Association of glycemia with insulin sensitivity and β-cell function in adults with early type 2 diabetes on metformin alone

J Diabetes Complications. 2021 May;35(5):107912. doi: 10.1016/j.jdiacomp.2021.107912. Epub 2021 Mar 17.


Aims: Evaluate the relationship between measures of glycemia with β-cell function and insulin sensitivity in adults with early type 2 diabetes mellitus (T2DM).

Methods: This cross-sectional analysis evaluated baseline data from 3108 adults with T2DM <10 years treated with metformin alone enrolled in the Glycemia Reduction Approaches in Diabetes. A Comparative Effectiveness (GRADE) Study. Insulin and C-peptide responses and insulin sensitivity were calculated from 2-h oral glucose tolerance tests. Regression models evaluated the relationships between glycemic measures (HbA1c, fasting and 2-h glucose), measures of β-cell function and insulin sensitivity.

Results: Insulin and C-peptide responses were inversely associated with insulin sensitivity. Glycemic measures were inversely associated with insulin and C-peptide responses adjusted for insulin sensitivity. HbA1c demonstrated modest associations with β-cell function (range: r - 0.22 to -0.35). Fasting and 2-h glucose were associated with early insulin and C-peptide responses (range: r - 0.37 to -0.40) as well as late insulin and total insulin and C-peptide responses (range: r - 0.50 to -0.60).

Conclusion: Glycemia is strongly associated with β-cell dysfunction in adults with early T2DM treated with metformin alone. Efforts to improve glycemia should focus on interventions aimed at improving β-cell function. This Trial is registered in as NCT01794143.

Keywords: Beta-cell function; Glucose tolerance; Glycemic control; Insulin sensitivity; Type 2 diabetes.

Publication types

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

MeSH terms

  • Blood Glucose*
  • C-Peptide
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glycated Hemoglobin
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Insulin Resistance*
  • Insulin-Secreting Cells / physiology*
  • Metformin* / therapeutic use
  • Randomized Controlled Trials as Topic


  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Metformin

Associated data