Post-Glucose Load Plasma alpha-Dicarbonyl Concentrations Are Increased in Individuals With Impaired Glucose Metabolism and Type 2 Diabetes: The CODAM Study

OBJECTIVE There is increasing evidence that postprandial glucose excursions play an important role in the development of vascular complications. The underlying mechanism is unknown, but glucose-derived formation of reactive -dicarbonyl compounds may explain why acute hyperglycemia leads to increased risk for diabetes complications. In the current study, we investigated whether -dicarbonyls are increased after a glucose load in individuals without or with impaired glucose metabolism (IGM) and type 2 diabetes.RESEARCH DESIGN AND METHODSCross-sectional, linear analyses were performed in the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM [n = 574, 61% men, 60 years old]) study. Individuals with normal glucose metabolism (n = 279), IGM (n = 120), and type 2 diabetes (n = 92) who had complete data on an oral glucose tolerance test (OGTT) and were not on insulin treatment were included in the study population. Plasma -dicarbonyl (methylglyoxal [MGO], glyoxal [GO], and 3-deoxyglucosone [3-DG]) levels were measured in the fasting state and in samples of the OGTT by ultra-performance liquid chromatography-tandem mass spectrometry.RESULTSThe presence of both IGM and type 2 diabetes was significantly associated with higher -dicarbonyl incremental areas under the curve (iAUCs), as calculated from the OGTT (for IGM, MGO = 0.190 [95% CI 0.106-0.274], GO = 0.287 [95% CI 0.172-0.401], and 3-DG = 0.285 [95% CI 0.221-0.349]; for type 2 diabetes, MGO = 0.293 [95% CI 0.180-0.405], GO = 0.536 [95% CI 0.382-0.689], and 3-DG = 0.542 [95% CI 0.456-0.628]). Adjustment for glucose iAUC attenuated these associations. iAUCs of the -dicarbonyls correlated highly with glucose iAUC but not with fasting glucose levels or HbA(1c).CONCLUSIONSThe increased levels of -dicarbonyls during an OGTT in individuals with IGM and type 2 diabetes underline the potential importance of -dicarbonyl stress as a candidate to explain the increased risk of diabetes complications in individuals with postprandial hyperglycemia