Peripheral microvascular response to muscle contraction is unaltered by early diabetes but decreases with age

Abstract

Long-term or untreated diabetes leads to micro- and macrovascular complications. However, there are few tests to evaluate microvascular function. A postcontraction blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) technique was exploited to measure peripheral microvascular function in diabetics and healthy controls matched with respect to age, body mass index, and physical activity. Postcontraction BOLD microvascular response was measured following 1-s maximal isometric ankle dorsiflexion in individuals with diabetes mellitus type I [DMI, n = 15, age 33 ± 3 yr (means ± SE), median diabetes duration = 5.5 yr] and type II (DMII, n = 16, age 45 ± 2 yr, median duration = 2.4 yr); responses were compared with controls (CONI and CONII). Peripheral macrovascular function of the popliteal and tibial arteries was assessed during exercise hyperemia with phase contrast magnetic resonance angiography following repetitive exercise. There were no group differences as a result of diabetes in peripheral microvascular function (peak BOLD response: DMI = 2.04 ± 0.38% vs. CONI = 2.08 ± 0.48%; DMII = 0.93 ± 0.24% vs. CONII = 1.13 ± 0.24%; mean ± SE), but the BOLD response was significantly influenced by age (partial r = -0.384, P = 0.003), supporting its sensitivity as a measure of microvascular function. Eleven individuals had no microvascular BOLD response, including three diabetics with neuropathy and four controls with a family history of diabetes. There were no differences in peripheral macrovascular function between groups when assessing exercise hyperemia or the pulsitility and resistive indexes. Although the BOLD microvascular response was not impaired in early diabetes, these results encourage further investigation of muscle BOLD as it relates to peripheral microvascular health.

Hemodynamic responses during graded and constant-load plantar flexion exercise in middle-aged men and women with type 2 diabetes

“…These results are in agreement with significantly reduced steady-state LBF responses during submaximal cycling (15) and leg-extension exercise (16) in humans with T2D. In contrast, Womack et al reported similar large artery or capillary recruitment to submaximal handgrip exercise in uncomplicated diabetes (49), and Slade et al showed similar single dorsiflexion exercise induced peak muscle blood oxygen leveldependent magnetic resonance imaging signals (39). Also, in diabetic animal models, unaltered LBF responses (5) or microvascular PO 2 responses (27) were reported in GK rats and normal capillary flow responses in Zucker diabetic fatty rats (46).…”

“…Considerations for these differences include the different exercise models employed, muscle groups studied, differences in blood flow measurement techniques utilized, and the fact that the GK rat represents a nonhyperinsulinemic diabetic model, whereas human participants are typically hyperinsulinemic. In addition, tissue and/or body mass content was significantly different between those with T2D and controls in some studies (5,49) whereas others matched participants to body composition/mass (15,39).…”

Blood oxygenation level‐dependent (BOLD) MRI of human skeletal muscle at 1.5 and 3 T

“…For the evaluation of vascular and muscle diseases it is feasible and worth performing muscle BOLD measurements at higher magnetic field strengths in order to be able to detect more pronounced changes of the muscle BOLD signal time courses. For instance, it could be of value to repeat studies that have demonstrated interesting trends at 1.5 T though not reaching significance level at 3.0 T or even higher field strength to establish significance (7,21). As the availability of 3.0 T MRI devices is increasing, high field muscle BOLD MRI might improve the diagnostics of physiological and pathological alterations of peripheral limb perfusion.…”

Age Reduces Microvascular Function in the Leg Independent of Physical Activity

“…In addition capillary density is also reduced in chronic disease (11, 31) and aging (13, 14). We have previously shown an inverse relationship between age (19–58 years old) and microvascular function of the anterior compartment (AC) using MRI blood oxygen-level dependent (BOLD) (37). In agreement, contraction mediated large artery flow (rapid onset vasodilation) with brief contraction is reduced in elderly adults in the brachial and femoral artery (4, 17).…”

“…Functional MRI BOLD imaging of skeletal muscle has been used increasingly over the last decade to examine peripheral microvascular function (23, 37, 41). Skeletal muscle BOLD responses arise largely from changes in blood volume and oxygenation from small veins, i.e.…”