Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.

Abstract

BACKGROUND:

Globally, 1 in 11 adults has diabetes mellitus, and most of these cases are type 2 diabetes (T2D). The risk of T2D is influenced by many factors, including diet. The synthesis of long-chain n-6 polyunsaturated fatty acids (LC n-6 PUFA) has been posited as a risk factor for T2D; however, its causal role is uncertain.

AIM:

To test the causal effect of LC n-6 PUFA synthesis on insulin resistance and transgenerational T2D risk in a large cohort of men and women.

METHODS:

Two-sample mendelian randomization (MR) was conducted to evaluate the effect of low or high levels of LC n-6 PUFA synthesis on glycemia and development of T2D in the UK Biobank (n = 463,010) and Meta-Analysis of Glucose- and Insulin-Related Traits Consortium (MAGIC; n = 5,130) cohorts. The increased likelihood of a predisposition to low or high LC n-6 PUFA synthesis and the risk of T2D was also investigated using the participants' siblings and parents. In MR-Base, 4 genetic variants associated with LC n-6 PUFA synthesis were found (p < 10-8). After pruning, 1 variant (rs174547) on the FADS1 gene was retained.

RESULTS:

Lower LC n-6 PUFA synthesis and abundance (per % unit decrease) are associated with small reductions in the insulin disposition index (-0.038 ± 0.012 mM-1; p = 0.002) within MAGIC. In the UK Biobank, we report negligible effects of low n-6 PUFA synthesis on the odds of T2D (OR <1%; p < 0.05). Additionally, reduced LC n-6 PUFA synthesis does not appear to be a contributor to familial T2D risk. No significant association was observed between LC n-6 PUFA synthesis and BMI.

CONCLUSION:

In a primarily white European population, LC n-6 PUFA synthesis is not a major contributor to T2D risk.

• Authors: Michael A Zulyniak, Harriett Fuller, Mark M Iles
• Journal: Lifestyle genomics (Lifestyle Genom) Vol. 13 Issue 5 Pg. 146-153 ( 2020) ISSN: 2504-3188 [Electronic] Switzerland
• PMID: 32791511 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s) Published by S. Karger AG, Basel.

Chemical References

• Blood Glucose
• Delta-5 Fatty Acid Desaturase
• Fatty Acids, Omega-3
• Fatty Acids, Unsaturated
• Insulin
• Fatty Acid Desaturases
• FADS1 protein, human

Topics

• Blood Glucose (metabolism)
• Body Mass Index
• Cohort Studies
• Delta-5 Fatty Acid Desaturase
• Diabetes Mellitus, Type 2 (blood, genetics, therapy)
• Diet
• Fatty Acid Desaturases (genetics)
• Fatty Acids, Omega-3
• Fatty Acids, Unsaturated (metabolism)
• Female
• Genetic Variation
• Genotype
• Humans
• Insulin (metabolism)
• Male
• Mendelian Randomization Analysis
• Meta-Analysis as Topic
• Phenotype
• Polymorphism, Single Nucleotide
• Risk
• United Kingdom