Microvascular development and remodeling
Authors: Draghici Adina , Yu Elaine , Bouxsein Mary , Taylor J. Andrew 
Published: May 2024

Skeletal fragility is an important complication of Type 1 Diabetes (T1D), particularly among older adults. Microvascular disease (MVD) has been linked to worse bone health in T1D, suggesting a potential direct pathophysiologic link between vascular disease and bone deficits. However, bone vascular control has not been explored in the context of T1D. Thus, this preliminary work investigates key mechanisms of regulation of the bone vasculature in older adults with T1D. Myogenic vasoconstriction and reactive hyperemia of tibial blood flow were assessed in older healthy adults (n=9, 65 ± 7 yrs) and older adults with T1D (n=10, 63 ± 6 yrs). Myogenic vasoconstriction was assessed in response to leg dependency (two levels of increased arterial transmural pressure obtained by lowering the leg below heart level) and reactive hyperemia was assessed in response to lower leg arterial occlusion via thigh cuff inflation. The initial peak reactive hyperemic response was considered a surrogate of myogenic vasodilation. For both stimuli, tibial blood flow was assessed via NIRS as total hemoglobin (tHb) and whole leg blood flow velocity (LBF) in the popliteal artery of the same leg was measured via Doppler ultrasound. Data are presented as mean±standard error. In response to leg dependency, with increased perfusion pressure, older adults had a tendency for smaller declines in LBF (L1: -3.85 ± 2.01 cm/s; L2: -6.22 ± 4.19 cm/s) compared to older adults with T1D (L1: -6.14 ±2.24 cm/s; L2: -10.4 ± 1.90 cm/s; group p=0.06, level p=0.07). Tibial tHb did not decline in older adults (L1: 1.16 ± 7.27 M; L2: 9.11 ± 13.8 M), but decreased progressively in those with T1D (L1: - 3.40 ± 2.79 M, L2: -6.14 ± 2.24 M, group p<0.01, group*level p=0.07), indicating pronounced tibial myogenic vasoconstriction. In response to reactive hyperemia, LBF increased rapidly with cuff release in both groups (older adults: 50.8 ±22.7cm/s; T1D: 40.0 ± 13.4cm/s). Despite similar responses in LBF, tibial tHb surpassed baseline values in older adults (1.50 ± 5.35M), whereas tibial tHb did not reach baseline values within 5 min post cuff release in T1D (-2.85 ± 5.09M, p=0.09), indicating impaired tibial myogenic vasodilation. Interestingly, older adults with T1D and MVD (n=5) had a stronger tendency for greater tibial myogenic vasoconstriction at both levels and significantly impaired reactive hyperemic response compared to those with no MVD (n=5). Our preliminary results indicate that older adults with T1D have greater myogenic vasoconstriction and impaired reactive hyperemic responses that appear to be worse in the presence of MVD. Alterations in myogenic control act to compromise blood flow regulation, restricting blood flow to bone, and potentially contributing to diabetes-inducted skeletal fragility. NIH NIDDK R01 DK124710. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.