Factors in the pathogenesis of experimental nonketotic and ketoacidotic diabetic stupor.

Abstract

In an attempt to elucidate some of the factors responsible for the absence of significant ketosis in hyperosmolar nonketotic diabetic stupor, an experimental model was created in rats. This involved the intravenous administration of alloxan (40 mg. per kilogram) to produce moderate hyperglycemia, followed by daily hydrocortisone injections and dextrose feeding. For comparison, ketoacidotic diabetic rats and various control situations were also studied. The biochemical profiles of the nonketotic and ketoacidotic diabetic rats resembled those of their clinical counterparts, although some discrepancies were apparent. Attention was. directed at measuring plasma free fatty acid (FFA) and ketone body levels, as well as hepatic glycogen and portal and peripheral plasma immunoreactive insulin (IRI) concentrations in the diabetic and control groups. The hyperosmolar nonketotic diabetic rats were characterized by: a mean plasma FFA level intermediate between that of the controls and that of the ketotics; modest rises in 3-hydroxybutyrate and acetoacetate; and a striking elevation in hepatic glycogen concentration. In addition, their mean portal IRI value resembled that of the control animals (both significantly greater than ketotics) but their mean peripheral plasma IRI value was similar to that of the ketotics (both significantly lower than controls). It is suggested that the absence of severe ketosis in the hyperosmolar nonketotic diabetic rats was, at least in part, due to the ability of their glycogen-rich, ‘insulinized’ livers to metabolize incoming FFA largely along nonketogenic pathways. The relevance of these findings to the clinical situation is briefly considered.