title: Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgical Sciences, Karolinska Hospital, Stockholm, Sweden.
authors.forename: B L
authors.initials: BL
authors.lastname: Johansson
authors.forename: K
authors.initials: K
authors.lastname: Borg
authors.forename: E
authors.initials: E
authors.lastname: Fernqvist-Forbes
authors.forename: A
authors.initials: A
authors.lastname: Kernell
authors.forename: T
authors.initials: T
authors.lastname: Odergren
authors.forename: J
authors.initials: J
authors.lastname: Wahren
mesh_terms: D000328:Adult; D000419:Albuminuria; D001342:Autonomic Nervous System Diseases / Q000188:drug therapy; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004311:Double-Blind Method; D006339:Heart Rate; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D007668:Kidney / Q000503:physiopathology; D010919:Placebos
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D010919:Placebos