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.

Figures

Fig. 1.

Single contraction exercise and microvascular response in the dorsiflexors. Axial MRI slice of the leg is shown: anatomical image with the dorsiflexor muscles outlined (A) and corresponding echo planar images (B) to assess muscle blood oxygen level-dependent (BOLD) microvascular responses (D and E). Force (C), muscle BOLD signal intensity (SI) with all points displayed (D), and the average BOLD response (E: this is the average transient response from D) are shown for a representative type I diabetic (left), representative type II diabetic (middle), and a type II diabetic with no BOLD response (right).

Fig. 2.

Microvascular function measured by muscle BOLD. There was no significant effect of diabetes on peak muscle BOLD response to single isometric contractions (A). Time to peak response was faster for CONII vs. DMII (*P = 0.032; B). DM, subjects with diabetes mellitus type I or II; CON, control subjects matching DM.

Fig. 3.

Muscle BOLD relation with age (P = 0.004, partial r = −0.355).

Fig. 4.

Peak muscle BOLD response for control individuals with and without a family history of diabetes. There was a trend for the group with a family history to have lower single contraction-induced BOLD responses (P = 0.08).

Fig. 5.

Vascular network of the leg showing the popliteal vessels (pop) branching into the anterior (at) and posterior (pt) tibial arteries (A; 2D time of flight MRI over 14 cm). Large artery magnitude (B) and velocity encoded phase images at rest (C) and postexercise (D: ∼2-min postexercise; E: ∼4.5 min postexercise) in the popliteal (top) and tibial arteries (bottom) acquired with magnetic resonance angiography; the phase images were used to measure large artery blood flow/large artery peripheral vascular function. Arrows in A mark the location of the images shown in B–E. Note the increased velocity (increased brightness) in the images postexercise in the popliteal and anterior tibial arteries (D and E).

Fig. 6.

Peripheral macrovascular function. Mean blood flow in the popliteal (top) and anterior tibial arteries (bottom) before and in response to dynamic dorsiflexion for DMI (left) DMII (right) and their respective controls (CONI and CONII). Group means ± SE are shown.

Fig. 7.

Group averaged cardiac gated waveforms from the anterior tibial artery before and after dynamic exercise protocol. There were no differences between the groups in the pulsatility index or the resistive index calculated from these waveforms. Group means ± SE are shown.