Bisphenol A (BPA) is a widely used endocrine disruptor. Recent epidemiologic results have suggested an association between exposure to BPA and cardiovascular disease, type 2 diabetes, and obesity. We investigated thein vivoeffects of long-term oral exposure to BPA on insulin resistance and glucose intolerance. In the present study, 4- to 6-week-old male mice on a high-fat diet (HFD) were treated with 50 μg/kg body weight per day of BPA orally for 12 weeks. Long-term oral exposure to BPA along with an HFD for 12 weeks induced glucose intolerance in growing male mice. Intraperitoneal glucose tolerance tests showed that the mice that received an HFD and BPA exhibited a significantly larger area under the curve than did those that received an HFD only (119.9±16.8 vs 97.9±18.2 mM/min,P=0.027). Body weight, percentage of white adipose tissue, and percentage of body fat did not differ between the two groups of mice. However, treatment with BPA reduced Akt phosphorylation at position Thr308 and GSK3β phosphorylation at position Ser9 in skeletal muscle. BPA tended to decrease serum adiponectin levels and to increase serum interleukin 6 and tumor necrosis factor α, although these findings were not statistically significant. Treatment with BPA did not induce any detrimental changes in the islet area or morphology or the insulin content of β cells. In conclusion, long-term oral exposure to BPA induced glucose intolerance and insulin resistance in growing mice. Decreased Akt phosphorylation in skeletal muscle by way of altered serum adipocytokine levels might be one mechanism by which BPA induces glucose intolerance.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%–25% of patients with diabetes experience neuropathic pain, referred to as “painful DPN.” Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.

Context: There is a substantial interindividual variation in the association between glycated hemoglobin (HbA1c) and plasma glucose concentrations. Its impact on cardiovascular disease (CVD) has not been comprehensively evaluated. Objective: We examined associations between interindividual variations in HbA1c, which was estimated as the hemoglobin glycation index (HGI), and CVD. Design, Setting, and Participants: We performed a cross-sectional analysis with 1248 treatment-naïve subjects with prediabetes or diabetes. The HGI was defined as the measured HbA1c minus predicted HbA1c which was calculated from the linear relationship between HbA1c and fasting plasma glucose levels. Main outcome measures: The prevalence of composite and individual CVDs including coronary artery disease (CAD), stroke, and peripheral artery disease (PAD). Results: The overall prevalence of composite CVD, and individual prevalence of CAD, stroke, and PAD were 10.3%, and 5.7%, 5.1%, and 1.3%, respectively. All these prevalences significantly increased from 1st to 3rd tertile of HGI. In multivariate analysis, the highest HGI tertile was independently associated with composite CVD (odds ratio [95% confidence interval]: 2.81 [1.59-4.98]), and individual CAD (2.30 [1.12-4.73]), stroke (3.40 [1.50-7.73]), and PAD (6.37 [1.18-34.33]) after adjustment for other CVD risk factors including HbA1c levels. Two consecutive measurements of HGI obtained on different days showed good correlation (r = 0.651, P <0.001) and high concordance rate in the tertile classification (69.1%). Conclusions: High HGI was independently associated with overall and individual CVDs. This result suggests that discrepancy between HbA1c and fasting glucose levels can reflect vascular health in subjects with impaired glucose metabolism.

Context Body-weight fluctuation (weight cycling) has been found to be associated with higher mortality and cardiovascular events in patients with coronary artery disease. However, there are very limited data regarding the relationship between body-weight fluctuation and health-related outcomes in the general population. Methods We examined whether body-weight fluctuation can associate incident diabetes mellitus and cardiovascular events, and mortality in a Korean population from the Korean Genome and Epidemiology Study. The intra-individual fluctuations of body weight were calculated by average successive variability (ASV), and health-related outcomes were collected every 2 years for 16 years in 3,678 participants. Results Participants with a high ASV of body weight were more obese and had higher blood pressure and HbA1c levels at baseline than those with a low ASV of body weight. A one-unit increase in ASV of body weight was associated with increase in mortality (HR 1.46, 95% CI 1.32−1.62, P < 0.001). However, the association between the ASV of body weight and incident diabetes mellitus seemed to be influenced by baseline body mass index (BMI); negative effect in subjects with BMI < 25 kg/m² (HR 1.36, 95% CI 1.11−1.65, P = 0.003) and protective effect in those with BMI ≥ 25 kg/m² (HR 0.76, 95% CI 0.60−0.95, P = 0.014). There was no association between the ASV of body weight and cardiovascular event. Conclusion Body-weight fluctuation was associated with mortality. In addition, the effect of body-weight fluctuation on incident diabetes mellitus depended on the presence of obesity at baseline.

Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that increases glucose-stimulated insulin secretion in pancreatic β-cells. Since mitochondrial function is crucial to insulin secretion, we hypothesized that GLP-1 may increase mitochondrial biogenesis in pancreatic β-cells. We treated INS-1 rat insulinoma cells with GLP-1 or exendin-4 for 48 hours and measured mitochondrial mass and function. Both GLP-1 and exendin-4 increased mitochondrial mass by approximately 20%. The mitochondria/cytosol ratio was increased from 7.60±3.12% to 10.53±2.70% by exendin-4. In addition, GLP-1 increased the mitochondrial membrane potential and oxygen consumption. Proliferator-activated receptor-gamma coactivator 1α expression was increased approximately 2-fold by GLP-1 treatment. In conclusion, the present study presents evidence for a new mechanism of action by which GLP-1 improves pancreatic β-cell function via enhanced mitochondrial mass and performance.