C-Peptide Replacement Therapy and Sensory Nerve Function in Type 1 Diabetic Neuropathy
- Karin Ekberg, PHD1,
- Tom Brismar, MD, PHD2,
- Bo-Lennart Johansson, MD, PHD1,
- Per Lindström, MD, PHD3,
- Lisa Juntti-Berggren, MD, PHD1,
- Anders Norrby, MD4,
- Christian Berne, MD, PHD5,
- Hans J. Arnqvist, MD, PHD6,
- Jan Bolinder, MD, PHD7 and
- John Wahren, MD, PHD1
- 1Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- 2Clinical Neuroscience, Section of Clinical Neurophysiology, Karolinska Institutet, Stockholm, Sweden
- 3Section of Neurology, Karolinska Institutet, Stockholm, Sweden
- 4Medicine at Lundby Hospital, Gothenburg, Sweden
- 5Section of Medicine, Uppsala University Hospital, Uppsala, Sweden
- 6Section of Medicine, Linköping University Hospital, Linköping, Sweden
- 7Section of Medicine, Karolinska Institutet, Stockholm, Sweden
- Address correspondence and reprint requests to Karin Ekberg, PhD, Creative Peptides, Fogdevreten 2, SE-171 77 Stockholm, Sweden. E-mail: karin.ekberg{at}creativepeptides.se
Abstract
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.
- CMAP, compound muscle action potential amplitude
- MCV, motor nerve conduction velocity
- NIA, neuropathy impairment assessment
- QST, quantitative sensory testing
- SCV, sensory nerve conduction velocity
- SCVi, sensory nerve conduction velocity measured at initial potential deflection
- SCVp, sensory nerve conduction velocity measured at peak potential
- VPT, vibration perception threshold
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
DOI: 10.2337/dc06-1274. Clinical trial reg. no. NCT00278980, clinicaltrials.gov.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted August 30, 2006.
- Received June 20, 2006.
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