Histopathological changes in diabetic neuropathy

The term diabetic nephropathy (DN) encompasses changes in the glomerular, vascular, and tubulointerstitial compartments that are associated with diabetes mellitus. In the early stages of diabetes, there is an enlargement of the glomerular tuft due to an increase in extracellular matrix and a widening of the capillary lumina, which is associated with an increased glomerular filtration rate. The characteristic features of the diabetic glomerulopathy are glomerular basement membrane (GBM) thickening and mesangial matrix widening. Increasing amounts of collagen and laminin are produced by different cells: GBM components by podocytes and mesangial matrix by mesangial cells. The nodular lesions result from the confluence of the accumulated matrix together with the disappearance of capillaries from the central mesangial areas. Another mechanism in the progression of the DN may be the herniation of the matrix-overloaded glomerular tuft outwards through the glomerular hilus. This leads to major changes in the glomerular environment, including dissociation of the juxtaglomerular apparatus with displacement of the macula densa. At an advanced stage, the most common mechanism of nephron failure may begin with envelopment of the glomerular capillaries in the Bowman's capsule, releasing an exudate that spreads around the entire glomerular circumference and expands via the glomerulotubular junction to the tubule. This leads to glomerulosclerosis and chronic tubulointerstitial damage.