The alterations in the microvascular system of
diabetes mellitus patients are responsible for the most devastating complications of this widespread disease. In the kidney, the microangiopathy leads to thickening of the glomerular capillary basement membrane but also to the expansion of the mesangial matrix and thickening of the tubular basement membrane. Several mechanisms are implicated in the pathogenesis of diabetic renal microangiopathy. These include increased synthesis of
type IV collagen following hyperglycaemia-induced alteration of the pattern of podocyte-
integrin expression, decreased expression of
matrix metalloproteinases (
MMP-2 and 3), and increased expression of
tissue inhibitor of metalloproteinase (TIMP). An altered morphology of podocytes accompanies these basement membrane alterations. Other factors which may contribute to renal matrix accumulation include
vascular endothelial growth factor (
VEGF), since treatment with anti-
VEGF antibodies attenuates glomerular basement membrane thickening,
platelet-derived growth factor (PDGF) (B chain) and its receptor, which appear to be highly expressed in mesangial and visceral epithelial cells and might play a role in the development of
diabetic nephropathy. Also
oxygen radicals/oxidative stress may play a role in matrix accumulation in
diabetic nephropathy as
aminoguanidine, an inhibitor of the formation of
advanced glycation end-products but with
antioxidant properties, attenuates
diabetic nephropathy.
Retinal diabetic microangiopathy follows much the same principles, be it that microvascular proliferation is a distinctive
element in the retina. Nephropathy and retinopathy occur frequently but not always together, indicating that in their multifactorial pathogenesis much remains to be clarified.