Insulin Resistance Diagnosed by HOMA-IR may be Overestimated in Adults with Greater Fat-Free Mass: The ELSA-Brasil Study

Background Conflicting results have been reported on the association of fat-free mass (FFM) and insulin resistance (IR). The way of indexing FFM may be a bias. This study sought to test the association of FFM and IR after indexing FFM to avoid collinearity. Methods This cross-sectional study comprised 11,284 volunteers, ages 38-79 years. Body composition was assessed by multi-frequency bioelectrical impedance. FFM indexed to body surface area (FFMbsa) was calculated. Excess body fat was assigned to individuals with percent body fat ≥ 85th percentile for age and sex. Fasting insulin and glucose, and 2h glucose in the oral glucose tolerance test were obtained. Homeostasis model assessment-insulin resistance (HOMA-IR) > 3.0 was set as the cut-off for IR.Results Percent body fat decreased from the 1st to the 5th quintile of FFMbsa in both women (Eta 2 = 0.166) and men (Eta 2 = 0.133). In women, fasting insulin (Eta 2 = 0.002), glucose (Eta 2 = 0.006), and HOMA-IR (Eta 2 = 0.007) increased slightly, whereas 2h glucose did not change towards the highest quintile of FFMbsa. In men, fasting insulin and HOMA-IR were similar across the quintiles of FFMbsa, whereas fasting glucose increased slightly (Eta 2 = 0.002) and 2h glucose decreased (Eta 2 = 0.005) towards the highest quintile of FFMbsa. Greater FFMbsa explained 1.8% of the odds of IR among women and 0.9% among men.Conclusion The lack of association of FFM and 2h glucose contrasted with greater odds of IR (by HOMA-IR) associated with greater FFM. The association of greater FFM and IR may be overestimated when the diagnosis is provided by HOMA-IR.