title: Post-Glucose Load Plasma α-Dicarbonyl Concentrations Are Increased in Individuals With Impaired Glucose Metabolism and Type 2 Diabetes: The CODAM Study.
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.
  
  
  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.
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Dionne E
authors.initials: DE
authors.lastname: Maessen
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Nordin M
authors.initials: NM
authors.lastname: Hanssen
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Scheijen
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: van der Kallen
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Marleen M
authors.initials: MM
authors.lastname: van Greevenbroek
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Coen D
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: 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.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
mesh_terms: D050197:Atherosclerosis / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002853:Chromatography, Liquid; D003430:Cross-Sectional Studies; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003925:Diabetic Angiopathies / Q000097:blood*; D005215:Fasting / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006037:Glyoxal / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology; D011765:Pyruvaldehyde / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D003847:Deoxyglucose; D006442:Glycated Hemoglobin; D006037:Glyoxal; D011765:Pyruvaldehyde; C016350:3-deoxyglucosone