Basement membrane reduplication and pericyte degeneration precede development of diabetic polyneuropathy and are associated with its severity

Abstract

In a recent paper, we showed that the number of endoneurial microvessels per square millimeter and the average luminal area and size distribution of these microvessels are not significantly different in sural nerves of patients with diabetes mellitus as compared to control subjects. Mural area, especially the component due to basement membrane reduplication and cellular debris, was unequivocally increased in diabetes mellitus. Because these latter changes are associated with a decrease in periendothelial cell area, we hypothesized that cellular degeneration, especially of pericytes, may account for basement membrane reduplication and increased frequency of cellular debris. In the present study, we showed that endoneurial microvessels undergo a statistically significant increase in basement membrane area, mural area, and frequency of cellular debris in diabetics without polyneuropathy and an even greater increase in diabetics with polyneuropathy. We also found that duration of diabetes mellitus was significantly associated with area occupied by reduplicated basement membrane and cellular debris, but not with mural and periendothelial area. None of the examined measurements was associated with age. Since the microvessel abnormalities we describe are already present before the development of polyneuropathy and increase with severity of polyneuropathy, it is likely that they reflect functional derangements of pericytes and microvessel function which precede and might be implicated in fiber degeneration.