High-risk individuals with islet autoantibody positivity (Ab+) vary in their rates of progression to T1D. We hypothesized that changes in C-peptide over time account for some of this variation. Among Ab+ children (<18.0 years) followed with 2-hour OGTTs for development of T1D in DPT-1, we compared Progressors to T1D with Non-Progressors for the change in AUC C-peptide from the baseline OGTT to the last available OGTT (last before diagnosis in Progressors). Results were stratified by low or high baseline DPT-1 Risk Score (DPTRS: fasting C-peptide, sum C-peptide and sum glucose values from 30-120 minutes, age and BMI; DPTRS <7.00= lower risk and ≥7.00= higher risk). As shown in the Table, Non-Progressors from each group exhibited increases in AUC C-peptide over time, while Progressors showed no significant changes in AUC C-peptide. A logistic regression model with adjustment for age indicated an inverse association of T1D development with increasing AUC-C-peptide/year [Odds ratio: 0.587 (0.430, 0.802), p<0.001].

In conclusion, even in individuals with high baseline risk assessments, increasing AUC C-peptide over time is associated with decreased progression to T1D. This persistent C-peptide responsiveness could result from increased β-cell reserve (either functional or mass) or β-cell regeneration.


E.K. Sims: None. H.M. Ismail: None. B.M. Nathan: None. J.M. Sosenko: None.


National Institutes of Health

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