Amelioration of sensory nerve dysfunction by C-Peptide in patients with type 1 diabetes.
Studies have demonstrated that proinsulin C-peptide stimulates the activities of Na(+),K(+)-ATPase and endothelial nitric oxide synthase, both of which are enzyme systems of importance for nerve function and known to be deficient in type 1 diabetes. The aim of this randomized double-blind placebo-controlled study was to investigate whether C-peptide replacement improves nerve function in patients with type 1 diabetes. Forty-nine patients without symptoms of peripheral neuropathy were randomized to either 3 months of treatment with C-peptide (600 nmol/24 h, four doses s.c.) or placebo. Forty-six patients (15 women and 31 men, aged 29 years, diabetes duration 10 years, and HbA(1c) 7.0%) completed the study. Neurological and neurophysiological measurements were performed before and after 6 and 12 weeks of treatment. At baseline the patients showed reduced nerve conduction velocities in the sural nerve (sensory nerve conduction velocity [SCV]: 50.9 +/- 0.70 vs. 54.2 +/- 1.2 m/s, P < 0.05) and peroneal nerve (motor nerve conduction velocity: 45.7 +/- 0.55 vs. 53.5 +/- 1.1 m/s, P < 0.001) compared with age-, height-, and sex-matched control subjects. In the C-peptide treated group there was a significant improvement in SCV amounting to 2.7 +/- 0.85 m/s (P < 0.05 compared with placebo) after 3 months of treatment, representing 80% correction of the initial reduction in SCV. The change in SCV was accompanied by an improvement in vibration perception in the patients receiving C-peptide (P < 0.05 compared with placebo), whereas no significant change was detectable in cold or heat perception. In conclusion, C-peptide administered for 3 months as replacement therapy to patients with early signs of diabetic neuropathy ameliorates nerve dysfunction.
Ekberg
Karin
K
Department of Surgical Sciences, Section of Clinical Physiology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Brismar
Tom
T
Johansson
Bo-Lennart
BL
Jonsson
Björn
B
Lindström
Per
P
Wahren
John
J
D000328:Adult; D017668:Age of Onset; D001794:Blood Pressure; D001835:Body Weight; D002096:C-Peptide / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D009460:Neurologic Examination; D018579:Patient Selection; D010523:Peripheral Nervous System Diseases / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D010919:Placebos; D013997:Time Factors
D002096:C-Peptide; D006442:Glycated Hemoglobin; D007328:Insulin; D010919:Placebos