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Updated: May 23, 2025

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
Published on: January 7, 2018
Effect of Oral Insulin on Early Combined Glucose and C-Peptide Endpoints in Individuals at High-Risk for Type 1
Taylor M Triolo1, Laura M Jacobsen2, David Cuthbertson3
1The Barbara Davis Center for Diabetes University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Abstract:
Background: The TrialNet Oral Insulin (OI) prevention trial showed no overall treatment effect, using the diagnosis of type 1 diabetes as an endpoint. A significant delay in onset was only found in a high-risk stratum (termed secondary stratum 1) of participants with low first-phase insulin release (FPIR). Methods: Since trials with an endpoint of type 1 diabetes take years to complete, in this post hoc analysis, we assessed whether a novel combination of glucose and C-peptide markers could identify a therapeutic benefit after 1 year of follow-up (trial participants followed for a median 2.7 years). Results: Participants were relatives with multiple islet autoantibodies and low FPIR (n = 40). Glucose rose, and C-peptide declined in the placebo group, whereas glucose rose minimally, and C-peptide increased in the OI group. When glucose and C-peptide were plotted on two-dimensional grids using 30-120-min oral glucose tolerance test (OGTT) time points, changes in ratios of their central points (centroid ratio) differed between groups (p=0.037 adjusted for age, BMI, and baseline C-peptide and glucose). Conclusions: These findings support a favorable early effect of OI on combined glucose and C-peptide endpoints in high-risk individuals, indicating metabolic benefit. With further study, these measures may allow for shorter trials compared to the standard endpoint of type 1 diabetes diagnosis.
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