Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus

Diabet Med. 2000 Mar;17(3):181-9. doi: 10.1046/j.1464-5491.2000.00274.x.


Aims: Recent studies have indicated that proinsulin C-peptide shows specific binding to cell membrane binding sites and may exert biological effects when administered to patients with Type 1 diabetes mellitus. This study was undertaken to determine if combined treatment with C-peptide and insulin might reduce the level of microalbuminuria in patients with Type 1 diabetes and incipient nephropathy.

Methods: Twenty-one normotensive patients with microalbuminuria were studied for 6 months in a double-blind, randomized, cross-over design. The patients received s.c. injections of either human C-peptide (600 nmol/24 h) or placebo plus their regular insulin regimen for 3 months.

Results: Glycaemic control improved slightly during the study and to a similar extent in both treatment groups. Blood pressure was unaltered throughout the study. During the C-peptide treatment period, urinary albumin excretion decreased progressively on average from 58 microg/min (basal) to 34 microg/min (3 months, P < 0.01) and it tended to increase, but not significantly so, during the placebo period. The difference between the two treatment periods was statistically significant (P < 0.01). In the 12 patients with signs of autonomic neuropathy prior to the study, respiratory heart rate variability increased by 21 +/- 9% (P < 0.05) during treatment with C-peptide but was unaltered during placebo. Thermal thresholds were significantly improved during C-peptide treatment in comparison to placebo (n = 6, P < 0.05).

Conclusion: These results indicate that combined treatment with C-peptide and insulin for 3 months may improve renal function by diminishing urinary albumin excretion and ameliorate autonomic and sensory nerve dysfunction in patients with Type 1 diabetes mellitus.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria
  • Autonomic Nervous System Diseases / drug therapy
  • Blood Glucose / metabolism
  • C-Peptide / therapeutic use*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Neuropathies / drug therapy*
  • Double-Blind Method
  • Heart Rate
  • Humans
  • Insulin / therapeutic use
  • Kidney / physiopathology
  • Placebos


  • Blood Glucose
  • C-Peptide
  • Insulin
  • Placebos