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

中文翻译：

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十二指肠内奎宁对 2 型糖尿病男性血浆葡萄糖、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

 目标/假设

奎宁以 600 毫克的剂量在十二指肠内给药以激活苦味受体时，可刺激胰高血糖素样肽-1 （GLP-1） 和胰岛素，减缓胃排空并降低健康人的餐后血糖，从而对 2 型糖尿病的管理产生影响;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

患有 2 型糖尿病的男性参与者（年龄：68±5 岁;HbA_1c：49.0±5.0 mmol/mol [6.7±0.4%]，BMI：30±1 kg/m²）分两个研究部分（A 和 B，每个 n=12），在三个不同的场合，以随机、交叉的方式，对照或 300 毫克 （QHCl-300） 或 600 毫克 （QHCl-600） 盐酸奎宁，十二指肠内注射，在营养饮料（2092 kJ，74 克碳水化合物）（A 部分）或标准化自助午餐（B 部分）前 30 分钟十二指肠内注射。执行研究程序的参与者和研究人员都对治疗不知情。在 A 部分，在基线、单独使用奎宁后 30 分钟和饮后 3 小时测量血浆葡萄糖、GLP-1、C 肽和胰高血糖素。用 ¹³C-乙酸盐呼气试验测量饮料的胃排空量。在 B 部分，对自助餐的能量摄入进行了量化。

 结果

单独使用奎宁没有效果。饮后，两种奎宁剂量均显著降低血浆峰值葡萄糖 （QHCl-600 降低 2.8±0.6 mmol/l） 并减慢胃排空 （均 p<0.05;n=12，胃排空除外，n=11）。QHCl-600 而非 QHCl-300 适度刺激血浆 GLP-1 和 C 肽 （均为 p<0.05）。奎宁不影响能量摄入。

结论/解释

在 2 型糖尿病中，奎宁的急性十二指肠内给药显着降低血浆葡萄糖对口服碳水化合物的反应，但不影响能量摄入。这些发现支持奎宁可能用于降低 2 型糖尿病的餐后血糖水平。

 试用注册

anzctr.org.au ACTRN12620000972921/ACTRN12621000218897

 资金

该研究由澳大利亚糖尿病研究项目资助。

 图形摘要