Association of Adipose Tissue Insulin Resistance with Risk of Diabetes Incidents in Middle-aged Japanese Workers according to BMI states: 17 years of Follow-up of Aichi Worker's Cohort study.

Abstract

BackgroundInsulin 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).MethodsA 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.ResultsDuring 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).ConclusionAdipo-IR was positively associated with T2DM risk in overweight/obese men and women.