Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training.

Aims: To determine if type 2 diabetes mellitus (T2D) differentiates endothelial function and plasma nitrite response (a marker of nitric oxide bioavailability) during exercise in peripheral arterial disease (PAD) subjects prior to and following 3 months supervised exercise training (SET).

Methods: In subjects with T2D+PAD (n = 13) and PAD-only (n = 14), endothelial function was measured using brachial artery flow-mediated dilation. On a separate day, venous blood draws were performed at rest and 10 min following a symptom-limited graded treadmill test (SL-GXT). Plasma samples were snap-frozen for analysis of nitrite by reductive chemiluminescence. All testing was repeated following 3 months of SET.

Results: Prior to training both groups demonstrated endothelial dysfunction, which was correlated with a net decrease in plasma nitrite following a SL-GXT (p ≤ 0.05). Following SET, the PAD-only group demonstrated an improvement in endothelial function (p ≤ 0.05) and COT (p ≤ 0.05), which was related to a net increase in plasma nitrite following the SL-GXT (both p ≤ 0.05). The T2D+PAD group had none of these increases.

Conclusions: T2D in the presence of PAD attenuated improvements in endothelial function, net plasma nitrite, and COT following SET. This suggests that T2D maybe associated with an inability to endogenously increase vascular NO bioavailability to SET.