Patrícia Molz

DNA damage and cytotoxicity in adult subjects with prediabetes.

Prediabetes (intermediate hyperglycemia) is a high-risk state for diabetes that is defined by higher than normal glycemic levels that are below the level required for a diagnosis of diabetes. Prediabetes is characterized by oxidative stress, yet the associated DNA damage and cytotoxicity remain unknown to date. Therefore, we evaluated the relationship between glycemic alterations, DNA damage and cytotoxicity in the lymphocytes of individuals with pre-diabetes. Fasting plasma glucose (FPG) and glycated hemoglobin (A1C) levels were quantified and used as inclusion criteria. Anthropometric parameters were also evaluated. The cytokinesis-block micronucleus cytome assay (CBMN Cyt) was used to evaluate DNA damage and cytotoxicity. FPG correlated with A1C (r=0.562, p=0.002). Because A1C is the best predictor of diabetes complications, the association between A1C and the evaluated variables was assessed. The waist-hip ratio correlated with A1C (p<0.01). Regarding DNA damage, the frequency of nucleoplasmic bridges correlated with A1C (p<0.05). Both apoptosis and necrosis correlated with A1C (p<0.05). The overall frequency of DNA damage and cytotoxicity also correlated with A1C (p<0.01). Additional studies evaluating cell cycle and cell death patterns in prediabetes are necessary.

Vitamin C Intake Reduces the Cytotoxicity Associated with Hyperglycemia in Prediabetes and Type 2 Diabetes

Hyperglycemia leads to the formation of free radicals and advanced glycation end-products (AGEs). Antioxidants can reduce the level of protein glycation and DNA damage. In this study, we compared the levels of vitamin C intake, which is among the most abundant antioxidants obtained from diet, with the levels of fasting plasma glucose (FPG), glycated hemoglobin (A1C), DNA damage, and cytotoxicity in prediabetic subjects and type 2 diabetic subjects. Our results indicated that there was no significant correlation between FPG or A1C and DNA damage parameters (micronuclei, nucleoplasmic bridges, and nuclear buds). FPG and A1C correlated with necrosis (r = 0.294; P = 0.013 and r = 0.401; P = 0.001, resp.). Vitamin C intake correlated negatively with necrosis and apoptosis (r = −0.246; P = 0.040, and r = −0.276; P = 0.021, resp.). The lack of a correlation between the FPG and A1C and DNA damage could be explained, at least in part, by the elimination of cells with DNA damage by either necrosis or apoptosis (cytotoxicity). Vitamin C appeared to improve cell survival by reducing cytotoxicity. Therefore, the present results indicate the need for clinical studies to evaluate the effect of low-dose vitamin C supplementation in type 2 diabetes.

Vitamin C decreases the obesogenic and hyperglycemic effect of invert sugar in prediabetic rats

Objective: To evaluate whether vitamin C can help to prevent obesity and hyperglycemia in Wistar rats treated with excess invert sugar to induce prediabetes. Methods: One hundred-day-old Male Wistar rats with a mean weight of 336.58±23.43g were randomly assigned to the following groups: (1) control, receiving water (C); (2) invert sugar control, receiving a 32% watery solution of invert sugar; (3) vitamin C control, receiving a watery solution of vitamin C (60mg/L), and (4) vitamin C plus invert sugar, receiving a watery solution of vitamin C and invert sugar. All animals had access to chow and water ad libitum and were treated for 17 weeks. Prediabetes was assessed according to two criteria: obesity (based on body mass indexand peritoneal fat content) and impaired glucose tolerance (assessed by the intraperitoneal glucose tolerance test and expressed as area under the curve) . Results: Group invert sugar control gained significantly more weight (p=0.035) and visceral fat (p<0.001) than groups vitamin C control and vitamin C plus invert sugar. Consequently, groups vitamin C control and vitamin C plus invert sugar had gained as little body mass index as group C by the end of the experiment. Vitamin C decreased the fasting glycemia of both groups supplemented with vitamin C and normalized the glucose tolerance of group vitamin C plus invert sugar, whose area under the curve matched that of group C. Conclusion: Vitamin C has anti-obesogenic and glycemia-lowering effects in Wistar rats, which might be promising to prediabetics. Future studies are needed to understand the anti-obesogenic and anti-hyperglycemic mechanisms of vitamin C in prediabetes.