Obesity and insulin resistance are both closely associated with type 2 diabetes mellitus (T2DM). It is, however, not clear whether the role of obesity in the development of T2DM is dependent on insulin resistance. This study aims to assess the hypothesis that insulin-sensitive adiposity is associated with a relatively lower risk of T2DM than insulin-resistant adiposity, and the adiposity-T2DM association is modified by insulin resistance in middle-aged black and white adults. The longitudinal study cohort consisted of 1588 middle-aged normoglycemic black and white adults aged 18-44 years at baseline who were followed for 16 years on average. Overweight/obesity at baseline was defined as BMI ≥25, and insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA). The prevalence of incident pre-diabetes and T2DM was compared between the insulin-sensitive and insulin-resistant adiposity groups. The prevalence of both incident pre-diabetes and T2DM was higher in the insulin-resistant adiposity than in the insulin-sensitive adiposity group (11.5 vs. 7.5 %, p = 0.023 for pre-diabetes; 16.7 vs. 2.7 %, p < 0.001 for T2DM). In multivariable logistic analyses, adjusted for baseline age, race, sex, follow-up years, and smoking, baseline insulin-resistant obesity was associated with incident pre-diabetes (odds ratio, OR = 2.07, p = 0.046) and T2DM (OR = 8.19, p < 0.001). ORs did not differ between blacks and whites. The ORs for the association of BMI with pre-diabetes and T2DM significantly increased across increasing quartiles of baseline HOMA (p for trend = 0.032 for pre-diabetes and <0.001 for T2DM). Slopes of increasing follow-up glucose with baseline BMI, measured as regression coefficients (β), were significantly greater in insulin-resistant than in insulin-sensitive individuals (β = 0.86 vs. 0.38, p = 0.009 for difference in slopes). These findings suggest that insulin resistance amplifies the obesity-diabetes association and underscore the importance of preventing both adiposity and insulin resistance in young adults.
Keywords: Insulin resistance; Longitudinal cohort; Obesity; Type 2 diabetes.