Elevated free fatty acid level is associated with insulin-resistant state in nondiabetic Chinese people

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/m(2)) and nonobese subjects (BMI <24 kg/m(2)). Clinical and multiple glucolipid metabolism data were collected. The homeostasis model assessment for insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta) 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 [beta]=-0.9, P=0.0111, for the nonobese group; beta=0.2, P=0.5094, for the obese group) and then increased (beta=0.9, P=0.0069, for the nonobese group; beta=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.