C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy.
OBJECTIVE
C-peptide replacement in animals results in amelioration of diabetes-induced functional and structural abnormalities in peripheral nerves. The present study was undertaken to examine whether C-peptide administration to patients with type 1 diabetes and peripheral neuropathy improves sensory nerve function.


METHODS
This was an exploratory, double-blinded, randomized, and placebo-controlled study with three study groups that was carried out at five centers in Sweden. C-peptide was given as a replacement dose (1.5 mg/day, divided into four subcutaneous doses) or a dose three times higher (4.5 mg/day) during 6 months. Neurological examination and neurophysiological measurements were performed before and after 6 months of treatment with C-peptide or placebo.


RESULTS
The age of the 139 patients who completed the protocol was 44.2 +/- 0.6 (mean +/- SE) years and their duration of diabetes was 30.6 +/- 0.8 years. Clinical neurological impairment (NIA) (score >7 points) of the lower extremities was present in 86% of the patients at baseline. Sensory nerve conduction velocity (SCV) was 2.6 +/- 0.08 SD below body height-corrected normal values at baseline and improved similarly within the two C-peptide groups (P < 0.007). The number of patients responding with a SCV peak potential improvement >1.0 m/s was greater in C-peptide-treated patients than in those receiving placebo (P < 0.03). In the least severely affected patients (SCV < 2.5 SD below normal at baseline, n = 70) SCV improved by 1.0 m/s (P < 0.014 vs. placebo). NIA score and vibration perception both improved within the C-peptide-treated groups (P < 0.011 and P < 0.002). A1C levels (7.6 +/- 0.1% at baseline) decreased slightly but similarly in C-peptide-and placebo-treated patients during the study.


CONCLUSIONS
C-peptide treatment for 6 months improves sensory nerve function in early-stage type 1 diabetic neuropathy.
Ekberg
Karin
K
Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. karin.ekberg@creativepeptides.se
Brismar
Tom
T
Johansson
Bo-Lennart
BL
Lindström
Per
P
Juntti-Berggren
Lisa
L
Norrby
Anders
A
Berne
Christian
C
Arnqvist
Hans J
HJ
Bolinder
Jan
J
Wahren
John
J
D000328:Adult; D017668:Age of Onset; D002096:C-Peptide / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D006801:Humans; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology*; D009460:Neurologic Examination; D018579:Patient Selection; D013497:Sural Nerve / Q000503:physiopathology; D013548:Sweden
D002096:C-Peptide