Dose-related effects of intraduodenal quinine on plasma glucose, glucoregulatory hormones and gastric emptying of a nutrient drink, and energy intake, in men with type 2 diabetes: a double-blind, randomised, crossover study

Abstract

Aims/hypothesis

Quinine, when administered intraduodenally to activate bitter-taste receptors, in a dose of 600 mg, stimulates glucagon-like peptide-1 (GLP-1) and insulin, slows gastric emptying and lowers postprandial glucose in healthy people, with consequent implications for the management of type 2 diabetes; the effect of quinine on energy intake is uncertain. We have investigated the dose-related effects of quinine on postprandial blood glucose levels and energy intake in people with type 2 diabetes.

Methods

Male participants with type 2 diabetes (age: 68±5 years; HbA_1c: 49.0±5.0 mmol/mol [6.7±0.4%], BMI: 30±1 kg/m²) received in two study parts (A and B, n=12 each), on three separate occasions each, in randomised, crossover fashion, control, or 300 mg (QHCl-300) or 600 mg (QHCl-600) quinine hydrochloride, intraduodenally 30 min before a nutrient drink (2092 kJ, 74 g carbohydrate) (part A) or a standardised buffet-lunch (part B). Both the participants and investigators performing the study procedures were blinded to the treatments. In part A, plasma glucose, GLP-1, C-peptide and glucagon were measured at baseline, for 30 min after quinine alone and for 3 h post drink. Gastric emptying of the drink was measured with a ¹³C-acetate breath test. In part B, energy intake from the buffet-lunch was quantified.

Results

Quinine alone had no effect. Post drink, both quinine doses reduced peak plasma glucose markedly (QHCl-600 by 2.8±0.6 mmol/l) and slowed gastric emptying (all p<0.05; n=12, except for gastric emptying, n=11). QHCl-600, but not QHCl-300, stimulated plasma GLP-1 and C-peptide modestly (both p<0.05). Quinine did not affect energy intake.

Conclusions/interpretation

In type 2 diabetes, acute intraduodenal administration of quinine markedly reduces the plasma glucose response to oral carbohydrate, but does not affect energy intake. These findings support the potential use of quinine to reduce postprandial blood glucose levels in type 2 diabetes.

Trial registration

anzctr.org.au ACTRN12620000972921/ACTRN12621000218897

Funding

The study was funded by a Diabetes Australia Research Project Grant.

Graphical Abstract