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 x 10(-3); SAT: P = 0.018; percent variation explained: similar to 1.00%). Increasing levels of circulating FFA were associated with decreasing S-I (P = 8.10 x 10(-11)). Increasing BMI, VAT, and SAT were also associated with decreasing S-I (BMI: P = 4.98 x 10(-71); VAT: P = 1.48 x 10(-64); SAT: P = 4.21 x 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 S-I, they do not appear to mediate the association between levels of adiposity and S-I in this large cohort of Hispanic-Americans. These results may indicate that FFA contribute to insulin resistance independent of adiposity. (J Clin Endocrinol Metab 97: 3285-3291, 2012)