Random C-peptide and islet antibodies at onset predict B cell function trajectory and insulin dependence in pediatric diabetes

Authors: TOSUR, MUSTAFA - Children'S Nutrition Research Center (CNRC); DEEN, SAIMA - Baylor College Of Medicine; HUANG, XIAOFAN - Baylor College Of Medicine; UYSAL, SERIFE - Texas Children'S Hospital; ASTUDILLO, MARCELA - Texas Children'S Hospital; ORAM, RICHARD - University Of Exeter; REDONDO, MARIA - Texas Children'S Hospital; JAHOOR, FAROOK - Children'S Nutrition Research Center (CNRC); BALASUBRAMANYAM, ASHOK - Baylor College Of Medicine

Submitted to: Endocrine Practice
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/27/2024
Publication Date: 10/2/2024
Citation: Tosur, M., Deen, S., Huang, X., Uysal, S., Astudillo, M., Oram, R.A., Redondo, M.J., Jahoor, F., Balasubramanyam, A. 2024. Random C-peptide and islet antibodies at onset predict B cell function trajectory and insulin dependence in pediatric diabetes. Endocrine Practice. 30(12):1149-1157. https://doi.org/10.1016/j.eprac.2024.09.116.
DOI: https://doi.org/10.1016/j.eprac.2024.09.116

Interpretive Summary: Diabetes in children is rising quickly and can lead to serious lifelong health problems. Knowing early on which children will need long-term insulin, and which may not is important for guiding treatment. We studied 72 children with new-onset diabetes and found that two simple tests at the time of diagnosis—a C-peptide test (which shows how much insulin the body is still making) and a test for islet autoantibodies (which show if the immune system is attacking the pancreas)—can help predict how their diabetes will progress in the first year. We found that children who had no autoantibodies and still made good amounts of insulin (the A–b+ group) were often older, had higher body weight, and were more likely to come off insulin therapy within a year. This group also had a strong link to features of type 2 diabetes, which is often related to obesity and insulin resistance. These findings highlight how weight status and nutrition may affect the development and treatment of diabetes in kids. By using these early tests, doctors may be able to give more personalized care, avoid unnecessary insulin, and focus on healthy lifestyle changes—including better nutrition and physical activity—for those most at risk.

Technical Abstract: Identification of prognostic biomarkers in pediatric diabetes is important for precision medicine. We assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes. We prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the AB classification system ("A+": islet autoantibody positive, "B+": random serum C-peptide >/-1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2 hours postprandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6 to 12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score for each participant, and compared characteristics at baseline, and clinical outcomes at V2. The cohort was 50% male. Racial distribution was 76.4% White, 20.8% Black, and 2.8% Asian or other races. A total of 46.5% participants were Hispanic. Median age (Q1-Q3) was 12.4 (8.3-14.5) years. The Aß subgroup frequencies were 46 A+B-(63.9%), 1 A-B-(1.4%), 4 A+B+(5.6%), and 21 A-B+(29.2%). Baseline serum C-peptide correlated with UCPCR at both V1 (r = 0.36, P = .002) and V2 (r = 0.47, P < .001). There were significant subgroup differences in age, race, frequency of diabetic ketoacidosis, and type 1 diabetes genetic risk score (P < .01). At V2, the 2 B-subgroups had lower UCPCR and higher hemoglobin A1c compared with the 2 B+ subgroups (P < .001 and P = .02, respectively). Thirty-eight percent of A-B+ but none of the other subgroups were insulin-independent at V2 (P < .001). C-peptide and islet autoimmunity at diagnosis define distinct phenotypes and predict beta-cell function and insulin dependence 6 to 12 months later in racially/ethnically diverse children with new-onset diabetes.