Association of Baseline Characteristics With Insulin Sensitivity and β-Cell Function in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study Cohort

Objective: We investigated sex and racial differences in insulin sensitivity, β-cell function and HbA1c, and the associations with selected phenotypic characteristics. Research Design and Methods: This is a cross-sectional analysis of baseline data from 3,108 GRADE participants. All had type 2 diabetes diagnosed <10 years and were on metformin monotherapy. Insulin sensitivity and β-cell function were evaluated using the homeostasis model assessment of insulin sensitivity (HOMA2-S) and estimates from oral glucose tolerance tests including the Matsuda index, insulinogenic index (IGI), C-peptide index (CPI) and oral disposition index (DI). Results: The cohort was 56.6±10 years of age (mean±SD), 63.8% male, with BMI 34.2±6.7 kg/m2, HbA1c 7.5±0.5% and type 2 diabetes duration 4.0±2.8 years. Women had higher DI than men but similar insulin sensitivity. DI was the highest in Black/African Americans, followed by American Indians/Alaska Natives, Asians and Whites in descending order. Compared to white, American Indian/Alaska Native had significantly higher HbA1c but Black/African Americans and Asians had lower HbA1c. However, when adjusted for glucose levels, Black/African Americans had higher HbA1c than whites. Insulin sensitivity correlated inversely with BMI, waist to hip ratio, triglyceride to HDL cholesterol ratio (TG/HDL- C) and the presence of metabolic syndrome; whereas DI was associated directly with age and inversely with BMI, HbA1c and TG/HDL-C. Conclusion: In the GRADE cohort, β-cell function differed by sex and race and was associated with the concurrent level of HbA1c. HbA1c also differed among the races, but not sex. Age, BMI and TG/HDL-C were associated with multiple measures of β-cell function and insulin sensitivity.