Clinical prediction models combining routine clinical measures identify participants with youth-onset diabetes who maintain insulin secretion in the range associated with type 2 diabetes: The SEARCH for Diabetes in Youth Study

OBJECTIVE: With the high prevalence of pediatric obesity and overlapping features between diabetes subtypes, accurately classifying youth-onset diabetes can be challenging. We aimed to develop prediction models that, using characteristics available at diabetes diagnosis, can identify youth who will retain endogenous insulin secretion at levels consistent with type 2 diabetes (T2D). METHODS: We studied 2,966 youth with diabetes in the prospective SEARCH study (diagnosis age ≤19 years) to develop prediction models to identify participants with fasting c-peptide ≥250 pmol/L (≥0.75ng/ml) after >3 years (median 74 months) of diabetes duration. Models included clinical measures at baseline visit, at a mean diabetes duration of 11 months (age, BMI, sex, waist circumference, HDL-C), with and without islet autoantibodies (GADA, IA-2A) and a Type 1 Diabetes Genetic Risk Score (T1DGRS). RESULTS: Models using routine clinical measures with or without autoantibodies and T1DGRS were highly accurate in identifying participants with c-peptide ≥0.75 ng/ml (17% of participants; 2.3% and 53% of those with and without positive autoantibodies) (area under receiver operator curve [AUCROC] 0.95–0.98). In internal validation, optimism was very low, with excellent calibration (slope=0.995–0.999). Models retained high performance for predicting retained c-peptide in older youth with obesity (AUCROC 0.88–0.96), and in subgroups defined by self-reported race/ethnicity (AUCROC 0.88–0.97), autoantibody status (AUCROC 0.87–0.96), and clinically diagnosed diabetes types (AUCROC 0.81–0.92). CONCLUSION: Prediction models combining routine clinical measures at diabetes diagnosis, with or without islet autoantibodies or T1DGRS, can accurately identify youth with diabetes who maintain endogenous insulin secretion in the range associated with type 2 diabetes.