Vasomotion Becomes Less Random as Diabetes Progresses in Monkeys

Abstract

Objective Changes in vasomotion may precede other global indices of autonomic dysfunction that track the onset and progression of diabetes. Recently we showed that baseline spectral properties of vasomotion can discriminate among normoglycemic (N), prediabetic (PreDM), and diabetic (T2DM) nonhuman primates. In this study, our aims were 1. To determine the time-dependence and complexity of the spectral properties of vasomotion in three metabolic groups of monkeys; 2. To examine the effects of heat-provoked vasodilatation on the power spectrum; and 3. To compare the effects of exogenous insulin on the vasomotion. Materials and Methods Laser Doppler flow rates were measured from the foot in 9 N, 11 PreDM, and 7 T2DM monkeys. Baseline flow was measured at 34 °C, and under heat stimulation at 44 °C. Euglycemic, hyperinsulinemic clamps were performed to produce acute hyperinsulinemia. The Lempel-Ziv complexity, prediction error, and covariance complexity of 5-dimensional embeddings were calculated as measures of randomness. Results and Conclusions With progression of diabetes, measures of randomness of the vasomotion progressively decreased, suggesting a progressive loss of the homeostatic capacity of the peripheral circulation to respond to environmental changes. Power spectral density among T2DM animals resided mostly in the 0 – 1.45 Hz range, which excluded the cardiac component, suggesting that with progression of the disease, regulation of flow shifts toward local rather than central (autonomic) mechanisms. Heating increased all components of the spectral power in all groups. In N, insulin increased the vasomotion contributed by endothelial, neurogenic, vascular myogenic and respiratory processes but diminished that due to heart rate. By contrast, in T2DM, insulin failed to stimulate the vascular myogenic and respiratory activities, but increased the neural/endothelial and heart rate components. Interestingly, acute hyperinsulinemia resulted in no significant vasomotion changes in the chronically hyperinsulinemic PreDM, suggesting yet another form of “insulin resistance” during this stage of the disease.

Time-dependent Behavior of Microvascular Blood Flow and Oxygenation: a Predictor of Functional Outcomes

“…The decline in randomness during local warming that we see in healthy human forearm skin is consistent with that reported by Tigno et al [15] in the skin of primates. These authors have also reported that the LZ-complexity of the BF signal reduces with disease severity and is more than 30 % lower in primates with type 2 diabetes than their normoglycaemic controls [15].…”

“…These authors have also reported that the LZ-complexity of the BF signal reduces with disease severity and is more than 30 % lower in primates with type 2 diabetes than their normoglycaemic controls [15].…”

“…Studies in a primate model of diabetes have shown a reduced complexity of the BF signal using a Lempel-Ziv (L-Z) complexity algorithm [15].…”

Blunted temporal activity of microvascular perfusion heterogeneity in metabolic syndrome: a new attractor for peripheral vascular disease?

“…Essentially, the development of nonatherosclerotic PVD in OZR is defined by a loss of flexibility in the control systems contributing to the regulation of perfusion distribution in skeletal muscle, thus severely compromising the ability to effectively adapt to changing conditions. This is a particularly striking outcome and it may represent the more functionally integrated extension of a similar process identified by Tigno et al (54) in diabetic monkeys, where the randomness of arterial vasomotion was found to be dampened with disease progression. Taken together, it is not simply that we have dysfunction and can identify it in a series of reduced preparations.…”

Prospects of Laser Doppler flowmetry application in assessment of skin microcirculation in diabetes

“…Так, X. Tigno и соавт., 2011, в исследовании на макаках-резус с разными стади-ями развития СД продемонстрировали, что хаотичность вазомоций снижается при прогрессировании СД [41]. Это можно объяснить нарушением гомеостатической функции микроциркуляторной сети и утратой возмож-ности постоянного быстрого реагирования на изменения окружающей среды [42].…”