Intragastric administration of leucine and isoleucine does not reduce the glycaemic response to, or slow gastric emptying of, a carbohydrate-containing drink in type 2 diabetes

Diabetes Res Clin Pract. 2021 Jan:171:108618. doi: 10.1016/j.diabres.2020.108618. Epub 2020 Dec 10.

Abstract

Aims: In healthy individuals, intragastric administration of the branched-chain amino acids, leucine and isoleucine, diminishes the glycaemic response to a mixed-nutrient drink, apparently by stimulating insulin and slowing gastric emptying, respectively. This study aimed to evaluate the effects of leucine and isoleucine on postprandial glycaemia and gastric emptying in type-2 diabetes mellitus (T2D).

Methods: 14 males with T2D received, on 3 separate occasions, in double-blind, randomised fashion, either 10 g leucine, 10 g isoleucine or control, intragastrically 30 min before a mixed-nutrient drink (500 kcal; 74 g carbohydrates, 18 g protein, 15 g fat). Plasma glucose, insulin and glucagon were measured from 30 min pre- until 120 min post-drink. Gastric emptying of the drink was also measured.

Results: Leucine and isoleucine stimulated insulin, both before and after the drink (all P < 0.05; peak (mU/L): control: 70 ± 15; leucine: 88 ± 17; isoleucine: 74 ± 15). Isoleucine stimulated (P < 0.05), and leucine tended to stimulate (P = 0.078), glucagon before the drink, and isoleucine stimulated glucagon post-drink (P = 0.031; peak (pg/mL): control: 62 ± 5; leucine: 70 ± 9; isoleucine: 69 ± 6). Neither amino acid affected gastric emptying or plasma glucose (peak (mmol/L): control: 12.0 ± 0.5; leucine: 12.5 ± 0.7; isoleucine: 12.0 ± 0.6).

Conclusions: In contrast to health, in T2D, leucine and isoleucine, administered intragastrically in a dose of 10 g, do not lower the glycaemic response to a mixed-nutrient drink. This finding argues against a role for 'preloads' of either leucine or isoleucine in the management of T2D.

Keywords: Blood glucose; Branched-chain amino acids; Glucagon; Glucoregulatory hormones; Human; Insulin.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amino Acids, Branched-Chain / pharmacology
  • Amino Acids, Branched-Chain / therapeutic use*
  • Blood Glucose / drug effects*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Dietary Supplements
  • Double-Blind Method
  • Energy Drinks
  • Gastric Emptying / drug effects*
  • Humans
  • Isoleucine / pharmacology
  • Isoleucine / therapeutic use*
  • Leucine / pharmacology
  • Leucine / therapeutic use*
  • Male
  • Middle Aged
  • Postprandial Period / drug effects*

Substances

  • Amino Acids, Branched-Chain
  • Blood Glucose
  • Isoleucine
  • Leucine