Association of Adipose Tissue Insulin Resistance With Risk of Diabetes Incidence in Middle-aged Japanese Workers According to BMI States: 17 Years of Follow-up of the Aichi Worker’s Cohort Study

Background: Insulin resistance in adipocytes, manifested as high basal circulating free fatty acid (FFA) is thought to contribute to the development of type 2 diabetes mellitus (T2DM). However, the association between adipocyte insulin resistance (Adipo-IR) index and T2DM has rarely been explored in prospective studies. We examined this association in a middle-aged Japanese workers’ cohort. Since the association may differ according to the degree of overall adiposity, the analysis was stratified by the presence of overweight/obesity defined with body mass index (BMI). Methods: A total of 3,257 subjects (men 2501, women 756) aged 35–66 years were followed-up for up to 17 years. T2DM incidence was defined as fasting blood glucose level ≥126 mg/dL, glycated hemoglobin level ≥6.5%, or self-reported initiation of glucose-lowering medications. Adipo-IR was calculated as the product of FFA (mmol/L) and insulin (pmol/L) obtained from baseline fasting blood samples and divided into sex- and BMI category (<25 or ≥25 kg/m²)-specific tertiles. Cox-proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, BMI, smoking status, physical activity, drinking habit, and family history of diabetes. Results: During a median of 14.6 years of follow-up, 365 developed T2DM. Compared with the lowest tertile, T2DM risk was significantly increased among the highest tertile category in overweight/obese men (HR 2.94; 95% CI, 1.76–4.90) and women (HR 4.24; 95% CI, 1.08–16.61). Conclusion: Adipo-IR was positively associated with T2DM risk in overweight/obese men and women.