title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and University of Washington, Seattle, WA. Electronic address: magda3@u.washington.edu.
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Szkudlinska
authors.affiliation: Post-Graduate Endocrinology Program, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: anize.frankenberg@gmail.com.
authors.forename: Anize D
authors.initials: AD
authors.lastname: von Frankenberg
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and University of Washington, Seattle, WA. Electronic address: kutzschn@u.washington.edu.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Utzschneider
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015992:Body Mass Index; D003131:Combined Modality Therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000178:diet therapy* / Q000378:metabolism / Q000628:therapy; D019587:Dietary Supplements; D028441:F2-Isoprostanes / Q000652:urine; D019270:Fructosamine / Q000097:blood; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D018384:Oxidative Stress; D010865:Pilot Projects; D014861:Washington
chemical_list: D000111:Acetylcysteine; D000975:Antioxidants; D015415:Biomarkers; D028441:F2-Isoprostanes; D019270:Fructosamine; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human
keywords: Antioxidant; N-Acetylcysteine; Oxidative stress; Supplement; β-cell function