A pharmacokinetic model of the insulin-glucose system was used to examine the effectiveness of insulin administered by a variety of routes and regimens for diabetic ketoacidosis. The blood plasma concentration of glucose was set at 1,000 mg. per dl., and the effects of the following insulin regimens on the glucose plasma level were compared: low dose (90mU. per kg. per hr.) administered by hourly intramuscular injection, constant-rate infusion, hourly intravenous bolus, constant-rate infusion with intravenous loading dose, and high dose (2 U. per kg.) with half given as an intravenous bolus and the remainder administered subcutaneously. Computer simulations showed that the high-dose regimen reduced the plasma glucose concentration rapidly to a hypoglycemic level (< 34 mg. per dl. at three hours postadministration). The low-dose regimens reduced the plasma glucose level more slowly than did the high-dose regimen. Differences among the low-dose regimens were noted. The initial decline of the plasma glucose level was relatively slow with both the intramuscular and constant-rate infusion regimens. An additional problem with the intramuscular regimen was the accumulation of insulin at sites of administration. This accumulation could make judgment of the appropriate time to discontinue insulin difficult. Both the hourly intravenous bolus and the constant-rate infusion with loading-dose regimens caused a prompt decline in the plasma glucose level. Their potential for causing hypoglycemia was low provided insulin was discontinued when the plasma glucose level reached 180 mg. per dl.

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