Abstract
Aims/hypothesisDicarbonyl 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.MethodsIn 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.ResultsObese 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.Conclusions/interpretationThis 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.Trial registration:ClinicalTrials.gov NCT01167959Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-016-4009-1) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Highlights
MethodsPostprandial glucose excursions are a detrimental factor in diabetic complications [1]
Conclusions/interpretation 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 Roux-en-Y gastric bypass (RYGB)
Fasting and postprandial α-dicarbonyl stress is higher in obese women with type 2 diabetes When we compared obese individuals with normal glucose tolerance (NGT) and those with type 2 diabetes at baseline, we found significantly higher fasting plasma levels of α-dicarbonyls (ESM Table 1, p < 0.01 for all) in those with type 2 diabetes
Summary
Postprandial glucose excursions are a detrimental factor in diabetic complications [1]. An important mechanism for postprandial glucose peaks contributing to increased risk of diabetic complications may be the formation of α-dicarbonyls, which have been linked to a range of detrimental effects on cellular function [2]. We recently showed that individuals with type 2 diabetes had higher plasma levels of the α-dicarbonyls methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), after a glucose load [3]. These highly reactive α-dicarbonyls are mainly formed as glycolytic intermediates during glucose metabolism and rapidly interact with protein residues [2]. Whether type 2 diabetes is associated with higher plasma α-dicarbonyls after a meal is unknown
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