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

Abstract

Following a diagnosis of type 1 diabetes (T1D), persisting C-peptide secretion leads to improved glycemic control and outcomes. Residual β-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 β-cell glucose sensitivity (βGS) to assess changes in β-cell function, incorporating insulin secretion for a given serum glucose into the assessment of β-cell function. We evaluated changes in βGS in individuals enrolled in the placebo arm of 10 T1D trials performed at diabetes onset. We found that βGS showed a more rapid decline in children, as compared with adolescents and adults. Individuals in the top quartile of βGS 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 βGS significantly improved the overall model. Taken together, these data suggest that βGS 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. Article highlights: We undertook this study to better predict β-cell loss following type 1 diabetes diagnosis. We set out to answer whether β-cell glucose sensitivity (βGS) improves means to evaluate β-cell function postdiagnosis and whether βGS correlates with clinical outcomes. We found that βGS declines faster in children, subjects in the top baseline quartile of βGS exhibit slower β-cell decline (half are children), and incorporating βGS into multivariate Cox models for glycemic improves the model. The implications of our findings are that βGS predicts those likely to have robust clinical remissions and may help with clinical trials design.