Application of Multiscale Entropy in Assessing Plantar Skin Blood Flow Dynamics in Diabetics with Peripheral Neuropathy

Diabetic foot ulcer (DFU) is a common complication of diabetes mellitus, while tissue ischemia caused by impaired vasodilatory response to plantar pressure is thought to be a major factor of the development of DFUs, which has been assessed using various measures of skin blood flow (SBF) in the time or frequency domain. These measures, however, are incapable of characterizing nonlinear dynamics of SBF, which is an indicator of pathologic alterations of microcirculation in the diabetic foot. This study recruited 18 type 2 diabetics with peripheral neuropathy and eight healthy controls. SBF at the first metatarsal head in response to locally applied pressure and heating was measured using laser Doppler flowmetry. A multiscale entropy algorithm was utilized to quantify the regularity degree of the SBF responses. The results showed that during reactive hyperemia and thermally induced biphasic response, the regularity degree of SBF in diabetics underwent only small changes compared to baseline and significantly differed from that in controls at multiple scales (p < 0.05). On the other hand, the transition of regularity degree of SBF in diabetics distinctively differed from that in controls (p < 0.05). These findings indicated that multiscale entropy could provide a more comprehensive assessment of impaired microvascular reactivity in the diabetic foot compared to other entropy measures based on only a single scale, which strengthens the use of plantar SBF dynamics to assess the risk for DFU.