2082-P: Effects of Puberty and Metabolic Risk in Youth: Results from the PANTHER Study

Introduction and Objective: Puberty is associated with physiologic insulin resistance (IR), which accelerates at puberty onset (Tanner stage [TS] 2) and peaks at mid-puberty (TS3). Understanding factors associated with IR and its relationship with puberty is essential in assessing risk of youth-onset type 2 diabetes (T2D). We examined intravenous glucose tolerance test (IVGTT) data in youth at increased risk for T2D (BMI ≥95th %tile and/or HbA1c ≥6.0%) or with established T2D (combined “high-risk”), as well as healthy controls (BMI <85th percentile, HbA1c ≤5.6%, “low-risk”) across TS. Methods: We analyzed blood glucose (BG) and C-peptide from morning IVGTTs after an 8-hour fast via mixed-effects longitudinal models in youth at low- or high-risk. TS was assessed via exam. Results: We included 88 youth (12.5±1.6 yrs, 53% female), 59 high-risk (BMI 28.3 kg/m2, HbA1c 5.7%) and 29 low-risk (BMI 18.1 kg/m2, HbA1c 5.2%). High-risk youth exhibited higher BG (p<0.0001) and C-peptide (p<0.0001) compared to low-risk youth (Figure). In models adjusted for risk group, BG differed by TS (p=0.02), with highest BG in TS3 (Figure). There was no significant difference in C-peptide by TS (p=0.35). Conclusion: Metabolic risk and TS synergistically elevate BG, with TS3 representing a critical window of vulnerability. The absence of TS differences in C-peptide suggests compensatory insulin secretion is insufficient at mid-puberty. These findings support targeting interventions to high-risk youth during this period. Disclosure M. Sethi: None. K. Tommerdahl: Advisory Panel; Current; Sanofi. Y. Choi: None. P. Narongkiatikhun: None. C.L. Birznieks: None. N. Nguyen: None. L. Driscoll: None. K.J. Nadeau: None. M. Moriarty Kelsey: Research Support; Current; Rhythm Pharmaceuticals, Inc. P. Bjornstad: Consultant; Current; Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk. L. Pyle: None. K. Bocek: None. Funding NIH/NIDDK (R01 DK129211)