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

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 10g leucine, 10g isoleucine or control, intragastrically 30 min before a mixed-nutrient drink (500 kcal; 74g carbohydrates, 18g protein, 15g 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.