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

Abstract

Objective: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA_1c) and the associations with selected phenotypic characteristics.

Research design and methods: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosed <10 years earlier and were on metformin monotherapy. Insulin sensitivity and β-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, 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, HbA_1c 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 with Whites, American Indians/Alaska Natives had significantly higher HbA_1c, but Black/African Americans and Asians had lower HbA_1c. However, when adjusted for glucose levels, Black/African Americans had higher HbA_1c 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, HbA_1c, and TG/HDL-C.

Conclusions: In the GRADE cohort, β-cell function differed by sex and race and was associated with the concurrent level of HbA_1c. HbA_1c also differed among the races, but not by sex. Age, BMI, and TG/HDL-C were associated with multiple measures of β-cell function and insulin sensitivity.

Trial registration: ClinicalTrials.gov NCT01794143.

Figure 1

A: Distributions of insulin sensitivity, insulin and C-peptide responses, insulin clearance, and HbA_1c for men and women. The box plots are adjusted for age, race, and diabetes duration. The P values are for comparisons between men and women adjusted for covariates including age, race, and diabetes duration. B: Distributions of insulin sensitivity, insulin and C-peptide responses, insulin clearance, and HbA_1c by race for American Indian (AI), Asian (As), Black/African American (AA), and White (W). The box plots are adjusted for age, sex, and diabetes duration. The P values are for comparisons among different races adjusted for covariates including age, sex, and diabetes duration.

Figure 2

Partial Spearman correlations (Corr) of measures of insulin sensitivity and insulin/C-peptide response with participant characteristics. Correlations are adjusted for age, sex, race, and diabetes duration (excluding the variable being correlated with insulin response or sensitivity). Insulin and C-peptide responses (IGI, C-peptide index, late insulin response, and insulin clearance) are also adjusted for HOMA2-S. The gray band marks correlations that are smaller than ±0.1, and the dotted line marks the correlation of 0. Partial correlations are shown as a black dot if they are nominally significant at the 0.05 level and at least 0.1 in absolute value and as a white dot otherwise. There were no meaningful correlations with diuretics, β-blockers, calcium channel blockers, statins, or fibrates.