Effects of mixing short- and intermediate-acting insulins on absorption course and biologic effect of short-acting preparation.

The effects of mixing short- and intermediate-acting insulins (Actrapid MC and Monotard MC) were studied in seven diabetic patients. On different days, 0.16 IU/kg of Actrapid and 0.24 IU/kg of Monotard were administered to each subject in separate injections and combined in the same syringe. Free-insulin curves and the biologic effect of insulin, assessed by the glucose-clamp technique, were compared. The absorption rate of regular insulin was higher when injected separately from the intermediate-acting preparation: the incremental areas of free insulin above basal levels, up to 90 min after the administration of the hormone, were 32 +/- 5 vs. 21 +/- 3 microU X ml-1 X min-1 (P less than .02). In the same period, glucose infused to sustain glycemia showed no significant differences (2.8 +/- 0.4 vs. 2.4 +/- 0.3 mg X kg-1 X min-1 after the administration of insulin in separate and combined injection, respectively). The difference in insulin profiles is not translated into a significant difference in glucose requirement. This might be a consequence of a flattening of the insulin dose-response curve due to insulin resistance of diabetic subjects. The slight delay in insulin action of Actrapid when mixed with Monotard is probably irrelevant in clinical practice.