2763-LB: Sex-Specific Endocrine and Skeletal Muscle Responses to a Weight-Stable, Plant-Based Diet in Adults with Prediabetes

Introduction and Objective: Preclinical research suggests there is heterogeneity in how males and females respond to low protein diets. We examined how a lower protein, plant-based diet alters insulin sensitivity, circulating fibroblast growth factor-21 (FGF-21), and skeletal muscle gene expression in men and women. Methods: Adults with prediabetes were provided with a fully plant-based diet for 4 weeks (n=6; 3 men, 3 women). Before and after the intervention, body composition was assessed using iDXA and glucose, insulin, and FGF-21 were measured during an OGTT. Skeletal muscle biopsies were collected 1 hour after a standard meal, and RNA was extracted. Sequencing and preliminary bioinformatics were completed by Novogene. Results: Men and women showed reductions in android fat, but body weight remained stable. Protein intake decreased from 81.4 ± 30.1 g from baseline to 60.3 ± 11.3 g (p=0.043). Insulin resistance improved in both groups with lower HOMA-IR after the intervention, while women showed greater improvements in the Matsuda insulin sensitivity index. Men showed an increase in FGF-21 AUC0–120 in response to the OGTT (47992 ± 28854 pg·min/mL) after the intervention while women decreased (-24101 ± 47299 pg·min/mL); p=0.087). RNA-sequencing revealed sex-specific transcriptional responses in men, including increased expression of FOS (log2FC=2.32, FDR=0.001) and EGR1 (log2FC=1.84, p=1.2×10−5, FDR= 0.132). Conclusion: A lower protein, plant-based diet improved metabolic markers in both sexes but elicited sex-specific endocrine and skeletal muscle transcriptional responses. These findings suggest sex-dependent metabolic adaptation to plant-based dietary patterns that may inform precision nutrition strategies for diabetes prevention. Disclosure J.L. Fry: None. K.R. Anderson: None. Z. Leicht: None. D.E. Long: None. P. Kern: None. Funding Gene Haas Foundation and the University of Kentucky Barnstable Brown Diabetes Center