β-Cell Glucose Sensitivity to Assess Changes in β-Cell Function in Recent-Onset Stage 3 Type 1 Diabetes

Following a diagnosis of type 1 diabetes (T1D), persisting C-peptide secretion leads to improved glycemic control and outcomes. Residual beta-cell function is often assessed with serial mixed-meal tolerance tests, but these tests do not correlate well with clinical outcomes. Herein, we instead use beta-cell glucose sensitivity (beta GS) to assess changes in beta-cell function, incorporating insulin secretion for a given serum glucose into the assessment of beta-cell function. We evaluated changes in beta GS in individuals enrolled in the placebo arm of 10 T1D trials performed at diabetes onset. We found that beta GS showed a more rapid decline in children, as compared with adolescents and adults. Individuals in the top quartile of beta GS baseline distribution had a slower rate in loss of glycemic control time over time. Notably, half of this group were children and adolescents. Finally, to identify predictors of glycemic control throughout follow-up, we ran multivariate Cox models and found that incorporating beta GS significantly improved the overall model. Taken together, these data suggest that beta GS may be of great utility in predicting those more likely to have a more robust clinical remission and may be of use in design of new-onset diabetes clinical trials and in evaluating response to therapies.