Abstract

Changes in desaturase activity are associated with insulin sensitivity and may be associated with type 2 diabetes mellitus (T2DM). Polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster have been associated with the homeostasis model assessment of insulin sensitivity (HOMA-IS) and serum fatty acid composition. Objective: To investigate whether common genetic variations in the FADS gene cluster influence fasting glucose (FG) and fasting insulin (FI) responses following a 6-week n-3 polyunsaturated fatty acids (PUFA) supplementation. Methods: 210 subjects completed a 2-week run-in period followed by a 6-week supplementation with 5 g/d of fish oil (providing 1.9 g–2.2 g of EPA + 1.1 g of DHA). Genotyping of 18 SNPs of the FADS gene cluster covering 90% of all common genetic variations (minor allele frequency ≥ 0.03) was performed. Results: Carriers of the minor allele for rs482548 (FADS2) had increased plasma FG levels after the n-3 PUFA supplementation in a model adjusted for FG levels at baseline, age, sex, and BMI. A significant genotype*supplementation interaction effect on FG levels was observed for rs482548 (p = 0.008). For FI levels, a genotype effect was observed with one SNP (rs174456). For HOMA-IS, several genotype*supplementation interaction effects were observed for rs7394871, rs174602, rs174570, rs7482316 and rs482548 (p = 0.03, p = 0.01, p = 0.03, p = 0.05 and p = 0.07; respectively). Conclusion: Results suggest that SNPs in the FADS gene cluster may modulate plasma FG, FI and HOMA-IS levels in response to n-3 PUFA supplementation.

Highlights

  • Type 2 diabetes mellitus (T2DM) and cardiovascular diseases are major public health concerns worldwide and especially in North America where 40 millions people are going to be affected by2030 [1]

  • The objective of the present study was to investigate whether the fasting plasma glucose (FG), the fasting insulin (FI), and the homeostasis model assessment of insulin sensitivity (HOMA-IS) responses to a 6-week n-3 polyunsaturated fatty acids (PUFA) supplementation were influenced by common genetic variations in the fatty acid desaturase (FADS) gene cluster

  • Gender differences are evident with respect to weight, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, HDL-C, TG and C-reactive protein (CRP) levels

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Summary

Introduction

Type 2 diabetes mellitus (T2DM) and cardiovascular diseases are major public health concerns worldwide and especially in North America where 40 millions people are going to be affected by2030 [1]. The degree of obesity, the presence of the metabolic syndrome, family history of diabetes, impaired glucose tolerance, a low physical activity level, high blood levels of triglycerides (TG), high-density lipoprotein cholesterol (HDL-c) levels under 0.91 mmol/L as well as certain ethnic groups are well-known T2DM risk factors [2]. Fish oil and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are of particular interest because of their roles in improving the plasma lipid profile, especially by reducing plasma TG [3]. A review of 18 trials with 823 subjects on the effects of fish oil supplementation on plasma lipid levels and glycemic controls showed that the pooled weight mean difference for FG was an increase of 0.26 mmol/L after an n-3 PUFA supplementation with doses ranging from 3 to 18 g/d of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [6]

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