Diabetic Microangiopathy

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Abstract
The patient with growth-onset diabetes displays, quite early in the course of his disease, capillary microangiopathy. The initial lesion is thickening of the capillary basement membrane which occurs in the capillaries of the retina, glomerulus, muscle and subcutaneous tissue. For some as yet unexplained reason, capillaries in adipose tissue apparently do not show this lesion. Occasional investigations have suggested that this lesion may precede the appearance of clinical diabetes. This has led to speculation that the diabetic may have an hereditary defect in the formation or maintenance of the capillary basement membrane. As the microangiopathy becomes more severe, there is not only further thickening but reduplication of the basement membrane and, in the glomerulus, proliferation of basement membrane branches into the cytoplasm of the endothelial cell. Thus, fundamentally, diabetic capillary microangiopathy would appear to represent overproduction of basement membrane material. It is assumed that the endothelial cell is responsible for the formation of the basement membrane of the capillary. However, intimately associated with the basement membrane of many capillaries is a second cell, the pericyte. The nature of the function of this cell is not understood. Some investigators postulate that lesions of the pericyte may instigate capillary microangiopathy. Additional information is needed on the chemical nature and source of origin of the capillary basement membrane. Although current information suggests that endothelial cells or pericytes are the cells responsible for diabetic microangiopathy, diabetes mellitus is also associated with thickening of basement membranes of Bowman''s capsule of the glomerulus, renal tubules, sweat glands of skin and other nonvascular structures. An hereditary origin of basement membrane disease is appealing. However, in light of past reports of microangiopathy in patients with pancreatic diabetes and the recent production of typical nodular diabetic glomerulosclerosis in alloxan and pituitary-diabetic dogs, one must suspect that diabetic microangiopathy is due to metabolic abnormalities of the diabetic state which are very mild or not yet understood.