Circulating Fatty Acids and Genetic Predisposition to Type 2 Diabetes: Gene-Nutrient Interaction Analysis

作者：Pan Zhuang, Xiaohui Liu, Yin Li, Haoyu Li, Lange Zhang, Xuzhi Wan, Yuqi Wu, Yu Zhang, Jingjing Jiao · 发表于：Diabetes Care · 年份：2022 · DOI：10.2337/dc21-2048 · 被引用次数：52 · 研究领域：Fatty Acid Research and Health、Nutrition, Genetics, and Disease、Liver Disease Diagnosis and Treatment

OBJECTIVE: To assess the relationship of circulating fatty acids (FA) with risk of type 2 diabetes (T2D) and potential interactions with genetic risk. RESEARCH DESIGN AND METHODS: A total of 95,854 participants with complete data on plasma FA from the UK Biobank were enrolled between 2006 and 2010 and were followed up to the end of 2020. Plasma concentrations of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) were analyzed by a high-throughput nuclear magnetic resonance-based biomarker profiling platform. The genetic risk scores (GRS) were calculated on the basis of 424 variants associated with T2D. Pathway-specific GRS were calculated based on robust clusters of T2D loci. RESULTS: There were 3,052 instances of T2D documented after an average follow-up of 11.6 years. Plasma concentrations of SFA and MUFA were positively associated with T2D risk, while plasma PUFA were inversely associated. After adjustment for major risk factors, hazard ratios (95% CI) of T2D for 1-SD increment were 1.03 (1.02-1.04) for SFA, 1.03 (1.02-1.05) for MUFA, 0.62 (0.56-0.68) for PUFA, 0.67 (0.61-0.73) for n-6 PUFA, 0.90 (0.85-0.95) for n-3 PUFA, and 1.01 (0.98-1.04) for n-6-to-n-3 ratio. Plasma MUFA had significant interactions with the overall GRS and GRS for proinsulin and liver/lipid clusters on T2D risk. The protective associations of n-3 PUFA with T2D risk were weaker among individuals with higher obesity GRS (P interaction = 0.040) and li...