2167-LB: Proteomic Changes in Mexican-Americans before and after Meals in Response to Semaglutide Therapy

• Published in: Diabetes (New York, N.Y.) Vol. 74; no. Supplement_1; p. 1
• Main Authors: BELOW, JENNIFER E., ROSHANI, RASHEDEH, HIGHLAND, HEATHER M., BIAN, DAYI, FRANKEL, ELIZABETH G., NORTH, KARI E., MCCORMICK, JOSEPH B., GUTIERREZ, ABSALON D.
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 20.06.2025
• Subjects: Beta cells; Breast feeding; Coronary artery disease; Diabetes mellitus; Down-regulation; Fasting; Glucagon; Glucagon-like peptide 1; Heart diseases; Hispanic Americans; Liver diseases; Metabolism; Movement disorders; Neurodegenerative diseases; Parkinson's disease; Proteins; Proteomes; Proteomics; Trypsin; Tumor suppression; Tumorigenesis
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db25-2167-LB

Introduction and Objective: Glucagon-like peptide-1 receptor agonists (GLP-1Ras) utilize multiple mechanisms to achieve their therapeutic effects, resulting in lower blood glucose, weight loss, and improved cardiovascular and renal health (GLP-1RAs). Many of their beneficial metabolic effects occur in the postprandial state. Data from prior randomized controlled trials have linked fasting levels of the circulating proteome to semaglutide (GLP-1RA) efficacy. We link both fasting and prandial levels of the circulating proteome to 3 months of semaglutide (GLP-1RA) therapy in a community-based Mexican-American cohort Methods: We conducted pre- and post-treatment, fasting and 2-hour postprandial circulating proteomic analysis on adults with prediabetes receiving semaglutide therapy (n=61) for 12 weeks. Subjects with prior diabetes, recent use of antidiabetic or glucotoxic medications, severe cardiac/hepatic/pancreatic/renal disease, and/or current pregnancy/breastfeeding were excluded. Results: In the fasting state (pre- to posttreatment), semaglutide downregulated proteins associated with tumorigenesis and Parkinson’s disease, while upregulating proteins involved in trypsin metabolism, lipase metabolism, beta cell regulation, tumor suppression, and visual refractive error. In the prandial state (pre- to posttreatment), proteins involving trypsin metabolism, tumor suppression, visual refractive error were upregulated. Proglucagon was upregulated in both fasting and prandial states. Comparing states, proglucagon was downregulated in the prandial state. Conclusion: Therapy with GLP-1RA semaglutide significantly modifies protein regulation in the context of physiologic changes in Mexican-Americans with prediabetes.