Mixed-Meal Tolerance Test Versus Glucagon Stimulation Test for the Assessment of β-Cell Function in Therapeutic Trials in Type 1 Diabetes

Abstract

OBJECTIVE -␤-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 Cpeptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS -In randomized sequences, 148TrialNet 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, Ͼ85% 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 ϭ 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 ␤-cell function in therapeutic trials in type 1 diabetes.

Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients

“…A limitation of our study is that all relatives received prophylactic insulin injections after the initial clamp test, but this intervention did not affect clinical outcome [9] nor the ability of clamp variables to predict it. The hyperglycaemic clamp is more laborious to perform than acute stimulation tests that have been widely used in diabetes prediction and prevention studies [20,[24][25][26][27][28], but compliance of relatives or patients was high in our hands [3,8,9]. The glucagon injection is the most burdening part of the test and does not seem to provide much additional information: one may therefore consider omitting it.…”

Fasting and meal-stimulated residual beta cell function is positively associated with serum concentrations of proinflammatory cytokines and negatively associated with anti-inflammatory and regulatory cytokines in patients with longer term type 1 diabetes

“…Patients underwent a standardised MMT by drinking a high-protein liquid formula (Boost HP; Mead Johnson Nutrition, Evansville, IN, USA) [20]. At −5, 0, 30, 90 and 120 min, blood samples were drawn for metabolic and immunological analyses.…”

“…The measurements of blood glucose, C-peptide and HbA 1c were performed at the central laboratory of the Steno Diabetes Center, Copenhagen, Denmark using fluoroimmunometric assay (AutoDELFIA; Perkin Elmer Wallac) as described elsewhere [20]. The interassay CV was <6% [20].…”

Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial

“…We were concerned that excessive demands might cause patients to refuse to participate in the follow-up. We therefore decided to perform a mixed meal tolerance test (MMTT) in accordance with the European study on estimation of beta cell function [31] in only those 31 patients (21 in the GAD-alum group and 10 in the placebo-group) who at the 30 month follow-up had a maximal C-peptide response >0.20 nmol/l. This test includes ingestion of 6 ml Sustacal (Sustacal; Mead Johnson, Evansville, IN, USA)/kg of body weight, with a maximum of 360 ml, to be ingested within 5 min.…”