PMID- 24408401
OWN - NLM
STAT- MEDLINE
DCOM- 20150818
LR  - 20220318
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Linking)
VI  - 37
IP  - 5
DP  - 2014
TI  - Evaluation of long-term treatment effect in a type 1 diabetes intervention trial: 
      differences after stimulation with glucagon or a mixed meal.
PG  - 1384-91
LID - 10.2337/dc13-1392 [doi]
AB  - 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. RESEARCH DESIGN AND 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.
FAU - Pozzilli, Paolo
AU  - Pozzilli P
AD  - Corresponding author: Itamar Raz, ntv502@netvision.net.il.
FAU - Raz, Itamar
AU  - Raz I
FAU - Peled, Dana
AU  - Peled D
FAU - Elias, Dana
AU  - Elias D
FAU - Avron, Ann
AU  - Avron A
FAU - Tamir, Merana
AU  - Tamir M
FAU - Eren, Rachel
AU  - Eren R
FAU - Dagan, Shlomo
AU  - Dagan S
FAU - Cohen, Irun R
AU  - Cohen IR
LA  - eng
SI  - ClinicalTrials.gov/NCT00058981
SI  - ClinicalTrials.gov/NCT00615264
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Retracted Publication
DEP - 20140109
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Blood Glucose)
RN  - 0 (C-Peptide)
RN  - 0 (Chaperonin 60)
RN  - 0 (DiaPep 277)
RN  - 0 (Gastrointestinal Agents)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Peptide Fragments)
RN  - 9007-92-5 (Glucagon)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
CIN - Diabetes Care. 2014;37(5):1173-5. PMID: 24757221
RIN - Diabetes Care. 2015 Jan;38(1):179. PMID: 25538318
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Blood Glucose/analysis/metabolism
MH  - C-Peptide/metabolism
MH  - Chaperonin 60/*therapeutic use
MH  - Diabetes Mellitus, Type 1/*drug therapy
MH  - Double-Blind Method
MH  - Fasting/blood
MH  - Female
MH  - *Food
MH  - Gastrointestinal Agents/*pharmacology
MH  - Glucagon/*pharmacology
MH  - Glucose/pharmacology
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Insulin/metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/drug effects
MH  - Male
MH  - Meals
MH  - Middle Aged
MH  - Peptide Fragments/*therapeutic use
MH  - Young Adult
EDAT- 2014/01/11 06:00
MHDA- 2015/08/19 06:00
CRDT- 2014/01/11 06:00
PHST- 2014/01/11 06:00 [entrez]
PHST- 2014/01/11 06:00 [pubmed]
PHST- 2015/08/19 06:00 [medline]
AID - dc13-1392 [pii]
AID - 10.2337/dc13-1392 [doi]
PST - ppublish
SO  - Diabetes Care. 2014;37(5):1384-91. doi: 10.2337/dc13-1392. Epub 2014 Jan 9.