Assessment of Body Composition in Adolescents with T2D on Glucagon-like-peptide receptor agonists (GLP-1RAs) (ABC Study) - PROJECT SUMMARY The prevalence of type 2 diabetes (T2D) is increasing in adolescents, and metformin, the first-line FDA-approved therapy for T2D, often fails to achieve durable glycemic improvement. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide have transformed the treatment landscape, offering substantial benefits, including weight loss, glycemic improvement, and β-cell preservation. However, their unintended effects on skeletal muscle loss and eating behaviors in adolescents remain poorly understood. Understanding these benefits is crucial for optimizing treatment safety and efficacy during adolescence, a key developmental period. To address this unmet medical need, Sujatha Seetharaman, MD, proposes a study through this career development with the following aims (1a) assess changes in body composition and functional outcomes over six months of semaglutide therapy in adolescents with T2D (1b) examine how the rate of weight loss with semaglutide relates to changes in muscle mass in adolescents with T2D (2) investigate the effect of semaglutide on the risk of disordered eating and internalized weight stigma in adolescents with T2D. She will enroll 50 adolescents (ages 12–17.99 years) with new-onset T2D from UCSF Diabetes Clinics, treated with metformin for at least 3 months, and initiating semaglutide per their routine clinical care. In aim 1, she will assess changes in fat mass using magnetic resonance imaging, skeletal muscle mass using the D3 creatine dilution method, muscle quality, strength, and function at baseline and 6 months. In aim 2, she will calculate the rate of weight loss over 6 months and correlate it with skeletal muscle mass loss, strength, and function. In aim 3, she will examine changes in eating attitudes and internalized weight-related stigma at baseline and at 6 months to identify individuals who are at risk for disordered eating. Results from this proposal will inform an R01 in which targeted interventions such as an integrated exercise program and eating disorder prevention strategies will be tested in a large randomized controlled trial and expanded to include emerging dual/triple agents in adolescents with T2D. Dr. Seetharaman’s long-term career goal is to become an independently funded clinician-investigator advancing research that integrates novel pharmacotherapies with tailored interventions to improve health outcomes in adolescents with T2D. In this career development award, her career goals are to gain targeted training in body composition analysis, become proficient in advanced biostatistical methods, become proficient in utilizing person-reported outcome metrics, gain experience in conducting pediatric clinical trials, and engage in career development activities in preparation for R01 funding. She will accomplish these goals with the advice and mentoring from a world-class multidisciplinary mentoring team, participation in relevant didactic coursework, and hands-on research experience, all necessary for future independent success. This project aligns with NIDDK’s mission to improve the health and well-being of individuals affected by diabetes and related conditions.
