Diabetic ketoacidosis: new concepts and trends in pathogenesis and treatment.

New concepts concerning the pathogenesis and therapy of diabetic ketoacidosis are reviewed. The regulation of ketogenesis by intrahepatic enzymic processes and the roles of insulin deficiency or glucagon or other counterregulatory hormone excess are summarized. Major emphasis is placed on an analysis of the use of low-dose insulin regimens for the treatment of ketoacidosis. Most patients with diabetic ketoacidosis will respond to low-dose, hourly, intravenous or intramuscular regular insulin. Low doses of insulin are as effective as high doses and have fewer associated complications of hypoglycemia and hypokalemia. Phosphorus deficiency is common in diabetic ketoacidosis and hypophosphatemia usually becomes manifest within 4 to 12 h of institution of therapy. Phosphorus supplementation is now generally recommended to replete erythrocyte 2,3-diphosphoglycerate and improve oxygen delivery to tissues. Coexistent and biochemically significant lactic acidosis is a relatively infrequent complication of diabetic ketoacidosis and when present is usually due to underlying disorders associated with poor tissue perfusion.