**Background:** Type 1 diabetes (T1D) is preceded by islet autoimmunity (IA), in which autoantibodies appear in the blood. The incidence of T1D peaks around 10–14 years, coinciding with puberty, and insulin sensitivity decreases during puberty, potentially accelerating β-cell stress and autoimmune progression. However, direct evidence linking puberty to IA development or progression to T1D has been limited. This study aimed to determine whether puberty and its timing are associated with the development of IA and subsequent progression to clinical T1D.
**Methods:** The study included 6,920 participants (3,117 girls, 45.0%; 3,803 boys) from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) prospective birth cohort, all carrying HLA-DQB1-conferred genetic susceptibility to T1D. Children were followed from birth through age 15 years or until T1D diagnosis. Age at pubertal onset was estimated using a validated time-to-pubertal onset model based on individual growth characteristics (peak height velocity, age at peak height velocity) and pre-pubertal overweight status. The mean estimated age at pubertal onset was 10.6 years (SD: 0.98) for girls and 11.6 years (SD: 0.62) for boys. IA was defined using two definitions: (1) repeated positivity for islet cell antibodies (ICA) plus at least one biochemical autoantibody (ICA+1), and (2) repeated positivity for at least one biochemical autoantibody (BC1). Progressive three-state survival models (state 1: no IA; state 2: IA; state 3: T1D) with Weibull-distributed hazards were used. Puberty was incorporated as a novel time-dependent function with data-driven selection of origin (1 year before estimated onset), duration (3 years), and shape (10% ramping-up, 80% steady, 10% fading-off). Models were adjusted for sex and overweight status (ISO-BMI >25) at age 7 years. Timing of pubertal onset was categorized into tertiles (girls: <10.0, 10.0–11.0, >11.0 years; boys: <11.3, 11.3–11.8, >11.8 years).
**Key Results:** Of the 6,920 participants, 303 (4.4%) tested positive for IA by ICA+1 definition and 435 (6.3%) by BC1 definition by age 7. During follow-up, 211 (3.2%) developed IA by ICA+1 and 198 (5.3%) by BC1. A total of 172 (2.5%) participants developed T1D at a median age of 11.3 years (IQR: 9.3–13.3). Puberty was not significantly associated with the risk of developing IA (ICA+1: adjusted HR 1.25, 95% CI 0.90–1.74; BC1: adjusted HR 1.24, 95% CI 0.87–1.77). However, puberty was significantly associated with an increased risk of progression from ICA+1-defined IA to T1D (adjusted HR 1.57, 95% CI 1.14–2.16). For BC1-defined IA, the association was in the same direction but did not reach statistical significance (adjusted HR 1.31, 95% CI 0.95–1.80). The timing of pubertal onset did not significantly modify the association (p=0.659 for ICA+1 progression). Sensitivity analyses accounting for uncertainty in pubertal onset estimation and using alternative functional forms for the pubertal effect confirmed the robustness of the findings. Neither sex nor overweight status at age 7 was significantly associated with IA risk or progression risk.
**Clinical Implications:** This study provides novel evidence that puberty may accelerate the progression from islet autoimmunity to clinical type 1 diabetes, with a 57% increased hazard during the pubertal period, but does not appear to trigger the initial development of autoimmunity. These findings suggest that the well-documented peak in T1D incidence during adolescence may be attributable to pubertal development rather than age per se. The results support the hypothesis that puberty-related insulin resistance and increased metabolic demand may stress pancreatic β-cells in individuals who already have autoimmunity, accelerating β-cell destruction and clinical disease onset. Clinically, this implies that children with IA entering puberty may warrant closer monitoring for progression to T1D. The study's strengths include its large, well-characterized longitudinal cohort with long follow-up and novel multi-state modeling approach. Limitations include the lack of systematic biochemical autoantibody measurements in children born before 2003, reliance on growth-based estimation of pubertal onset rather than physical examination, and restriction to children with HLA-conferred genetic risk, which may limit generalizability.