Lesions specific for diabetes have been observed in the arterioles and capillaries of the foot and other organs that are the typical targets of diabetic chronic complications.
From: Contemporary Diabetes: Diabetic Neuropathy: Clinical Management, Second Edition Edited by: A. Veves and R. Malik © Humana Press Inc., Totowa, NJ
A contemporary historical histological study demonstrated the presence of PAS-positive material in the arterioles of amputated limb specimens from patients with diabetes (1). Although it was believed for several years that the anatomic changes described were occlusive in nature, in 1984, Logerfo and Coffmann (2) recognized that in patients with diabetes, there is no evidence of an occlusive microvascular disease. Subsequent prospective anatomic staining and arterial casting studies have demonstrated the absence of an arteriolar occlusive lesion thus dispelling the hopeless notion of diabetic "occlusive small vessel disease" (3,4).
Although there is no occlusive lesion in the diabetic microcirculation, other structural changes do exist. The thickening of the capillary basement membrane is the dominant structural change in both diabetic retinopathy and neuropathy and is because of an increase in the extracellular matrix. It might represent a response to the metabolic changes related to diabetes and hyperglycemia. However, this alteration does not lead to occlusion of the capillary lumen, and arteriolar blood flow might be normal or even increased despite these changes (5). On the contrary, it might act as a barrier to the exchange of nutrients and/or increase the rigidity of the vessels further limiting their ability to dilate in response to different stimuli (6).
In the kidney, nonenzymatic glycosylation reduces the charge on the basement membrane, which might account for transudation of albumin, an expanded mesangium, and albuminuria (7). Similar increases in vascular permeability occur in the eye and probably contribute to macular exudate formation and retinopathy (8). In simplest terms, micro-vascular structural alterations in diabetes result in an increased vascular permeability and impaired autoregulation of blood flow and vascular tone.
Many studies have identified a correlation between the development of diabetic chronic complication and metabolic control with perhaps the strongest evidence coming from the Diabetes Control and Complications Trial (DCCT), which enrolled patients with type 1 diabetes, and the United Kingdom Prospective Diabetes Study (UKPDS), which enrolled patients with type 2 diabetes (9,10). The results from both clinical trials clearly showed a delay in the development and progression of retinopathy, nephropathy, and neuropathy with intensive glycemic control, thus supporting the direct causal relationship between hyperglycemia and microcirculation impairment. This was less evident for macrovascular disease, assessed only in the UKPDS.
Although the structural alterations observed in the microcirculation do not affect the basal blood flow, some functional abnormalities of the microvascular circulation that might eventually result in a relative ischemia have been extensively documented. This aspect will be deeply discussed in the "Pathophysiology of microvascular disease and endothelial dysfunction in diabetes" section.
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