Abstract

BackgroundThe rate of gastric emptying and glucoregulatory hormones are key determinants of postprandial glycaemia. Intragastric administration of L-tryptophan slows gastric emptying and reduces the glycaemic response to a nutrient drink in lean individuals and those with obesity. We investigated whether tryptophan decreases postprandial glycaemia and slows gastric emptying in type 2 diabetes (T2D).MethodsTwelve men with T2D (age: 63 ± 2 years, HbA1c: 49.7 ± 2.5 mmol/mol, BMI: 30 ± 1 kg/m2) received, on three separate occasions, 3 g (‘Trp-3’) or 1.5 g (‘Trp-1.5’) tryptophan, or control (0.9% saline), intragastrically, in randomised, double-blind fashion, 30 min before a mixed-nutrient drink (500 kcal, 74 g carbohydrates), containing 3 g 3-O-methyl-D-glucose (3-OMG) to assess glucose absorption. Venous blood samples were obtained at baseline, after tryptophan, and for 2 h post-drink for measurements of plasma glucose, C-peptide, glucagon and 3-OMG. Gastric emptying of the drink was quantified using two-dimensional ultrasound.ResultsTryptophan alone stimulated C-peptide (P = 0.002) and glucagon (P = 0.04), but did not affect fasting glucose. In response to the drink, Trp-3 lowered plasma glucose from t = 15–30 min and from t = 30–45 min compared with control and Trp-1.5, respectively (both P < 0.05), with no differences in peak glucose between treatments. Gastric emptying tended to be slower after Trp-3, but not Trp-1.5, than control (P = 0.06). Plasma C-peptide, glucagon and 3-OMG increased on all days, with no major differences between treatments.ConclusionsIn people with T2D, intragastric administration of 3 g tryptophan modestly slows gastric emptying, associated with a delayed rise, but not an overall lowering of, postprandial glucose.

Highlights

  • Gastric emptying and the release of the glucoregulatory hormones, insulin and glucagon, are important determinants of the postprandial blood glucose response to carbohydrate-containing meals, in health, obesity and type 2 diabetes (T2D)[1]

  • Study design We investigated the effects of intragastric administration of (i) 3 g (Trp-3) or (ii) 1.5 g (Trp-1.5) tryptophan, or (iii) control (0.9% saline) on plasma glucose, C-peptide, and glucagon concentrations and glucose absorption in response to, and gastric emptying of, a mixed-nutrient drink, consumed 30 min after the intragastric treatments

  • C-peptide and glucagon concentrations at t = −1 min, which we reported previously to correlate with subsequent glycaemic control[15], peak plasma glucose, time to peak glucose and gastric half-emptying time (T50) were analysed using repeated-measures analysis of variance (ANOVA)

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Summary

Introduction

Gastric emptying and the release of the glucoregulatory hormones, insulin and glucagon, are important determinants of the postprandial blood glucose response to carbohydrate-containing meals, in health, obesity and type 2 diabetes (T2D)[1]. In T2D, whey protein, when given as a preload 30 min before a high-carbohydrate meal, slowed gastric emptying and stimulated insulin, leading to a reduction in the glycaemic response[6]. These effects of protein appear to be mediated, at least in part, by their digestion products, amino acids — both circulating amino acids and as a result of the interaction of amino acids with the small intestine[7,8,9,10]. We investigated whether tryptophan decreases postprandial glycaemia and slows gastric emptying in type 2 diabetes (T2D)

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