Introduction and Objective: Type 2 Diabetes (T2D) shortens lifespan largely via increased CVD risk. Cardiorespiratory fitness (CRF), a strong predictor of CVD mortality, is lower in people with T2D. Our previous work showed lower muscle oxidative flux in vivo in T2D compared to overweight controls, despite similar ex vivo mitochondrial oxygen consumption. Supplemental oxygen or single-leg exercise training corrected this deficit, implicating oxygen delivery limitations in reduced CRF. Skeletal muscle architecture, a key determinant of oxygen delivery, remains unexamined in relation to CRF. The extracellular matrix (ECM), composed of collagen, hyaluronic acid, dystrophin, elastin, and proteoglycans, underpins muscle structure. We hypothesize that ECM remodeling in T2D negatively impacts oxygen delivery.Methods: In participants with T2D (n=12) and BMI-matched controls (n=15), the gastrocnemius was biopsied and near-infrared spectroscopy (NIRS) to assess blood flow was performed before and after 2 weeks of single-leg exercise training (5 days/week).Muscle samples were analyzed using second harmonic generation (collagen) and immunohistochemistry (hyaluronic acid, dystrophin, elastin, and proteoglycans).Results: T2D participants had greater collagen area than controls (p=0.04); there was a suggestion of decreased collagen area with training (p=0.08). Collagen mass remained unchanged, suggesting lower density in T2D. No significant differences were observed in hyaluronic acid, dystrophin, elastin, or proteoglycans. ECM remodeling did not correlate with oxygen delivery, as measured by NIRS.Conclusion: Collagen area is greater but less dense in people with T2D. ECM does not explain the reduced oxygen delivery in people with T2D.
N.A. Hulett: None. L. Knaub: None. I.E. Schauer: None. J.G. Regensteiner: None. R.L. Scalzo: None. J.E. Reusch: Advisory Panel; Medtronic.
American Diabetes Association (1-12-CT-64); Veterans Administration Career Development Award (BX004533)National Institutes of Health (NIH)/National Center for Research Resources (T32-DK-063687, K23-DK-107871)NIH Building Interdisciplinary Research Careers in Women’s Health (2K12-HD-057022)Veterans Administration Merit Award (CVP BX002046)University of Colorado “Integrative Physiology of Aging” Training Grant (T32AG000279)
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