ß-cell glucose sensitivity to assess changes in ß-cell function in recent onset stage 3 type 1 diabetes

Following a diagnosis of type 1 diabetes, persisting C-peptide secretion leads to improved glycemic control and outcomes. Residual ß-cell function is often assessed with serial mixed meal tolerance tests, but these tests do not correlate well with clinical outcomes. Herein, we instead employ ß-cell glucose sensitivity (bGS) to assess changes in ß-cell function, incorporating insulin secretion for a given serum glucose into the assessment of ß-cell function. We evaluated changes in bGS in individuals enrolled in the placebo arm of ten type 1 diabetes trials performed at diabetes onset. We found that bGS showed a more rapid decline in children, as compared to adolescents and adults. Individuals in the top quartile of bGS 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 bGS significantly improved the overall model. Taken together, these data suggest that bGS may be of great utility in predicting those more likely to have a more robust clinical remission, and may be of use in new onset clinical trials design and in evaluating response to therapies.