Hypothesis: insulin is responsible for the vascular complications of diabetes.
It is proposed that the systemic hyperinsulinemia and hepatic portal hypoinsulinemia that occurs with conventional injectable preparations of insulin currently used in the treatment of patients with diabetes mellitus is largely responsible for the morbidity associated with this disease. Epidemiological evidence and animal experimentation strongly support systemic hyperinsulinemia as a major factor in genesis of atherosclerosis in diabetic patients. In addition, in vitro studies demonstrate a direct effect of insulin on endothelial cell and arterial smooth muscle proliferation. On the other hand, inadequate hepatic delivery of insulin is associated with overproduction of renal vasoregulatory factors leading to glomerular hyperfiltration and ultimately to glomerulosclerosis and its clinical endpoint--end-stage renal disease. In the absence of widespread success of pancreatic and islet-cell transplantation as a means to deliver insulin physiologically into the hepatic portal circulation, methods must be devised and perfected to accomplish such delivery using approaches such as orally administering insulin in intestinal-enzyme protected capsules. Until such methods of delivery are available for safe and widespread use, one should abandon the illusory goal of rigid glucose control in favor of methods that reduce insulin requirement. Along these lines, dietary restriction and aerobic exercise should be the major life style changes advised for diabetic patients. Reduction of glomerular hyperfiltration in diabetic patients can be promoted with the use of low protein diets and/or angiotensin converting enzyme inhibitors.
Gwinup
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Department of Medicine, University of California, Irvine 92717.
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D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D003925:Diabetic Angiopathies / Q000209:etiology*; D003928:Diabetic Nephropathies / Q000209:etiology; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D008954:Models, Biological
D007328:Insulin