2525-P: HbA1c Determines Serum Proteomic Response to Acute Exercise in Type 1 Diabetes

Introduction and Objective: High HbA1c is linked to lower aerobic exercise capacity (VO2peak), even when exercise-training levels are matched, suggesting hyperglycemia may alter the adaptive response to exercise. Each acute bout of exercise induces changes in circulating proteins that mediate exercise response. We determined how T1D alters circulating proteins at rest and with exercise and whether these changes are linked to lower VO2peak. Methods: VO2peak and HbA1c were measured in N=11 participants with T1D and N=8 age-matched participants without diabetes (CON). All participants performed one bout of 45 min moderate aerobic exercise (60% VO2peak), and pre- and post-exercise plasma samples were analyzed by SomaScan proteomics. Results: VO2peak was inversely correlated with HbA1c, with a strong relationship observed in those with T1D (r=-0.70, P=0.01). We detected regulation of 754 circulating proteins by a bout of aerobic exercise. Exercise-regulated proteins were remarkably different between T1D and CON, with 348 proteins being uniquely regulated by exercise in T1D. Mediators of inflammation (e.g., SAA1, C3) and metabolism (e.g., VRK1) were among the differentially regulated proteins at rest and with exercise in T1D. Further stratification of participants by HbA1c revealed alterations in serum proteome and VO2peak in T1D were HbA1c-dependent, indicating that tight glucose management may preserve exercise response. Conclusion: T1D profoundly alters the circulating proteome at rest and in response to acute exercise, with those having the highest HbA1c diverging most significantly from controls without diabetes. Divergent regulation of the serum proteome with exercise may contribute to low VO2peak in those with hyperglycemia. Disclosure P. Pattamaprapanont: None. R. Nogueira Soares: None. H. Pan: None. J. Dreyfuss: None. S. Lessard: None.