十二指肠内注射奎宁对2型糖尿病男性患者血糖、糖调节激素、营养饮料胃排空及能量摄入的剂量相关效应：一项双盲、随机、交叉研究
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.
作者信息
Bitarafan Vida, Anjom-Shoae Javad, Rezaie Peyman, Fitzgerald Penelope C E, Lange Kylie, Horowitz Michael, Feinle-Bisset Christine
机构信息
Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, SA, Australia.
出版信息
Diabetologia. 2025 Apr;68(4):727-738. doi: 10.1007/s00125-024-06344-9. Epub 2024 Dec 18.
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: 49.0±5.0 mmol/mol [6.7±0.4%], BMI: 30±1 kg/m) 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 C-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.
目的/假设：将600毫克奎宁经十二指肠给药以激活苦味受体时，可刺激健康人的胰高血糖素样肽-1（GLP-1）和胰岛素分泌，减缓胃排空并降低餐后血糖，这对2型糖尿病的治疗具有重要意义；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型糖尿病男性参与者（年龄：68±5岁；糖化血红蛋白：49.0±5.0 mmol/mol [6.7±0.4%]，体重指数：30±1 kg/m²）在两个研究部分（A和B，各n = 12）中，每次以随机交叉方式，分别接受三次对照、300毫克（盐酸奎宁-300）或600毫克（盐酸奎宁-600）盐酸奎宁，在饮用营养饮料（2092千焦，74克碳水化合物）前30分钟经十二指肠给药（A部分）或在标准化自助午餐前给药（B部分）。参与研究的参与者和研究人员均对治疗方案不知情。在A部分，在基线、单独服用奎宁后30分钟以及饮用饮料后3小时测量血浆葡萄糖、GLP-1、C肽和胰高血糖素。通过¹⁴C-醋酸呼气试验测量饮料的胃排空情况。在B部分，对自助午餐的能量摄入进行量化。
结果
单独服用奎宁无效果。饮用饮料后, 两种奎宁剂量均显著降低血浆葡萄糖峰值（盐酸奎宁-600降低2.8±0.6 mmol/l）并减缓胃排空（所有p<0.05；n = 12，胃排空情况n = 11除外）。盐酸奎宁-600适度刺激血浆GLP-1和C肽分泌（均p<0.05），但盐酸奎宁-300无此作用。奎宁不影响能量摄入。
结论/解读：在2型糖尿病患者中，经十二指肠急性给予奎宁可显著降低口服碳水化合物后血浆葡萄糖反应，但不影响能量摄入。这些发现支持了奎宁在降低2型糖尿病患者餐后血糖水平方面的潜在用途。
试验注册
anzctr.org.au ACTRN12620000972921/ACTRN12621000218897 资助：本研究由澳大利亚糖尿病研究项目基金资助。
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