Peripheral microvascular disease in diabetes

In recent years a variety of techniques have been developed fbr studying peripheral microvascular function in man, which have provided important information regarding the functional breakdown of the microcirculation in diabetes mellitus. In insulin dependent diabetes a sequence of physiological changes have been described which support the so-called haemodynamic hypothesis: control-dependent increases in capillary pressure result in microvascular sclerosis leading to limitation of hyperaemia and loss of autoregulation. Furthermore, capillary pressure appears to be especially raised in patients with incipient nephropathy who are at particular risk of microangiopathy. The limitation of maximum hyperaemia is duration related, may be observed in early childhood, and is correlated with the degree of basement membrane thickening. In contrast in normotensive non-insulin dependent patients a different array of functional disturbances are described: Capillary pressure and capillary filtration coefficient are normal whereas maximum hyperaemia is profoundly depressed even at diagnosis. This differential pattern of abnormalities arguably reflects the impact of a prediabetic insulin resistant phase on the subsequent expression of microangiopathy. An understanding of the physiological breakdown of the microcirculation in diabetes permits the generation of plausible candidate cellular and molecular mechanisms, knowledge of which will accelerate the development of protective therapy.