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High proinsulin:C‑peptide ratio identifies individuals with stage 2 type 1 diabetes at high risk for progression to clinical diagnosis and responses to teplizumab treatment – published online 04/09/2023

Sims graphical abstract

Emily K. Sims, Susan M. Geyer, S. Alice Long, Kevan C. Herold

Heterogeneity exists in type 1 diabetes progression, even within the different stages of the disease. In this issue, Sims et al ( show that, in individuals with stage 2 type 1 diabetes, an elevation in proinsulin:C-peptide (PI:C) ratio, a biomarker reflecting beta cell stress, is highly predictive of progression to stage 3 type 1 diabetes. They report that teplizumab weakened this relationship between beta cell stress and progression, and participants with a high baseline ratio treated with the drug showed reduced progression rates compared with participants who were treated with placebo. The authors conclude that the PI:C ratio may identify subgroups of individuals who are most likely to benefit from rapid consideration for teplizumab treatment, given their imminent risk of clinical presentation with stage 3 type 1 diabetes.

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