Failure of Insulin Therapy to Prevent Cardiovascular Lesions in Diabetic Rats Fed an Atherogenic Diet

In previous experiments, partially depancreatized diabetic rats, fed an atherogenic diet, consistently developed higher levels of serum cholesterol and more numerous and severe cardiovascular lesions than did similarly fed non-diabetic animals. In the present experiment, insulin therapy prevented glucosuria from 80 to 95 per cent of the time in a group of diabetic rats fed an atherogenic diet. This therapeutic regimen was effective in promoting weight gain, improving food utilization, preventing ketonuria and, except during the first two weeks, in restricting the concentrations of serum cholesterol to within the same range as those of raline-treated nondiabetics. But this restriction in concentrations of serum cholesterol in the treated diabetics did not decrease the incidence or severity of their vascular lesions, as occurred when a comparable reduction of hyper-cholesterolemia had been effected by dietary methods. Moreover, within groups, individual concentrations of serum cholesterol bore no relation to the severity of vascular lesions. We conclude that in this model, factors other than concentration of serum cholesterol must be important in the pathogenesis of vascular lesions.