MON-217 Growth Hormone Receptor and Insulin-Like Growth Factor 1 Have Sex-Specific Associations with Body Composition in Pediatric Type 2 Diabetes

Abstract Disclosure: C. Hommel: None. C. Lu: None. L. El ghormli: None. L.M. Laffel: None. E. Isganaitis: None. Background: Youth-onset type 2 diabetes (YOT2D) has an aggressive phenotype and typically arises during puberty, a period of rapid growth. Peri-pubertal changes in growth hormone (GH) signaling may contribute to dysglycemia, insulin resistance, and altered body composition. We previously showed that higher GH receptor (GHR) levels predicted adverse glycemic measures in a YOT2D cohort, while insulin-like growth factor 1 (IGF-1) was associated with improved glycemia. It remains unclear whether GHR and IGF-1 have synergistic or opposing associations with body composition, and whether changes in body composition may mediate the association of GHR and IGF-1 with glycemic outcomes in YOT2D. Hypothesis: We hypothesized that both GHR and IGF-1 are predictive of changes in lean mass (LM), percent body fat (%BF), and bone mineral density (BMD) in YOT2D, in a sex-specific manner. Methods: The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study was a large multi-center randomized controlled trial conducted from 2004 to 2014 in adolescents with T2D. Using a subset of the TODAY cohort with available baseline (BL) plasma samples for GHR and IGF-1 measurements (ELISA) and dual-energy x-ray absorptiometry measurements at BL and 24-month timepoints (N=224), we examined the association of BL GHR and IGF-1 (ng/mL) with the change in body composition measures, including whole body BMD, LM, and %BF using linear regressions adjusted for age, sex, race/ethnicity, baseline Tanner stage, treatment arm, with or without baseline HbA1c. Subgroup analyses were performed based on sex. Results: This subcohort included 144 females (ages 13.4 ± 2.0 years (mean ± SD)) and 80 males (ages 14.4 ± 1.9 years). Compared with males, females had less accrual of BMD between BL and 24 months (0.05 ± 0.05 g/cm2 vs. 0.07 ± 0.06 g/cm2, p=0.005), less accrual of LM (2.4 ± 3.5 kg vs. 5.6 ± 5.0 kg, p<0.001), and an increase in %BF over time (1.6 ± 2.9 vs. -1.8 ± 4.1, p<0.001). Higher BL GHR was associated with less accrual of LM between BL and 24 months (B = -1.1, SE = 0.47, P=0.02), but this association was attenuated with HbA1c adjustment. In males, higher BL GHR was associated with less accrual of LM (B= -2.8, SE=1.0, p=0.006). In females, higher BL GHR was associated with greater accrual of BMD in females (B=0.02, SE=0.007, p=0.02). Higher BL IGF-1 was associated with greater increase in BMD (B=5.2, SE=2.2e-5, p=0.018), with associations not significant when stratified by sex. Conclusion: In a YOT2D cohort, higher plasma GHR was associated with less LM gain in males and greater BMD gain in females, which implicates potential roles for sex hormones. However, GHR was not associated with fat mass accrual. Higher IGF-1 was associated with greater accrual of BMD. Together, our data suggest that the associations of GHR and IGF-1 with glycemic outcomes may be mediated by changes in body composition. Presentation: Monday, July 14, 2025