title: Evaluation of long-term treatment effect in a type 1 diabetes intervention trial: differences after stimulation with glucagon or a mixed meal.
abstract: OBJECTIVE
  Endogenous insulin secretion, measured by C-peptide area under the curve (AUC), can be tested using both the glucagon stimulation test (GST) and the mixed-meal tolerance test (MMTT). This study compares these two stimulation methods using long-term data from patients newly diagnosed with type 1 diabetes or with latent autoimmune diabetes.
  
  
  METHODS
  A recently completed phase 3 intervention study with DiaPep277 demonstrated improved glycemic control and a significant treatment effect of glucagon-stimulated C-peptide secretion. Unexpectedly, MMTT failed to detect differences between the treated and control groups. Data from 343 patients in two balanced-randomized, double-blind, placebo-controlled, parallel-group trials of DiaPep277 were used to compare and correlate between GST- and MMTT-derived C-peptide AUC. Pearson's correlations were calculated for absolute C-peptide AUC at baseline and 12 and 24 months and for long-term changes in AUC (AUC).
  
  
  RESULTS
  The absolute AUC values obtained at any single time point by the two tests were well correlated in both data sets (r = 0.74-0.9). However, the correlations between the AUC were much weaker (r = 0.39-0.58). GST-stimulated C-peptide secretion was stable over the fasting glucose range permitted for the test (4-11.1 mmol/L), but MMTT-stimulated C-peptide secretion decreased over the same range, implying differences in sensitivity to glucose.
  
  
  CONCLUSIONS
  Measurement of long-term changes in stimulated C-peptide, reflecting endogenous insulin secretion, during the course of intervention trials may be affected by the method of stimulation, possibly reflecting different sensitivities to the physiological status of the tested subject.
authors.affiliation: Corresponding author: Itamar Raz, ntv502@netvision.net.il.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.forename: Dana
authors.initials: D
authors.lastname: Peled
authors.forename: Dana
authors.initials: D
authors.lastname: Elias
authors.forename: Ann
authors.initials: A
authors.lastname: Avron
authors.forename: Merana
authors.initials: M
authors.lastname: Tamir
authors.forename: Rachel
authors.initials: R
authors.lastname: Eren
authors.forename: Shlomo
authors.initials: S
authors.lastname: Dagan
authors.forename: Irun R
authors.initials: IR
authors.lastname: Cohen
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D018834:Chaperonin 60 / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005260:Female; D005502:Food; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects; D008297:Male; D062407:Meals; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D018834:Chaperonin 60; C447781:DiaPep 277; D005765:Gastrointestinal Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D005934:Glucagon; D005947:Glucose