Activation of Oxidative Stress by Acute Glucose Fluctuations Compared With Sustained Chronic Hyperglycemia in Patients with Type 2 Diabetes.

Context: Glycemic disorders, one of the main risk factors for cardiovascular disease, are associated with activation of oxidative stress. Objective To assess the respective contributions of sustained chronic hyperglycemia and of acute glucose fluctuations to oxidative stress in type 2 diabetes. Design, Setting, and Participants: Case-control study of 21 patients with type 2 diabetes (studied 2003-2005) compared with 21 age- and sex-matched controls (studied in 2001) in Montpellier, France. Main Outcome Measures: Oxidative stress, estimated from 24-hour urinary excretion rates of free 8-iso prostaglandin F2α (8-iso PGF2α). Assessment of glucose fluctuations was obtained from continuous glucose monitoring system data by calculating the mean amplitude of glycemic excursions (MAGE). Postprandial contribution to glycemic instability was assessed by determining the postprandial increment of glucose level above preprandial values (mean postprandial incremental area under the curve [AUCpp]). Long-term exposure to glucose was estimated from hemoglobin A1c, from fasting glucose levels, and from mean glucose concentrations over a 24-hour period. Results: Mean (SD) urinary 8-iso PGF2α excretion rates were higher in the 21 patients with diabetes (482 [206] pg/mg of creatinine) compared with controls (275 [85] pg/mg of creatinine). In univariate analysis, only MAGE (r = 0.86; P