Energy restriction and Roux-en-Y gastric bypass reduce postprandial α-dicarbonyl stress in obese women with type 2 diabetes.
Dicarbonyl compounds are formed as byproducts of glycolysis and are key mediators of diabetic complications. However, evidence of postprandial α-dicarbonyl formation in humans is lacking, and interventions to reduce α-dicarbonyls have not yet been investigated. Therefore, we investigated postprandial α-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 α-dicarbonyl stress in obese women with type 2 diabetes.



In lean (n = 12) and obese women without (n = 27) or with type 2 diabetes (n = 27), we measured the α-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.



Obese women with type 2 diabetes had higher fasting and particularly higher postprandial plasma α-dicarbonyl levels, compared with those without diabetes. After three weeks of a VLCD, postprandial α-dicarbonyl levels in diabetic women were significantly reduced (AUC MGO -14%, GO -16%, 3-DG -25%), mainly through reduction of fasting plasma α-dicarbonyls (MGO -13%, GO -13%, 3-DG -33%). Similar results were found after RYGB.



This study shows that type 2 diabetes is characterised by increased fasting and postprandial plasma α-dicarbonyl stress, which can be reduced by improving glucose metabolism through a VLCD or RYGB. These data highlight the potential to reduce reactive α-dicarbonyls in obese individuals with type 2 diabetes.



ClinicalTrials.gov NCT01167959.
Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Peter Debeyelaan 25, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands.
Dionne E
DE
Maessen
Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Peter Debeyelaan 25, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands.
Nordin M
NM
Hanssen
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands.
Mirjam A
MA
Lips
Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Peter Debeyelaan 25, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands.
Jean L
JL
Scheijen
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands.|Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden, the Netherlands.
Ko
K
Willems van Dijk
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden, the Netherlands.
Hanno
H
Pijl
Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Peter Debeyelaan 25, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands.
Coen D
CD
Stehouwer
Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Peter Debeyelaan 25, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands. C.Schalkwijk@maastrichtuniversity.nl.
Casper G
CG
Schalkwijk
D000328:Adult; D031204:Caloric Restriction / Q000379:methods*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000601:surgery* / Q000628:therapy*; D005215:Fasting / Q000097:blood; D005260:Female; D015390:Gastric Bypass / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000601:surgery* / Q000628:therapy*; D018384:Oxidative Stress / Q000502:physiology; D019518:Postprandial Period / Q000502:physiology
Advanced glycation endproducts; Obesity; Type 2 diabetes; Weight loss interventions; α-Dicarbonyls