Cis-Vaccenic Acid Is Associated with Lower HOMA-IR and Incident T2D in Participants from the MESA Cohort

The de novo lipogenesis pathway may play a key role in metabolic regulation. The omega-7 monounsaturated fatty acid cis-vaccenic acid (VA) is an endogenous downstream product of this pathway, and in vitro studies have suggested that it may downregulate gluconeogenesis and liver fat accumulation. However, it has been inconsistently shown to be associated with lower risk of type 2 diabetes (T2D). Previous studies have been in primarily homogeneous cohorts with few studies examining its effects on insulin resistance. Therefore, we aimed to evaluate if VA is associated with HOMA-IR and risk of incident T2D in 5,889 participants of the Multi-Ethnic Study of Atherosclerosis (MESA).

Phosphoplipid fatty acid profiles were determined by GC-FID. A multivariable linear regression model adjusted for age, sex, BMI, education status, smoking, ever used alcohol, and race/ethnicity was used to determine associations between baseline VA levels (quartiles) and HOMA-IR; a Cox proportional hazards model estimated risk of incident T2D over a median 12 year follow-up (n cases=663).

Individuals in the three upper quartiles of VA had a significantly lower log HOMA-IR compared to those in the reference quartile (Q1) (coefficient, [p-value]): Q2: -0.13 [p<0.001]; Q3: -0.22 [p<0.001]; Q4: -0.32 [p<0.001]. Race stratified analysis showed similar results for all four races. Risk of incident T2D significantly decreased with increasing levels of VA (Hazard Ratio, [p-value]): Q1: referent; Q2: 0.98 [p>0.05]; Q3: 0.72 [p<0.01]; Q4: 0.48 [p<0.001]. Race stratification showed similar results for Chinese, black, and hispanic but not white participants. Test for interaction shows the difference between Chinese and whites is statistically significant (p<0.001).

In a multi-racial cohort, VA demonstrated graded associations with lower insulin resistance and risk of diabetes. More studies are needed to elucidate the roles of VA and the de novo lipogenesis pathway in glycemic regulation.