Urinary F2‐Isoprostanes Are Not Associated with Increased Risk of Type 2 Diabetes

Objective: Free radicals have been implicated in the etiology of type 2 diabetes. Cross‐sectional studies have demonstrated associations between oxidative damage and type 2 diabetes. However, no prospective data on this association are available. Research Methods and Procedures: A case control study was conducted within the prospective cohort of the Insulin Resistance Atherosclerosis Study: 26 cases who developed type 2 diabetes in the follow‐up period and 26 controls who remained free of type 2 diabetes were randomly selected. Oxidative status was assessed by measuring 2, 3‐dinor‐5, 6‐dihydro‐15‐F_2t‐isoprostane (F₂‐IsoPM) in baseline urine samples using gas chromatography/mass spectroscopy. Type 2 diabetes was defined by serial oral glucose tolerance tests and World Health Organization criteria. Results: Urinary F₂‐IsoPM varied between 0.18 and 2.60 ng/mg creatinine; 25th/50th/75th percentiles were 0.42, 0.60, and 0.89, respectively. A trend toward higher levels were observed in women and in persons with impaired glucose tolerance at baseline (p = 0.1). F₂‐IsoPM increased with BMI (r = 0.36, p = 0.01). After adjustment for age, gender, baseline impaired glucose tolerance status, and BMI, F₂‐IsoPM levels were inversely associated with development of type 2 diabetes: odds ratio = 0.32 (95% confidence interval, 0.12 to 0.81) for the difference between the 75th and 25th percentiles. Discussion: These results suggest that oxidative damage is not a cause of type 2 diabetes. Positive cross‐sectional associations of F₂‐IsoPM with the risk factors for diabetes, BMI, and impaired glucose tolerance and inverse associations with development of type 2 diabetes indicate that F₂‐IsoPM might reflect a compensatory mechanism.