Impact of C-peptide preservation on metabolic and clinical outcomes in the Diabetes Control and Complications Trial

Diabetes. 2014 Feb;63(2):739-48. doi: 10.2337/db13-0881. Epub 2013 Oct 2.


The Diabetes Control and Complications Trial established that a stimulated C-peptide concentration ≥0.2 nmol/L at study entry among subjects with up to a 5-year diabetes duration is associated with favorable metabolic and clinical outcomes over the subsequent 7 years of follow-up. Herein we further examine the association of both fasting and stimulated C-peptide numerical values with outcomes. In the intensive treatment group, for a 50% higher stimulated C-peptide on entry, such as from 0.10 to 0.15 nmol/L, HbA1c decreased by 0.07% (0.8 mmol/mol; P = 0.0003), insulin dose decreased by 0.0276 units/kg/day (P < 0.0001), hypoglycemia risk decreased by 8.2% (P < 0.0001), and the risk of sustained retinopathy was reduced by 25% (P = 0.0010), all in unadjusted analyses. Other than HbA1c, these effects remained significant after adjusting for the HbA1c on entry. While C-peptide was not significantly associated with the incidence of nephropathy, it was strongly associated with the albumin excretion rate. The fasting C-peptide had weaker associations with outcomes. As C-peptide decreased to nonmeasurable concentrations, the outcomes changed in a nearly linear manner, with no threshold or breakpoint. While preservation of stimulated C-peptide at ≥0.2 nmol/L has clinically beneficial outcomes, so also does an increase in the concentration of C-peptide across the range of values.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • C-Peptide
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / pathology
  • Diabetic Retinopathy / metabolism
  • Female
  • Glycated Hemoglobin
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Male
  • Time Factors
  • Young Adult


  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin