C-Peptide Replacement Therapy and Sensory Nerve Function in Type 1 Diabetic Neuropathy

• Published in: Diabetes care Vol. 30; no. 1; pp. 71 - 76
• Main Authors: Ekberg, Karin, Brismar, Tom, Johansson, Bo-Lennart, Lindström, Per, Juntti-Berggren, Lisa, Norrby, Anders, Berne, Christian, Arnqvist, Hans J, Bolinder, Jan, Wahren, John
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 2007
• Subjects: Adult; Age of Onset; Apoptosis; Biological and medical sciences; C-Peptide - therapeutic use; Care and treatment; Clinical medicine; Compliance; Diabetes; Diabetes Mellitus, Type 1 - complications; Diabetes. Impaired glucose tolerance; Diabetic neuropathies; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - physiopathology; Diabetic neuropathy; Diagnosis; Double-Blind Method; Early intervention; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Health aspects; Humans; Hyperglycemia; Informed consent; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Middle Aged; Neural Conduction - physiology; Neurologic Examination; Nitric oxide; Patient outcomes; Patient Selection; Patients; Peptides; Physical examinations; Plasma; Proteins; Sural Nerve - physiopathology; Sweden; Velocity; Sweden; Endocrinopathy; Human; Immunopathology; Nervous system diseases; Replacement therapy; Type 1 diabetes; Peptide hormone; Autoimmune disease; Sensory nerve; Neuropathy; C-Peptide
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc06-1274

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.