Omega-6 Eicosadienoic Acid Is Associated with Lower HOMA-IR and Incident T2D in Participants from the MESA Cohort

Abstract

Linoleic acid (LA) and related omega-6 fatty acids have been implicated in contributing to metabolic dysfunction. However, there is some evidence to support that certain omega-6 fatty acids, such as eicosadienoic acid (EDA), may play a beneficial role in inflammation. Although, studies have inconsistently shown EDA to be inversely associated with insulin resistance and type 2 diabetes (T2D). The present study evaluated associations of EDA with log HOMA-IR and risk of incident T2D in 5,889 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Phospholipid fatty acid profiles were determined by GC-FID. A multivariable linear regression model adjusted for age, sex, BMI, education status, smoking status, ever used alcohol, and race/ethnicity was used to determine associations between baseline EDA levels (quartiles) and log HOMA-IR; a Cox proportional hazards model estimated risk of incident T2D over a median 12 year follow-up. Individuals in the three upper quartiles of EDA had a significantly lower log HOMA-IR compared to those in the reference quartile (Q1) (coefficient, [p-value]): Q2: -0.[p<0.01]; Q3: -0.[p<0.01]; Q4: -0.10 [p<0.001]. Race-stratified analyses showed similar results across all races. Risk of incident T2D was significantly lower across successive quartiles of EDA (Hazard Ratio, [p-value]): Q1: referent; Q2: 0.76 [p<0.01]; Q3: 0.62 [p<0.001]; Q4: 0.58 [p<0.001]. After race stratification, all four races showed lower risk of incident T2D but the association was only significant in Blacks; however, the interaction test for race was not significant. We hypothesize that upregulation of EDA synthesis through preferential elongation of linoleic acid may be associated with increased insulin sensitivity leading to lowered risk for T2D. Further in vitro and in vivo studies are required to elucidate the role of EDA in mitigating insulin resistance and lowered risk of diabetes and the associated states of inflammation. Disclosure N.L. Weir: None. W. Guan: None. B. Steffen: None. L.M. Steffen: None. A.B. Karger: Research Support; Self; Siemens. M.Y. Tsai: None.