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

IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetologia Pub Date : 2024-12-18 DOI:10.1007/s00125-024-06344-9

Vida Bitarafan, Javad Anjom-Shoae, Peyman Rezaie, Penelope C. E. Fitzgerald, Kylie Lange, Michael Horowitz, Christine Feinle-Bisset

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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

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胃十二指肠内奎宁对 2 型糖尿病男性患者血浆葡萄糖、糖调节激素和营养饮料胃排空以及能量摄入的剂量相关影响：一项双盲、随机、交叉研究

目的/假设：600毫克剂量的奎宁经十二指肠注射激活苦味受体，刺激胰高血糖素样肽-1 （GLP-1）和胰岛素，减缓胃排空，降低健康人餐后血糖，从而对2型糖尿病的治疗有影响；奎宁对能量摄入的影响尚不确定。我们研究了奎宁对2型糖尿病患者餐后血糖水平和能量摄入的剂量相关影响。方法2型糖尿病患者(年龄：68±5岁；HbA1c: 49.0±5.0 mmol/mol[6.7±0.4%],BMI: 30±1 kg/m2)分为两个研究部分（A和B，各n=12），分别在三个不同的情况下，随机，交叉方式，对照，或300 mg （qhl -300）或600 mg （qhl -600）盐酸奎宁，在营养饮料（2092 kJ， 74 g碳水化合物）（A部分）或标准化自助午餐（B部分）前30分钟内服药。执行研究程序的参与者和研究者对治疗都是盲法的。在A部分，分别在基线、单独使用奎宁后30分钟和饮用奎宁后3小时测量血浆葡萄糖、GLP-1、c肽和胰高血糖素。用13c -醋酸盐呼气试验测定饮料的胃排空量。在B部分，对自助午餐的能量摄入进行量化。结果单用奎宁治疗无效。饮用后，两种奎宁剂量均显著降低血浆葡萄糖峰值（QHCl-600降低2.8±0.6 mmol/l），减缓胃排空(p < 0.05；N =12，胃排空除外，N =11)。QHCl-600能适度刺激血浆GLP-1和c肽（p < 0.05），而QHCl-300则没有。奎宁不影响能量摄入。结论/解释在2型糖尿病患者中，急性十二指肠内给药奎宁可显著降低血糖对口服碳水化合物的反应，但不影响能量摄入。这些发现支持奎宁在降低2型糖尿病患者餐后血糖水平方面的潜在应用。本研究由澳大利亚糖尿病研究项目基金资助。图形抽象

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来源期刊

Diabetologia 医学-内分泌学与代谢

CiteScore

18.10

自引率

2.40%

发文量

193

审稿时长

1 months

期刊介绍： Diabetologia, the authoritative journal dedicated to diabetes research, holds high visibility through society membership, libraries, and social media. As the official journal of the European Association for the Study of Diabetes, it is ranked in the top quartile of the 2019 JCR Impact Factors in the Endocrinology & Metabolism category. The journal boasts dedicated and expert editorial teams committed to supporting authors throughout the peer review process.