Dogs were made alloxan-diabetic and randomly distributed into either of two prospective treatment groups. In one group it was intended that the metabolic signs of diabetes be controlled poorly, and commercial insulin was administered in doses inadequate to prevent chronic, severe hyperglycemia and glucosuria. In the other group it was intended that the metabolic disorder be well controlled, and the animals received food and commercial insulin twice daily such that the hyperglycemia and glucosuria became mild or infrequent. Experimental improvement of the carbohydrate disorder was accompanied by amelioration of hyperlipemia and other clinical signs of deficient insulin activity. By 60 months of diabetes, retinal capillary aneurysms, pericyte ghosts, obliterated vessels, and other microvascular abnormalities typical of diabetes were apparent in each animal of the poor-control group. Better control was found to reduce significantly the incidence and severity of microvascular lesions. The data suggest that the mechanism responsible for diabetic retinopathy is initiated as a result of deficient insulin activity and that the development of the microvascular complications of diabetes are preventable and may be inhibited by careful control of the metabolic disorder.

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With the advent of adequate replacement therapy for diabetes mellitus and the subsequent prolongation of life, degenerative vascular disease has become a problem of paramount importance. Unfortunately the study of degenerative vascular disease is complicated by its chronicity. The nodular glomerular lesions described by Kimmelstiel and Wilson in 1936 remain obscure in origin, but—if critical histologic criteria are met—represent a form of degenerative vascular disease seen only in patients with diabetes mellitus. The study of these lesions as well as of degenerative vascular disease in general would benefit greatly by the availability of an experimental method for the rapid production of diabetic glomerulosclerosis. In 1951 Rich et al reported that rabbits treated with cortisone for three weeks developed nodular glomerular lesions. Following this report we undertook the study of glomerular changes produced by the administration of various adrenal CQrtical steroids in the hope that we might produce typical diabetic glomerulosclerosis.

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