Effects of a D-xylose preload with or without sitagliptin on gastric emptying, glucagon-like peptide-1, and postprandial glycemia in type 2 diabetes

Tongzhi Wu, Michelle J Bound, Beiyi R Zhao, Scott D Standfield, Max Bellon, Karen L Jones, Michael Horowitz, Christopher K Rayner, Tongzhi Wu, Michelle J Bound, Beiyi R Zhao, Scott D Standfield, Max Bellon, Karen L Jones, Michael Horowitz, Christopher K Rayner

Abstract

Objective: Macronutrient "preloads" can reduce postprandial glycemia by slowing gastric emptying and stimulating glucagon-like peptide-1 (GLP-1) secretion. An ideal preload would entail minimal additional energy intake and might be optimized by concurrent inhibition of dipeptidyl peptidase-4 (DPP-4). We evaluated the effects of a low-energy D-xylose preload, with or without sitagliptin, on gastric emptying, plasma intact GLP-1 concentrations, and postprandial glycemia in type 2 diabetes.

Research design and methods: Twelve type 2 diabetic patients were studied on four occasions each. After 100 mg sitagliptin (S) or placebo (P) and an overnight fast, patients consumed a preload drink containing either 50 g D-xylose (X) or 80 mg sucralose (control [C]), followed after 40 min by a mashed potato meal labeled with (13)C-octanoate. Blood was sampled at intervals. Gastric emptying was determined.

Results: Both peak blood glucose and the amplitude of glycemic excursion were lower after PX and SC than PC (P < 0.01 for each) and were lowest after SX (P < 0.05 for each), while overall blood glucose was lower after SX than PC (P < 0.05). The postprandial insulin-to-glucose ratio was attenuated (P < 0.05) and gastric emptying was slower (P < 0.01) after D-xylose, without any effect of sitagliptin. Plasma GLP-1 concentrations were higher after D-xylose than control only before the meal (P < 0.05) but were sustained postprandially when combined with sitagliptin (P < 0.05).

Conclusions: In type 2 diabetes, acute administration of a D-xylose preload reduces postprandial glycemia and enhances the effect of a DPP-4 inhibitor.

Figures

Figure 1
Figure 1
Effects of d-xylose or sucralose (control) with or without sitagliptin on blood glucose (A), serum insulin (B), insulin-to-glucose ratio (C), and plasma intact GLP-1 (D) in response to a carbohydrate meal (n = 12). The four treatments were SX, SC, PX, and PC. Repeated-measures ANOVA was used to determine statistical difference. Post hoc comparisons were adjusted by Bonferroni-Holm correction. P = 0.000 for each treatment × time interaction; *P < 0.05, PX vs. PC; #P < 0.05, SC vs. PC; αP < 0.05, SX vs. PC; δP < 0.05, SX vs. PX; εP < 0.05, SX vs. SC. Data are means ± SEM.
Figure 2
Figure 2
Effects of d-xylose or sucralose (control) with or without sitagliptin on breath hydrogen production in response to a carbohydrate meal (n = 12). The four treatments were SX (■), SC (●), PX (), and PC (○). Repeated-measures ANOVA was used to determine statistical difference. *P = 0.000, PX vs. PC and SC; #P = 0.000, SX vs. PC and SC. Data are means ± SEM.
Figure 3
Figure 3
Effects of d-xylose or sucralose (control) with or without sitagliptin on gastric emptying (half-emptying time [T50]) (n = 12). The four treatments were SX, SC, PX, and PC. One-factor repeated-measures ANOVA was used to determine statistical difference. Post hoc comparisons were adjusted by Bonferroni-Holm correction. P = 0.000 for a treatment effect; *P < 0.01, PX vs. PC and SC; #P < 0.001, SX vs. PC and SC. Data are means ± SEM.

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