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

Aims Recent studies have indicated that proinsulin C-peptide shows specific binding to cell membrane binding sites and may exert biological effects wh en administered to patients with Type 1 diabetes mellitus. This study was u ndertaken to determine if combined treatment with C-peptide and insulin mig ht reduce the level of microalbuminuria in patients with Type 1 diabetes an d incipient nephropathy. Methods Twenty-one normotensive patients with microalbuminuria were studied for 6 months in a double-blind, randomized, cross-over design. The patient s received s.c. injections of either human C-peptide (600 nmo1/24 h) or pla cebo plus their regular insulin regimen for 3 months. Results Glycaemic control improved slightly during the study and to a simil ar extent in both treatment groups. Blood pressure was unaltered throughout the study. During the C-peptide treatment period, urinary albumin excretio n decreased progressively on average from 58 mu g/min (basal) to 34 mu g/mi n (3 months, P < 0.01) and it tended to increase, but not significantly so, during the placebo period. The difference between the two treatment period s was statistically significant (P < 0.01). In the 12 patients with signs o f autonomic neuropathy prior to the study, respiratory heart rate variabili ty increased by 21 +/- 9% (P < 0.05) during treatment with C-peptide but wa s 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 an d insulin for 3 months may improve renal function by diminishing urinary al bumin excretion and ameliorate autonomic and sensory nerve dysfunction in p atients with Type 1 diabetes mellitus.