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Leongatha, Australia

Bo S.,University of Turin | Castiglione A.,University of Turin | Ghigo E.,University of Turin | Gentile L.,Diabetes Clinic | And 3 more authors.
European Journal of Endocrinology | Year: 2013

Objective: Available data about mortality of type 2 diabetic patients treated with different sulphonylureas are scarce and contradictory. Design: We evaluated the associations between all-cause and cause-specific mortality and treatments with different sulphonylureas in a retrospective cohort of type 2 diabetic patients from a diabetes clinic. Methods: All 1277 patients treated with sulphonylureas during 1996-1997 were enrolled: 159 patients were treated with tolbutamide, 977 glibenclamide and 141 gliclazide. The baseline data (centralised laboratory parameters, anthropometric data and presence of chronic complications) were abstracted from the clinical records. Information on vital status was collected from demographic files after 14-year follow-up. Adjusted hazard ratios (HR) were estimated with Cox (all-cause mortality) or Fine and Gray models (cause-specific mortality), including several potential confounders. Results: Five hundred and fifty-six patients died during the follow-up: 262 from cardiovascular causes, 158 from cancer and 136 from other causes. When compared with the glibenclamide users, the gliclazide and tolbutamide users showed a significantly lower cancer mortality (HRZ0.30; 95% CI 0.16-0.55, and HRZ0.48; 95% CI 0.29-0.79 respectively). These results were strongly confirmed in the 555 patients on sulphonylurea monotherapy. None of the patients who were treated with gliclazide monotherapy died from cancer during the follow-up, and the patients on tolbutamide treatment exhibited a lower cancer mortality than the glibenclamide users (HRZ0.40; 95% CI 0.22-0.71). Data did not change after stratification for the duration of sulphonylurea treatment from diabetes diagnosis to the study enrolment. Conclusions: Cancer mortality was markedly reduced in the patients on gliclazide and tolbutamide treatment. These results suggest additional benefits for these drugs beyond their blood glucoselowering effect and strongly advocate for further investigation. © 2013 European Society of Endocrinology. Source

Neuman R.J.,University of Washington | Neuman R.J.,Washington University in St. Louis | Wasson J.,University of Washington | Atzmon G.,Yeshiva University | And 7 more authors.
PLoS ONE | Year: 2010

Background: Evidence has accumulated that multiple genetic and environmental factors play important roles in determining susceptibility to type 2 diabetes (T2D). Although variants from candidate genes have become prime targets for genetic analysis, few studies have considered their interplay. Our goal was to evaluate interactions among SNPs within genes frequently identified as associated with T2D. Methods/Principal Findings: Logistic regression was used to study interactions among 4 SNPs, one each from HNF4A[rs1884613], TCF7L2[rs12255372], WFS1[rs10010131], and KCNJ11[rs5219] in a case-control Ashkenazi sample of 974 diabetic subjects and 896 controls. Nonparametric multifactor dimensionality reduction (MDR) and generalized MDR (GMDR) were used to confirm findings from the logistic regression analysis. HNF4A and WFS1 SNPs were associated with T2D in logistic regression analyses [P<0.0001, P<0.0002, respectively]. Interaction between these SNPs were also strong using parametric or nonparametric methods: the unadjusted odds of being affected with T2D was 3 times greater in subjects with the HNF4A and WFS1 risk alleles than those without either (95% CI = [1.7-5.3]; P≤0.0001). Although the univariate association between the TCF7L2 SNP and T2D was relatively modest [P = 0.02], when paired with the HNF4A SNP, the OR for subjects with risk alleles in both SNPs was 2.4 [95% CI = 1.7-3.4; P≤0.0001]. The KCNJ11 variant reached significance only when paired with either the HNF4A or WFSI SNPs: unadjusted ORs were 2.0 [95% CI = 1.4-2.8; P≤0.0001] and 2.3 [95% CI = 1.2-4.4; P≤0.0001], respectively. MDR and GMDR results were consistent with the parametric findings. Conclusions: These results provide evidence of strong independent associations between T2D and SNPs in HNF4A and WFS1 and their interaction in our Ashkenazi sample. We also observed an interaction in the nonparametric analysis between the HNF4A and KCNJ11 SNPs (P≤0.001), demonstrating that an independently non-significant variant may interact with another variant resulting in an increased disease risk. © 2010 Neuman et al. Source

Kianbakht S.,Tehran University of Medical Sciences | Kianbakht S.,Research Institute of Medicinal Plants | Abasi B.,Diabetes Clinic | Dabaghian F.H.,Tehran University of Medical Sciences
Forschende Komplementarmedizin | Year: 2013

Background: Type 2 diabetes mellitus is a common disease. Preliminary data indicate that Vaccinium arctostaphylos L. (Caucasian whortleberry) has a potential effect in glycemic control. Thus, the efficacy and safety of a standardized whortleberry fruit hydroalcoholic extract in the treatment of type 2 diabetic patients were studied. Methods: This randomized double-blind placebo-controlled clinical trial consisted of 37 patients aged 40-60 years with type 2 diabetes who were resistant to conventional oral anti-hyperglycemic drugs. The patients were treated with the whortleberry fruit hydroalcoholic extract (1 capsule = 350 mg, every 8 h for 2 months) in combination with anti-hyperglycemic drugs, and the effects on the blood levels of fasting glucose, 2-hour postprandial glucose, glycosylated hemoglobin (HbA1c), and liver/kidney function were tested, evaluated, and compared with a placebo group (n = 37). Results: The extract significantly lowered the blood levels of fasting glucose, 2-h postprandial glucose, and HbA1c (p = 0.007, p <0.001, and p = 0.005, respectively) without any significant effects on the liver/kidney function (p >0.05) compared with placebo at the end. No adverse effects were reported. Conclusion: Whortleberry may safely improve glycemic control in type 2 diabetic patients. © 2013 S. Karger AG, Basel. Source

Verma S.K.,View Medical | Luo N.,National University of Singapore | Subramaniam M.,Institute of Mental Health | Sum C.F.,Diabetes Clinic | And 3 more authors.
Annals of the Academy of Medicine Singapore | Year: 2010

Introduction: Diabetes mellitus (DM) is a serious chronic illness that has a major impact on the quality of life of the individuals. Our aim was to examine the determinants of health-related quality of life (HRQOL) in patients with DM. Materials and Methods: Adult outpatients attending a Diabetes Centre were recruited on consecutive basis between August 2006 and February 2007. Clinical data were collected from interviews with the subjects and from medical records. Assessment of depressive symptoms was done using the Center for Epidemiologic Studies Depression Scale (CES-D) and HRQOL using the Short Form 36 Health Survey (SF-36). A two-step regression analysis was conducted for identifying factors affecting patients' quality of life. Results: Five hundred and thirty-seven patients participated in the study. The mean (SD) age of the participants was 54.7 (13.3) years and 315 (58.7%) were males. The prevalence of depressive symptoms was 31.1% (n = 167). After adjusting for other variables, the effects of depressive symptoms persisted for all the 8 domains of SF-36 (P <0.001 for all). The medical factors that were negatively associated with HRQOL were a diagnosis of Type 1 DM, duration of the illness of more than 10 years, HbA1c levels of ≥7%, and comorbidity of stroke and retinopathy. Being male and a regular exerciser had a positive effect on HRQOL. Conclusion: These fi ndings highlight the importance of detecting and treating comorbid depression in DM. Source

Papaetis G.S.,Diabetes Clinic | Papaetis G.S.,National and Kapodistrian University of Athens | Papakyriakou P.,Paphos General Hospital | Panagiotou T.N.,National and Kapodistrian University of Athens
Archives of Medical Science | Year: 2015

The prevalence of type 2 diabetes (T2D) is rapidly increasing. This is strongly related to the contemporary lifestyle changes that have resulted in increased rates of overweight individuals and obesity. Central (intra-abdominal) obesity is observed in the majority of patients with T2D. It is associated with insulin resistance, mainly at the level of skeletal muscle, adipose tissue and liver. The discovery of macrophage infiltration in the abdominal adipose tissue and the unbalanced production of adipocyte cytokines (adipokines) was an essential step towards novel research perspectives for a better understanding of the molecular mechanisms governing the development of insulin resistance. Furthermore, in an obese state, the increased cellular uptake of non-esterified fatty acids is exacerbated without any subsequent β-oxidation. This in turn contributes to the accumulation of intermediate lipid metabolites that cause defects in the insulin signaling pathway. This paper examines the possible cellular mechanisms that connect central obesity with defects in the insulin pathway. It discusses the discrepancies observed from studies organized in cell cultures, animal models and humans. Finally, it emphasizes the need for therapeutic strategies in order to achieve weight reduction in overweight and obese patients with T2D. Copyright © 2015 Termedia & Banach. Source

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