C-Peptide Replacement Therapy and Sensory Nerve Function in Type 1 Diabetic Neuropathy
KARIN EKBERG, PHD
TOM BRISMAR, MD, PHD
BO-LENNART JOHANSSON, MD, PHD
PER LINDSTR ¨OM, MD, PHD
LISA JUNTTI-BERGGREN, MD, PHD
ANDERS NORRBY, MD
CHRISTIAN BERNE, MD, PHD
HANS J. ARNQVIST, MD, PHD
JAN BOLINDER, MD, PHD
JOHNWAHREN, MD, PHD
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.
RESEARCH DESIGN AND 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.
