PERSPECTIVES IN DIABETES MICROVASCULAR FUNCTION IN HUMAN DIABETES - A PHYSIOLOGICAL PERSPECTIVE

The late complications of diabetes represent in large part microvascular dysfunction. The development of techniques to measure microvascular function has resulted in a clearer picture of the stages of development of microangiopathy and the key pathophysiological processes involved. Considerable evidence supports the hemodynamic hypothesis of pathogenesis, which argues that early insulin-dependent diabetes is characterized by increased microvascular pressure and flow. Resultant injury to the microvascular endothelium causes adaptive microvascular sclerosis contributing to a loss of vasodilatory reserve and autoregulatory capacity with increasing disease duration. High susceptibility to microangiopathy appears to be characterized by both high capillary pressure and increased permeability, although the interrelationship between these variables needs to be better defined. in normotensive non-insulin-dependent diabetes subjects, a different pattern of microvascular functional abnormalities is apparent; it is hypothesized that these differences represent the impact of a prediabetic insulin-resistant phase on microvascular behavior and may in part explain the differential expression of vascular pathology in the two major types of diabetes. The physiological framework that has been defined reveals those pivotal processes upon which scientific attention should be centered and facilitates the generation of plausible molecular and cellular mechanisms that fit the physiological facts.