgenic mice that express a constitutively active mutant (CAM) form of the receptor, assessing subtype-selective functions. CAM mice increased glucose tolerance while KO mice display impaired glucose tolerance. CAM mice increased while KO decreased glucose uptake into white fat tissue and skeletal muscle with the CAM α 1A -AR showing selective glucose uptake into the heart. Using indirect calorimetry, both CAM mice demonstrated increased whole body fatty acid oxidation, while KO mice preferentially oxidized carbohydrate. CAM α 1A -AR mice displayed significantly decreased fasting plasma triglycerides and glucose levels while α 1A -AR KO displayed increased levels of triglycerides and glucose. Both CAM mice displayed increased plasma levels of leptin while KO mice decreased leptin levels. Most metabolic effects were more efficacious with the α 1A -AR subtype. Our results suggest that stimulation of α 1 -ARs results in a favorable metabolic profile of increased glucose tolerance, cardiac glucose uptake, leptin secretion and increased whole body lipid metabolism that may contribute to its previously recognized cardioprotective and neuroprotective benefits.

A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study.

PubMed

Tripathy, Devjit; Cobb, Jeff E; Gall, Walter; Adam, Klaus-Peter; George, Tabitha; Schwenke, Dawn C; Banerji, MaryAnn; Bray, George A; Buchanan, Thomas A; Clement, Stephen C; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Reaven, Peter D; Musi, Nicolas; Ferrannini, Ele; DeFronzo, Ralph A

2015-05-01

The objective was to test the clinical utility of Quantose M(Q) to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose M(Q) is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal. Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.4 years. At baseline and study end, fasting plasma metabolites required for determination of Quantose, glycated hemoglobin, and oral glucose tolerance test with frequent plasma insulin and glucose measurements to calculate the Matsuda index of insulin sensitivity were obtained. Pioglitazone treatment lowered IGT conversion to diabetes (hazard ratio = 0.25; 95% confidence interval = 0.13-0.50; P < .0001). Although glycated hemoglobin did not track with insulin sensitivity, Quantose M(Q) increased in pioglitazone-treated subjects (by 1.45 [3.45] mg·min(-1)·kgwbm(-1)) (median [interquartile range]) (P < .001 vs placebo), as did the Matsuda index (by 3.05 [4.77] units; P < .0001). Quantose M(Q) correlated with the Matsuda index at baseline and change in the Matsuda index from baseline (rho, 0.85 and 0.79, respectively; P < .0001) and was progressively higher across closeout glucose tolerance status (diabetes, IGT, normal glucose tolerance). In logistic models including only anthropometric and fasting measurements, Quantose M(Q) outperformed both Matsuda and fasting insulin in predicting incident diabetes. In IGT subjects, Quantose M(Q) parallels changes in insulin sensitivity and glucose tolerance with pioglitazone therapy. Due to its strong correlation with improved insulin sensitivity and its ease of use, Quantose M(Q) may serve as a useful clinical test to identify and monitor therapy in insulin-resistant patients.

A Novel Insulin Resistance Index to Monitor Changes in Insulin Sensitivity and Glucose Tolerance: the ACT NOW Study

PubMed Central

Tripathy, Devjit; Cobb, Jeff E.; Gall, Walter; Adam, Klaus-Peter; George, Tabitha; Schwenke, Dawn C.; Banerji, MaryAnn; Bray, George A.; Buchanan, Thomas A.; Clement, Stephen C.; Henry, Robert R.; Kitabchi, Abbas E.; Mudaliar, Sunder; Ratner, Robert E.; Stentz, Frankie B.; Reaven, Peter D.; Musi, Nicolas; Ferrannini, Ele

2015-01-01

Objective: The objective was to test the clinical utility of Quantose MQ to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose MQ is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal. Research Design and Methods: Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.4 years. At baseline and study end, fasting plasma metabolites required for determination of Quantose, glycated hemoglobin, and oral glucose tolerance test with frequent plasma insulin and glucose measurements to calculate the Matsuda index of insulin sensitivity were obtained. Results: Pioglitazone treatment lowered IGT conversion to diabetes (hazard ratio = 0.25; 95% confidence interval = 0.13–0.50; P < .0001). Although glycated hemoglobin did not track with insulin sensitivity, Quantose MQ increased in pioglitazone-treated subjects (by 1.45 [3.45] mg·min−1·kgwbm−1) (median [interquartile range]) (P < .001 vs placebo), as did the Matsuda index (by 3.05 [4.77] units; P < .0001). Quantose MQ correlated with the Matsuda index at baseline and change in the Matsuda index from baseline (rho, 0.85 and 0.79, respectively; P < .0001) and was progressively higher across closeout glucose tolerance status (diabetes, IGT, normal glucose tolerance). In logistic models including only anthropometric and fasting measurements, Quantose MQ outperformed both Matsuda and fasting insulin in predicting incident diabetes. Conclusions: In IGT subjects, Quantose MQ parallels changes in insulin sensitivity and glucose tolerance with pioglitazone therapy. Due to its strong correlation with improved insulin sensitivity and its ease of use, Quantose MQ may serve as a useful clinical test to identify and monitor therapy in

Acute Inactivity Impairs Glycemic Control but Not Blood Flow to Glucose Ingestion

PubMed Central

Reynolds, Leryn J; Credeur, Daniel P; Holwerda, Seth W; Leidy, Heather J; Fadel, Paul J; Thyfault, John P

2014-01-01

Purpose Insulin-stimulated increases in skeletal muscle blood flow play a role in glucose disposal. Indeed, 7 days of aerobic exercise in type 2 diabetes patients increased blood flow responses to an oral glucose tolerance test (OGTT) and improved glucose tolerance. More recent work suggests that reduced daily physical activity impairs glycemic control (GC) in healthy individuals. Herein, we sought to determine if an acute reduction in daily activity (from >10,000 to <5,000 steps/day) for 5 days (RA5) in healthy individuals reduced insulin-stimulated blood flow and GC in parallel and if a 1 day return to activity (RTA1) improved these outcomes. Methods OGTTs were performed as a stimulus to increase insulin in 14 healthy, recreationally active men (24±1.1 yrs) at baseline, RA5, and RTA1. Measures of insulin sensitivity (Matsuda index) and femoral and brachial artery blood flow were made during the OGTT. Free living measures of GC including peak postprandial glucose (peak PPG) were also made via continuous glucose monitoring. Results Femoral and brachial artery blood flow increased during the OGTT but neither was significantly impacted by changes in physical activity (p>0.05). However, insulin sensitivity was decreased by RA5 (11.3±1.5 to 8.0±1.0; p<0.05). Likewise, free living GC measures of peak post prandial blood glucose (113±3 to 123±5 mg/dL; p<0.05) was significantly increased at RA5. Interestingly, insulin sensitivity and GC as assessed by peak PPG were not restored after RTA1 (p>0.05). Conclusions Thus, acute reductions in physical activity impaired GC and insulin sensitivity; however blood flow responses to an OGTT were not affected. Further, a 1 day return to activity was not sufficient to normalize GC following 5 days of reduced daily physical activity. PMID:25207931

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.

Reversal of diuretic-associated impaired glucose tolerance and new-onset diabetes: results of the STAR-LET study.

PubMed

Bakris, George; Molitch, Mark; Zhou, Qian; Sarafidis, Pantelis; Champion, Annette; Bacher, Peter; Sowers, James R

2008-01-01

Reversal of new-onset diabetes secondary to thiazide diuretic use remains questionable. STAR-LET was a 6-month extension of the Study of Trandolapril/Verapamil SR and Insulin Resistance (STAR), which assessed the effects of a fixed-dose renin-angiotensin system inhibitor (RASI)/hydrochlorothiazide (HCTZ) combination on changes in 2-hour oral glucose tolerance test (OGTT) results. STAR-LET explored whether the glycemic impact of HCTZ could be reversed by conversion to a RASI/verapamil combination. The primary outcome was change in 2-hour OGTT results. Fifty-one percent of the STAR patients were enrolled in STAR-LET. The 2-hour OGTT value (mmol/L) was unchanged from STAR baseline in the RASI/verapamil group (7.7+/-2.4 vs 8.1+/-3.3; P=.18) and improved in those who were switched from RASI/HCTZ to RASI/verapamil (8.5+/-3.0 vs 7.2+/-2.3; P<.001). This exploratory study suggests that the impairment in glycemic control seen with use of a thiazide diuretic combined with a RASI can be reversed by switching to a regimen that does not include a diuretic.

Prevalence of diabetes mellitus and impaired glucose tolerance in a New Zealand multiracial workforce.

PubMed

Scragg, R; Baker, J; Metcalf, P; Dryson, E

1991-09-25

A cross sectional survey was carried out among a multiracial workforce of 5677 staff aged 40 to 64 years at worksites in Auckland and Tokoroa to determine the prevalence of diabetes mellitus and impaired glucose tolerance (IGT). The prevalences of diabetes mellitus and IGT were both similar for men and women, but increased with age. The relative risks for diabetes mellitus and for IGT were both inversely associated with gross annual household income, independent of age and ethnicity, being 1.61 (95% Cl = 1.10, 2.37) and 1.80 (95% Cl = 1.21, 2.67) respectively, in the lowest income group (less than $30,000) compared with the highest (greater than $40,000). Compared with Europeans, the relative risk of diabetes mellitus was significantly increased among Maori (3.63; 95% Cl = 2.48, 5.32), Pacific Islanders (2.34; 95% Cl = 1.50, 3.66) and Asians (5.97; 95% Cl = 2.61, 13.65), after controlling for age, income and body mass index. The increased prevalence of diabetes mellitus among Maori and Pacific Islanders, but not in Asians, could be partly attributed to their increased levels of obesity compared with Europeans. However, other factors, in addition to obesity, explain the increased diabetes prevalence in nonEuropean groups.

Improving glucose tolerance by muscle-damaging exercise.

PubMed

Ho, Chien-Te; Otaka, Machiko; Kuo, Chia-Hua

2017-04-01

Tissue damage is regarded as an unwanted medical condition to be avoided. However, introducing tolerable tissue damages has been used as a therapeutic intervention in traditional and complementary medicine to cure discomfort and illness. Eccentric exercise is known to cause significant necrosis and insulin resistance of skeletal muscle. The purpose of this study was to determine the magnitude of muscle damage and blood glucose responses during an oral glucose tolerance test (OGTT) after eccentric training in 21 young participants. They were challenged by 5 times of 100-meter downhill sprinting and 20 times of squats training at 30 pounds weight load for 3 days, which resulted in a wide spectrum of muscle creatine kinase (CK) surges in plasma, 48 h after the last bout of exercise. Participants were then divided into two groups according the magnitude of CK increases (low CK: +48% ± 0.3; high CK: +137% ± 0.5, P < 0.05). Both groups show comparable decreases in blood glucose levels in OGTT, suggesting that this muscle-damaging exercise does not appear to decrease but rather improve glycemic control in men. The result of the study rejects the hypothesis that eccentric exercise decreases glucose tolerance. Improved glucose tolerance with CK increase implicates a beneficial effect of replacing metabolically weaker muscle fibers by eccentric exercise in Darwinian natural selection fashion.

Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.

PubMed

Sheikh, Saba; Gudipaty, Lalitha; De Leon, Diva D; Hadjiliadis, Denis; Kubrak, Christina; Rosenfeld, Nora K; Nyirjesy, Sarah C; Peleckis, Amy J; Malik, Saloni; Stefanovski, Darko; Cuchel, Marina; Rubenstein, Ronald C; Kelly, Andrea; Rickels, Michael R

2017-01-01

Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced β-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite "normal" glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF. © 2017 by the American Diabetes Association.

Coexistence of insulin resistance and increased glucose tolerance in pregnant rats: a physiological mechanism for glucose maintenance.

PubMed

Carrara, Marcia Aparecida; Batista, Márcia Regina; Saruhashi, Tiago Ribeiro; Felisberto, Antonio Machado; Guilhermetti, Marcio; Bazotte, Roberto Barbosa

2012-06-06

The contribution of insulin resistance (IR) and glucose tolerance to the maintenance of blood glucose levels in non diabetic pregnant Wistar rats (PWR) was investigated. PWR were submitted to conventional insulin tolerance test (ITT) and glucose tolerance test (GTT) using blood sample collected 0, 10 and 60 min after intraperitoneal insulin (1 U/kg) or oral (gavage) glucose (1g/kg) administration. Moreover, ITT, GTT and the kinetics of glucose concentration changes in the fed and fasted states were evaluated with a real-time continuous glucose monitoring system (RT-CGMS) technique. Furthermore, the contribution of the liver glucose production was investigated. Conventional ITT and GTT at 0, 7, 14 and 20 days of pregnancy revealed increased IR and glucose tolerance after 20 days of pregnancy. Thus, this period of pregnancy was used to investigate the kinetics of glucose changes with the RT-CGMS technique. PWR (day 20) exhibited a lower (p<0.05) glucose concentration in the fed state. In addition, we observed IR and increased glucose tolerance in the fed state (PWR-day 20 vs. day 0). Furthermore, our data from glycogenolysis and gluconeogenesis suggested that the liver glucose production did not contribute to these changes in insulin sensitivity and/or glucose tolerance during late pregnancy. In contrast to the general view that IR is a pathological process associated with gestational diabetes, a certain degree of IR may represent an important physiological mechanism for blood glucose maintenance during fasting. Copyright © 2012 Elsevier Inc. All rights reserved.

Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats.

PubMed

Appleton, D J; Rand, J S; Sunvold, G D; Priest, J

2002-03-01

The effect of dietary chromium supplementation on glucose and insulin metabolism in healthy, non-obese cats was evaluated. Thirty-two cats were randomly divided into four groups and fed experimental diets consisting of a standard diet with 0 ppb (control), 150 ppb, 300 ppb, or 600 ppb added chromium as chromium tripicolinate. Intravenous glucose tolerance, insulin tolerance and insulin sensitivity tests with minimal model analysis were performed before and after 6 weeks of feeding the test diets. During the glucose tolerance test, glucose concentrations, area under the glucose concentration-time curve, and glucose half-life (300 ppb only), were significantly lower after the trial in cats supplemented with 300 ppb and 600 ppb chromium, compared with values before the trial. Fasting glucose concentrations measured on a different day in the biochemistry profile were also significantly lower after supplementation with 600 ppb chromium. There were no significant differences in insulin concentrations or indices in either the glucose or insulin tolerance tests following chromium supplementation, nor were there any differences between groups before or after the dietary trial.Importantly, this study has shown a small but significant, dose-dependent improvement in glucose tolerance in healthy, non-obese cats supplemented with dietary chromium. Further long-term studies are warranted to determine if the addition of chromium to feline diets is advantageous. Cats most likely to benefit are those with glucose intolerance and insulin resistance from lack of exercise, obesity and old age. Healthy cats at risk of glucose intolerance and diabetes from underlying low insulin sensitivity or genetic factors may also benefit from long-term chromium supplementation. Copyright 2002 ESFM and AAFP.

Glucose in vaginal secretions before and after oral glucose tolerance testing in women with and without recurrent vulvovaginal candidiasis.

PubMed

Ehrström, Sophia; Yu, Anna; Rylander, Eva

2006-12-01

To measure the change of glucose in vaginal secretions during glucose tolerance testing in women with recurrent vulvovaginal candidiasis and in healthy control subjects. Thirty-eight women with recurrent vulvovaginal candidiasis and 45 healthy, age-matched controls completed a health questionnaire regarding general and gynecologic health and food and alcohol habits. They all underwent an oral glucose tolerance test and a vaginal examination. Vaginal secretion was collected from the proximal part of the vagina. Glucose in plasma and in vaginal secretions were measured at fasting and after 2 hours and analyzed with the hexokinase method. A sample size analysis showed that the number of subjects included in the study was sufficient for a beta value of 0.80, at the significance level of alpha=.05, at a difference in glucose in vaginal secretions of 30% after oral glucose tolerance test. In healthy women, the median level of glucose in vaginal secretions was 5.2 mM before and 3.7 mM after oral glucose tolerance test, and plasma glucose was 5.0 mM before and 5.8 mM after oral glucose tolerance test. No significant difference was seen regarding change of glucose level in vaginal secretions and plasma glucose after testing, compared with before oral glucose tolerance testing. There were no differences between women with recurrent vulvovaginal candidiasis and control subjects regarding change in glucose level in vaginal secretions or in plasma during oral glucose tolerance test. II-2.

The GLP-1 response to glucose does not mediate beta and alpha cell dysfunction in Hispanics with abnormal glucose metabolism.

PubMed

Adams, Elizabeth; Genter, Pauline; Keefe, Emma; Sandow, Kevin; Gray, Virginia; Rotter, Jerome I; Chen, Yii-Der Ida; Ipp, Eli

2018-01-01

Glucagon-like peptide-1 (GLP-1) contributes to insulin secretion after meals. Though Hispanics have increased risk for type 2 diabetes mellitus, it is unknown if impaired GLP-1 secretion contributes to this risk. We therefore studied plasma GLP-1 secretion and action in Hispanic adults. Hispanic (H; n = 31) and non-Hispanic (nH; n = 15) participants underwent an oral glucose tolerance test (OGTT). All participants were categorized by glucose tolerance into four groups: normal glucose tolerant non-Hispanic (NGT-nH; n = 15), normal glucose tolerant Hispanic (NGT-H; n = 12), impaired glucose tolerant Hispanic (IGT-H; n = 11), or newly diagnosed type 2 diabetes mellitus, Hispanic (T2D-H; n = 8). Glucose-induced increments in plasma GLP-1 (Δ-GLP-1) were not different in NGT-H and NGT-nH (p = .38), nor amongst Hispanic subgroups with varying degrees of glucose homeostasis (p = .6). In contrast, the insulinogenic index in T2D-H group was lower than the other groups (p = .016). Subjects with abnormal glucose homeostasis (AGH), i.e., T2D-H plus IGT-H, had a diminished glucagon suppression index compared to patients with normal glucose homeostasis (NGT-H plus NGT-nH) (p = .035). GLP-1 responses to glucose were similar in Hispanic and Non-Hispanic NGT. Despite similar glucose-induced Δ-GLP-1, insulin and glucagon responses were abnormal in T2D-H and AGH, respectively. Thus, impaired GLP-1 secretion is unlikely to play a role in islet dysfunction in T2D. Although GLP-1 therapeutics enhance insulin secretion and glucagon suppression, it is likely due to pharmacological amplification of the GLP-1 pathways rather than treatment of hormonal deficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

Coffee and caffeine improve insulin sensitivity and glucose tolerance in C57BL/6J mice fed a high-fat diet.

PubMed

Matsuda, Yuji; Kobayashi, Misato; Yamauchi, Rie; Ojika, Makoto; Hiramitsu, Masanori; Inoue, Takashi; Katagiri, Takao; Murai, Atsushi; Horio, Fumihiko

2011-01-01

We have previously demonstrated that coffee and caffeine ameliorated hyperglycemia in spontaneously diabetic KK-A(y) mice. This present study evaluates the antidiabetic effects of coffee and caffeine on high-fat-diet-induced impaired glucose tolerance in C57BL/6J mice. C57BL/6J mice fed a high-fat diet were given regular drinking water (control group), or a 2.5-fold-diluted coffee or caffeine solution (200 mg/L) for 17 weeks. The ingestion of coffee or caffeine improved glucose tolerance, insulin sensitivity, and hyperinsulinemia when compared with mice in the control group. The adipose tissue mRNA levels of inflammatory adipocytokines (MCP-1 and IL-6) and the liver mRNA levels of genes related to fatty acid synthesis were lower in the coffee and caffeine groups than those in the control group. These results suggest that coffee and caffeine exerted an ameliorative effect on high-fat-diet-induced impaired glucose tolerance by improving insulin sensitivity. This effect might be attributable in part to the reduction of inflammatory adipocytokine expression.

Improved glucose tolerance four hours after taking guar with glucose.

PubMed

Jenkins, D J; Wolever, T M; Nineham, R; Sarson, D L; Bloom, S R; Ahern, J; Alberti, K G; Hockaday, T D

1980-07-01

To gain some insights about the possible cumulative metabolic effect after a high-fibre meal, 6 subjects took two 80 g oral glucose loads, 4 h apart. Addition of 22.3 g guar to the first load decreased the rise in blood glucose and insulin after the second (guar-free) load by 50% (p less than 0.002) and 31% (p less than 0.02) respectively. This corresponded with decreased 3-hydroxybutyrate levels at the start of the glucose tolerance test after guar (by 20%, p less than 0.02). When no guar was added to the first glucose load, both 3-hydroxybutyrate and non-esterified fatty acids tended to rise before the second test. No significant effect was seen in the responses of the gut hormones, gastric inhibitory peptide and enteroglucagon. Spreading the intake of the first 80 g of glucose over the initial 4 h (2 subjects) similarly flattened the glycaemic but increased the insulin response. The effect of guar on carbohydrate and fat metabolism, therefore, lasts at least 4 h and may result in improved carbohydrate tolerance to subsequent guar-free meals.

Dual specificity phosphatase 6 deficiency is associated with impaired systemic glucose tolerance and reversible weight retardation in mice

PubMed Central

Schriever, Sonja C.; Müller, Timo D.; Tschöp, Matthias H.

2017-01-01

Here, we aimed to investigate the potential role of DUSP6, a dual specificity phosphatase, that specifically inactivates extracellular signal-regulated kinase (ERK), for the regulation of body weight and glucose homeostasis. We further assessed whether metabolic challenges affect Dusp6 expression in selected brain areas or white adipose tissue. Hypothalamic Dusp6 mRNA levels remained unchanged in chow-fed lean vs. high fat diet (HFD) fed obese C57Bl/6J mice, and in C57Bl/6J mice undergoing prolonged fasting or refeeding with fat free diet (FFD) or HFD. Similarly, Dusp6 expression levels were unchanged in selected brain regions of Lepob mice treated with 1 mg/kg of leptin for 6 days, compared to pair-fed or saline-treated Lepob controls. Dusp6 expression levels remained unaltered in vitro in primary adipocytes undergoing differentiation, but were increased in eWAT of HFD-fed obese C57Bl/6J mice, compared to chow-fed lean controls. Global chow-fed DUSP6 KO mice displayed reduced body weight and lean mass and slightly increased fat mass at a young age, which is indicative for early-age weight retardation. Subsequent exposure to HFD led to a significant increase in lean mass and body weight in DUSP6 deficient mice, compared to WT controls. Nevertheless, after 26 weeks of high-fat diet exposure, we observed comparable body weight, fat and lean mass in DUSP6 WT and KO mice, suggesting overall normal susceptibility to develop obesity. In line with the increased weight gain to compensate for early-age weight retardation, HFD-fed DUSP6 KO displayed increased expression levels of anabolic genes involved in lipid and cholesterol metabolism in the epididymal white adipose tissue (eWAT), compared to WT controls. Glucose tolerance was perturbed in both chow-fed lean or HFD-fed obese DUSP6 KO, compared to their respective WT controls. Overall, our data indicate that DUSP6 deficiency has limited impact on the regulation of energy metabolism, but impairs systemic glucose tolerance

A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study.

PubMed

Saad, M F; Anderson, R L; Laws, A; Watanabe, R M; Kades, W W; Chen, Y D; Sands, R E; Pei, D; Savage, P J; Bergman, R N

1994-09-01

An insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis was compared with the glucose clamp in 11 subjects with normal glucose tolerance (NGT), 20 with impaired glucose tolerance (IGT), and 24 with non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity index (SI) was calculated from FSIGTT using 22- and 12-sample protocols (SI(22) and SI(12), respectively). Insulin sensitivity from the clamp was expressed as SI(clamp) and SIP(clamp). Minimal model parameters were similar when calculated with SI(22) and SI(12). SI could not be distinguished from 0 in approximately 50% of diabetic patients with either protocol. SI(22) correlated significantly with SI(clamp) in the whole group (r = 0.62), and in the NGT (r = 0.53), IGT (r = 0.48), and NIDDM (r = 0.41) groups (P < 0.05 for each). SI(12) correlated significantly with SI(clamp) in the whole group (r = 0.55, P < 0.001) and in the NGT (r = 0.53, P = 0.046) and IGT (r = 0.58, P = 0.008) but not NIDDM (r = 0.30, P = 0.085) groups. When SI(22), SI(clamp), and SIP(clamp) were expressed in the same units, SI(22) was 66 +/- 5% (mean +/- SE) and 50 +/- 8% lower than SI(clamp) and SIP(clamp), respectively. Thus, minimal model analysis of the insulin-modified FSIGTT provides estimates of insulin sensitivity that correlate significantly with those from the glucose clamp. The correlation was weaker, however, in NIDDM. The insulin-modified FSIGTT can be used as a simple test for assessment of insulin sensitivity in population studies involving nondiabetic subjects. Additional studies are needed before using this test routinely in patients with NIDDM.

Sensitivity and specificity of different methods for cystic fibrosis-related diabetes screening: is the oral glucose tolerance test still the standard?

PubMed

Mainguy, Catherine; Bellon, Gabriel; Delaup, Véronique; Ginoux, Tiphanie; Kassai-Koupai, Behrouz; Mazur, Stéphane; Rabilloud, Muriel; Remontet, Laurent; Reix, Philippe

2017-01-01

Cystic fibrosis-related diabetes (CFRD) is a late cystic fibrosis (CF)-associated comorbidity whose prevalence is increasing sharply lifelong. Guidelines for glucose metabolism (GM) monitoring rely on the oral glucose tolerance test (OGTT). However, this test is neither sensitive nor specific. The aim of this study was to compare sensitivity and specificity of different methods for GM monitoring in children and adolescents with CF. Continuous glucose monitoring system (CGMS), used as the reference method, was compared with the OGTT, intravenous glucose tolerance test (IGTT), homeostasis model assessment index of insulin resistance (HOMA-IR), homeostasis model assessment index of β-cell function (HOMA-%B) and glycated haemoglobin A1C. Patients were classified into three groups according to CGMS: normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM). Twenty-nine patients (median age: 13.1 years) were recruited. According to CGMS, 11 had DM, 12 IGT and six NGT, whereas OGTT identified three patients with DM and five with IGT. While 13 of 27 had insulin deficiency according to IGTT, there was 19 of 28 according to HOMA-%B. According to HOMA-IR, 12 of 28 had insulin resistance. HOMA-%B was the most sensitive method for CFRD screening [sensitivity 91% (95% CI), specificity 47% (95% CI) and negative predictive value 89% (95% CI)]. OGTT showed the weak capacity to diagnose DM in CF and should no longer be considered as the reference method for CFRD screening in patients with CF. In our study, HOMA-%B showed promising metrics for CFRD screening. Finally, CGMS revealed that pathological glucose excursions were frequent even early in life.

Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial.

PubMed

Holman, Rury R; Coleman, Ruth L; Chan, Juliana C N; Chiasson, Jean-Louis; Feng, Huimei; Ge, Junbo; Gerstein, Hertzel C; Gray, Richard; Huo, Yong; Lang, Zhihui; McMurray, John J; Rydén, Lars; Schröder, Stefan; Sun, Yihong; Theodorakis, Michael J; Tendera, Michal; Tucker, Lynne; Tuomilehto, Jaakko; Wei, Yidong; Yang, Wenying; Wang, Duolao; Hu, Dayi; Pan, Changyu

2017-11-01

The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced. The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, double-blind, placebo-controlled, phase 4 trial, with patients recruited from 176 hospital outpatient clinics in China. Chinese patients with coronary heart disease and impaired glucose tolerance were randomly assigned (1:1), in blocks by site, by a centralised computer system to receive oral acarbose (50 mg three times a day) or matched placebo, which was added to standardised cardiovascular secondary prevention therapy. All study staff and patients were masked to treatment group allocation. The primary outcome was a five-point composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospital admission for unstable angina, and hospital admission for heart failure, analysed in the intention-to-treat population (all participants randomly assigned to treatment who provided written informed consent). The secondary outcomes were a three-point composite outcome (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, development of diabetes, and development of impaired renal function. The safety population comprised all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT00829660, and the International Standard Randomised Controlled Trial Number registry, number ISRCTN91899513. Between March 20, 2009

A novel test for IGT utilizing metabolite markers of glucose tolerance.

PubMed

Cobb, Jeff; Eckhart, Andrea; Perichon, Regis; Wulff, Jacob; Mitchell, Matthew; Adam, Klaus-Peter; Wolfert, Robert; Button, Eric; Lawton, Kay; Elverson, Robert; Carr, Bernadette; Sinnott, Margaret; Ferrannini, Ele

2015-01-01

The oral glucose tolerance test (OGTT) is the only method to diagnose patients having impaired glucose tolerance (IGT), but its use has diminished considerably in recent years. Metabolomic profiling studies have identified a number of metabolites whose fasting levels are associated with dysglycemia and type 2 diabetes. These metabolites may serve as the basis of an alternative test for IGT. Using the stable isotope dilution technique, quantitative assays were developed for 23 candidate biomarker metabolites. These metabolites were measured in fasting plasma samples taken just prior to an OGTT from 1623 nondiabetic subjects: 955 from the Relationship between Insulin Sensitivity and Cardiovascular Disease Study (RISC Study; 11.7% IGT) and 668 subjects from the Diabetes Mellitus and Vascular Health Initiative (DMVhi) cohort from the DEXLIFE project (11.8% IGT). The associations between metabolites, anthropometric, and metabolic parameters and 2hPG values were assessed by Pearson correlation coefficients and Random Forest classification analysis to rank variables for their ability to distinguish IGT from normal glucose tolerance (NGT). Multivariate logistic regression models for estimating risk of IGT were developed and evaluated using AUCs calculated from the corresponding ROC curves. A model based on the fasting plasma levels of glucose, α-hydroxybutyric acid, β-hydroxybutyric acid, 4-methyl-2-oxopentanoic acid, linoleoylglycerophosphocholine, oleic acid, serine and vitamin B5 was optimized in the RISC cohort (AUC = 0.82) and validated in the DMVhi cohort (AUC = 0.83). A novel, all-metabolite-based test is shown to be a discriminate marker of IGT. It requires only a single fasted blood draw and may serve as a more convenient surrogate for the OGTT or as a means of identifying subjects likely to be IGT. © 2014 Diabetes Technology Society.

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.

Obese mice on a high-fat alternate-day fasting regimen lose weight and improve glucose tolerance.

PubMed

Joslin, P M N; Bell, R K; Swoap, S J

2017-10-01

Alternate-day fasting (ADF) causes body weight (BW) loss in humans and rodents. However, it is not clear that ADF while maintaining a high-fat (HF) diet results in weight loss and the accompanying improvement in control of circulating glucose. We tested the hypotheses that a high-fat ADF protocol in obese mice would result in (i) BW loss, (ii) improved glucose control, (iii) fluctuating phenotypes on 'fasted' days when compared to 'fed' days and (iv) induction of torpor on 'fasted days'. We evaluated the physiological effects of ADF in diet-induced obese mice for BW, heart rate (HR), body temperature (T b ), glucose tolerance, insulin responsiveness, blood parameters (leptin, insulin, free fatty acids) and hepatic gene expression. Diet-induced obese male C57BL/6J mice lost one-third of their pre-diet BW while on an ADF diet for 10 weeks consisting of HF food. The ADF protocol improved glucose tolerance and insulin sensitivity, although mice on a fast day were less glucose tolerant than the same mice on a fed day. ADF mice on a fast day had low circulating insulin, but had an enhanced response to an insulin-assisted glucose tolerance test, suggesting the impaired glucose tolerance may be a result of insufficient insulin production. On fed days, ADF mice were the warmest, had a high HR and displayed hepatic gene expression and circulating leptin that closely mimicked that of mice fed an ad lib HF diet. ADF mice never entered torpor as assessed by HR and T b . However, on fast days, they were the coolest, had the slowest HR, and displayed hepatic gene expression and circulating leptin that closely mimicked that of Chow-Fed mice. Collectively, the ADF regimen with a HF diet in obese mice results in weight loss, improved blood glucose control, and daily fluctuations in selected physiological and biochemical parameters in the mouse. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Normal adiponectin levels despite abnormal glucose tolerance (or diabetes) and inflammation in adult patients with cystic fibrosis.

PubMed

Hammana, I; Malet, A; Costa, M; Brochiero, E; Berthiaume, Y; Potvin, S; Chiasson, J-L; Coderre, L; Rabasa-Lhoret, R

2007-06-01

Circulating adiponectin levels are negatively associated with glucose intolerance, inflammation and central adiposity. Since these conditions are common in cystic fibrosis (CF), we examined whether adiponectin values are altered in these patients. To determine if CF patients have altered adiponectin levels and if these levels correlate with glucose tolerance categories (normal, impaired glucose tolerance (IGT) and cystic fibrosis-related diabetes (CFRD)), insulin resistance or inflammatory markers such as fibrinogen and C-reactive protein (CRP). Oral glucose tolerance tests (OGTTs) were performed and adiponectin levels were measured in 90 CF patients not known to be diabetic and 15 healthy controls matched for age, sex and body mass index (BMI). Inflammatory markers, serum albumin concentrations and the clinical status of CF patients (i.e. pulmonary function) were also examined. CF pathology was characterized by a high prevalence (43.5%) of glucose tolerance abnormalities: 26.5% of IGT and 17.0% of newly diagnosed CFRD. CF patients also presented systemic inflammation as revealed by a significant increase of fibrinogen (P=0.029) in all patients and higher CRP levels in CFRD patients compared to the controls (P<0.05). On the other hand, CF and control subjects had similar albumin serum concentration. While CF patients and controls had similar serum adiponectin values, women had significantly higher hormone levels than men (P<0.001). Adiponectin levels did not correlate with glucose tolerance, inflammatory markers or insulin resistance. On the other hand, they correlated positively with both total and HDL-cholesterol (P<0.001). CF patients did not show any alterations in adiponectin levels despite insulin resistance, glucose intolerance and sub clinical chronic inflammation. Thus, CF appears to be one of the rare conditions in which discordance between adiponectin values and insulin resistance or inflammation is evident.

Short-term effects of non-surgical periodontal therapy on clinical measures of impaired glucose tolerance in people with prediabetes and chronic periodontitis.

PubMed

Giblin, Lori J; Boyd, Linda D; Rainchuso, Lori; Chadbourne, Dianne

2014-01-01

Diabetes and periodontal disease are conditions considered to be biologically linked. Prediabetes is a condition in which individuals have blood glucose levels, impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) or glycated hemoglobin (A1C) levels higher than normal but not high enough to be classified as diabetes. Few human studies address the relationship between periodontitis and prediabetes or clarify an association between periodontitis and prediabetes. The purpose of this pilot study was to examine the impact of non-surgical periodontal therapy (NSPT) on clinical measures of glycemic control in prediabetes. Prediabetes measures of IFG, IGT, A1C and periodontal measures of pocket depth (PD), clinical attachment level (CAL), plaque index (PI) and gingival index (GI) were taken at baseline and 3 months in 12 subjects with prediabetes and chronic slight to moderate periodontitis. Blood samples were taken from each subject following an 8 hour fast. This study controlled for changes in medications, body-mass index, physical activity and diet. Comparison of mean prediabetes and periodontal measures from baseline and post-treatment at 3 months demonstrated clinical improvement for both periodontal and prediabetes measures. A mean reduction in PD of 0.27 (p=0.003), CAL of 0.32 (p=0.050) and A1C of 0.19 (p=0.015) reached statistical significance. This pilot study suggests NSPT improves A1C and periodontal measures at 3 months. The robustness of measures is limited due to the small sample size and lack of a control group. Further larger scale studies using a randomized control design would be informative. Copyright © 2014 The American Dental Hygienists’ Association.

Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

PubMed Central

Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

2014-01-01

The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

Glucose Tolerance and Hyperkinesis.

ERIC Educational Resources Information Center

Langseth, Lillian; Dowd, Judith

Examined were medical records of 265 hyperkinetic children (7-9 years old). Clinical blood chemistries, hematology, and 5-hour glucose tolerance test (GTT) results indicated that hematocrit levels were low in 27% of the Ss, eosinophil levels were abnormally high in 86% of the Ss, and GTT results were abnormal in a maority of Ss. (CL)

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.

Strong Association between Plasma Dipeptidyl Peptidase-4 Activity and Impaired Cognitive Function in Elderly Population with Normal Glucose Tolerance.

PubMed

Chen, Bo; Zheng, Tianpeng; Qin, Linyuan; Hu, Xueping; Zhang, Xiaoxi; Liu, Yihong; Liu, Hongbo; Qin, Shenghua; Li, Gang; Li, Qinghua

2017-01-01

Objective: Inflammation, oxidative stress, and decreased glucagon-like peptide-1 (GLP-1) are risk factors for cognitive impairment. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing these risk factors. Hence, we investigated the relationship between plasma DPP4 activity and impaired cognitive function in elderly Chinese population with normal glucose tolerance (NGT). Methods: We performed a cross-sectional study using data from 1229 elderly participants (60 years or older) in Guilin. Plasma DPP4 activity, oxidative stress parameters, fasting active GLP-1, and inflammatory markers were measured in all participants. Impaired cognitive function was diagnosed according to the National Institute on Aging-Alzheimer's Association workgroups criteria. Results: Participants in the upper quartile of plasma DPP4 activity had higher C-reactive protein (CRP), interleukin-6 (IL-6), 8-iso-PGF2a, nitrotyrosine, and lower GLP-1 and Montreal Cognitive Assessment (MoCA) scores compared with those in the lowest quartile ( P < 0.001). The odds ratios (ORs) for increased CRP, IL-6, 8-iso-PGF2a, nitrotyrosine, and decreased active GLP-1 were higher with increasing DPP4 quartiles after adjustment for confounders (all P < 0.001). In the highest DPP4 quartile, impaired cognitive function risk was higher (OR, 2.26; 95% confidence interval, 1.36-3.76) than in the lowest quartile after adjustment for potential confounders. The risk for impaired cognitive function increased more with higher levels of DPP4 activity, nitrotyrosine and 8-iso-PGF2a ( P < 0.05), but not with higher IL-6, CRP or lower GLP-1. Conclusion: Plasma DPP4 activity is significantly and independently associated with impaired cognitive function, mainly executive, in elderly Chinese population with NGT. The underlying mechanisms for this association may be partly attributed to the effect of DPP4 on oxidative stress. Plasma DPP4 activity might serve as a risk biomarker or therapeutic target

Carotid arterial remodeling: a maladaptive phenomenon in type 2 diabetes but not in impaired glucose metabolism: the Hoorn study.

PubMed

Henry, Ronald M A; Kostense, Piet J; Dekker, Jacqueline M; Nijpels, Giel; Heine, Robert J; Kamp, Otto; Bouter, Lex M; Stehouwer, Coen D A

2004-03-01

Deteriorating glucose tolerance is associated with an increased cardiovascular disease (CVD) risk. The underlying mechanisms remain unclear. Arterial remodeling is the change in structural properties through time in response to atherogenic and/or hemodynamic alterations and aims to maintain circumferential wall stress constant (sigma(C)). Arterial remodeling has not been studied in relation to glucose tolerance. The study population consisted of 278 people with normal glucose metabolism, 168 with impaired glucose metabolism, and 301 with type 2 diabetes (DM-2); their mean age was 67.8 years. We assessed carotid intima-media thickness (IMT), interadventitial diameter (IAD), lumen diameter (LD), and sigma(C). After adjustment for age, sex, height, body mass index, and prior CVD, DM-2 was associated with increased IAD, IMT, and sigma(C) but not LD (regression coefficients: 0.24 mm; 95% confidence interval [CI], 0.07 to 0.41; 0.050 mm; 95% CI, 0.024 to 0.077; 5.00 kPa; 95% CI, 0.92 to 9.08; and 0.13 mm; 95% CI, -0.03 to 0.29, respectively). After additional adjustment for pulse pressure, the association between DM-2 and IAD disappeared, whereas the association with IMT remained. After adjustment, impaired glucose metabolism was not significantly associated with LD (0.12 mm; 95% CI, -0.06 to 0.33), sigma(C) (0.25 kPa; 95% CI, -4.49 to 4.98), IAD (0.08 mm; 95% CI, -0.11 to 0.27), or IMT (0.029 mm; 95% CI, -0.002 to 0.060). However, the IMT regression coefficient was half that of DM-2. DM-2 is associated with preserved LD at increased IMT, which, however, does not normalize the increased sigma(C). In contrast, impaired glucose metabolism is not associated with changes in LD or IAD, whereas IMT is moderately increased but sigma(C) remains constant. Carotid remodeling in DM-2 thus appears maladaptive, which may explain the increased CVD risk, especially stroke, in DM-2.

Continuous glucose monitoring system in the screening of early glucose derangements in children and adolescents with cystic fibrosis.

PubMed

Franzese, Adriana; Valerio, Giuliana; Buono, Pietro; Spagnuolo, Maria Immacolata; Sepe, Angela; Mozzillo, Enza; De Simone, Ilaria; Raia, Valeria

2008-02-01

In cystic fibrosis (CF), diabetes mellitus (DM) is associated with progression of pulmonary disease and nutritional impairment. To compare oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS) in patients with CF with early glucose derangements. Thirty-two patients with CF (5-20 years) with intermediate glucose values > 7.7 mmol/l during OGTT received a CGMS registration. Patients were classified into those with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and DM, according to glucose values at 120 min of OGTT and during CGMS. Furthermore BMI z-scores, forced expiratory volume in 1 second (FEV1%), number of respiratory infections/year, enzyme supplementation, and HbA1c were evaluated. OGTT and CGMS derangements were in agreement in 43.7% of the patients. BMI z-scores, FEV1%, number of respiratory infections/ year, enzyme supplementation, and HbA1c did not differ among the three groups. HbA1c, correlated positively with 120 min OGTT (r = 0.34; p = 0.059), CGMS area (r = 0.35; p = 0.048) and the number of respiratory infections, and negatively with FEV1%. Intermediate glucose values during OGTT should be considered as a screening test in patients with CF. CGMS can be useful in studying the early occurrence of glucose derangements in selected patients.

Effect of Acarbose on Long-Term Prognosis in Acute Coronary Syndromes Patients with Newly Diagnosed Impaired Glucose Tolerance.

PubMed

Yun, Peng; Du, Ai-ming; Chen, Xue-jun; Liu, Jing-cheng; Xiao, Hu

2016-01-01

To investigate the effect of acarbose therapy on the long-term prognosis of patients with acute coronary syndromes (ACS) complicating newly diagnosed impaired glucose tolerance (IGT). 135 patients hospitalized for ACS who had been newly diagnosed with IGT were randomly assigned to acarbose group (150 mg/day, n = 67) or control group (no acarbose, n = 68). All cases in each group were given the same elementary treatment. Mean follow-up was 2.3 years. The incidence of major adverse cardiovascular event (MACE) and carotid intima-middle thickness (CIMT) were statistically analyzed. During the mean follow-up of 2.3 years, the risk of recurrent MACE in acarbose group was decreased significantly compared with that in control group (26.67% versus 46.88%, P < 0.05); at the same time, thickening of the CIMT was significantly slower than the control group ((1.28 ± 0.42) mm versus (1.51 ± 0.64) mm, P < 0.05). Acarbose can effectively reduce the risk of MACE in ACS patients with newly diagnosed IGT, simultaneously retarding the progression of carotid intima-media thickness.

Contribution of Hepatic Retinaldehyde Dehydrogenase Induction to Impairment of Glucose Metabolism by High-Fat Diet Feeding in C57BL/6J Mice.

PubMed

Xu, Jiong; Zhang, Mian; Zhang, Xiangping; Yang, Hanyu; Sun, Binbin; Wang, Zhongjian; Zhou, Yaqian; Wang, Shuting; Liu, Xiaodong; Liu, Li

2018-05-12

Obesity and insulin resistance are associated with overexpression of retinaldehyde dehydrogenase 1 (RALDH1). We aimed to investigate the roles of hepatic RALDH1 induction in glucose metabolism impairment using mice fed with high-fat diet (HFD). Mice were fed with HFD for 8 weeks and treated with RALDH inhibitor citral for another 4 weeks. Oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT) and insulin tolerance test (ITT) were operated. Expressions of Phosphoenolpyruvate carboxykinase 1 (PCK1), glucokinase (GCK) and RALDH1 were measured. Therapeutic effects of citral were also conducted in diabetic rats. Effects of retinaldehyde on PCK1 and GCK expressions were examined in rat primary hepatocytes and HepG2 cells. The results showed that HFD mice were characterized by hyperlipidaemia and insulin resistance, accompanied by significantly increased RALDH1 activity and expression. Citral (10 and 50 mg/kg) ameliorated HFD-induced hyperlipidaemia and insulin resistance, as evidenced by the improved fasting glucose, insulin levels and lipid profiles. OGTT and PTT demonstrated that citral reversed HFD-induced glucose disposal impairment and glucose production enhancement. Citral also reversed the increased PCK1 expression and decreased GCK expression by HFD. Citral therapeutic effects were reconfirmed in diabetic rats. In vitro data indicated that retinaldehyde had the strongest PCK1 induction in primary hepatocytes of diabetic rats compared with HFD rats and control rats, in line with the increased RALDH1 expression. Citral reversed the retinaldehyde-induced PCK1 expression in primary rat hepatocytes and HepG2 cells. In conclusion, RALDH1 induction impaired glucose metabolism partly via modulating PCK1 and GCK expression. Citral improved glucose metabolism through inhibiting RALDH activity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Type 2 diabetes and impaired glucose tolerance are associated with word memory source monitoring recollection deficits but not simple recognition familiarity deficits following water, low glycaemic load, and high glycaemic load breakfasts.

PubMed

Lamport, Daniel J; Lawton, Clare L; Mansfield, Michael W; Moulin, Chris A J; Dye, Louise

2014-01-30

It has been established that type 2 diabetes, and to some extent, impaired glucose tolerance (IGT), are associated with general neuropsychological impairments in episodic memory. However, the effect of abnormalities in glucose metabolism on specific retrieval processes such as source monitoring has not been investigated. The primary aim was to investigate the impact of type 2 diabetes and IGT on simple word recognition (familiarity) and complex source monitoring (recollection). A secondary aim was to examine the effect of acute breakfast glycaemic load manipulations on episodic memory. Data are presented from two separate studies; (i) 24 adults with type 2 diabetes and 12 controls aged 45-75years, (ii) 18 females with IGT and 47 female controls aged 30-50years. Controls were matched for age, IQ, BMI, waist circumference, and depression. Recognition of previously learned words and memory for specifically which list a previously learned word had appeared in (source monitoring) was examined at two test sessions during the morning after consumption of low glycaemic load, high glycaemic load and water breakfasts according to a counterbalanced, crossover design. Type 2 diabetes (p<0.05) and IGT (p<0.01) were associated with significant source monitoring recollection deficits but not impairments in familiarity. Impairments were only observed in the late postprandial stage at the second test session. These impairments were not attenuated by the breakfast glycaemic load manipulations. Isolated source monitoring recollection deficits indicate that abnormalities in glucose metabolism are not detrimental for global episodic memory processes. This enhances our understanding of how metabolic disorders are associated with memory impairments. © 2013.

Effectiveness of glucose monitoring systems modified for the visually impaired.

PubMed

Bernbaum, M; Albert, S G; Brusca, S; McGinnis, J; Miller, D; Hoffmann, J W; Mooradian, A D

1993-10-01

To compare three glucose meters modified for use by individuals with diabetes and visual impairment regarding accuracy, precision, and clinical reliability. Ten subjects with diabetes and visual impairment performed self-monitoring of blood glucose using each of the three commercially available blood glucose meters modified for visually impaired users (the AccuChek Freedom [Boehringer Mannheim, Indianapolis, IN], the Diascan SVM [Home Diagnostics, Eatontown, NJ], and the One Touch [Lifescan, Milpitas, CA]). The meters were independently evaluated by a laboratory technologist for precision and accuracy determinations. Only two meters were acceptable with regard to laboratory precision (coefficient of variation < 10%)--the Accuchek and the One Touch. The Accuchek and the One Touch did not differ significantly with regard to laboratory estimates of accuracy. A great discrepancy of the clinical reliability results was observed between these two meters. The Accuchek maintained a high degree of reliability (y = 0.99X + 0.44, r = 0.97, P = 0.001). The visually impaired subjects were unable to perform reliable testing using the One Touch system because of a lack of appropriate tactile landmarks and auditory signals. In addition to laboratory assessments of glucose meters, monitoring systems designed for the visually impaired must include adequate tactile and audible feedback features to allow for the acquisition and placement of appropriate blood samples.

Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM

PubMed Central

Ma, Dan; Shield, Julian P.H.; Dean, Wendy; Leclerc, Isabelle; Knauf, Claude; Burcelin, Rémy; Rutter, Guy A.; Kelsey, Gavin

2004-01-01

Transient neonatal diabetes mellitus (TNDM) is a rare inherited diabetic syndrome apparent in the first weeks of life and again during early adulthood. The relative contributions of reduced islet β cell number and impaired β cell function to the observed hypoinsulinemia are unclear. The inheritance pattern of this imprinted disorder implicates overexpression of one or both genes within the TNDM locus: ZAC, which encodes a proapoptotic zinc finger protein, and HYMAI, which encodes an untranslated mRNA. To investigate the consequences for pancreatic function, we have developed a high-copy transgenic mouse line, TNDM29, carrying the human TNDM locus. TNDM29 neonates display hyperglycemia, and older adults, impaired glucose tolerance. Neonatal hyperglycemia occurs only on paternal transmission, analogous to paternal dependence of TNDM in humans. Embryonic pancreata of TNDM29 mice showed reductions in expression of endocrine differentiation factors and numbers of insulin-staining structures. By contrast, β cell mass was normal or elevated at all postnatal stages, whereas pancreatic insulin content in neonates and peak serum insulin levels after glucose infusion in adults were reduced. Expression of human ZAC and HYMAI in these transgenic mice thus recapitulates key features of TNDM and implicates impaired development of the endocrine pancreas and β cell function in disease pathogenesis. PMID:15286800

Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes.

PubMed

Prabu, Paramasivam; Rome, Sophie; Sathishkumar, Chandrakumar; Aravind, Sankaramoorthy; Mahalingam, Balakumar; Shanthirani, Coimbatore Subramanian; Gastebois, Caroline; Villard, Audrey; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

2015-01-01

Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

PubMed

Murovets, Vladimir O; Bachmanov, Alexander A; Zolotarev, Vasiliy A

2015-01-01

The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+) inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-). Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain.

Unmasking glucose metabolism alterations in stable renal transplant recipients: a multicenter study.

PubMed

Delgado, Patricia; Diaz, Juan Manuel; Silva, Irene; Osorio, José M; Osuna, Antonio; Bayés, Beatriz; Lauzurica, Ricardo; Arellano, Edgar; Campistol, Jose Maria; Dominguez, Rosa; Gómez-Alamillo, Carlos; Ibernon, Meritxell; Moreso, Francisco; Benitez, Rocio; Lampreave, Ildefonso; Porrini, Esteban; Torres, Armando

2008-05-01

Emerging information indicates that glucose metabolism alterations are common after renal transplantation and are associated with carotid atheromatosis. The aims of this study were to investigate the prevalence of different glucose metabolism alterations in stable recipients as well as the factors related to the condition. A multicenter, cross-sectional study was conducted of 374 renal transplant recipients without pre- or posttransplantation diabetes. A standard 75-g oral glucose tolerance test was performed. Glucose metabolism alterations were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most common disorder was impaired glucose tolerance (17.9%), and an abnormal oral glucose tolerance test was observed for 21.5% of recipients with a normal fasting glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high-density lipoprotein cholesterol ratio, and beta blocker use were shown to be factors related to glucose metabolism alterations. Remarkably, triglyceride levels, triglyceride/high-density lipoprotein cholesterol ratio, and the proportion of recipients with impaired fasting glucose were already higher throughout the first posttransplantation year in recipients with a current glucose metabolism alteration as compared with those without the condition. Glucose metabolism alterations are common in stable renal transplant recipients, and an oral glucose tolerance test is required for its detection. They are associated with a worse metabolic profile, which is already present during the first posttransplantation year. These findings may help planning strategies for early detection and intervention.

Glucosamine enhances body weight gain and reduces insulin response in mice fed chow diet but mitigates obesity, insulin resistance and impaired glucose tolerance in mice high-fat diet.

PubMed

Hwang, Ji-Sun; Park, Ji-Won; Nam, Moon-Suk; Cho, Hyeongjin; Han, Inn-Oc

2015-03-01

This study investigated the potential of glucosamine (GlcN) to affect body weight gain and insulin sensitivity in mice normal and at risk for developing diabetes. Male C57BL/6J mice were fed either chow diet (CD) or a high fat diet (HFD) and the half of mice from CD and HFD provided with a solution of 10% (w/v) GlcN. Total cholesterol and nonesterified free fatty acid levels were determined. Glucose tolerance test and insulin tolerance test were performed. HepG2 human hepatoma cells or differentiated 3T3-L1 adipocytes were stimulated with insulin under normal (5 mM) or high glucose (25 mM) conditions. Effect of GlcN on 2-deoxyglucose (2-DG) uptake was determined. JNK and Akt phosphorylation and nucleocytoplasmic protein O-GlcNAcylation were assayed by Western blotting. GlcN administration stimulated body weight gain (6.58±0.82 g vs. 11.1±0.42 g), increased white adipose tissue fat mass (percentage of bodyweight, 3.7±0.32 g vs. 5.61±0.34 g), and impaired the insulin response in livers of mice fed CD. However, GlcN treatment in mice fed HFD led to reduction of body weight gain (18.02±0.66 g vs. 16.22±0.96 g) and liver weight (2.27±0.1 vs. 1.85±0.12 g). Furthermore, obesity-induced insulin resistance and impaired Akt insulin signaling in the liver were alleviated by GlcN administration. GlcN inhibited the insulin response under low (5 mM) glucose conditions, whereas it restored the insulin response for Akt phosphorylation under high (25 mM) glucose conditions in HepG2 and 3T3-L1 cells. Uptake of 2-DG increased upon GlcN treatment under 5 mM glucose compared to control, whereas insulin-stimulated 2-DG uptake decreased under 5 mM and increased under 25 mM glucose in differentiated 3T3-L1 cells. Our results show that GlcN increased body weight gain and reduced the insulin response for glucose maintenance when fed to normal CD mice, whereas it alleviated body weight gain and insulin resistance in HFD mice. Therefore, the current data support the integrative

Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119

PubMed Central

Kim, Mi-Hwi; Choung, Jin-Seung; Oh, Yoon-Sin; Moon, Hong-Sub; Jun, Hee-Sook

2016-01-01

G protein-coupled receptor (GPR) 119 is expressed in pancreatic β-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. We screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo. Human GPR119 activation was measured in GeneBLAzer T-Rex GPR119-CRE-bla CHO-K1 cells; intracellular cAMP levels and insulin secretion were measured in INS-1 cells; and GLP-1 release was measured in GLUTag cells. Glucose tolerance tests and serum plasma insulin levels were measured in normal C57BL6 mice and diabetic db/db mice. AD extract-treated cells showed significant increases in GPR119 activation, intracellular cAMP levels, GLP-1 levels and glucose-stimulated insulin secretion as compared with controls. In normal mice, a single treatment with AD extract improved glucose tolerance and increased insulin secretion. Treatment with multiple doses of AD extract or n-hexane fraction improved glucose tolerance in diabetic db/db mice. Imperatorin, phellopterin and isoimperatorin were identified in the active fraction of AD extract. Among these, phellopterin activated GPR119 and increased active GLP-1 and insulin secretion in vitro and enhanced glucose tolerance in normal and db/db mice. We suggest that phellopterin might have a therapeutic potential for the treatment of type 2 diabetes. PMID:27391814

Risk factors associated with abnormal glucose tolerance in the early postpartum period among Japanese women with gestational diabetes.

PubMed

Kugishima, Yukari; Yasuhi, Ichiro; Yamashita, Hiroshi; Fukuda, Masashi; Kuzume, Akiko; Sugimi, So; Umezaki, Yasushi; Suga, Sachie; Kusuda, Nobuko

2015-04-01

To identify the risk factors associated with abnormal glucose tolerance (AGT) on the first postpartum oral glucose tolerance test (OGTT) among Japanese women with gestational diabetes (GDM). In a retrospective study, data were analyzed from women with GDM who underwent their first postpartum OGTT 6-8weeks post partum at a center in Omura, Japan, between January 1, 2007, and December 31, 2011. Women with diabetes or impaired glucose tolerance were deemed to have postpartum AGT. The association between postpartum AGT and various risk factors was analyzed. Among 169 women who underwent a postpartum OGTT, 58 (34.3%) had AGT. The significant risk factors associated with postpartum AGT in univariate analysis were pre-pregnancy body mass index (P=0.096), 1-hour plasma glucose (P=0.006), hemoglobin A1c (P<0.001), insulinogenic index (P=0.05), an insulinogenic index of less than 0.4 (P=0.006), and insulin therapy during pregnancy (P<0.001). Independent risk factors identified by multivariate logistic regression models were insulinogenic index (odds ratio [OR] 0.10, 95% confidence interval [CI] 0.01-0.74; P=0.002), an insulinogenic index of less than 0.4 (OR 5.70, 95% CI 1.69-21.66; P=0.005), and insulin therapy during pregnancy (OR 3.43, 95% CI 1.03-12.55; P=0.044). Among Japanese women with GDM, a lower insulinogenic index and use of insulin therapy during pregnancy are associated with early postpartum AGT. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Adipocytokines and insulin resistance across various degrees of glucose tolerance in pregnancy.

PubMed

Skvarca, A; Tomazic, M; Krhin, B; Blagus, R; Janez, A

2012-01-01

Gestational diabetes mellitus is characterized by progressive insulin resistance. Adipocytokines are thought to be associated with insulin resistance. This cross-sectional study evaluated the associations between serum concentrations of several adipocytokines and insulin resistance at different stages of glucose tolerance in pregnancy, using the homeostasis model assessment of insulin resistance (HOMA-IR) as a reference. According to oral glucose tolerance test results, 74 pregnant women were divided into three groups: normal glucose tolerance (n = 25); intermediate glucose tolerance (n = 19); gestational diabetes mellitus (n = 30). Adiponectin, leptin, resistin, visfatin and retinol-binding protein 4 (RBP4) concentrations were measured using enzyme-linked immuno sorbent assays. Groups were comparable regarding age, week of gestation and body mass index before gestation. There were statistically significant between-group differences in HOMA-IR, but no significant differences regarding serum adipocytokine concentrations. Adipo nectin, leptin, resistin, visfatin and RBP4 were not associated with the degree of glucose tolerance in pregnancy. Concentrations of these adipocytokines are not sufficiently sensitive to replace HOMA- IR in pregnancy.

Effect of Acarbose on Long-Term Prognosis in Acute Coronary Syndromes Patients with Newly Diagnosed Impaired Glucose Tolerance

PubMed Central

Yun, Peng; Du, Ai-ming; Chen, Xue-jun; Liu, Jing-cheng; Xiao, Hu

2016-01-01

Objective. To investigate the effect of acarbose therapy on the long-term prognosis of patients with acute coronary syndromes (ACS) complicating newly diagnosed impaired glucose tolerance (IGT). Methodology. 135 patients hospitalized for ACS who had been newly diagnosed with IGT were randomly assigned to acarbose group (150 mg/day, n = 67) or control group (no acarbose, n = 68). All cases in each group were given the same elementary treatment. Mean follow-up was 2.3 years. The incidence of major adverse cardiovascular event (MACE) and carotid intima-middle thickness (CIMT) were statistically analyzed. Results. During the mean follow-up of 2.3 years, the risk of recurrent MACE in acarbose group was decreased significantly compared with that in control group (26.67% versus 46.88%, P < 0.05); at the same time, thickening of the CIMT was significantly slower than the control group ((1.28 ± 0.42) mm versus (1.51 ± 0.64) mm, P < 0.05). Conclusions. Acarbose can effectively reduce the risk of MACE in ACS patients with newly diagnosed IGT, simultaneously retarding the progression of carotid intima-media thickness. PMID:26770983

Circulating Prolactin Associates With Diabetes and Impaired Glucose Regulation

PubMed Central

Wang, Tiange; Lu, Jieli; Xu, Yu; Li, Mian; Sun, Jichao; Zhang, Jie; Xu, Baihui; Xu, Min; Chen, Yuhong; Bi, Yufang; Wang, Weiqing; Ning, Guang

2013-01-01

OBJECTIVE Prolactin is a major stimulus for the β-cell adaptation during gestation and guards postpartum women against gestational diabetes. Most studies of the role of prolactin on glucose metabolism have been conducted in humans and animals during pregnancy. However, little is known concerning the association between circulating prolactin and glucose metabolism outside pregnancy in epidemiological studies. We aimed to determine whether the variation of circulating prolactin concentration associates with diabetes and impaired glucose regulation (IGR) in a cross-sectional study. RESEARCH DESIGN AND METHODS We recruited 2,377 participants (1,034 men and 1,343 postmenopausal women) without hyperprolactinemia, aged 40 years and older, in Shanghai, China. Diabetes and IGR were determined by an oral glucose tolerance test. Multinomial logit analyses were performed to evaluate the relationship of prolactin with diabetes and IGR. RESULTS Prolactin levels decreased from normal glucose regulation to IGR to diabetes. Multinomial logit analyses, adjusted for potential confounding factors, showed that high circulating prolactin was associated with lower prevalence of diabetes and IGR. The adjusted odds ratios (95% CI) for IGR and diabetes for the highest compared with the lowest quartile of prolactin were 0.54 (95% CI 0.33–0.89) and 0.38 (0.24–0.59) in men and 0.54 (0.36–0.81) and 0.47 (0.32–0.70) in women. CONCLUSIONS High circulating prolactin associates with lower prevalence of diabetes and IGR in the current study. Further studies are warranted to confirm this association. PMID:23340889

The prevalence of impaired glucose regulation in anxiety disorder patients and the relationship with hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-thyroid axis activity.

PubMed

Zhou, Yaling; Dong, Zaiquan; A, Ruhan; Liao, Zongbing; Guo, Jing; Liu, Cancan; Sun, Xueli

2016-08-29

To investigate the prevalence of impaired glucose regulation (IGR) in patients with anxiety disorders and the relationship with hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes function. From September 2013 to May 2015, a total of 646 patients with anxiety disorders who matched the criteria of the 10 th revision of the International Statistical Classification of Diseases and Related Health Problems participated in our study, which was conducted in the Psychiatric Inpatient Department of the West China Hospital of Sichuan University. The results from 75-g glucose tolerance tests, and morning (8:00 am) serum cortisol (PTC), adrenocorticotropic hormone༈ACTH), thyroid-stimulating hormone (TSH), TT3, TT4, FT3, and FT4 levels were collected. The Hamilton Anxiety Scale was administered to assess the severity of anxiety. SPSS 17.0 software was used for statistical analysis. The crude prevalence of impaired glucose regulation was 24.61% in patients with anxiety disorders patients. In the 18-40 year age group with impaired glucose regulation (IGR), both ACTH and PTC levels were higher than the control group (P<0.05). In the 61-75 year age group with IGR, the TSH level was lower and the FT4 level was higher than the control group (P<0.05). The results herein partially confirm that the prevalence of IGR in patients with anxiety disorders is high. Impaired glucose in the younger age group is closely associated with HPA axis function, while impaired glucose in the older age group is closely associated with HPT axis alteration. Therefore, routine blood glucose and endocrine function testing in patients with anxiety disorder is of clinical importance to prevent the development of diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Unmasking Glucose Metabolism Alterations in Stable Renal Transplant Recipients: A Multicenter Study

PubMed Central

Delgado, Patricia; Diaz, Juan Manuel; Silva, Irene; Osorio, José M.; Osuna, Antonio; Bayés, Beatriz; Lauzurica, Ricardo; Arellano, Edgar; Campistol, Jose Maria; Dominguez, Rosa; Gómez-Alamillo, Carlos; Ibernon, Meritxell; Moreso, Francisco; Benitez, Rocio; Lampreave, Ildefonso; Porrini, Esteban; Torres, Armando

2008-01-01

Background and objectives: Emerging information indicates that glucose metabolism alterations are common after renal transplantation and are associated with carotid atheromatosis. The aims of this study were to investigate the prevalence of different glucose metabolism alterations in stable recipients as well as the factors related to the condition. Design, setting, participants, & measurements: A multicenter, cross-sectional study was conducted of 374 renal transplant recipients without pre- or posttransplantation diabetes. A standard 75-g oral glucose tolerance test was performed. Results: Glucose metabolism alterations were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most common disorder was impaired glucose tolerance (17.9%), and an abnormal oral glucose tolerance test was observed for 21.5% of recipients with a normal fasting glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high-density lipoprotein cholesterol ratio, and β blocker use were shown to be factors related to glucose metabolism alterations. Remarkably, triglyceride levels, triglyceride/high-density lipoprotein cholesterol ratio, and the proportion of recipients with impaired fasting glucose were already higher throughout the first posttransplantation year in recipients with a current glucose metabolism alteration as compared with those without the condition. Conclusions: Glucose metabolism alterations are common in stable renal transplant recipients, and an oral glucose tolerance test is required for its detection. They are associated with a worse metabolic profile, which is already present during the first posttransplantation year. These findings may help planning strategies for early detection and intervention. PMID:18322043

Chromium Supplementation Improves Glucose Tolerance in Diabetic Goto-Kakizaki Rats

PubMed Central

Abdourahman, Aicha; Edwards, John G.

2016-01-01

Summary Chromium supplementation (Cr) may be useful in the management of diabetes and appears to improve some aspects of glucose handling. However, several studies have used either high doses of Cr supplementation or have placed control animals on a Cr-deficient diet. We therefore wanted to test whether Cr dosages in the ranges that more closely approximate recommended levels of supplementation in humans are efficacious in glycemic control under normal dietary conditions. Euglycemic Wistar or diabetic Goto-Kakizaki (GK) rats (a model of nonobese NIDDM) were assigned to water (control) or chromium picolinate (Cr-P) supplementation (1 or 10 mg/kg/day) groups for up to 32 weeks. Glucose tolerance was tested following an overnight fast by injecting sterile glucose (1.0 g/kg, i.p.) and then measuring blood glucose at select times to determine the sensitivity to glucose by calculation of the area under the curve. Cr-P did not significantly alter the growth of the animals. In the euglycemic Wistar rats, Cr-P supplementation did not alter the response to a glucose tolerance test. In the GK rats, Cr-P supplementation significantly improved glucose tolerance at both levels of Cr-P supplementation (1 mg/kg/day: H20; 100 ± 11%; Cr-P 70 6 8%; 10 mg/kg/day: H20; 100 ± 10%; Cr-P 66 ± 9 %). Cr-P supplementation produced a small improvement in some indices of glycemic control. There were no differences observed for the two levels of Cr-P supplementation suggested that we did not identify a threshold for Cr-P effects, and future studies may use lower doses to find a threshold effect for improving glucose tolerance in diabetics. PMID:18629917

Circulating MiRNAs of ‘Asian Indian Phenotype’ Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes

PubMed Central

Prabu, Paramasivam; Rome, Sophie; Sathishkumar, Chandrakumar; Aravind, Sankaramoorthy; Mahalingam, Balakumar; Shanthirani, Coimbatore Subramanian; Gastebois, Caroline; Villard, Audrey; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

2015-01-01

Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians—an ethnic population characterized to represent ‘Asian Indian phenotype’ known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a ‘New Lead’ in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes. PMID:26020947

The lipid accumulation product as a useful index for identifying abnormal glucose regulation in young Korean women.

PubMed

Oh, J-Y; Sung, Y-A; Lee, H J

2013-04-01

The lipid accumulation product, a combination of waist circumference and triglycerides concentration, has been suggested as a better marker for abnormal glucose regulation than BMI. We aimed to compare the lipid accumulation product and BMI as useful markers for abnormal glucose regulation in young Korean women. The lipid accumulation product was calculated using the formula [waist circumference (cm) - 58] × triglycerides (mmol/l). Glucose tolerance status was determined using a 75-g oral glucose tolerance test in 2810 Korean women aged 18-39 years from the general population. The prevalence of abnormal glucose regulation was 6.8% (isolated impaired fasting glucose 1.8%, isolated impaired glucose tolerance 4.0%; impaired fasting glucose + impaired glucose tolerance 0.4% and diabetes mellitus 0.6%). According to the quintile distributions of the lipid accumulation product and BMI, women with a lipid accumulation product quintile greater than their BMI quintile exhibited significantly greater areas under the curve and higher levels of 2-h post-load glucose, insulin, homeostasis model analysis of insulin resistance and lipid profiles than did women with a BMI quintile greater than their lipid accumulation product quintile. Multiple logistic regression revealed that the lipid accumulation product exhibited a higher odds ratio for abnormal glucose regulation than did BMI after adjusting for age, systolic blood pressure, HDL cholesterol, previous history of gestational diabetes and family history of diabetes (odds ratios 3.5 and 2.6 of the highest vs. the lowest quintiles of lipid accumulation product and BMI, respectively). The lipid accumulation product could be useful for identifying the young Korean women with abnormal glucose regulation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Glucose, Insulin and C-peptide Kinetics during an Oral Glucose Tolerance Test in Patients with Chronic Liver Disease

PubMed Central

Min, Yong Ki; Suh, Kyo II; Choi, Sang Jeon; Lee, Hong Kyu; Kim, Chung Yong; Koh, Chang-Soon; Min, Hun Ki

1987-01-01

To elucidate the mechanism of glucose intolerance in patients with chronic liver disease(CLD), we measured the levels of plasma glucose, insulin and C-peptide during oral glucose tolerance test and urinary excretion of C-peptide per 24 hours during a weight maintenance diet in 20 patients with CLD who had fasting plasma glucose(FBS) of less than 100 mg/dl. The patients with CLD who had normal FBS(FBS less than 100 mg/dl) were divided into two groups by the National Diabetes Data Group Criteria: one with abnormal glucose tolerance (abnormal GTT, Group 1) and the other with normal glucose tolerance (normal GTT. Group 2). Group 1 patients showed significantly higher plasma insulin (p<0.02 and p<0.01, respectively) and C-peptide concentrations (p<0.01) in the fasting state and 2 hours after a 75gram oral glucose loading (PP2) than group 2 patients. Urinary excretion of C-peptide per 24 hours was also higher in group 1 patients than in group 2 patients (p<0.01). Group 2 patients demonstrated similar plasma insulin, C-peptide and urinary excretion of C-peptide per 24 hours to normal subjects (p>0.05). These results suggest that patients with CLD who had normal FBS can be divided into two groups by oral glucose tolerance test(GTT) and those with abnormal GTT have hyperinsulinemia the mechanism of which is insulin hypersecretion from pancreatic B-cell. PMID:3154815

Effect of saturated fatty acid-rich dietary vegetable oils on lipid profile, antioxidant enzymes and glucose tolerance in diabetic rats

PubMed Central

Kochikuzhyil, Benson Mathai; Devi, Kshama; Fattepur, Santosh Raghunandan

2010-01-01

Objective: To study the effect of saturated fatty acid (SFA)-rich dietary vegetable oils on the lipid profile, endogenous antioxidant enzymes and glucose tolerance in type 2 diabetic rats. Materials and Methods: Type 2 diabetes was induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rats. Twenty-eight-day-old normal (N) and diabetic (D) male Wistar rats were fed for 45 days with a fat-enriched special diet (10%) prepared with coconut oil (CO) – lauric acid-rich SFA, palm oil (PO) – palmitic acid-rich SFA and groundnut oil (GNO) – control (N and D). Lipid profile, endogenous antioxidant enzymes and oral glucose tolerance tests were monitored. Results: D rats fed with CO (D + CO) exhibited a significant decrease in the total cholesterol and non-high-density lipoprotein cholesterol. Besides, they also showed a trend toward improving antioxidant enzymes and glucose tolerance as compared to the D + GNO group, whereas D + PO treatment aggravated the dyslipidemic condition while causing a significant decrease in the superoxide dismutase levels when compared to N rats fed with GNO (N + GNO). D + PO treatment also impaired the glucose tolerance when compared to N + GNO and D + GNO. Conclusion: The type of FA in the dietary oil determines its deleterious or beneficial effects. Lauric acid present in CO may protect against diabetes-induced dyslipidemia. PMID:20871763

Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults

PubMed Central

Malin, Steven K.; Nightingale, Joy; Choi, Sung-Eun; Chipkin, Stuart R.; Braun, Barry

2012-01-01

Impaired glucose tolerant (IGT) adults are at elevated risk for cardiovascular disease (CVD). Exercise or metformin reduce CVD risk, but the efficacy of combining treatments is unclear. To determine the effects of exercise training plus metformin, compared to each treatment alone, on CVD risk factors in IGT adults. Subjects were assigned to: placebo (P), metformin (M), exercise plus placebo (EP), or exercise plus metformin (EM) (8/group). In a double-blind design, P or 2000mg/d of M were administered for 12 weeks and half performed aerobic and resistance training 3 days/week for approximately 60 minutes/day at 70% pre-training heart rate peak. Outcomes included: adiposity, blood pressure (BP), lipids and high sensitivity C-reactive protein (hs-CRP). Z-scores were calculated to determine metabolic syndrome severity. M and EM, but not EP, decreased body weight compared to P (p <0.05). M and EP lowered systolic BP by 6% (p < 0.05), diastolic BP by 6% (p < 0.05), and hs-CRP by 20% (M: trend p = 0.06; EP: p < 0.05) compared to P. Treatments raised HDL-cholesterol (p < 0.05; EM: trend p = 0.06) compared to P and lowered triacyglycerol (p < 0.05) and metabolic syndrome Z-score compared to baseline (EP; trend p = 0.07 and EM or M; p < 0.05). Although exercise and/or metformin improve some CVD risk factors, only training or metformin alone lowered hs-CRP and BP. Thus, metformin may attenuate the effects of training on some CVD risk factors and metabolic syndrome severity in IGT adults. PMID:23505172

135-Day Interventions of Yam Dioscorin and the Dipeptide Asn-Trp (NW) To Reduce Weight Gains and Improve Impaired Glucose Tolerances in High-Fat Diet-Induced C57BL/6 Mice.

PubMed

Wu, Guang-Cheng; Lin, Shyr-Yi; Liang, Hong-Jen; Hou, Wen-Chi

2018-01-24

The C57BL/6J mice were fed a 135-day normal diet or a high-fat diet (HFD) without, or concurrent with, a single yam dioscorin (80 mg/kg) or dipeptide NW (40 mg/kg) intervention every day. The final body weights (g) of mice were 26.1 ± 1.4, 34.97 ± 2.1, 31.75 ± 2.6, and 31.66 ± 3.1, respectively, for normal diet-fed, HFD-fed, dioscorin-intervened, and NW-intervened group. The mice in both intervened groups showed similar less weight gains and had significant differences (P < 0.05) compared to those in the HFD group under the same cumulative HFD intakes. The blood biochemical index of mice with dioscorin interventions showed significantly lower contents in total cholesterol and low-density lipoprotein, and NW interventions showed significantly lower total triglyceride contents compared to those of the HFD group (P < 0.05). Both intervened mice exhibited similar reductions in total visceral lipid contents and have significant differences compared to those of the HFD group (P < 0.05). The dioscorin intervention was better than NW interventions in lowering blood glucose levels by oral glucose tolerance tests and both showed significant differences (P < 0.05) compared to those in the HFD group. Yam dioscorin or dipeptide NW will potentially be used for preventive functional foods of less body weight gains and impaired glucose tolerance controls, which require further clinical trial investigations.

Aspartame intake is associated with greater glucose intolerance in individuals with obesity.

PubMed

Kuk, Jennifer L; Brown, Ruth E

2016-07-01

This study examined whether sucrose, fructose, aspartame, and saccharin influences the association between obesity and glucose tolerance in 2856 adults from the NHANES III survey. Aspartame intake significantly influenced the association between body mass index (BMI) and glucose tolerance (interaction: P = 0.004), wherein only those reporting aspartame intake had a steeper positive association between BMI and glucose tolerance than those reporting no aspartame intake. Therefore, consumption of aspartame is associated with greater obesity-related impairments in glucose tolerance.

An imidazopyridine anxiolytic alters glucose tolerance in patients: a pilot investigation.

PubMed

Bottaï, T; Cartault, F; Pouget, R; Blayac, J P; Petit, P

1995-02-01

We have recently shown that compounds with high affinity for peripheral-type benzodiazepine receptors inhibited glucose-induced insulin secretion in vitro. We therefore performed an oral glucose tolerance test in anxious inpatients treated with the imidazopyridine derivative alpidem, which has been shown to display high affinity for these binding sites. The test was performed before and after 1 week of daily administration of the drug. As compared with pretreatment values, a significant alteration of the insulin response to glucose was observed. It is suggested that daily administration of alpidem, at therapeutically effective doses for the treatment of anxiety, may alter glucose tolerance.

Light at night acutely impairs glucose tolerance in a time-, intensity- and wavelength-dependent manner in rats.

PubMed

Opperhuizen, Anne-Loes; Stenvers, Dirk J; Jansen, Remi D; Foppen, Ewout; Fliers, Eric; Kalsbeek, Andries

2017-07-01

Exposure to light at night (LAN) has increased dramatically in recent decades. Animal studies have shown that chronic dim LAN induced obesity and glucose intolerance. Furthermore, several studies in humans have demonstrated that chronic exposure to artificial LAN may have adverse health effects with an increased risk of metabolic disorders, including type 2 diabetes. It is well-known that acute exposure to LAN affects biological clock function, hormone secretion and the activity of the autonomic nervous system, but data on the effects of LAN on glucose homeostasis are lacking. This study aimed to investigate the acute effects of LAN on glucose metabolism. Male Wistar rats were subjected to i.v. glucose or insulin tolerance tests while exposed to 2 h of LAN in the early or late dark phase. In subsequent experiments, different light intensities and wavelengths were used. LAN exposure early in the dark phase at ZT15 caused increased glucose responses during the first 20 min after glucose infusion (p < 0.001), whereas LAN exposure at the end of the dark phase, at ZT21, caused increased insulin responses during the first 10 min (p < 0.01), indicating that LAN immediately induces glucose intolerance in rats. Subsequent experiments demonstrated that the effect of LAN was both intensity- and wavelength-dependent. White light of 50 and 150 lx induced greater glucose responses than 5 and 20 lx, whereas all intensities other than 5 lx reduced locomotor activity. Green light induced glucose intolerance, but red and blue light did not, suggesting the involvement of a specific retina-brain pathway. Together, these data show that exposure to LAN has acute adverse effects on glucose metabolism in a time-, intensity- and wavelength-dependent manner.

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.

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

PubMed Central

Morris, Christopher J.; Yang, Jessica N.; Garcia, Joanna I.; Myers, Samantha; Bozzi, Isadora; Wang, Wei; Buxton, Orfeu M.; Shea, Steven A.; Scheer, Frank A. J. L.

2015-01-01

Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show—by using two 8-d laboratory protocols—in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower early-phase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers. PMID:25870289

The effects of glucose ingestion and glucose regulation on memory performance in older adults with mild cognitive impairment.

PubMed

Riby, L M; Marriott, A; Bullock, R; Hancock, J; Smallwood, J; McLaughlin, J

2009-04-01

Previous research investigating the impact of glucose ingestion and/or improvements in glucose regulation has found selective cognitive facilitation on episodic memory tasks in successful ageing and dementia. The present study aimed to extend this research to mild cognitive impairment (MCI). In a repeated-measures design, 24 older adults with and 24 older adults without MCI performed a battery of memory and attention tasks after 25 g of glucose or a sweetness matched placebo. In addition, to assess the impact of individual differences in glucose regulation, blood glucose measurements were taken throughout the testing session. Consistent with previous research, cognitive facilitation was observed for episodic memory tasks only in both successful ageing and MCI. Older adults with MCI had a similar glucose regulatory response as controls but their fasting levels were elevated. Notably, higher levels of blood glucose were associated with impaired memory performance in both the glucose and placebo conditions. Importantly, both blood glucose and memory performance indices were significant predictors of MCI status. The utility of glucose supplementation and the use of glucose regulation as a biological marker are discussed in relation to these data.

Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes.

PubMed

Kim, Ye An; Ku, Eu Jeong; Khang, Ah Reum; Hong, Eun Shil; Kim, Kyoung Min; Moon, Jae Hoon; Choi, Sung Hee; Park, Kyong Soo; Jang, Hak Chul; Lim, Soo

2014-11-01

The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes. We recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3-6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7-6.4%, 39-46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated. Eighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥ 165 mg/dL and a 30-min C-peptide < 5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98-26.16) of developing diabetes than other prediabetic subjects. In Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population. Copyright © 2014. Published by Elsevier Ireland Ltd.

Hyperuricemia Is a Risk Factor for the Onset of Impaired Fasting Glucose in Men with a High Plasma Glucose Level: A Community-Based Study

PubMed Central

Miyake, Teruki; Kumagi, Teru; Furukawa, Shinya; Hirooka, Masashi; Kawasaki, Keitarou; Koizumi, Mitsuhito; Todo, Yasuhiko; Yamamoto, Shin; Abe, Masanori; Kitai, Kohichiro; Matsuura, Bunzo; Hiasa, Yoichi

2014-01-01

Background It is not clear whether elevated uric acid is a risk factor for the onset of impaired fasting glucose after stratifying by baseline fasting plasma glucose levels. We conducted a community-based retrospective longitudinal cohort study to clarify the relationship between uric acid levels and the onset of impaired fasting glucose, according to baseline fasting plasma glucose levels. Methods We enrolled 6,403 persons (3,194 men and 3,209 women), each of whom was 18–80 years old and had >2 annual check-ups during 2003–2010. After excluding persons who had fasting plasma glucose levels ≥6.11 mM and/or were currently taking anti-diabetic agents, the remaining 5,924 subjects were classified into quartiles according to baseline fasting plasma glucose levels. The onset of impaired fasting glucose was defined as fasting plasma glucose ≥6.11 mM during the observation period. Results In the quartile groups, 0.9%, 2.1%, 3.4%, and 20.2% of the men developed impaired fasting glucose, respectively, and 0.1%, 0.3%, 0.5%, and 5.6% of the women developed impaired fasting glucose, respectively (P trend <0.001). After adjusting for age, body mass index, systolic blood pressure, triacylglycerols, high density lipoprotein-cholesterol, creatinine, fatty liver, family history of diabetes, alcohol consumption, and current smoking, uric acid levels were positively associated with onset of impaired fasting glucose in men with highest-quartile fasting plasma glucose levels (adjusted hazard ratio, 1.003; 95% confidence interval, 1.0001–1.005, P = 0.041). Conclusions Among men with high fasting plasma glucose, hyperuricemia may be independently associated with an elevated risk of developing impaired fasting glucose. PMID:25237894

Glucose, insulin and C-peptide secretion in obese and non obese women with polycystic ovarian disease.

PubMed

Mahabeer, S; Naidoo, C; Joubert, S M

1990-06-01

Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during oral glucose tolerance testing (OGTT) were evaluated in 10 non obese women with polycystic ovarian disease (NOB-PCOD) and 10 obese women with polycystic ovarian disease (OB-PCOD). Mean plasma glucose response at 120 minutes in OB-PCOD showed impaired glucose tolerance. Also in this group, 1 patient had frank diabetes mellitus, whilst 3 other patients had impaired glucose tolerance 1 NOB-PCOD patient had impaired glucose tolerance. Mean plasma glucose levels and mean incremental glucose areas were higher in the OB-PCOD at all time intervals and reached statistical significance at 60 and 90 minutes. Mean plasma IRI levels were also higher in OB-PCOD at all time intervals, and reached statistically significant higher levels at 0, 60 and 90 minutes. Mean serum C-peptide valves were also higher at all time intervals in OB-PCOD. The relationship between acanthosis nigricans, obesity and PCOD was also analysed. It is evident from this study that obesity has a significant negative impact on the overall carbohydrate status in women with PCOD.

The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test Heralds Biomarkers of Type 2 Diabetes Risk in Obese Youth

PubMed Central

Kim, Joon Young; Michaliszyn, Sara F.; Nasr, Alexis; Lee, SoJung; Tfayli, Hala; Hannon, Tamara; Hughan, Kara S.; Bacha, Fida; Arslanian, Silva

2016-01-01

OBJECTIVE The shape of the glucose response curve during an oral glucose tolerance test (OGTT), monophasic versus biphasic, identifies physiologically distinct groups of individuals with differences in insulin secretion and sensitivity. We aimed to verify the value of the OGTT-glucose response curve against more sensitive clamp-measured biomarkers of type 2 diabetes risk, and to examine incretin/pancreatic hormones and free fatty acid associations in these curve phenotypes in obese adolescents without diabetes. RESEARCH DESIGN AND METHODS A total of 277 obese adolescents without diabetes completed a 2-h OGTT and were categorized to either a monophasic or a biphasic group. Body composition, abdominal adipose tissue, OGTT-based metabolic parameters, and incretin/pancreatic hormone levels were examined. A subset of 106 participants had both hyperinsulinemic-euglycemic and hyperglycemic clamps to measure in vivo insulin sensitivity, insulin secretion, and β-cell function relative to insulin sensitivity. RESULTS Despite similar fasting and 2-h glucose and insulin concentrations, the monophasic group had significantly higher glucose, insulin, C-peptide, and free fatty acid OGTT areas under the curve compared with the biphasic group, with no differences in levels of glucagon, total glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and pancreatic polypeptide. Furthermore, the monophasic group had significantly lower in vivo hepatic and peripheral insulin sensitivity, lack of compensatory first and second phase insulin secretion, and impaired β-cell function relative to insulin sensitivity. CONCLUSIONS In obese youth without diabetes, the risk imparted by the monophasic glucose curve compared with biphasic glucose curve, independent of fasting and 2-h glucose and insulin concentrations, is reflected in lower insulin sensitivity and poorer β-cell function, which are two major pathophysiological biomarkers of type 2 diabetes in youth. PMID:27293201

High serum selenium levels are associated with impaired fasting glucose and elevated fasting serum glucose in Linyi, China.

PubMed

Li, Zhe; Li, Xia; Ju, Wen; Wu, Guanrui; Yang, Xiaomei; Fu, Xiaofeng; Gao, Xibao

2018-01-01

The relationship between selenium level and impaired fasting glucose or elevated fasting serum glucose remains controversial. This study aimed to evaluate these associations in China. This observational population study adopted a cluster sampling approach to enroll participants. Baseline information on selenium categories was tested using one-way analysis of variance and Kruskal-Wallis equality-of-populations rank tests. Multivariable logistic regression was used to investigate the association between serum selenium level and impaired fasting glucose or elevated fasting serum glucose. The mean serum selenium concentration was 121.5μg/L which in a relatively high baseline Se status. Differences were observed among individuals with normal, impaired fasting glucose and elevated fasting serum glucose levels in their basic information, physical examination results and laboratory findings. After adjusting for their basic information, physical examination results and laboratory findings, compared with the low-selenium group, the high-selenium groups (124.9-143.9 and above 143.9μg/L) had ORs for elevated fasting serum glucose of 2.31 (1.37-3.90) and 2.67 (1.59-4.48), respectively (both P<0.05). A sex-difference was observed, and a significant association between selenium levels and impaired fasting glucose was observed for males but not for females. The findings of this observational study suggest that relatively high selenium levels might be positively associated with elevated fasting serum glucose and relatively high selenium levels might be positively associated with impaired fasting glucose in men. Copyright © 2017 Elsevier GmbH. All rights reserved.

Effect of Different Insulin Response Patterns During Oral Glucose Tolerance Test on Glycemia in Individuals with Normal Glucose Tolerance.

PubMed

Praveen, Edavan Pulikkanath; Chouhan, Sunil; Sahoo, Jayaprakash; Goel, Sudhir K; Dwivedi, Sada Nand; Khurana, Madan Lal; Kulshreshtha, Bindu; Ammini, Ariachery C

2016-05-01

Research is still going on for detecting the earliest glucose homeostasis derangements in individuals, which is crucial for the prevention of glucose intolerance. This cross-sectional study analyzes different insulin response patterns during the oral glucose tolerance test (OGTT) and their implications on glycemia in normoglycemic individuals. The sample frame was the "Offspring of Individuals with Diabetes Study" database. All participants underwent OGTT. Blood samples were collected at 0, 30, 60, and 120 min for measurement of insulin, C-peptide, and proinsulin levels. Normal glucose tolerant individuals were selected for analysis. Four hundred fifty subjects (mean age, 25 years) were included and divided into two groups according to timing of plasma insulin peaking during OGTT: Group 1, peaking at 30 min; and Group 2, peaking at 60 or 120 min. Body mass index (BMI) and insulin resistance were comparable between the groups; however, Group 2 showed a significantly higher 60- and 120-min glucose level and lower disposition index. Based on the magnitude of the insulin levels, Group 1 was subdivided into Group N (normal pattern) and Group E (exaggerated pattern) with a 30-min insulin cutoff of 74 μU/mL (Group E, ≥74 μU/mL). Group 2 was subdivided into Group DL (delayed and limited pattern; 60-min insulin <73.0 μU/mL and 120-min insulin <80.0 μU/mL) and Group DE (delayed and exaggerated pattern; 60-min insulin ≥73.0 μU/mL or 120-min insulin ≥80.0 μU/mL). Group DE showed a significantly higher area under the curve (AUC) of glucose compared with the other groups and had a lower disposition index and high-density lipoprotein levels. Group DL had significantly lower insulin resistance and BMI compared with Group E but showed a similar AUC of glucose. A delayed insulin pattern was associated with higher postprandial glucose levels. Individuals with delayed and exaggerated insulin secretion may have a higher risk for glucose intolerance.

Blueberries improve glucose tolerance and lipid handling without altering body composition in obese postmenopausal mice

PubMed Central

Elks, Carrie M.; Terrebonne, Jennifer D.; Ingram, Donald K.; Stephens, Jacqueline M.

2014-01-01

Objective Metabolic syndrome (MetS) risk increases significantly during menopause and remains elevated post-menopause. Several botanicals, including blueberries (BB), have been shown to delay MetS progression, but few studies have been conducted in postmenopausal animal models. Here, we examined the effects of BB supplementation on obese postmenopausal mice using a chemically-induced menopause model. Design and Methods After induction of menopause, mice were fed a high-fat diet or the same diet supplemented with 4% BB powder for 12 weeks. Body weight and body composition were measured, and mice were subjected to glucose and insulin tolerance tests. Serum triglycerides and adiponectin were measured, and liver histology and hepatic gene expression were assessed. Results: Menopausal and BB-supplemented mice had significantly higher body weights and fat mass than control mice, while menopausal mice had impaired glucose tolerance and higher serum triglycerides when compared with control and BB-supplemented mice. Menopausal mice also had hepatic steatosis that was prevented by BB supplementation and correlated with expression of genes involved in hepatic fatty acid oxidation. Conclusions We conclude that BB supplementation prevents the glucose intolerance and hepatic steatosis that occur in obese postmenopausal mice, and that these effects are independent of body weight. PMID:25611327

Glucose metabolism disorder in obese children assessed by continuous glucose monitoring system.

PubMed

Zou, Chao-Chun; Liang, Li; Hong, Fang; Zhao, Zheng-Yan

2008-02-01

Continuous glucose monitoring system (CGMS) can measure glucose levels at 5-minute intervals over a few days, and may be used to detect hypoglycemia, guide insulin therapy, and control glucose levels. This study was undertaken to assess the glucose metabolism disorder by CGMS in obese children. Eighty-four obese children were studied. Interstitial fluid (ISF) glucose levels were measured by CGMS for 24 hours covering the time for oral glucose tolerance test (OGTT). Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), type 2 diabetic mellitus (T2DM) and hypoglycemia were assessed by CGMS. Five children failed to complete CGMS test. The glucose levels in ISF measured by CGMS were highly correlated with those in capillary samples (r=0.775, P<0.001). However, the correlation between ISF and capillary glucose levels was lower during the first hour than that in the later time period (r=0.722 vs r=0.830), and the ISF glucose levels in 69.62% of children were higher than baseline levels in the initial 1-3 hours. In 79 obese children who finished the CGMS, 2 children had IFG, 2 had IGT, 3 had IFG + IGT, and 2 had T2DM. Nocturnal hypoglycemia was noted during the overnight fasting in 11 children (13.92%). Our data suggest that glucose metabolism disorder including hyperglycemia and hypoglycemia is very common in obese children. Further studies are required to improve the precision of the CGMS in children.

Cost-Effectiveness of a Short Message Service Intervention to Prevent Type 2 Diabetes from Impaired Glucose Tolerance.

PubMed

Wong, Carlos K H; Jiao, Fang-Fang; Siu, Shing-Chung; Fung, Colman S C; Fong, Daniel Y T; Wong, Ka-Wai; Yu, Esther Y T; Lo, Yvonne Y C; Lam, Cindy L K

2016-01-01

Aims. To investigate the costs and cost-effectiveness of a short message service (SMS) intervention to prevent the onset of type 2 diabetes mellitus (T2DM) in subjects with impaired glucose tolerance (IGT). Methods. A Markov model was developed to simulate the cost and effectiveness outcomes of the SMS intervention and usual clinical practice from the health provider's perspective. The direct programme costs and the two-year SMS intervention costs were evaluated in subjects with IGT. All costs were expressed in 2011 US dollars. The incremental cost-effectiveness ratio was calculated as cost per T2DM onset prevented, cost per life year gained, and cost per quality adjusted life year (QALY) gained. Results. Within the two-year trial period, the net intervention cost of the SMS group was $42.03 per subject. The SMS intervention managed to reduce 5.05% onset of diabetes, resulting in saving $118.39 per subject over two years. In the lifetime model, the SMS intervention dominated the control by gaining an additional 0.071 QALY and saving $1020.35 per person. The SMS intervention remained dominant in all sensitivity analyses. Conclusions. The SMS intervention for IGT subjects had the superiority of lower monetary cost and a considerable improvement in preventing or delaying the T2DM onset. This trial is registered with ClinicalTrials.gov NCT01556880.

Gestational Protein Restriction Impairs Insulin-Regulated Glucose Transport Mechanisms in Gastrocnemius Muscles of Adult Male Offspring

PubMed Central

Blesson, Chellakkan S.; Sathishkumar, Kunju; Chinnathambi, Vijayakumar

2014-01-01

Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that caused by a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP diet–exposed male offspring to understand their role in LP-induced insulin resistance. Pregnant Wistar rats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pups from LP diet–fed mothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor

Metabolomic biomarkers of impaired glucose tolerance and type 2 diabetes mellitus with a potential for risk stratification in women with polycystic ovary syndrome.

PubMed

Galazis, Nicolas; Iacovou, Christos; Haoula, Zeina; Atiomo, William

2012-02-01

There is a need to identify biomarkers of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) risk in women with PCOS to facilitate screening and the development of novel strategies to prevent disease progression. Metabolomic technologies may address this need. All published studies on metabolomic biomarkers of IGT and/or T2DM identified through MEDLINE (1966-December 2010), EMBASE (1980-December 2010) and Cochrane (1993-December 2010) were retrieved. Eligible studies were screened and specific study characteristics recorded including study design, number of participants, selection criteria, type of metabolomic technique used, site of sample collection, and a list of metabolites identified to have been altered in IGT and/or T2DM versus healthy controls was created. Nine metabolomic biomarkers that could potentially be used to identify women with PCOS at risk of developing IGT and/or T2DM were identified including leucine, isoleucine, citrate, glucose, creatinine, valine, glutamine, alanine and HDL. Of these biomarkers, a panel of four biomarkers were consistently either elevated or reduced including glucose (elevated), valine (reduced), HDL (reduced) and alanine (reduced) in IGT/T2DM compared with controls. These biomarkers may predict the development of IGT/T2DM in young women with PCOS. More studies are required to test this hypothesis and translate the findings into patient benefit by reducing the morbidity/mortality associated with IGT/T2DM in PCOS. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity.

PubMed

de Haan, Willeke; Bhattacharjee, Alpana; Ruddle, Piers; Kang, Martin H; Hayden, Michael R

2014-03-01

Adipose tissue contains one of the largest reservoirs of cholesterol in the body. Adipocyte dysfunction in obesity is associated with intracellular cholesterol accumulation, and alterations in cholesterol homeostasis have been shown to alter glucose metabolism in cultured adipocytes. ABCA1 plays a major role in cholesterol efflux, suggesting a role for ABCA1 in maintaining cholesterol homeostasis in the adipocyte. However, the impact of adipocyte ABCA1 on adipose tissue function and glucose metabolism is unknown. Our aim was to determine the impact of adipocyte ABCA1 on adipocyte lipid metabolism, body weight, and glucose metabolism in vivo. To address this, we used mice lacking ABCA1 specifically in adipocytes (ABCA1(-ad/-ad)). When fed a high-fat, high-cholesterol diet, ABCA1(-ad/-ad) mice showed increased cholesterol and triglyceride stores in adipose tissue, developed enlarged fat pads, and had increased body weight. Associated with these phenotypic changes, we observed significant changes in the expression of genes involved in cholesterol and glucose homeostasis, including ldlr, abcg1, glut-4, adiponectin, and leptin. ABCA1(-ad/-ad) mice also demonstrated impaired glucose tolerance, lower insulin sensitivity, and decreased insulin secretion. We conclude that ABCA1 in adipocytes influences adipocyte lipid metabolism, body weight, and whole-body glucose homeostasis.

Let’s prevent diabetes: study protocol for a cluster randomised controlled trial of an educational intervention in a multi-ethnic UK population with screen detected impaired glucose regulation

PubMed Central

2012-01-01

Background The prevention of type 2 diabetes is a globally recognised health care priority, but there is a lack of rigorous research investigating optimal methods of translating diabetes prevention programmes, based on the promotion of a healthy lifestyle, into routine primary care. The aim of the study is to establish whether a pragmatic structured education programme targeting lifestyle and behaviour change in conjunction with motivational maintenance via the telephone can reduce the incidence of type 2 diabetes in people with impaired glucose regulation (a composite of impaired glucose tolerance and/or impaired fasting glucose) identified through a validated risk score screening programme in primary care. Design Cluster randomised controlled trial undertaken at the level of primary care practices. Follow-up will be conducted at 12, 24 and 36 months. The primary outcome is the incidence of type 2 diabetes. Secondary outcomes include changes in HbA1c, blood glucose levels, cardiovascular risk, the presence of the Metabolic Syndrome and the cost-effectiveness of the intervention. Methods The study consists of screening and intervention phases within 44 general practices coordinated from a single academic research centre. Those at high risk of impaired glucose regulation or type 2 diabetes are identified using a risk score and invited for screening using a 75 g-oral glucose tolerance test. Those with screen detected impaired glucose regulation will be invited to take part in the trial. Practices will be randomised to standard care or the intensive arm. Participants from intensive arm practices will receive a structured education programme with motivational maintenance via the telephone and annual refresher sessions. The study will run from 2009–2014. Discussion This study will provide new evidence surrounding the long-term effectiveness of a diabetes prevention programme conducted within routine primary care in the United Kingdom. Trial registration Clinicaltrials

Effects of celiac superior mesenteric ganglionectomy on glucose homeostasis and hormonal changes during oral glucose tolerance testing in rats.

PubMed

Kumakura, Atsushi; Shikuma, Junpei; Ogihara, Norikazu; Eiki, Jun-ichi; Kanazawa, Masao; Notoya, Yōko; Kikuchi, Masatoshi; Odawara, Masato

2013-01-01

The liver plays an important role in maintaining glucose homeostasis in the body. In the prandial state, some of the glucose which is absorbed by the gastrointestinal tract is converted into glycogen and stored in the liver. In contrast, the liver produces glucose by glycogenolysis and gluconeogenesis while fasting. Thus, the liver contributes to maintaining blood glucose level within normoglycemic range. Glycogenesis and glycogenolysis are regulated by various mechanisms including hormones, the sympathetic and parasympathetic nervous systems and the hepatic glucose content. In this study, we examined a rat model in which the celiac superior mesenteric ganglion (CSMG) was resected. We attempted to elucidate how the celiac sympathetic nervous system is involved in regulating glucose homeostasis by assessing the effects of CSMG resection on glucose excursion during an oral glucose tolerance test, and by examining hepatic glycogen content and hepatic glycogen phosphorylase (GP) activity. On the oral glucose tolerance test, CSMG-resected rats demonstrated improved glucose tolerance and significantly increased GP activity compared with sham-operated rats, whereas there were no significant differences in insulin, glucagon or catecholamine levels between the 2 groups. These results suggest that the celiac sympathetic nervous system is involved in regulating the rate of glycogen consumption through GP activity. In conclusion, the examined rat model showed that the celiac sympathetic nervous system regulates hepatic glucose metabolism in conjunction with vagal nerve innervations and is a critical component in the maintenance of blood glucose homeostasis.

Genetically determined schizophrenia is not associated with impaired glucose homeostasis.

PubMed

Polimanti, Renato; Gelernter, Joel; Stein, Dan J

2018-05-01

Here, we used data from large genome-wide association studies to test the presence of causal relationships, conducting a Mendelian randomization analysis; and shared molecular mechanisms, calculating the genetic correlation, among schizophrenia, type 2 diabetes (T2D), and impaired glucose homeostasis. Although our Mendelian randomization analysis was well-powered, no causal relationship was observed between schizophrenia and T2D, or traits related to glucose impaired homeostasis. Similarly, we did not observe any global genetic overlap among these traits. These findings indicate that there is no causal relationships or shared mechanisms between schizophrenia and impaired glucose homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

PubMed Central

Satin, Leslie S.; Butler, Peter C.; Ha, Joon; Sherman, Arthur S.

2015-01-01

Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM. PMID:25637831

Air Pollution Exposure and Abnormal Glucose Tolerance during Pregnancy: The Project Viva Cohort

PubMed Central

Gold, Diane R.; Rifas-Shiman, Sheryl L.; Koutrakis, Petros; Schwartz, Joel D.; Kloog, Itai; Melly, Steven; Coull, Brent A.; Zanobetti, Antonella; Gillman, Matthew W.; Oken, Emily

2014-01-01

Background: Exposure to fine particulate matter (PM with diameter ≤ 2.5 μm; PM2.5) has been linked to type 2 diabetes mellitus, but associations with hyperglycemia in pregnancy have not been well studied. Methods: We studied Boston, Massachusetts–area pregnant women without known diabetes. We identified impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) during pregnancy from clinical glucose tolerance tests at median 28.1 weeks gestation. We used residential addresses to estimate second-trimester PM2.5 and black carbon exposure via a central monitoring site and spatiotemporal models. We estimated residential traffic density and roadway proximity as surrogates for exposure to traffic-related air pollution. We performed multinomial logistic regression analyses adjusted for sociodemographic covariates, and used multiple imputation to account for missing data. Results: Of 2,093 women, 65 (3%) had IGT and 118 (6%) had GDM. Second-trimester spatiotemporal exposures ranged from 8.5 to 15.9 μg/m3 for PM2.5 and from 0.1 to 1.7 μg/m3 for black carbon. Traffic density was 0–30,860 vehicles/day × length of road (kilometers) within 100 m; 281 (13%) women lived ≤ 200 m from a major road. The prevalence of IGT was elevated in the highest (vs. lowest) quartile of exposure to spatiotemporal PM2.5 [odds ratio (OR) = 2.63; 95% CI: 1.15, 6.01] and traffic density (OR = 2.66; 95% CI: 1.24, 5.71). IGT also was positively associated with other exposure measures, although associations were not statistically significant. No pollutant exposures were positively associated with GDM. Conclusions: Greater exposure to PM2.5 and other traffic-related pollutants during pregnancy was associated with IGT but not GDM. Air pollution may contribute to abnormal glycemia in pregnancy. Citation: Fleisch AF, Gold DR, Rifas-Shiman SL, Koutrakis P, Schwartz JD, Kloog I, Melly S, Coull BA, Zanobetti A, Gillman MW, Oken E. 2014. Air pollution exposure and abnormal glucose

The interaction between impaired acute insulin response and insulin resistance predict type 2 diabetes and impairment of fasting glucose.

PubMed

Zethelius, Björn; Berglund, Lars; Hänni, Arvo; Berne, Christian

2008-01-01

Impaired acute insulin response (AIR) and insulin resistance (IR) are characteristics of Type 2 diabetes (T2DM). The aim was to develop risk models for T2DM and impaired fasting glucose (IFG), reflecting estimates both of AIR and IR, and of their interaction, as predictors over 20 years of follow-up. We developed predictive models using hierarchic multiple regression analyses in a population-based cohort of 1227 men with normal fasting blood glucose at baseline (1970-73) and were reinvestigated after 10 and after 20 years. Using IVGTT-variables correlated either to AIR or to IR, separate models were developed. Combined models were also estimated from which prediction scores, representing individual risk, were calculated. In combined models, interaction between prediction scores reflecting AIR and IR predicted T2DM and IFG. Lowest tertile of AIR and the highest tertile of IR showed a relative risk (RR) of 15.3 (95%-CI=5.58-41.84) for T2DM compared to the contrast group (high AIR and low IR). Corresponding RR for IFG was 13.23 (95%-CI=6.53-26.78). C-statistic increased from 0.76 to 0.79 (p=0.018) for T2DM and from 0.77 to 0.80 for IFG (p=0.062) taking interaction into account. Main effects of lowest tertile of AIR and highest tertile of IR versus best were: RR for T2DM, 8.80 (95%-CI=4.25-18.21) and 6.31 (95%-CI=3.26-12.21); for IFG, 9.07, (95%-CI=5.38-15.29) and 4.49 (95%-CI=2.98-6-76). The interaction between low AIR and high IR revealed a high relative risk for T2DM or IFG reflecting the interplay between these factors over long time on worsening glucose tolerance and development of manifest disease.

Oral administration of soybean peptide Vglycin normalizes fasting glucose and restores impaired pancreatic function in Type 2 diabetic Wistar rats.

PubMed

Jiang, Hua; Feng, Jueping; Du, Zhongxia; Zhen, Hui; Lin, Mei; Jia, Shaohui; Li, Tao; Huang, Xinyuan; Ostenson, Claes-Goran; Chen, Zhengwang

2014-09-01

Vglycin, a natural 37-residue polypeptide isolated from pea seeds in which six half-cysteine residues are embedded in three pairs of disulfide bonds, is resistant to digestive enzymes and has antidiabetic potential. To investigate the pharmacological activity of Vglycin in vivo and to examine the mechanisms involved, the therapeutic effect of Vglycin in diabetic rats was examined. Diabetes was induced in Wistar rats by high-fat diet and multiple streptozotocin intraperitoneal injections. Diabetic rats were treated daily with Vglycin for 4 weeks. Body weight, food intake, fasting plasma glucose and insulin levels were assayed weekly. Glucose and insulin tolerance tests were conducted on Day 29. Subsequently, levels of p-Akt in the liver and pancreas and cleaved PARP, Pdx-1 and insulin in the pancreas were detected by immunoblotting. The morphology of the pancreas and the insulin expression in the pancreas were analyzed by hematoxylin-eosin staining and immunohistochemistry, respectively. Furthermore, human liver-derived cell lines were used to explore the in vitro effects of Vglycin on insulin sensitivity and glucose uptake. Chronic treatment with Vglycin normalized fasting glucose levels in diabetic rats. The improvement in glucose homeostasis and the increased insulin sensitivity mediated by restored insulin signaling likely contributed to decreased food intake and reduced body weight. Vglycin protected pancreatic cells from damage by streptozotocin. Although insulin synthesis and secretion in impaired β-cell were not significantly elevated, islets morphology was improved in the Vglycin-treated groups. These results suggest that Vglycin could be useful in Type 2 diabetes for restoring impaired insulin signaling, glucose tolerance and pancreatic function. Copyright © 2014 Elsevier Inc. All rights reserved.

Physical Activity Dimensions Associated with Impaired Glucose Metabolism.

PubMed

Amadid, Hanan; Johansen, Nanna B; Bjerregaard, Anne-Louise; Vistisen, Dorte; Færch, Kristine; Brage, Søren; Lauritzen, Torsten; Witte, Daniel R; Sandbæk, Annelli; Jørgensen, Marit E

2017-11-01

Physical activity (PA) is important in the prevention of Type 2 diabetes, yet little is known about the role of specific dimensions of PA, including sedentary time in subgroups at risk for impaired glucose metabolism (IGM). We applied a data-driven decision tool to identify dimensions of PA associated with IGM across age, sex, and body mass index (BMI) groups. This cross-sectional study included 1501 individuals (mean (SD) age, 65.6 (6.8) yr) at high risk for Type 2 diabetes from the ADDITION-PRO study. PA was measured by an individually calibrated combined accelerometer and heart rate monitor worn for 7 d. PA energy expenditure, time spent in different activity intensities, bout duration, and sedentary time were considered determinants of IGM together with age, sex, and BMI. Decision tree analysis was applied to identify subgroup-specific dimensions of PA associated with IGM. IGM was based on oral glucose tolerance test results and defined as a fasting plasma glucose level of ≥6.1 mmol·L and/or a 2-h plasma glucose level of ≥7.8 mmol·L. Among overweight (BMI ≥25 kg·m) men, accumulating less than 30 min·d of moderate-to-vigorous PA was associated with IGM, whereas among overweight women, sedentary time was associated with IGM. Among individuals older than 53 yr with normal weight (BMI <25 kg·m), time spent in light PA was associated with IGM. None of the dimensions of PA were associated with IGM among individuals ≤53 yr of age with normal weight. We identified subgroups in which different activity dimensions were associated with IGM. Methodology and results from this study may suggest a preliminary step toward the goal of tailoring and targeting PA interventions aimed at Type 2 diabetes prevention.

Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance.

PubMed

Haus, Jacob M; Solomon, Thomas P J; Marchetti, Christine M; Edmison, John M; González, Frank; Kirwan, John P

2010-01-01

The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans. Obese men and women (n = 23) with impaired glucose tolerance were randomly assigned to either exercise training with a eucaloric (EU; approximately 1800 kcal; n = 11) or hypocaloric (HYPO; approximately 1300 kcal; n = 12) diet for 12 wk. Hepatic glucose production (HGP; milligrams per kilogram fat-free mass(-1) per minute(-1)) and hepatic insulin resistance were determined using a two-stage sequential hyperinsulinemic (40 mU/m(2) . min(-1)) euglycemic (5.0 mm) clamp with [3-(3)H]glucose. Measures were obtained at basal, during insulin infusion (INS; 120 min), and insulin plus intralipid/heparin infusion (INS/FFA; 300 min). At baseline, basal HGP was similar between groups; hyperinsulinemia alone did not completely suppress HGP, whereas INS/FFA exhibited less suppression than INS (EU, 4.6 +/- 0.8, 2.0 +/- 0.5, and 2.6 +/- 0.4; HYPO, 3.8 +/- 0.5, 1.2 +/- 0.3, and 2.3 +/- 0.4, respectively). After the intervention the HYPO group lost more body weight (P < 0.05) and fat mass (P < 0.05). However, both lifestyle interventions reduced hepatic insulin resistance during basal (P = 0.005) and INS (P = 0.001) conditions, and insulin-mediated suppression of HGP during INS was equally improved in both groups (EU: -42 +/- 22%; HYPO: -50 +/- 20%, before vs. after, P = 0.02). In contrast, the ability of insulin to overcome FFA-induced hepatic insulin resistance and HGP was improved only in the HYPO group (EU: -15 +/- 24% vs. HYPO: -58 +/- 19%, P = 0.02). Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions. However, the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention.

Free Fatty Acid-Induced Hepatic Insulin Resistance is Attenuated Following Lifestyle Intervention in Obese Individuals with Impaired Glucose Tolerance

PubMed Central

Haus, Jacob M.; Solomon, Thomas P. J.; Marchetti, Christine M.; Edmison, John M.; González, Frank; Kirwan, John P.

2010-01-01

Objective: The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans. Research Design and Methods: Obese men and women (n = 23) with impaired glucose tolerance were randomly assigned to either exercise training with a eucaloric (EU; ∼1800 kcal; n = 11) or hypocaloric (HYPO; ∼1300 kcal; n = 12) diet for 12 wk. Hepatic glucose production (HGP; milligrams per kilogram fat-free mass−1 per minute−1) and hepatic insulin resistance were determined using a two-stage sequential hyperinsulinemic (40 mU/m2 · min−1) euglycemic (5.0 mm) clamp with [3-3H]glucose. Measures were obtained at basal, during insulin infusion (INS; 120 min), and insulin plus intralipid/heparin infusion (INS/FFA; 300 min). Results: At baseline, basal HGP was similar between groups; hyperinsulinemia alone did not completely suppress HGP, whereas INS/FFA exhibited less suppression than INS (EU, 4.6 ± 0.8, 2.0 ± 0.5, and 2.6 ± 0.4; HYPO, 3.8 ± 0.5, 1.2 ± 0.3, and 2.3 ± 0.4, respectively). After the intervention the HYPO group lost more body weight (P < 0.05) and fat mass (P < 0.05). However, both lifestyle interventions reduced hepatic insulin resistance during basal (P = 0.005) and INS (P = 0.001) conditions, and insulin-mediated suppression of HGP during INS was equally improved in both groups (EU: −42 ± 22%; HYPO: −50 ± 20%, before vs. after, P = 0.02). In contrast, the ability of insulin to overcome FFA-induced hepatic insulin resistance and HGP was improved only in the HYPO group (EU: −15 ± 24% vs. HYPO: −58 ± 19%, P = 0.02). Conclusions: Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions. However, the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention. PMID:19906790

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

PubMed

Méndez-Del Villar, Miriam; Puebla-Pérez, Ana M; Sánchez-Peña, María J; González-Ortiz, Luis J; Martínez-Abundis, Esperanza; González-Ortiz, Manuel

2016-05-01

To evaluate the effect of Artemisia dracunculus on glycemic control, insulin sensitivity, and insulin secretion in patients with impaired glucose tolerance (IGT). A randomized, double blind, placebo-controlled clinical trial was performed in 24 patients with diagnosis of IGT. Before and after the intervention, glucose and insulin levels were measured every 30 min for 2 h after a 75-g dextrose load, along with glycated hemoglobin A1c (A1C) and lipid profile. Twelve patients received A. dracunculus (1000 mg) before breakfast and dinner for 90 days; the remaining 12 patients received placebo. Area under the curve (AUC) of glucose and insulin, total insulin secretion, first phase of insulin secretion, and insulin sensitivity were calculated. Wilcoxon signed-rank, Mann-Whitney U, and chi-square tests were used for statistical analyses. The institutional ethics committee approved the protocol. After A. dracunculus administration, there were significant decreases in systolic blood pressure (SBP; 120.0 ± 11.3 vs. 113.0 ± 11.2 mmHg, P < .05), A1C (5.8 ± 0.3 vs. 5.6% ± 0.4%, P < .05), AUC of insulin (56,136.0 ± 27,426.0 vs. 44,472.0 ± 23,370.0 pmol/L, P < .05), and total insulin secretion (0.45 ± 0.23 vs. 0.35 ± 0.18, P < .05), with a significant increase in high-density lipoprotein cholesterol (HDL-C) (1.3 ± 0.3 vs. 1.4 ± 0.3 mmol/L, P < .05). There were no significant differences after placebo administration. A. dracunculus administration for 90 days in patients with IGT significantly decreased SBP, A1C, AUC of insulin, and total insulin secretion with a significant increase in HDL-C levels.

Psychosocial stress predicts abnormal glucose metabolism: the Australian Diabetes, Obesity and Lifestyle (AusDiab) study.

PubMed

Williams, Emily D; Magliano, Dianna J; Tapp, Robyn J; Oldenburg, Brian F; Shaw, Jonathan E

2013-08-01

The evidence supporting a relationship between stress and diabetes has been inconsistent. This study examined the effects of stress on abnormal glucose metabolism, using a population-based sample of 3,759, with normoglycemia at baseline, from the Australian Diabetes, Obesity and Lifestyle study. Perceived stress and stressful life events were measured at baseline, with health behavior and anthropometric information also collected. Oral glucose tolerance tests were undertaken at baseline and 5-year follow-up. The primary outcome was the development of abnormal glucose metabolism (impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes), according to WHO 1999 criteria. Perceived stress predicted incident abnormal glucose metabolism in women but not men, after multivariate adjustment. Life events showed an inconsistent relationship with abnormal glucose metabolism. Perceived stress predicted abnormal glucose metabolism in women. Healthcare professionals should consider psychosocial adversity when assessing risk factor profiles for the development of diabetes.

Should glycated haemoglobin (HbA1c) be used to detect people with type 2 diabetes mellitus and impaired glucose regulation?

PubMed

Mostafa, Samiul A; Davies, Melanie J; Srinivasan, Balasubramanian Thiagarajan; Carey, Marian E; Webb, David; Khunti, Kamlesh

2010-11-01

There is a need to simplify screening tests for type 2 diabetes mellitus (T2DM) so patients can be identified earlier and more efficiently. Glycated haemoglobin (HbA1c) has been recommended by some international organisations as a diagnostic tool for detecting T2DM and impaired glucose regulation (IGR, also termed prediabetes and includes impaired fasting glucose and/or impaired glucose tolerance). The HbA1c cut-point of ≥6.5% (48 mmol/mol) has been selected as diagnostic for T2DM, while the cut-points for IGR are debated by the different international organisations: an International Expert Committee has suggested using HbA1c 6.0-6.4% (42-46 mmol/mol); however, the American Diabetes Association has recommended using HbA1c 5.7-6.4% (39-46 mmol/mol). Some countries will adopt a new method of reporting HbA1c values in millimoles per mole (mmol/mol). Use of HbA1c has some logistical advantages over using an oral glucose tolerance test (OGTT). As patients do not need to fast, appointments do not need to be limited to the morning. The HbA1c result reflects longer term glycaemia and is less affected by recent physical/emotional stress. However, there is some debate as to whether HbA1c should replace fasting plasma glucose or the OGTT. As the two tests detect different people, some individuals with diabetes detected on OGTT will no longer be classified as having T2DM using HbA1c ≥6.5% criteria. Furthermore, some medical conditions can result in HbA1c assay measurements not reflecting glycaemic control over the last 2-3 months; these include haematological disorders, renal failure, and chronic excess alcohol consumption.

The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice.

PubMed

Chambers, Adam P; Sorrell, Joyce E; Haller, April; Roelofs, Karen; Hutch, Chelsea R; Kim, Ki-Suk; Gutierrez-Aguilar, Ruth; Li, Bailing; Drucker, Daniel J; D'Alessio, David A; Seeley, Randy J; Sandoval, Darleen A

2017-04-04

Glucagon-like peptide 1 (GLP-1) is necessary for normal gluco-regulation, and it has been widely presumed that this function reflects the actions of GLP-1 released from enteroendocrine L cells. To test the relative importance of intestinal versus pancreatic sources of GLP-1 for physiological regulation of glucose, we administered a GLP-1R antagonist, exendin-[9-39] (Ex9), to mice with tissue-specific reactivation of the preproglucagon gene (Gcg). Ex9 impaired glucose tolerance in wild-type mice but had no impact on Gcg-null or GLP-1R KO mice, suggesting that Ex9 is a true and specific GLP-1R antagonist. Unexpectedly, Ex-9 had no effect on blood glucose in mice with restoration of intestinal Gcg. In contrast, pancreatic reactivation of Gcg fully restored the effect of Ex9 to impair both oral and i.p. glucose tolerance. These findings suggest an alternative model whereby islet GLP-1 also plays an important role in regulating glucose homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Postprandial glucose response to selected tropical fruits in normal glucose-tolerant Nigerians.

PubMed

Edo, A; Eregie, A; Adediran, O; Ohwovoriole, A; Ebengho, S

2011-01-01

The glycemic response to commonly eaten fruits in Nigeria has not been reported. Therefore, this study assessed the plasma glucose response to selected fruits in Nigeria. Ten normal glucose-tolerant subjects randomly consumed 50 g carbohydrate portions of three fruits: banana (Musa paradisiaca), pineapple (Ananus comosus), and pawpaw (Carica papaya), and a 50-g glucose load at 1-week intervals. Blood samples were collected in the fasting state and half-hourly over a 2-h period post-ingestion of the fruits or glucose. The samples were analyzed for plasma glucose concentrations. Plasma glucose responses were assessed by the peak plasma glucose concentration, maximum increase in plasma glucose, 2-h postprandial plasma glucose level, and incremental area under the glucose curve and glycemic index (GI). The results showed that the blood glucose response to these three fruits was similar in terms of their incremental areas under the glucose curve, maximum increase in plasma glucose, and glycemic indices (GIs). The 2-h postprandial plasma glucose level of banana was significantly higher than that of pineapple, P < 0.025. The mean ± SEM GI values were as follows: pawpaw; 86 ± 26.8%; banana, 75.1 ± 21.8%; pineapple, 64.5 ± 11.3%. The GI of glucose is taken as 100. The GI of pineapple was significantly lower than that of glucose (P < 0.05). Banana, pawpaw, and pineapple produced a similar postprandial glucose response. Measured portions of these fruits may be used as fruit exchanges with pineapple having the most favorable glycemic response.

The shape of the glucose response curve during an oral glucose tolerance test heralds biomarkers of type 2 diabetes risk in obese youth

USDA-ARS?s Scientific Manuscript database

The shape of the glucose response curve during an oral glucose tolerance test (OGTT), monophasic versus biphasic, identifies physiologically distinct groups of individuals with differences in insulin secretion and sensitivity. We aimed to verify the value of the OGTT-glucose response curve against m...

TNF-Alpha in Peripheral Neuropathy Patients with Impaired Glucose Regulation.

PubMed

Li, Xia; Zhu, Ju; Liu, Na; Liu, Jie; Zhang, Zhecheng

2017-01-01

Impaired glucose regulation (IGR) is the prestate of diabetes; about 1/3 of IGR patients will develop to diabetes finally. In this study, we investigated the serum tumor necrosis factor-alpha (TNF- α ) and interleukin-6 (IL-6) levels in peripheral neuropathy impaired patients with impaired glucose regulation (IGR). A total of 70 IGR patients received the conventional nerve conduction test, including 30 patients with peripheral neuropathy (PN) and 40 patients without peripheral neuropathy (NPN). The other 40 healthy individuals were recruited as controls. The serum TNF- α and IL-6 in IGR patients were higher than in control group, and serum TNF- α and IL-6 levels in IGR-PN group were higher than in IGR-NPN group (27.7 ± 17.8 versus 13.1 ± 6.7 pg/mL and 18.1 ± 17.7 versus 6.4 ± 3.7 pg/mL, resp., both p < 0.05). Multifactors logistic regression analysis showed that TNF- α (OR = 0.893; p = 0.009) was an independent factor affecting whether IGR could combine with peripheral neuropathy. TNF- α and IL-6 could aggregate peripheral neuropathy in impaired glucose regulation patients; TNF- α might be independent risk factor for peripheral neuropathy in glucose regulation impaired patients.

The effect of PCSK1 variants on waist, waist-hip ratio and glucose metabolism is modified by sex and glucose tolerance status.

PubMed

Gjesing, Anette P; Vestmar, Marie A; Jørgensen, Torben; Heni, Martin; Holst, Jens J; Witte, Daniel R; Hansen, Torben; Pedersen, Oluf

2011-01-01

We aimed to evaluate the effects of the G-allele of rs6232 and the C-allele of rs6235 within PCSK1 on measures of body fat and glucose homeostasis in Danish individuals and to assess interactions of genotypes with age, sex and glucose tolerance status. Data were included in meta-analyses of additional Europeans. Rs6232 and rs6235 were genotyped in 6,164 Danes from the Inter99 study of middle-aged people. Results from these analyses were combined with previously published studies in meta-analyses of a total of 27,786 individuals. The impact of the variants was also investigated in a subset of 62 glucose-tolerant men during a meal challenge including measures of serum incretins. In men we found an effect on body composition in sex-stratified analyses where the rs6235 C-allele conferred an increased waist circumference of 0.8 cm per allele (0.2-1.5, p = 0.008) and increased waist-to-hip ratio of 0.004 (0.0005-0.008, p = 0.027). In the meta-analyses where men and women were combined, the rs6232 G-allele associated with increased waist-to-hip ratio (p = 0.02) and the rs6235 C-allele associated with increased waist circumference (p = 0.01). Furthermore, the rs6235 C-allele was associated nominally with a 0.6% (0.1-1%, p = 0.01) reduction in fasting glucose, it interacted with glucose tolerance status for traits related to glucose metabolism and analysis among individuals having abnormal glucose tolerance revealed a 5% (-0.7-9%, p = 0.02) elevated level of acute insulin response for this variant. Finally, we found that the rs6232 G-allele associated with higher levels of GLP-1, GLP-2 and glucagon and that the rs6235 C-allele associated with higher levels of GIP and glucagon during a meal-test. PCSK1 rs6232 G-allele and rs6235 C-allele have an effect on body composition which may be modified by sex, whereas the effect of rs6235 C-allele on fasting and stimulated circulating plasma glucose and hormone levels may be influenced by glucose tolerance

Association of serum orosomucoid with 30-min plasma glucose and glucose excursion during oral glucose tolerance tests in non-obese young Japanese women.

PubMed

Tsuboi, Ayaka; Minato, Satomi; Yano, Megumu; Takeuchi, Mika; Kitaoka, Kaori; Kurata, Miki; Yoshino, Gen; Wu, Bin; Kazumi, Tsutomu; Fukuo, Keisuke

2018-01-01

Inflammatory markers are elevated in insulin resistance (IR) and diabetes. We tested whether serum orosomucoid (ORM) is associated with postload glucose, β-cell dysfunction and IR inferred from plasma insulin kinetics during a 75 g oral glucose tolerance test (OGTT). 75 g OGTTs were performed with multiple postload glucose and insulin measurements over a 30-120 min period in 168 non-obese Japanese women (aged 18-24 years). OGTT responses, serum adiponectin and high-sensitivity C reactive protein (hsCRP) were cross-sectionally analyzed by analysis of variance and then Bonferroni's multiple comparison procedure. Stepwise multivariate linear regression analyses were used to identify most important determinants of ORM. Of 168 women, 161 had normal glucose tolerance. Postload glucose levels and the area under the glucose curve (AUCg) increased in a stepwise fashion from the first through the third ORM tertile. In contrast, there was no or modest, if any, association with fat mass index, trunk/leg fat ratio, adiponectin, hsCRP, postload insulinemia, the Matsuda index and homeostasis model assessment IR. In multivariable models, which incorporated the insulinogenic index, the Matsuda index and HOMA-IR, 30 min glucose (standardized β: 0.517) and AUCg (standardized β: 0.495) explained 92.8% of ORM variations. Elevated circulating orosomucoid was associated with elevated 30 min glucose and glucose excursion in non-obese young Japanese women independently of adiposity, IR, insulin secretion, adiponectin and other investigated markers of inflammation. Although further research is needed, these results may suggest a clue to identify novel pathways that may have utility in monitoring dysglycemia within normal glucose tolerance.