2178-P: Effects of Lowering Carbohydrate Amount and Glycemic Index on Whole-Body and Organ-Specific Aging Proteins and Postprandial Glucose Metabolism: The OmniCarb Trial

Introduction and Objective: Carbohydrate digestion and glucose tolerance decline with age. Proteomics has emerged as a powerful tool for assessing biological aging. We investigated whether reducing carbohydrate (carb) intake and dietary glycemic index (GI) altered aging-related proteins and their associations with postprandial glucose metabolism. Methods: The study included participants from the OmniCarb crossover feeding trial, who consumed a high-carb, high-GI diet and a low-carb, low-GI diet for 5 weeks each. Participants completed 12-hour meal tests (n = 48); the area under the curve of glucose (AUC-glu) was calculated. We analyzed 231 validated aging-related proteins measured by Olink proteomics. Results: Lowering carb amount and GI modified several liver- and brain-aging proteins (PFDR <0.05), including fibroblast growth factor 21 (FGF21), oxytocin (OXT), and carnosine dipeptidase 1 (CNDP1). Whole-body aging proteins and epidermal growth factor receptor (EGFR) were also altered (Figure). Diet-responsive proteins were associated with differences in AUC-glu (β 2690 [SE 1108]; P = 0.019 per 1 SD increase of FGF21 on a high-carb and high-GI diet). Between-diet changes in CNDP1 and EGFR were also related to changes in AUC-glu (P < 0.05). Conclusion: Reducing carb and GI levels modified proteomic pathways related to biological aging and were linked to regulation of half-day postprandial hyperglycemia. Disclosure Y. Heianza: None. Q. Sun: None. F. Hu: None. L.J. Appel: Other - Payment for chapters in UpToDate on the relationship of hypertension with sodium, weight, exercise and smoking; Current; Wolters Kluwer.