Diabetic glomerulosclerosis without glucose intolerance

Abstract

The pathophysiology of the microangiopathy of diabetes mellitus is poorly understood, and the relevance of carbohydrate intolerance remains uncertain. Four patients are presented with renal abnormalities suggestive of diffuse diabetic glomerulosclerosis. These patients have no evidence of carbohydrate intolerance by standard clinical technics. A familial incidence of diabetes mellitus and delayed insulin response to an oral glucose load support a classification of prediabetes or suspected diabetes mellitus for these patients. Early intercapillary nodule formation was seen in only two of the four patients. In the absence of this infrequent pathognomonic finding, an alternate approach to the diagnosis of diabetic glomerulosclerosis is suggested. Diffuse glomerular capillary basement membrane thickening, consistently present with diabetic glomerulosclerosis, is demonstrated by measurements utilizing the latex microsphere technic. The mean glomerular capillary basement membrane thickness of these patients was 4,403 Å, compared with the control value of 3,098 Å (P < 0.001). Other pathologic findings suggestive of diabetic nephropathy include efferent arteriolosclerosis and linear immunofluorescence without electron dense deposits or inflammation. Skeletal muscle capillary basement membranes of all four patients also demonstrated significant thickening. The mean value for the patients was 1,510 Å, as compared with a control value of 961 Å (P < 0.001). The importance of this muscle capillary basement membrane thickening to the diagnosis of diabetic microangiopathy is discussed. The pathologic alterations in the renal biopsy specimens and the demonstration of muscle capillary basement membrane thickening strongly suggest that diabetic glomerulosclerosis may occur in the absence of overt clinical carbohydrate intolerance.