A randomized controlled trial of an internet-based mentoring program for type 1 diabetes patients with inadequate glycemic control.

PubMed

Suh, Sunghwan; Jean, Cheol; Koo, Mihyun; Lee, Sun Young; Cho, Min Ja; Sim, Kang-Hee; Jin, Sang-Man; Bae, Ji Cheol; Kim, Jae Hyeon

2014-04-01

To determine whether an internet-based mentoring program can improve glycemic control in subjects with type 1 diabetes mellitus (T1DM). Subjects with T1DM on intensive insulin therapy and with hemoglobin A1c (HbA1c) ≥8.0% were randomized to mentored (glucometer transmission with feedback from mentors) or control (glucometer transmission without feedback) groups and were examined for 12 weeks. Five mentors were interviewed and selected, of which two were T1DM patients themselves and three were parents with at least one child diagnosed with T1DM since more than 5 years ago. A total of 57 T1DM adult subjects with a mean duration after being diagnosed with diabetes of 7.4 years were recruited from Samsung Medical Center. Unfortunately, the mentored group failed to show significant improvements in HbA1c levels or other outcomes, including the quality of life, after completion of the study. However, the mentored group monitored their blood glucose (1.41 vs. 0.30) and logged into our website (http://ubisens.co.kr/) more frequently (20.59 times vs. 5.07 times) than the control group. A 12-week internet-based mentoring program for T1DM patients with inadequate glycemic control did not prove to be superior to the usual follow-up. However, the noted increase in the subjects' frequency of blood glucose monitoring may lead to clinical benefits.

A Randomized Controlled Trial of an Internet-Based Mentoring Program for Type 1 Diabetes Patients with Inadequate Glycemic Control

PubMed Central

Suh, Sunghwan; Jean, Cheol; Koo, Mihyun; Lee, Sun Young; Cho, Min Ja; Sim, Kang-Hee; Jin, Sang-Man; Bae, Ji Cheol

2014-01-01

Background To determine whether an internet-based mentoring program can improve glycemic control in subjects with type 1 diabetes mellitus (T1DM). Methods Subjects with T1DM on intensive insulin therapy and with hemoglobin A1c (HbA1c) ≥8.0% were randomized to mentored (glucometer transmission with feedback from mentors) or control (glucometer transmission without feedback) groups and were examined for 12 weeks. Five mentors were interviewed and selected, of which two were T1DM patients themselves and three were parents with at least one child diagnosed with T1DM since more than 5 years ago. Results A total of 57 T1DM adult subjects with a mean duration after being diagnosed with diabetes of 7.4 years were recruited from Samsung Medical Center. Unfortunately, the mentored group failed to show significant improvements in HbA1c levels or other outcomes, including the quality of life, after completion of the study. However, the mentored group monitored their blood glucose (1.41 vs. 0.30) and logged into our website (http://ubisens.co.kr/) more frequently (20.59 times vs. 5.07 times) than the control group. Conclusion A 12-week internet-based mentoring program for T1DM patients with inadequate glycemic control did not prove to be superior to the usual follow-up. However, the noted increase in the subjects' frequency of blood glucose monitoring may lead to clinical benefits. PMID:24851207

Validation of the Economic and Health Outcomes Model of Type 2 Diabetes Mellitus (ECHO-T2DM).

PubMed

Willis, Michael; Johansen, Pierre; Nilsson, Andreas; Asseburg, Christian

2017-03-01

The Economic and Health Outcomes Model of Type 2 Diabetes Mellitus (ECHO-T2DM) was developed to address study questions pertaining to the cost-effectiveness of treatment alternatives in the care of patients with type 2 diabetes mellitus (T2DM). Naturally, the usefulness of a model is determined by the accuracy of its predictions. A previous version of ECHO-T2DM was validated against actual trial outcomes and the model predictions were generally accurate. However, there have been recent upgrades to the model, which modify model predictions and necessitate an update of the validation exercises. The objectives of this study were to extend the methods available for evaluating model validity, to conduct a formal model validation of ECHO-T2DM (version 2.3.0) in accordance with the principles espoused by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the Society for Medical Decision Making (SMDM), and secondarily to evaluate the relative accuracy of four sets of macrovascular risk equations included in ECHO-T2DM. We followed the ISPOR/SMDM guidelines on model validation, evaluating face validity, verification, cross-validation, and external validation. Model verification involved 297 'stress tests', in which specific model inputs were modified systematically to ascertain correct model implementation. Cross-validation consisted of a comparison between ECHO-T2DM predictions and those of the seminal National Institutes of Health model. In external validation, study characteristics were entered into ECHO-T2DM to replicate the clinical results of 12 studies (including 17 patient populations), and model predictions were compared to observed values using established statistical techniques as well as measures of average prediction error, separately for the four sets of macrovascular risk equations supported in ECHO-T2DM. Sub-group analyses were conducted for dependent vs. independent outcomes and for microvascular vs. macrovascular vs. mortality

Influence of CSN1S2 protein from Caprine milk Etawah Breed (EB) on histology of microglial cells in rat (Rattus norvegicus) Type-2 diabetes mellitus (T2DM)

NASA Astrophysics Data System (ADS)

Rika, Margareth; Fatchiyah

2017-11-01

Type-2 diabetes mellitus (T2DM) is a degenerative disease that causes an imbalance in the metabolism. The aim of this research is to determine the influences of CSN1S2 on the structure of microglial cells in T2DM. Rats (Rattus norvegicus) were divided into eight groups of treatment with looping three times each between treatment groups (CM) Control. The control is given a milk treatment with doses of 375 mg/kg (CM375), 750 mg/kg (CM750), and 1500 mg/kg (CM1500), T2DM (DMK), and T2DM with CSN1S2 375 mg/kg dose (DM375), 750mg/kg (DM750), and 1500 mg/kg (DM1500). The animal model T2DM was induced by a high-fat diet in the form of feed followed by injection of STZ (dose of 25 mg/kg of animal treatment) and treatment of CSN1S2 for 28 days. Brain organs were taken and analysed in histopathology stained by Hematoxylin-eosin (HE) and observed using Olympus BX53. Based on the results, it was concluded that CSN1S2 protein is influential for induction of microglial cell proliferation in animal models of T2DM, as immunity responds to the inflammatory condition in T2DM.

Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model

PubMed Central

Piccolo, Brian D.; Graham, James L.; Stanhope, Kimber L.; Fiehn, Oliver; Havel, Peter J.

2016-01-01

Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasma BCAA and other metabolites were assessed in lean control Sprague-Dawley rats (LC) and temporally during diabetes development in the UCD-T2DM rat model, i.e., prediabetic (PD) and 2 wk (D2W), 3 mo (D3M), and 6 mo (D6M) post-onset of diabetes. Plasma leucine, isoleucine, and valine concentrations were elevated only in D6M rats compared with D2W rats (by 28, 29, and 30%, respectively). This was in contrast to decreased plasma concentrations of several other amino acids in D3M and/or D6M relative to LC rats (Ala, Arg, Glu, Gln, Met, Ser, Thr, and Trp). BCAAs were positively correlated with fasting glucose and negatively correlated with plasma insulin, total body weight, total adipose tissue weight, and gastrocnemius muscle weight in the D3M and D6M groups. Multivariate analysis revealed that D3M and D6M UCD-T2DM rats had lower concentrations of amino acids, amino acid derivatives, 1,5-anhydroglucitol, and conduritol-β-opoxide and higher concentrations of uronic acids, pantothenic acids, aconitate, benzoic acid, lactate, and monopalmitin-2-glyceride relative to PD and D2W UCD-T2DM rats. The UCD-T2DM rat does not display elevated plasma BCAA concentrations until 6 mo post-onset of diabetes. With the acknowledgement that this is a rodent model of T2DM, the results indicate that elevated plasma BCAA concentrations are not necessary or sufficient to elicit an insulin resistance or T2DM onset. PMID:27094034

[Effect of CPAP therapy on dynamic glucose level in OSAHS patients with newly diagnosed T2DM].

PubMed

Zhao, Lijun; Hui, Peilin; Xie, Yuping; Hou, Yiping; Wei, Xiaoquan; Ma, Wei; Wang, Jinfeng; Zhou, Liya; Zhang, Wenjuan

2015-11-24

To investigate the characteristic of dynamic glucose level in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients with newly diagnosed type 2 diabetes mellitus (T2DM) and to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the glucose level. A total of 65 cases of patients with T2DM who were newly diagnosed by oral glucose tolerance test (OGTT) were enrolled from April 2014 to April 2015 in Gansu Provincial Hospital, and divided into simple T2DM group (n=30) and OSAHS with T2DM group (n=35) according to aponea-hypopnea index (AHI) which was monitored by polysomnography (PSG). Their general clinical data were collected, and glucose level of different periods was monitored by continuous glucose moitoring system (CGMS). Changes of glucose level were compared between two groups before and after CPAP treatment. Age, gender proportion, BMI, smoking and drinking history, glycosylated hemoglobin (HbA1c) and blood lipid profile had no significantly difference between two groups. Longer neck circumstance and higher waist-hip ration (WHR), higher systolic blood pressure and diastolic blood pressure, higher fasting plasma glucose (FPG) [(9.4 ± 3.2) vs (7.3 ± 2.1) mmol/L, P=0.028] and fasting insulin (FINS) [(19.2 ± 8.7) vs (11.1 ± 4.7) mU/L, P=0.044] level, more serious homeostasis model assessment insulin resistance (HOMA-IR) were found in OSAHS patients with T2DM when compared to patients in simple T2DM group. The average dynamic glucose level of 24 hours, daytime, nocturnal and sleep time in OSAHS with T2DM group were higher than that in the simple T2DM group (all P<0.05). The alarming times when the average dynamic glucose level of nocturnal time was more than 0.1 mmol·L⁻¹·min⁻¹ in T2DM with OSAHS was more than that in control group (P=0.001). After treatment of CPAP, the level of AHI [(5.9 ± 3.6) vs (56.7 ± 11.4) times/h, P<0.001], average dynamic glucose level of 24 hours, day, nocturnal and sleep time were obviously

Retracted: Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population.

PubMed

Liu, Guohui; Zhou, Tian-Biao; Jiang, Zongpei; Zheng, Dongwen

2015-03-01

The association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism with type-2 diabetic nephropathy (T2DN) susceptibility and the risk of type-2 diabetes mellitus (T2DM) developing into T2DN in Caucasian populations is still controversial. A meta-analysis was performed to evaluate the association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in Caucasian populations. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic databases. Sixteen articles were identified for the analysis of the association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in Caucasian populations. ACE I/D gene polymorphism was not associated with T2DN susceptibility and the risk of patients with T2DM developing T2DN in Caucasian populations. Sensitivity analysis according to sample size of case (<100 vs. ≥100) was also performed, and the results were similar to the non-sensitivity analysis. ACE I/D gene polymorphism was not associated with T2DN susceptibility and the risk of patients with T2DM developing T2DN in Caucasian populations. However, more studies should be performed in the future. © The Author(s) 2014.

Polymorphism rs189037C > T in the promoter region of the ATM gene may associate with reduced risk of T2DM in older adults in China: a case control study.

PubMed

Ding, Xiang; Hao, Qiukui; Yang, Ming; Chen, Tie; Chen, Shanping; Yue, Jirong; Leng, Sean X; Dong, Birong

2017-08-14

Recent evidence indicates that ataxia telangiectasia mutated (ATM) is a cytoplasmic protein that involves in insulin signaling pathways. When ATM gene is mutated, this event appears to contribute to the development of insulin resistance and type 2 diabetes mellitus (T2DM). Up to date, little information about the relationship between ATM gene polymorphism and T2DM is available. This study aimed to explore potential association between a genetic variant [single nucleotide polymorphism (SNP), i.e. rs189037C > T] in the ATM promoter region and T2DM in older adults in China. We conducted a 1:1 age- and sex-matched case-control study. It enrolled 160 patients including 80 type 2 diabetic and 80 nondiabetic patients who were aged 60 years and above. Genotyping of the polymorphism rs189037 in the promoter of the ATM gene was performed using polymerase chain reaction-restriction fragment length polymorphism. Chi-square test or Fisher's exact test (when an expected cell count was <5) and unpaired Student's t test were used for categorical and continuous variables, respectively. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) with adjustment for factors associated with T2DM. Significant association was found between the genotypes of the ATM rs189037 polymorphism and T2DM (P = 0.037). The frequency of CT genotype is much higher in patients without T2DM than in diabetics (60.0% versus 40.0%, P = 0.012). After adjustment of the major confounding factors, such difference remained significant (OR for non-T2DM is 2.62, 95%CI = 1.05-6.53, P = 0.038). Similar effect of CT genotype on T2DM was observed in male population (adjusted: OR = 0.27, 95%CI = 0.09-0.84, P = 0.024). In addition, the percentage of TT genotype in diabetics with coronary artery disease (CAD) was considerably lower than in those without CAD (17.9% versus 61.5%, P = 0.004). Our study suggests that the ATM rs189037 polymorphism is associated with reduced

Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model.

PubMed

Piccolo, Brian D; Graham, James L; Stanhope, Kimber L; Fiehn, Oliver; Havel, Peter J; Adams, Sean H

2016-06-01

Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasma BCAA and other metabolites were assessed in lean control Sprague-Dawley rats (LC) and temporally during diabetes development in the UCD-T2DM rat model, i.e., prediabetic (PD) and 2 wk (D2W), 3 mo (D3M), and 6 mo (D6M) post-onset of diabetes. Plasma leucine, isoleucine, and valine concentrations were elevated only in D6M rats compared with D2W rats (by 28, 29, and 30%, respectively). This was in contrast to decreased plasma concentrations of several other amino acids in D3M and/or D6M relative to LC rats (Ala, Arg, Glu, Gln, Met, Ser, Thr, and Trp). BCAAs were positively correlated with fasting glucose and negatively correlated with plasma insulin, total body weight, total adipose tissue weight, and gastrocnemius muscle weight in the D3M and D6M groups. Multivariate analysis revealed that D3M and D6M UCD-T2DM rats had lower concentrations of amino acids, amino acid derivatives, 1,5-anhydroglucitol, and conduritol-β-opoxide and higher concentrations of uronic acids, pantothenic acids, aconitate, benzoic acid, lactate, and monopalmitin-2-glyceride relative to PD and D2W UCD-T2DM rats. The UCD-T2DM rat does not display elevated plasma BCAA concentrations until 6 mo post-onset of diabetes. With the acknowledgement that this is a rodent model of T2DM, the results indicate that elevated plasma BCAA concentrations are not necessary or sufficient to elicit an insulin resistance or T2DM onset. Copyright © 2016 the American Physiological Society.

Efficacy and safety of trastuzumab emtansine (T-DM1) in the treatment of HER2-positive metastatic breast cancer (MBC): a meta-analysis of randomized controlled trial

PubMed Central

Yan, Hongjing; Yu, Kewei; Zhang, Kaile; Liu, Linxia; Li, Yue

2017-01-01

Aims Trastuzumab emtansine (T-DM1), an antibody-drug conjugate against human epidermal growth factor receptor 2 (HER2), has been used in the treatment of patients with HER2-positive metastatic breast cancer (MBC). We conducted a meta-analysis to evaluate the efficacy and toxicity of T-DM1 for the treatment of patients with HER2-positive MBC. Materials and Methods Randomized controlled trials (RCTs), published in Pubmed, Embase, and Web of Science were systematically reviewed to assess the survival benefits and toxicity profile of HER2-positive patients with MBC who were treated with T-DM1. Outcomes included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and toxicities. Results were expressed as the hazard ratio (HR) with 95% confidence intervals (CIs). Results A total of 5 RCTs involving 3,720 patients met the inclusion criteria and were included in this meta-analysis. T-DM1 significantly prolonged PFS (HR = 0.73, 95% CI: 0.61, 0.86; P < 0.05), OS (HR = 0.68, 95% CI: 0.62, 0.74; P < 0.05), but it did not increase ORR (RR = 1.25, 95% CI: 0.94, 1.66; P = 0.148). Subgroup analysis indicated that T-DM1 significantly improved PFS when it was used as first-line (HR = 0.86, 95% CI: 0.74, 1.00; P < 0.05) or non-first-line treatment (HR = 0.65, 95% CI: 0.53, 0.81; P < 0.05). T-DM1 was associated with more frequent adverse events, including fatigue, elevated ALT, elevated AST, and thrombocytopenia, than other anti-HER2 therapies. Conclusions Based on the current evidence, T-DM1 significantly prolonged PFS and OS with a tolerated toxicity than other anti-HER2 therapies in patients with HER2-positive MBC. These findings confirm the use of T-DM1 for the treatment of patients with HER2-positive MBC. Further well-designed, multi-center RCTs needed to identify these findings. PMID:29254261

[HDL-C/apoA-I]: A multivessel cardiometabolic risk marker in women with T2DM.

PubMed

Hermans, Michel P; Valensi, Paul; Ahn, Sylvie A; Rousseau, Michel F

2018-01-01

Although women have higher high-density lipoprotein cholesterol (HDL-C) than have men, their HDL particles are also prone to become small, dense, and dysfunctional in case of type 2 diabetes mellitus (T2DM). To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL-C to its main apolipoprotein (apoA-I) as [HDL-C/apoA-I]. This ratio estimates HDL sizes and provides indices as to their number, cholesterol load, and density. We stratified 280 Caucasian T2DM women according to [HDL-C/apoA-I] quartiles (Q) to determine how they are segregated according to cardiometabolic risk, β-cell function, glycaemic control, and vascular complications. Five parameters were derived from combined determination of HDL-C and apoA-I: HDL size, HDL number, cholesterol load per particle (pP), apoA-I pP, and HDL density. An adverse cardiometabolic profile characterized QI and QII patients whose HDLs were denser and depleted in apoA-I, whereas QIII patients had HDLs with characteristics closer to those of controls. QIV patients had HDLs of supernormal size/composition and a more favourable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, and β-cell function (32% vs 23%); exogenous insulin (44 vs 89 U·d -1 ); and glycaemic control (glycated haemoglobin, 56 vs 61 mmol·mol -1 ), associated with lower prevalence of microvascular/macrovascular complications: all-cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all-cause macroangiopathy 19% vs 31%; and coronary artery disease 6% vs 24% (P < .05). [HDL-C/apoA-I] can stratify T2DM women according to metabolic phenotype, macrovascular and coronary damage, β-cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women. Copyright © 2017 John Wiley & Sons, Ltd.

Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea.

PubMed

Lukashevich, V; Del Prato, S; Araga, M; Kothny, W

2014-05-01

The broadly used combination of metformin and sulphonylurea (SU) often fails to bring patients to glycaemic goal. This study assessed the efficacy and safety of vildagliptin as add-on therapy to metformin plus glimepiride combination in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control. A multicentre, double-blind, placebo-controlled study randomized patients to receive treatment with vildagliptin 50 mg bid (n = 158) or placebo (n = 160) for 24 weeks. After 24 weeks, the adjusted mean change in haemoglobin A1c (HbA1c) was -1.01% with vildagliptin (baseline 8.75%) and -0.25% with placebo (baseline 8.80%), with a between-treatment difference of -0.76% (p < 0.001). Significantly more patients on vildagliptin achieved the HbA1c target <7% (28.3% vs. 5.6%; p < 0.001). The difference in fasting plasma glucose reduction between vildagliptin and placebo was -1.13 mmol/l (p < 0.001). In subgroup of patients with baseline HbA1c ≤8%, vildagliptin reduced HbA1c by 0.74% from baseline 7.82% (between-treatment difference: -0.97%; p < 0.001) with significantly more patients achieving the HbA1c target <7% (38.6% vs. 13.9%; p = 0.014). Vildagliptin was well tolerated with low incidence of hypoglycaemia, slightly higher than with placebo (5.1% vs. 1.9%) and no clinically relevant weight gain. Vildagliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin plus glimepiride combination. The addition of vildagliptin was well tolerated with low risk of hypoglycaemia and weight gain. This makes vildagliptin an attractive treatment option for patients failing on metformin plus SU particularly in patients with baseline HbA1c ≤8%. © 2013 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea

PubMed Central

Lukashevich, V; Del Prato, S; Araga, M; Kothny, W

2014-01-01

Aim The broadly used combination of metformin and sulphonylurea (SU) often fails to bring patients to glycaemic goal. This study assessed the efficacy and safety of vildagliptin as add-on therapy to metformin plus glimepiride combination in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control. Methods A multicentre, double-blind, placebo-controlled study randomized patients to receive treatment with vildagliptin 50 mg bid (n = 158) or placebo (n = 160) for 24 weeks. Results After 24 weeks, the adjusted mean change in haemoglobin A1c (HbA1c) was −1.01% with vildagliptin (baseline 8.75%) and −0.25% with placebo (baseline 8.80%), with a between-treatment difference of −0.76% (p < 0.001). Significantly more patients on vildagliptin achieved the HbA1c target <7% (28.3% vs. 5.6%; p < 0.001). The difference in fasting plasma glucose reduction between vildagliptin and placebo was −1.13 mmol/l (p < 0.001). In subgroup of patients with baseline HbA1c ≤8%, vildagliptin reduced HbA1c by 0.74% from baseline 7.82% (between-treatment difference: –0.97%; p < 0.001) with significantly more patients achieving the HbA1c target <7% (38.6% vs. 13.9%; p = 0.014). Vildagliptin was well tolerated with low incidence of hypoglycaemia, slightly higher than with placebo (5.1% vs. 1.9%) and no clinically relevant weight gain. Conclusions Vildagliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin plus glimepiride combination. The addition of vildagliptin was well tolerated with low risk of hypoglycaemia and weight gain. This makes vildagliptin an attractive treatment option for patients failing on metformin plus SU particularly in patients with baseline HbA1c ≤8%. PMID:24199686

Pioglitazone improves the ability of learning and memory via activating ERK1/2 signaling pathway in the hippocampus of T2DM rats.

PubMed

Gao, F; Zang, L; Wu, D Y; Li, Y J; Zhang, Q; Wang, H B; Tian, G L; Mu, Y M

2017-06-09

To explore the correlation between effect of PIO (pioglitazone, PIO) on learning as well as memory and ERK1/2 (extracellular signal regulated kinase 1/2, ERK1/2) pathway in T2DM (type 2 diabetes mellitus, T2DM) rats, further to elucidate the potential mechanism of PIO in improvement of learning and memory. 12-week-old male SD rats (number of 10 per group) were randomly divided into control group (CON), T2DM group (DM) and T2DM +PIO group (DM+PG). Rats in DM and DM+PG groups were given high fat diet for 20 weeks, then treated with Streptozotocin (27mg/kg) by intraperitoneal injection at 21week. After 72h, the FBG (fasting blood glucose, FBG) was greater than 7.0mmol/L can considered T2DM rats. DM+PG group was treated with PIO (10 mg·kg -1 ·d -1 ) by gavage daily. After Hyperinsulinemic-Euglycemic Clamp Study and Morris water maze test at 30-week, all of animals were sacrificed. The expressions of RKIP (Raf-1 kinase inhibitor protein, RKIP) and ERK1/2 in hippocampus were detected using Western Blot and real-time PCR. The FBG level: DM group (7.68±0.54mmol/L) was higher than CON group (5.35±0.63mmol/L) and DM+PG group (6.07±0.84mmol/L), the differences were considered statistically significant (P <0.05). Hyperinsulinemic-Euglycemic Clamp Studies: GIR (glucose infusion rate, GIR) of DM group (21.02±5.10 mg·kg -1 ·d -1 ) was less than CON group (27.64±3.87 mg·kg -1 ·d -1 ) and DM+PG group (26.04 ±5.41 mg·kg -1 ·d -1 ), the differences were considered statistically significant (P <0.05). Morris water maze training: The escape latencies and searching platform performance of DM group (24.54±5.02s) decreased significantly compared with CON group (16.73±4.02s) and DM+PG group (18.05±4.12s) (P <0.05). Changes of RKIP, ERK, p-ERK protein relative content in rat hippocampus: Compared with CON groupand DM+PG group, the relative content of RKIP in DM group remarkably increased (P<0.01); ERK protein levels were not considered statistically significant among the

Prevalence of type 2 diabetes mellitus complications among palestinians with T2DM.

PubMed

Abu Al-Halaweh, Ahmad; Davidovitch, Nadav; Almdal, Thomas Peter; Cowan, Anna; Khatib, Samah; Nasser-Eddin, Lana; Baradia, Ziad

2017-12-01

To assess the prevalence of microvascular and macrovascular complications of type 2 diabetes (T2DM) among Palestinians. 1308 diagnosed T2DM attending four main Primary Health Care Clinics on the Southern West Bank of Palestine examined by a Mobile Diabetes Clinic team. All diabetes patients visiting the clinics during a one-month period for each clinic were included. Interviews, anthropometric measurements, physical examination, and laboratory tests: HbA1c, lipid profile, and kidney function tests analyzed in a central laboratory were obtained RESULTS: 1308 diabetes patients, including 839 females (64%), with a mean age of 57 years (SD=8.7), and mean diabetes duration 7.1 years(SD=6.25), participated. 95.3% presented as overweight (BMI >25kg/m 2 ) or obese (BMI>30kg/m 2 ) with mean BMI of 33.46 (SD=5.95). The mean HbA1c (tested in 1221 patients) was 9.21(SD=2). Only 16.1% had HbA1c <7.0%. Hypertension (blood pressure>140/90mmHg) were found in 23%, and dyslipidemia (total cholesterol>200mg/dl) was present in 37.3% of patients. 213(16.3%) had a history of the macrovascular disease (previous myocardial infarction or stroke), and 290 (25.9%) had microvascular complications. Moreover, 40 (4.9%) had advanced kidney disease with serum creatinine>1.4mg/dl. The present cross-sectional study shows poor glycemic control in Palestine, while blood pressure and lipids are less poorly controlled. The study emphasizes the need to optimize the glucose-lowering treatment and to implement diabetes care program that could face the challenge of high uncontrolled diabetes as well as complications of diabetes. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Living with diabetes: a group-based self-management support programme for T2DM patients in the early phases of illness and their partners, study protocol of a randomised controlled trial.

PubMed

van Puffelen, Anne L; Rijken, Mieke; Heijmans, Monique J W M; Nijpels, Giel; Rutten, Guy E H M; Schellevis, François G

2014-04-01

The present article presents the protocol for a randomised controlled trial to test the effectiveness of a group-based self-management support programme for recently diagnosed type 2 diabetes mellitus (T2DM) patients (one to three years post-diagnosis) and their partners. The course aims to support T2DM patients and their partners in successfully integrating diabetes care into their daily lives and hereby enhance self-management and diabetes-specific health-related quality of life. The content of the course is based on the Common-Sense Model of Self-Regulation (CSM). Furthermore, principles from the Social Cognitive Theory (SCT) and social support theories are integrated. We aim to recruit 160 recently diagnosed T2DM patients and their partners from general practices in six different regions in the Netherlands. Patients need to be diagnosed with T2DM for one to three years and have to experience some degree of diabetes-related difficulties, as measured with a three-item screener. Participating patients and their partners are randomly allocated to the intervention or control condition. Participants in the intervention condition receive three monthly group sessions and a booster session three months later. Participants in the control condition receive a single information meeting. Data will be collected at baseline (T0), directly after the programme (T1) and six months post-programme (T2), including: self-management, diabetes-specific health-related quality of life, illness perceptions, attitudes, social support and empowerment. A three-level multilevel model will be used to compare change-scores between the conditions (intervention/control) on each outcome. Our study will be the first to determine whether a group-based support programme based on the CSM is effective in enhancing self-management and diabetes-specific health-related quality of life in recently diagnosed T2DM patients. The important role of patients' partners in effective diabetes care is also

A cross-sectional study on the associations of insulin resistance with sex hormone, abnormal lipid metabolism in T2DM and IGT patients

PubMed Central

Wang, Xiaoxia; Xian, Tongzhang; Jia, Xiaofan; Zhang, Lina; Liu, Li; Man, Fuli; Zhang, Xianbo; Zhang, Jie; Pan, Qi; Guo, Lixin

2017-01-01

Abstract Type 2 diabetes mellitus (T2DM) is a long-term metabolic disorder. It is characterized by hyperglycemia, insulin resistance (IR), and relative impairment in insulin secretion. IR plays a major role in the pathogenesis of T2DM. Many previous studies have investigated the relationship between estrogen, androgen, and obesity, but few focused on the relationship between sex hormones, abnormal lipid metabolism, and IR. The goal for the present study was to identify the association of IR with sex hormone, abnormal lipid metabolism in type 2 diabetes, and impaired glucose tolerance (IGT) patients. In total 13,400 participants were analyzed based on the results of the glucose tolerance test. Using a cross-sectional study, we showed the relationship between IR and the level of sex hormones among 3 different glucose tolerance states: normal control people, IGT, and T2DM patients. We also analyzed the relationship between IR and abnormal lipid metabolism. Significantly, luteinizing, progesterone, estradiol, prolactin, and follicle-stimulating hormone levels decreased in T2DM and IGT patients compared with those in normal control people. The association between IR and lipid metabolism disorders in T2DM and IGT patients was also observed. Our clinical findings may offer new insights into understanding the mechanism of metabolic disorders and in new therapeutic methods for the treatment of the prevalence of type 2 diabetes. PMID:28658166

Deterioration of plasticity and metabolic homeostasis in the brain of the UCD-T2DM rat model of naturally occurring type-2 diabetes.

PubMed

Agrawal, Rahul; Zhuang, Yumei; Cummings, Bethany P; Stanhope, Kimber L; Graham, James L; Havel, Peter J; Gomez-Pinilla, Fernando

2014-09-01

The rising prevalence of type-2 diabetes is becoming a pressing issue based on emerging reports that T2DM can also adversely impact mental health. We have utilized the UCD-T2DM rat model in which the onset of T2DM develops spontaneously across time and can serve to understand the pathophysiology of diabetes in humans. An increased insulin resistance index and plasma glucose levels manifested the onset of T2DM. There was a decrease in hippocampal insulin receptor signaling in the hippocampus, which correlated with peripheral insulin resistance index along the course of diabetes onset (r=-0.56, p<0.01). T2DM increased the hippocampal levels of 4-hydroxynonenal (4-HNE; a marker of lipid peroxidation) in inverse proportion to the changes in the mitochondrial regulator PGC-1α. Disrupted energy homeostasis was further manifested by a concurrent reduction in energy metabolic markers, including TFAM, SIRT1, and AMPK phosphorylation. In addition, T2DM influenced brain plasticity as evidenced by a significant reduction of BDNF-TrkB signaling. These results suggest that the pathology of T2DM in the brain involves a progressive and coordinated disruption of insulin signaling, and energy homeostasis, with profound consequences for brain function and plasticity. All the described consequences of T2DM were attenuated by treatment with the glucagon-like peptide-1 receptor agonist, liraglutide. Similar results to those of liraglutide were obtained by exposing T2DM rats to a food energy restricted diet, which suggest that normalization of brain energy metabolism is a crucial factor to counteract central insulin sensitivity and synaptic plasticity associated with T2DM. Copyright © 2014 Elsevier B.V. All rights reserved.

Application of the integrated glucose–insulin model for cross‐study characterization of T2DM patients on metformin background treatment

PubMed Central

Hamrén, Bengt; Kjellsson, Maria C.; Skrtic, Stanko

2016-01-01

Aim The integrated glucose–insulin (IGI) model is a semi‐mechanistic physiological model which can describe the glucose–insulin homeostasis system following various glucose challenge settings. The aim of the present work was to apply the model to a large and diverse population of metformin‐only‐treated type 2 diabetes mellitus (T2DM) patients and identify patient‐specific covariates. Methods Data from four clinical studies were pooled, including glucose and insulin concentration–time profiles from T2DM patients on stable treatment with metformin alone following mixed‐meal tolerance tests. The data were collected from a wide range of patients with respect to the duration of diabetes and level of glycaemic control. Results The IGI model was expanded by four patient‐specific covariates. The level of glycaemic control, represented by baseline glycosylated haemoglobin was identified as a significant covariate for steady‐state glucose, insulin‐dependent glucose clearance and the magnitude of the incretin effect, while baseline body mass index was a significant covariate for steady‐state insulin levels. In addition, glucose dose was found to have an impact on glucose absorption rate. The developed model was used to simulate glucose and insulin profiles in different groups of T2DM patients, across a range of glycaemic control, and it was found accurately to characterize their response to the standard oral glucose challenge. Conclusions The IGI model was successfully applied to characterize differences between T2DM patients across a wide range of glycaemic control. The addition of patient‐specific covariates in the IGI model might be valuable for the future development of antidiabetic treatment and for the design and simulation of clinical studies. PMID:27450071

T-DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo

PubMed Central

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-01-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody–drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. PMID:24890382

Uncontrolled Hypertension and Its Determinants in Patients with Concomitant Type 2 Diabetes Mellitus (T2DM) in Rural South Africa.

PubMed

Adeniyi, Oladele Vincent; Yogeswaran, Parimalaranie; Longo-Mbenza, Benjamin; Ter Goon, Daniel

2016-01-01

Paucity of data on the prevalence, treatment and control of hypertension in individuals living with type 2 diabetes mellitus (T2DM) in the rural communities of South Africa may undermine efforts to reduce the morbidity and mortality associated with cardiovascular diseases. This study examines the socio-demographic and clinical determinants of uncontrolled hypertension among individuals living with T2DM in the rural communities of Mthatha, South Africa. This cross-sectional study involved a serially selected sample of 265 individuals living with T2DM and hypertension at Mthatha General Hospital, Mthatha. Uncontrolled hypertension was defined as systolic blood pressure greater than or equal to 140 mmHg and diastolic blood pressure greater than or equal to 90mmHg in accordance with the Eight Joint National Committee Report (JNC 8) (2014). We performed univariate and multivariate logistic regression analyses to identify the significant determinants of uncontrolled hypertension. Of the total participants (n = 265), the prevalence of uncontrolled hypertension was 75.5% (n = 200). In univariate analysis of all participants, male gender (p = 0.029), age≥65 years (p = 0.016), unemployed status (p<0.0001), excessive alcohol intake (p = 0.005) and consumption of western-type diet (p<0.0001) were positively associated with uncontrolled hypertension. In multivariate logistic regression (LR method) analysis, unemployed status (p<0.0001), excessive alcohol intake (p = 0.007) and consumption of western-type diet (p<0.0001) were independently and significantly associated with uncontrolled hypertension. There is significant association between increasing number and classes of anti-hypertensive drugs and uncontrolled hypertension (p = 0.05 and 0.02, respectively). Prevalence of uncontrolled hypertension was high in individuals with concomitant hypertension and T2DM in the study population. Male sex, aging, clinic inertia, unemployed status and nutritional transitions are the most

Glutathione S-Transferase Pi-Ile 105 Val Polymorphism and Susceptibility to T2DM in Population from Turabah Region of Saudi Arabia.

PubMed

Mergani, Adil; Mansour, Ahmed Abdelkhalik; Askar, Tamer; Zahran, Rasha Nabeel; Mustafa, Adil Musa; Mohammed, Mukhtar Ahmed; Saleh, Osama Mosailhy

2016-08-01

Type 2 diabetes mellitus is characterized by chronic hyperglycemia and associated with oxidative stress resulting from accumulation of free radicals in body's tissues, which especially affects beta cells in pancreas and is an important factor in the development of diabetes and its complications. Glutathione S-transferases (GSTs) are a family of antioxidant enzymes that play important roles in decreasing ROS species and act as a kind of antioxidant defense. In a case-control study, we investigated the role of GSTP1 Ile105Val polymorphism in predisposition to T2DM in patients from Tarabah province, Saudi Arabia. The polymorphism was screened by PCR-RFLP in 90 T2DM patients and 87 healthy controls. The genotypes and alleles frequencies in cases and controls were assessed using Cochran-Armitage trend test and odds ratios (ORs), and 95 % confidence intervals (CIs) in different genetic models of inheritance were calculated. Our data indicate that G allele (Val) is associated with an increased risk for T2DM in this population in any combination (OR 4.101, 95 % CI 1.986-8.469, P = 0.00008). This indicates that individuals who are carriers for the mutant allele, either in homozygous (GG) or heterozygous (AG) state, are at fourfold higher risk for development of T2DM than other subjects in this population.

T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo.

PubMed

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-10-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

LC-MS/MS method for the simultaneous determination of Lys-MCC-DM1, MCC-DM1 and DM1 as potential intracellular catabolites of the antibody-drug conjugate trastuzumab emtansine (T-DM1).

PubMed

Liu, Yazhong; Zhou, Fang; Sang, Hua; Ye, Hui; Chen, Qianying; Yao, Lan; Ni, Ping; Wang, Guangji; Zhang, Jingwei

2017-04-15

Lysine-MCC-DM1, MCC-DM1 and DM1 are potential catabolites of trastuzumab emtansine (T-DM1). A convenient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to detect these catabolites simultaneously in in vitro investigations for the first time. Protein precipitation was utilized to prepare the samples. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100×2.1mm, 2.6μm) with mobile-phase gradient elution. The calibration curves of each analyte ranging from 1 to 100nM showed good linearity (r 2 >0.995). The method was validated successfully and applied to the intracellular catabolism and regulation of T-DM1. Copyright © 2017 Elsevier B.V. All rights reserved.

Rare sugar D-psicose prevents progression and development of diabetes in T2DM model Otsuka Long-Evans Tokushima Fatty rats.

PubMed

Hossain, Akram; Yamaguchi, Fuminori; Hirose, Kayoko; Matsunaga, Toru; Sui, Li; Hirata, Yuko; Noguchi, Chisato; Katagi, Ayako; Kamitori, Kazuyo; Dong, Youyi; Tsukamoto, Ikuko; Tokuda, Masaaki

2015-01-01

The fundamental cause of overweight and obesity is consumption of calorie-dense foods. We have introduced a zero-calorie sweet sugar, d-psicose (d-allulose), a rare sugar that has been proven to have strong antihyperglycemic and antihyperlipidemic effects, and could be used as a replacement of natural sugar for the obese and diabetic subjects. Above mentioned efficacy of d-psicose (d-allulose) has been confirmed in our previous studies on type 2 diabetes mellitus (T2DM) model Otsuka Long-Evans Tokushima Fatty (OLETF) rats with short-term treatment. In this study we investigated the long-term effect of d-psicose in preventing the commencement and progression of T2DM with the mechanism of preservation of pancreatic β-cells in OLETF rats. Treated OLETF rats were fed 5% d-psicose dissolved in water and control rats only water. Nondiabetic control rats, Long-Evans Tokushima Otsuka (LETO), were taken as healthy control and fed water. To follow the progression of diabetes, periodic measurements of blood glucose, plasma insulin, and body weight changes were continued till sacrifice at 60 weeks. Periodic in vivo body fat mass was measured. On sacrifice, pancreas, liver, and abdominal adipose tissues were collected for various staining tests. d-Psicose prevented the commencement and progression of T2DM till 60 weeks through the maintenance of blood glucose levels, decrease in body weight gain, and the control of postprandial hyperglycemia, with decreased levels of HbA1c in comparison to nontreated control rats. This improvement in glycemic control was accompanied by the maintenance of plasma insulin levels and the preservation of pancreatic β-cells with the significant reduction in inflammatory markers. Body fat accumulation was significantly lower in the treatment group, with decreased infiltration of macrophages in the abdominal adipose tissue. Our findings suggest that the rare sugar d-psicose could be beneficial for the prevention and control of obesity and

Vildagliptin versus insulin in patients with type 2 diabetes mellitus inadequately controlled with sulfonylurea: results from a randomized, 24 week study.

PubMed

Forst, Thomas; Koch, Cornelia; Dworak, Markus

2015-06-01

There is limited evidence to guide the selection of second-line anti-hyperglycemic agents in patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with sulfonylurea monotherapy and are intolerant to metformin. We compared the efficacy and safety of vildagliptin 50 mg qd and Neutral Protamine Hagedorn (NPH) insulin qd in such patients. This was a 24 week, multicenter, randomized, open-label study. The co-primary endpoints were (i) proportion of patients achieving HbA1c <7.0% without any confirmed hypoglycemic events (HEs) or weight gain ≥3% (composite endpoint); (ii) rate of confirmed HEs. Treatment satisfaction was assessed using the TSQM-9 questionnaire at study end. A total of 162 patients were randomly assigned to vildagliptin (n = 83) and NPH insulin (n = 79). Similar proportion of patients achieved the composite endpoint in vildagliptin versus NPH insulin group (35.4% versus 34.2%; OR 0.985; 95% CI 0.507, 1.915; p = 0.96). After 24 weeks, 48.8% of patients in the vildagliptin group and 60.8% in the NPH insulin group achieved HbA1c <7.0%; 13.4% in the vildagliptin group and 29.1% in the insulin group had at least one confirmed HE; while 11.0% in the vildagliptin group and 22.8% in the insulin group experienced weight gain. The rate of confirmed HEs was significantly lower in patients receiving vildagliptin versus NPH insulin (1.3 versus 5.1 events per year). The TSQM-9 score for 'convenience' at week 24 increased significantly more with vildagliptin than with NPH insulin. Addition of vildagliptin and NPH insulin resulted in a similar number of patients reaching HbA1c target without HEs or weight gain in T2DM patients inadequately controlled with sulfonylurea. The addition of vildagliptin to sulfonylurea could be considered as a treatment option prior to intensification with insulin, with the advantages of a lower HE rate and greater patient convenience. Study results are limited by a higher drop-out rate in the

Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database.

PubMed

Schober, E; Rami, B; Grabert, M; Thon, A; Kapellen, Th; Reinehr, Th; Holl, R W

2009-05-01

To analyse and compare clinical characteristics in young patients with maturity-onset diabetes of the young (MODY) and Type 2 diabetes mellitus (T2DM). We conducted an observational investigation using the DPV-Wiss database containing clinical data on 40 757 diabetic patients < 20 years of age from Germany and Austria. Three hundred and thirty-nine cases were clinically categorized as MODY (0.83%); 562 patients were diagnosed as T2DM (1.4%). In 20% of cases, the diagnosis of MODY was based on clinical findings only. Of the 272 subjects where genetic testing was available, 3% did not carry mutations in the three examined MODY genes. Glucokinase-MODY was commoner than HNF1A-MODY and HNF4A-MODY. Age at diagnosis was younger in MODY patients. The body mass index of T2DM was significantly higher compared with all MODY subgroups. Macrovascular risk factors such as dyslipidaemia and hypertension were commoner in T2DM, but 23% of MODY patients had dyslipidaemia and 10% hypertension. Glycaemic control was within the therapeutic target (HbA(1c) < 7.5%) in 86% of MODY and 70% of T2DM patients. The prevalence of MODY in children and adolescents in Germany and Austria is lower than that of T2DM in this age group. Dyslipidaemia and hypertension are less frequent in MODY compared with T2DM patients, but do occur.

Comparison of vildagliptin as an add-on therapy and sulfonylurea dose-increasing therapy in patients with inadequately controlled type 2 diabetes using metformin and sulfonylurea (VISUAL study): A randomized trial.

PubMed

Hong, A Ram; Lee, Jeun; Ku, Eu Jeong; Hwangbo, Yul; Kim, Kyoung Min; Moon, Jae Hoon; Choi, Sung Hee; Jang, Hak Chul; Lim, Soo

2015-07-01

The aim of present study is to compare the efficacy and safety of adding vildagliptin with sulfonylurea dose-increasing as an active comparator in patients who had inadequately controlled type 2 diabetes mellitus (T2DM) using metformin plus sulfonylurea in real clinical practice. Patients using metformin plus sulfonylurea were assigned to either vildagliptin add-on (50 mg twice a day, n=172) or sulfonylurea dose-increasing by 50% (n=172) treatment groups. The primary endpoint was a change in HbA(1c) after 24 weeks. The secondary endpoints were patients achieving HbA(1c)≤7.0% (53 mmol/mol) and changes in the fasting plasma glucose (FPG), 2-h postprandial glucose (2pp), lipid profiles, and urine albumin-to-creatinine ratio. Body weight and hypoglycemia were also investigated. The mean HbA(1c) at baseline was 8.6% (70 mmol/mol) in both groups. At week 24, the adjusted mean HbA(1c) levels decreased by -1.19% (-13.09 mmol/mol) with vildagliptin add-on and -0.46% (-5.06 mmol/mol) with sulfonylurea (P<0.001). Significantly more vildagliptin add-on patients achieved HbA(1c)≤7.0% (53 mmol/mol) than did sulfonylurea patients (40.1% vs. 7.9%; P<0.001). Greater reductions in FPG and 2pp were observed with vildagliptin add-on than with sulfonylurea (P<0.001). The vildagliptin add-on group exhibited no clinically relevant weight gain and had a lower incidence of hypoglycemia compared with the sulfonylurea group. Vildagliptin add-on therapy might be a suitable option for patients with T2DM that is controlled inadequately by metformin and sulfonylurea, based on its greater glucose control and better safety profile (ClinicalTrial.gov: NCT01099137). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Complications and comorbidities of T2DM in adolescents: findings from the TODAY clinical trial

PubMed Central

Tryggestad, Jeanie B.; Willi, Steven M.

2014-01-01

Summary With the rise in childhood obesity, type 2 diabetes mellitus (T2DM) has been recognized to occur in adolescents with increasing frequency. Although much is known about T2DM in adults, few studies have examined the treatment and complications of T2DM in youth. The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study was designed to evaluate the efficacy of various treatments and provided a unique opportunity to study the disease progression and appearance of complications in a pediatric cohort with recent onset of the disease. In the TODAY study, hypertension was present in 11.6% of the population at baseline and increased to 33.8% by the end of the study. Prevalence of high-risk LDL-cholesterol rose from 4.5% at baseline to 10.7% at the end of the study. Microalbuminuria was found in 6.3% of the cohort at baseline and increased to 16.6%. Retinopathy was not assessed upon entry into TODAY, but was present in 13.9% of the TODAY cohort at the end of the study. Experience to date indicates that these complications and comorbidities are similar to that seen in adults, but occur on an accelerated timeline. The early manifestation of diabetes complications in youth-onset T2DM suggests that this group will be burdened with the tangible consequences of cardiovascular disease, nephropathy, and retinopathy in the third and fourth decades of life. It is hoped that through an early, aggressive approach to treatment and prevention, we may be able to curb the onset and progression of these potentially devastating outcomes. PMID:25468310

Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM).

PubMed

Kakleas, Kostas; Soldatou, Alexandra; Karachaliou, Feneli; Karavanaki, Kyriaki

2015-09-01

Type 1 diabetes (T1DM) is an autoimmune disease with aberrant immune responses to specific β-cell autoantigens, resulting in insulin deficiency. Children and adolescents with T1DM may also develop organ-specific multiple autoimmunity in the context of APS (autoimmune polyendocrine syndrome) type 1, 2 or 3. The most frequently encountered associated autoimmune disorders in T1DM are autoimmune thyroid, followed by celiac, autoimmune gastric disease and other rare autoimmune conditions. There are limited previous studies on the prevalence of associated autoimmunity, especially multiple, in children with T1DM. The present review reports on the classification of autoimmune diabetes, and on the prevalence, pathogenesis, predictive factors and clinical presentation of pancreatic autoimmunity and of all associated autoimmune disorders in children with T1DM. The impact of associated autoimmunity on diabetes control and general health is also discussed, along with suggestions regarding screening strategies and follow-up for early detection and management of the autoimmunity. Copyright © 2015 Elsevier B.V. All rights reserved.

DS-8201a, a new HER2-targeting antibody-drug conjugate incorporating a novel DNA topoisomerase I inhibitor, overcomes HER2-positive gastric cancer T-DM1 resistance.

PubMed

Takegawa, Naoki; Nonagase, Yoshikane; Yonesaka, Kimio; Sakai, Kazuko; Maenishi, Osamu; Ogitani, Yusuke; Tamura, Takao; Nishio, Kazuto; Nakagawa, Kazuhiko; Tsurutani, Junji

2017-10-15

Anti-HER2 therapies are beneficial for patients with HER2-positive breast or gastric cancer. T-DM1 is a HER2-targeting antibody-drug conjugate (ADC) comprising the antibody trastuzumab, a linker, and the tubulin inhibitor DM1. Although effective in treating advanced breast cancer, all patients eventually develop T-DM1 resistance. DS-8201a is a new ADC incorporating an anti-HER2 antibody, a newly developed, enzymatically cleavable peptide linker, and a novel, potent, exatecan-derivative topoisomerase I inhibitor (DXd). DS-8201a has a drug-to-antibody-ratio (DAR) of 8, which is higher than that of T-DM1 (3.5). Owing to these unique characteristics and unlike T-DM1, DS-8201a is effective against cancers with low-HER2 expression. In the present work, T-DM1-resistant cells (N87-TDMR), established using the HER2-positive gastric cancer line NCI-N87 and continuous T-DM1 exposure, were shown to be susceptible to DS-8201a. The ATP-binding cassette (ABC) transporters ABCC2 and ABCG2 were upregulated in N87-TDMR cells, but HER2 overexpression was retained. Furthermore, inhibition of ABCC2 and ABCG2 by MK571 restored T-DM1 sensitivity. Therefore, resistance to T-DM1 is caused by efflux of its payload DM1, due to aberrant expression of ABC transporters. In contrast to DM1, DXd payload of DS-8201a inhibited the growth of N87-TDMR cells in vitro. This suggests that either DXd may be a poor substrate of ABCC2 and ABCG2 in comparison to DM1, or the high DAR of DS-8201a relative to T-DM1 compensates for increased efflux. Notably, N87-TDMR xenograft tumor growth was prevented by DS-8201a. In conclusion, the efficacy of DS-8201a as a treatment for patients with T-DM1-resistant breast or gastric cancer merits investigation. © 2017 UICC.

Cost-effectiveness analysis of trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2): positive advanced breast cancer.

PubMed

Le, Quang A; Bae, Yuna H; Kang, Jenny H

2016-10-01

The EMILIA trial demonstrated that trastuzumab emtansine (T-DM1) significantly increased the median profession-free and overall survival relative to combination therapy with lapatinib plus capecitabine (LC) in patients with HER2-positive advanced breast cancer (ABC) previously treated with trastuzumab and a taxane. We performed an economic analysis of T-DM1 as a second-line therapy compared to LC and monotherapy with capecitabine (C) from both perspectives of the US payer and society. We developed four possible Markov models for ABC to compare the projected life-time costs and outcomes of T-DM1, LC, and C. Model transition probabilities were estimated from the EMILIA and EGF100151 clinical trials. Direct costs of the therapies, major adverse events, laboratory tests, and disease progression, indirect costs (productivity losses due to morbidity and mortality), and health utilities were obtained from published sources. The models used 3 % discount rate and reported in 2015 US dollars. Probabilistic sensitivity analysis and model averaging were used to account for model parametric and structural uncertainty. When incorporating both model parametric and structural uncertainty, the resulting incremental cost-effectiveness ratios (ICER) comparing T-DM1 to LC and T-DM1 to C were $183,828 per quality-adjusted life year (QALY) and $126,001/QALY from the societal perspective, respectively. From the payer's perspective, the ICERs were $220,385/QALY (T-DM1 vs. LC) and $168,355/QALY (T-DM1 vs. C). From both perspectives of the US payer and society, T-DM1 is not cost-effective when comparing to the LC combination therapy at a willingness-to-pay threshold of $150,000/QALY. T-DM1 might have a better chance to be cost-effective compared to capecitabine monotherapy from the US societal perspective.

Administration of pioglitazone alone or with alogliptin delays diabetes onset in UCD-T2DM rats

PubMed Central

Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L; Stanhope, Kimber; Haj, Fawaz G; Havel, Peter J

2015-01-01

There is a need to identify strategies for type 2 diabetes prevention. Therefore, we investigated the efficacy of pioglitazone and alogliptin alone and in combination to prevent type 2 diabetes onset in UCD-T2DM rats, a model of polygenic obese type 2 diabetes. At 2 months of age, rats were divided into four groups: control, alogliptin (20 mg/kg per day), pioglitazone (2.5 mg/kg per day), and alogliptin+pioglitazone. Non-fasting blood glucose was measured weekly to determine diabetes onset. Pioglitazone alone and in combination with alogliptin lead to a 5-month delay in diabetes onset despite promoting increased food intake and body weight (BW). Alogliptin alone did not delay diabetes onset or affect food intake or BW relative to controls. Fasting plasma glucose, insulin, and lipid concentrations were lower and adiponectin concentrations were threefold higher in groups treated with pioglitazone. All treatment groups demonstrated improvements in glucose tolerance and insulin secretion during an oral glucose tolerance test with an additive improvement observed with alogliptin+pioglitazone. Islet histology revealed an improvement of islet morphology in all treatment groups compared with control. Pioglitazone treatment also resulted in increased expression of markers of mitochondrial biogenesis in brown adipose tissue and white adipose tissue, with mild elevations observed in animals treated with alogliptin alone. Pioglitazone markedly delays the onset of type 2 diabetes in UCD-T2DM rats through improvements of glucose tolerance, insulin sensitivity, islet function, and markers of adipose mitochondrial biogenesis; however, addition of alogliptin at a dose of 20 mg/kg per day to pioglitazone treatment does not enhance the prevention/delay of diabetes onset. PMID:24627447

Long-term efficacy and safety of ertugliflozin monotherapy in patients with inadequately controlled T2DM despite diet and exercise: VERTIS MONO extension study.

PubMed

Aronson, Ronnie; Frias, Juan; Goldman, Allison; Darekar, Amanda; Lauring, Brett; Terra, Steven G

2018-06-01

This phase III, multicentre, randomized study (ClinicalTrials.gov; NCT01958671) evaluated the efficacy and safety of ertugliflozin monotherapy in adults with inadequately controlled type 2 diabetes (glycated haemoglobin [HbA1c], 7.0% to 10.5% [53-91 mmol/mol]) despite diet and exercise. The 52-week study comprised a 26-week, double-blind, placebo-controlled period (Phase A) during which 461 participants received placebo, ertugliflozin 5 mg/d or ertugliflozin 15 mg/d. This was followed by a 26-week active-controlled period (Phase B) during which participants in the placebo group who had not received glycaemic rescue therapy had blinded metformin added. Results to Week 52 are reported. Because of the use of metformin in Phase B, no statistical comparisons of efficacy were made between the ertugliflozin and placebo/metformin groups at Week 52. The mean (standard error) change from baseline to Week 52 in HbA1c was -0.9% (0.1) and -1.0% (0.1) in the ertugliflozin 5 and 15 mg groups, respectively. The proportions of participants with HbA1c <7.0% at Week 52 were 25.6% and 28.5%, respectively. Ertugliflozin reduced fasting plasma glucose, body weight and systolic blood pressure (SBP). The incidence of genital mycotic infections (GMIs) in females was significantly higher in both ertugliflozin groups (5 mg, 26.9%; 15 mg, 29.0%) vs the placebo/metformin group (9.9%), and in males was significantly higher in the 15 mg group (7.8%) vs the placebo/metformin group (1.2%). Ertugliflozin was not associated with increased incidence of urinary tract infections, symptomatic hypoglycaemia or hypovolaemia adverse events compared with placebo/metformin. Ertugliflozin treatment over 52 weeks improved glycaemic control and reduced body weight and SBP, but increased GMIs. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Diabetes Medication Assistance Service: the pharmacist's role in supporting patient self-management of type 2 diabetes (T2DM) in Australia.

PubMed

Mitchell, Bernadette; Armour, Carol; Lee, Mary; Song, Yun Ju; Stewart, Kay; Peterson, Greg; Hughes, Jeff; Smith, Lorraine; Krass, Ines

2011-06-01

To evaluate the capacity and effectiveness of trained community pharmacists in delivering the Diabetes Medication Assistance Service (DMAS) via (1) number and types of self-management support interventions (SMSIs); (2) number of goals set and attained by patients and (3) patient outcomes (glycaemic control, medication adherence and satisfaction). Pharmacists (n=109) from 90 community pharmacies in Australia were trained and credentialed to deliver the DMAS. The training focused on developing pharmacists' knowledge and skills in supporting patients' diabetes self-management. A total of 387 patients completed the trial. The mean number of SMSIs per patient was 35 (SD ±31) and the majority (87%) had at least one documented goal that was fully or partially attained. There were significant health benefits for patients including improved glycaemic control and a reduced risk of non-adherence to medications. Over 90% of DMAS patients reported improvements in their knowledge about diabetes self-management. The DMAS provides self management support in the community pharmacy for people with T2DM which may result in improved clinical outcomes. Given appropriate training in diabetes care and behavior change strategies, community pharmacists can offer programs which provide self-management support to their patients with T2DM and improve their health outcomes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Inadequate Vitamin C Status in Prediabetes and Type 2 Diabetes Mellitus: Associations with Glycaemic Control, Obesity, and Smoking.

PubMed

Wilson, Renée; Willis, Jinny; Gearry, Richard; Skidmore, Paula; Fleming, Elizabeth; Frampton, Chris; Carr, Anitra

2017-09-09

Vitamin C (ascorbate) is an essential micronutrient in humans, being required for a number of important biological functions via acting as an enzymatic cofactor and reducing agent. There is some evidence to suggest that people with type 2 diabetes mellitus (T2DM) have lower plasma vitamin C concentrations compared to those with normal glucose tolerance (NGT). The aim of this study was to investigate plasma vitamin C concentrations across the glycaemic spectrum and to explore correlations with indices of metabolic health. This is a cross-sectional observational pilot study in adults across the glycaemic spectrum from NGT to T2DM. Demographic and anthropometric data along with information on physical activity were collected and participants were asked to complete a four-day weighed food diary. Venous blood samples were collected and glycaemic indices, plasma vitamin C concentrations, hormone tests, lipid profiles, and high-sensitivity C-reactive protein (hs-CRP) were analysed. A total of 89 participants completed the study, including individuals with NGT ( n = 35), prediabetes ( n = 25), and T2DM managed by diet alone or on a regimen of Metformin only ( n = 29). Plasma vitamin C concentrations were significantly lower in individuals with T2DM compared to those with NGT (41.2 µmol/L versus 57.4 µmol/L, p < 0.05) and a higher proportion of vitamin C deficiency (i.e. <11.0 µmol/L) was observed in both the prediabetes and T2DM groups. The results showed fasting glucose ( p = 0.001), BMI ( p = 0.001), smoking history ( p = 0.003), and dietary vitamin C intake ( p = 0.032) to be significant independent predictors of plasma vitamin C concentrations. In conclusion, these results suggest that adults with a history of smoking, prediabetes or T2DM, and/or obesity, have greater vitamin C requirements. Future research is required to investigate whether eating more vitamin C rich foods and/or taking vitamin C supplements may reduce the risk of progression to, and

Relationship between perception with the quality of life of T2DM patients in Dok II Jayapura Hospital

NASA Astrophysics Data System (ADS)

Perwitasari, D. A.; Faridah, I. N.; Kulle, Y.; Yulistika, M.

2017-11-01

Diabetes mellitus disease is one of the chronic diseases which can cause a fatal risk if its management is not appropriate. The purpose of this study was to determine the relationship between perception and quality of life in Dok II Jayapura hospital. This study used an observational research design with cross sectional approach with prospective sampling in diabetic patients in internal disease policemen who were underwent outpatient treatment at Dok II Jayapura hospital. Research instruments used EQ-5D (European Quality-5 Dimension) and B-IPQ (Brief Illness Perception Quetionare). Data analysis used was univariate analysis by using percentage or mean value, bivariate using T-test or Mann-Whitney test, and multivariate using multiple linear regression. There were 80 T2DM patients who met the inclusion criteria. Based on patient demographic data, there were 29 people (36.6%) male patients and 51 people (63.8%) female patients, with mean age of patient (55.79±10.52) year. Perception has correlation with quality of life influenced by index value on treatment control (6.73±1.475) and emotional response (3.11±2.199) and by visual analog scale on understanding (5.99±1.587), duration (6.50±2.968), and personal controls (6.20±1.641). Based on the results obtained to improve the quality of life of T2DM patients that is on the index value on the control of treatment and emotional response and on visual analog scale on the understanding, duration and personal control should be changed so that the quality of life of patients increases. The family history, social status and type of treatment factors also affect the quality of life.

The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus (T2DM) rats with insulin resistance.

PubMed

Dai, Bing; Wu, Qinxuan; Zeng, Chengxi; Zhang, Jiani; Cao, Luting; Xiao, Zizeng; Yang, Menglin

2016-11-04

Liuwei Dihaung decoction (LWDHT) is a well-known classic traditional Chinese medicine formula, consists of six herbs including Rehmannia glutinosa Libosch.(family: Scrophulariaceae), Cornus officinalis Sieb.(family: Cornaceae), Dioscorea opposite Thunb.(family: Dioscoreaceae), Alisma orientale(G. Samuelsson) Juz (family: Alismataceae), Poria cocos (Schw.) Wolf (family: Polyporaceae) and Paeonia suffruticosa Andrews (family: Paeoniaceae). It has been used in the treatment of many types of diseases with signs of deficiency of Yin in the kidneys in China clinically. This study is aimed at investigating the effect of Liuwei dihuang decoction on PI3K/Akt signaling pathway in liver of T2DM rats with insulin resistance. T2DM model was induced in male Sprague-Dawley (SD) rats by high sugar and high fat diets combined with small dose of streptozocin (STZ) injection. The successful T2DM rats were randomly allocated three group--vehicle group, positive control group and Liuwei Dihuang decoction group. After 12-weeks treatment with distilled water, rosiglitazone and LWDHT by intragastric administration respectively, the rats were put to death in batches. The variance of fasting blood glucose (FBG) and fasting insulin (FINS) in serum were determined, the pathological changes of each rats' liver were observed by hematoxylin-eosin (HE) staining, the expression of insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase (PI3K) and protein kinas B (Akt) involving the canonical PI3K/Akt signaling pathway were detected by Real-time fluorescent quantitative PCR (RT-PCR), and the expression level of IRS2, PI3K, Akt protein and phosphorylated IRS2, PI3K, Akt protein were evaluated by Western Blot. All the data were analyzed by SPSS 17.0. Four weeks of treatment with LWDHT could significantly decrease the level of FBG and FINS in serum, improve the cellular morphology of liver, kidney, pancreas tissue, and the expression of IRS2, PI3K, Akt mRNA and phosphorylated IRS2, PI3K, Akt

Increased expression of TLR9 associated with pro-inflammatory S100A8 and IL-8 in diabetic wounds could lead to unresolved inflammation in type 2 diabetes mellitus (T2DM) cases with impaired wound healing.

PubMed

Singh, Kanhaiya; Agrawal, Neeraj K; Gupta, Sanjeev K; Sinha, Pratima; Singh, Kiran

2016-01-01

Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia which causes a chain of abrupt biochemical and physiological changes. Immune dys-regulation is the hallmark of T2DM that could contribute to prolonged inflammation causing transformation of wounds into non-healing chronic ulcers. Toll like receptor -9 (TLR9) is a major receptor involved in innate immune regulation. TLR9 activation induces release of pro-inflammatory molecules like S100A8 and interleukin-8 (IL-8) by myeloid cells causing migration of myeloid cells to the site of inflammation. We hypothesized that pro-inflammatory S100A8 and IL-8 proteins could cause persistent inflammation in chronic wounds like diabetic foot ulcer (DFU) and may contribute to impaired wound healing in T2DM patients. Expression of TLR9 and its downstream effector molecules S100A8, and IL-8 were analyzed in chronic diabetic wound and non-diabetic control wound tissue samples by semiquantitative reverse transcriptase - polymerase chain reaction (RT-PCR), quantitative RT-PCR, western blot and immunofluorescence. CD11b(+)CD33(+) myeloid cells were analyzed by flow cytometry. TLR9 message and protein were higher in diabetic wounds compared to control wounds (p=0.03, t=2.21 for TLR9 mRNA; p=<0.001, t=4.21 for TLR9 protein). TLR9 down-stream effector molecules S100A8 and IL-8 were also increased in diabetic wounds (p=0.003, t=3.1 for S100A8 mRNA; p=0.04, t=2.04 for IL-8). CD11b(+) CD33(+) myeloid cells were decreased in T2DM as compared to non-diabetic controls (p=0.001, t=3.6). DFU subjects had higher levels of CD11b(+) CD33(+) myeloid cells as compared to non-DFU T2DM control (p=0.003, t=2.8). Infection in the wound microenvironment could be the cause of increase in CD11b(+)CD33(+) myeloid cells in DFU (p=0.03, t=2.5). The up-regulation of myeloid cell-derived pro-inflammatory molecules S100A8 and IL-8 in combination with lower levels of CD11b(+) CD33(+) myeloid cells may cause the impairment of wound healing in

RETRACTED: Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population.

PubMed

Zhong, Weiqiang; Jiang, Zongpei; Zhou, Tian-Biao

2015-12-01

This article has been included in a multiple retraction: Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10

Arsenic Exposure and Calpain-10 Polymorphisms Impair the Function of Pancreatic Beta-Cells in Humans: A Pilot Study of Risk Factors for T2DM

PubMed Central

Díaz-Villaseñor, Andrea; Cruz, Laura; Cebrián, Arturo; Hernández-Ramírez, Raúl U.; Hiriart, Marcia; García-Vargas, Gonzálo; Bassol, Susana; Sordo, Monserrat; Gandolfi, A. Jay; Klimecki, Walter T.; López-Carillo, Lizbeth; Cebrián, Mariano E.; Ostrosky-Wegman, Patricia

2013-01-01

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide and diverse environmental and genetic risk factors are well recognized. Single nucleotide polymorphisms (SNPs) in the calpain-10 gene (CAPN-10), which encodes a protein involved in the secretion and action of insulin, and chronic exposure to inorganic arsenic (iAs) through drinking water have been independently associated with an increase in the risk for T2DM. In the present work we evaluated if CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin secretion (beta-cell function) and insulin sensitivity were evaluated indirectly through validated indexes (HOMA2) in subjects with and without T2DM who have been exposed to a gradient of iAs in their drinking water in northern Mexico. The results were analyzed taking into account the presence of the risk factor SNPs SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell function and insulin sensitivity. An inverse association was found between beta-cell function and iAs exposure, the association being more pronounced in subjects with T2DM. Subjects without T2DM who were carriers of the at-risk genotype SNP-43 or -44, also had significantly lower beta-cell function. The association of SNP-43 with beta-cell function was dependent on iAs exposure, age, gender and BMI, whereas the association with SNP-44 was independent of all of these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in humans through the reduction of beta-cell function, with an enhanced effect seen in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 SNP-44 have also shown reduced beta-cell function. PMID:23349674

Platelet indices and glucose control in type 1 and type 2 diabetes mellitus: A case-control study.

PubMed

Zaccardi, F; Rocca, B; Rizzi, A; Ciminello, A; Teofili, L; Ghirlanda, G; De Stefano, V; Pitocco, D

2017-10-01

The relationship between platelet indices and glucose control may differ in type 1 (T1DM) and type 2 (T2DM) diabetes. We aimed to investigate differences in mean platelet volume (MPV), platelet count, and platelet mass between patients with T1DM, T2DM, and healthy controls and to explore associations between these platelet indices and glucose control. A total of 691 T1DM and 459 T2DM patients and 943 control subjects (blood donors) were included. HbA1c was measured in all subjects with diabetes and 36 T1DM patients further underwent 24 h-continuous glucose monitoring to estimate short-term glucose control (glucose mean and standard deviation). Adjusting for age and sex, platelet count was higher and MPV lower in both T1DM and T2DM patients vs control subjects, while platelet mass (MPV × platelet count) resulted higher only in T2DM. Upon further adjustment for HbA1c, differences in platelet count and mass were respectively 19.5 × 10 9 /L (95%CI: 9.8-29.3; p < 0.001) and 101 fL/nL (12-191; p = 0.027) comparing T2DM vs T1DM patients. MPV and platelet count were significantly and differently related in T2DM patients vs both T1DM and control subjects; this difference was maintained also accounting for HbA1c, age, and sex. Platelet mass and the volume-count relationship were significantly related to HbA1c only in T1DM patients. No associations were found between platelet indices and short-term glucose control. By accounting for confounders and glucose control, our data evidenced higher platelet mass and different volume-count kinetics in subjects with T2DM vs T1DM. Long-term glucose control seemed to influence platelet mass and the volume-count relationship only in T1DM subjects. These findings suggest different mechanisms behind platelet formation in T1DM and T2DM patients with long-term glycaemic control being more relevant in T1DM than T2DM. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the

Blood Glucagon Levels Predict the Hemoglobin A1c Response to Saxagliptin in Patients with Type 2 Diabetes Inadequately Controlled with Metformin.

PubMed

Liu, Hao; Hu, Yun; Li, Feng-Fei; Liu, Bing-Li; Su, Xiao-Fei; Ma, Jian-Hua

2016-12-01

Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as second-option medications when metformin fails. Variance of the glycated hemoglobin (HbA1c) response to DPP-4 inhibitions in patients with type 2 diabetes mellitus (T2DM) has been observed, but the characteristics which predict the response to DPP-4 inhibitor therapy are unclear. The aim of this study was to investigate the characteristics of α- and β-cell functions which might predict the efficacy of saxagliptin and facilitate personalization of treatment. We studied 60 patients with T2DM who had inadequate glycemic control [HbA1c7.0-13.0% (53-119 mmol/mol)) with metformin alone. The patients were treated with saxagliptin (5 mg, daily) and metformin (1000-2000 mg as former) for 12 weeks. Oral glucose tolerance tests were carried out at baseline and endpoint to evaluate α- and β-cell functions, and blood C-peptide, insulin, glucagon levels were tested. Blood glucose, HbA1c and weight were also observed. Significant reduction of weight, HbA1c and glucagon was observed after 12-week treatment, while C-peptide, insulin and homeostasis model assessment-β increased (P < 0.05). Linear regression and receiver operating characteristic analysis showed that baseline HbA1c and 30 min-glucagon were correlated with the HbA1c response to saxagliptin, while the weight loss was correlated with gender, age and fasting-insulin level. Further analysis showed the 30 min-glucagon of 49.1 pmol/L was the optimal cutoff value to predict the efficacy of saxagliptin. Saxagliptin added to metformin significantly improved glycemic control and α- and β-cell function. Blood glucagon level was a good predicting factor for the HbA1c response to saxagliptin, and it will help appropriate patient selection. Chinese Clinical Trial Register identifier, ChiCTR-PPR-15007045.

DNA Damage Observed in Unaffected Individuals with Family History of T2DM

NASA Astrophysics Data System (ADS)

Ramesh, Nikhila; Abilash, V. G.

2017-11-01

Diabetes has been documented to cause high levels of DNA fragmentation in some cases. As diabetes is inheritable and influenced by both genetic and environmental factors, an investigation into the genomic stability of individuals who are strongly at risk of inheriting diabetes was conducted by inducing oxidative stress, as DNA damage in unaffected individuals could be a sign of onset of the disease or the presence of genetic alterations that reduce cellular defences against reactive oxygen species. In this study, alkaline comet assay was performed on isolated human leukocytes to determine whether individuals with a family history of Type 2 Diabetes Mellitus (T2DM) are more prone to DNA damage under oxidative stress. Visual scoring of comets showed that these individuals have higher degree of DNA damage compared to a control individual with no family history of Type 2 Diabetes Mellitus. Further studies with large sample could determine the presence of disabled cellular defences against oxidative stress in unaffected individuals and intervention with antioxidants could prevent or manage Type 2 Diabetes Mellitus and its complications.

Preclinical safety profile of trastuzumab emtansine (T-DM1): Mechanism of action of its cytotoxic component retained with improved tolerability

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

Poon, Kirsten Achilles, E-mail: achilles.kirsten@gene.com; Flagella, Kelly; Beyer, Joseph

2013-12-01

Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The therapeutic premise of ADCs is based on the hypothesis that targeted delivery of potent cytotoxic drugs to tumors will provide better tolerability and efficacy compared with non-targeted delivery, where poor tolerability can limit efficacious doses. Here, we present results from preclinical studies characterizing the toxicity profile of T-DM1, including limited assessment of unconjugated DM1. T-DM1 binds primate ErbB2 and human HER2 but not the rodent homolog c-neu. Therefore, antigen-dependent and non-antigen-dependent toxicity was evaluated in monkeysmore » and rats, respectively, in both single- and repeat-dose studies; toxicity of DM1 was assessed in rats only. T-DM1 was well tolerated at doses up to 40 mg/kg (∼ 4400 μg DM1/m{sup 2}) and 30 mg/kg (∼ 6000 μg DM1/m{sup 2}) in rats and monkeys, respectively. In contrast, DM1 was only tolerated up to 0.2 mg/kg (1600 μg DM1/m{sup 2}). This suggests that at least two-fold higher doses of the cytotoxic agent are tolerated in T-DM1, supporting the premise of ADCs to improve the therapeutic index. In addition, T-DM1 and DM1 safety profiles were similar and consistent with the mechanism of action of DM1 (i.e., microtubule disruption). Findings included hepatic, bone marrow/hematologic (primarily platelet), lymphoid organ, and neuronal toxicities, and increased numbers of cells of epithelial and phagocytic origin in metaphase arrest. These adverse effects did not worsen with chronic dosing in monkeys and are consistent with those reported in T-DM1-treated patients to date. - Highlights: • T-DM1 was well tolerated in preclinical studies in rats and cynomolgus monkeys. • T-DM1 is associated with bone marrow/hematologic, hepatic, and neuronal toxicities. • T-DM1 toxicities are related to DM1 mechanisms of action and

The Nile Rat (Arvicanthis niloticus) as a Superior Carbohydrate-Sensitive Model for Type 2 Diabetes Mellitus (T2DM)

PubMed Central

Landstrom, Michelle; Luu, Alice; Hayes, K. C.

2018-01-01

Type II diabetes mellitus (T2DM) is a multifactorial disease involving complex genetic and environmental interactions. No single animal model has so far mirrored all the characteristics or complications of diabetes in humans. Since this disease represents a chronic nutritional insult based on a diet bearing a high glycemic load, the ideal model should recapitulate the underlying dietary issues. Most rodent models have three shortcomings: (1) they are genetically or chemically modified to produce diabetes; (2) unlike humans, most require high-fat feeding; (3) and they take too long to develop diabetes. By contrast, Nile rats develop diabetes rapidly (8–10 weeks) with high-carbohydrate (hiCHO) diets, similar to humans, and are protected by high fat (with low glycemic load) intake. This review describes diabetes progression in the Nile rat, including various aspects of breeding, feeding, and handling for best experimental outcomes. The diabetes is characterized by a striking genetic permissiveness influencing hyperphagia and hyperinsulinemia; random blood glucose is the best index of disease progression; and kidney failure with chronic morbidity and death are outcomes, all of which mimic uncontrolled T2DM in humans. Non-alcoholic fatty liver disease (NAFLD), also described in diabetic humans, results from hepatic triglyceride and cholesterol accumulation associated with rising blood glucose. Protection is afforded by low glycemic load diets rich in certain fibers or polyphenols. Accordingly, the Nile rat provides a unique opportunity to identify the nutritional factors and underlying genetic and molecular mechanisms that characterize human T2DM. PMID:29463026

Comparison between SGLT2 inhibitors and DPP4 inhibitors added to insulin therapy in type 2 diabetes: a systematic review with indirect comparison meta-analysis.

PubMed

Min, Se Hee; Yoon, Jeong-Hwa; Hahn, Seokyung; Cho, Young Min

2017-01-01

Both sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors can be used to treat patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled with insulin therapy, and yet there has been no direct comparison of these two inhibitors. We searched MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov through June 2015. Randomized controlled trials published in English that compare SGLT2 inhibitor plus insulin (SGLT2i/INS) with placebo plus insulin or DPP4 inhibitor plus insulin (DPP4i/INS) with placebo plus insulin in patients with T2DM were selected. Data on the study characteristics, efficacy and safety outcomes were extracted. We compared the efficacy and safety between SGLT2i/INS and DPP4i/INS indirectly with covariates adjustment. Risk of potential bias was assessed. Fourteen eligible randomized controlled trials comprising 6980 patients were included (five SGLT2 inhibitor studies and nine DPP4 inhibitor studies). Covariate-adjusted indirect comparison using meta-regression analyses revealed that SGLT2i/INS achieved greater reduction in HbA 1c [weighted mean difference (WMD) -0.24%, 95% confidence interval (CI) -0.43 to -0.05%], fasting plasma glucose (WMD -18.0 mg/dL, 95% CI -28.5 to -7.6 mg/dL) and body weight (WMD -2.38 kg, 95% CI -3.18 to -1.58 kg) from baseline than DPP4i/INS without increasing the risk of hypoglycaemia (relative risks 1.19, 95% CI 0.78 to 1.82). Sodium glucose cotransporter 2 inhibitors achieved better glycaemic control and greater weight reduction than DPP4 inhibitors without increasing the risk of hypoglycaemia in patients with T2DM that is inadequately controlled with insulin. There has been no direct comparison of SGLT2 inhibitors and DPP4 inhibitors in patients with T2DM inadequately controlled with insulin therapy. In this study, we performed indirect meta-analysis comparing SGLT2 inhibitors and DPP4 inhibitors added to insulin

Ethnic sensitivity assessment of the antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with HER2-positive locally advanced or metastatic breast cancer.

PubMed

Li, Chunze; Wang, Bei; Lu, Dan; Jin, Jin Y; Gao, Yuying; Matsunaga, Kiyoshi; Igawa, Yuriko; Nijem, Ihsan; Lu, Michael; Strasak, Alexander; Chernyukhin, Nataliya; Girish, Sandhya

2016-09-01

Trastuzumab emtansine (T-DM1) is indicated for previously treated HER2-positive metastatic breast cancer. Ethnic sensitivity assessment of T-DM1 was conducted using data from eight clinical studies to ensure that the clinically recommended dose is appropriate across ethnicities. Four approaches were used: (1) non-compartmental analysis (NCA) comparing pharmacokinetic parameters of T-DM1 and relevant analytes across ethnic groups, (2) population pharmacokinetic (popPK) analysis assessing the impact of ethnicity on pharmacokinetics, (3) comparison of T-DM1 pharmacokinetics in Japanese patients versus the global population, and (4) exposure-response analyses assessing the impact of ethnicity on safety and efficacy. NCA pharmacokinetic parameters (T-DM1, total trastuzumab, DM1) were comparable across ethnic groups; mean cycle 1 T-DM1 AUCinf was 475, 442, and 518 day µg/mL for white (n = 461), Asian (n = 68), and others (n = 57), respectively. PopPK analysis showed that ethnicity (white, Asian, and others) was not a significant covariate for T-DM1 pharmacokinetics (n = 671). Additionally, visual predictive check plots indicated that observed pharmacokinetic profiles in Japanese patients (n = 42) were within the prediction interval generated from the final PopPK model. Exposure-response analyses showed that ethnicity was not a significant covariate impacting efficacy or hepatotoxicity risk, but there was a trend of greater thrombocytopenia risk among Asians versus non-Asians, which could not be explained by similar exposure between the ethnic groups. Most Asians with thrombocytopenia were able to continue T-DM1 using dose-adjustment rules recommended for the global population. These results suggest that T-DM1 pharmacokinetics are comparable across ethnic groups and that use of the current dosing regimen is appropriate across ethnicities.

Efficacy and safety of ipragliflozin as an add-on therapy to sitagliptin and metformin in Korean patients with inadequately controlled type 2 diabetes mellitus: a randomized controlled trial.

PubMed

Han, Kyung-Ah; Chon, Suk; Chung, Choon Hee; Lim, Soo; Lee, Kwan-Woo; Baik, SeiHyun; Jung, Chang Hee; Kim, Dong-Sun; Park, Kyong Soo; Yoon, Kun-Ho; Lee, In-Kyu; Cha, Bong-Soo; Sakatani, Taishi; Park, Sumi; Lee, Moon-Kyu

2018-06-04

To evaluate the efficacy and safety of ipragliflozin versus placebo as add-on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM). This double-blind, placebo-controlled, multi-center, phase 3 study was conducted in Korea in 2015-2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to end of treatment (EOT). In total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90% (0.69) for ipragliflozin add-on and 7.92% (0.79) for placebo. The corresponding mean (SD) changes from baseline to EOT were -0.79% (0.59) and 0.03% (0.84), respectively, in favor of ipragliflozin (adjusted mean difference: -0.83% [95% CI -1.07 to -0.59%]) (P<0.0001). More ipragliflozin-treated patients than placebo-treated patients achieved HbA1c target levels of <7.0% (44.4% vs. 12.1%) and <6.5% (12.5% vs. 1.5%) at EOT (P<0.05 for both). Fasting plasma glucose, fasting serum insulin, body weight, and homeostatic model assessment for insulin resistance decreased significantly at EOT, in favor of ipragliflozin (adjusted mean difference: -29.55 mg/dL, -1.50 μU/mL, -1.72 kg, and -0.99, respectively) (P<0.05 for all). Adverse event rates were similar between groups (ipragliflozin: 51.4%; placebo: 50.0%). No previously unreported safety concerns were noted. Ipragliflozin add-on to metformin and sitagliptin significantly improved glycemic parameters and demonstrated a good safety profile in Korean patients with inadequately controlled T2DM. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

An integrated multiple-analyte pharmacokinetic model to characterize trastuzumab emtansine (T-DM1) clearance pathways and to evaluate reduced pharmacokinetic sampling in patients with HER2-positive metastatic breast cancer.

PubMed

Lu, Dan; Joshi, Amita; Wang, Bei; Olsen, Steve; Yi, Joo-Hee; Krop, Ian E; Burris, Howard A; Girish, Sandhya

2013-08-01

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate recently approved by the US Food and Drug Administration for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer previously treated with trastuzumab and taxane chemotherapy. It comprises the microtubule inhibitory cytotoxic agent DM1 conjugated to the HER2-targeted humanized monoclonal antibody trastuzumab via a stable linker. To characterize the pharmacokinetics of T-DM1 in patients with metastatic breast cancer, concentrations of multiple analytes were quantified, including serum concentrations of T-DM1 conjugate and total trastuzumab (the sum of conjugated and unconjugated trastuzumab), as well as plasma concentrations of DM1. The clearance of T-DM1 conjugate is approximately 2 to 3 times faster than its parent antibody, trastuzumab. However, the clearance pathways accounting for this faster clearance rate are unclear. An integrated population pharmacokinetic model that simultaneously fits the pharmacokinetics of T-DM1 conjugate and total trastuzumab can help to elucidate the clearance pathways of T-DM1. The model can also be used to predict total trastuzumab pharmacokinetic profiles based on T-DM1 conjugate pharmacokinetic data and sparse total trastuzumab pharmacokinetic data, thereby reducing the frequency of pharmacokinetic sampling. T-DM1 conjugate and total trastuzumab serum concentration data, including baseline trastuzumab concentrations prior to T-DM1 treatment, from phase I and II studies were used to develop this integrated population pharmacokinetic model. Based on a hypothetical T-DM1 catabolism scheme, two-compartment models for T-DM1 conjugate and trastuzumab were integrated by assuming a one-step deconjugation clearance from T-DM1 conjugate to trastuzumab. The ability of the model to predict the total trastuzumab pharmacokinetic profile based on T-DM1 conjugate pharmacokinetics and various sampling schemes of total trastuzumab

Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model

USDA-ARS?s Scientific Manuscript database

Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasm...

The Expression of Activating Receptor Gene of Natural Killer Cells (KLRC3) in Patients with 
Type 1 Diabetes Mellitus (T1DM)

PubMed Central

Shalaby, Dalia; Saied, Marwa; Khater, Doaa; Abou Zeid, Abla

2017-01-01

Objectives To identify the possible role of natural killer (NK) cells in the pathogenesis of type 1 diabetes mellitus (T1DM) through studying the expression of the KLRC3 gene, which encodes the NK cell activating receptor (NKG2E). Methods This study was conducted at Alexandria University Children’s Hospital from April to October 2015. The study was conducted with 30 newly diagnosed T1DM patients (15 males and 15 females), aged 7–13 years (10.6±1.8 years) and 20 non-diabetic subjects served as age- and sex-matched controls. The patients were further sub-divided into two groups; group I included patients who first presented with classical symptoms of DM (polyuria, polydipsia, and polyphagia) without diabetes ketoacidosis (DKA) and group II included patients who first presented with DKA. The expression of the KLRC3 gene was measured in each group using the real-time polymerase chain reaction. Results KLRC3 gene expression was significantly downregulated in T1DM cases compared to healthy controls (p = 0.001). Expression was more downregulated in group I patients (p = 0.008). Moreover, there was higher mean value of glycated heamoglobin and lower C-peptide levels in group I than group II. Serum pancreatic amylase showed no significant difference between the two groups. Conclusions KLRC3 gene expression was downregulated in patients with T1DM compared to healthy controls. Downregulation of expression was greater in DKA patients compared to those who presented with classical symptoms. Expression of KLRC3 in T1DM might play a role in the pathogenesis of T1DM and could be a predictor of its severity. PMID:28804584

Exercise for the diabetic brain: how physical training may help prevent dementia and Alzheimer's disease in T2DM patients.

PubMed

Bertram, Sebastian; Brixius, Klara; Brinkmann, Christian

2016-08-01

Epidemiological studies indicate that patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing dementia/Alzheimer's disease (AD). This review, which is based on recent studies, presents a molecular framework that links the two diseases and explains how physical training could help counteract neurodegeneration in T2DM patients. Inflammatory, oxidative, and metabolic changes in T2DM patients cause cerebrovascular complications and can lead to blood-brain-barrier (BBB) breakdown. Peripherally increased pro-inflammatory molecules can then pass the BBB more easily and activate stress-activated pathways, thereby promoting key pathological features of dementia/AD such as brain insulin resistance, mitochondrial dysfunction, and accumulation of neurotoxic beta-amyloid (Aβ) oligomers, leading to synaptic loss, neuronal dysfunction, and cell death. Ceramides can also pass the BBB, induce pro-inflammatory reactions, and disturb brain insulin signaling. In a vicious circle, oxidative stress and the pro-inflammatory environment intensify, leading to further cognitive decline. Low testosterone levels might be a common risk factor in T2DM and AD. Regular physical exercise reinforces antioxidative capacity, reduces oxidative stress, and has anti-inflammatory effects. It improves endothelial function and might increase brain capillarization. Physical training can further counteract dyslipidemia and reduce increased ceramide levels. It might also improve Aβ clearance by up-regulating Aβ transporters and, in some cases, increase basal testosterone levels. In addition, regular physical activity can induce neurogenesis. Physical training should therefore be emphasized as a part of prevention programs developed for diabetic patients to minimize the risk of the onset of neurodegenerative diseases among this specific patient group.

Policaptil Gel Retard significantly reduces body mass index and hyperinsulinism and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children and adolescents with family history of obesity and T2DM.

PubMed

Stagi, Stefano; Lapi, Elisabetta; Seminara, Salvatore; Pelosi, Paola; Del Greco, Paolo; Capirchio, Laura; Strano, Massimo; Giglio, Sabrina; Chiarelli, Francesco; de Martino, Maurizio

2015-02-15

Treatments for childhood obesity are critically needed because of the risk of developing co-morbidities, although the interventions are frequently time-consuming, frustrating, difficult, and expensive. We conducted a longitudinal, randomised, clinical study, based on a per protocol analysis, on 133 obese children and adolescents (n = 69 males and 64 females; median age, 11.3 years) with family history of obesity and type 2 diabetes mellitus (T2DM). The patients were divided into three arms: Arm A (n = 53 patients), Arm B (n = 45 patients), and Arm C (n = 35 patients) patients were treated with a low-glycaemic-index (LGI) diet and Policaptil Gel Retard, only a LGI diet, or only an energy-restricted diet (ERD), respectively. The homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda, insulinogenic and disposition indexes were calculated at T0 and after 1 year (T1). At T1, the BMI-SD scores were significantly reduced from 2.32 to 1.80 (p < 0.0001) in Arm A and from 2.23 to 1.99 (p < 0.05) in Arm B. Acanthosis nigricans was significantly reduced in Arm A (13.2% to 5.6%; p < 0.05), and glycosylated-haemoglobin levels were significantly reduced in Arms A (p < 0.005). The percentage of glucose-metabolism abnormalities was reduced, although not significantly. However, the HOMA-IR index was significantly reduced in Arms A (p < 0.0001) and B (p < 0.05), with Arm A showing a significant reduction in the insulinogenic index (p < 0.05). Finally, the disposition index was significantly improved in Arms A (p < 0.0001) and B (p < 0.05). A LGI diet, particularly associated with the use of Policaptil Gel Retard, may reduce weight gain and ameliorate the metabolic syndrome and insulin-resistance parameters in obese children and adolescents with family history of obesity and T2DM.

T2DM Self-Management via Smartphone Applications: A Systematic Review and Meta-Analysis.

PubMed

Cui, Mingxuan; Wu, Xueyan; Mao, Jiangfeng; Wang, Xi; Nie, Min

2016-01-01

Mobile health interventions (mHealth) based on smartphone applications (apps) are promising tools to help improve diabetes care and self-management; however, more evidence on the efficacy of mHealth in diabetes care is needed. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effect of mHealth apps on changes in hemoglobin A1c (HbA1c), blood glucose, blood pressure, serum lipids, and body weight in type 2 diabetes mellitus (T2DM) patients. Two independent reviewers searched three online databases (PubMed, the Cochrane Library, and EMBASE) to identify relevant studies published between January 2005 and June 2016. Of the 2,596 articles retrieved, 13 RCTs were included. We used random effects model to estimate the pooled results. Thirteen studies were selected for the systematic review, six of which with data available containing 1,022 patients were included for the meta-analysis. There was a moderate effect on glycemic control after the mHealth app-based interventions. The overall effect on HbA1c shown as mean difference (MD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.11% [-7.54 to -1.20 mmol/mol]; p = 0.007) and standardized mean differences (SMD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.10% [-7.54 to -1.09 mmol/mol]; p = 0.008). A subgroup analysis showed a similar effect with -0.33% (-3.61 mmol/mol) (95% CI -0.59 to -0.06% [-6.45 to -0.66 mmol/mol]; p = 0.02) in MD and -0.38% (-4.15 mmol/mol) (95% CI -0.71 to -0.05% [-7.76 to -0.55 mmol/mol]; p = 0.02) in SMD in studies where patients' baseline HbA1c levels were less than 8.0%. No effects of mHealth app interventions were found on blood pressure, serum lipids, or weight. Assessment of overall study quality and publication bias demonstrated a low risk of bias among the six studies. Smartphone apps offered moderate benefits for T2DM self-management. However, more research with

T2DM Self-Management via Smartphone Applications: A Systematic Review and Meta-Analysis

PubMed Central

Cui, Mingxuan; Wu, Xueyan; Mao, Jiangfeng; Wang, Xi; Nie, Min

2016-01-01

Background Mobile health interventions (mHealth) based on smartphone applications (apps) are promising tools to help improve diabetes care and self-management; however, more evidence on the efficacy of mHealth in diabetes care is needed. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effect of mHealth apps on changes in hemoglobin A1c (HbA1c), blood glucose, blood pressure, serum lipids, and body weight in type 2 diabetes mellitus (T2DM) patients. Methods Two independent reviewers searched three online databases (PubMed, the Cochrane Library, and EMBASE) to identify relevant studies published between January 2005 and June 2016. Of the 2,596 articles retrieved, 13 RCTs were included. We used random effects model to estimate the pooled results. Results Thirteen studies were selected for the systematic review, six of which with data available containing 1,022 patients were included for the meta-analysis. There was a moderate effect on glycemic control after the mHealth app-based interventions. The overall effect on HbA1c shown as mean difference (MD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.11% [-7.54 to -1.20 mmol/mol]; p = 0.007) and standardized mean differences (SMD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.10% [-7.54 to -1.09 mmol/mol]; p = 0.008). A subgroup analysis showed a similar effect with -0.33% (-3.61 mmol/mol) (95% CI -0.59 to -0.06% [-6.45 to -0.66 mmol/mol]; p = 0.02) in MD and -0.38% (-4.15 mmol/mol) (95% CI -0.71 to -0.05% [-7.76 to -0.55 mmol/mol]; p = 0.02) in SMD in studies where patients’ baseline HbA1c levels were less than 8.0%. No effects of mHealth app interventions were found on blood pressure, serum lipids, or weight. Assessment of overall study quality and publication bias demonstrated a low risk of bias among the six studies. Conclusions Smartphone apps offered moderate benefits for T2DM self

An analysis of cognitive functioning of children and youth with type 1 diabetes (T1DM) in the context of glycemic control.

PubMed

Stanisławska-Kubiak, M; Mojs, E; Wójciak, R W; Piasecki, B; Matecka, M; Sokalski, J; Kopczyński, P; Fichna, P

2018-06-01

The aim of the study was to evaluate the cognitive functioning of children and youth with type 1 diabetes (T1DM). The study included 68 children with type 1 diabetes, aged 6-17 years, divided into 3 groups according to the level of glycated hemoglobin (HbA1c): group 1: HbA1c ≤ 6.0-7.5%; group 2: HbA1c 7.6-8.5%; group 3: HbA1c over 8.6%. Wechsler's intelligence scale (WISC-R), the Trail of 10 words and Brickenkamp's and Zillmer's d2 Test of Attention were used to assess cognitive functioning. The research demonstrated a significant influence of low, medium or high glycaemic control on lowering the general level of functioning in verbal intelligence, and in WISC-R subtests: information, vocabulary, comprehension, number sequencing and block design. Children with type 1 diabetes mellitus can experience difficulties in cognitive functioning, as a consequence of high HbA1c. Additional research, involving a larger group of patients and a wider age range when the disease was diagnosed, will enable further findings on the occurrence of cognitive impairment in T1DM.

Saxagliptin/Dapagliflozin: A Review in Type 2 Diabetes Mellitus.

PubMed

Garnock-Jones, Karly P

2017-03-01

Saxagliptin/dapagliflozin fixed-dose combination tablets (Qtern ® ) are indicated in the EU for the improvement of glycaemic control in adults with type 2 diabetes mellitus (T2DM), either when treatment with metformin and/or a sulfonylurea plus a monocomponent of saxagliptin/dapagliflozin provides inadequate glycaemic control, or when the patient is already being treated with the free combination of saxagliptin + dapagliflozin. This narrative review summarizes pharmacological, efficacy and tolerability data relevant to the use of saxagliptin/dapagliflozin in this indication. The agents have complementary mechanisms of action, and saxagliptin/dapagliflozin fixed-dose combination tablets are bioequivalent to free combination of saxagliptin + dapagliflozin. In three phase III trials, saxagliptin + dapagliflozin + metformin was more effective at providing glycaemic control than saxagliptin + metformin or dapagliflozin + metformin in previously treated patients with T2DM and inadequate glycaemic control on metformin monotherapy or metformin plus one of the monocomponents. The combination is associated with decreased bodyweight and a low risk of hypoglycaemia. As the first dipeptidyl peptidase-4 (DPP-4) inhibitor/sodium-glucose co-transporter (SGLT2) inhibitor fixed-dose combination available in the EU for glycaemic control in patients with T2DM, saxagliptin/dapagliflozin is a useful new option in this setting.

Epidemiology of urinary tract infections in type 2 diabetes mellitus patients: An analysis based on a large sample of 456,586 German T2DM patients.

PubMed

Wilke, Thomas; Boettger, Bjoern; Berg, Bjoern; Groth, Antje; Mueller, Sabrina; Botteman, Marc; Yu, Shengsheng; Fuchs, Andreas; Maywald, Ulf

2015-01-01

This analysis was conducted to investigate urinary tract infection (UTI) incidence among Type 2 Diabetes mellitus (T2DM) patients in Germany in a real-world setting and to identify risk factors associated with UTI incidence/recurrence. Our cohort study was conducted based on an anonymized dataset from a regional German sickness fund (2010-2012). A UTI event was mainly identified through observed outpatient/inpatient UTI diagnoses. We reported the number of UTI events per 1000 patient-years. Furthermore, the proportion of patients affected by ≥1 and ≥2 UTI events in the observational period was separately reported. Finally, three multivariate Cox regression analyses were conducted to identify factors that may be associated with UTI event risk or recurrent UTI event risk. A total of 456,586 T2DM-prevalent patients were identified (mean age 72.8years, 56.1% female, mean Charlson Comorbidity Index (CCI) of 7.3). Overall, the UTI event rate was 87.3 events per 1000 patient-years (111.8/55.8 per 1000 patient-years for women/men (p<0.001)). The highest UTI event rates were observed for those aged >89years. After 730days after first observed T2DM diagnosis, the proportion of women/men still UTI-event-free was 80.9%/90.2% (p<0.001). Most important factors associated with UTI risk in our three models were older age (Hazard Ratio (HR)=1.56-1.70 for >79years), female gender (HR=1.38-1.57), UTIs in the previous two years (HR=2.77-5.94), number of comorbidities as measured by the CCI (HR=1.32-1.52 for CCI>6) and at least one cystoscopy in the previous year (HR=2.06-5.48). Furthermore, high HbA1c values in the previous year (HR=1.29-1.4 referring to HbA1c>9.5%) and a poor kidney function (HR=1.11-1.211 referring to glomerular filtration rate (GFR)<60ml/min) increased the UTI event risk. Our study confirms that UTI event risk is high in T2DM patients. Older female patients having experienced previous UTIs face an above-average UTI risk, especially if these risk factors are

Efficacy and safety of insulin pump treatment in adult T1DM patients--influence of age and social environment.

PubMed

Grzanka, Małgorzata; Matejko, Bartłomiej; Cyganek, Katarzyna; Kozek, Elżbieta; Małecki, Maciej T; Klupa, Tomasz

2012-01-01

Continuous subcutaneous insulin infusion (CSII) via personal insulin pump is a valuable therapeutic tool in T1DM patients. However, adherence to recommended CSII-related behaviours may be of concern to young adults with intensive, variable daily activities (students, young professionals). The aim of this observational study was to estimate treatment outcomes in young adult patients with T1DM, and compare them with older individuals. Overall, 140 adults with T1DM on CSII were examined, divided into 2 subgroups: 77 patients younger than 26 years of age (mean 20.6 years) and 63 older subjects (mean 39.0). We compared the glycaemic control in both groups of T1DM subjects and analyzed treatment attitudes to identify potentially modifiable behaviours influencing the efficacy of the treatment. The younger individuals were characterized by significantly worse treatment outcomes, compared to the older ones: the mean HbA1c levels were 7.6 ± 1.3% and 6.9±1.3% (p=0.00001), while the mean glucose levels based on glucometer downloads were 161±33.6 mg/dL and 136±21.8 mg/dL (p=0.00001), respectively. The frequency of self-monitoring of blood glucose (SMBG) was lower in younger individuals (5.3±2.1 vs. 7.0±2.8 daily, p=0.0005, respectively); they were also less frequently used advanced pump functions, e.g. the bolus calculator (48% vs. 67% users, p=0.0014, respectively). The efficacy of CSII treatment observed in young T1DM adults was worse than in older patients. The reason for this phenomenon remains unclear, it may be due simply to age-dependend behaviours, to social environment, or both.

A Systematic Review and Meta-Analysis of Proteomics Literature on the Response of Human Skeletal Muscle to Obesity/Type 2 Diabetes Mellitus (T2DM) Versus Exercise Training.

PubMed

Srisawat, Kanchana; Shepherd, Sam O; Lisboa, Paulo J; Burniston, Jatin G

2017-11-11

We performed a systematic review and meta-analysis of proteomics literature that reports human skeletal muscle responses in the context of either pathological decline associated with obesity/T2DM and physiological adaptations to exercise training. Literature was collected from PubMed and DOAJ databases following PRISMA guidelines using the search terms 'proteom*', and 'skeletal muscle' combined with either 'obesity, insulin resistance, diabetes, impaired glucose tolerance' or 'exercise, training'. Eleven studies were included in the systematic review, and meta-analysis was performed on a sub-set (four studies) of the reviewed literature that reported the necessary primary data. The majority of proteins ( n = 73) more abundant in the muscle of obese/T2DM individuals were unique to this group and not reported to be responsive to exercise training. The main response of skeletal muscle to exercise training was a greater abundance of proteins of the mitochondrial electron transport chain, tricarboxylic acid cycle and mitochondrial respiratory chain complex I assembly. In total, five proteins were less abundant in muscle of obese/T2DM individuals and were also reported to be more abundant in the muscle of endurance-trained individuals, suggesting one of the major mechanisms of exercise-induced protection against the deleterious effects of obesity/T2DM occurs at complex I of the electron transport chain.

A Systematic Review and Meta-Analysis of Proteomics Literature on the Response of Human Skeletal Muscle to Obesity/Type 2 Diabetes Mellitus (T2DM) Versus Exercise Training

PubMed Central

Srisawat, Kanchana; Shepherd, Sam O.; Lisboa, Paulo J.

2017-01-01

We performed a systematic review and meta-analysis of proteomics literature that reports human skeletal muscle responses in the context of either pathological decline associated with obesity/T2DM and physiological adaptations to exercise training. Literature was collected from PubMed and DOAJ databases following PRISMA guidelines using the search terms ‘proteom*’, and ‘skeletal muscle’ combined with either ‘obesity, insulin resistance, diabetes, impaired glucose tolerance’ or ‘exercise, training’. Eleven studies were included in the systematic review, and meta-analysis was performed on a sub-set (four studies) of the reviewed literature that reported the necessary primary data. The majority of proteins (n = 73) more abundant in the muscle of obese/T2DM individuals were unique to this group and not reported to be responsive to exercise training. The main response of skeletal muscle to exercise training was a greater abundance of proteins of the mitochondrial electron transport chain, tricarboxylic acid cycle and mitochondrial respiratory chain complex I assembly. In total, five proteins were less abundant in muscle of obese/T2DM individuals and were also reported to be more abundant in the muscle of endurance-trained individuals, suggesting one of the major mechanisms of exercise-induced protection against the deleterious effects of obesity/T2DM occurs at complex I of the electron transport chain. PMID:29137117

Vildagliptin as add-on therapy to insulin improves glycemic control without increasing risk of hypoglycemia in Asian, predominantly Chinese, patients with type 2 diabetes mellitus.

PubMed

Ning, Guang; Wang, Weiqing; Li, Ling; Ma, Jianhua; Lv, Xiaofeng; Yang, Ming; Wang, Wei; Woloschak, Michael; Lukashevich, Valentina; Kothny, Wolfgang

2016-05-01

The aim of the present study was to investigate the efficacy and safety of vildagliptin added onto insulin with or without metformin in an Asian, predominantly Chinese, population with type 2 diabetes mellitus (T2DM). In this 24-week, multicenter, double-blind, placebo-controlled trial, patients with T2DM inadequately controlled (HbA1c 7.5%-11.0%) on stable therapy with long-acting, intermediate-acting, or premixed insulin, with or without concomitant metformin, were randomized to receive vildagliptin 50 mg b.i.d. or placebo. Of 293 patients randomized, 146 received vildagliptin and 147 received placebo treatment. At baseline, the overall mean age of patients was 58.1 years, mean T2DM duration was 11.3 years, and mean HbA1c was 8.7%. The adjusted mean (±SE) change in HbA1c at Week 24 in the vildagliptin and placebo groups was -1.08 ± 0.12% and -0.38 ± 0.12%, respectively (between-treatment difference -0.70 ± 0.16%; P < 0.001). The between-group difference in fasting plasma glucose was -0.43 ± 0.38 mmol/L (P = 0.259). Significantly, more patients achieved HbA1c <7.0% with vildagliptin than with placebo (23.6% vs. 11.2%; P = 0.006). The incidence of adverse events in the vildagliptin and placebo groups was 43.8% and 46.3%, whereas that of serious adverse events was 3.4% and 6.8%, respectively. The frequency of hypoglycemia was lower in the vildagliptin than placebo group (2.7% vs. 5.4%). The addition of vildagliptin 50 mg b.i.d. significantly improved glycemic control without an increased risk of hypoglycemia in Asian, predominantly Chinese, patients with T2DM inadequately controlled on insulin, with or without metformin. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley Sons Australia, & Ltd.

Efficacy and safety of teneligliptin added to canagliflozin monotherapy in Japanese patients with type 2 diabetes mellitus: A multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group comparative study

PubMed Central

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

2017-01-01

Dipeptidyl peptidase‐4 (DPP‐4) inhibitors and sodium glucose co‐transporter 2 (SGLT2) inhibitors are frequently used in combination for the treatment of type 2 diabetes mellitus (T2DM). We examined the efficacy and safety of teneligliptin (a DPP‐4 inhibitor) added to canagliflozin (an SGLT2 inhibitor) monotherapy in Japanese patients with poorly controlled T2DM as part of the development of a fixed‐dose combination of teneligliptin and canagliflozin. Japanese patients treated with canagliflozin (100 mg) for ≥12 weeks were randomized to receive add‐on teneligliptin (20 mg; C + T group) or placebo (C + P group) for 24 weeks. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to Week 24. The between‐group differences in reductions from baseline to Week 24 were significantly greater in the C + T group for HbA1c (−0.94%; P < .001). The incidence of adverse events was similar in both groups (55.8% and 49.4% in the C + T and C + P groups, respectively). No episodes of hypoglycaemia were reported. Teneligliptin added to ongoing canagliflozin monotherapy improved glycaemic control and was well tolerated in Japanese patients with inadequately controlled T2DM. PMID:28786530

Correlation between heat shock proteins, adiponectin, and T lymphocyte cytokine expression in type 2 diabetics.

PubMed

Mahmoud, Fadia F; Haines, David; Dashti, Ali A; El-Shazly, Sherief; Al-Najjar, Fawzia

2018-05-11

Type 2 diabetes mellitus (T2DM) features insulin resistance, hyperglycemia, dyslipidemia, overproduction of inflammatory cytokines, and systemic oxidative stress. Here, heat shock proteins Hsp70 and Hsp 90, adiponectin, and heme oxygenase-1 (HO-1, Hsp32) are profiled in peripheral blood mononuclear cells (PBMC) and serum from 25 T2DM patients and 25 healthy control subjects. Cells cultured with phorbol 12-myristate 13-acetate/ionomycin were evaluated by three-color flow cytometry for immunophenotypic biomarkers. Plasma HO-1, Hsp, and adiponectin levels were assayed by enzyme-linked immunosorbent assay (ELISA). Relative to healthy controls, T2DM patients exhibited significantly elevated plasma Hsp70, and representation of T helper immunophenotypes activated to express inflammatory cytokines, including CD4+ IFN-γ+, CD4+ TNF-α+, CD4+ IL-6+, CD4+ IL-1β+ T cells, significantly lower representation of CD4+ IL-10+ T cells, plasma adiponectin and cell-associated HO-1 expression-with no significant differences in plasma Hsp90 between T2DM and healthy controls. Plasma HO-1 and adiponectin in T2DM patients inversely correlated with TNF-α and showed inverse correlation between serum LDL and plasma HO-1. Moreover, TNF-α and Hsp90 in T2DM patients correlated positively with fasting blood glucose (FBG). These results demonstrate correlation between potentially pathogenic T cells, HO-1, and adiponectin, additionally revealing a T helper (Th)1-related character of T2DM immunopathogenesis, suggesting potential for novel T cell-related management strategies for T2DM and related co-morbidities.

Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison.

PubMed

Wang, Jun-Sing; Lin, Shi-Dou; Lee, Wen-Jane; Su, Shih-Li; Lee, I-Te; Tu, Shih-Te; Tseng, Yao-Hsien; Lin, Shih-Yi; Sheu, Wayne Huey-Herng

2011-12-01

(acarbose, n = 28; glibenclamide, n = 23). HbA(1c) decreased significantly in both treatment groups (acarbose: 8.2 [0.8]% to 7.5 [0.8]% [P < 0.001]; glibenclamide: 8.6 [1.6]% to 7.4 [1.2]% [P < 0.001]). MAGE did not change significantly in glibenclamide-treated patients (6.2 [2.8] mmol/L to 6.3 [2.3] mmol/L; P = 0.82), whereas ox-LDL (242.4 [180.9] ng/mL to 470.7 [247.3] ng/mL; P = 0.004) and urinary excretion of 8-iso PGF(2α) (121.6 [39.6] pmol/mmol creatinine to 152.5 [41.8] pmol/mmol creatinine; P = 0.03) increased significantly. Acarbose decreased MAGE (5.6 [1.5] mmol/L to 4.0 [1.4] mmol/L; P < 0.001) without significant change in ox-LDL levels (254.4 [269.1] ng/mL to 298.5 [249.8) ng/mL; P = 0.62) or 8-iso PGF(2α) excretion rates (117.9 [58.1] pmol/mmol creatinine to 137.8 [64.4] pmol/mmol creatinine; P = 0.12). Body weight and serum triglycerides (fasting and 2-hour postprandial) decreased (all, P < 0.01) and serum adiponectin increased (P < 0.05) after treatment with acarbose, whereas HDL-C decreased (P < 0.01) after treatment with glibenclamide. β-cell response to postprandial glucose increments was negatively correlated with MAGE (r = 0.570, P < 0.001) and improved significantly with acarbose (35.6 [32.2] pmol/mmol to 56.4 [43.7] pmol/mmol; P = 0.001) but not with glibenclamide (27.9 [17.6] pmol/mmol to 36.5 [24.2] pmol/mmol; P = 0.12). In this select population of adult Taiwanese patients with T2DM who were inadequately controlled by metformin, add-on acarbose or glibenclamide significantly reduced HbA(1c). However, treatment with acarbose decreased MAGE, body weight, and serum triglyceride and increased serum adiponectin without significant effect on oxidative stress. Treatment with glibenclamide had no statistically significant effect on MAGE but increased oxidative stress and decreased HDL-C. ClinicalTrials.gov identifier: NCT00417729. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

Design and rationale of the ODYSSEY DM-DYSLIPIDEMIA trial: lipid-lowering efficacy and safety of alirocumab in individuals with type 2 diabetes and mixed dyslipidaemia at high cardiovascular risk.

PubMed

Müller-Wieland, Dirk; Leiter, Lawrence A; Cariou, Bertrand; Letierce, Alexia; Colhoun, Helen M; Del Prato, Stefano; Henry, Robert R; Tinahones, Francisco J; Aurand, Lisa; Maroni, Jaman; Ray, Kausik K; Bujas-Bobanovic, Maja

2017-05-25

Type 2 diabetes mellitus (T2DM) is often associated with mixed dyslipidaemia, where non-high-density lipoprotein cholesterol (non-HDL-C) levels may more closely align with cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). We describe the design and rationale of the ODYSSEY DM-DYSLIPIDEMIA study that assesses the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk with non-HDL-C inadequately controlled despite maximally tolerated statin therapy. For the first time, atherogenic cholesterol-lowering with a PCSK9 inhibitor will be assessed with non-HDL-C as the primary endpoint with usual care as the comparator. DM-DYSLIPIDEMIA is a Phase 3b/4, randomised, open-label, parallel group, multinational study that planned to enrol 420 individuals. Main inclusion criteria were T2DM and mixed dyslipidaemia (non-HDL-C ≥100 mg/dl [≥2.59 mmol/l], and triglycerides ≥150 and <500 mg/dl [≥1.70 and <5.65 mmol/l]) with documented atherosclerotic cardiovascular disease or ≥1 additional cardiovascular risk factor. Participants were randomised (2:1) to alirocumab 75 mg every 2 weeks (Q2W) or lipid-lowering usual care on top of maximally tolerated statin (or no statin if intolerant). If randomised to usual care, investigators were able to add their pre-specified choice of one of the following to the patient's current statin regimen: ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid, in accordance with local standard-of-care. Alirocumab-treated individuals with non-HDL-C ≥100 mg/dl at week 8 will undergo a blinded dose increase to 150 mg Q2W at week 12. The primary efficacy endpoint is non-HDL-C change from baseline to week 24 with alirocumab versus usual care; other lipid levels (including LDL-C), glycaemia-related measures, safety and tolerability will also be assessed

[Prevalence of type 2 diabetes mellitus in overweight or obese outpatients in Spain. OBEDIA Study].

PubMed

Gomis, Ramón; Artola, Sara; Conthe, Pedro; Vidal, Josep; Casamor, Ricard; Font, Beatriu

2014-06-06

The increase in the prevalence of type 2 diabetes mellitus (T2DM) is related to the increase of obesity. We aimed to determine the Spanish prevalence of T2DM in patients with overweight or obesity attended by either family or specialist physicians. Cross-sectional, multicenter and simultaneous 2-phase design, performed under clinical conditions. Phase A was designed to determine T2DM prevalence: 169,023 patients were recruited. Phase B was designed to define socio-demographic, clinical and metabolic profile of T2DM according to the body mass index (BMI): 7,754 patients were included. T2DM prevalence in overweight or obese patients was 23.6%; 17.8% of overweight patients were diabetic and T2DM was present in 34.8% of obese people. According to sex, 20.2% of men and 16.4% of women had T2DM. Overall, the mean of risk factors related to T2DM was 4.4 (SD 0,8); out of them, 92.6% patients had dyslipidemia, 73.7% hypertension and 62.5% performed a low physical activity. 37.8% of diabetic patients had vascular involvement. Only 43.1% of patients showed a proper metabolic control of T2DM (glycosilated hemoglobin<7%). T2DM is related to overweight and obesity and higher the BMI is, higher the T2DM prevalence. Dyslipidemia, hypertension and a low physical activity in diabetic patients are more frequent when BMI increases. Patients with inadequate metabolic control have a higher BMI. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Association between IGF2BP2 Polymorphisms and Type 2 Diabetes Mellitus: A Case–Control Study and Meta-Analysis

PubMed Central

Rao, Ping; Wang, Hao; Fang, Honghong; Gao, Qing; Zhang, Jie; Song, Manshu; Zhou, Yong; Wang, Youxin; Wang, Wei

2016-01-01

Background: Genome-wide association studies (GWAS) found that IGF2BP2 rs4402960 and rs1470579 polymorphisms were associated with type 2 diabetes mellitus (T2DM) risk. Many studies have replicated this association, but yielded inconsistent results. Materials and Methods: A case-control study consisting of 461 T2DM patients and 434 health controls was conducted to detect the genetic susceptibility of IGF2BP2 in a northern Han Chinese population. A meta-analysis was to evaluate the association more precisely in Asians. Results: In the case-control study, the carriers of TT genotype at rs4402960 had a higher T2DM risk than the G carriers (TG + GG) (adjusted odd ratio (AOR) = 1.962, 95% confidence interval (95% CI) = 1.065–3.612, p = 0.031]; CC carriers at rs1470579 were more susceptible to T2DM than A carriers (CA + AA) (AOR = 2.014, 95% CI = 1.114–3.642, p = 0.021). The meta-analysis containing 36 studies demonstrated that the two polymorphisms were associated with T2DM under the allele comparison, genetic models of dominant and recessive in Asians (p < 0.05). The rs4402960 polymorphisms were significantly associated with the T2DM risk after stratification by diagnostic criterion, size of sample and average age and BMI of cases, while there’re no consistent results for rs1470579. Conclusions: Our data suggests that IGF2BP2 polymorphisms are associated with T2DM in Asian populations. PMID:27294943

Comparison of glycemic control and variability in patients with type 2 and posttransplantation diabetes mellitus.

PubMed

Werzowa, Johannes; Pacini, Giovanni; Hecking, Manfred; Fidler, Catharina; Haidinger, Michael; Brath, Helmut; Thomas, Andreas; Säemann, Marcus D; Tura, Andrea

2015-01-01

Posttransplantation diabetes mellitus (PTDM) is a common complication after renal transplantation leading to increased cardiovascular morbidity and mortality. In subjects with type 2 diabetes (T2DM) increased glycemic variability and poor glycemic control have been associated with cardiovascular complications. We therefore aimed at determining glycemic variability and glycemic control in subjects with PTDM in comparison to T2DM subjects. In this observational study we analyzed 10 transplanted subjects without diabetes (Control), 10 transplanted subjects with PTDM, and 8 non-transplanted T2DM subjects using Continuous Glucose Monitoring (CGM). Several indices of glycemic control quality and variability were computed. Many indices of both glycemic control quality and variability were different between control and PTDM subjects, with worse values in PTDM. The indices of glycemic control, such as glucose mean, GRADE and M-value, were similar in PTDM and T2DM, but some indices of glycemic variability, that is CONGA, lability index and shape index, showed a markedly higher (i.e., worse) value in T2DM than in PTDM (P value range: 0.001-0.035). Although PTDM and T2DM subjects showed similar glycemic control quality, glycemic variability was significantly higher in T2DM. These data underscore potential important pathophysiological differences between T2DM and PTDM indicating that increased glycemic variability may not be a key factor for the excess cardiovascular mortality in patients with PTDM. Copyright © 2015 Elsevier Inc. All rights reserved.

A retrospective analysis of a societal experiment among the Danish population suggests that exposure to extra doses of vitamin A during fetal development may lower type 2 diabetes mellitus (T2DM) risk later in life.

PubMed

Keller, Amélie; Ängquist, Lars; Jacobsen, Ramune; Vaag, Allan; Heitmann, Berit L

2017-03-01

Vitamin A deficiency has been associated with impaired fetal pancreatic development and increased risk of developing type 2 diabetes mellitus (T2DM). In 1962, mandatory margarine fortification with vitamin A was increased by 25 % in Denmark. We aimed to determine whether offspring of mothers who had been exposed to the extra vitamin A from fortification during pregnancy had a lower risk of developing T2DM in adult life, compared with offspring of mothers exposed to less vitamin A. Individuals from birth cohorts with the higher prenatal vitamin A exposure (born 1 December 1962-31 March 1964) and those with lower prenatal exposure (born 1 September 1959-31 December 1960) were followed up with regard to development of T2DM before 31 December 2012 in the Danish National Diabetes Registry and National Patient Register. Logistic and Cox regression analyses were performed to determine the risk of T2DM by vitamin A exposure level. A total of 193 803 individuals were followed up until midlife. Our results showed that individuals exposed prenatally to extra vitamin A from fortified margarine had a lower risk of developing T2DM than those exposed to lower levels: OR 0·88; 95 % CI 0·81, 0·95, P=0·001, after adjustment for sex. Fetal exposure to small, extra amounts of vitamin A from food fortification may reduce the risk of T2DM. These results may have public health relevance, as they demonstrate that one of the most costly chronic diseases may be prevented by food fortification - a simple and affordable public health nutrition intervention.

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period.

PubMed

Kadowaki, Takashi; Kondo, Kazuoki; Sasaki, Noriyuki; Miyayama, Kyoko; Yokota, Shoko; Terata, Ryuji; Gouda, Maki

2017-09-01

To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was -0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P < 0.001). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. NCT02081599.

[Relationship between brachial-ankle pulse wave velocity and glycemic control of type 2 diabetes mellitus patients in Beijing community population].

PubMed

Sun, Ke-xin; Liu, Zhi-ke; Cao, Ya-ying; Juan, Juan; Xiang, Xiao; Yang, Cheng; Huang, Shao-ping; Liu, Xiao-fen; Li, Na; Tang, Xun; Li, Jin; Wu, Tao; Chen, Da-fang; Hu, Yong-hua

2015-06-18

To explore the correlation between glycemic control of type 2 diabetes mellitus (T2DM) patients and brachial-ankle pulse velocity (baPWV). A community-based cross-sectional study was conducted in Beijing, China. Every subject underwent physical examinations, glycated hemoglobin (HbA1c), blood lipid and baPWV measurements and completed a standardized questionnaire. T2DM patients were divided into well controlled and poorly controlled groups according to HbA1c levels. The correlation between glycemic control of T2DM patients and baPWV was analyzed. In this study, 1 341 subjects were recruited, including 733 T2DM patients and 608 non-diabetes subjects. Compared with non-diabetes subjects, abnormal baPWV (baPWV≥1 700 cm/s) rate for T2DM patients was higher (40.8% vs. 26.8%, P<0.001). With HbA1c<6.5% or <7.0% as the aim of glycemic control in T2DM patients, the abnormal baPWV rates for non-diabetes subjects, well controlled and poorly controlled T2DM patients were significantly different (non-diabetes vs. HbA1c<6.5% T2DM vs. HbA1c≥6.5% T2DM: 26.8% vs. 32.8% vs. 42.6%, P<0.001; non-diabetes vs. HbA1c<7.0% T2DM vs. HbA1c≥7.0% T2DM: 26.8% vs. 36.1% vs. 43.4%, P<0.001). After being adjusted for gender, age, smoking status, diabetes mellitus family history, T2DM duration, cardiovascular diseases (CVD), waist hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), total triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C), the Logistic regression models suggested that glycemic control status of T2DM patients was associated with abnormal baPWV. Compared with non-diabetes subjects, the ORs for abnormal baPWV in HbA1c<6.5% T2DM patients and HbA1c≥6.5% T2DM patients were 0.927(95%CI 0.560-1.537) and 1.826 (95%CI 1.287-2.591). Compared with non-diabetes subjects, the ORs for abnormal baPWV in HbA1c<7.0% T2DM patients and HbA1c≥7.0% T2DM patients were 1.210 (95%CI 0.808-1.811) and 1

Relationship between tumor biomarkers and efficacy in TH3RESA, a phase III study of trastuzumab emtansine (T-DM1) vs. treatment of physician's choice in previously treated HER2-positive advanced breast cancer.

PubMed

Kim, Sung-Bae; Wildiers, Hans; Krop, Ian E; Smitt, Melanie; Yu, Ron; Lysbet de Haas, Sanne; Gonzalez-Martin, Antonio

2016-11-15

In the phase III TH3RESA study (NCT01419197), 602 patients with HER2-positive advanced breast cancer who received prior taxane therapy and ≥2 HER2-directed regimens, including trastuzumab and lapatinib (advanced setting), were randomized to trastuzumab emtansine (T-DM1) or treatment of physician's choice (TPC). A statistically significant progression-free survival (PFS) benefit favoring T-DM1 was demonstrated. Here, we examine the relationship between HER2-related biomarkers and PFS in an exploratory analysis. Biomarkers assessed included HER2 (n = 505) and HER3 (n = 505) mRNA expression, PIK3CA mutation status (n = 410) and PTEN protein expression (n = 358). For biomarkers with continuous data (HER2, HER3, PTEN), subgroups were defined using median values (>median and ≤median). For all biomarker subgroups, median PFS was longer with T-DM1 vs. TPC. The PFS benefit favoring T-DM1 vs. TPC was numerically greater in the HER2 mRNA >median subgroup (7.2 vs. 3.4 months; unstratified hazard ratio [HR], 0.40; 95% CI, 0.28-0.59; p < 0.0001) vs. ≤median subgroup (5.5 vs. 3.9 months; HR, 0.68; 95% CI, 0.49-0.92; p = 0.0131). The PFS benefit with T-DM1 was similar among HER3, PIK3CA and PTEN subgroups. Consistent with other reports, benefit was seen with T-DM1 regardless of PIK3CA mutation status. In a multivariate analysis including an interaction term (treatment group by log2-transformed HER2 mRNA), patients with higher HER2 mRNA levels benefited more from receiving T-DM1 (HR, 0.84; 95% CI, 0.75-0.94; interaction p value = 0.0027). In summary, T-DM1 prolonged median PFS in all biomarker subgroups analyzed, including activating PIK3CA mutations, with numerically greater benefit in patients with tumors expressing HER2 mRNA >median vs. ≤median. © 2016 UICC.

Intermittent Vagal Nerve Block for Improvements in Obesity, Cardiovascular Risk Factors, and Glycemic Control in Patients with Type 2 Diabetes Mellitus: 2-Year Results of the VBLOC DM2 Study.

PubMed

Shikora, Scott A; Toouli, James; Herrera, Miguel F; Kulseng, Bård; Brancatisano, Roy; Kow, Lilian; Pantoja, Juan P; Johnsen, Gjermund; Brancatisano, Anthony; Tweden, Katherine S; Knudson, Mark B; Billington, Charles J; Billingto, Charles J

2016-05-01

One-year results of the VBLOC DM2 study found that intermittent vagal blocking (VBLOC therapy) was safe among subjects with obesity and type 2 diabetes mellitus (T2DM) and led to significant weight loss and improvements in glycemic parameters and cardiovascular risk factors. Longer-term data are needed to determine whether the results are sustained. VBLOC DM2 is a prospective, observational study of 28 subjects with T2DM and body mass index (BMI) between 30 and 40 kg/m(2) to assess mid-term safety and weight loss and improvements in glycemic parameters, and other cardiovascular risk factors with VBLOC therapy. Continuous outcome variables are reported using mixed models. At 24 months, the mean percentage of excess weight loss was 22% (95% CI, 15 to 28, p < 0.0001) or 7.0% total body weight loss (95% CI, 5.0 to 9.0, p < 0.0001). Hemoglobin A1c decreased by 0.6 percentage points (95% CI, 0.2 to 1.0, p = 0.0026) on average from 7.8% at baseline. Fasting plasma glucose declined by 15 mg/dL (95% CI, 0 to 29, p = 0.0564) on average from 151 mg/dL at baseline. Among subjects who were hypertensive at baseline, systolic blood pressure declined 10 mmHg (95% CI, 2 to 19, p = 0.02), diastolic blood pressure declined by 6 mmHg (95% CI, 0 to 12, p = 0.0423), and mean arterial pressure declined 7 mmHg (95% CI, 2 to 13, p = 0.014). Waist circumference was significantly reduced by 7 cm (95% CI, 4 to 10, p < 0.0001) from a baseline of 120 cm. The most common adverse events were mild or moderate heartburn, implant site pain, and constipation. Improvements in obesity and glycemic control were largely sustained after 2 years of treatment with VBLOC therapy with a well-tolerated risk profile.

Vildagliptin added to sulfonylurea improves glycemic control without hypoglycemia and weight gain in Chinese patients with type 2 diabetes mellitus.

PubMed

Yang, Wenying; Xing, Xiaoping; Lv, Xiaofeng; Li, Yiming; Ma, Jianhua; Yuan, Guoyue; Sun, Feifei; Wang, Wei; Woloschak, Michael; Lukashevich, Valentina; Kozlovski, Plamen; Kothny, Wolfgang

2015-03-01

The aim of the present study was to assess the efficacy and safety of vildagliptin as add-on to sulfonylurea therapy in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on sulfonylurea monotherapy. The 24-week randomized double-blind placebo-controlled study compared vildagliptin 50 mg, q.d., with placebo as add-on to glimepiride in T2DM patients who were inadequately controlled (HbA1c 7.5%-11.0% [58-97 mmol/mol]) on a stable dose of sulfonylurea for ≥12 weeks before study entry. In all, 279 patients were randomized to receive either vildagliptin (n = 143) or placebo (n = 136). At baseline, overall mean age was 58.5 years, body weight 68.1 kg, duration of diabetes 6.9 years and daily glimepiride dose 3.3 mg. After 24 weeks, the adjusted mean change (AMΔ) in HbA1c was -0.7% (-8 mmol/mol; baseline 8.6%, 70 mmol/mol) in the vildagliptin group and -0.2% (-2 mmol/mol; baseline 8.7%, 72 mmol/mol) in the placebo group, with a treatment difference of -0.5% (-5 mmol/mol; P < 0.001). The between-group difference in AMΔ in fasting plasma glucose was -0.4 mmol/L (P = 0.160). There was a slight, but not significant, decrease in body weight in both groups. No hypoglycemic events were reported in either group, including those patients reaching HbA1c <7.0%. Patients in the vildagliptin and placebo groups reported low and comparable incidences of adverse events (14.0% vs. 17.8%) and serious adverse events (0.7% in each group). Vildagliptin 50 mg, q.d., added to sulfonylurea monotherapy is effective in Chinese patients with T2DM, without increasing the risk of hypoglycemia and weight gain. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

42 CFR 70.2 - Measures in the event of inadequate local control.

Code of Federal Regulations, 2013 CFR

2013-10-01

... control. Whenever the Director of the Centers for Disease Control and Prevention determines that the... 42 Public Health 1 2013-10-01 2013-10-01 false Measures in the event of inadequate local control...) are insufficient to prevent the spread of any of the communicable diseases from such State or...

42 CFR 70.2 - Measures in the event of inadequate local control.

Code of Federal Regulations, 2010 CFR

2010-10-01

... control. Whenever the Director of the Centers for Disease Control and Prevention determines that the... 42 Public Health 1 2010-10-01 2010-10-01 false Measures in the event of inadequate local control...) are insufficient to prevent the spread of any of the communicable diseases from such State or...

42 CFR 70.2 - Measures in the event of inadequate local control.

Code of Federal Regulations, 2011 CFR

2011-10-01

... control. Whenever the Director of the Centers for Disease Control and Prevention determines that the... 42 Public Health 1 2011-10-01 2011-10-01 false Measures in the event of inadequate local control...) are insufficient to prevent the spread of any of the communicable diseases from such State or...

42 CFR 70.2 - Measures in the event of inadequate local control.

Code of Federal Regulations, 2012 CFR

2012-10-01

... control. Whenever the Director of the Centers for Disease Control and Prevention determines that the... 42 Public Health 1 2012-10-01 2012-10-01 false Measures in the event of inadequate local control...) are insufficient to prevent the spread of any of the communicable diseases from such State or...

42 CFR 70.2 - Measures in the event of inadequate local control.

Code of Federal Regulations, 2014 CFR

2014-10-01

... control. Whenever the Director of the Centers for Disease Control and Prevention determines that the... 42 Public Health 1 2014-10-01 2014-10-01 false Measures in the event of inadequate local control...) are insufficient to prevent the spread of any of the communicable diseases from such State or...

Development of a patient decision aid for type 2 diabetes mellitus for patients not achieving glycemic control on metformin alone

PubMed Central

Shillington, Alicia C; Col, Nananda; Bailey, Robert A; Jewell, Mark A

2015-01-01

Purpose To describe the process used to develop an evidence-based patient decision aid (PDA) that facilitates shared decision-making for treatment intensification in inadequately controlled type 2 diabetes mellitus (T2DM) consistent with International Patient Decision Aids Standards. Methods A PDA was developed by a multidisciplinary steering committee of clinicians, patient advocate, nurse, certified diabetes educators, and decision scientist, using a systematic development process. The process included defining the PDA scope and purpose, outlining the framework, content creation, and designing for integration into clinical practice. This was accomplished through a review of the literature and publically available educational materials and input from practicing clinicians and patients during development and iteratively refining content based on input. Patients with poorly controlled T2DM on metformin considering additional medication assessed the PDA during a pilot. Results Testing identified six preference-sensitive domains important for choosing T2DM treatment: degree of glycemic response, avoiding weight gain, hypoglycemia risk and other adverse events, avoiding injections, convenience of dose administration, blood glucose monitoring, and cost of therapy. Patient feedback guided content revision. Treatment options were offered after presenting medication class risk–benefit information and eliciting patient values, goals, and preferences. The PDA received the highest International Patient Decision Aids Standards global score to date, 88/100, with 100% of criteria fully met for the following dimensions: development process, disclosures, evaluation process, evidence quality, guidance for users, information quality, language/readability, testing, and eliciting patient values. Conclusion A PDA was developed to help T2DM patients make decisions regarding medication choice. This approach may be applicable to other chronic conditions. PMID:25995622

Analysis of MTMR1 expression and correlation with muscle pathological features in juvenile/adult onset myotonic dystrophy type 1 (DM1) and in myotonic dystrophy type 2 (DM2).

PubMed

Santoro, Massimo; Modoni, Anna; Masciullo, Marcella; Gidaro, Teresa; Broccolini, Aldobrando; Ricci, Enzo; Tonali, Pietro Attilio; Silvestri, Gabriella

2010-10-01

Among genes abnormally expressed in myotonic dystrophy type1 (DM1), the myotubularin-related 1 gene (MTMR1) was related to impaired muscle differentiation. Therefore, we analyzed MTMR1 expression in correlation with CUG-binding protein1 (CUG-BP1) and muscleblind-like1 protein (MBNL1) steady-state levels and with morphological features in muscle tissues from DM1 and myotonic dystrophy type 2 (DM2) patients. Semi-quantitative RT-PCR for MTMR1 was done on muscle biopsies and primary muscle cultures. The presence of impaired muscle fiber maturation was evaluated using immunochemistry for neural cell adhesion molecule (NCAM), Vimentin and neonatal myosin heavy chain. CUG-BP1 and MBNL1 steady-state levels were estimated by Western blot. RNA-fluorescence in situ hybridization combined with immunochemistry for CUG-BP1, MBNL1 and NCAM were performed on serial muscle sections. An aberrant splicing of MTMR1 and a significant amount of NCAM-positive myofibers were detected in DM1 and DM2 muscle biopsies; these alterations correlated with DNA repeat expansion size only in DM1. CUG-BP1 levels were increased only in DM1 muscles, while MBNL1 levels were similar among DM1, DM2 and controls. Normal and NCAM-positive myofibers displayed no differences either in the amount of ribonuclear foci and the intracellular distribution of MBNL1 and CUG-BP1. In conclusion, an aberrant MTMR1 expression and signs of altered myofiber maturation were documented in both DM1 and in DM2 muscle tissues. The more severe dysregulation of MTMR1 expression in DM1 versus DM2, along with increased CUG-BP1 levels only in DM1 tissues, suggests that the mutual antagonism between MBNL1 and CUG-BP1 on alternative splicing is more unbalanced in DM1. Copyright © 2010 Elsevier Inc. All rights reserved.

The influence of aspirin dose and glycemic control on platelet inhibition in patients with type 2 diabetes mellitus.

PubMed

Lemkes, B A; Bähler, L; Kamphuisen, P W; Stroobants, A K; Van Den Dool, E J; Hoekstra, J B; Nieuwland, R; Gerdes, V E; Holleman, F

2012-04-01

Low-dose aspirin seems to offer no benefit in the primary prevention of cardiovascular disease in type 2 diabetes mellitus (DM2). The anti-platelet effect may be diminished by poor glycemic control or inadequate dosing of aspirin. To study the effects of both glycemic control and increasing aspirin dose on platelet response to aspirin in DM2 patients and matched controls. Platelet effects of increasing doses of aspirin (30, 100 and 300 mg daily) were prospectively assessed in 94 DM2 patients and 25 matched controls by measuring thromboxane levels in urine (11-dhTxB2) and platelet aggregation using VerifyNow(®) and light transmission aggregometry (LTA). DM2 patients were stratified for glycemic control (hemoglobin-A1c [HbA1c] ≤ 53, 53-69, ≥ 69 mmol mol(-1)). At baseline, median 11-dhTxB2 excretion was higher in the poorly controlled patients (77 ng mmol(-1)), and the moderately controlled (84 ng mmol(-1)) compared with the well-controlled patients (64 ng mmol(-1)) and controls (53 ng mmol(-1)), P < 0.01. Next, 30 mg of aspirin reduced 11-dhTxB2 excretion to 31, 29 and 24 ng mmol(-1) in the poorly, moderately and well-controlled patients, respectively, and to 19 ng mmol(-1) in controls, P < 0.001. VerifyNow(®) and LTA were also incompletely suppressed in DM2 patients using 30 mg of aspirin, but 100 mg resulted in similar platelet suppression in all groups, with no additional effect of 300 mg. DM2 patients with inadequate glycemic control (HbA1c > 53 mmol mol(-1)) have higher baseline platelet activity and incomplete suppression of platelet activity with 30 mg of aspirin. However, 100 mg of aspirin leads to optimal inhibition irrespective of glycemic control, and 300 mg does not further improve platelet suppression. © 2012 International Society on Thrombosis and Haemostasis.

Tolerability and Efficacy of Ipragliflozin in The Management of Inadequately Controlled Type 2 Diabetes mellitus: A Systematic Review and Meta-analysis.

PubMed

Elgebaly, Ahmed; Abdelazeim, Nesrine; Abdelazeim, Bassant; El Ashal, Gehad; Mattar, Omar; Namous, Lubaba; Nasreldin, Noha

2018-06-18

Ipragliflozin is a new antidiabetic agent that works through enhancing renal glucose excretion. We aim to synthesize evidence from published randomized controlled trials (RCTs) on the safety and efficacy of ipragliflozin in the management of type 2 diabetes mellitus (T2DM). We searched PubMed, Scopus, Web of Science, and Cochrane Central register of clinical trials using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup and sensitivity analyses were conducted. We included 13 RCTs (N=2535 patients) in the final analysis. The overall effect estimates favoured ipragliflozin 50mg monotherapy group over placebo in terms of: HbA1c (Standardized mean difference (SMD)=-1.20%, 95% Confidence interval (95% CI)=[-1.47, -0.93]; p<0.001), fasting plasma glucose (SMD=-1.30 mg/dL, 95% CI [-1.93, -0.67]; p<0.001), fasting serum insulin (SMD=-1.64 μU/mL, 95% CI [-2.70, -0.59]; p=0.002), and body weight (SMD=-0.85 kg, 95% CI [-1.19, -0.51]; p<0.001). Similarly, better glycemic control and significant body weight reduction compared to placebo were attained in ipragliflozin 50 mg combination with metformin, insulin with/without dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone. Ipragliflozin, either alone or in combination, exhibits acceptable safety profile. The presented meta-analysis provides class one evidence that ipragliflozin is safe and effective in the management of T2DM either as monotherapy or an add-on. © Georg Thieme Verlag KG Stuttgart · New York.

The Relationship between Self-Management and Glycemic Control in a Cohort of Children with Type 1 and Type 2 Diabetes.

PubMed

Rodriguez, Luisa M; Hassan, Krishnavathana V; Rhodes, Jeffrey; McKay, Siripoom V; Heptulla, Rubina A

2013-12-15

Self-management of diabetes improves glycemic control. The development of a quick, objective questionnaire in the clinic setting may provide data to the clinician caring for the patient in overall evaluation. We developed a 23 question tool (clinic preparedness score) and administered it to type 1 and 2 (T1DM & T2DM) diabetes patients. Clinicians of patients were surveyed to determine their perception of adherence by patients. A total of 350 T1DM patients and families and 137 T2DM families were administered the questionnaire. Additionally, HbA1C was correlated to the various parameters that are related to improved glycemic control such as having a meter, carrying glucose tablets for hypoglycemia, and downloading/ writing blood sugars in log book in T1DM and T2DM. T1DM subjects had a lower HbA1C with better clinic preparedness (8.2 ± 1.3 vs. 9.4 ± 1.9%) However, this did not hold true for T2DM (p NS). If T1DM subjects adjusted their insulin dose and reported that their parent was involved they had better HbA1C than those that did not change insulin dose and if parent was uninvolved in the care. Clinicians of patients were able to accurately predict that appropriate dose adjustments resulted in good glycemic control. Pediatric T2DM adherence measures do not mirror similar characteristics of T1DM in childhood. The variability in glucose monitoring, medication and insulin administration may affect T2DM differently than T1DM.

Evolution of Antibody-Drug Conjugate Tumor Disposition Model to Predict Preclinical Tumor Pharmacokinetics of Trastuzumab-Emtansine (T-DM1).

PubMed

Singh, Aman P; Maass, Katie F; Betts, Alison M; Wittrup, K Dane; Kulkarni, Chethana; King, Lindsay E; Khot, Antari; Shah, Dhaval K

2016-07-01

A mathematical model capable of accurately characterizing intracellular disposition of ADCs is essential for a priori predicting unconjugated drug concentrations inside the tumor. Towards this goal, the objectives of this manuscript were to: (1) evolve previously published cellular disposition model of ADC with more intracellular details to characterize the disposition of T-DM1 in different HER2 expressing cell lines, (2) integrate the improved cellular model with the ADC tumor disposition model to a priori predict DM1 concentrations in a preclinical tumor model, and (3) identify prominent pathways and sensitive parameters associated with intracellular activation of ADCs. The cellular disposition model was augmented by incorporating intracellular ADC degradation and passive diffusion of unconjugated drug across tumor cells. Different biomeasures and chemomeasures for T-DM1, quantified in the companion manuscript, were incorporated into the modified model of ADC to characterize in vitro pharmacokinetics of T-DM1 in three HER2+ cell lines. When the cellular model was integrated with the tumor disposition model, the model was able to a priori predict tumor DM1 concentrations in xenograft mice. Pathway analysis suggested different contribution of antigen-mediated and passive diffusion pathways for intracellular unconjugated drug exposure between in vitro and in vivo systems. Global and local sensitivity analyses revealed that non-specific deconjugation and passive diffusion of the drug across tumor cell membrane are key parameters for drug exposure inside a cell. Finally, a systems pharmacokinetic model for intracellular processing of ADCs has been proposed to highlight our current understanding about the determinants of ADC activation inside a cell.

Family intervention to control type 2 diabetes: a controlled clinical trial.

PubMed

García-Huidobro, Diego; Bittner, Marcela; Brahm, Paulina; Puschel, Klaus

2011-02-01

Chilean patients with type 2 diabetes mellitus (T2DM) have a low rate of blood sugar control. We studied the effectiveness of a culturally sensitive family oriented intervention designed to improve metabolic control in primary care patients with uncontrolled T2DM. Patients with T2DM from three primary care clinics in Santiago, Chile were randomly selected for inclusion if they had a recent HbA1c ≥7%, were between 18 and 70 years old and lived with a family member. Patients from one clinic received the family oriented intervention; patients from the other two (control) clinics received standard care. The intervention involved family members in care and included family counselling during clinic visits, family meetings and home visits. The primary outcome was HbA1c, measured at 6 and 12 months. A total of 243 patients were enrolled and 209 (86%) completed the study. The intervention was fully administered to only 34% of patients in the intervention clinic. The reduction in the HbA1c from baseline to 12 months was not significantly different between clinics. During the second 6-month period, when the intervention was more intensive, the patients in the intervention clinic significantly improved their HbA1c (P < 0.001) compared to the control patients. A family intervention for the control of T2DM was associated with a significant reduction in HbA1c when the intervention was provided. Incomplete implementation, low statistical power and potential confounding variables between groups could be some of the main factors that explain the lack of difference between clinics in the 12-month period.

DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1.

PubMed

Ogitani, Yusuke; Aida, Tetsuo; Hagihara, Katsunobu; Yamaguchi, Junko; Ishii, Chiaki; Harada, Naoya; Soma, Masako; Okamoto, Hiromi; Oitate, Masataka; Arakawa, Shingo; Hirai, Takehiro; Atsumi, Ryo; Nakada, Takashi; Hayakawa, Ichiro; Abe, Yuki; Agatsuma, Toshinori

2016-10-15

An anti-HER2 antibody-drug conjugate with a novel topoisomerase I inhibitor, DS-8201a, was generated as a new antitumor drug candidate, and its preclinical pharmacologic profile was assessed. In vitro and in vivo pharmacologic activities of DS-8201a were evaluated and compared with T-DM1 in several HER2-positive cell lines and patient-derived xenograft (PDX) models. The mechanism of action for the efficacy was also evaluated. Pharmacokinetics in cynomolgus monkeys and the safety profiles in rats and cynomolgus monkeys were assessed. DS-8201a exhibited a HER2 expression-dependent cell growth-inhibitory activity and induced tumor regression with a single dosing at more than 1 mg/kg in a HER2-positive gastric cancer NCI-N87 model. Binding activity to HER2 and ADCC activity of DS-8201a were comparable with unconjugated anti-HER2 antibody. DS-8201a also showed an inhibitory activity to Akt phosphorylation. DS-8201a induced phosphorylation of Chk1 and Histone H2A.X, the markers of DNA damage. Pharmacokinetics and safety profiles of DS-8201a were favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys, supporting DS-8201a as being well tolerated in humans. DS-8201a was effective in a T-DM1-insensitive PDX model with high HER2 expression. DS-8201a, but not T-DM1, demonstrated antitumor efficacy against several breast cancer PDX models with low HER2 expression. DS-8201a exhibited a potent antitumor activity in a broad selection of HER2-positive models and favorable pharmacokinetics and safety profiles. The results demonstrate that DS-8201a will be a valuable therapy with a great potential to respond to T-DM1-insensitive HER2-positive cancers and low HER2-expressing cancers. Clin Cancer Res; 22(20); 5097-108. ©2016 AACR. ©2016 American Association for Cancer Research.

JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitor, improves glucose metabolism in diet-induced obesity and genetic T2DM mice.

PubMed

Tomimoto, Daisuke; Okuma, Chihiro; Ishii, Yukihito; Kobayashi, Akio; Ohta, Takeshi; Kakutani, Makoto; Imanaka, Tsuneo; Ogawa, Nobuya

2015-09-01

Type 2 diabetes mellitus (T2DM) arises primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important in the development of T2DM, including obesity. JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase 1 inhibitor, reduced body weight depending on dietary fat in diet-induced obesity (DIO) rats in our previous study. Here, the effect of JTT-553 on glucose metabolism was evaluated using body weight reduction in T2DM mice. JTT-553 was repeatedly administered to DIO and KK-A(y) mice. JTT-553 reduced body weight gain and fat weight in both mouse models. In DIO mice, JTT-553 decreased insulin, non-esterified fatty acid (NEFA), total cholesterol (TC), and liver triglyceride (TG) plasma concentrations in non-fasting conditions. JTT-553 also improved insulin-dependent glucose uptake in adipose tissues and glucose intolerance in DIO mice. In KK-A(y) mice, JTT-553 decreased glucose, NEFA, TC and liver TG plasma concentrations in non-fasting conditions. JTT-553 also decreased glucose, insulin, and TC plasma concentrations in fasting conditions. In addition, JTT-553 decreased TNF-α mRNA levels and increased GLUT4 mRNA levels in adipose tissues in KK-A(y) mice. These results suggest that JTT-553 improves insulin resistance in adipose tissues and systemic glucose metabolism through reductions in body weight. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Do Perceptions of Empowerment Affect Glycemic Control and Self-Care Among Adults with Type 2 Diabetes?

PubMed

D'Souza, Melba Sheila; Karkada, Subrahmanya Nairy; Hanrahan, Nancy P; Venkatesaperumal, Ramesh; Amirtharaj, Anandhi

2015-02-24

The Arab adult with T2DM is understudied with less known facts about the perception of empowerment and its relationship with self-care and glycemic control. The purpose of this study was to determine the extent to which perception of empowerment by Arab adults living with Type 2 Diabetes Mellitus (T2DM) was associated with better glycemic control and self-care management. A cross-sectional descriptive study was led among 300 Arab adults living in Oman with T2DM in an outpatient diabetes clinic. The Diabetes Empowerment Scale (DES), glycosylated haemaglobin (HbA1c) and Body mass index was assessed. The DES was found to be valid and reliable for the population. ANOVA, Regression analysis, and Structural equation modeling was used for analysis. The composite score and three subscales of DES were a significant and strong predictor of good glycemic control among Omani adults with T2DM (p<0.001). Age, education, duration of DM, prior DM education program and medications were significantly associated with DES. Diabetes nurse educators engaged in the care of adults with T2DM should assess self-empowerment and tailor interventions to increase empowerment for better glycemic control. Patient empowerment plays an essential role in maintaining self-care behaviours and HbA1c.

Cerebral Hemodynamics and Systemic Endothelial Function Are Already Impaired in Well-Controlled Type 2 Diabetic Patients, with Short-Term Disease

PubMed Central

Altavilla, Riccardo; Di Flaviani, Alessandra; Giordani, Ilaria; Malandrucco, Ilaria; Picconi, Fabiana; Passarelli, Francesco; Pasqualetti, Patrizio; Ercolani, Matilde; Vernieri, Fabrizio; Frontoni, Simona

2013-01-01

Objective Impaired cerebral vasomotor reactivity (VMR) and flow-mediated dilation (FMD) were found in selected subgroups of type 2 diabetes mellitus (T2DM) patients with long-term disease. Our study aimed to evaluate cerebral hemodynamics, systemic endothelial function and sympatho-vagal balance in a selected population of well-controlled T2DM patients with short-term disease and without cardiac autonomic neuropathy (CAN). Research Design and Methods Twenty-six T2DM patients with short-term (4.40±4.80 years) and well-controlled (HbA1C = 6.71±1.29%) disease, without any complications, treated with diet and/or metformin, were consecutively recruited. Eighteen controls, comparable by sex and age, were enrolled also. Results FMD and shear rate FMD were found to be reduced in T2DM subjects with short-term disease (8.5% SD 3.5 and 2.5 SD 1.3, respectively) compared to controls (15.4% SD 4.1 and 3.5 SD 1.4; p<.001 and p<.05). T2DM patients also displayed reduced VMR values than controls (39.4% SD 12.4 vs 51.7%, SD 15.5; p<.05). Sympatho-vagal balance was not different in T2DM patients compared to healthy subjects. FMD and shear rate FMD did not correlate with VMR in T2DM patients or in controls (p>.05). Conclusions In well-controlled T2DM patients with short-term disease cerebral hemodynamics and systemic endothelial function are altered while autonomic balance appeared to be preserved. PMID:24391751

The association of lifestyle and stress with poor glycemic control in patients with diabetes mellitus type 2: a Croatian nationwide primary care cross-sectional study.

PubMed

Bralić Lang, Valerija; Bergman Marković, Biserka; Vrdoljak, Davorka

2015-08-01

To assess lifestyle habits and self-reported stress levels among type 2 diabetes mellitus (T2DM) patients and their association with hemoglobin A1c (HbA1c) in general practitioners' (GP) offices in Croatia. 449 GPs from all Croatian regions from 2008 to 2010 consecutively recruited up to 20-25 participants diagnosed with T2DM at least 3 years prior to the study, aged ≥40 years, and scheduled for diabetes control check-ups. The recruitment period lasted six months. Lifestyle habits and self-reported stress were assessed using the questionnaire from the Croatian Adult Health Survey. The study included 10285 patients with T2DM with mean (±standard deviation) age of 65.7±10.05 years (48.1% men). Mean HbA1c level was 7.57±1.58%. 79% of participants reported insufficient physical activity, 24% reported inappropriate dietary patterns, 56% reported current alcohol consumption, 19% were current smokers, and 85% reported at least medium level of stress. Multivariate analysis showed that having received advice to stop drinking alcohol, inadequate physical activity, consumption of milk and dairy products, adding extra salt, and high level of stress were significantly associated with increased HbA1c (P < 0.05). Poor glycemic control was more frequent in patients who had several "unhealthy" lifestyle habits. These results suggest that diabetes patients in Croatia require more specific recommendations on diet, smoking cessation, exercise, and stress control.

Intelligent ensemble T-S fuzzy neural networks with RCDPSO_DM optimization for effective handling of complex clinical pathway variances.

PubMed

Du, Gang; Jiang, Zhibin; Diao, Xiaodi; Yao, Yang

2013-07-01

Takagi-Sugeno (T-S) fuzzy neural networks (FNNs) can be used to handle complex, fuzzy, uncertain clinical pathway (CP) variances. However, there are many drawbacks, such as slow training rate, propensity to become trapped in a local minimum and poor ability to perform a global search. In order to improve overall performance of variance handling by T-S FNNs, a new CP variance handling method is proposed in this study. It is based on random cooperative decomposing particle swarm optimization with double mutation mechanism (RCDPSO_DM) for T-S FNNs. Moreover, the proposed integrated learning algorithm, combining the RCDPSO_DM algorithm with a Kalman filtering algorithm, is applied to optimize antecedent and consequent parameters of constructed T-S FNNs. Then, a multi-swarm cooperative immigrating particle swarm algorithm ensemble method is used for intelligent ensemble T-S FNNs with RCDPSO_DM optimization to further improve stability and accuracy of CP variance handling. Finally, two case studies on liver and kidney poisoning variances in osteosarcoma preoperative chemotherapy are used to validate the proposed method. The result demonstrates that intelligent ensemble T-S FNNs based on the RCDPSO_DM achieves superior performances, in terms of stability, efficiency, precision and generalizability, over PSO ensemble of all T-S FNNs with RCDPSO_DM optimization, single T-S FNNs with RCDPSO_DM optimization, standard T-S FNNs, standard Mamdani FNNs and T-S FNNs based on other algorithms (cooperative particle swarm optimization and particle swarm optimization) for CP variance handling. Therefore, it makes CP variance handling more effective. Copyright © 2013 Elsevier Ltd. All rights reserved.

T3 supplementation affects ventilatory timing & glucose levels in type 2 diabetes mellitus model.

PubMed

Bollinger, Stephen S; Weltman, Nathen Y; Gerdes, A Martin; Schlenker, Evelyn H

2015-01-01

Type II diabetes mellitus (T2DM) can affect ventilation, metabolism, and fasting blood glucose levels. Hypothyroidism may be a comorbidity of T2DM. In this study T2DM was induced in 20 female Sprague Dawley rats using Streptozotocin (STZ) and Nicotinamide (N). One of experimental STZ/N groups (N=10 per group) was treated with a low dose of triiodothyronine (T3). Blood glucose levels, metabolism and ventilation (in air and in response to hypoxia) were measured in the 3 groups. STZ/N-treated rats increased fasting blood glucose compared to control rats eight days and 2 months post-STZ/N injections indicating stable induction of T2DM state. Treatments had no effects on ventilation, metabolism or body weight. After one month of T3 supplementation, there were no physiological indications of hyperthyroidism, but T3 supplementation altered ventilatory timing and decreased blood glucose levels compared to STZ/N rats. These results suggest that low levels of T3 supplementation could offer modest effects on blood glucose and ventilatory timing in this T2M model. Copyright © 2014 Elsevier B.V. All rights reserved.

Do Perceptions of Empowerment Affect Glycemic Control and Self-Care Among Adults with Type 2 Diabetes?

PubMed Central

D’Souza, Melba Sheila; Karkada, Subrahmanya Nairy; Hanrahan, Nancy P.; Venkatesaperumal, Ramesh; Amirtharaj, Anandhi

2015-01-01

Background: The Arab adult with T2DM is understudied with less known facts about the perception of empowerment and its relationship with self-care and glycemic control. Purpose: The purpose of this study was to determine the extent to which perception of empowerment by Arab adults living with Type 2 Diabetes Mellitus (T2DM) was associated with better glycemic control and self-care management. Methods: A cross-sectional descriptive study was led among 300 Arab adults living in Oman with T2DM in an outpatient diabetes clinic. The Diabetes Empowerment Scale (DES), glycosylated haemaglobin (HbA1c) and Body mass index was assessed. The DES was found to be valid and reliable for the population. ANOVA, Regression analysis, and Structural equation modeling was used for analysis. Results: The composite score and three subscales of DES were a significant and strong predictor of good glycemic control among Omani adults with T2DM (p<0.001). Age, education, duration of DM, prior DM education program and medications were significantly associated with DES. Conclusion: Diabetes nurse educators engaged in the care of adults with T2DM should assess self-empowerment and tailor interventions to increase empowerment for better glycemic control. Patient empowerment plays an essential role in maintaining self-care behaviours and HbA1c. PMID:26156908

Hypogonadism in DM1 and its relationship to erectile dysfunction.

PubMed

Antonini, Giovanni; Clemenzi, Alessandro; Bucci, Elisabetta; De Marco, Emanuela; Morino, Stefania; Di Pasquale, Antonella; Latino, Pamela; Ruga, Gilda; Lenzi, Andrea; Vanacore, Nicola; Radicioni, Antonio F

2011-07-01

Myotonic dystrophy type 1 (DM1) is characterized by both a premature appearance of age-related phenotypes and multiple organ involvement, which affects skeletal and smooth muscle as well as the eye, heart, central nervous system, and endocrine system. Although erectile dysfunction (ED) is a frequent complaint in patients with DM1, it has not been investigated in great depth. Hypogonadism, which is reported to be one of the physical causes of ED in the general population, frequently occurs in DM1. We planned this case-control study to evaluate the relationship between hypogonadism, as defined by the sexual hormone profile (FSH, LH, testosterone (T) and prolactin) and ED, as assessed by means of an internationally validated self-administered questionnaire (IIEF). DM1 patients had significantly increased mean levels of both gonadotropins (FSH and LH) (p < 0.0001) and a reduced mean level of T (p < 0.0001) when compared to controls. Twelve patients were eugonadic (normal LH, T, and FSH), while 18 displayed hormonal evidence of hypogonadism, characterized by tubular failure (increased FSH) in all the subjects and associated with interstitial failure in 14 subjects: seven with primary hypogonadism (increased LH and reduced T) and seven with compensated hypogonadism (increased LH and normal T). Patients with hormonal evidence of interstitial failure had a larger CTG expansion (p = 0.008), longer disease duration (p = 0.013), higher grade of disease (p = 0.004) and lower erectile function score (p = 0.02) than eugonadic patients. Impotence occurred in 13/14 hypogonadic patients with interstitial failure and in 5/12 eugonadic patients (p = 0.017, OR = 18.2).

GPR119 agonists: a promising approach for T2DM treatment? A SWOT analysis of GPR119.

PubMed

Kang, Sang-Uk

2013-12-01

Ever since its advent as a promising therapeutic target for type 2 diabetes mellitus (T2DM), G-protein-coupled receptor 119 (GPR119) has received much interest from the pharmaceutical industry. This interest peaked in June 2010, when Sanofi-Aventis agreed to pay Metabolex (Cymabay Therapeutics) US$375 million for MBX-2982, which was a representative orally active GPR119 agonist. However, Sanofi-Aventis opted to terminate the deal in May 2011 and another leading GPR119 agonist, GSK1292263, had a loss of efficacy during its clinical trial. In this review, I discuss the pros and cons of GPR119 through a strengths, weaknesses, opportunities, and threats (SWOT) analysis and propose development strategies for the eventual success of a GPR119 agonist development program. Copyright © 2013 Elsevier Ltd. All rights reserved.

A functional polymorphism of the TNF-{alpha} gene that is associated with type 2 DM

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

Susa, Shinji; Daimon, Makoto; Sakabe, Jun-Ichi

2008-05-09

To examine the association of the tumor necrosis factor-{alpha} (TNF-{alpha}) gene region with type 2 diabetes (DM), 11 single-nucleotide polymorphisms (SNPs) of the region were analyzed. The initial study using a sample set (148 cases vs. 227 controls) showed a significant association of the SNP IVS1G + 123A of the TNF-{alpha} gene with DM (p = 0.0056). Multiple logistic regression analysis using an enlarged sample set (225 vs. 716) revealed the significant association of the SNP with DM independently of any clinical traits examined (OR: 1.49, p = 0.014). The functional relevance of the SNP were examined by the electrophoreticmore » mobility shift assays using nuclear extracts from the U937 and NIH3T3 cells and luciferase assays in these cells with Simian virus 40 promoter- and TNF-{alpha} promoter-reporter gene constructs. The functional analyses showed that YY1 transcription factor bound allele-specifically to the SNP region and, the IVS1 + 123A allele had an increase in luciferase expression compared with the G allele.« less

Morningness-eveningness questionnaire score and metabolic parameters in patients with type 2 diabetes mellitus.

PubMed

Osonoi, Yusuke; Mita, Tomoya; Osonoi, Takeshi; Saito, Miyoko; Tamasawa, Atsuko; Nakayama, Shiho; Someya, Yuki; Ishida, Hidenori; Kanazawa, Akio; Gosho, Masahiko; Fujitani, Yoshio; Watada, Hirotaka

2014-11-01

"Morningness" and "Eveningness" represent lifestyle patterns including sleep-wake patterns. Although previous studies described a relationship between the morningness-eveningness trait and glycemic control in patients with type 2 diabetes mellitus (T2DM), the mechanism underlying this association remains unknown. The study participants comprised 725 Japanese T2DM outpatients free of history of cardiovascular diseases. Various lifestyles were analyzed using self-reported questionnaires, including morningness-eveningness questionnaire (MEQ). The relationships between morningness-eveningness trait and various biochemical parameters were investigated by linear regression analysis and logistic regression analysis. We classified the study patients into three groups, morning type (n=117), neither type (n=424) and evening type (n=184). Subjects of the evening type had high levels of alanine aminotransferase, triglyceride, fasting blood glucose and HbA1c and low high-density lipoprotein-cholesterol level in a model adjusted for age and gender. Furthermore, multivariate analysis showed that the evening type was associated with high HbA1c and estimated glomerular filtration rate even after adjustment for other lifestyle factors known to affect metabolic control. The results suggest that T2DM patients with eveningness trait are under inadequate metabolic control independent of other lifestyle factors. Thus, the evening trait of T2DM patients represents an important target for intervention to ensure appropriate metabolic function.

Association of functional SNP-1562C>T in MMP9 promoter with proliferative diabetic retinopathy in north Indian type 2 diabetes mellitus patients.

PubMed

Singh, Kanhaiya; Goyal, Prabhjot; Singh, Manju; Deshmukh, Sujit; Upadhyay, Divyesh; Kant, Sri; Agrawal, Neeraj K; Gupta, Sanjeev K; Singh, Kiran

2017-12-01

Retinal angiogenesis is a hallmark of diabetic retinopathy. Matrix Metalloproteinases (MMPs) are involved in degradation of extracellular matrix (ECM). Functional SNP-1562C>T in the promoter of the MMP-9 gene results increase in transcriptional activity. The present work was designed to evaluate the contribution of functional SNP-1562C>T of MMP-9 gene to the risk of proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM) patients in north Indian Population. This Case control study comprised of a total of 645 individuals in which 320 were T2DM patients out of which 73 had PDR, 98 had non- proliferative diabetic retinopathy (NPDR), 149 T2DM cases without any eye related disease (DM) and 325 non diabetic healthy individuals as controls (non DM controls). Genotyping for SNP-1562C>T of MMP-9 was done by polymerase chain reactions followed by restriction analyses with specific endonucleases (PCR-RFLP). DNA sequencing was used to ascertain PCR-RFLP results. T allele frequency in PDR patients was 32.1%, 20.4% in NPDR, 15.4% in DM and 13.7% in controls. Statistically significant difference was observed in both allele and genotype distribution between the PDR versus non-DM control group (p<0.0001 by T allele; p=0.002 by TT and p<0.0001 by CT genotype). The present study suggests that the functional SNP-1562C>T in the promoter of the MMP-9 gene could be regarded as a major risk factor for PDR as increased MMP-9 production from high expressing T allele may promote retinal angiogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Size, density and cholesterol load of HDL predict microangiopathy, coronary artery disease and β-cell function in men with T2DM.

PubMed

Hermans, Michel P; Amoussou-Guenou, K Daniel; Bouenizabila, Evariste; Sadikot, Shaukat S; Ahn, Sylvie A; Rousseau, Michel F

The role of high-density lipoprotein cholesterol (HDL-C) as modifiable risk factor for cardiovascular (CV) disease is increasingly debated, notwithstanding the finding that small-dense and dysfunctional HDL are associated with the metabolic syndrome and T2DM. In order to better clarify the epidemiological risk related to HDL of different size/density, without resorting to direct measures, it would seem appropriate to adjust HDL-C to the level of its main apolipoprotein (apoA-I), thereby providing an [HDL-C/apoA-I] ratio. The latter allows not only to estimate an average size for HDLs, but also to derive indices on particle number, cholesterol load, and density. So far, the potential usefulness of this ratio in diabetes is barely addressed. To this end, we sorted 488 male patients with T2DM according to [HDL-C/apoA-I] quartiles (Q), to determine how the ratio relates to cardiometabolic risk, β-cell function, glycaemic control, and micro- and macrovascular complications. Five lipid parameters were derived from the combined determination of HDL-C and apoA-I, namely HDL size; particle number; cholesterol load/particle; apoA-I/particle; and particle density. An unfavorable cardiometabolic profile characterized patients from QI and QII, in which HDLs were pro-atherogenic, denser and apoA-I-depleted. By contrast, QIII patients had an [HDL-C/apoA-I] ratio close to that of non-diabetic controls. QIV patients had better than average HDL size and composition, and in those patients whose [HDL-C/apoA-I] ratio was above normal, a more favorable phenotype was observed regarding lifestyle, anthropometry, metabolic comorbidities, insulin sensitivity, MetS score/severity, glycaemic control, and target-organ damage pregalence in small or large vessels. In conclusion, [HDL-C/apoA-I] and the resulting indices of HDL composition and functionality predict macrovascular risk and β-cell function decline, as well as overall microangiopathic risk, suggesting that this ratio could serve

Inverse Association of Plasma Chromium Levels with Newly Diagnosed Type 2 Diabetes: A Case-Control Study

PubMed Central

Chen, Sijing; Jin, Xiaoling; Shan, Zhilei; Li, Shuzhen; Yin, Jiawei; Sun, Taoping; Luo, Cheng; Yang, Wei; Yao, Ping; Yu, Kaifeng; Zhang, Yan; Cheng, Qian; Cheng, Jinquan; Bao, Wei; Liu, Liegang

2017-01-01

Chromium has long been known as an enhancer of insulin action. However, the role of chromium in the development of type 2 diabetes mellitus (T2DM) in humans remains controversial. The current study aimed to examine the associations of plasma chromium levels with T2DM and pre-diabetes mellitus (pre-DM). We conducted a case-control study involving 1471 patients with newly diagnosed T2DM, 682 individuals with newly diagnosed pre-DM, and 2290 individuals with normal glucose tolerance in a Chinese population from 2009 to 2014. Plasma chromium was measured by inductively coupled plasma mass spectrometry. Plasma chromium levels were lower in the T2DM and pre-DM groups than in the control group (median: 3.68 μg/L, 3.61 μg/L, 3.97 μg/L, respectively, p < 0.001). After adjustment for potential confounding factors, the odds ratios (95% confidence interval) for T2DM across increasing quartiles of plasma chromium levels were 1 (referent), 0.67 (0.55–0.83), 0.64 (0.51–0.79), and 0.58 (0.46–0.73), respectively (p for trend <0.001). The corresponding odds ratios (95% confidence interval) for pre-DM were 1 (referent), 0.70 (0.54–0.91), 0.67 (0.52–0.88), and 0.58 (0.43–0.78), respectively (p for trend < 0.001). Our results indicated that plasma chromium concentrations were inversely associated with T2DM and pre-DM in Chinese adults. PMID:28304331

Inverse Association of Plasma Chromium Levels with Newly Diagnosed Type 2 Diabetes: A Case-Control Study.

PubMed

Chen, Sijing; Jin, Xiaoling; Shan, Zhilei; Li, Shuzhen; Yin, Jiawei; Sun, Taoping; Luo, Cheng; Yang, Wei; Yao, Ping; Yu, Kaifeng; Zhang, Yan; Cheng, Qian; Cheng, Jinquan; Bao, Wei; Liu, Liegang

2017-03-17

Chromium has long been known as an enhancer of insulin action. However, the role of chromium in the development of type 2 diabetes mellitus (T2DM) in humans remains controversial. The current study aimed to examine the associations of plasma chromium levels with T2DM and pre-diabetes mellitus (pre-DM). We conducted a case-control study involving 1471 patients with newly diagnosed T2DM, 682 individuals with newly diagnosed pre-DM, and 2290 individuals with normal glucose tolerance in a Chinese population from 2009 to 2014. Plasma chromium was measured by inductively coupled plasma mass spectrometry. Plasma chromium levels were lower in the T2DM and pre-DM groups than in the control group (median: 3.68 μg/L, 3.61 μg/L, 3.97 μg/L, respectively, p < 0.001). After adjustment for potential confounding factors, the odds ratios (95% confidence interval) for T2DM across increasing quartiles of plasma chromium levels were 1 (referent), 0.67 (0.55-0.83), 0.64 (0.51-0.79), and 0.58 (0.46-0.73), respectively ( p for trend <0.001). The corresponding odds ratios (95% confidence interval) for pre-DM were 1 (referent), 0.70 (0.54-0.91), 0.67 (0.52-0.88), and 0.58 (0.43-0.78), respectively ( p for trend < 0.001). Our results indicated that plasma chromium concentrations were inversely associated with T2DM and pre-DM in Chinese adults.

Identification of individualised empirical models of carbohydrate and insulin effects on T1DM blood glucose dynamics

NASA Astrophysics Data System (ADS)

Cescon, Marzia; Johansson, Rolf; Renard, Eric; Maran, Alberto

2014-07-01

One of the main limiting factors in improving glucose control for type 1 diabetes mellitus (T1DM) subjects is the lack of a precise description of meal and insulin intake effects on blood glucose. Knowing the magnitude and duration of such effects would be useful not only for patients and physicians, but also for the development of a controller targeting glycaemia regulation. Therefore, in this paper we focus on estimating low-complexity yet physiologically sound and individualised multi-input single-output (MISO) models of the glucose metabolism in T1DM able to reflect the basic dynamical features of the glucose-insulin metabolic system in response to a meal intake or an insulin injection. The models are continuous-time second-order transfer functions relating the amount of carbohydrate of a meal and the insulin units of the accordingly administered dose (inputs) to plasma glucose evolution (output) and consist of few parameters clinically relevant to be estimated. The estimation strategy is continuous-time data-driven system identification and exploits a database in which meals and insulin boluses are separated in time, allowing the unique identification of the model parameters.

Psyllium fiber improves glycemic control proportional to loss of glycemic control: a meta-analysis of data in euglycemic subjects, patients at risk of type 2 diabetes mellitus, and patients being treated for type 2 diabetes mellitus.

PubMed

Gibb, Roger D; McRorie, Johnson W; Russell, Darrell A; Hasselblad, Vic; D'Alessio, David A

2015-12-01

A number of health benefits are associated with intake of soluble, viscous, gel-forming fibers, including reduced serum cholesterol and the attenuation of postprandial glucose excursions. We assess the effects of psyllium, which is a soluble, gel-forming, nonfermented fiber supplement, on glycemic control in patients who were being treated for type 2 diabetes mellitus (T2DM) and in patients who were at risk of developing T2DM. A comprehensive search was performed of available published literature (Scopus scientific database) and clinical records stored by Procter & Gamble with the use of key search terms to identify clinical studies that assessed the glycemic effects of psyllium in nondiabetic, pre-T2DM, and T2DM patients. We identified 35 randomized, controlled, clinical studies that spanned 3 decades and 3 continents. These data were assessed in 8 meta-analyses. In patients with T2DM, multiweek studies (psyllium dosed before meals) showed significant improvement in both the fasting blood glucose (FBG) concentration (-37.0 mg/dL; P < 0.001) and glycated hemoglobin (HbA1c) [-0.97% (-10.6 mmol/mol); P = 0.048]. Glycemic effects were proportional to baseline FBG; no significant glucose lowering was observed in euglycemic subjects, a modest improvement was observed in subjects with pre-T2DM, and the greatest improvement was observed in subjects who were being treated for T2DM. These data indicate that psyllium would be an effective addition to a lifestyle-intervention program. The degree of psyllium's glycemic benefit was commensurate with the loss of glycemic control. Because the greatest effect was seen in patients who were being treated for T2DM, additional studies are needed to determine how best to incorporate psyllium into existing prevention and treatment algorithms with concomitant hypoglycemic medications. © 2015 American Society for Nutrition.

Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes

PubMed Central

Fields, Aaron J.; Berg-Johansen, Britta; Metz, Lionel N.; Miller, Stephanie; La, Brandan; Liebenberg, Ellen C.; Coughlin, Dezba G.; Graham, James L.; Stanhope, Kimber L.; Havel, Peter J.; Lotz, Jeffrey C.

2015-01-01

Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis and biomechanical behavior. Coccygeal motion segments were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 ± 7 days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end-product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia-inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress and AGE/RAGE-mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D. PMID:25641259

Poor glycemic control is associated with the risk of subclinical hypothyroidism in patients with type 2 diabetes mellitus.

PubMed

Cho, Jae Ho; Kim, Ho Jin; Lee, Jun Ho; Park, Il Rae; Moon, Jun Sung; Yoon, Ji Sung; Lee, In-Kyu; Won, Kyu Chang; Lee, Hyoung Woo

2016-07-01

Overt hypothyroidism is frequently found in patients with type 2 diabetes mellitus (T2DM), but it remains unknown the relationship between subclinical hypothyroidism (SCH) and T2DM. We attempt to evaluate the difference in prevalence of SCH between patients with T2DM and general population, and the association between SCH and glycemic control status ofdiabetic patients. This was cross-sectional study. Total 8,528 subjects who visited for health check-up were recruited. SCH was defined as an elevated level of serum thyroid stimulating hormone (> 4.0 mIU/L) with a normal level of free thyroxine. T2DM group was categorized into three groups by glycosylated hemoglobin (HbA1c): < 7% (reference), ≥ 7% and < 9%, ≥ 9%. Finally, 7,966 subjects were included. The prevalence of SCH was not different between healthy controls and subjects with T2DM (8.1% vs. 7.4%, p = 0.533; in men, 5.7% vs. 5.1%, p = 0.573; in women, 10.9% vs. 11.7%, p = 0.712), but it was increased with highest HbA1c group more than well controlled group, especially in women. The risk of SCH was increased by group with poorer glycemic control; the odds ratio for HbA1c ≥ 9% compared to < 7% was 2.52 (95% confidence interval [CI], 1.09 to 5.86; p = 0.031), and 4.58 (95% CI, 1.41 to 14.87; p = 0.011) in women, but not significant in men. The prevalence of SCH was similar between T2DM and healthy group. Poor glycemic control in T2DM was obviously associated with the risk of SCH, especially in elderly women. These results suggest SCH as comorbidity may be considered in elderly women with poor glycemic control.

Prevalence and control of type 2 diabetes mellitus among primary care physicians in Spain. PRISMA Study.

PubMed

Franch-Nadal, Josep; Mediavilla-Bravo, Javier; Mata-Cases, Manuel; Mauricio, Didac; Asensio, David; Sarroca, Jordi

2017-05-01

To describe the prevalence of known and ignored type 2 diabetes mellitus (T2DM) among primary care physicians (PCP), as well as the treatment used and the degree of metabolic control reached. Descriptive cross-sectional study on national level. The participants were randomly selected PCPs, members of the redGDPS Foundation. A total of 495 PCP were enrolled. Capillary HbA 1c measurement was done with a A1CNow+ ® device and a diabetes-related survey specifically designed for the study was administered to the participants. The total prevalence of T2DM was 11.1% (95% CI 8.33-13.9) (known disease 8,1% and ignored disease 3.0%). The prevalence of prediabetes was 16.2% (95% CI 13.0-19.4). A total of 62.5% of PCPs with known T2DM reached HbA 1c <7% and 15% had HbA 1c >8.5%. Control of blood pressure (BP<140/90mmHg) was reached in 87.5% and control of LDL cholesterol<130mg/dl with no history of cardiovascular disease was reached in 88.6% of cases of known T2DM. In the PCPs with a history of macrovascular disease, good control of LDL was reached in 42.9% of the cases. A total of 12.5% were active smokers. A total of 71.4% of PCPs with known T2DM self-treated their own disease, usually with 2 or more drugs (51.4%). The most commonly used drug was metformin (74.3%) followed by iDPP4 (48.6%). PCPs with T2DM have better metabolic control than the general population. It is necessary to study whether PCPs with T2DM may have greater adherence to treatment and do they achieve a better metabolic control. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Economic burden of inadequate symptom control among US commercially insured patients with irritable bowel syndrome with diarrhea.

PubMed

Buono, Jessica L; Mathur, Kush; Averitt, Amelia J; Andrae, David A

2017-04-01

To assess healthcare resource use and costs among irritable bowel syndrome (IBS) with diarrhea (IBS-D) patients with and without evidence of inadequate symptom control on current prescription therapies and estimate incremental all-cause costs associated with inadequate symptom control. IBS-D patients aged ≥18 years with ≥1 medical claim for IBS (ICD-9-CM 564.1x) and either ≥2 claims for diarrhea (ICD-9-CM 787.91, 564.5x), ≥1 claim for diarrhea plus ≥1 claim for abdominal pain (ICD-9-CM 789.0x), or ≥1 claim for diarrhea plus ≥1 pharmacy claim for a symptom-related prescription within 1 year of an IBS diagnosis were identified from the Truven Health MarketScan database. Inadequate symptom control, resource use, and costs were assessed up to 1 year following the index date. Inadequate symptom control included any of the following: (1) switch or (2) addition of new symptom-related therapy; (3) IBS-D-related inpatient or emergency room (ER) admission; (4) IBS-D-related medical procedure; (5) diagnosis of condition indicating treatment failure; or (6) use of a more aggressive prescription. Generalized linear models assessed incremental costs of inadequate symptom control. Of 20,624 IBS-D patients (mean age = 48.5 years; 77.8% female), 66.4% had evidence of inadequate symptom control. Compared to those without inadequate symptom control, patients with evidence of inadequate symptom control had significantly more hospitalizations (12.0% vs 6.0%), ER visits (37.1% vs 22.6%), use of outpatient services (73.0% vs 60.7%), physician office visits (mean 11.0 vs 8.1), and prescription fills (mean 40.0 vs 26.7) annually (all p < .01). Incremental costs associated with inadequate symptom control were $3,065 (2013 US dollars), and were driven by medical service costs ($2,391; 78%). Study included US commercially insured patients only and inferred IBS-D status and inadequate symptom control from claims. Inadequate symptom control associated with available IBS

Comparison of nutrient intakes in South Asians with type 2 diabetes mellitus and controls living in the United States.

PubMed

Shah, Meena; Vasandani, Chandna; Adams-Huet, Beverley; Garg, Abhimanyu

2018-04-01

Despite having a high risk for type 2 diabetes mellitus (T2DM), little is known about the relationship between nutrient intakes and T2DM in South Asians (SA) in the U.S. In addition, the available data are limited to a few macronutrients and collected using subjective measures. Therefore, we compared macro- and micro-nutrient intakes of SA migrants with and without T2DM using an objective measure. SA in the U.S. with T2DM (n = 44) and controls (n = 33) reported their dietary intake using image-assisted dietary assessment method. They took pictures of all foods/drinks consumed on two weekdays and one weekend day. Age, gender distribution, and body mass index were similar across the two groups. SA with T2DM, as compared to controls, consumed less total energy (mean difference: 499 kcal/d; p < .0001), linoleic acid (3.6 g/d; p = .003), dietary fiber (8.6 g/d; p < .0001), vitamin A (262 µg/d; p = .003), vitamin E (2.7 mg/d; p = .007), calcium (133 mg/d; p = .01), magnesium (116 mg/d; p < .0001), zinc (1.4 mg/d; p = .004), potassium (754 mg/d; p < .0001), and β-carotene (1761 µg/d; p = .03). SA with T2DM, as compared to controls, were significantly more likely not to meet the requirements for linoleic acid, dietary fiber, vitamin E, calcium, magnesium, zinc, and potassium (p < .05). SA with T2DM, compared to controls, consume less total energy and have lower consumption of many nutrients associated with reduced risk of T2DM. Dietary interventions to reduce risk for T2DM are warranted in SA. Copyright © 2018 Elsevier B.V. All rights reserved.

RETRACTED: Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population.

PubMed

Zhou, Tian-Biao; Guo, Xue-Feng; Jiang, Zongpei; Li, Hong-Yan

2015-12-01

The following article has been included in a multiple retraction: Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January

Attitudes and Barriers to Exercise in Adults with Type 1 Diabetes (T1DM) and How Best to Address Them: A Qualitative Study

PubMed Central

Lascar, Nadia; Kennedy, Amy; Hancock, Beverley; Jenkins, David; Andrews, Robert C.

2014-01-01

Background Regular physical activity has recognised health benefits for people with T1DM. However a significant proportion of them do not undertake the recommended levels of activity. Whilst questionnaire-based studies have examined barriers to exercise in people with T1DM, a formal qualitative analysis of these barriers has not been undertaken. Our aims were to explore attitudes, barriers and facilitators to exercise in patients with T1DM. Methodology A purposeful sample of long standing T1DM patients were invited to participate in this qualitative study. Twenty-six adults were interviewed using a semi-structured interview schedule to determine their level of exercise and barriers to initiation and maintenance of an exercise programme. Principal findings Six main barriers to exercise were identified: lack of time and work related factors; access to facilities; lack of motivation; embarrassment and body image; weather; and diabetes specific barriers (low levels of knowledge about managing diabetes and its complications around exercise). Four motivators to exercise were identified: physical benefits from exercise; improvements in body image; enjoyment and the social interaction of exercising at gym or in groups. Three facilitators to exercise were identified: free or reduced admission to gyms and pools, help with time management, and advice and encouragement around managing diabetes for exercise. Significance Many of the barriers to exercise in people with T1DM are shared with the non-diabetic population. The primary difference is the requirement for education about the effect of exercise on diabetes control and its complications. There was a preference for support to be given on a one to one basis rather than in a group environment. This suggests that with the addition of the above educational requirements, one to one techniques that have been successful in increasing activity in patients with other chronic disease and the general public should be successful in

Attitudes and barriers to exercise in adults with type 1 diabetes (T1DM) and how best to address them: a qualitative study.

PubMed

Lascar, Nadia; Kennedy, Amy; Hancock, Beverley; Jenkins, David; Andrews, Robert C; Greenfield, Sheila; Narendran, Parth

2014-01-01

Regular physical activity has recognised health benefits for people with T1DM. However a significant proportion of them do not undertake the recommended levels of activity. Whilst questionnaire-based studies have examined barriers to exercise in people with T1DM, a formal qualitative analysis of these barriers has not been undertaken. Our aims were to explore attitudes, barriers and facilitators to exercise in patients with T1DM. A purposeful sample of long standing T1DM patients were invited to participate in this qualitative study. Twenty-six adults were interviewed using a semi-structured interview schedule to determine their level of exercise and barriers to initiation and maintenance of an exercise programme. Six main barriers to exercise were identified: lack of time and work related factors; access to facilities; lack of motivation; embarrassment and body image; weather; and diabetes specific barriers (low levels of knowledge about managing diabetes and its complications around exercise). Four motivators to exercise were identified: physical benefits from exercise; improvements in body image; enjoyment and the social interaction of exercising at gym or in groups. Three facilitators to exercise were identified: free or reduced admission to gyms and pools, help with time management, and advice and encouragement around managing diabetes for exercise. Many of the barriers to exercise in people with T1DM are shared with the non-diabetic population. The primary difference is the requirement for education about the effect of exercise on diabetes control and its complications. There was a preference for support to be given on a one to one basis rather than in a group environment. This suggests that with the addition of the above educational requirements, one to one techniques that have been successful in increasing activity in patients with other chronic disease and the general public should be successful in increasing activity in patients with T1DM.

An Integrative Review of Self-Efficacy Measurement Instruments in Youth with Type 1 Diabetes (T1DM)

PubMed Central

Rasbach, Lisa; Jenkins, Carolyn; Laffel, Lori

2014-01-01

Purpose The purpose of this study is to assess the extant literature on instruments used to measure self-efficacy in youth with type 1 diabetes (T1DM) and their caregivers and to critically evaluate these measurements. Methods An integrative review (2003–2013) was conducted searching PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and U.S. National Library of Medicine PubMed service (PubMed) databases using key words diabetes, type 1 diabetes, and self-efficacy. The authors reviewed the resulting294 references for inclusion criteria of (a) sample of youth with T1DM or sample of caregivers of youth with T1DM, (b) description of the self-efficacy instrument as primary research, and (c) the instrument measured self-efficacy specifically related to diabetes management. Forty-five articles out of the initial 294 met criteria. Results Of the 45 articles, 10 different self-efficacy instruments were identified. The primary theoretical framework used was Bandura’s social cognitive theory and model of self-efficacy. Most participants were white middle class T1DM youth. Evaluations to assess validity often were not reported; however, a majority of studies reported high internal consistency of the instruments. Conclusions Sample homogeneity could limit the applicability of results to certain patient populations. Further psychometric analysis, including validity assessments, should be conducted in more diverse samples. Development of valid and reliable instruments for measuring self-efficacy that are sensitive to change across a wider caregiver base over time is necessary. While this review examined reliable and valid instruments used in research, future opportunities include evaluation of measuring self-efficacy in T1DM youth exposed to recent advances in diabetes management technologies. PMID:25216655

Association between Low-density Lipoprotein Receptor-related Protein 5 Polymorphisms and Type 2 Diabetes Mellitus in Han Chinese: a Case-control Study.

PubMed

You, Hai Fei; Zhao, Jing Zhi; Zhai, Yu Jia; Yin, Lei; Pang, Chao; Luo, Xin Ping; Zhang, Ming; Wang, Jin Jin; Li, Lin Lin; Wang, Yan; Wang, Qian; Wang, Bing Yuan; Ren, Yong Cheng; Hu, Dong Sheng

2015-07-01

To investigate the association between low-density lipoprotein receptor-related protein 5 (LRP5) variants (rs12363572 and rs4930588) and type 2 diabetes mellitus (T2DM) in Han Chinese. A total of 1842 T2DM cases (507 newly diagnosed cases and 1335 previously diagnosed cases) and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms (SNPs). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to describe the strength of the association by logistic regression. In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2DM, even after adjusting for relevant covariates. When stratified by body mass index (BMI), the two SNPs were also not associated with T2DM. Among the 3 common haplotypes, only haplotype TT was associated with reduced risk of T2DM (OR 0.820, 95% CI 0.732-0.919). In addition, rs12363572 was associated with BMI (P<0.001) and rs4930588 was associated with triglyceride levels (P=0.043) in 507 newly diagnosed T2DM cases but not in healthy controls. No LRP5 variant was found to be associated with T2DM in Han Chinese, but haplotype TT was found to be associated with T2DM. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Roux-en-Y Gastric Bypass Surgery Suppresses Hepatic Gluconeogenesis and Increases Intestinal Gluconeogenesis in a T2DM Rat Model.

PubMed

Yan, Yong; Zhou, Zhou; Kong, Fanzhi; Feng, Suibin; Li, Xuzhong; Sha, Yanhua; Zhang, Guangjun; Liu, Haijun; Zhang, Haiqing; Wang, Shiguang; Hu, Cheng; Zhang, Xueli

2016-11-01

Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and intestinal morphological adaption, as well as hepatic and intestinal gluconeogenesis. Twenty adult male T2DM rats induced by high-fat diet and low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, and serum lipid profiles were assessed to evaluate metabolic changes. Intestinal sections were stained with hematoxylin and eosin (H&E) for light microscopy examination. The messenger RNA (mRNA) and protein expression levels of key regulatory enzymes of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase)] were determined through reverse-transcription PCR (RT-PCR) and Western blotting, respectively. RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum triglyceride (TG) and free fatty acid (FFA) levels. The jejunum and ileum exhibited a marked increase in the length and number of intestinal villi after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK and G6Pase in the liver and upregulated expression of these enzymes in the jejunum and ileum tissues. RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The small intestine shows hyperplasia and hypertrophy after RYGB. Meanwhile, our study demonstrated that the reduced hepatic gluconeogenesis and increased intestinal gluconeogenesis may contribute to improved glucose homeostasis after RYGB.

Glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with renal complications

PubMed Central

Huri, Hasniza Zaman; Lim, Lay Peng; Lim, Soo Kun

2015-01-01

Background Good glycemic control can delay the progression of kidney diseases in type 2 diabetes mellitus (T2DM) patients with renal complications. To date, the association between antidiabetic agents and glycemic control in this specific patient population is not well established. Purpose This study aimed to identify antidiabetic regimens as well as other factors that associated with glycemic control in T2DM patients with different stages of chronic kidney disease (CKD). Patients and methods This retrospective, cross-sectional study involved 242 T2DM inpatients and outpatients with renal complications from January 2009 to March 2014 and was conducted in a tertiary teaching hospital in Malaysia. Glycated hemoglobin (A1C) was used as main parameter to assess patients’ glycemic status. Patients were classified to have good (A1C <7%) or poor glycemic control (A1C ≥7%) based on the recommendations of the American Diabetes Association. Results Majority of the patients presented with CKD stage 4 (43.4%). Approximately 55.4% of patients were categorized to have poor glycemic control. Insulin (57.9%) was the most commonly prescribed antidiabetic medication, followed by sulfonylureas (43%). Of all antidiabetic regimens, sulfonylureas monotherapy (P<0.001), insulin therapy (P=0.005), and combination of biguanides with insulin (P=0.038) were found to be significantly associated with glycemic control. Other factors including duration of T2DM (P=0.004), comorbidities such as anemia (P=0.024) and retinopathy (P=0.033), concurrent medications such as erythropoietin therapy (P=0.047), α-blockers (P=0.033), and antigouts (P=0.003) were also correlated with A1C. Conclusion Identification of factors that are associated with glycemic control is important to help in optimization of glucose control in T2DM patients with renal complication. PMID:26300627

The relationship between vitronectin and hepatic insulin resistance in type 2 diabetes mellitus.

PubMed

Cao, Yan; Li, Xinyu; Lu, Chong; Zhan, Xiaorong

2018-05-18

The World Health Organization (WHO) estimates that approximately 300 million people will suffer from diabetes mellitus by 2025. Type 2 diabetes mellitus (T2DM) is much more prevalent. T2DM comprises approximately 90% of diabetes mellitus cases, and it is caused by a combination of insulin resistance and inadequate compensatory insulin secretory response. In this study, we aimed to compare the plasma vitronectin (VN) levels between patients with T2DM and insulin resistance (IR) and healthy controls. Seventy patients with IR and 70 age- and body mass index (BMI)-matched healthy controls were included in the study. The insulin, Waist-to-Hip Ratio (WHR), C-peptide (CP) and VN levels of all participants were examined. The homeostasis model of assessment for insulin resistence index (HOMA-IR (CP)) formula was used to calculate insulin resistance. The levels of BMI, fasting plasma gluose (FPG), 2-hour postprandial glucose (2hPG), glycated hemoglobins (HbA1c), and HOMA-IR (CP) were significantly elevated in case group compared with controls. VN was found to be significantly decreased in case group. (VN Mean (Std): 8.55 (2.92) versus 12.88 (1.26) ng/mL p < 0.001). Multiple linear regression analysis was performed. This model explained 43.42% of the total variability of VN. Multiple linear regression analysis showed that HOMA-IR (CP) and age independently predicted VN levels. The VN may be a candidate target for the appraisal of hepatic insulin resistance in patients with T2DM.

The influence of selenium status on body composition, oxidative DNA damage and total antioxidant capacity in newly diagnosed type 2 diabetes mellitus: A case-control study.

PubMed

Othman, Fatimah Binti; Mohamed, Hamid Jan Bin Jan; Sirajudeen, K N S; Noh, Mohd Fairulnizal B Md; Rajab, Nor Fadilah

2017-09-01

Selenium is involved in the complex system of defense against oxidative stress in diabetes through its biological function of selenoproteins and the antioxidant enzyme. A case-control study was carried out to determine the association of plasma selenium with oxidative stress and body composition status presented in Type 2 Diabetes Mellitus (T2DM) patient and healthy control. This study involved 82 newly diagnosed T2DM patients and 82 healthy controls. Plasma selenium status was determined with Graphite Furnace Atomic Absorption Spectrometry. Body Mass Index, total body fat and visceral fat was assessed for body composition using Body Composition Analyzer (TANITA). Oxidative DNA damage and total antioxidant capacity were determined for oxidative stress biomarker status. In age, gender and BMI adjustment, no significant difference of plasma selenium level between T2DM and healthy controls was observed. There was as a significant difference of Oxidative DNA damage and total antioxidant capacity between T2DM patients and healthy controls with tail DNA% 20.62 [95% CI: 19.71,21.49] (T2DM), 17.67 [95% CI: 16.87,18.56] (control); log tail moment 0.41[95% CI: 0.30,0.52] (T2DM), 0.41[95% CI: 0.30,0.52] (control); total antioxidant capacity 0.56 [95% CI: 0.54,0.58] (T2DM), 0.60 [95% CI: 0.57,0.62] (control). Waist circumference, BMI, visceral fat, body fat and oxidative DNA damage in the T2DM group were significantly lower in the first plasma selenium tertile (38.65-80.90μg/L) compared to the second (80.91-98.20μg/L) and the third selenium tertiles (98.21-158.20μg/L). A similar trend, but not statistically significant, was observed in the control group. Copyright © 2016 Elsevier GmbH. All rights reserved.

PPARγ gene C161T substitution alters lipid profile in Chinese patients with coronary artery disease and type 2 diabetes mellitus

PubMed Central

2010-01-01

Background Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor, which regulates gene expression of the key proteins involved in lipid metabolism, vascular inflammation, and proliferation. PPARγ may contribute to attenuating atherogenesis and postangioplasty restenosis. PPARγ C161→T substitution is associated with a reduced risk of coronary artery disease (CAD). Whether or not the gene substitution alters the risk of CAD in type 2 diabetes mellitus (T2DM) patients remains unclear. Methods A total of 556 unrelated subjects from a Chinese Han population, including 89 healthy subjects, 78 CAD patients, 86 T2DM patients, and 303 CAD combined with T2DM patients, were recruited to enroll in this study. PPARγC161→T gene polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphisms. Plasma levels of lipoproteins, apolipoproteins, glucose, and insulin were measured by ELISA or radioimmunoassay (RIA). The coronary artery lesions were evaluated by coronary angiography. Results The frequency of the 161T allele in CAD, T2DM, and CAD combined with T2DM patients was similar to that observed in the healthy control group. However, in CAD combined with T2DM patients, the group with angiographically documented moderate stenoses had a higher frequency of the 161T allele in comparison to the group with severe stenoses (P < 0.05). Moreover, in CAD with T2DM patients, the triglyceride levels and apoB in CC homozygote carriers were significantly higher than those in "T" allele carriers. Conclusions PPARγC161→T genotypes weren't significantly associated with the risk of CAD, but were markedly correlated with severity of disease vessels in patients with CAD and T2DM. Furthermore, PPARγC161→T substitution was associated with an altered adipose, but not glucose metabolism. These results indicate that the PPARγ C161→T polymorphism may reduce the risk of severe atherogenesis by modulation of

Cost-effectiveness of dapagliflozin (Forxiga®) added to metformin compared with sulfonylurea added to metformin in type 2 diabetes in the Nordic countries.

PubMed

Sabale, Ugne; Ekman, Mattias; Granström, Ola; Bergenheim, Klas; McEwan, Phil

2015-02-01

The aim of this study was to assess the long-term cost-effectiveness of dapagliflozin (Forxiga(®)) added to metformin, compared with sulfonylurea (SU) added to metformin, in Nordic Type 2 diabetes mellitus (T2DM) patients inadequately controlled on metformin. Data from a 52-week clinical trial comparing dapagliflozin and SU in combination with metformin was used in a Cardiff simulation model to estimate long term diabetes-related complications in a cohort of T2DM patients. Costs and QALYs were calculated from a healthcare provider perspective and estimated over a patient's lifetime. Compared with metformin+SU, the cost per QALY gained with dapagliflozin+metformin was €7944 in Denmark, €5424 in Finland, €4769 in Norway, and €6093 in Sweden. Metformin+dapagliflozin was associated with QALY gains ranging from 0.236 in Norway to 0.278 in Sweden and incremental cost ranging from €1125 in Norway to €1962 in Denmark. Results were robust across both one-way and probabilistic sensitivity analyses. Results were driven by weight changes associated with each treatment. Results indicate that metformin+dapagliflozin is associated with gains in QALY compared with metformin+SU in Nordic T2DM patients inadequately controlled on metformin. Dapagliflozin treatment is a cost-effective treatment alternative for Type 2 diabetes in all four Nordic countries. Copyright © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Association between glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with cardiovascular complications

PubMed Central

Huri, Hasniza Zaman; Ling, Doris Yew Hui; Ahmad, Wan Azman Wan

2015-01-01

Purpose Cardiovascular disease (CVD) is a macrovascular complication in patients with type 2 diabetes mellitus (T2DM). To date, glycemic control profiles of antidiabetic drugs in cardiovascular (CV) complications have not been clearly elucidated. Therefore, this study was conducted retrospectively to assess the association of antidiabetic drugs and glycemic control with CV profiles in T2DM patients. The association of concurrent medications and comorbidities with glycemic control was also investigated. Methods A total of 220 T2DM patients from the University of Malaya Medical Centre, Malaysia, who had at least one CV complication and who had been taking at least one antidiabetic drug for at least 3 months, were included. The associations of antidiabetics, cardiovascular diseases, laboratory parameters, concurrent medications, comorbidities, demographics, and clinical characteristics with glycemic control were investigated. Results Sulfonylureas in combination (P=0.002) and sulfonylurea monotherapy (P<0.001) were found to be associated with good glycemic control, whereas insulin in combination (P=0.051), and combination biguanides and insulin therapy (P=0.012) were found to be associated with poor glycemic control. Stroke (P=0.044) was the only type of CVD that seemed to be significantly associated with good glycemic control. Other factors such as benign prostatic hyperplasia (P=0.026), elderly patients (P=0.018), low-density lipoprotein cholesterol levels (P=0.021), and fasting plasma glucose (P<0.001) were found to be significantly correlated with good glycemic control. Conclusion Individualized treatment in T2DM patients with CVDs can be supported through a better understanding of the association between glycemic control and CV profiles in T2DM patients. PMID:26316711

Management of obesity in patients with type 2 diabetes mellitus in primary care.

PubMed

Mohammad, Shoaib; Ahmad, Jamal

2016-01-01

Obesity and being overweight is the most powerful risk factor accounting for 80-90% of patients with type 2 diabetes mellitus (T2DM). The epidemic of obesity is driving the diabetes epidemic to alarming levels and primary care is becoming an important setting for obesity management in T2DM in India. Yet many primary care providers feel ill-equipped or inadequately supported to address obesity in patients with diabetes. This article reviews the most recent and strongest evidence-based strategies that may aid physicians in management of obesity in patients with T2DM in primary care. A systematic literature search of MEDLINE using the search terms Obesity, Obesity in T2DM, weight loss and Primary Care was conducted. The American Diabetes Association, National Institute for Health, National Institute of Health and Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN) and World Health Organization websites were also searched. Most studies in this area are observational in design with few randomized controlled trials (RCTs). Articles and studies involving meta-analysis or RCTs were preferred over other types. Effective weight management treatment in T2DM patient can be implemented in the primary care setting. Evidence based individualized lifestyle and pharmacologic measures supported by behavioral intervention and counseling with appropriate and informed surgical referrals has the potential to improve the success of weight management within primary care. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Clinical characteristics and patient-reported outcomes in patients with inadequately controlled rheumatoid arthritis despite ongoing treatment.

PubMed

Taylor, Peter C; Alten, Rieke; Gomez-Reino, Juan J; Caporali, Roberto; Bertin, Philippe; Sullivan, Emma; Wood, Robert; Piercy, James; Vasilescu, Radu; Spurden, Dean; Alvir, Jose; Tarallo, Miriam

2018-01-01

Despite the wide array of treatments available for rheumatoid arthritis (RA), some patients continue to report unmet clinical needs. We investigated the extent of inadequate disease control in patients with RA. Data were drawn from the Adelphi 2014 RA Disease-Specific Program in France, Germany, Italy, Spain and the UK. Rheumatologists provided patient demographics, comorbidities, satisfaction with RA control and other clinical details. Patients reported their level of satisfaction and completed the EuroQoL 5-Dimensions Health Questionnaire and Work Productivity and Activity Impairment Questionnaire. Patients had been on their current therapy ≥3 months and had 28-joint disease activity scores (DAS28) reported. Adequately controlled (DAS28 ≤3.2) and inadequately controlled (DAS28 >3.2) patient cohorts were compared using univariate tests. Of 1147 patients, 74% were women, the mean age was 52 years and the mean time since RA diagnosis was 7 years. Twenty-seven percent of patients had inadequately controlled RA, whereas 73% had adequately controlled RA. Inadequately controlled patients were more affected clinically versus adequately controlled patients; 69% vs 13% had moderate/severe RA, the current level of pain was 4.6 vs 2.3, and 67% vs 41% experienced flares, respectively (all p<0.0001). Inadequately controlled patients had higher rates of depression (16% vs 5%; p<0.0001), worse health state, greater work and activity impairment, and lower satisfaction rates among the patients and their physicians than the adequately controlled cohort. RA was insufficiently controlled in over a quarter of patients despite their current therapy and this had a negative impact on the patients.

Once-daily prandial lixisenatide versus once-daily rapid-acting insulin in patients with type 2 diabetes mellitus insufficiently controlled with basal insulin: analysis of data from five randomized, controlled trials.

PubMed

Raccah, Denis; Lin, Jay; Wang, Edward; Germé, Maeva; Perfetti, Riccardo; Bonadonna, Riccardo C; de Pablos-Velasco, Pedro; Roussel, Ronan; Rosenstock, Julio

2014-01-01

To compare the efficacy and safety of lixisenatide (LIXI), a once-daily prandial glucagon-like peptide-1 (GLP-1) receptor agonist, as add-on to basal insulin (Basal+LIXI) versus once-daily rapid-acting insulin (Basal+RAI) in patients with type 2 diabetes mellitus (T2DM). Data were extracted from five randomized controlled trials assessing the efficacy and safety of basal insulin+insulin glulisine (n=3) or basal insulin+LIXI (n=2). Patients in the Basal+LIXI cohort were matched to patients in the Basal+RAI cohort using propensity score matching. In the matched population, Basal+LIXI was twice as likely to reach composite outcomes of glycated haemoglobin (HbA1c) <7% and no symptomatic hypoglycaemia compared with the Basal+RAI group (odds ratio [OR]: 1.90; 95% confidence interval [CI]: 1.01, 3.55; P=0.0455), as well as HbA1c <7% and no severe hypoglycaemia (OR: 1.97; 95 CI: 1.06, 3.66; P=0.0311). Furthermore, Basal+LIXI was more than twice as likely to reach HbA1c <7%, no weight gain and no symptomatic hypoglycaemia (OR: 2.58; 95% CI: 1.23, 5.40; P=0.0119). Both basal+LIXI and Basal+RAI improved glycaemic control in patients with T2DM with inadequate glycaemic control on basal insulin. Basal+LIXI offers an effective therapeutic option to advance basal insulin therapy, improving glucose control without weight gain and with less risk of hypoglycaemia than prandial insulin. © 2013.

Association of irisin and FNDC5 rs16835198 G>T gene polymorphism with type 2 diabetes mellitus and diabetic nephropathy. An Egyptian pilot study.

PubMed

Khidr, Emad Gamil; Ali, Shawkey Saddik; Elshafey, Mostafa Mahmoud; Fawzy, Olfat Ahmed

2017-08-30

Diabetes mellitus is a fast-growing health problem in Egypt affecting morbidity, mortality and health care resources. Irisin, a new exercise-induced myokine inducing browning of white adipose tissues, has gained a great interest as a potential new target for combating type 2 diabetes mellitus (T2DM) and its complications. In this study, we assessed serum irisin levels in T2DM and diabetic nephropathy to elucidate possible relationships between irisin and metabolic parameters and renal functions. We also investigated, for the first time in Egypt, the association of FNDC5 rs16835198 G>T polymorphism with T2DM, diabetic nephropathy and irisin levels. One hundred type 2 diabetic patients (40 normoalbuminuric and 60 with nephropathy) as well as fifty control subjects were enrolled in this study. Serum irisin and insulin were evaluated by ELISA. Genomic DNA was genotyped for FNDC5 rs16835198 polymorphism using TaqMan genotyping assay. Serum irisin levels were lower in diabetic patients compared to controls and this decrease was more pronounced in diabetic nephropathy. Irisin correlates with metabolic parameters and renal functions. Frequencies of T allele and TT genotype were significantly lower among T2DM and diabetic nephropathy patients compared to controls. Moreover, G allele was associated with elevated insulin resistance and dyslipidemia without effect on circulating irisin levels. T2DM and diabetic nephropathy are associated with decreased levels of irisin. FNDC5 rs16835198 TT genotype associates with decreased risk of T2DM in Egyptians with no effect on renal complications. Also, G allele has insulin desensitizing action with no association with circulating irisin levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Anticipating the next meal using meal behavioral profiles: a hybrid model-based stochastic predictive control algorithm for T1DM.

PubMed

Hughes, C S; Patek, S D; Breton, M; Kovatchev, B P

2011-05-01

Automatic control of Type 1 Diabetes Mellitus (T1DM) with subcutaneous (SC) measurement of glucose concentration and subcutaneous (SC) insulin infusion is of great interest within the diabetes technology research community. The main challenge with the so-called "SC-SC" route to control is sensing and actuation delay, which tends to either destabilize the system or inhibit the aggressiveness of the controller in responding to meals and exercise. Model predictive control (MPC) is one strategy for mitigating delay, where optimal insulin infusions can be given in anticipation of future meal disturbances. Unfortunately, exact prior knowledge of meals can only be assured in a clinical environment and uncertainty about when and if meals will arrive could lead to catastrophic outcomes. As a follow-on to our recent paper in the IFAC symposium on Biological and Medical Systems (MCBMS 2009), we develop a control law that can anticipate meals given a probabilistic description of the patient's eating behavior in the form of a random meal (behavioral) profile. Preclinical in silico trials using the oral glucose meal model of Dalla Man et al. show that the control strategy provides a convenient means of accounting for uncertain prior knowledge of meals without compromising patient safety, even in the event that anticipated meals are skipped. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Association of polymorphism in adiponectin (+45 T/G) and leptin (–2548 G/A) genes with type 2 diabetes mellitus in male Egyptians

PubMed Central

Motawi, Tarek; Salman, Tarek; Shaker, Olfat

2015-01-01

Introduction Adiponectin is an adipose tissue-specific protein with insulin-sensitizing properties. Many investigators have explored the association between adiponectin single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM) in different ethnic populations from different regions. Leptin is a protein hormone constituting an important signal in the regulation of adipose tissue mass and body weight. The aim of this study was to explore potential associations between SNP +45 T>G of the adiponectin gene and SNP 2548G/A of leptin with T2DM and the effect of SNPs on serum adiponectin and leptin levels. Material and methods From the Egyptian population, we enrolled 110 T2DM patients and 90 non-diabetic controls. Serum lipid profile, blood glucose, serum adiponectin, and leptin were measured. Genotyping for two common SNPs of the adiponectin and leptin genes was performed by polymerase chain reaction–restriction fragment length polymorphism. Results The G allele and TG/GG genotype of SNP 45 occurred more frequently than the T allele and TT genotype in T2DM patients compares to the controls. Subjects with the GG + TG genotype of SNP 45 were at increased risk for T2DM (OR = 6.476; 95% CI: 3.401–12.33) and associated with a low serum adiponectin level compared with the TT genotype. The serum leptin concentration of GA + AA genotype carriers was not significantly different from that of the GG genotype in the diabetic group. Conclusions The G allele carriers who have reduced plasma concentrations of adiponectin may have an association with T2DM, while leptin SNP 2548 G/A is not associated with the risk of development of T2DM in the Egyptian population. PMID:26528333

Tolerability of saxagliptin in patients with inadequately controlled type 2 diabetes: results from 6 phase III studies.

PubMed

Davidson, Jaime A

2014-02-01

Oral antihyperglycemic drugs used to treat type 2 diabetes mellitus (T2DM) vary in safety and tolerability. Treatment-related hypoglycemia and weight gain can exacerbate underlying disease.  To evaluate the tolerability of saxagliptin using data from phase III clinical trials.  Six 24-week randomized studies in 4,214 patients with T2DM were assessed. Saxagliptin 2.5 mg or 5 mg was compared with placebo in 2 trials of monotherapy in treatment-naïve patients and in 3 trials of add-on therapy to metformin, glyburide, or a thiazolidinedione; initial combination therapy with saxagliptin 5 mg plus metformin was compared with metformin monotherapy in treatment-naïve patients. Data from the monotherapy and add-on studies were pooled; data from the initial combination study were analyzed separately. No statistical analyses of between-group comparisons across studies were conducted for these safety analyses because of multiplicity of end points and relative lack of statistical power and because small differences not reaching statistical significance have the potential to be clinically relevant.   In the pooled analysis, incidence rates for adverse events (AEs) with saxagliptin 2.5 mg, 5 mg, and placebo were 72.0% (635/882), 72.2% (637/882), and 70.6% (564/799), respectively; rates for serious AEs (SAEs) were 3.5% (31/882), 3.4% (30/882), and 3.4% (27/799); rates of discontinuation due to AEs were 2.2% (19/882), 3.3% (29/882), and 1.8% (14/799). AEs reported in ≥ 2% of patients receiving saxagliptin and occurring ≥ 1% more frequently with saxagliptin than with placebo were sinusitis, gastroenteritis, abdominal pain, and vomiting. In the initial combination study, AE incidence rates with saxagliptin 5 mg plus metformin and metformin monotherapy were 55.3% (177/320) and 58.5% (192/328), respectively; incidence rates for SAEs were 2.5% (8/320) and 2.4% (8/328); and rates of discontinuation due to AEs were 2.5% (8/320) and 3.4% (11/328).  Saxagliptin 2.5 mg or 5 mg

The role of NOS2A -954G/C and vascular endothelial growth factor +936C/T polymorphisms in type 2 diabetes mellitus and diabetic nonproliferative retinopathy risk management.

PubMed

Porojan, Mihai Dumitru; Cătană, Andreea; Popp, Radu A; Dumitrascu, Dan L; Bala, Cornelia

2015-01-01

Type 2 diabetes mellitus (T2DM) remains one of the major health problems in Europe. Retinopathy is one of the major causes of morbidity in T2DM, strongly influencing the evolution and prognosis of these patients. In the last 2 decades, several studies have been conducted to identify the possible genetic susceptibility factors involved in the pathogenesis of the disease. However, there is little data related to the involvement of vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS) gene polymorphisms in the T2DM Caucasian population. The objective of this study was to identify a possible connection between NOS2A -954G/C (rs2297518) and VEGF +936C/T (rs3025039) polymorphisms and the risk of developing T2DM and nonproliferative diabetic retinopathy in a Caucasian population group. We investigated 200 patients diagnosed with T2DM and 208 controls. Genotypes were determined by multiplex polymerase chain reaction-restriction fragment length polymorphism. Statistical and comparative analyses (Fisher's exact test) for dominant and recessive models of NOS2A -954G/C and VEGF +936C/T polymorphisms revealed an increased risk of T2DM (χ (2)=8.14, phi =0.141, P=0.004, odds ratio [OR] =2.795, 95% confidence interval [CI] =1.347-5.801; χ (2)=18.814, phi =0.215, P<0.001, OR =2.59, 95% CI =1.675-4.006, respectively). Also, comparative analysis for the recessive model (using Pearson's chi-square test [χ (2)] and the phi coefficient [phi]) reveals that the variant CC genotype of NOS2A gene is more frequently associated with T2DM without retinopathy (χ (2)=3.835, phi =-0.138, P=0.05, OR =0.447, 95% CI =0.197-1.015). In conclusion, the results of the study place VEGF +936C/T polymorphisms among the genetic risk factor for T2DM, whereas NOS2A -954G/C polymorphisms act like a protective individual factor for nonproliferative retinopathy.

α-2-Macroglobulin in Saliva Is Associated with Glycemic Control in Patients with Type 2 Diabetes Mellitus

PubMed Central

Aitken, Juan Pablo; Ortiz, Carolina; Morales-Bozo, Irene; Rojas-Alcayaga, Gonzalo; Baeza, Mauricio; Beltran, Caroll

2015-01-01

Background. Subjects with type 2 diabetes mellitus (DM2) require an adequate glycemic control to avoid diabetic complications. Currently, saliva biomarkers are used as a diagnostic tool and can be indicative of the degree of progression and control of various diseases. Several studies indicate that α-2-macroglobulin levels are elevated in diabetic patients. Methods. 120 subjects with DM2 were enrolled and classified into two groups according to their glycemic control (percentage of glycated hemoglobin-A1c (HbA1c), <7% adequate glycemic control group; >7% inadequate glycemic control group). The relationship between α-2-macroglobulin levels from saliva samples and HbA1c was subsequently evaluated. Results. We found a positive correlation between α-2-macroglobulin and HbA1c (r = 0.778 and P < 0.0001). Area under the receivers operating characteristic (ROC) curve of α-2-macroglobulin indicated a positive discrimination threshold of α-2-macroglobulin (AUC = 0.903, CI 95%: 0.847–0.959, P < 0.0001) to diagnose glycemic control. Conclusions. Our data strongly suggest that the level of saliva α-2-macroglobulin is an indicator for the degree of glycemic control in diabetic patients and represents a promising alternative method to evaluate this parameter. PMID:25821337

Reduction of Sulfonylurea with the Initiation of Basal Insulin in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Undergoing Long-Term Sulfonylurea-Based Treatment.

PubMed

Yang, Yeoree; Shin, Jeong Ah; Yang, Hae Kyung; Lee, Seung Hwan; Ko, Seung Hyun; Ahn, Yu Bae; Yoon, Kun Ho; Cho, Jae Hyoung

2016-12-01

There were a limited number of studies about β-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of β-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin. In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT. Among 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group. Long-acting basal insulin replacement could improve the glycemic status and restore β-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.

Medical claims-based case-control study of temporal relationship between clinical visits for hand syndromes and subsequent diabetes diagnosis: implications for identifying patients with undiagnosed type 2 diabetes mellitus.

PubMed

Hou, Wen-Hsuan; Li, Chung-Yi; Chen, Lu-Hsuan; Wang, Liang-Yi; Kuo, Li-Chieh; Kuo, Ken N; Shen, Hsiu-Nien; Chiu, Chang-Ta

2016-10-20

To investigate whether a temporal relationship is present between clinical visits for diabetes-related hand syndromes (DHSs) and subsequent type 2 diabetes mellitus (T2DM) diagnosis and, accordingly, whether DHSs can be used for identifying patients with undiagnosed T2DM. This study had a case-control design nested within a cohort of 1 million people from the general population, which was followed from 2005 to 2010. The odds of prior clinical visits for DHSs, namely carpal tunnel syndrome (CTS), flexor tenosynovitis, limited joint mobility and Dupuytren's disease, were estimated for cases and controls. We used a conditional logistic regression model to estimate the OR and 95% CI of T2DM in association with a history of DHSs. The validity and predictive value of using the history of DHSs in predicting T2DM diagnosis were calculated. Taiwan National Health Insurance medical claims. We identified 33 571 patients receiving a new diagnosis of T2DM (cases) between 2005 and 2010. Each T2DM case was matched with 5 controls who had the same sex and birth year and were alive on the date of T2DM diagnosis. The primary outcome measure was T2DM diagnosis. The OR of T2DM in association with prior clinical visits was significantly increased for overall DHS and CTS, being 1.15 (95% CI 1.10 to 1.20) and 1.22 (95% CI 1.16 to 1.29), respectively. Moreover, 11% of patients with T2DM made clinical visits for CTS within 3 months prior to T2DM diagnosis. The history of DHSs had low sensitivity (<0.1% to 5.2%) and a positive predictive value (9.9% to 11.7%) in predicting T2DM. Despite the unsatisfactory validity and performance of DHSs as a clinical tool for detecting patients with undiagnosed T2DM, this study provided evidence that clinical visits for DHSs, particularly for CTS, can be a sign of undiagnosed T2DM. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

NAMPT -3186C/T polymorphism affects repaglinide response in Chinese patients with Type 2 diabetes mellitus.

PubMed

Sheng, Fei-Feng; Dai, Xing-Ping; Qu, Jian; Lei, Guang-Hua; Lu, Hong-Bin; Wu, Jing; Xu, Xiao-Jing; Pei, Qi; Dong, Min; Liu, Ying-Zi; Zhou, Hong-Hao; Liu, Zhao-Qian

2011-08-01

1. In the present study, we investigated the associations of nicotinamide phosphoribosyltransferase (NAMPT)-3186 C/T and -948G/T polymorphisms with the risk of Type 2 diabetes mellitus (T2DM) and their impact on the efficacy of repaglinide in Chinese Han T2DM patients. 2. In all, 170 patients with T2DM and 129 healthy controls were genotyped for NAMPT-948G>T and -3186C>T polymorphisms. Thirty-five patients with different NAMPT -3186 C/T genotypes and the same organic anion-transporting polypeptide 1B1 (OATP1B1521) T/C genotype were randomly selected to undergo 8 weeks preprandial repaglinide treatment (1 mg, three times daily). Serum fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), glycated haemoglobin (HbAlc), fasting serum insulin (FINS), post-prandial serum insulin (PINS), triglyceride (TG), total cholesterol (CHO), homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were determined before and after repaglinide treatment. 3. After repaglinide treatment for 8 consecutive weeks, there were significantly decreases in PFG, PPG, HbAlc, CHO and LDL-C, and increases in FINS, HDL-C and the HDL-C : LDL-C ratio, in T2DM patients. The elevated PINS value in patients with CT genotypes was significantly lower than that in patients with the CC and TT genotypes (P < 0.05) and there were significant differences in CHO between patients with the CT genotype and the CC or TT genotype (P < 0.05). 4. The data suggest that the NAMPT -3186C>T polymorphism is significantly associated with plasma levels of PINS and CHO in Chinese T2DM patients with repaglinide monotherapy. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

Glucose-dependent leukocyte activation in patients with type 2 diabetes mellitus, familial combined hyperlipidemia and healthy controls.

PubMed

de Vries, Marijke A; Alipour, Arash; Klop, Boudewijn; van de Geijn, Gert-Jan M; Janssen, Hans W; Njo, Tjin L; van der Meulen, Noëlle; Rietveld, Arie P; Liem, Anho H; Westerman, Elsbeth M; de Herder, Wouter W; Cabezas, Manuel Castro

2015-02-01

Leukocyte activation has been associated with vascular complications in type 2 diabetes mellitus (T2DM). Hyperglycemia may be involved in this leukocyte activation. Our aim was to investigate the role of elevated glucose concentrations on leukocyte activation in patients with a wide range of insulin sensitivity. Leukocyte activation was determined after ingestion of 75 gram glucose in subjects with T2DM, familial combined hyperlipidemia (FCH) and healthy controls. Leukocyte activation markers were measured by flow cytometry. Postprandial changes were calculated as the area under the curve (AUC), and the incremental area under the curve corrected for baseline values (dAUC). 51 Subjects (20 T2DM, 17 FCH and 14 controls) were included. Fasting neutrophil CD66b expression and CD66b-AUC were respectively 36% and 39% higher in T2DM patients than in controls (p=0.004 and p=0.003). Fasting neutrophil CD66b expression correlated positively with glucose-AUC (Spearman's rho 0.481, p<0.001) and HbA1c (rho 0.433, p=0.002). Although fasting monocyte CD11b expression was not significantly different between subjects, monocyte CD11b-AUC was 26% higher in T2DM than in controls (p=0.006). Similar trends were observed for FCH patients. Monocyte CD11b-dAUC correlated positively with glucose-AUC (rho 0.322, p=0.022) and HbA1c (rho 0.319, p=0.023). These data suggest that both acute and chronic hyperglycemia, associated with insulin resistance as seen in T2DM and FCH, are involved in the increased fasting and postprandial leukocyte activation observed in these conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Initial combination therapy with vildagliptin plus metformin in drug-naïve patients with T2DM: a 24-week real-life study from Asia.

PubMed

Chawla, Manoj; Kim, Tae Ho; Mirasol, Roberto C; Faruque, Pathan; Cooke, Kathryn; Hours-Zesiger, Peggy; Shete, Abhijit

2018-06-12

To assess the effectiveness and safety of vildagliptin/metformin initial combination therapy in drug-naïve patients with type 2 diabetes mellitus (T2DM). INITIAL was a 24-week prospective, observational study in T2DM patients with glycated hemoglobin (HbA1c) ≥ 7.5%, and prescribed vildagliptin/metformin as initial combination therapy. The primary endpoint was change in HbA1c from baseline to week 24. Key secondary endpoints were HbA1c change from baseline to week 12, proportion of patients achieving HbA1c ≤7.0%, change in body weight at 12 and 24 weeks, change in HbA1c by sub-groups (baseline HbA1c, age, body mass index [BMI], dosage strength, co-morbidities) from baseline to week 24, and safety. A total of 532 patients were enrolled. The mean age, HbA1c, and BMI were 49.6 ± 11.27 years, 9.3 ± 1.57%, and 26.7 ± 4.50 kg/m 2 , respectively. Cardiovascular risk factors present at baseline were dyslipidemia (30.1%), hypertension (29.7%), and obesity (20.9%). The mean reductions in HbA1c from baseline to week 12 (-1.6 ± 1.59%) and 24 (-1.9 ± 1.70%) were statistically significant (p < .001). At 24 weeks, 39.6% of patients achieved HbA1c ≤ 7.0%, and the mean body weight reduction was -1.1 ± 2.62 kg. HbA1c reductions were consistently seen from baseline to weeks 12 and 24 in the various sub-groups. Overall, 48 (9.0%) patients reported adverse events, including one hypoglycemic episode. There were no serious adverse events or deaths. Overall, in a relatively young drug-naïve T2DM Asian study population with high baseline HbA1c and often associated with cardiovascular risk factors, vildagliptin/metformin combination therapy was associated with significant and clinically relevant HbA1c reduction from baseline. This effect was seen at week 12, was maintained over 24 weeks, and was accompanied by good tolerability.

Linagliptin improves glycemic control after 1 year as add-on therapy to basal insulin in Asian patients with type 2 diabetes mellitus.

PubMed

Sheu, Wayne H-H; Park, Sung Woo; Gong, Yan; Pinnetti, Sabine; Bhattacharya, Sudipta; Patel, Sanjay; Seck, Thomas; Woerle, Hans-Juergen

2015-03-01

To evaluate the efficacy and long-term safety of linagliptin added to basal insulin in Asian patients with type 2 diabetes mellitus (T2DM) inadequately controlled by basal insulin with/without oral agents. This was a post hoc analysis of Asian patients from a global ≥52 week study in which patients on basal insulin were randomized (1:1) to double-blind treatment with linagliptin 5 mg once daily or placebo (NCT00954447). Basal insulin dose remained stable for 24 weeks, after which adjustments could be made according to the investigator's discretion to improve glycemic control. The primary endpoint was the mean change in glycated hemoglobin (HbA1c) from baseline to 24 weeks. Data were available for 154 Asian patients (80 linagliptin, 74 placebo). Baseline HbA1c (standard deviation [SD]) was 8.6 (0.9)% (70 [10] mmol/mol). The placebo-corrected mean change (standard error [SE]) in HbA1c from baseline was -0.9 (0.1)% (-10 [1] mmol/mol) (95% confidence interval [CI]: -1.2, -0.7; p<0.0001) at Week 24 and -0.9 (0.1)% (-10 [1] mmol/mol) (95% CI: -1.1, -0.6; p<0.0001) at Week 52. The frequency of adverse events (linagliptin 81.3%, placebo 91.9%) and hypoglycemia (Week 24: linagliptin 25.0%, placebo 25.7%; treatment end: linagliptin 28.8%, placebo 35.1%) was similar between groups. By Week 52, changes (SE) in mean body weight were similar in both groups (linagliptin -0.67 [0.26] kg, placebo -0.38 [0.25] kg). This study was limited by the post hoc nature of the analysis and the small number of patients in the subgroup. However, the results suggest that linagliptin significantly improves glycemic control in Asian patients with T2DM inadequately controlled by basal insulin, without increasing the risk for hypoglycemia or weight gain. ClinicalTrials identifier: NCT00954447.

Glycemic control and pregnancy outcomes in women with type 2 diabetes from Poland. The impact of pregnancy planning and a comparison with type 1 diabetes subjects.

PubMed

Cyganek, Katarzyna; Hebda-Szydlo, Alicja; Skupien, Jan; Katra, Barbara; Janas, Izabela; Borodako, Alicja; Kaim, Irena; Klupa, Tomasz; Reron, Alfred; Malecki, Maciej T

2011-10-01

The number of pregnancies complicated by type 2 diabetes mellitus (T2DM) is growing; however, their clinical characteristics remain incomplete. We aimed to assess clinical characteristics, glycemic control, and selected pregnancy outcomes in pregestational T2DM from Poland and to compare them with those of T1DM. We analyzed 415 consecutive singleton pregnancies; among them, there were 70 women with T2DM and 345 with T1DM. As compared to T1DM patients, women with T2DM were older (mean age 33.1 years vs. 27.8, respectively), heavier before pregnancy (mean BMI 30.8 kg/m² vs. 23.9), and had a shorter duration of diabetes (mean 3.3 years vs. 11.4); ( P<0.0001 for all comparisons). The gestational age at the first visit was higher in T2DM (mean 11.4 weeks vs. 8.6; P=0.0004). Nevertheless, they had better glycemic control in the first trimester (mean HbA1c 6.2% vs. 7.0; P=0.003); in subsequent months, the differences in HbA1c were no longer significant. T2DM women gained less weight during pregnancy (mean 9.9 kgs vs. 14.1; P<0.0001). The proportion of miscarriages (10.0 vs. 7.3%; P=0.32), preterm deliveries (12.7 vs. 17.8%; P=0.32), combined infant deaths, and congenital malformations were similar in both groups (9.5 vs. 8.8%; P=0.4) as was the frequency of caesarean sections (58.7 vs. 64.1%; P=0.30). Macrosomic babies were more than twice less frequent in T2DM and the difference reached borderline significance (7.9 vs. 17.5%, P=0.07). Pregnancy planning in T2DM had a significant impact on HbA1c in the first trimester (5.7 vs. 6.4% in the planning vs. the not planning group, P=0.02); the difference was not significant in the second and third trimester. T2DM women had better glycemic control in the first trimester than T1DM subjects and gained less weight during pregnancy. This could have been the reason for the slightly lower number of macrosomic babies but did not affect other outcomes. In T2DM, pregnancy planning had a beneficial glycemic effect in the first trimester.

[Risk of type 2 diabetes mellitus in the Kyrgyz population in the presence of ADIPOQ (G276T), KCNJ11 (Glu23Lys), TCF7L2 (IVS3C>T) gene polymorphisms].

PubMed

Isakova, Zh T; Talaibekova, E T; Asambaeva, D A; Kerimkulova, A S; Lunegova, O S; Aldasheva, N M; Aldashev, A A

To analyze the association of genotype combinations of the polymorphic markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population. The investigation enrolled 23 Kyrgyz people, of whom there were 114 patients with T2DM and 109 without T2DM (a control group). T2DM was diagnosed in accordance with the WHO criteria (1999). The genotypes of ADIPOQ (G276T), KCNJ11 (Glu23Lys), and TCF7L2 (IVS3C>T) gene polymorphisms were identified using the restriction fragment length polymorphism analysis. When typing at the polymorphic loci G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene, the development of T2DM in the Kyrgyz population was associated with the T allele (odds ratio (OR), 1.68; p=0.025), the heterozygous G276T genotype (OR 1,8; p=0.036) in the ADIPOQ gene; the 23Lys allele (OR, 1.62; p=0.019) in the KCNJ11 gene; a two-locus genotype combination in the genes ADIPOQ/KCNJ11: G276T/Glu23Lys (OR, 4.88; p=0.0013), G276G/Lys23Lys (OR, 4.65; p=0.019), G276T/Glu23Glu (OR, 3.10; p=0.022), a two-locus genotype combination in the genes ADIPOQ/TCF7L2: G276T/СС (OR, 1.97; p=0.04); two-locus genotype combinations in the genes KCNJ11/TCF7L2: Lys23Lys/CC (ОR, 2.65; p=0.042), Glu23Lys/CT (OR, 3.88; p=0.027); and a three-locus genotype combination in the genes ADIPOQ/KCNJ11/TCF7L2: G276T/Glu23Lys/CT (OR, 14.48; p=0.02). The development of T2DM in the Kyrgyz population is genetically determined by ADIPOQ (G276T) gene, KCNJ11 (Glu23Lys), and TCF7L (IVS3C>T) gene polymorphisms with the predisposing value of the T allele of the heterozygous G276T genotype in the ADIPOQ gene; the 23Lys allele in the KCNJ1 gene; as well as by genotype combinations in the genes ADIPOQ/KCNJ11 (G276T/Glu23Lys, G276G/Lys23Lys, G276T/Glu23Glu); ADIPOQ/TCF7L2 (G276T/SS); KCNJ11/TCF7L2 (Lys23Lys/CC, Glu23Lys/CT); ADIPOQ/KCNJ11/TCF7L2 (G276T/Glu23Lys /CT). The IVS3C>T

A review of clinical efficacy and safety of canagliflozin 300 mg in the management of patients with type 2 diabetes mellitus

PubMed Central

Prasanna Kumar, K. M.; Ghosh, Sujoy; Canovatchel, William; Garodia, Nishant; Rajashekar, Sujith

2017-01-01

Currently available antihyperglycemic agents, despite being effective, provide inadequate glycemic control and/or are associated with side effects or nonadherence. Canagliflozin, a widely used orally active inhibitor of sodium-glucose cotransporter 2 (SGLT2), is a new addition to the therapeutic armamentarium of glucose-lowering drugs. This review summarizes findings from different clinical and observational studies of canagliflozin 300 mg in patients with type 2 diabetes mellitus (T2DM). By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose, thereby increasing urinary glucose excretion in patients with T2DM. Canagliflozin 300 mg has been shown to be effective in lowering glycated hemoglobin, fasting plasma glucose, and postprandial glucose in patients with T2DM. Canagliflozin 300 mg also demonstrated significant reductions in body weight and blood pressure and has a low risk of causing hypoglycemia, when not used in conjunction with insulin and insulin secretagogues. Canagliflozin 300 mg was generally well tolerated in clinical studies. The most frequently reported adverse events include genital mycotic infections, urinary tract infections, osmotic diuresis, and volume depletion-related events. PMID:28217522

21 CFR 1240.30 - Measures in the event of inadequate local control.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Measures in the event of inadequate local control. 1240.30 Section 1240.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... CONTROL OF COMMUNICABLE DISEASES Administrative Procedures § 1240.30 Measures in the event of inadequate...

21 CFR 1240.30 - Measures in the event of inadequate local control.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Measures in the event of inadequate local control. 1240.30 Section 1240.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... CONTROL OF COMMUNICABLE DISEASES Administrative Procedures § 1240.30 Measures in the event of inadequate...

21 CFR 1240.30 - Measures in the event of inadequate local control.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Measures in the event of inadequate local control. 1240.30 Section 1240.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... CONTROL OF COMMUNICABLE DISEASES Administrative Procedures § 1240.30 Measures in the event of inadequate...

21 CFR 1240.30 - Measures in the event of inadequate local control.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Measures in the event of inadequate local control. 1240.30 Section 1240.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... CONTROL OF COMMUNICABLE DISEASES Administrative Procedures § 1240.30 Measures in the event of inadequate...

[Dapagliflozin: Beyond glycemic control in the treatment of type 2 diabetes mellitus].

PubMed

Sanz-Serra, Pol; Pedro-Botet, Juan; Flores-Le Roux, Juana A; Benaiges, David; Chillarón, Juan J

2015-01-01

Patients with type 2 diabetes mellitus (T2DM) have a high or very high cardiovascular risk. The clinical practice guidelines focus on the need to achieve optimal glycemic control, and strategies for a multifactorial therapeutic approach have shown significant cardiovascular benefits in these patients. Inhibitors of sodium-glucose co-transporter 2 (SGLT-2) are a new class of orally administered drugs in the treatment of T2DM, which act by inhibiting reabsorption of glucose in the renal proximal tubule with consequent glycosuric effect and lowering of blood glucose. Dapagliflozin, SGLT-2 inhibitor marketed in Europe and Australia, has been shown to achieve glycosylated hemoglobin reductions similar to other oral agents, as well as beneficial effects on major comorbidities associated with T2DM. Therefore, it is considered of interest to review the clinical efficacy of this new oral hypoglycemic on glycemic control, risk of hypoglycemia, and its impact on body weight, blood pressure, lipid profile and renal function. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Long-term effect of periodontal surgery on oral health and metabolic control of diabetics.

PubMed

Pranckeviciene, Alma; Siudikiene, Jolanta; Ostrauskas, Rytas; Machiulskiene, Vita

2017-04-01

The objective of this study was to evaluate impact of periodontal surgery on periodontal health and on glycaemia control of type 1 and type 2 (T1DM; T2DM) diabetics with severe periodontitis, during 12 months follow-up, in comparison with non-diabetic controls. A total of 23 T1DM and 10 T2DM patients with respective number of matched non-diabetics were examined prior to, and 3, 6 and 12 months after periodontal surgery. Glycosylated haemoglobin (HbA1c) reflected control of DM. Periodontal parameters were oral debris (DI-S), probing pocket depth (PPD), clinical attachment loss (CAL) and bleeding on probing (BOP). Periodontal status in all diabetics improved after 3 months and remained so during follow-up: mean (SD) DI-S > 1 (T1DM 1.1(0.5)/0.9(0.7); T2DM 1.2(0.4)/0.8(0.4)), PPD >5 mm (T1DM 35.1(32.2)/5.1(7.8); T2DM 46.3(24.2)/13.0(10.9)), CAL ≥6 mm (T1DM 44.4(37.0)/24.52(27.2)); mean % BOP >50 % (T1DM 57.1(25.1)/22.8(20.8)), T2DM 59.4(20.8)/18.9(15.7)), p < 0.05. Mean HbA1c values decreased in T2DM patients after 3 months and remained stable during follow-up. No improvement of glycaemia control was observed in T1DM patients. Positive correlation between mean HbA1c and CAL changes was observed (r = 0.842, p < 0.05). Mean changes of periodontal parameters did not differ between diabetics and controls. Periodontal surgery improved significantly periodontal status of all patients and metabolic control of T2DM patients. Research findings concerning long-term effect of periodontal surgery among patients with diabetes mellitus are scarce. We found that surgical periodontal treatment positively affects periodontal health of all diabetics and improves metabolic control of type 2 DM. There is a positive correlation between clinical attachment loss and glycosylated haemoglobin levels.

Excess body iron and the risk of type 2 diabetes mellitus: a nested case-control in the PREDIMED (PREvention with MEDiterranean Diet) study.

PubMed

Arija, Victoria; Fernández-Cao, José C; Basora, Josep; Bulló, Mònica; Aranda, Nuria; Estruch, Ramón; Martínez-González, Miguel A; Salas-Salvadó, Jordi

2014-12-14

A prospective nested case-control study within the PREvention with MEDiterranean Diet (PREDIMED) was conducted to evaluate the relationship between excess body Fe (measured as serum ferritin (SF), soluble transferrin receptor (sTfR) and sTfR:ferritin ratio) and the risk of type 2 diabetes mellitus (T2DM) in a Mediterranean population at a high risk of CVD, without T2DM at the start of the study. The study contained 459 subjects, 153 with incident T2DM (cases) and 306 without incident T2DM (controls). The follow-up period was for 6.0 (interquartile range 3.9-6.5) years. For each incident diabetic subject, two subjects were selected as controls who were matched broadly for age as well as for sex, intervention group and BMI. We observed a relationship between SF values >257 μg/l in males and >139 μg/l in females and the risk of T2DM, following adjustment in the conditional logistic regression model for high-sensitivity C-reactive protein, fasting glucose and other components of the metabolic syndrome (OR 3.62, 95% CI 1.32, 19.95; P= 0.022). We also found an association between low sTfR:ferritin ratio levels and the incidence of T2DM (OR 3.02, 95% CI 1.09, 8.39; P= 0.042), but no association with sTfR (OR 1.29, 95% CI 0.51, 3.23; P= 0.722). Oxidative stress has been hypothesised to contribute to the development of insulin resistance and β-cell dysfunction, the two key events in the clinical development of T2DM. Following adjustment for other risk factors for T2DM, excess body Fe (measured as SF and sTfR:ferritin ratio) was associated with an increased risk of developing T2DM in a Mediterranean population at a high risk of CVD.

Quality-of-life and treatment satisfaction in actual clinical practice of patients with Type 1 diabetes mellitus (T1DM) and hypoglycemia treated with insulin degludec.

PubMed

Lecumberri, Edurne; Ortega, Maite; Iturregui, Marta; Quesada, José Antonio; Vázquez, Clotilde; Orozco, Domingo

2018-01-15

The frequency of hypoglycemia in patients with T1DM is high and results in a poorer quality-of-life and low treatment satisfaction. The aim of this study is to demonstrate the effect of changing the basal insulin (glargine or detemir) to insulin degludec. An observational analytical study was conducted on a cohort of 110 patients with T1DM. The patients were administered three questionnaires to assess treatment satisfaction (DTSQ-s), fear of hypoglycemia (HFS-II) and quality-of-life (EQ-5D), before the change and at 6 months. A statistical analysis was performed for repeated measures. The 110 patients with T1DM had a mean diabetes duration of 19.1 (11.6) years, 53.6% were men, the mean age was 43.4 (15.4) years, and the mean BMI was 25.2 (4.2) kg/m 2 . After 6 months, there was a significant reduction in baseline fasting plasma glucose (from 159.1 [68.6] to 132.9 [56.6] mg/dL; p < .001) and HbA1c levels (from 7.82% [1.2] to 7.6% [1.2]; p = .002). A reduction in the number of severe hypoglycemic episodes (0.17 [0.5] vs 0.05 [0.2]; p = .03) was observed. At 6 months, an improvement in the DTSQ-s (from 24.3 [5.5] to 27.3 [5.4]; p < .001) was observed. There was a decrease in the mean number of perceived hypoglycemia (from 2.9 [1.4] to 2.3 [1.4]; p = .003) and hyperglycemia (from 3.5 [1.3] to 2.7 [1.4]; p < .001). There was also a decrease in the mean HFS-II score (from 24.1 [14.0] to 20.0 [13.0]; p < .001). There were no significant differences in the EQ-5D index (from 0.91 [0.14] to 0.89 [0.16]; p = .13). However, there was significant improvement in the EQ-5D as measured by VAS (from 70.5 [16.5] to 73.6 [14.4]; p = .04). The change to insulin degludec in patients with T1DM improved their metabolic control, increased their satisfaction with the insulin therapy, and offered them improved quality-of-life.

Cancer risk of sulfonylureas in patients with type 2 diabetes mellitus: A systematic review.

PubMed

Chen, Yuehong; Du, Liang; Li, Ling; Ma, Jun; Geng, Xingyuan; Yao, Xun; Liu, Guanjian; Sun, Xin

2017-05-01

Increasing evidence suggests that oral hypoglycemic agents used in type 2 diabetes mellitus (T2DM) may affect cancer risk. Sulfonylureas (SUs) are the most frequently used antidiabetic medications for T2DM. Whether using SUs has any effect on cancer has received considerable attention. The aim of this study was to assess the effects of SUs on cancer risk in T2DM patients. Published studies were identified in PubMed, EMBASE, and the Cochrane Register of Clinical Studies, and ClinicalTrials.gov was searched for additional information to identify randomized controlled trials (RCTs), cohort studies, and case-control studies. The abstracts and full text were screened, data collected, and the risk of bias assessed for each individual study. Seventy-seven studies (33 RCTs, 27 cohort studies, and 17 case-control studies) were analyzed. The RCTs did not report a difference in the risk of malignant tumor between SU-treated T2DM patients and controls (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.78-1.18); cohort studies showed that cancer risk was higher in patients using SUs than metformin (relative risk 1.60 [95%CI 1.37-1.87]; adjusted hazard ratio 1.13 [95%CI 1.06-1.19]), and case-control studies suggested a trend for increased cancer risk in those using SUs compared with non-SU users (adjusted OR 1.13; 95%CI 0.93-1.37). The available evidence clearly shows that SUs can significantly increase the risk of cancer compared with metformin. Although the evidence suggests the possibility that SU users may have a higher risk of cancer than those using alternative medications in addition to metformin, it remains inadequate to enable definitive conclusions to be drawn. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

A randomized controlled study to evaluate the effect of pharmacist-led educational intervention on glycemic control, self-care activities and disease knowledge among type 2 diabetes patients: A consort compliant study protocol.

PubMed

Bukhsh, Allah; Nawaz, Muhammad Sarfraz; Ahmed, Hafiz Sajjad; Khan, Tahir Mehmood

2018-03-01

Diabetes self-care activities, like, healthy diet, regular exercise, self-monitoring of blood glucose, and rational use of medicines are considered to play a vital role in establishing euglycemia. Health literacy among type 2 diabetes mellitus (T2DM) patients in Pakistan is very low, which is the most likely cause for poor clinical outcomes. This study is designed to investigate the impact of pharmacist-led educational intervention on glycemic control, self-care activities and disease knowledge among T2DM patients in Pakistan. In this randomized controlled trail, effectiveness of a 6-month pharmacist-led educational intervention will be examined on glycemic control, diabetes self-care activities and disease knowledge of 80 adult T2DM patients (age >30 years) with poorly controlled T2DM (HbA1c> 7%), after randomizing them into intervention and control groups, at diabetes care clinic of Capital Hospital Islamabad, Pakistan. The primary outcome is change in patients' HbA1c, whereas, changes in self-care activities and patients' disease knowledge are the secondary outcomes. After baseline assessment of their self-care activities and disease knowledge by using validated Urdu versions of Diabetes Self-management Questionnaire (DSMQ) and Diabetes Knowledge Questionnaire (DKQ), respectively, interventional group patients will be supplemented with a face-to-face pharmacist-led educational intervention, whereas, the control group will receive usual care. Intervention arm patients will be educated successively at their first follow-up visit (12th week) and telephonically after every 4 weeks. All assessments will be made at baseline and end of trail for both intervention and control groups. Multivariate general linear model will be applied to analyze the effects of the intervention. Glycemic control in T2DM patients requires optimum self-care activities. This study is an attempt to improve self-care behaviors among poorly controlled T2DM patients who are at higher risk of

Expansion of Pathogen-Specific T-Helper 1 and T-Helper 17 Cells in Pulmonary Tuberculosis With Coincident Type 2 Diabetes Mellitus

PubMed Central

Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.; Nutman, Thomas B.; Babu, Subash

2013-01-01

Background. Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, although the immunological mechanisms underlying this interaction remain unexplored. The influence of poorly controlled diabetes on pathogen-specific T-helper 1 (Th1) and T-helper 17 (Th17) responses have not been examined. Methods. To identify the role of Th1 and Th17 cells in tuberculosis with coincident DM, we examined mycobacteria-specific immune responses in the whole blood of individuals who had tuberculosis with DM and compared them to those in individuals who had tuberculosis without DM. Results. Tuberculosis coincident with DM is characterized by elevated frequencies of monofunctional and dual-functional CD4+ Th1 cells following Mycobacterium tuberculosis antigen stimulation and elevated frequencies of Th17 subsets at both baseline and following antigen stimulation. This was associated with increased systemic (plasma) levels of both Th1 and Th17 cytokines and decreased baseline frequencies of natural regulatory T cells but not interleukin 10 or transforming growth factor β. Conclusions. Therefore, our data reveal that tuberculosis in persons with DM is characterized by elevated frequencies of Th1 and Th17 cells, indicating that DM is associated with an alteration in the immune response to tuberculosis, leading to a biased induction of Th1- and Th17-mediated cellular responses and likely contributing to increased immune pathology in M. tuberculosis infection. PMID:23715661

Frequency and determinants of thyroid autoimmunity in Ghanaian type 2 diabetes patients: a case-control study.

PubMed

Sarfo-Kantanka, Osei; Sarfo, Fred Stephen; Ansah, Eunice Oparebea; Yorke, Ernest; Akpalu, Josephine; Nkum, Bernard C; Eghan, Benjamin

2017-01-17

The link between type 1 diabetes and thyroid autoimmunity is well described. The same cannot be said for type 2 diabetes where results have been mixed so far. We investigated the prevalence and determinants of thyroid autoimmunity among Ghanaian type 2 diabetes patients. This was a case-control study involving 302 type 2 diabetes patients and 310 non - diabetic controls aged 40-80 years. Anthropometric and blood pressure measurements were obtained. Fasting samples were analyzed for glucose, thyroid function, and antibodies to thyroglobulin and thyroid peroxidase. The prevalence of thyroid autoimmunity was significantly higher among T2DM subjects (12.2% vs. 3.9%, p = 0.0004). Among T2DM subjects, 44 (14.7%) tested positive for TPOAb, 5 (1.7%) tested positive for TGAb and 15 (5.0%) tested positive for both autoantibodies. Females T2DM subjects showed a 3-fold increased risk of thyroid autoimmunity compared to males (OR:3.16, p =0.004), T2DM subjects with hyperthyroidism had a 41% increased risk of thyroid autoimmunity (OR: 1.41, p < 0.001), sub-clinical hyperthyroidism increased the risk of thyroid autoimmunity by 2 fold, (OR:2.19, p < 0.001), subclinical hypothyroidism increased the risk of autoimmunity by 4-fold, (OR:3.57 95% p < 0.0001), and hypothyroidism was associated with a 61% increased risk of thyroid autoimmunity (OR: 1.61,1.35-2.23). Dyslipidaemia was associated with a 44% increased risk of thyroid autoimmunity (OR: 1.44, p = 0.01) and a percentage increase in HbA1c was associated with 46% increased risk of thyroid autoimmunity (OR:1.46, p < 0.0001). We observed a high prevalence of thyroid autoimmunity in Ghanaian T2DM subjects compared to the general population. Thyroid autoimmunity in T2DM subjects was significantly associated with female gender, thyroid dysfunction, dyslipidaemia and poor glycemic control.

Association of TNF-α 308 G/A Polymorphism With Type 2 Diabetes: A Case-Control Study in the Iranian Kurdish Ethnic Group.

PubMed

Golshani, Hasan; Haghani, Karimeh; Dousti, Majid; Bakhtiyari, Salar

2015-04-01

Tumor necrosis factor-α (TNF-α) plays roles in the development of obesity, insulin resistance, and possibility of Type 2 diabetes mellitus (T2DM). The objective of the current study was to evaluate the association of TNF-α promoter-308 G/A polymorphism with T2DM. In all, 1038 patients with T2DM and 1023 normoglycemic controls were included in this study. All participants were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Genotypic and allelic frequencies were then analyzed in each group. Serum lipids, fasting glucose, fasting serum insulin, homeostatic model assessment of insulin resistance, and hemoglogin A1c levels were determined by conventional methods. The allelic frequency of the A allele was significantly different between case and control participants (p = 0.006). Genotypes GA and AA were found to be significantly associated with 2.24- and 3.18-fold increased risk for T2DM, respectively. Similarly, the dominant model of -308 G/A polymorphism was found to have a higher risk for T2DM (odds ratio = 2.34, p = 0.001). Individuals with T2DM carrying the GA + AA genotypes of -308 G/A variation had significantly lower fasting plasma insulin than those carrying GG genotype. Our findings revealed that there is an association between the TNF-α promoter -308 G/A polymorphism and T2DM in this population.

Reducing Glucose Variability Due to Meals and Postprandial Exercise in T1DM Using Switched LPV Control: In Silico Studies.

PubMed

Colmegna, Patricio H; Sánchez-Peña, Ricardo S; Gondhalekar, Ravi; Dassau, Eyal; Doyle, Francis J

2016-05-01

Time-varying dynamics is one of the main issues for achieving safe blood glucose control in type 1 diabetes mellitus (T1DM) patients. In addition, the typical disturbances considered for controller design are meals, which increase the glucose level, and physical activity (PA), which increases the subject's sensitivity to insulin. In previous works the authors have applied a linear parameter-varying (LPV) control technique to manage unannounced meals. A switched LPV controller that switches between 3 LPV controllers, each with a different level of aggressiveness, is designed to further cope with both unannounced meals and postprandial PA. Thus, the proposed control strategy has a "standard" mode, an "aggressive" mode, and a "conservative" mode. The "standard" mode is designed to be applied most of the time, while the "aggressive" mode is designed to deal only with hyperglycemia situations. On the other hand, the "conservative" mode is focused on postprandial PA control. An ad hoc simulator has been developed to test the proposed controller. This simulator is based on the distribution version of the UVA/Padova model and includes the effect of PA based on Schiavon.(1) The test results obtained when using this simulator indicate that the proposed control law substantially reduces the risk of hypoglycemia with the conservative strategy, while the risk of hyperglycemia is scarcely affected. It is demonstrated that the announcement, or anticipation, of exercise is indispensable for letting a mono-hormonal artificial pancreas deal with the consequences of postprandial PA. In view of this the proposed controller allows switching into a conservative mode when notified of PA by the user. © 2016 Diabetes Technology Society.

The Relationship between Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease Measured by Controlled Attenuation Parameter.

PubMed

Chon, Young Eun; Kim, Kwang Joon; Jung, Kyu Sik; Kim, Seung Up; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Chon, Chae Yoon; Chung, Jae Bock; Park, Kyeong Hye; Bae, Ji Cheol; Han, Kwang Hyub

2016-07-01

The severity of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) population compared with that in normal glucose tolerance (NGT) individuals has not yet been quantitatively assessed. We investigated the prevalence and the severity of NAFLD in a T2DM population using controlled attenuation parameter (CAP). Subjects who underwent testing for biomarkers related to T2DM and CAP using Fibroscan® during a regular health check-up were enrolled. CAP values of 250 dB/m and 300 dB/m were selected as the cutoffs for the presence of NAFLD and for moderate to severe NAFLD, respectively. Biomarkers related to T2DM included fasting glucose/insulin, fasting C-peptide, hemoglobin A1c (HbA1c), glycoalbumin, and homeostasis model assessment of insulin resistance of insulin resistance (HOMA-IR). Among 340 study participants (T2DM, n=66; pre-diabetes, n=202; NGT, n=72), the proportion of subjects with NAFLD increased according to the glucose tolerance status (31.9% in NGT; 47.0% in pre-diabetes; 57.6% in T2DM). The median CAP value was significantly higher in subjects with T2DM (265 dB/m) than in those with pre-diabetes (245 dB/m) or NGT (231 dB/m) (all p<0.05). Logistic regression analysis showed that subjects with moderate to severe NAFLD had a 2.8-fold (odds ratio) higher risk of having T2DM than those without NAFLD (p=0.02; 95% confidence interval, 1.21-6.64), and positive correlations between the CAP value and HOMA-IR (ρ0.407) or fasting C-peptide (ρ0.402) were demonstrated. Subjects with T2DM had a higher prevalence of severe NAFLD than those with NGT. Increased hepatic steatosis was significantly associated with the presence of T2DM, and insulin resistance induced by hepatic fat may be an important mechanistic connection.

Type 2 diabetes exaggerates exercise effort and impairs exercise performance in older women.

PubMed

Huebschmann, A G; Kohrt, W M; Herlache, L; Wolfe, P; Daugherty, S; Reusch, J Eb; Bauer, T A; Regensteiner, J G

2015-01-01

Type 2 diabetes mellitus (T2DM) is associated with high levels of disability and mortality. Regular exercise prevents premature disability and mortality, but people with T2DM are generally sedentary for reasons that are not fully established. We previously observed that premenopausal women with T2DM report greater effort during exercise than their counterparts without diabetes, as measured by the Rating of Perceived Exertion (RPE) scale. We hypothesized that RPE is greater in older women with T2DM versus no T2DM. We enrolled overweight, sedentary women aged 50-75 years with (n=26) or without T2DM (n=28). Participants performed submaximal cycle ergometer exercise at 30 W and 35% of individually-measured peak oxygen consumption (35% VO2peak). We assessed exercise effort by RPE (self-report) and plasma lactate concentration. VO2peak was lower in T2DM versus controls (p=0.003). RPE was not significantly greater in T2DM versus controls (30 W: Control, 10.4±3.2, T2DM, 11.7±2.3, p=0.08; 35% VO2peak: Control, 11.1±0.5, T2DM, 12.1±0.5, p=0.21). However, lactate was greater in T2DM versus controls (p=0.004 at 30 W; p<0.05 at 35% VO2peak). Greater RPE was associated with higher lactate, higher heart rate, and a hypertension diagnosis (p<0.05 at 30 W and 35% VO2peak). Taken together, physiological measures of exercise effort were greater in older women with T2DM than controls. Exercise effort is a modifiable and thereby targetable end point. In order to facilitate regular exercise, methods to reduce exercise effort in T2DM should be sought. NCT00785005.

The role of NOS2A −954G/C and vascular endothelial growth factor +936C/T polymorphisms in type 2 diabetes mellitus and diabetic nonproliferative retinopathy risk management

PubMed Central

Porojan, Mihai Dumitru; Cătană, Andreea; Popp, Radu A; Dumitrascu, Dan L; Bala, Cornelia

2015-01-01

Type 2 diabetes mellitus (T2DM) remains one of the major health problems in Europe. Retinopathy is one of the major causes of morbidity in T2DM, strongly influencing the evolution and prognosis of these patients. In the last 2 decades, several studies have been conducted to identify the possible genetic susceptibility factors involved in the pathogenesis of the disease. However, there is little data related to the involvement of vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS) gene polymorphisms in the T2DM Caucasian population. The objective of this study was to identify a possible connection between NOS2A −954G/C (rs2297518) and VEGF +936C/T (rs3025039) polymorphisms and the risk of developing T2DM and nonproliferative diabetic retinopathy in a Caucasian population group. We investigated 200 patients diagnosed with T2DM and 208 controls. Genotypes were determined by multiplex polymerase chain reaction-restriction fragment length polymorphism. Statistical and comparative analyses (Fisher’s exact test) for dominant and recessive models of NOS2A −954G/C and VEGF +936C/T polymorphisms revealed an increased risk of T2DM (χ2=8.14, phi =0.141, P=0.004, odds ratio [OR] =2.795, 95% confidence interval [CI] =1.347–5.801; χ2=18.814, phi =0.215, P<0.001, OR =2.59, 95% CI =1.675–4.006, respectively). Also, comparative analysis for the recessive model (using Pearson’s chi-square test [χ2] and the phi coefficient [phi]) reveals that the variant CC genotype of NOS2A gene is more frequently associated with T2DM without retinopathy (χ2=3.835, phi =−0.138, P=0.05, OR =0.447, 95% CI =0.197–1.015). In conclusion, the results of the study place VEGF +936C/T polymorphisms among the genetic risk factor for T2DM, whereas NOS2A −954G/C polymorphisms act like a protective individual factor for nonproliferative retinopathy. PMID:26664124

Type 1 diabetes (T1DM) in children and adolescents of immigrated families in Emilia-Romagna (Italy).

PubMed

Banin, Patrizia; Rimondi, Fiorenza; De Togni, Aldo; Cantoni, Stefano; Chiari, Giovanni; Iughetti, Lorenzo; Salardi, Silvana; Zucchini, Stefano; Marsciani, Alberto; Suprani, Tosca; Tarchini, Luis; Tozzola, Anna; Xella, Rossella; Marsella, Maria; De Sanctis, Vincenzo

2010-12-01

The etiology and natural history of T1DM are still unknown but certainly both genetics and environmental factors contribute to the development of the disease. Migration studies are an important tool to better understand the role of the environment. The aim of this study was to investigate some variables in diabetic children of immigrant families living in Emilia-Romagna compared with Italian diabetic children living in the same region. We recruited 73 diabetic children from immigrant families and 707 Italian diabetic children. All children were cared by Pediatric Diabetes Units of Emilia-Romagna (10 centers). The investigated variables were: gender, current age, place of birth, parents' country of origin, age at diagnosis, HbA1c and insulin regimen. No significant difference with reference to gender neither among the two ethnic groups, nor in the current mean age was observed. Mean age at diagnosis in the Italian children was lower than in immigrant patients born outside Italy--group A- (7.4 vs. 9.6, p < 0.000) and higher compared to those born in Italy--group B- (7.4 vs. 5.7 p < 0.003; A vs. B p < 0.000). The immigrant patients showed higher mean HbA1c than Italian patients (8.8 vs. 8.2, p < 0.009). A younger age at diagnosis of T1DM in immigrant children, born in Italy compared with those born in the country of origin, and with Italian patients, suggests the existence of some environmental determinants acquired with a more westernised lifestyle. Immigrant children have significantly poorer metabolic control compared with western patients. (www.actabiomedica.it)

Effectiveness of smartphone technologies on glycaemic control in patients with type 2 diabetes: systematic review with meta-analysis of 17 trials.

PubMed

Wu, I X Y; Kee, J C Y; Threapleton, D E; Ma, R C W; Lam, V C K; Lee, E K P; Wong, S Y S; Chung, V C H

2018-06-01

Patient education and behavioural interventions for self-management of type 2 diabetes mellitus (T2DM) are effective but place demands on manpower resources. This systematic review aimed to investigate the effectiveness of smartphone technologies (STs) for improving glycaemic control among T2DM patients. CENTRAL, MEDLINE, Embase, CINAHL and ScienceDirect were searched through December 2016. Randomized controlled trials comparing STs with usual diabetes care among T2DM patients and reporting change in glycated haemoglobin (HbA1c) level were included. Seventeen trials (2,225 participants) were included. There was a significant reduction in HbA1c (pooled weighted mean difference: -0.51%; 95% confidence interval: -0.71% to -0.30%; p < 0.001), favouring ST intervention. The pooled weighted mean difference was -0.83% in patients with T2DM <8.5 years and -0.22% in patients with T2DM ≥8.5 years, with significant subgroup difference (p = 0.007). No subgroup differences were found among different follow-up durations, trial locations, patients' age, healthcare provider contract time, baseline body mass index and baseline HbA1c. Compared with usual diabetes care, STs improved glycaemic control among T2DM patients, especially for patients at earlier disease stages (duration of diagnosis <8.5 years). STs could be a complement or alternative to labour-intensive patient education and behavioural interventions, but more studies on up-to-date technologies are needed. © 2018 World Obesity Federation.

Efficacy and safety of empagliflozin twice daily versus once daily in patients with type 2 diabetes inadequately controlled on metformin: a 16-week, randomized, placebo-controlled trial.

PubMed

Ross, S; Thamer, C; Cescutti, J; Meinicke, T; Woerle, H J; Broedl, U C

2015-07-01

Patients with type 2 diabetes mellitus (T2DM) with a glycated haemoglobin (HbA1c) level ≥7 and ≤10% were randomized to receive empagliflozin 12.5 mg twice daily (n = 219), 25 mg once daily (n = 218), 5 mg twice daily (n = 219) or 10 mg once daily (n = 220), or placebo (n = 107) as add-on to stable-dose metformin immediate release (IR) twice daily for 16 weeks. The primary endpoint was change from baseline in HbA1c at week 16. At week 16, change from baseline in HbA1c with empagliflozin twice daily was non-inferior to empagliflozin once daily and vice versa. The adjusted mean (95% confidence interval) difference in change from baseline in HbA1c with empagliflozin 12.5 mg twice daily versus 25 mg once daily was -0.11% (-0.26, 0.03), and with empagliflozin 5 mg twice daily versus 10 mg once daily it was -0.02% (-0.16, 0.13). All empagliflozin regimens were well tolerated; thus, when used as add-on to metformin IR in patients with T2DM, the therapeutic effect of empagliflozin twice-daily and once-daily regimens can be considered equivalent. © 2015 John Wiley & Sons Ltd.

Impact of Muscarinic M3 Receptor Antagonism on the Risk of Type 2 Diabetes in Antidepressant-Treated Patients: A Case-Controlled Study.

PubMed

Tran, Yen-Hao; Schuiling-Veninga, Catharina C M; Bergman, Jorieke E H; Groen, Henk; Wilffert, Bob

2017-06-01

M 3 muscarinic receptor antagonism has been associated with glucose intolerance and disturbance of insulin secretion. Our objective was to examine the risk of type 2 diabetes mellitus (T2DM) in patients using antidepressants with and without M 3 muscarinic receptor antagonism (AD_antaM 3 and AD_nonantaM 3 , respectively). We designed a case-control study using a pharmacy prescription database. We selected a cohort of patients who initiated antidepressant use between the ages of 20 and 40 years and who did not receive any anti-diabetic prescriptions at baseline. Cases were defined as those who developed T2DM [i.e., receiving oral anti-diabetic medication, Anatomical Therapeutic Chemical (ATC) code A10B] during the follow-up period (1994-2014), and ten random controls were picked for each case from the cohort of patients who did not develop T2DM. A total of 530 cases with incident T2DM and 5300 controls were included. Compared with no use of antidepressants during the previous 2 years, recent (within the last 6 months) exposure to AD_antaM 3 was associated with a moderately increased risk of T2DM: adjusted odds ratio 1.55 (95% confidence interval 1.18-2.02). In the stratified analyses, this association was dose dependent (>365 defined daily doses) and significant for patients who were in the younger age group (<45 years at the end of follow-up), were female and had no co-morbidity. On the other hand, recent exposure to AD_nonantaM 3 was not associated with a risk for T2DM in any of our analyses. Our results suggest that exposure to AD_antaM 3 was associated with the development of T2DM among antidepressant users.

Psychological Interventions for the Management of Glycemic and Psychological Outcomes of Type 2 Diabetes Mellitus in China: A Systematic Review and Meta-Analyses of Randomized Controlled Trials.

PubMed

Chapman, Anna; Liu, Shuo; Merkouris, Stephanie; Enticott, Joanne C; Yang, Hui; Browning, Colette J; Thomas, Shane A

2015-01-01

China has the largest number of type 2 diabetes mellitus (T2DM) cases globally, and T2DM management has become a critical public health issue in China. Individuals with T2DM have an increased risk of developing mental health disorders, psychological disturbances, and functional problems associated with living with their condition. Previous systematic reviews have demonstrated that, generally, psychological interventions are effective in the management of T2DM-related outcomes; however, these reviews have predominantly included studies conducted within English-speaking countries and have not determined the efficacy of the varying types of psychological interventions. As such, this paper aims to synthesize evidence and quantify the efficacy of psychological therapies for the management of glycemic and psychological outcomes of T2DM in China, relative to control conditions. A systematic search (MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wangfang Data) for all years to December 2014 identified all available literature. Eligibility criteria included: peer-reviewed journal articles, randomized controlled trials (RCTs) assessing the efficacy of a psychological therapy for the management of T2DM, adult participants (≥18 years) diagnosed with T2DM or non-insulin-dependent diabetes mellitus, and Chinese speaking participants only (in mainland China). Outcome measures were glycated hemoglobin, blood glucose concentration, depression, anxiety, and quality of life. Effect sizes were pooled using a random effects model. Negative effect sizes corresponded to positive outcomes favoring the intervention. Forty-five RCTs were eligible for the meta-analyses. Cognitive behavioral therapy (CBT) and motivational interviewing (MI) were more effective than the control condition in the reduction of glycated hemoglobin [CBT: -0.97 (95% CI -1.37 to -0.57); MI: -0.71 (95% CI -1.00 to -0.43)]. CBT and client

Left ventricular diastolic function in patients with type 2 diabetes treated with a dipeptidyl peptidase-4 inhibitor- a pilot study.

PubMed

Nogueira, Katia Camarano; Furtado, Meive; Fukui, Rosa Tsuneshiro; Correia, Marcia Regina Silva; Dos Santos, Rosa Ferreira; Andrade, José Lázaro; Rossi da Silva, Maria Elizabeth

2014-01-01

Blood glucose control is fundamental albeit not enough to prevent diabetic macrovascular complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in improving metabolic parameters in patients with type 2 diabetes mellitus (T2DM) but little is known about its cardiovascular effects. We compared the DPP-4 inhibitor sitagliptin with bedtime NPH insulin (NPH) as add-on therapy in patients with T2DM, aiming to ascertain which drug would have additional cardioprotective effects. Thirty-five T2DM patients inadequately controlled with metformin plus glyburide were randomized to receive sitagliptin (n = 18) or NPH (n = 17) for 24 weeks. Fasting plasma glucose, HbA1c, lipid profile, C-reactive protein, active glucagon-like peptide (aGLP-1) levels, 24-hour ambulatory blood pressure measurement and comprehensive 2-dimensional echocardiogram were determined before and after treatments. Both sitagliptin and NPH therapies decreased HbA1c levels after 24 weeks. Fasting plasma glucose and triglyceride levels decreased in the NPH group whereas only sitagliptin increased aGLP-1 levels. Left ventricular diastolic dysfunction (LVDD) was detected in 58.6% of twenty-nine patients evaluated. Beneficial effects in LVDD were observed in 75% and 11% of patients treated with sitagliptin and NPH, respectively (p = 0.015). Neither therapy changed C-reactive protein or blood pressure. Sitagliptin and bedtime NPH were similarly effective on glucose control. Improvement in LVDD in T2DM patients treated with sitagliptin was suggested, probably related to the increase of aGLP-1 levels. Therefore, DPP-4 inhibitor seems to have cardioprotective effects independent of glucose control and may have a role in the prevention of diabetic cardiomyopathy.

Psychiatric referral and glycemic control of Egyptian type 2 diabetes mellitus patients with depression.

PubMed

Fawzi, Mounir H; Said, Nagwa S; Fawzi, Maggie M; Kira, Ibrahim A; Fawzi, Mohab M; Abdel-Moety, Hanaa

2016-01-01

To evaluate the relationship between psychiatric referral acceptance for fluoxetine treatment and glycemic control in type 2 diabetes mellitus (T2DM) Egyptian patients with depression. Patients with T2DM who attended the diabetes outpatients clinic at Zagazig University Hospital, Egypt, between May 2013 and April 2015 and who scored ≥20 on screening with the Major Depression Inventory (MDI) (n=196) were offered a psychiatric referral for fluoxetine treatment and monitoring. Decliners (56.1%) received time/attention matched care via diabetologist visits (attentional controls). Fluoxetine patients and controls were compared at the time of the offer (T1) and 8weeks later (T2). Factors that significantly correlated with glycemic control were used in a linear regression analysis as the independent variables. Eighty-six patients (43.9%) accepted psychiatric referral. Most of them (97.7%) remained throughout the study adherent to fluoxetine (mean daily dose=31.9mg). At T2, these patients, in comparison to controls, showed a reduction from baseline in MDI, fasting plasma glucose and glycosylated hemoglobin (HbA1c) levels (P for all comparisons <.001). In the final model of a regression analysis, 65.9% of the variation in percentage change in HbA1c was explained by adherence to antidiabetics, psychiatric referral acceptance and Internalized Stigma of Mental Illness (ISMI) and MDI scores. In T2DM patients with depression, psychiatric referral acceptance for fluoxetine treatment is a significant predictor of both depression and glycemic control improvements. Copyright © 2016 Elsevier Inc. All rights reserved.

Factors Associated with Long-Term Control of Type 2 Diabetes Mellitus.

PubMed

Badedi, Mohammed; Solan, Yahiya; Darraj, Hussain; Sabai, Abdullah; Mahfouz, Mohamed; Alamodi, Saleh; Alsabaani, Abdullah

2016-01-01

Aims. This study assessed factors associated with glycemic control among Saudi patients with Type 2 diabetes mellitus (T2DM). Methods. We conducted an analytical cross-sectional study, which included a random sample of 288 patients with T2DM proportional to the diabetes population of each primary health care center in Jazan city, Kingdom of Saudi Arabia. Results. More than two-thirds (74%) of patients had poor glycemic control. Lack of education, polypharmacy, and duration of diabetes ≥ 7 years were significantly associated with higher glycated hemoglobin (HbA1c). Moreover, patients who were smoker or divorced were significantly more likely to have higher HbA1c. The patients who did not comply with diet or take their medications as prescribed had poor glycemic control. The study found lower HbA1c levels among patients who received family support or had close relationship with their physicians. Similarly, knowledgeable patients towards diabetes or those with greater confidence in ability to manage self-care behaviors had a lower HbA1c. In contrast, risk factors such as depression or stress were significantly correlated with poorer glycemic control. Conclusion. The majority of T2DM patients had poor glycemic control. The study identified several factors associated with glycemic control. Effective and tailored interventions are needed to mitigate exposure to these risk factors. This would improve glycemic control and reduce the risks inherent to diabetes complications.

Effects of vildagliptin as add-on treatment in patients with type 2 diabetes mellitus: insights from long-term clinical studies in Japan.

PubMed

Odawara, Masato; Sagara, Rieko

2015-01-01

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is wildly used to treat type 2 diabetes mellitus (T2DM) with mono- or combination-therapy. We review two previously published open-label studies to extract insights on the long-term efficacy and safety of vildagliptin. Two studies were conducted in Japan to assess the efficacy and safety of vildagliptin as an add-on to other oral antidiabetes drugs (OADs) for 52 weeks. These studies were performed under the similar protocol in Japanese patients with T2DM who were inadequately controlled with OAD monotherapy [excluding other dipeptidyl peptidase-4 (DPP-4) inhibitors]. Addition of vildagliptin (50 mg twice daily) to other OAD monotherapy [sulfonylurea (SU), metformin, thiazolidinedione, alpha-glucosidase inhibitor and glinide] reduced glycated hemoglobin (HbA1c) levels by -0.64 %,-0.75 %,-0.92 %,-0.94 % and - 0.64 %, respectively, over 52 weeks of treatment. Overall, the incidence of hypoglycemia was low and was slightly higher in the add-on to SU treatment group compared with the other groups. The incidences of adverse events were comparable among the treatment groups, and vildagliptin was well-tolerated as add-on therapy to other OADs. The evidence from the two studies indicates that vildagliptin as an add-on therapy to other OADs is a clinically reasonable option for Japanese patients with T2DM who respond inadequately to other OAD monotherapy.

Comparison of periodontal and peri-implant inflammatory parameters among patients with prediabetes, type 2 diabetes mellitus and non-diabetic controls.

PubMed

Abduljabbar, Tariq; Al-Sahaly, Faisal; Al-Kathami, Mohammed; Afzal, Sibtain; Vohra, Fahim

2017-07-01

The aim was to compare periodontal and periimplant inflammatory parameters (plaque index [PI], bleeding on probing [BOP], probing depth [PD] and marginal bone loss [MBL]) among patients with prediabetes, type-2 diabetes mellitus (T2DM) and non-diabetic controls. Forty-five patients with prediabetes (Group-1), 43 patients with T2DM (Group-2) and 42 controls (Group-3) were included. Demographic data was recorded using a questionnaire. Full mouth and periimplant clinical (PI, BOP and PD) were assessed and the radiographic MBL were measured on digital radiographs. In all groups, haemoglobin A1c (HbA1c) levels were also measured. p values less than .05 were considered statistically significant. The mean HbA1c levels of participants in groups 1, 2 and 3 were 6.1%, 8.4% and 4.8%, respectively. The mean duration of prediabetes and T2DM among patients in groups 1 and 2 were 1.9 ± 0.3 and 3.1 ± 0.5 years, respectively. Periodontal and periimplant PI, BOP, PD and MBL were higher in groups 1 (p < .05) and 2 (p < .05) than group 3. There was no difference in these parameters in groups 1 and 2. Periodontal and periimplant inflammatory parameters were worse among patients with prediabetes and T2DM compared with controls; however, these parameters were comparable among patients with prediabetes and T2DM.

A Study of Autoimmune Polyglandular Syndrome (APS) in Patients with Type1 Diabetes Mellitus (T1DM) Followed Up at a Teritiary Care Hospital

PubMed Central

Shaikh, Shaheen Banu; Haji, Ismail M.; Doddamani, Parveen; Rahman, M.

2014-01-01

Background: Type1 diabetes mellitus (T1DM) results from auto- immune destruction of insulin-producing β cells and is characterized by the presence of insulitis and β-cell autoantibodies. Up to one third of patients develop an autoimmune polyglandular syndrome (APS). Presence of other autoimmune disorders in patients with T1DM has been associated with increased morbidity and mortality. Hypoglycemia resulting from concurrent hypothyroidism or adrenal crisis can be dangerous; starting replacement therapy for hypothyroidism may result in adrenal crisis if background hypocortisolism is not recognized. Early detection of antibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown disease. Aims: The objectives of this study were to assess the concurrence of various autoimmune disorders in patients with T1DM, to review the concept and detect the overt forms of Autoimmune Thyroid Disease (AITD), Addison’s Disease (AD), Vitamin B 12, vitiligo in T1DM and to find their correlation according to age and sex of the patients. Methods: It is a retrospective study where medical records between January 2007-June 2010 of all the patients diagnosed with T1DM, followed up at Department of Endocrinology were reviewed to find out the presence of (AD), AITD, vitiligo, Vitamin B12 deficiency and Primary Gonadal Failure, which were diagnosed clinically with available investigational procedures. Results: A total of 100 cases of T1DM were evaluated during the present study. The age group of patients ranged from 8 to 40 years, with the average being 21.56 years. 64% of the patients were males and the rest were females. 29 % of T1DM subjects had AITD (Hashimoto’s or Graves’disease), 5% were diagnosed with Vitamin B12 deficiency, 4% had AD, and 6% showed Vitiligo. 28 % had family history of autoimmune endocrinopathy. Conclusion: The commonest autoimmune disorder associated with T1DM found in our study was

Real-world antidiabetic drug use and fracture risk in 12,277 patients with type 2 diabetes mellitus: a nested case-control study.

PubMed

Losada, E; Soldevila, B; Ali, M S; Martínez-Laguna, D; Nogués, X; Puig-Domingo, M; Díez-Pérez, A; Mauricio, D; Prieto-Alhambra, D

2018-06-02

We conducted a nested case-control study to study the association between antidiabetic treatments (alone or in combination) use and fracture risk among incident type 2 Diabetes mellitus patients. We found an increased risk of bone fracture with insulin therapy compared to metformin monotherapy. Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures, to which antidiabetic therapies may contribute. We aimed to characterize the risk of fracture associated with different antidiabetic treatments as usually prescribed to T2DM patients in actual practice conditions. A case-control study was nested within a cohort of incident T2DM patients registered in 2006-2012 in the Information System for Research Development in Primary Care (Catalan acronym, SIDIAP), a database which includes records for > 5.5 million patients in Catalonia (Spain). Each case (incident major osteoporotic fracture) was risk-set matched with up to five same-sex controls by calendar year of T2DM diagnosis and year of birth (± 10 years). Study exposure included previous use of all antidiabetic medications (alone or in combination), as dispensed in the 6 months before the index date, with metformin (MTF) monotherapy, the most commonly used drug, as a reference group (active comparator). Data on 12,277 T2DM patients (2049 cases and 10,228 controls) were analyzed. Insulin use was associated with increased fracture risk (adjusted OR 1.63 (95% CI 1.30-2.04)), as was the combination of MTF and sulfonylurea (SU) (adjusted OR 1.29 (1.07-1.56)), compared with MTF monotherapy. Sensitivity analyses suggest possible causality for insulin therapy but not for the MTF + SU combination association. No significant association was found with any other antidiabetic medications. Insulin monotherapy was associated with an increased fracture risk compared to MTF monotherapy in T2DM patients. Fracture risk should be taken into account when starting a glucose-lowering drug as part

Dose titration of repaglinide in patients with inadequately controlled type 2 diabetes.

PubMed

Kølendorf, Klaus; Eriksson, Johan; Birkeland, Kåre I; Kjellström, Thomas; Hreidarsson, Astradur B

2004-04-01

A total of 385 drug-therapy naïve patients, with inadequately controlled type 2 diabetes, were randomised into a multinational, parallel-group study to compare two strategies for dose titration of the oral hypoglycaemic agent repaglinide. Patients were allocated to either a fasting blood glucose (FBG) monitoring group with titration target 4.4-6.1 mmol/l or to a post-prandial blood glucose (PPBG) monitoring group with titration target 4.4-8.0 mmol/l. An initial titration period of up to 8 weeks was followed by a 12-week treatment period. Glycaemic control and hypoglycaemic outcomes were compared for the respective groups. HbA(1c) decreased significantly more in the FBG monitoring group by a mean of 1.38% compared to the PPBG group by a mean of 1.22% (P=0.03). The glycaemic control targets were met by fewer patients in the FBG group than in the PPBG group (57% versus 86% (P<0.001)) despite a higher mean dose of repaglinide in the FBG group. The within-patient blood glucose variability was significantly lower in the FBG group than in the PPBG group (P<0.001). In conclusion, repaglinide lowered the HbA(1c) effectively and safely in both groups and self-monitored FBG is a suitable parameter for titration of repaglinide. Whether a lower PPBG target might be as good a guide as FBG for titration of repaglinide should be addressed in a future study.

Association of angiotensin-converting enzyme (ACE) and fatty acid binding protein 2 (FABP2) genes polymorphism with type 2 diabetes mellitus in Northern India.

PubMed

Raza, Syed Tasleem; Fatima, Jalees; Ahmed, Faisal; Abbas, Shania; Zaidi, Zeashan Haider; Singh, Seema; Mahdi, Farzana

2014-12-01

Type 2 diabetes mellitus (T2DM) is growing in an epidemic manner across the world with an expected doubling of the incidence to millions of affected individuals in the last decades. At present, adequate data are not available regarding the ACE and FABP2 polymorphisms and their susceptibility with T2DM cases in the North Indian population. Thus we conceived the need for further study of ACE (I/D) and FABP2 (Ala54Thr) genes polymorphism and its susceptibility to T2DM in the North Indian population. In this study, a total of 300 subjects (including 190 T2DM cases and 110 controls) participated. ACE and FABP2 gene polymorphisms in the cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism. The frequencies of ACE I/I, I/D and D/D genotypes in T2DM cases and controls were 28.73%, 55.17%, 16.09% and 13.63%, 57.95%, 28.40%, respectively. The frequencies of FABP2 Ala54Ala, Ala54Thr and Thr54Thr in T2DM cases were 18.39%, 66.66%, 14.94% and 22.72%, 61.36%, 15.90% in controls, respectively. ACE I/I genotype was significantly more frequent in cases as compared to controls (p = 0.003, χ(2) = 9.13). It appears that the ACE I/I genotype frequency was significantly higher in the T2DM cases as compared to the controls. © The Author(s) 2013.

Association of TNF-α 308 G/A Polymorphism With Type 2 Diabetes: A Case–Control Study in the Iranian Kurdish Ethnic Group

PubMed Central

Golshani, Hasan; Haghani, Karimeh; Dousti, Majid; Bakhtiyari, Salar

2015-01-01

Objectives Tumor necrosis factor-α (TNF-α) plays roles in the development of obesity, insulin resistance, and possibility of Type 2 diabetes mellitus (T2DM). The objective of the current study was to evaluate the association of TNF-α promoter−308 G/A polymorphism with T2DM. Methods In all, 1038 patients with T2DM and 1023 normoglycemic controls were included in this study. All participants were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Genotypic and allelic frequencies were then analyzed in each group. Serum lipids, fasting glucose, fasting serum insulin, homeostatic model assessment of insulin resistance, and hemoglogin A1c levels were determined by conventional methods. Results The allelic frequency of the A allele was significantly different between case and control participants (p = 0.006). Genotypes GA and AA were found to be significantly associated with 2.24- and 3.18-fold increased risk for T2DM, respectively. Similarly, the dominant model of -308 G/A polymorphism was found to have a higher risk for T2DM (odds ratio = 2.34, p = 0.001). Individuals with T2DM carrying the GA + AA genotypes of -308 G/A variation had significantly lower fasting plasma insulin than those carrying GG genotype. Conclusion Our findings revealed that there is an association between the TNF-α promoter -308 G/A polymorphism and T2DM in this population. PMID:25938018

Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster.

PubMed

Blenau, Wolfgang; Daniel, Stöppler; Balfanz, Sabine; Thamm, Markus; Baumann, Arnd

2017-01-01

Serotonin (5-hydroxytryptamine, 5-HT) is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects) and deuterostomes (e.g., mammals). In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In Drosophila melanogaster , a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT 1A , Dm5-HT 1B , and Dm5-HT 7 couple to cAMP signaling cascades, the Dm5-HT 2A receptor leads to Ca 2+ signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth D. melanogaster gene was uncovered coding for a Dm5-HT 2B receptor. Knowledge about this receptor's pharmacological properties is very limited. This is quite surprising because Dm5-HT 2B has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT 2B mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT 2B 's pharmacology, we evaluated the receptor's response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT 2B signaling in vitro and in vivo .

Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster

PubMed Central

Blenau, Wolfgang; Daniel, Stöppler; Balfanz, Sabine; Thamm, Markus; Baumann, Arnd

2017-01-01

Serotonin (5-hydroxytryptamine, 5-HT) is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects) and deuterostomes (e.g., mammals). In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In Drosophila melanogaster, a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT1A, Dm5-HT1B, and Dm5-HT7 couple to cAMP signaling cascades, the Dm5-HT2A receptor leads to Ca2+ signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth D. melanogaster gene was uncovered coding for a Dm5-HT2B receptor. Knowledge about this receptor’s pharmacological properties is very limited. This is quite surprising because Dm5-HT2B has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT2B mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT2B’s pharmacology, we evaluated the receptor’s response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT2B signaling in vitro and in vivo. PMID:28553207

Association between ADIPOQ +45T>G Polymorphism and Type 2 Diabetes: A Systematic Review and Meta-Analysis

PubMed Central

Fan, Yaofu; Wang, Kun; Xu, Shuhang; Chen, Guofang; Di, Hongjie; Cao, Meng; Liu, Chao

2014-01-01

Recently, a number of studies have reported the association between the single nucleotide polymorphisms (SNPs) +45T>G polymorphism in the adiponectin (ADIPOQ) gene and type 2 diabetes mellitus (T2DM) risk, though the results are inconsistent. In order to obtain a more precise estimation of the relationship, a meta-analysis was performed. In this current study, the Medline, Embase, Pubmed, ISI Web of Knowledge, Ovid, Science Citation Index Expanded Database, Wanfang Database, and China National Knowledge Infrastructure were searched for eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of association. Forty-five publications were included in the final meta-analysis with 9986 T2DM patients and 16,222 controls for ADIPOQ +45T>G polymorphism according to our inclusion and exclusion criteria. The +45T>G polymorphism was associated with an overall significantly increased risk of T2DM (G vs. T: OR = 1.18, 95% CI = 1.06–1.32; The dominant model: OR = 1.18, 95% CI = 1.03–1.33; The recessive model: OR = 1.47, 95% CI = 1.20–1.78; The homozygous model: OR = 1.62, 95% CI = 1.25–2.09; Except the heterozygous model: OR = 1.11, 95% CI = 0.98–1.24). Subgroup analysis revealed a significant association between the +45T>G polymorphism and T2D in an Asian population. Thus, this meta-analysis indicates that the G allele of the ADIPOQ +45T>G polymorphisms associated with a significantly increased risk of T2DM in the Asian population. PMID:25561226

Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

PubMed

Hong, S; Park, C-Y; Han, K A; Chung, C H; Ku, B J; Jang, H C; Ahn, C W; Lee, M-K; Moon, M K; Son, H S; Lee, C B; Cho, Y-W; Park, S-W

2016-05-01

We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Vitreous advanced glycation endproducts and α-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls

PubMed Central

Mulder, Douwe J.; Schalkwijk, Casper G.; Scheijen, Jean L.; Smit, Andries J.; Los, Leonoor I.

2017-01-01

Purpose Advanced glycation endproducts (AGEs) and their precursors α-dicarbonyls are implicated in the progression of diabetic retinopathy. The purpose of this study was to assess AGEs and α-dicarbonyls in the vitreous of patients with type 2 diabetes mellitus (T2DM) with early stages or absence of diabetic retinopathy. Methods We examined vitreous samples obtained during vitrectomy from 31 T2DM patients presenting themselves with rhegmatogenous retinal detachment and compared these to 62 non-diabetic rhegmatogenous retinal detachment patients, matched on age, estimated glomerular filtration rate, smoking, intra-ocular lens implantation, and proliferative vitreoretinopathy. AGEs (pentosidine, Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and 5-hydro-5-methylimidazolone) and α-dicarbonyls (3-deoxyglucosone, methylglyoxal, and glyoxal) were measured by ultra performance liquid chromatography or high performance liquid chromatography. Skin autofluorescence was measured by the AGE Reader. Results Mean age was 64 ± 7.6 years for T2DM patients and 63 ± 8.1 years for controls. For T2DM patients, median diabetes duration was 2.2 (0.3–7.4) years. Non-proliferative diabetic retinopathy was present in 1 patient and classified as absent or background retinopathy in 30 patients. Vitreous levels of pentosidine (2.20 vs. 1.59 μmol/mol lysine, p = 0.012) and 3-deoxyglucosone (809 vs. 615 nmol/L, p = 0.001) were significantly elevated in T2DM patients compared to controls. Other AGEs and α-dicarbonyls in the vitreous were not significantly different. There was a trend for increased skin autofluorescence in T2DM patients as compared to controls (p = 0.07). Conclusions Pentosidine and 3-deoxyglucosone concentrations were increased in the vitreous of rhegmatogenous retinal detachment patients with a relatively short duration of diabetes compared to non-diabetic rhegmatogenous retinal detachment patients. PMID:28264049

A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.

PubMed

Ikeda, S; Takano, Y; Cynshi, O; Tanaka, R; Christ, A D; Boerlin, V; Beyer, U; Beck, A; Ciorciaro, C; Meyer, M; Kadowaki, T

2015-10-01

To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). In a 12-week, multicentre, multinational, randomized, double-blind, parallel-group, placebo-controlled, dose-finding study, patients with inadequate glycaemic control from diet and exercise alone, or from diet and exercise plus a stable dose of metformin, were randomized to one of five doses of tofogliflozin (2.5, 5, 10, 20, or 40 mg) or placebo. The primary efficacy endpoint was absolute change at week 12 from baseline in glycated haemoglobin (HbA1c), minus the change in the placebo group. Statistically significant dose-dependent reductions in HbA1c were shown in all treated groups except the 2.5-mg dose group, with a maximum reduction of 0.56% (placebo-subtracted) at the 40-mg dose, along with increased urinary glucose excretion. Metformin treatment had no substantial influence on tofogliflozin efficacy. Dose-dependent reductions in fasting plasma glucose and body weight were observed, and glucose intolerance was improved, with a trend towards blood pressure reduction. Slight increases were observed for mean ketone bodies with no abnormal change in ketone body ratio. No deaths or treatment-related serious adverse events were reported. The incidence of adverse events was similar in the placebo (37.9%) to that in the tofogliflozin group (35.9-46.3%). Withdrawal because of adverse events was rare (≤2 patients per treatment group), with similar rates of withdrawal in the placebo and tofogliflozin groups. A once-daily dose of tofogliflozin for 12 weeks was an effective, safe and well-tolerated treatment for T2DM. © 2015 John Wiley & Sons Ltd.

Effectiveness of chamomile tea on glycemic control and serum lipid profile in patients with type 2 diabetes.

PubMed

Rafraf, M; Zemestani, M; Asghari-Jafarabadi, M

2015-02-01

This study aimed at assessing the effects of chamomile tea consumption on glycemic control and serum lipid profile in patients with type 2 diabetes mellitus (T2DM). This single-blind randomized controlled clinical trial was conducted on 64 individuals with T2DM (males and females) aged between 30 and 60 years. The intervention group (n = 32) consumed chamomile tea (3 g/150 mL hot water) three times per day immediately after meals for 8 weeks. The control group (n = 32) followed a water regimen for the same intervention period. Fasting blood samples, anthropometric measurements, and 3-day, 24-h dietary recalls were collected at the baseline and at the end of the trial. Data were analyzed by independent t test, paired t test, Pearson correlation test, and analysis of covariance. Chamomile tea significantly decreased concentration of HbA1C (p = 0.03), serum insulin levels (p < 0.001), homeostatic model assessment for insulin resistance (p < 0.001), total cholesterol (p = 0.001), triglyceride (p < 0.001), and low-density lipoprotein cholesterol (p = 0.05) compared with control group. No significant changes were shown in serum high-density lipoprotein cholesterol levels in both groups. Chamomile tea has some beneficial effects on glycemic control and serum lipid profile in T2DM patients.

T-cell receptor repertoire variation may be associated with type 2 diabetes mellitus in humans.

PubMed

Frankl, Joseph A; Thearle, Marie S; Desmarais, Cindy; Bogardus, Clifton; Krakoff, Jonathan

2016-03-01

Recent work in Pima Indians, a population with high rates of obesity and type 2 diabetes mellitus (T2DM), demonstrated that human leukocyte antigen haplotype DRB1*02 carriers have an increased acute insulin response and decreased risk for the development of T2DM, implicating loss of self-tolerance in the pathogenesis of T2DM. Advances in genomic sequencing have made T-cell receptor repertoire analysis a practical mode of investigation. High-throughput sequencing of T-cell receptor complementarity-determining region 3 was carried out in male Pima Indians with normal glucose regulation (n = 11; age = 31 ± 8 years; %fat = 30.2 ± 8.7%) and the protective DRB1*02 haplotype versus those with T2DM without DRB1*02 (n = 7; age = 34 ± 8 years; %fat = 31.2 ± 4.7%). Findings were partially replicated in another cohort by assessing the predictive ability of T-cell receptor variation on risk of T2DM in Pima Indian men (n = 27; age = 28.9 ± 7.1 years; %fat = 28.8 ± 7.1%) and women (n = 20; age = 29 ± 7.0 years; %fat = 37.1 ± 6.8%) with baseline normal glucose regulation but without the protective haplotype who were invited to follow-up examinations as frequently as every 2 years where diabetes status was assessed by a 75-g oral glucose tolerance test. Of these subjects, 13 developed diabetes. T-cell receptor complementarity-determining region 3 length was shorter in those with T2DM, and a one-nucleotide decrease in complementarity-determining region 3 length was associated with a nearly threefold increase in risk for future diabetes. The frequency of one variable gene, TRBV7-8, was higher in those with T2DM. A 1% increase in TRBV7-8 frequency was associated with a greater than threefold increase in diabetes risk. These results indicate that T-cell autoimmunity may be an important component in progression to T2DM in Pima Indians. Copyright © 2015 John Wiley & Sons, Ltd.

Design and methods for a pilot randomized clinical trial involving exercise and behavioral activation to treat comorbid type 2 diabetes and major depressive disorder

PubMed Central

Schneider, Kristin L.; Pagoto, Sherry L.; Handschin, Barbara; Panza, Emily; Bakke, Susan; Liu, Qin; Blendea, Mihaela; Ockene, Ira S.; Ma, Yunsheng

2011-01-01

Background The comorbidity of type 2 diabetes mellitus (T2DM) and depression is associated with poor glycemic control. Exercise has been shown to improve mood and glycemic control, but individuals with comorbid T2DM and depression are disproportionately sedentary compared to the general population and report more difficulty with exercise. Behavioral activation, an evidence-based depression psychotherapy, was designed to help people with depression make gradual behavior changes, and may be helpful to build exercise adherence in sedentary populations. This pilot randomized clinical trial will test the feasibility of a group exercise program enhanced with behavioral activation strategies among women with comorbid T2DM and depression. Methods/Design Sedentary women with inadequately controlled T2DM and depression (N=60) will be randomly assigned to one of two conditions: exercise or usual care. Participants randomized to the exercise condition will attend 38 behavioral activation-enhanced group exercise classes over 24 weeks in addition to usual care. Participants randomized to the usual care condition will receive depression treatment referrals and print information on diabetes management via diet and physical activity. Assessments will occur at baseline and 3-, 6-, and 9-months following randomization. The goals of this pilot study are to demonstrate feasibility and intervention acceptability, estimate the resources and costs required to deliver the intervention and to estimate the standard deviation of continuous outcomes (e.g., depressive symptoms and glycosylated hemoglobin) in preparation for a fully-powered randomized clinical trial. Discussion A novel intervention that combines exercise and behavioral activation strategies could potentially improve glycemic control and mood in women with comorbid type 2 diabetes and depression. Trial registration NCT01024790 PMID:21765864

A pilot three-month sitagliptin treatment increases serum adiponectin level in Japanese patients with type 2 diabetes mellitus--a randomized controlled trial START-J study.

PubMed

Hibuse, Toshiyuki; Maeda, Norikazu; Kishida, Ken; Kimura, Takekazu; Minami, Tomoko; Takeshita, Eriko; Hirata, Ayumu; Nakagawa, Yasuhiko; Kashine, Susumu; Oka, Akemi; Hayashi, Masumi; Nishizawa, Hitoshi; Funahashi, Tohru; Shimomura, Iichiro

2014-05-24

The dipeptidyl-peptidase-IV (DPP-4) inhibitors, including sitagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM). Adiponectin, an adipocyte-derived circulating protein, has anti-atherosclerotic and anti-diabetic properties and is effectively elevated in bloodstream by thiazolidinediones, an insulin sensitizer. However, the effect of sitagliptin treatment on serum adiponectin level in T2DM has not fully elucidated in Japanese T2DM patients. The aim of the present study was to examine the effect of sitagliptin treatment on serum adiponectin levels in T2DM subjects. Twenty-six consecutive Japanese T2DM outpatients were recruited between April 2011 and March 2013, and randomized into the control (conventional treatment, n = 10) group and sitagliptin treatment group (n = 16). Serum adiponectin was measured by enzyme-linked immunosorbent assay. Indices of glycemic control, such as hemoglobin A1c, glycated albumin, and 1.5-anhydro-D-glucitol, were significantly improved after the three-month treatment in both the control and sitagliptin groups. Serum adiponectin level was significantly increased in sitagliptin group from 6.7 ± 0.8 to 7.4 ± 1.0 μg/mL without change of body mass index (p = 0.034), while serum adiponectin level was not altered in the control group (p = 0.601). In Japanese T2DM patients, serum adiponectin level was elevated by three-month treatment with sitagliptin without change of body weight. UMIN000004721.

Cost-Effectiveness of Canagliflozin versus Sitagliptin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus in Mexico.

PubMed

Neslusan, Cheryl; Teschemaker, Anna; Johansen, Pierre; Willis, Michael; Valencia-Mendoza, Atanacio; Puig, Andrea

2015-12-01

To assess the cost-effectiveness of canagliflozin versus sitagliptin for the treatment of type 2 diabetes mellitus (T2DM) as an add-on to metformin in Mexico. A validated model (Economic and Health Outcomes [ECHO]-T2DM) was used to estimate the cost-effectiveness of canagliflozin 300 or 100 mg versus sitagliptin 100 mg in patients with T2DM inadequately controlled on metformin monotherapy. Data from a head-to-head, phase III clinical trial, including patients' baseline demographic characteristics, biomarker values, and treatment effects, were used to simulate outcomes and resource use over 20 years from the perspective of the Mexican health care system. Costs of complications and adverse events were tailored to the Mexican setting and discounted at 5%. Cost-effectiveness was assessed using willingness-to-pay thresholds equivalent to 1 times the gross domestic product per capita (locally perceived to be "very cost-effective") and 3 times the gross domestic product per capita (locally perceived to be "cost-effective") on the basis of recommendations of the Mexican government and the World Health Organization. Owing primarily to better glycated hemoglobin (HbA 1c ), body weight, and systolic blood pressure values, canagliflozin 300 and 100 mg were associated with an incremental benefit of 0.16 and 0.06 quality-adjusted life-years (QALYs) versus sitagliptin 100 mg, respectively, over 20 years. The mean differences in cost for canagliflozin 300 and 100 mg versus sitagliptin 100 mg were Mexican pesos (MXP) 1797 (US $134) and MXP 7262 (US $540), respectively, resulting in a cost per QALY gained of MXP 11,210 (US $834) and MXP 128,883 (US $9590), respectively. Both of these cost-effectiveness ratios are below the very cost-effective willingness-to-pay threshold in Mexico. The general finding that canagliflozin is cost-effective versus sitagliptin in Mexico was supported by sensitivity analyses. In Mexico, both doses of canagliflozin are likely to be cost-effective versus

Comparing type 1 and type 2 diabetes in pregnancy- similar conditions or is a separate approach required?

PubMed

Owens, Lisa A; Sedar, Jon; Carmody, Louise; Dunne, Fidelma

2015-03-27

Pregnancy in women with type 1 (T1DM) or type 2 diabetes (T2DM) is associated with increased risk. These conditions are managed similarly during pregnancy, and compared directly in analyses, however they affect women of different age, body mass index and ethnicity. We assess if differences exist in pregnancy outcomes between T1DM and T2DM by comparing them directly and with matched controls. We also analyze the effect of glycemic control on pregnancy outcomes and analyze predictive variables for poor outcome. We include 323 women with diabetes and 660 glucose-tolerant controls. T2DM women had higher BMI, age and parity with a shorter duration of diabetes and better glycemic control. Preeclampsia occurred more in women with T1DM only. Rates of elective cesarean section were similar between groups but greater than in controls, emergency cesarean section was increased in women with type 1 diabetes. Maternal morbidity in T1DM was double that of matched controls but T2DM was similar to controls. Babies of mothers with diabetes were more likely to be delivered prematurely. Neonatal hypoglycemia occurred more in T1DM than T2DM and contributed to a higher rate of admission to neonatal intensive care for both groups. Adverse neonatal outcomes including stillbirths and congenital abnormalities were seen in both groups but were more common in T1DM pregnancies. HbA1C values at which these poor outcomes occurred differed between T1 and T2DM. Pregnancy outcomes in T1DM and T2DM are different and occur at different levels of glycemia. This should be considered when planning and managing pregnancy and when counseling women.

Evaluating the impact of type 2 diabetes mellitus on CYP450 metabolic activities: protocol for a case-control pharmacokinetic study.

PubMed

Gravel, Sophie; Chiasson, Jean-Louis; Dallaire, Suzanne; Turgeon, Jacques; Michaud, Veronique

2018-02-08

Diabetes affects more than 9% of the adult population worldwide. Patients with type 2 diabetes mellitus (T2DM) show variable responses to some drugs which may be due, in part, to variability in the functional activity of drug-metabolising enzymes including cytochromes P450 (CYP450s). CYP450 is a superfamily of enzymes responsible for xenobiotic metabolism. Knowledge must be gained on the impact of T2DM and related inflammatory processes on drug metabolism and its consequences on drug response. The aim of this study is to characterise the activity of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4/5 in T2DM versus non-T2DM subjects following the administration of a cocktail of probe drug substrates. This single-centre clinical study proposes the first detailed characterisation of T2DM impacts on major CYP450 drug-metabolising enzyme activities. We intend to recruit 42 patients with controlled T2DM (A1C≤7%), 42 patients with uncontrolled T2DM (A1C>7%) and 42 non-diabetic control subjects. The primary objective is to determine and compare major CYP450 activities in patients with T2DM versus non-diabetic subjects by dosing in plasma and urine probe drug substrates and metabolites following the oral administration of a drug cocktail: caffeine (CYP1A2), bupropion (CYP2B6), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4/5). Secondary objectives will evaluate the influence of variables such as glycaemia, insulinaemia, genetic polymorphisms and inflammation. The value of an endogenous biomarker of CYP3A activity is also evaluated. The first patient was recruited in May 2015 and patients will be enrolled up to completion of study groups. Approval was obtained from the ethic review board of the CHUM research centre (Montreal, Canada). NCT02291666. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is

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

PubMed Central

Dwyer, Johanna T.; Bailey, Regan L.

2016-01-01

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

Identifying patients with chronic hepatitis B at high risk of type 2 diabetes mellitus: a cross-sectional study with pair-matched controls.

PubMed

Shen, Yi; Zhang, Jian; Cai, Hui; Shao, Jian-Guo; Zhang, You-Yi; Liu, Yan-Mei; Qin, Gang; Qin, Yan

2015-03-19

The presence of diabetes mellitus (DM) is associated with increased liver morbidity and mortality risk in patients with chronic hepatitis B (CHB). Aim of this study was to identify factors associated with type 2 diabetes mellitus (T2DM) in CHB patients. A cross-sectional study with pair-matched controls was conducted in Nantong Third People's Hospital, Nantong University, China. From January 2008 to December 2012, a total of 1783 CHB patients were screened for study subjects, among whom 207 patients with T2DM were enrolled as cases and 207 sex- and age-matched non-DM patients as controls. Demographic, anthropometric, lifestyle, clinical, and laboratory data were obtained from each subject. In the univariate model, thirteen variables showed marked differences between the DM group and non-DM group. Patients with longer duration of CHB (≥15 years) and alcoholic steatosis showed the highest likelihood of T2DM (odds ratio = 5.39 and 4.95; 95% confidence intervals 2.76-10.53 and 1.65-14.91). In the multivariate adjusted analysis, three CHB-related factors, namely high viral load, long duration of illness, and presence of cirrhosis, contributed to substantially increase the likelihood of T2DM, in addition to the other five risk factors including family history of DM, low education level, elevated triglycerides (TG), gamma-glutamyl transferase (GGT) levels, and presence of alcoholic steatosis. Our findings suggest that high viral load, long duration of CHB, presence of cirrhosis, alcoholic steatosis and several other factors may be potential risk factors for development of T2DM in CHB patients. It is of vital importance to monitor glucose in high-risk CHB patients and aggressively intervene on modifiable risk factors.

Association of Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor gamma 2 (PPARγ2) Gene with Type 2 Diabetes Mellitus in Ethnic Kashmiri Population.

PubMed

Majid, Misbah; Masood, Akbar; Kadla, Showkat Ahmad; Hameed, Iqra; Ganai, Bashir A

2017-02-01

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia associated with insulin resistance and relative insulin deficiency. T2DM is believed to be attributable to the combined effect of genetic and environmental factors. Peroxisome proliferator-activated receptor gamma 2 (PPARγ2) is one of the main candidate genes that are implicated in T2DM. A common proline 12 alanine (Pro12Ala) polymorphism in PPARγ2 has been shown to be associated with T2DM. The aim of this work was to investigate the possible role of PPARγ2 gene polymorphism, as a genetic risk factor for T2DM. The study comprised 200 ethnic unrelated subjects (100 T2DM patients and 100 controls). PCR-RFLP technique was used for genotyping analysis. The frequency of the Pro allele was 79 and 91.5 % for controls and cases, respectively (P < 0.05; OR 3.2; 95 % CI 1.64-6.3). The Pro12Ala polymorphism was in Hardy-Weinberg equilibrium in both patients and controls (χ 2  = 0.13, P > 0.05). We found a significant association of Pro12Ala polymorphism of PPARγ2 gene with T2DM, however the genotypes showed statistically significant association only with few clinical parameters including body mass index, total cholesterol, and low-density lipoprotein (P < 0.05). The study signifies that Pro allele in PPARγ2 may be a genotypic risk factor that confers susceptibility to T2DM in ethnic Kashmiri population.

N-acetyltransferase 1 and 2 polymorphisms and risk of diabetes mellitus type 2 in a Saudi population.

PubMed

Al-Shaqha, Waleed M; Alkharfy, Khalid M; Al-Daghri, Nasser M; Mohammed, Abdul Khader

2015-01-01

There have been inconsistent reports on N-acetyltransferase (NAT) gene polymorphism in type 2 diabetes mellitus (T2DM), and data is particularly limited in the Arab population. Therefore, the main objective of this study was to identify whether the genetic polymorphisms of NAT1 and NAT2 play a role in susceptibility to T2DM in the Saudi population. A population-based, prospective genetic association case-control study on a Saudi population. Whole blood, anthropometric measurements and biochemistry data were collected from 369 Saudi individuals (186 T2DM patients and 183 healthy controls). DNA was isolated from the blood. Polymorphism of NAT1 and NAT2 SNPs [NAT2*7B, rs1041983(C > T); NAT2*7, rs1799931(G > A); NAT2*6A, rs1799930(G > A); NAT2*5A, rs1799929(C > T); and NAT1*11A, rs4986988(C > T)] were evaluated by allelic discrimination using real-time PCR. Subjects with T2DM had a significantly increased body mass index (BMI), waist circumference, sys.tolic and diastolic blood pressure, glucose, triglycerides, and LDL-cholesterol compared with healthy controls (P < .05). The rs1799931(G > A) genotype was detected in the control population but not in the T2DM population (P < .001). The wild type (G) allele frequency was higher in T2DM than controls (P=.038). The mutant allele (A) in rs1799931(G > A) had a protective effect for T2DM (OR 0.32, 95% CI 0.16-0.62; P=.001). Regression analysis showed that BMI, systolic BP and triglycerides are potential risk factors for T2DM. The genotypes as well as the individual alleles of rs1799931(G > A) differed significantly be.tween the case and control populations. The variation in the data reported so far suggest that polymorphism of the NAT gene may vary among different geographical areas. Environmental or dietary factors may also contribute to disease manifestation.

Efficacy and Safety of Vildagliptin as an Add-On Therapy in Inadequately Controlled Type 2 Diabetes Patients Treated With Basal Insulin.

PubMed

Saito, Daisuke; Kanazawa, Akio; Shigihara, Nayumi; Sato, Fumihiko; Uchida, Toyoyoshi; Sato, Junko; Goto, Hiromasa; Miyatsuka, Takeshi; Ikeda, Fuki; Ogihara, Takeshi; Ohmura, Chie; Watada, Hirotaka

2017-03-01

The aim of this study was to investigate the efficacy and safety of vildagliptin as an add-on therapy for patients with type 2 diabetes mellitus inadequately controlled with basal insulin. Twenty-four patients treated with basal insulin and oral anti-diabetes drugs were randomly allocated into two groups: the control group (did not receive any add-on drugs) and vildagliptin group (received vildagliptin 100 mg/day for 6 months). The primary outcome was changes in hemoglobin A1c (HbA1c) from baseline to end of study. Treatment with vildagliptin significantly reduced HbA1c from 8.1±0.7% at baseline to 7.1±0.7% (P < 0.01), while there was no significant change of HbA1c in the control group. Vildagliptin group showed significant reduction of HbA1c compared with control group (-1.0±0.3% vs. 0.2±0.8%, P < 0.01). In addition, vildagliptin group showed a significant increase in 1,5-anhydroglucitol compared with the control group (4.5 ± 3.4 vs. 0.5 ± 4.1 μg/mL, P < 0.05). Mild hypoglycemia was reported in one patient of the vildagliptin group and two patients of the control group. Vildagliptin improved glycemic control without increasing hypoglycemia in Japanese type 2 diabetes inadequately controlled with basal insulin treatment and other oral anti-diabetes drugs. This study was registered with UMIN (University Hospital Medical Information Network ID#000010849).

Polyuria with the Concurrent manifestation of Central Diabetes Insipidus (CDI) & Type 2 Diabetes Mellitus (DM)

PubMed Central

Shin, Hyun-Jong; Kim, Jae-Ha; Han, Sang-Woong; Kim, Ho-Jung

2012-01-01

We report a rare case of the concurrent manifestation of central diabetes insipidus (CDI) and type 2 diabetes mellitus (DM). A 56 year-old man was diagnosed as a type 2 DM on the basis of hyperglycemia with polyuria and polydipsia at a local clinic two months ago and started an oral hypoglycemic medication, but resulted in no symptomatic improvement at all. Upon admission to the university hospital, the patient's initial fasting blood sugar level was 140 mg/dL, and he showed polydipsic and polyuric conditions more than 8 L urine/day. Despite the hyperglycemia controlled with metformin and diet, his symptoms persisted. Further investigations including water deprivation test confirmed the coexisting CDI of unknown origin, and the patient's symptoms including an intense thirst were markedly improved by desmopressin nasal spray (10 µg/day). The possibility of a common origin of CDI and type 2 DM is raised in a review of the few relevant adult cases in the literature. PMID:23508726

Polyuria with the Concurrent manifestation of Central Diabetes Insipidus (CDI) & Type 2 Diabetes Mellitus (DM).

PubMed

Shin, Hyun-Jong; Kim, Jae-Ha; Yi, Joo-Hark; Han, Sang-Woong; Kim, Ho-Jung

2012-12-01

We report a rare case of the concurrent manifestation of central diabetes insipidus (CDI) and type 2 diabetes mellitus (DM). A 56 year-old man was diagnosed as a type 2 DM on the basis of hyperglycemia with polyuria and polydipsia at a local clinic two months ago and started an oral hypoglycemic medication, but resulted in no symptomatic improvement at all. Upon admission to the university hospital, the patient's initial fasting blood sugar level was 140 mg/dL, and he showed polydipsic and polyuric conditions more than 8 L urine/day. Despite the hyperglycemia controlled with metformin and diet, his symptoms persisted. Further investigations including water deprivation test confirmed the coexisting CDI of unknown origin, and the patient's symptoms including an intense thirst were markedly improved by desmopressin nasal spray (10 µg/day). The possibility of a common origin of CDI and type 2 DM is raised in a review of the few relevant adult cases in the literature.

Physical Exercise on Inflammatory Markers in Type 2 Diabetes Patients: A Systematic Review of Randomized Controlled Trials

PubMed Central

Melo, Luciana Costa; Dativo-Medeiros, Jaime; Menezes-Silva, Carlos Eduardo; de Sousa-Rodrigues, Célio Fernando

2017-01-01

Background. Type 2 diabetes mellitus (T2DM) is a serious disease associated with high morbidity and mortality. Scientific findings showed that physical exercise is an option for treatment of these patients. This study's objective is to investigate the effects of supervised aerobic and/or resistance physical training on inflammatory markers in subjects with T2DM. Methods. A systematic review was conducted on four databases, MEDLINE, CENTRAL, LILACS, and Scopus, and manual search from 21 to 30 November 2016. Randomized clinical trials involving individuals diagnosed with T2DM, who have undergone supervised training protocols, were selected in this study. Results. Eleven studies were included. Studies that evaluated control group versus aerobic exercise reported controversial results about the effectiveness of physical training in modifying C-reactive protein (CRP) and cytokine levels. The only variable analyzed by the six studies in comparison to the control group versus resistance exercise was CRP. This protein showed no significant difference between groups. Between the two modes of exercise (aerobic and resistance), only one study demonstrated that aerobic exercise was more effective in reducing CRP. Conclusion. The evidence was insufficient to prove that aerobic or resistance exercise improves systemic levels of inflammatory markers in patients with T2DM. PMID:28400914

Glycemic control and adipokines after periodontal therapy in patients with Type 2 diabetes and chronic periodontitis.

PubMed

Wang, Shunqin; Liu, Jingsong; Zhang, Junfeng; Lin, Jiancheng; Yang, Shuyu; Yao, Jiangwu; Du, Minquan

2017-11-27

The mechanism by which chronic periodontitis (CP) affects type 2 diabetes (T2DM) remains unclear. Therefore, the aim of this study is to evaluate the effects of periodontal therapy (PT) on the glycemic control and adipokines of patients with T2DM and CP with the purpose of elucidating the possible mechanisms by which CP influences T2DM. Forty-four patients with T2DM and CP were randomly divided into two groups according to whether they underwent PT. Periodontal status, blood glucose, and the levels of serum tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), adiponectin (APN), and fibroblast growth factor-21 (FGF-21) were measured at baseline and after 3 months. The results revealed that the probing depth (PD) and attachment loss (AL) were significantly improved, the serum levels of TNF-α and IL-6 were significantly decreased, and APN and FGF-21 exhibited substantial increases in the intervention group after 3 months (p < 0.05), whereas no significant changes were observed in the control group. The glycated hemoglobin (HbA1c) levels in both groups decreased significantly after 3 months compared with baseline (p < 0.05), but the intervention group exhibited a significantly greater change (p < 0.05). In conclusion, PT may relieve periodontal inflammation, which causes a reduction of insulin-antagonizing adipokines and an increase in insulin-sensitizing adipokines, thereby eliciting an improvement in glycemic control.

Stationary Treatment Compared with Individualized Chinese Medicine for Type 2 Diabetes Patients with Microvascular Complications: Study Protocol for a Randomized Controlled Trial.

PubMed

Huo, Jian; Liu, Li-Sha; Jian, Wen-Yuan; Zeng, Jie-Ping; Duan, Jun-Guo; Lu, Xue-Jing; Yin, Shuo

2018-06-18

Microvascular complications in type 2 diabetes (T2DM), including diabatic retinopathy (DR), diabetic kidney disease (DKD), diabetic peripheral neuropathy (DPN) are the leading causes of visual loss, end-stage renal disease or amputation, while the current therapies are still unsatisfactory. Chinese medicine (CM) has been widely used for treating diabetic mellitus. However, most of the previous studies focused on the single complication. The role of CM treatment in T2DM patients with 2 or multiple microvascular complications is not clear. To appraise the curative effect of CM in T2DM patients with 2 or multiple microvascular complications, and to compare the effects of stationary treatment and individualized treatment in T2DM patients with microvascular complications. This trial will be an 8-center, randomized, controlled study with 8 parallel groups. A total of 432 patients will be randomized to 8 groups: DR study group (32 cases) and a corresponding control group (32 cases), DR+DKD study group (64 cases) and a corresponding control group (64 cases), DR+DPN study group (64 cases) and a corresponding control group (64 cases), DR+DKD+DPN study group (56 cases) and a corresponding control group (56 cases). The control group will receive stationary treatment, and the study group will receive individualized treatment based on CM syndrome differentiation in addition to stationary treatment. The study duration will be 50 weeks, comprising a 2-week run-in period, 24 weeks of intervention, and 24 weeks of follow-up. The outcomes will assess efficacy of treatment, improvement in CM symptoms, safety assessments, adherence to the treatment, and adverse events. This study will provide evidence of evidence-based medicine for CM treatment in two or multiple microvascular complications caused by T2DM. (Registration No. ChiCTR-IPR-15007072).

Metabolic Demand of Driving Among Adults with Type 1 Diabetes Mellitus (T1DM)

PubMed Central

Cox, Daniel J.; Singh, Harsimran; Clarke, William L.; Anderson, Stacey M.; Kovatchev, Boris P.; Gonder-Frederick, Linda A.

2010-01-01

Recent research suggests that the frequency of driving mishaps is increased in people with Type 1 diabetes (T1DM) as compared to those with Type 2 diabetes or their non-diabetic spouses. This study involved a sample of T1DM drivers and was designed to investigate the metabolic and physiologic demands of driving compared to sitting passively. Participants (N=38) were divided into two groups: the -History group included those reporting no driving mishaps in the past two years, and the +History group included participants reporting at least two such mishaps in the past two years. Glucose utilization rates were determined in participants while: (a) they were driving a virtual reality driving simulator for 30 minutes, and (b) watching a 30-minute video. Blood glucose (BG) levels were maintained at similar levels during both procedures. Other biological variables including heart rate (HR) were monitored. Participants rated their hypoglycemia (low BG) symptoms before and after each of the two procedures. . Participants could self-treat if they perceived they were experiencing hypoglycemia. There were no differences between the two groups. However, glucose utilization rates were significantly higher during the driving scenario (3.83mg/kg/min + 1.7 vs. 3.37 mg/kg/min + 1.6, p=0.047). HR was significantly higher during the driving scenario. Drivers reported more autonomic symptoms during driving and 32% treated perceived hypoglycemia during driving. Driving a virtual reality simulator is associated with increased glucose utilization rates suggesting that driving per se has a metabolic cost and that BG should be measured prior to driving and periodically during long drives. PMID:21050619

Clinical variables associated with depression in patients with type 2 diabetes.

PubMed

Ferreira, Mari Cassol; Piaia, Camila; Cadore, Ana Carolina; Antoniolli, Marinez Amabile; Gamborgi, Geni Portela; Oliveira, Patrícia Pereira de

2015-08-01

the aim of the study was to evaluate the relationship between type 2 diabetes (T2DM), depression and depressive symptoms and their clinical impact on T2DM. the authors evaluated 214 outpatients, 105 with diabetes (T2DM group) and 109 non-diabetics (control group), with ages ranging between 50 and 75 years (T2DM group 65.1 ± 5.6 years, control group 63.4 ± 5.8 years). Use of antidepressant treatment or score ≥ 16 on the Beck depression inventory (BDI) was considered depression. Complications of diabetes and total symptom score (TSS) for peripheral neuropathy were reported by patients. diabetes group had a higher frequency of depression (35.2%) compared to controls (21.1%) (p=0,021), with 2.4 times increased risk of depression. The presence of depressive symptoms was also higher in T2DM group (mean BDI 9.5 ± 8.8 versus 6.9 ± 6.2; p=0.039). Symptoms of diabetic neuropathy were higher in depressed subjects. The metabolic control and presence of complications in T2DM group were not associated with depression. T2DM led to an increased risk of depression, but this did not influence the metabolic control or the presence of other complications.

Association of the proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene with type 2 diabetes in an African American population

PubMed Central

Leak, Tennille S.; Keene, Keith L.; Langefeld, Carl D.; Gallagher, Carla J.; Mychaleckyj, Josyf C.; Freedman, Barry I.; Bowden, Donald W.; Rich, Stephen S.; Sale, Michèle M.

2009-01-01

In a genome-wide scan for type 2 diabetes (T2DM) in African American (AA) families, ordered subsets analysis (OSA) provided evidence for linkage to chromosome 20p in a subset with later age at diagnosis (max. LOD 2.57, P = 0.008). The proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene is within the LOD-1 interval of this linkage peak. Twenty-nine single nucleotide polymorphisms (SNPs) were genotyped across this gene in 380 unrelated AA individuals with T2DM and end-stage renal disease (T2DM-ESRD), 278 AA controls, 96 European Americans (EA) and 120 Yoruba Nigerian (YRI) controls. In addition, 22 ancestry-informative markers (AIMs) were genotyped in all AA subjects, 120 YRI, and 96 EA controls. ADMIXMAP was used to model the distributions of admixture and generate score tests of allelic and haplotypic association. Association with T2DM was observed among 4 SNPs: rs2021785 (admixture-adjusted Pa = 0.00014), rs1609659 (Pa = 0.028), rs4814597 (Pa = 0.039) and rs2269023 (Pa = 0.043). None of the PCSK2 SNPs were associated with age at T2DM diagnosis. A variant in the PCKS2 gene, rs2021785, appears to play a role in susceptibility to T2DM in this AA population. PMID:17618154

Cost-effectiveness of exenatide twice daily vs insulin glargine as add-on therapy to oral antidiabetic agents in patients with type 2 diabetes in China.

PubMed

Gu, Shuyan; Wang, Xiaoyong; Qiao, Qing; Gao, Weiguo; Wang, Jian; Dong, Hengjin

2017-12-01

To estimate the long-term cost-effectiveness of exenatide twice daily vs insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM). The Cardiff Diabetes Model was used to simulate disease progression and estimate the long-term effects of exenatide twice daily vs insulin glargine once daily. Patient profiles and treatment effects required for the model were obtained from literature reviews (English and Chinese databases) and from a meta-analysis of 8 randomized controlled trials comparing exenatide twice daily with insulin glargine once daily add-on to OADs for T2DM in China. Medical expenditure data were collected from 639 patients with T2DM (aged ≥18 years) with and without complications incurred between January 1, 2014 and December 31, 2015 from claims databases in Shandong, China. Costs (2014 Chinese Yuan [¥]) and benefits were estimated, from the payers' perspective, over 40 years at a discount rate of 3%. A series of sensitivity analyses were performed. Patients on exenatide twice daily + OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic events and lower total costs compared with those on insulin glargine once daily + OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost saving of ¥117 706 gained was associated with exenatide twice daily vs insulin glargine once daily. (i.e. cost saving of ¥60 764/QALY) per patient. In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice daily is a cost-effective add-on therapy alternative to insulin glargine once daily, and may address the problem of an excess of medical needs resulting from weight gain and hypoglycaemia in T2DM treatment. © 2017 John Wiley & Sons Ltd.

Tolerability and efficacy of glycemic control with saxagliptin in older patients (aged ≥ 65 years) with inadequately controlled type 2 diabetes mellitus

PubMed Central

Karyekar, Chetan S; Ravichandran, Shoba; Allen, Elsie; Fleming, Douglas; Frederich, Robert

2013-01-01

Purpose To assess safety and efficacy of saxagliptin in older patients with type 2 diabetes mellitus (T2DM). Patients and methods This was a post hoc analysis of pooled data from older patients (≥65 years of age) from five 24-week phase III trials: three studies of saxagliptin versus placebo as an add-on therapy to metformin, glyburide, or a thiazolidinedione; and two studies of saxagliptin versus placebo as monotherapy in drug-naïve patients. Separate analyses were conducted on one study of initial combination therapy with saxagliptin plus metformin versus metformin monotherapy in drug-naïve patients. The safety analysis population for the five-study pool included 428 patients ≥ 65 years of age with baseline glycated hemoglobin (HbA1c) 7.0% to 10.5% who received saxagliptin 2.5 or 5 mg or placebo, and for the study of initial combination therapy included 69 patients ≥ 65 years of age with baseline HbA1c 8.0% to 12.0% who received saxagliptin 5 mg in combination with metformin or metformin monotherapy. The primary efficacy endpoint was change from baseline HbA1c. Results In the five-study pool, the differences in the adjusted mean change from baseline HbA1c among older patients receiving saxagliptin versus placebo were −0.60% (95% confidence interval [CI], −0.99% to −0.21%) for saxagliptin 2.5 mg and −0.55% (−0.97% to −0.14%) for saxagliptin 5 mg; in the initial combination study, the difference was −1.22% (−2.27% to −0.17%) among older patients receiving saxagliptin 5 mg plus metformin versus metformin monotherapy. The results were generally similar in older and younger patients. Saxagliptin was well tolerated; the incidence and types of adverse events were similar for saxagliptin and comparators. Hypoglycemia was reported in 3.0% to 9.4% of patients receiving saxagliptin (0%–8.0% for comparators) and was confirmed (finger stick glucose ≤ 50 mg/dL, with associated symptoms) in 0% to 0.7% (0%–0.7% for comparators); hypoglycemic

Salivary function impairment in type 2 Diabetes patients associated with concentration and genetic polymorphisms of chromogranin A.

PubMed

Kogawa, Evelyn Mikaela; Grisi, Daniela Corrêa; Falcão, Denise Pinheiro; Amorim, Ingrid Aquino; Rezende, Taia Maria Berto; da Silva, Izabel Cristina Rodrigues; Silva, Osmar Nascimento; Franco, Octávio Luiz; de Amorim, Rivadávio Fernandes Batista

2016-11-01

The purpose of this study was to evaluate the effect of type 2 diabetes mellitus (T2DM) on salivary function impairments according to glycemic control status and subsequently compare the concentration of chromogranin A (CHGA) with its genetic profile. Thirty-six patients with controlled T2DM, 36 with poorly controlled T2DM, and 38 nondiabetic subjects underwent salivary flow rate measurements by means of unstimulated labial (ULS), unstimulated whole (UWS), and stimulated whole saliva (SWS) collections. CHGA concentrations were determined in saliva and plasma with ELISA, and two CHGA polymorphisms (T-415C and Glu264Asp) were analyzed by polymerase chain reaction-restriction fragment length polymorphism. T2DM patients presented significantly lower ULS and UWS flow rates regardless of glycemic control status compared to controls (P = 0.002 and P = 0.027, respectively). The SWS flow rate in the poorly controlled T2DM was the lowest among the groups (P = 0.026). Significantly higher plasma and salivary CHGA levels were found in T2DM groups (P = 0.019 and P < 0.001, respectively). CHGA gene variants (T-415C and Glu264Asp) revealed significant differences between diabetics and control subjects when associated with lower salivary flow and higher salivary CHGA production (P < 0.05). T2DM causes abnormalities in the function of salivary glands. However, poorly controlled T2DM has the most influence on SWS flow rates. Our findings indicate an association between plasma and salivary CHGA levels and T2DM patients. Furthermore, the results suggest that CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. Nevertheless, further epidemiological studies are required to elucidate this clinical implication. Salivary impairments and high levels of CHGA are associated with T2DM patients. In addition, CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary

Control of type 2 diabetes mellitus among general practitioners in private practice in nine countries of Latin America.

PubMed

Lopez Stewart, Gloria; Tambascia, Marcos; Rosas Guzmán, Juan; Etchegoyen, Federico; Ortega Carrión, Jorge; Artemenko, Sofia

2007-07-01

To better understand how diabetes care and control are being administered by general practitioners/nonspecialists in private practice in nine countries of Latin America, and to identify the most significant patient- and physician-related barriers to care. A multicenter, cross-sectional, epidemiological survey was conducted in nine countries in Latin America: Argentina, Brazil, Chile, Costa Rica, Ecuador, Guatemala, Mexico, Peru, and Venezuela. General practitioners in private practice were asked to provide care and control data for patients 18 to 75 years of age with type 2 diabetes mellitus (T2DM), including demographics, medical and medication history, laboratory exams, and information on the challenges of patient management. Of the 3 592 patient questionnaires returned by 377 physicians, 60% of the patients had a family history of diabetes, 58% followed a poor diet, 71% were sedentary, and 79% were obese or overweight. Poor glycemic control (fasting blood glucose >or= 110 mg/dL) was observed in 78% of patients. The number of patients with HbA1c < 7.0% was 43.2%. Glycemic control decreased significantly with increased duration of T2DM. Comorbid conditions associated with T2DM were observed in 86% of patients; insulin use and comorbid conditions, especially those associated with microvascular complications, increased significantly disease duration. Ensuring compliance with recommended diet and exercise plans was the most-cited patient management challenge. Blood glucose levels are undercontrolled in T2DM patients in the private health care system in Latin America, particularly among those who have had the disease the longest (>15 years). Considering the differences between private and public health care in Latin America, especially regarding the quality of care and access to medication, further studies are called for in the public setting. Overall, a more efficient and intensive program of T2DM control is required, including effective patient education programs

Real-world crude incidence of hypoglycemia in adults with diabetes: Results of the InHypo-DM Study, Canada.

PubMed

Ratzki-Leewing, Alexandria; Harris, Stewart B; Mequanint, Selam; Reichert, Sonja M; Belle Brown, Judith; Black, Jason Edward; Ryan, Bridget L

2018-01-01

Very few real-world studies have been conducted to assess the incidence of diabetes-related hypoglycemia. Moreover, there is a paucity of studies that have investigated hypoglycemia among people taking secretagogues as a monotherapy or in combination with insulin. Accordingly, our research team developed and validated the InHypo-DM Person with Diabetes Mellitus Questionnaire (InHypo-DMPQ) with the aim of capturing the real-world incidence of self-reported, symptomatic hypoglycemia. The questionnaire was administered online to a national sample of Canadians (≥18 years old) with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) treated with insulin and/or insulin secretagogues. Self-report data obtained from the InHypo-DMPQ were descriptively analyzed to ascertain the crude incidence proportions and annualized incidence densities (rates) of 30-day retrospective non-severe and 1-year retrospective severe hypoglycemia, including daytime and nocturnal events. A total of 552 people (T2DM: 83%; T1DM: 17%) completed the questionnaire. Over half (65.2%) of the total respondents reported experiencing at least one event (non-severe or severe) at an annualized crude incidence density of 35.1 events per person-year. The incidence proportion and rate of non-severe events were higher among people with T1DM versus T2DM (77% and 55.7 events per person-year vs 54% and 28.0 events per person-year). Severe hypoglycemia was reported by 41.8% of all respondents, at an average rate of 2.5 events per person-year. The results of the InHypo-DMPQ, the largest real-world investigation of hypoglycemia epidemiology in Canada, suggest that the incidence of hypoglycemia among adults with diabetes taking insulin and/or insulin secretagogues is higher than previously thought.

Increased Trimethylamine N-Oxide Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus.

PubMed

Tang, W H Wilson; Wang, Zeneng; Li, Xinmin S; Fan, Yiying; Li, Daniel S; Wu, Yuping; Hazen, Stanley L

2017-01-01

Recent studies show a mechanistic link between intestinal microbial metabolism of dietary phosphatidylcholine and coronary artery disease pathogenesis. Concentrations of a proatherogenic gut microbe-generated metabolite, trimethylamine N-oxide (TMAO), predict increased incident cardiovascular disease risks in multiple cohorts. TMAO concentrations are increased in patients with type 2 diabetes mellitus (T2DM), but their prognostic value and relation to glycemic control are unclear. We examined the relationship between fasting TMAO and 2 of its nutrient precursors, choline and betaine, vs 3-year major adverse cardiac events and 5-year mortality in 1216 stable patients with T2DM who underwent elective diagnostic coronary angiography. TMAO [4.4 μmol/L (interquartile range 2.8-7.7 μmol/L) vs 3.6 (2.3-5.7 μmol/L); P < 0.001] and choline concentrations were higher in individuals with T2DM vs healthy controls. Within T2DM patients, higher plasma TMAO was associated with a significant 3.0-fold increased 3-year major adverse cardiac event risk (P < 0.001) and a 3.6-fold increased 5-year mortality risk (P < 0.001). Following adjustments for traditional risk factors and high-sensitivity C-reactive protein, glycohemoglobin, and estimated glomerular filtration rate, increased TMAO concentrations remained predictive of both major adverse cardiac events and mortality risks in T2DM patients [e.g., quartiles 4 vs 1, hazard ratio 2.05 (95% CI, 1.31-3.20), P < 0.001; and 2.07 (95% CI, 1.37-3.14), P < 0.001, respectively]. Fasting plasma concentrations of the proatherogenic gut microbe-generated metabolite TMAO are higher in diabetic patients and portend higher major adverse cardiac events and mortality risks independent of traditional risk factors, renal function, and relationship to glycemic control. © 2016 American Association for Clinical Chemistry.

A randomized controlled trial on the effects of combined aerobic-resistance exercise on muscle strength and fatigue, glycemic control and health-related quality of life of type 2 diabetes patients.

PubMed

Tomas-Carus, Pablo; Ortega-Alonso, Alfredo; Pietilainen, Kirsi H; Santos, Vitoria; Goncalves, Helena; Ramos, Jorge; Raimundo, Armando

2016-05-01

The aim of this paper was to evaluate the effects of a 12-weeks combined aerobic-resistance exercise therapy on fatigue and isokinetic muscle strength, glycemic control and health-related quality of life (HRQoL) in moderately affected type 2 diabetes (T2DM) patients. A randomized controlled trial design was employed. Forty-three T2DM patients were assigned to an exercise group (N.=22), performing 3 weekly sessions of 60 minutes of combined aerobic-resistance exercise for 12-weeks; or a no exercise control group (N.=21). Both groups were evaluated at a baseline and after 12-weeks of exercise therapy for: 1) muscle strength and fatigue by isokinetic dynamometry; 2) plasma glycated hemoglobin A1C (HbA1C); and 3) HRQoL utilizing the SF-36 questionnaire. The exercise therapy led to improvements in muscle fatigue in knee extensors (-55%) and increased muscle strength in knee flexors and extensors (+15 to +30%), while HbA1C decreased (-18%). In addition, the exercising patients showed sizeable improvements in HRQoL: physical function (+53%), vitality (+21%) and mental health (+40%). Twelve-weeks of combined aerobic-resistance exercise was highly effective to improve muscle strength and fatigue, glycemic control and several aspects of HRQoL in T2DM patients. These data encourage the use of aerobic and resistance exercise in the good clinical care of T2DM.

Altered sphingoid base profiles in type 1 compared to type 2 diabetes.

PubMed

Wei, Nancy; Pan, Jessica; Pop-Busui, Rodica; Othman, Alaa; Alecu, Irina; Hornemann, Thorsten; Eichler, Florian S

2014-10-11

Sphingolipids are increasingly recognized to play a role in insulin resistance and diabetes. Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). It is unknown whether 1-deoxySL in patients with diabetes type 1 (T1DM) are similarly elevated. We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 1-deoxySLs were significantly higher in the groups with T2DM but not different between T1DM and controls. In contrast to patients with T2DM, 1-deoxSL levels are not elevated in T1DM. Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels.

[Variation of insulin receptor substrate-2 gene 3'-untranslated region in patients with type 2 diabetes mellitus].

PubMed

Zeng, Wei-Min; Chen, Shu-Hua; Xie, Ping; Liu, Mei-Lian; Song, Hui-Ping

2003-08-01

Insulin receptor substrate-2(IRS-2) belongs to a family of cytoplasmic adaptor proteins, which link insulin, insulin-like growth factor-1(IGF-1), and cytokine receptor tyrosine kinases to signaling pathways regulating metabolism, growth, differentiation, reproduction, and homestasis. Deficiency of IRS-2 in mice causes type 2 diabetes mellitus (T2DM), suggesting that abnormal structure and dysfunction of the IRS-2 gene may contribute to the pathogenesis of T2DM. Variations in the open reading frame (ORF) and promoter region of IRS-2 gene in patients with T2DM have been reported over the past few years. These genetic variations are from ethnically different patients, confounding any analysis of the contribution of IRS-2 gene variations to the development of T2DM. The 3'-untranslated region(3'-UTR) of IRS-2 gene variation may be contribute to the T2DM. So far, the relationship between 3'-UTR of IRS-2 gene variations and T2DM have not been investigated. Based on the 3'-UTR of eukaryotic gene plays an important role in the eukaryotic gene regulation, we investigated abnormalities of IRS-2 gene 3'-UTR and their relation with T2DM in the Chinese population. Genomic DNA was extracted from leukocyte of 128 patients with T2DM and 125 control subjects in Hunan, China. A segment of IRS-2 gene 3'-UTR was scanned by polymerase chain reaction (PCR)-denaturing high-performance liquid chromatography (DHPLC). All PCR products with abnormal DHPLC pattern were submitted to DNA sequence analysis. A T-->C mutation at 4064 bp of IRS-2 gene 3'-UTR was found in 18 patients with T2DM, while it was only found in 5 control subjects. The incidence of the mutation in patients with T2DM were much higher than that in contol subjects (14.1% vs 4.0%, x2 = 7.748, P = 0.005). These results indicate that the T4064-->C in IRS-2 gene 3'-UTR may be related to Chinese patients with T2DM.

9 CFR 417.6 - Inadequate HACCP Systems.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Inadequate HACCP Systems. 417.6 Section 417.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS § 417.6 Inadequate HACCP Systems. A HACCP system may be...

9 CFR 417.6 - Inadequate HACCP Systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Inadequate HACCP Systems. 417.6 Section 417.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS § 417.6 Inadequate HACCP Systems. A HACCP system may be...

9 CFR 417.6 - Inadequate HACCP Systems.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Inadequate HACCP Systems. 417.6 Section 417.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS § 417.6 Inadequate HACCP Systems. A HACCP system may be...

9 CFR 417.6 - Inadequate HACCP Systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Inadequate HACCP Systems. 417.6 Section 417.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS § 417.6 Inadequate HACCP Systems. A HACCP system may be...

9 CFR 417.6 - Inadequate HACCP Systems.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Inadequate HACCP Systems. 417.6 Section 417.6 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS § 417.6 Inadequate HACCP Systems. A HACCP system may be...

Cost-Effectiveness of Bariatric Surgery for Type 2 Diabetes Mellitus: A Randomized Controlled Trial in China.

PubMed

Tang, Qi; Sun, Zhipeng; Zhang, Nengwei; Xu, Guangzhong; Song, Peipei; Xu, Lingzhong; Tang, Wei

2016-05-01

To compare the remission of type 2 diabetes mellitus (T2DM) through treatment with laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB), and to analyze the cost-effectiveness of medical treatment, LSG, and LRYGB in T2DM patients (BMI ≥ 28).A 2-group randomized controlled trial was conducted at Diabetes Surgery Centre, Beijing Shijitan Hospital in Beijing, China. Subjects were 80 patients ages 16 to 65 years with a body mass index of 28 kg/m or more and duration of T2DM no more than 15 years. Subjects were randomly assigned (1:1) to undergo either LSG (n = 40) or LRYGB (n = 40) between February 3, 2011 and October 31, 2013. Of those patients, 72 (90%) were available at follow-up at 2 years. These patients included 34 (85%) who underwent LSG and 38 (95%) who underwent LRYGB. This study presents the follow-up data at 2 years, which compared LSG and LRYGB in T2DM patients. Partial remission and complete remission were determined, and weight loss, BMI, changes in abdominal circumference, cholesterol, and triglycerides were measured. The cost-effectiveness of each type of bariatric surgery was analyzed with a Markov simulation model that yielded quality-adjusted life-years (QALYs) and costs.From our analysis results, LSG and LRYGB are both have taken a great effect on the reduction of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and bodyweight in patients with T2DM. The cost-effectiveness ratios of medical treatment, LSG, and LRYGB respectively are 1589.02, 1028.97, and 1197.44 dollars per QALY.Our analysis indicates that LSG appear to provide a cost-effective method of T2DM treatment for the patients.

Food label education does not reduce sodium intake in people with type 2 diabetes mellitus. A randomised controlled trial.

PubMed

Petersen, Kristina S; Torpy, David J; Chapman, Ian M; Guha, Sanghamitra; Clifton, Peter M; Turner, Kirsty; Keogh, Jennifer B

2013-09-01

Sodium intake is high in people with type 2 diabetes (T2DM). The aim of this study was to investigate whether urinary sodium excretion can be reduced by educating people with T2DM to read food labels and choose low sodium products. In a 3 month randomised controlled trial, 78 men (n=49) and women (n=29) with T2DM were recruited from a Diabetes Centre at a University teaching hospital. The intervention group was educated in a single session to use the nutrition information panel on food labels to choose products which complied with the Food Standards Australia New Zealand (FSANZ) guideline of <120 mg sodium/100 g food. The control group continued on their usual diet. The primary outcome measure was 24h urinary sodium excretion which was performed at baseline and 3 months. Data was analysed using repeated measures analysis of variance, independent samples t-test and Pearson's correlations. At 3 months mean urinary sodium excretion was unchanged in the intervention (174±13 mmol/24 h and 175±13 mmol/24 h) and control group (167±15mmol/24h and 161±13 mmol/24 h), and there was no between group difference (p>0.05). Sodium excretion was not reduced following the label reading education provided to this group of people with T2DM. Copyright © 2013 Elsevier Ltd. All rights reserved.

Use of parenteral glucocorticoids and the risk of new onset type 2 diabetes mellitus: A case-control study.

PubMed

Keyany, Ala; Nielen, Johannes T H; Souverein, Patrick C; de Vries, Frank; van den Bemt, Bart

2018-05-01

Use of oral glucocorticoids (GCs) has been associated with hyperglycaemia and type 2 diabetes mellitus (T2DM). However, unlike oral GCs, there is minimal or no data on the effect of parenteral GC use on T2DM. To assess the association between use of parenteral GCs and the risk of receiving a first prescription of a non-insulin antidiabetic drug (NIAD) as a proxy for new onset of T2DM. A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n = 177,154) were defined as patients >18 years of age who had their first ever NIAD prescription between January 1987 and October 2013. Controls were matched by age, gender and general practitioner practice. Conditional logistic regression analyses were used to estimate the risk of NIAD prescription and use of parenteral GCs. Our analyses were statistically adjusted for lifestyle factors, comorbidities and concomitant drug use. Although this study confirmed that oral GCs increases the risk of receiving a first prescription of a NIAD (OR 2.63 [95% CI 2.53-2.73]), there was no association between the use of parenterally administered GCs and the risk of receiving a first prescription of a NIAD (OR 0.88 [95% CI 0.76-1.02]). The number of GC prescriptions was not associated with risk of new onset T2DM compared to no parenteral GCs use; neither the type of GC. Our study does not demonstrate an association between the use of parenteral GCs and the risk of new onset of T2DM. Copyright © 2018 Elsevier B.V. All rights reserved.

Association of two Common Single Nucleotide Polymorphisms (+45T/G and +276G/T) of ADIPOQ Gene with Coronary Artery Disease in Type 2 Diabetic Patients

PubMed Central

Mohammadzadeh, Ghorban; Ghaffari, Mohammad-Ali; Heibar, Habib; Bazyar, Mohammad

2016-01-01

Background: Adiponectin, an adipocyte-secreted hormone, is known to have anti-atherogenic, anti-inflammatory, and anti-diabetic properties. In the present study, the association between two common single nucleotide polymorphisms (SNPs) (+45T/G and +276G/T) of ADIOPQ gene and coronary artery disease (CAD) was assessed in the subjects with type 2 diabetes (T2DM). Methods: Genotypes of two SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism in 200 subjects with T2DM (100 subjects with CAD and 100 without CAD). Results: The frequency of TT genotype of +276G/T was significantly elevated in CAD compared to controls (χ2=7.967, P=0.019). A similar difference was found in the allele frequency of +276G/T between two groups (χ2=3.895, P=0.048). The increased risk of CAD was associated with +276 TT genotype when compared to reference GG genotype (OR=5.158; 95% CI=1.016-26.182, P=0.048). However, no similar difference was found in genotype and allele frequencies of SNP +45T/G between two groups. There was a CAD protective haplotype combination of +276 wild-type and +45 mutant-type allele (276G-45G) (OR=0.37, 95% CI=0.16-0.86, P=0.022) in the subject population. Conclusion: Our findings indicated that T allele of SNP +276G/T is more associated with the increased risk of CAD in subjects with T2DM. Also, a haplotype combination of +45G/+276G of these two SNPs has a protective effect on the risk of CAD. PMID:26781170

The Effect of Low-Carbohydrate Diet on Glycemic Control in Patients with Type 2 Diabetes Mellitus.