Metformin alleviates monoamine oxidase-related vascular oxidative stress and endothelial dysfunction in rats with diet-induced obesity.

In the past decade, monoamine oxidase (MAO) with 2 isoforms, MAO-A and B, has emerged as an important source of mitochondrial reactive oxygen species (ROS) in cardio-metabolic pathologies. We have previously reported that MAO-related oxidative stress mediates endothelial dysfunction in rodent models of diabetes and diabetic patients; however, the role of MAO in the vascular impairment associated to obesity has not been investigated so far. Metformin (METF), the first-line drug in the therapy of type 2 diabetes mellitus, has been reported to elicit vasculoprotective effects via partially elucidated mechanisms. The present study was purported to assess the effects of METF on MAO expression, ROS production and vasomotor function of aortas isolated from rats with diet-induced obesity. After 24 weeks of high calorie junk food (HCJF) diet, isolated aortic rings were prepared and treated with METF (10 µM, 12 h incubation). Measurements of MAO expression (quantitative PCR and immune histochemistry), ROS production (spectrometry and immune-fluorescence) and vascular reactivity (myograph studies) were performed in rat aortic rings. MAO expression was upregulated in aortic rings isolated from obese rats together with an increase in ROS production and an impairment of vascular reactivity. METF decreased MAO expression and ROS generation, reduced vascular contractility and improved the endothelium-dependent relaxation in the diseased vascular preparations. In conclusion, METF elicited vascular protective effects via the mitigation of MAO-related oxidative stress in the rat model of diet-induced obesity.

The Impact of Diabetic Neuropathy on Balance and on the Risk of Falls in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

INTRODUCTION: Diabetic neuropathy (DN) is a prevalent complication of Type 2 Diabetes Mellitus (T2DM) with a major impact on the health of the affected patient. We hypothesized that mediated by the dysfunctionalities associated with DN's three major components: sensitive (lack of motion associated sensory), motor (impairments in movement coordination) and autonomic (the presence of postural hypotension), the presence of DN may impair the balance in the affected patients. Our study's main aim is to evaluate the possible association between the presence and severity of DN and both the balance impairment and the risk of falls in patients with T2DM. MATERIAL AND METHOD: In this cross-sectional study we enrolled, according to a consecutive-case population-based setting 198 patients with T2DM. The presence and severity of DN was evaluated using the Michigan Neuropathy Screening Instrument, a tool which allows both diagnosing and severity staging of DN. The balance impairment and the risk of falls were evaluated using four validated and standardized tools: Berg Balance Scale (BBS), Timed-up and Go test (TUG), Single Leg Stand test (SLS) and Fall Efficacy Scale (FES-I). RESULTS: The presence of DN was associated with significant decreases in the BBS score (40.5 vs. 43.7 points; p<0.001) and SLS time (9.3 vs. 10.3 seconds; p = 0.003) respectively increases in TUG time (8.9 vs. 7.6 seconds; p = 0.002) and FES-I score (38 vs. 33 points; p = 0.034). The MNSI score was reverse and significantly correlated with both BBS score (Spearman's r = -0.479; p<0.001) and SLS time (Spearman's r = -0.169; p = 0.017). In the multivariate regression model, we observed that patient's age, DN severity and depression's symptoms acted as independent, significant predictors for the risk of falls in patients with T2DM. CONCLUSIONS: The presence of DN in patients with DM is associated with impaired balance and with a consecutively increase in the risk of falls.