New light on ω-3 polyunsaturated fatty acids and diabetes debate: a population pharmacokinetic-pharmacodynamic modelling and intake threshold study.

IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Nutrition & Diabetes Pub Date : 2024-03-04 DOI:10.1038/s41387-024-00262-w
Ling Wang, Xiaomin Huang, Mingyao Sun, Tian Zheng, Luyan Zheng, Xiaolan Lin, Junshan Ruan, Fan Lin
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Abstract

Objective: ω-3 polyunsaturated fatty acids (PUFA) are a key modifiable factor in the intervention of type 2 diabetes, yet recommendations for dietary consumption of ω-3 PUFA in type 2 diabetes remain ambiguous and controversial. Here, we revisit the subject in the light of population pharmacokinetic-pharmacodynamic (PPK-PD) modeling and propose a threshold for intake.

Research design and methods: Plasma levels of ω-3 PUFA and glycosylated hemoglobin (HbA1c) were measured as pharmacokinetic and pharmacodynamic indicator, respectively. The nonlinear mixed effect analysis was used to construct a PPK-PD model for ω-3 PUFA and to quantify the effects of FADS gene polymorphism, age, liver and kidney function, and other covariables.

Results: Data from 161 patients with type 2 diabetes in the community were modeled in a two-compartment model with primary elimination, and HDL was a statistically significant covariate. The simulation results showed that HbA1c showed a dose-dependent decrease of ω-3 PUFA plasma level. A daily intake of ω-3 PUFA at 0.4 g was sufficient to achieve an HbA1c level of 7% in more than 95% of patients.

Conclusions: PPK/PD modeling was proposed as a multilevel analytical framework to quantitatively investigate finer aspects of the complex relationship between ω-3 PUFA and type 2 diabetes on genetic and non-genetic influence factors. The results support a beneficial role for ω-3 PUFA in type 2 diabetes and suggested the intake threshold. This new approach may provide insights into the interaction of the two and an understanding of the context in which changes occur.

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ω-3多不饱和脂肪酸与糖尿病之争的新启示:人群药代动力学-药效学模型和摄入阈值研究。
目的:ω-3 多不饱和脂肪酸(PUFA)是干预 2 型糖尿病的一个关键可调节因素,但关于 2 型糖尿病患者膳食中ω-3 多不饱和脂肪酸摄入量的建议仍不明确且存在争议。在此,我们根据群体药代动力学-药效学(PPK-PD)模型重新探讨了这一问题,并提出了摄入量的阈值:研究设计与方法:测量血浆中ω-3 PUFA和糖化血红蛋白(HbA1c)的水平,分别作为药代动力学和药效学指标。采用非线性混合效应分析构建了ω-3 PUFA的PPK-PD模型,并量化了FADS基因多态性、年龄、肝肾功能和其他协变量的影响:将 161 名社区 2 型糖尿病患者的数据建立在一级消除的二室模型中,高密度脂蛋白是一个具有统计学意义的协变量。模拟结果显示,HbA1c随ω-3 PUFA血浆水平的下降而呈剂量依赖性下降。每天摄入 0.4 克 ω-3 PUFA 就足以使 95% 以上的患者 HbA1c 水平达到 7%:PPK/PD模型是一个多层次的分析框架,用于定量研究ω-3 PUFA与2型糖尿病之间的复杂关系,以及遗传和非遗传影响因素。研究结果支持ω-3 PUFA对2型糖尿病的有益作用,并提出了摄入阈值。这一新方法可使人们深入了解两者之间的相互作用,并了解发生变化的背景。
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来源期刊
Nutrition & Diabetes
Nutrition & Diabetes ENDOCRINOLOGY & METABOLISM-NUTRITION & DIETETICS
CiteScore
9.20
自引率
0.00%
发文量
50
审稿时长
>12 weeks
期刊介绍: Nutrition & Diabetes is a peer-reviewed, online, open access journal bringing to the fore outstanding research in the areas of nutrition and chronic disease, including diabetes, from the molecular to the population level.
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