Spontaneous and induced diabetic microangiopathy.
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Biomedical subjects
Publications and source records attributed to R L Engerman.
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Blood viscosity was investigated in alloxan-diabetic dogs and in dogs made experimentally hyperglycemic by a galactose-rich diet. The diabetics were prospectively assigned to levels of glycemic control ranging from poor to good. After up to 5 years of study, the blood viscosity of hyperglycemic diabetic animals was significantly greater than normal at both high (100 sec-1) and low (0.1 sec-1) shear rates. Blood viscosity at the low shear rate correlated closely with fibrinogen concentration, (r = 0.75; p less than 0.02) but not with HbA1 concentration (r = 0.14) in the diabetics. Galactosemic animals likewise had elevated blood viscosity at the low shear rate, but the correlation of viscosity with fibrinogen concentration in those animals was not statistically significant (r = 0.42). Plasma viscosity tended to be elevated in both diabetes and galactosemia, but not to a statistically significant degree.
Effects of 5 years administration of an aldose reductase inhibitor (Sorbinil) on renal structure and albumin excretion were evaluated in diabetic dogs. Glycemia, estimated by frequent measurements of HbA1, glycated plasma proteins and glucosuria, was kept comparable between the placebo- and Sorbinil-treated diabetic groups. Kidney structure was evaluated using morphometric techniques by light and electron microscopy, and excretion of immunoreactive albumin was measured yearly. Placebo-treated diabetic dogs developed nephromegaly, glomerular enlargement, increased mesangial volume, and basement membrane thickening during the 5 years of study, and by the fifth year, excreted greater than normal quantities of albumin. Sorbinil treatment prevented sorbitol accumulation in erythrocytes and tended to have a similar effect in renal cortex, but had no beneficial effect on renal structure or albuminuria. Experimental galactosemia, another model of polyol over-production, failed to produce nephromegaly, glomerular enlargement, or mesangial expansion in dogs even after 5 years of galactose-feeding. The results suggest that polyol over-production and/or accumulation per se are not sufficient to account for the nephromegaly, glomerular enlargement, or increased mesangial volume observed in diabetic dogs.
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Capillary basement membrane thickening has been compared in retina, renal glomerulus, and leg muscle of dogs alloxan-diabetic 5 years and dogs experimentally galactosemic 5 years, and the effects of inhibition of aldose reductase have been examined. Basement membrane in each site became thickened as a result of either galactosemia or diabetes, but showed appreciable variation among the sites. The thickening of basement membrane in retina and muscle of galactosemic animals was similar in quantity and appearance to that seen in the diabetics, notwithstanding large differences between the two animal models with respect to tissue polyol concentrations and nonenzymatic glycation of hemoglobin and plasma protein. Aldose reductase inhibition was without influence on capillary basement membrane thickening in each tissue from dogs diabetic or galactosemic 5 years, despite substantial polyol path inhibition.
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