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

Diabetes Care. 2021 Feb;44(2):340-349. doi: 10.2337/dc20-1787. Epub 2020 Dec 17.


Objective: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (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 (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, 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 with Whites, American Indians/Alaska Natives 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.

Conclusions: 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 by sex. Age, BMI, and TG/HDL-C were associated with multiple measures of β-cell function and insulin sensitivity.

Trial registration: NCT01794143.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blood Glucose
  • C-Peptide
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2*
  • Female
  • Humans
  • Infant
  • Insulin
  • Insulin Resistance*
  • Male


  • Blood Glucose
  • C-Peptide
  • Insulin

Associated data

  • figshare/10.2337/figshare.13247033