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

Abstract

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 FA (SFA), monounsaturated FA (MUFA), and polyunsaturated FA (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% CIs) 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 liver/lipid GRS (P interaction = 0.012). Additionally, increased plasma n-3 PUFA concentration was associated with more reductions in T2D risk among participants carrying more docosapentaenoic acid-associated alleles (P interaction = 0.007). CONCLUSIONS Plasma concentrations of SFA and MUFA were associated with a higher T2D risk, whereas plasma PUFA and n-6 and n-3 PUFA were related to a lower risk. Circulating MUFA and n-3 PUFA had significant interactions with genetic predisposition to T2D and FA-associated variants.

Association of birth weight with type 2 diabetes mellitus and the mediating role of fatty acids traits: a two-step mendelian randomization study

“…Our study indicated a negative correlation between PUFA/SFA and PUFA/MUFA ratios with T2DM. A study exploring complete data on plasma fatty acids from 95,854 participants in the UK Biobank between 2006 and 2010 revealed a positive association of SFA (OR: 1.03) and MUFA (OR: 1.03) with T2DM, while PUFA (OR: 0.62) showed a negative association with T2DM [ 44 ]. Substituting dietary SFA with PUFA improved insulin sensitivity within just 5 weeks, thereby decreasing the risk of developing T2DM [ 45 ].…”

Monounsaturated and polyunsaturated fatty acids concerning prediabetes and type 2 diabetes mellitus risk among participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to March 2020

“…A prospective study of 11 offspring of obese and T2DM patients indicated that weight maintenance with a MUFA-rich diet improved homeostasis model assessment of insulin resistance and fasting pro-insulin levels in insulin-resistant subjects (28). Zhuang et al also conducted a follow-up study and found that plasma concentrations of MUFA were positively associated with T2DM risk (29). Notably, studies of MUFA and diabetes risk are limited and controversial.…”

Omega-3 polyunsaturated fatty acid biomarkers and risk of type 2 diabetes, cardiovascular disease, cancer, and mortality

“…Mean age of participants in the individual studies ranged from 41.1 to 80.5 years. For the measurements of omega-3 PUFA levels, 51 studies used GC analytic approach [16e18,32,34e41,43e54,57e59,61e64,66e70,73e79,81, 83,85,87e90,92], 13 used GLC [31,33,43,55,56,65,71,72,80,82,84,86,91], one in nuclear magnetic resonance-based profiling [42], and one used GCetandem mass spectrometry [60]. Fig.…”