VARIABILITY OF THE METABOLIC EFFECT OF SOLUBLE INSULIN AND THE RAPID-ACTING INSULIN ANALOG INSULIN ASPART

OBJECTIVE - To study the intra- and interindividual variability of the metabolic activity of soluble insulin and of the rapid-acting insulin analog insulin aspart after subcutaneous injection. RESEARCH DESIGN A ND METHODS - A total of nine healthy male volunteers received subcutan eous injections of soluble insulin (0.2 U/kg) in the abdominal region on each of the four study days. Another 10 volunteers received an inje ction of insulin aspart four times. Glucose infusion rates necessary t o neutralize the blood glucose-lowering effect of the administered ins ulin were registered during euglycemic glucose clamps (blood glucose 5 .0 mmol/l; basal intraveneous insulin infusion 0.15 mU.kg(-1).min(-1)) over the subsequent 600 min. We investigated the variation in metabol ic activity by calculating coefficients of variation (CVs). RESULTS - In comparison to soluble insulin, subcutaneous injections of insulin a spart led to a more rapid onset of action and a shorter duration of ac tion. Subcutaneous injection of the insulin preparations resulted in i ntraindividual CVs of the summary measures between 10 and 30% (soluble insulin vs. insulin aspart: maximal metabolic activity 15 +/- 7 vs. 1 6 +/- 10%, time to maximal metabolic activity 14 +/- 10 vs. 11 +/- 6%; NS between the preparations [means +/- SD]). The decline to half-maxi mal activity after maximal activity showed a lower intraindividual CV with insulin aspart (19 +/- 9 vs. 11 +/- 5%; P = 0.018). The interindi vidual CVs were higher than the intraindividual CVs (26 vs. 28, 23 vs. 19, and 26 vs. 17%). Generally, the pharmacodynamic variability was h igher than the pharmacokinetic variability. For the pharmacokinetic me asures, the intra- and interindividual variability in t(max) was lower for insulin aspart than for soluble insulin. CONCLUSIONS - The metabo lic effect of soluble insulin shows an intraindividual variability of 10-20% in healthy volunteers, even under strictly controlled experimen tal conditions. The overall variability of action of insulin aspart wa s comparable to that of soluble insulin.