The antioxidant N-Acetylcysteine does not improve glucose tolerance or [beta]-cell function in type 2 diabetes

Hyperglycemia induces oxidative stress and thereby may exacerbate β-cell dysfunction in type 2 diabetes (T2DM). Notably, glutathione (GSH), synthesized from N-Acetylcysteine (NAC), neutralizes reactive oxygen species within cells and is low in individuals with diabetes. Aim Determine if NAC supplementation improves β-cell function and glucose tolerance by decreasing oxidative stress in T2DM. Methods Thirteen subjects (6M/7F) with T2DM (duration: 0-13 years, median: 2years), treated with diet/exercise alone (n=7) or metformin (n=6), underwent a 2-h oral glucose tolerance test (OGTT) at baseline, after 2weeks supplementation with 600mg NAC orally twice daily, and again after 2weeks supplementation with 1200mg NAC twice daily. The following measurements were made: fasting glucose and fructosamine for glycemic control, incremental AUC glucose (0-120min) for glucose tolerance, and Δ insulin/Δ glucose (0-30min) for the early insulin response to glucose. Fasting erythrocyte GSH and GSSG (oxidized glutathione) levels, plasma thiobarbituric acid reactive substances (TBARS), and urine F2α isoprostanes were measured to assess oxidative status. Results Subjects were middle aged (mean±SEM: 53.9±3.2years), obese (BMI 37.3±2.8kg/m2), and relatively well-controlled (HbA1c 6.7±0.3%, 50mmol/mol). Glycemic control, glucose tolerance, insulin release, and oxidative markers did not change with either dose of NAC. Conclusions Based on the lack of any short-term benefit from NAC supplementation on markers of glucose metabolism, β-cell response, and oxidative status, it is unlikely to be a valuable therapeutic approach for treatment of type 2 diabetes.