Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.
OBJECTIVE
Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures.


METHODS
In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs.


RESULTS
Among individuals with up to 4 years' duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R(2) = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group.


CONCLUSIONS
The MMTT is preferred for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.
Greenbaum
Carla J
CJ
TrialNet Publications, The Biostatistics Center, Rockville, Maryland, USA. cjgreen@benaroyaresearch.org
Mandrup-Poulsen
Thomas
T
McGee
Paula Friedenberg
PF
Battelino
Tadej
T
Haastert
Burkhard
B
Ludvigsson
Johnny
J
Pozzilli
Paolo
P
Lachin
John M
JM
Kolb
Hubert
H
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood; D002096:C-Peptide / Q000097:blood*; D002648:Child; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000178:diet therapy* / Q000503:physiopathology; D003927:Diet, Diabetic; D005215:Fasting; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D044469:Racial Groups; D011897:Random Allocation; D012680:Sensitivity and Specificity
D015415:Biomarkers; D002096:C-Peptide; D005934:Glucagon