Background: Free fatty acids (FFAs) are associated with insulin secretion and insulin resistance. However, the associations among FFAs, obesity, and progression from a normal to a prediabetic state are unclear.
Methods: Nondiabetic subjects (5,952) were divided in two groups according to their body mass index (BMI): obese subjects (BMI ≥24 kg/m²) and nonobese subjects (BMI <24 kg/m²). Clinical and multiple glucolipid metabolism data were collected. The homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β) was used. HbA1c level between 5.7% and 6.4% was considered prediabetic. Nonparametric tests, one-way ANOVA, and linear correlation analysis were performed. R and SPSS 23.0 software programs were used to analyze the results.
Results: A U-shaped relationship between FFAs and HOMA-IR was observed. After adjusting for potential confounders, the turning points of FFA levels in the curves were 0.54 mmol/L in the nonobese group and 0.61 mmol/L in the obese group. HOMA-IR levels decreased with increasing FFA concentrations before the turning points (regression coefficient [β]= – 0.9, P =0.0111, for the nonobese group; β=0.2, P =0.5094, for the obese group) and then increased (β=0.9, P =0.0069, for the nonobese group; β=1.5, P =0.0263 for the obese group) after the points. Additionally, our study also identified that FFAs were associated with the prediabetes status in obese individuals.
Conclusion: FFA levels were associated with insulin resistance in nondiabetic subjects, and HOMA-IR in nonobese individuals was more sensitive to FFA changes. Monitoring and controlling plasma FFA levels in obese subjects is significant in decreasing insulin resistance and preventing diabetes.
Keywords: FFA, insulin resistance, T2DM, obesity, HOMA-IR