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

• Published in: Nutrition & diabetes Vol. 14; no. 1; pp. 8 - 9
• Main Authors: Wang, Ling, Huang, Xiaomin, Sun, Mingyao, Zheng, Tian, Zheng, Luyan, Lin, Xiaolan, Ruan, Junshan, Lin, Fan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.03.2024; Nature Publishing Group
• Subjects: 38/23; 631/92/287/1183; 692/163/2743/137/773; 692/499; 692/699/2743/137/773; 692/700/2814; 82/51; Clinical Nutrition; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Epidemiology; Fatty acids; Fatty Acids, Omega-3; Glycated Hemoglobin; Humans; Internal Medicine; Liver; Medicine; Medicine & Public Health; Metabolic Diseases; Pharmacodynamics; Pharmacokinetics; Polyunsaturated fatty acids
• ISSN: 2044-4052; 2044-4052
• DOI: 10.1038/s41387-024-00262-w

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 (HbA 1c ) 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 HbA 1c 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 HbA 1c 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.