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γ-氨基丁酸补充剂对糖尿病前期成年人血糖控制的影响:一项双盲、随机、安慰剂对照试验。

Effects of γ-aminobutyric acid supplementation on glucose control in adults with prediabetes: A double-blind, randomized, placebo-controlled trial.

机构信息

Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands; Wageningen Plant Research, Wageningen University & Research, Wageningen, The Netherlands.

Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.

出版信息

Am J Clin Nutr. 2023 Sep;118(3):708-719. doi: 10.1016/j.ajcnut.2023.07.017. Epub 2023 Jul 24.

Abstract

BACKGROUND

Gamma-aminobutyric acid (GABA) is mainly known as an endogenously produced neurotransmitter. However, GABA intake from dietary sources like tomatoes and fermented foods can be considerable. Studies in rodent models have shown beneficial effects of oral GABA supplementation on glucose homeostasis and cardiovascular health. Still, it is currently unknown whether oral GABA supplementation produces cardiometabolic benefits in humans.

OBJECTIVES

This study aimed to investigate whether oral GABA supplementation can improve glucose homeostasis in individuals at risk of developing type 2 diabetes.

METHODS

In a randomized, placebo-controlled, double-blind, parallel-arm trial, 52 individuals with prediabetes (classified by impaired glucose tolerance and/or impaired fasting glucose), aged 50 to 70 y with a body mass index ≥25 kg/m received either 500 mg GABA 3 times daily or a placebo for 95 days. The primary outcome was the effect of the intervention on glucose response after an OGTT. As exploratory secondary outcomes, markers of glycemic control (glycated hemoglobin, insulin, glucagon, mean amplitude of glycemic excursions, and standard deviation as measured with flash glucose monitoring), cardiovascular health (blood pressure, 24-h blood pressure, circulating triglycerides, cholesterol), and self-reported sleep quality were measured before and after the intervention.

RESULTS

Compared with placebo, GABA supplementation for 95 days did not change the postprandial glucose response (0.21 mmol/L; 95% confidence interval: -0.252, 0.674; P = 0.364). After correction for the false discovery rate, all other outcomes (including fasting plasma GABA concentration) showed no significant effects from GABA intervention at a group level.

CONCLUSIONS

GABA supplementation does not change the postprandial glucose response in individuals at risk of developing type 2 diabetes. However, based on findings in secondary outcome measures, further research is warranted in other study populations. Research could focus on the effects of GABA in individuals with advanced diabetes or other cardiometabolic disorders. This trial was registered at www.

CLINICALTRIALS

gov as NCT04303468.

摘要

背景

γ-氨基丁酸(GABA)主要作为内源性神经递质而被人们熟知。然而,人们也可以从番茄和发酵食品等饮食来源中摄取 GABA。啮齿动物模型的研究表明,口服 GABA 补充剂对葡萄糖稳态和心血管健康有益。不过,目前尚不清楚口服 GABA 补充剂是否会给人类带来心脏代谢益处。

目的

本研究旨在探究口服 GABA 补充剂是否能改善处于 2 型糖尿病前期的个体的葡萄糖稳态。

方法

在一项随机、安慰剂对照、双盲、平行臂试验中,52 名年龄在 50 至 70 岁、BMI≥25 kg/m²、患有前驱糖尿病(定义为糖耐量受损和/或空腹血糖受损)的个体接受了每日 3 次、每次 500mg GABA 或安慰剂的治疗,共 95 天。主要结局是干预对 OGTT 后葡萄糖反应的影响。作为探索性次要结局,测量了血糖控制标志物(糖化血红蛋白、胰岛素、胰高血糖素、血糖波动幅度的均值和标准差,通过瞬感血糖仪进行测量)、心血管健康(血压、24 小时血压、循环甘油三酯、胆固醇)和自我报告的睡眠质量在干预前后的变化。

结果

与安慰剂相比,95 天的 GABA 补充剂治疗并未改变餐后血糖反应(0.21mmol/L;95%置信区间:-0.252,0.674;P=0.364)。在进行虚假发现率校正后,在组水平上,GABA 干预对所有其他结局(包括空腹血浆 GABA 浓度)均无显著影响。

结论

GABA 补充剂不会改变处于 2 型糖尿病前期风险的个体的餐后血糖反应。然而,基于次要结局测量的发现,仍需要在其他研究人群中进行进一步研究。研究可以集中在 GABA 对糖尿病晚期或其他心脏代谢疾病患者的影响上。本试验在 www.clinicaltrials.gov 上注册,编号为 NCT04303468。

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