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

Abstract

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 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.

Fig. 1.

Predicted S_I, accounting for the interaction between levels of FFA and VAT. The model is adjusted for age, gender, clinic, admixture, VAT, FFA, and the interaction between VAT and FFA. Individuals were assigned into one of four categories based on their FFA and VAT levels: low FFA, low VAT (FFA ≤ 742 μmol and VAT ≤ 94.08 cm²); low FFA, high VAT (FFA ≤ 742 μmol and VAT > 94.08 cm²); high FFA, low VAT (FFA > 742 μmol and VAT ≤ 94.08 cm²); and high FFA, high VAT (FFA > 742 μmol and VAT > 94.08 cm²). Values displayed are the mean predicted S_I for each group. Error bars represent the sd.