Mixtures of human intermediate and human regular insulin in type 1 diabetic patients. Evaluation of free insulin levels and insulin action on glucose metabolism after combined and separate subcutaneous administration.

Recent resorption studies in healthy subjects suggest that intermediate human zinc insulin preparations might diminish the absorption and activity of human short-acting insulin when the two insulins are administered as a single, combined preparation. This study was designed to investigate whether combined and separate administration of human zinc or human NPH insulin with soluble human insulin have different pharmacokinetic characteristics, as evaluated by glucose clamp studies and determination of free insulin levels. Eight type 1 diabetic patients received, in random order, four different, subcutaneously injected preparations of human insulin. Zinc insulin (Monotard HM, Novo-M) and protamine insulin (Protaphan HM, Novo-P) were each given with short-acting insulin (Actrapid HM, Novo-A). These insulins were administered either as a single combined preparation (MA;PA) or as two separate injections (M + A; P + A). Prior to the insulin injection euglycemia was achieved by an overnight intravenous insulin infusion. After the subcutaneous injection of insulin, glucose was monitored at 10-min intervals and euglycemia was maintained by a variable glucose infusion rate for 6 h. The total glucose infusion rate during this period was significantly lower following MA compared with M + A (total glucose infusion: 643 +/- 117 vs. 817 +/- 130 mg/kg, P = 0.009) whereas the glucose infusion rate did not differ between PA and P + A (878 +/- 122 vs. 914 +/- 118 mg/kg, NS(ABSTRACT TRUNCATED AT 250 WORDS)