title: Long-Acting C-Peptide and Neuropathy in Type 1 Diabetes: A 12-Month Clinical Trial.
abstract: Lack of C-peptide in type 1 diabetes may be an important contributing factor in the development of microvascular complications. Replacement of native C-peptide has been shown to exert a beneficial influence on peripheral nerve function in type 1 diabetes. The aim of this study was to evaluate the efficacy and safety of a long-acting C-peptide in subjects with type 1 diabetes and mild to moderate peripheral neuropathy.
  
  
  
  A total of 250 patients with type 1 diabetes and peripheral neuropathy received long-acting (pegylated) C-peptide in weekly dosages of 0.8 mg (n = 71) or 2.4 mg (n = 73) or placebo (n = 106) for 52 weeks. Bilateral sural nerve conduction velocity (SNCV) and vibration perception threshold (VPT) on the great toe were measured on two occasions at baseline, at 26 weeks, and at 52 weeks. The modified Toronto Clinical Neuropathy Score (mTCNS) was used to grade the peripheral neuropathy.
  
  
  
  Plasma C-peptide rose during the study to 1.8-2.2 nmol/L (low dose) and to 5.6-6.8 nmol/L (high dose). After 52 weeks, SNCV had increased by 1.0 ± 0.24 m/s (P < 0.001 within group) in patients receiving C-peptide (combined groups), but the corresponding value for the placebo group was 1.2 ± 0.29 m/s. Compared with basal, VPT had improved by 25% after 52 weeks of C-peptide therapy (Δ for combined C-peptide groups: -4.5 ± 1.0 μm, placebo group: -0.1 ± 0.9 μm; P < 0.001). mTCNS was unchanged during the study.
  
  
  
  Once-weekly subcutaneous administration of long-acting C-peptide for 52 weeks did not improve SNCV, other electrophysiological variables, or mTCNS but resulted in marked improvement of VPT compared with placebo.
authors.affiliation: Cebix Inc., San Diego, CA Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden john.wahren@ki.se.
authors.forename: John
authors.initials: J
authors.lastname: Wahren
authors.affiliation: Cebix Inc., San Diego, CA.
authors.forename: Howard
authors.initials: H
authors.lastname: Foyt
authors.affiliation: Cebix Inc., San Diego, CA.
authors.forename: Mark
authors.initials: M
authors.lastname: Daniels
authors.affiliation: Albert Einstein College of Medicine, New York, NY.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Arezzo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002096:C-Peptide / Q000008:administration & dosage* / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010525:Peripheral Nerves / Q000378:metabolism; D012044:Regression Analysis; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide