Vasomotion Becomes Less Random as Diabetes Progresses in Monkeys

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 N, PreDM, and T2DM nonhuman primates. In this study, our aims were to: (i) determine the time dependence and complexity of the spectral properties of vasomotion in three metabolic groups of monkeys; (ii) examine the effects of heat-provoked vasodilatation on the power spectrum; and (iii) 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 degrees C, and under heat stimulation at 44 degrees C. Euglycemic-hyperinsulinemic clamps were performed to produce acute hyperinsulinemia. The Lempel-Ziv complexity, prediction error, and covariance complexity of five-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-to 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. In 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.