Energy restriction and Roux-en-Y gastric bypass reduce postprandial alpha-dicarbonyl stress in obese women with type 2 diabetes

Aims/hypothesis Dicarbonyl compounds are formed as byproducts of glycolysis and are keymediators of diabetic complications. However, evidence of postprandial alpha-dicarbonyl formation in humans is lacking, and interventions to reduce alpha-dicarbonyls have not yet been investigated. Therefore, we investigated postprandial alpha-dicarbonyl levels in obese women without and with type 2 diabetes. Furthermore, we evaluated whether a diet very low in energy (very low calorie diet [VLCD]) or Roux-en-Y gastric bypass (RYGB) reduces alpha-dicarbonyl stress in obese women with type 2 diabetes. Methods In lean (n = 12) and obese women without (n=27) or with type 2 diabetes (n = 27), we measured the alpha-dicarbonyls, methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), and glucose in fasting and postprandial plasma samples obtained during a mixed meal test. Obese women with type 2 diabetes underwent either a VLCD or RYGB. Three weeks after the intervention, individuals underwent a second mixed meal test. Results Obese women with type 2 diabetes had higher fasting and particularly higher postprandial plasma alpha-dicarbonyl levels, compared with those without diabetes. After three weeks of a VLCD, postprandial alpha-dicarbonyl levels in diabetic women were significantly reduced (AUCMGO-14%, GO-16%, 3-DG -25%), mainly through reduction of fasting plasma alpha-dicarbonyls (MGO -13%, GO -13%, 3-DG -33%). Similar results were found after RYGB. Conclusions/interpretation This study shows that type 2 diabetes is characterised by increased fasting and postprandial plasma alpha-dicarbonyl stress, which can be reduced by improving glucose metabolism through a VLCD or RYGB. These data highlight the potential to reduce reactive alpha-dicarbonyls in obese individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT01167959