Metabolic tests to determine risk for type 1 diabetes in clinical trials

Evaluate the reproducibility and relationship of various metabolic tests conducted as part of the Diabetes Prevention Trial-type 1 diabetes.

Coefficients of variation, intraclass correlation coefficients, and Pearson correlations between the same metabolic tests performed at different times as well as the different tests were determined.

Fasting samples on the same day had a coefficient of variation of < 10 for C-peptide, 11 for insulin, and 2 for glucose. Testing on separate days approximately doubled the variance. Stimulated insulin values had less variance than fasting values and there was only a moderate correlation between fasting and stimulated values on each test. While highly correlated, C-peptide values from mixed meal tolerance tests are significantly lower than that obtained during oral glucose tolerance tests (OGTTs). Neither peak nor area under the curve C-peptide on the oral glucose tolerance test was different between those with abnormal and normal glucose tolerance. Those with abnormal as compared with normal glucose tolerance had lower 30-min C-peptide and a longer time to peak C-peptide.

A large, multi-centre trial, with tests performed over a decade-long period, can provide robust data. C-peptide data from oral glucose tolerance tests and mixed meal tolerance tests differ; therefore, the same stimulation test should be used to evaluate changes in beta cell function over time. Worsening glucose tolerance is associated with lower C-peptide at 30 min and a delay in peak secretion on the oral glucose tolerance test. This Diabetes Prevention Trial-type 1 diabetes data can be used in planning parameters for future studies, including evaluation of new algorithms to determine risk of disease.