Association of adipose tissue insulin resistance and serum free fatty acid levels with the incidence of type 2 diabetes: a retrospective cohort study

Abstract Background Insulin resistance in adipose tissue attenuates the suppression of lipolysis, leading to increased free fatty acid (FFA) release. The excess FFA may be involved in the development of type 2 diabetes. Purpose In this study, we investigated the association of adipose tissue insulin resistance and serum free fatty acid levels with the incidence of type 2 diabetes. Methods This is an observational study involving 6800 participants (3451 women, mean age 69.2 years) without diabetes who underwent 75-g oral glucose tolerance test (OGTT) at baseline. The participants were divided into the obesity and nonobesity groups on the basis of body mass index of ≥25 and <25 kg/m2, respectively. Serum FFA levels were assessed before and 30, 60, and 120 min after glucose ingestion, and the total area under the FFA curve (AUCFFA) was calculated. Adipose tissue insulin resistance was assessed using adipose insulin resistance index (adipo-IR) calculated based on fasting FFA and insulin concentrations. The homeostasis model assessment of insulin resistance (HOMA-IR), and the Matsuda index were evaluated as measures of insulin resistance in the liver and whole-body, respectively. High adipo-IR, high fasting FFA, great AUCFFA high HOMA-IR, and low Matsuda index were determined based on the optimal cutoff values from ROC curve analysis. Results Over a mean 5.3-year follow-up period, 485 participants developed type 2 diabetes. Multivariate logistic regression analyses showed that high adipo-IR was a significant predicator for incident type 2 diabetes in the obesity group, but not in nonobesity group. AUCFFA, HOMA-IR, and Matsuda index were significantly associated with incident type 2 diabetes in both the two groups (Table). Conclusion Serum FFA levels after glucose loading predict the incidence of type 2 diabetes. Adipose tissue insulin resistance was associated with the risk of type 2 diabetes in individuals with obesity, but not in individuals without obesity. Funding Acknowledgement Type of funding sources: None.