Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials (TN03 MMTT-GST)
Number of Subjects in Study Archive: 148
Conditions: Diabetes Mellitus, Diabetes Mellitus, Type 1
Duration: 2004 – 2005
# Recruitment Centers: 18
Treatment: Diagnostic; Mixed Meal Tolerance Test (MMTT); Glucagon Stimulation Test (GST)
Available Genotype Data: No
Image Summary: No
Transplant Type: None
Does it have dialysis patients: No
Access to samples for Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials (TN03 MMTT-GST) is currently only available via collaboration. Please contact the parent study to ask about ancillary study opportunities.
Clinical Trials URL: http://www.clinicaltrials.gov/show/NCT00105352
Based on the understanding that Type 1 diabetes (T1D) results from an immune mediated loss of pancreatic beta cells, therapeutic trials and newer measures of beta cell function can be evaluated as endpoints for clinical trials. Direct assessment of residual beta cell function is an appropriate endpoint, as retention of beta cell function in patients with T1D is known to result in improved glycemic control and reduced hypoglycemia, retinopathy and nephropathy. Endogenous beta cell function or insulin secretion is best measured by determination of C-peptide (which is co-secreted with insulin in a 1:1 molar ratio). Intervention studies over the past few decades have usually used measurement of C-peptide. However, the relationship between these or other measures of beta cell function has not been well studied. The relative advantages of one measure over another in terms of variability, sensitivity and burden to the subject is unknown. In addition, the optimal conditions for the conduct of the test need to be determined.
This study was conducted by the Type 1 Diabetes TrialNet Study Group, funded by the National Institutes of Health, in collaboration with the European C-Peptide Group. The goal is to evaluate comparability and reproducibility of measures of beta cell function in type 1 diabetes comparing the mixed meal tolerance tests (MMTT) and glucagon stimulation test (GST). These two tests will be compared to assess the relationship between the MMTT and IV (intravenous) Glucagon stimulated C-peptide responses as measured by time to peak C-peptide and AUC (area under the curve) values. An important goal was to develop an international consensus about the conduct of metabolic tests in the context of large, multicenter trials involving type 1 diabetes by balancing the scientific data with the burden on the subject.
To compare the sensitivity, reproducibility and tolerability of MMTT and GST testing.
MMTT and GST results, adverse events and patient acceptability
Diabetes Mellitus Type 1 duration of 1 month to 3 years
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. The MMTT is preferred for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.