Huang Yueh-Hsiang, Liu Geng-Hao, Hsu Tzu-Yang, Yang Lan-Yan, Lee Ming-Chung, Huang Chun-Teng, Wu Yi-Hong
Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Front Pharmacol. 2021 Jan 25;11:597703. doi: 10.3389/fphar.2020.597703. eCollection 2020.
is a popular phytomedicine for the treatment of type 2 diabetes in Asia, but its effective dose for diabetes treatment remains confused because of diverse origins. This study aimed to investigate the dose-response effects of extract granules (RCEG), produced with standardized quality control, on hypoglycemic effects in patients with type 2 diabetes. We conducted a retrospective analysis of Chang Gung Research Database from January 01, 2008 to November 30, 2017. Outpatients visiting traditional Chinese medicine clinics and receiving RCEG for type 2 diabetes treatment were included. Plasma glucose, lipid, and other parameters were analyzed from 93 patients with a total of 737 visits within 60 weeks. Scatter plots with the LOESS analysis were used to explore the association between RCEG dose and hypoglycemic effect. The minimal effective dose was chosen to divide the study population into the high-dose and low-dose RCEG groups. Non-parametric tests were used for between-group and within-group comparisons. The multivariate nonlinear mixed-effects model was applied to access the effect of treatment length and groups simultaneously on the change of HbA1c and fasting plasma glucose. The "arule" package in R was used to present the network diagram of RCEG and other co-prescriptions. We first discovered a significant relationship between RCEG dose and HbA1c reduction when the dose reached 0.08 g/kg/day or higher. We thus defined 0.08 g/kg/day of RCEG as the minimum effective dose, and a threshold to separate patients into the high-dose (≥0.08 g/kg/d) and low-dose (<0.08 g/kg/d) RCEG groups. In the high-dose RCEG group, a significant decrease in total cholesterol and a trend toward triglyceride reduction were also noted. Patients more effectively responded to RCEG treatment if they had a higher initial HbA1c level, higher heart rates, better liver function tests, and better tolerance to the higher dose and treatment duration of RCEG. In addition, digestive/tonic/dampness draining formulas and blood regulation recipes were two of the most frequent co-prescriptions with RCEG. This study concluded that RCEG at a dose exceeding 0.08 g/kg/d had beneficial effects on glycemic and lipid control, without showing nephro- or hepatotoxicity, in patients with type 2 diabetes.
在亚洲，它是一种用于治疗2型糖尿病的常用植物药，但由于来源多样，其治疗糖尿病的有效剂量仍不明确。本研究旨在探讨采用标准化质量控制生产的提取物颗粒（RCEG）对2型糖尿病患者降血糖作用的剂量反应效应。我们对长庚研究数据库2008年1月1日至2017年11月30日的数据进行了回顾性分析。纳入在中医诊所就诊并接受RCEG治疗2型糖尿病的门诊患者。对93例患者在60周内共737次就诊时的血糖、血脂及其他参数进行了分析。采用带局部加权散点平滑法（LOESS）分析的散点图来探讨RCEG剂量与降血糖效果之间的关联。选择最小有效剂量将研究人群分为高剂量和低剂量RCEG组。采用非参数检验进行组间和组内比较。应用多元非线性混合效应模型同时评估治疗时长和组别对糖化血红蛋白（HbA1c）和空腹血糖变化的影响。使用R语言中的“arule”包展示RCEG与其他联合处方的网络图。我们首次发现，当RCEG剂量达到0.08 g/kg/天或更高时，其剂量与HbA1c降低之间存在显著关系。因此，我们将0.08 g/kg/天的RCEG定义为最小有效剂量，作为将患者分为高剂量（≥0.08 g/kg/d）和低剂量（<0.08 g/kg/d）RCEG组的阈值。在高剂量RCEG组中，总胆固醇也显著降低，甘油三酯有降低趋势。初始HbA1c水平较高、心率较快、肝功能检查较好以及对RCEG较高剂量和治疗时长耐受性较好的患者对RCEG治疗反应更有效。此外，消食/滋补/祛湿方剂和调血方剂是与RCEG最常联合使用的两种处方。本研究得出结论，对于2型糖尿病患者，剂量超过0.08 g/kg/d的RCEG对血糖和血脂控制有益，且未显示出肾毒性或肝毒性。
