Levels of Free Fatty Acids (FFA) are associated with insulin resistance but do not explain the relationship between adiposity and insulin resistance in hispanic americans: The IRAS family study

Context and Objective: We investigated whether free fatty acids (FFA) mediate the association between adiposity and insulin resistance in the Hispanic-American families of the Insulin Resistance Atherosclerosis Family Study. Design: In 815 Hispanic individuals in the Insulin Resistance Atherosclerosis Family Study, we tested for association between the following: 1) levels of adiposity [body mass index (BMI), visceral and sc adipose tissue area (VAT and SAT)] and circulating levels of FFA; 2) levels of circulating FFA and insulin sensitivity (S_I); and 3) levels of adiposity and S _I, additionally testing to see whether levels of FFA mediated or modified the relationship between adiposity and S_I. Results: After adjusting for age, sex, clinic site, and admixture, increasing levels of BMI, VAT, and SAT were weakly associated with increasing levels of circulating FFA (BMI: P = 0.024; VAT: P =2.33 × 10^-3; SAT: P = 0.018; percent variation explained: ∼1.00%). Increasing levels of circulating FFA were associated with decreasing S_I (P = 8.10 × 10^-11). Increasing BMI, VAT, and SAT were also associated with decreasing S_I (BMI: P = 4.98 × 10^-71; VAT: P = 1.48 × 10^-64; SAT: P = 4.21 × 10^-62), but this relationship was not significantly mediated by FFA. VAT, but not BMI or SAT, interacts with levels of FFA to influence S_I (P = 0.021). Conclusions: Although levels of circulating FFA are associated both with increasing adiposity and decreasing SI, they do not appear to mediate the association between levels of adiposity and SI in this large cohort of Hispanic-Americans. These results may indicate that FFA contribute to insulin resistance independent of adiposity.