Dionne E Maessen1, Nordin M Hanssen1, Jean L Scheijen1, Carla J van der Kallen1, Marleen M van Greevenbroek1, Coen D Stehouwer1, Casper G Schalkwijk2. 1. CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands. 2. CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands c.schalkwijk@maastrichtuniversity.nl.
Abstract
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 α-dicarbonyl compounds may explain why acute hyperglycemia leads to increased risk for diabetes complications. In the current study, we investigated whether α-dicarbonyls are increased after a glucose load in individuals without or with impaired glucose metabolism (IGM) and type 2 diabetes. RESEARCH DESIGN AND METHODS: Cross-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 α-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. RESULTS: The presence of both IGM and type 2 diabetes was significantly associated with higher α-dicarbonyl incremental areas under the curve (iAUCs), as calculated from the OGTT (for IGM, MGO β = 0.190 [95% CI 0.106-0.274], GO β = 0.287 [95% CI 0.172-0.401], and 3-DG β = 0.285 [95% CI 0.221-0.349]; for type 2 diabetes, MGO β = 0.293 [95% CI 0.180-0.405], GO β = 0.536 [95% CI 0.382-0.689], and 3-DG β = 0.542 [95% CI 0.456-0.628]). Adjustment for glucose iAUC attenuated these associations. iAUCs of the α-dicarbonyls correlated highly with glucose iAUC but not with fasting glucose levels or HbA1c. CONCLUSIONS: The increased levels of α-dicarbonyls during an OGTT in individuals with IGM and type 2 diabetes underline the potential importance of α-dicarbonyl stress as a candidate to explain the increased risk of diabetes complications in individuals with postprandial hyperglycemia.
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 α-dicarbonyl compounds may explain why acute hyperglycemia leads to increased risk for diabetes complications. In the current study, we investigated whether α-dicarbonyls are increased after a glucose load in individuals without or with impaired glucose metabolism (IGM) and type 2 diabetes. RESEARCH DESIGN AND METHODS: Cross-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 α-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. RESULTS: The presence of both IGM and type 2 diabetes was significantly associated with higher α-dicarbonyl incremental areas under the curve (iAUCs), as calculated from the OGTT (for IGM, MGO β = 0.190 [95% CI 0.106-0.274], GO β = 0.287 [95% CI 0.172-0.401], and 3-DG β = 0.285 [95% CI 0.221-0.349]; for type 2 diabetes, MGO β = 0.293 [95% CI 0.180-0.405], GO β = 0.536 [95% CI 0.382-0.689], and 3-DG β = 0.542 [95% CI 0.456-0.628]). Adjustment for glucose iAUC attenuated these associations. iAUCs of the α-dicarbonyls correlated highly with glucose iAUC but not with fasting glucose levels or HbA1c. CONCLUSIONS: The increased levels of α-dicarbonyls during an OGTT in individuals with IGM and type 2 diabetes underline the potential importance of α-dicarbonyl stress as a candidate to explain the increased risk of diabetes complications in individuals with postprandial hyperglycemia.
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