Disease duration and C-peptide at onset are key determinants of long-term residual β-cell function in children with type 1 diabetes

Abstract Objectives Residual β-cell function (RBCF) may persist in a subset of children with long-standing type 1 diabetes (T1D), offering metabolic benefits. We aimed to evaluate factors that determine the long-term persistence of RBCF. Methods We conducted a prospective study from July 2024 to December 2025 to assess RBCF in children with long-standing (≥7 years) T1D. Stimulated C-peptide (SCP) was measured 90 min after the mixed-meal tolerance test. Patients were grouped into RBCF-preserved (SCP ≥0.01 nmol/L) or RBCF-depleted (SCP <0.01 nmol/L). RBCF determinants, such as age, sex, ketoacidosis at onset, serum C-peptide concentration at diagnosis, number of pancreatic autoantibodies at diagnosis, glycemic control, and disease duration, were compared between the two groups. Results Seventy-two children (mean age 15.4 ± 3.3 years, 54 % boys) with a mean T1D duration of 9.8 ± 2.1 years were studied. RBCF was preserved in 30.6 % (22/72) of children. Shorter disease duration (median 8.8 vs. 9.7 years, p=0.027) and higher C-peptide at onset (0.17 vs. 0.04 nmol/L, p<0.001) strongly predicted preservation. Older age at T1D onset (7.3 vs. 4.9 years) showed a trend toward better-preserved RBCF, but the association did not attain statistical significance (p=0.11). Ketoacidosis at onset, the number of autoantibodies, and glycemic control did not affect RBCF persistence. Conclusions RBCF persists in about one-third of children with long-standing T1D, suggesting that endogenous insulin production does not vanish completely after diagnosis. Higher C-peptide levels at clinical onset strongly predicted long-term RBCF-preservation, suggesting that patients with a larger initial β-cell reserve are better poised for long-term endogenous insulin synthesis.