Impact of C-Peptide Preservation on Metabolic and Clinical Outcomes in the Diabetes Control and Complications Trial

  1. for the DCCT/EDIC Research Group*
  1. 1The Biostatistics Center, The George Washington University, Rockville Maryland
  2. 2Department of Medicine, University of Washington, Seattle, Washington; and the Department of Medicine, DVA Puget Sound Health Care System, Seattle, Washington

Abstract

The DCCT established that a stimulated C-peptide concentration ≥0.2 nmol/L at study entry among subjects with up to 5 years 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 HbA1c% (0.8 mmol/mol, p=0.0003); insulin dose decreased by 0.0276 U/kg/d (p<0.0001); hypoglycemia risk was 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 non-measureable 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.

Footnotes

  • * A complete list of the members of the DCCT/EDIC Research Group is provided in the supplementary appendix published in New England Journal of Medicine, 2011; 365:2366-76.

  • Received June 5, 2013.
  • Accepted September 19, 2013.

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