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

Abstract

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: 2 years), treated with diet/exercise alone (n=7) or metformin (n=6), underwent a 2-h oral glucose tolerance test (OGTT) at baseline, after 2 weeks supplementation with 600 mg NAC orally twice daily, and again after 2 weeks supplementation with 1200 mg NAC twice daily. The following measurements were made: fasting glucose and fructosamine for glycemic control, incremental AUC glucose (0-120 min) for glucose tolerance, and Δ insulin/Δ glucose (0-30 min) 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 ± 3.2 years), obese (BMI 37.3 ± 2.8 kg/m(2)), and relatively well-controlled (HbA1c 6.7 ± 0.3%, 50 mmol/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.

Keywords: Antioxidant; N-Acetylcysteine; Oxidative stress; Supplement; β-cell function.

Published by Elsevier Inc.

Figures

Figure 1

No significant differences in the incremental AUC glucose or fasting insulin were seen for subjects on Metformin (A and C) or not on Metformin (B and D) with use of low dose or high dose NAC.