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

Abstract

Aims/hypothesis: 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.

Methods: 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.

Results: 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.

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 RYGB. These data highlight the potential to reduce reactive α-dicarbonyls in obese individuals with type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT01167959.

Keywords: Advanced glycation endproducts; Obesity; Type 2 diabetes; Weight loss interventions; α-Dicarbonyls.

Figures

Fig. 1

Baseline plasma levels of α-dicarbonyls and glucose before and during a mixed meal test. Plasma levels during the MMT of (a) MGO, (c) GO, (e) 3-DG and (g) glucose and iAUC, as calculated from the MMT of (b) MGO, (d) GO, (f) 3-DG and (h) glucose. Data are shown as means (SEM). Triangles, lean, n = 12; squares, obese NGT, n = 27; circles, obese type 2 diabetic individuals, n = 27. Differences in postprandial curves during the mixed meal between the groups were tested with repeated-measures two-way ANOVA with Bonferroni correction. Differences in the iAUCs of MGO, GO, 3-DG and glucose between the groups were tested with one-way ANOVA with Bonferroni correction. *p < 0.05, **p < 0.01 and ***p < 0.001 compared with lean individuals and †††p < 0.001 compared with obese NGT individuals

Fig. 2

Plasma levels of α-dicarbonyls and glucose in obese individuals with type 2 diabetes after 3 weeks of a VLCD. Plasma levels during the MMT of (a) MGO, (c) GO, (e) 3-DG and (g) glucose and iAUC, as calculated from the MMT, of (b) MGO, (d) GO, (f) 3-DG and (h) glucose. Data are shown as means (SEM). Black circles, obese type 2 diabetes individuals before the VLCD; open circles, obese type 2 diabetes individuals 3 weeks after the VLCD, n = 12. Differences in fasting levels and the iAUCs of MGO, GO, 3-DG and glucose were tested with paired two-sided samples t tests. *p < 0.05 compared with baseline