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.


METHODS
A total of nine healthy male volunteers received subcutaneous injections of soluble insulin (0.2 U/kg) in the abdominal region on each of the four study days. Another 10 volunteers received an injection of insulin aspart four times. Glucose infusion rates necessary to neutralize the blood glucose-lowering effect of the administered insulin were registered during euglycemic glucose clamps (blood glucose 5.0 mmol/l; basal intravenous insulin infusion 0.15 mU x kg(-1) x min(-1) over the subsequent 600 min. We investigated the variation in metabolic activity by calculating coefficients of variation (CVs).


RESULTS
In comparison to soluble insulin, subcutaneous injections of insulin aspart led to a more rapid onset of action and a shorter duration of action. Subcutaneous injection of the insulin preparations resulted in intraindividual CVs of the summary measures between 10 and 30% (soluble insulin vs. insulin aspart: maximal metabolic activity 15+/-7 vs. 16+/-10%, time to maximal metabolic activity 14+/-10 vs. 11+/-6%; NS between the preparations [means +/- SD]). The decline to half-maximal activity after maximal activity showed a lower intraindividual CV with insulin aspart (19+/-9 vs. 11+/-5%; P = 0.018). The interindividual CVs were higher than the intraindividual CVs (26 vs. 28, 23 vs. 19, and 26 vs. 17%). Generally, the pharmacodynamic variability was higher than the pharmacokinetic variability. For the pharmacokinetic measures, the intra- and interindividual variability in t(max) was lower for insulin aspart than for soluble insulin.


CONCLUSIONS
The metabolic effect of soluble insulin shows an intraindividual variability of 10-20% in healthy volunteers, even under strictly controlled experimental conditions. The overall variability of action of insulin aspart was comparable to that of soluble insulin.
Heinemann
L
L
Department of Metabolic Diseases and Nutrition, WHO Collaborating Centre for Diabetes, Heinrich-Heine University, Düsseldorf, Germany. lutz.heinemann@uni-duesseldorf.de
Weyer
C
C
Rauhaus
M
M
Heinrichs
S
S
Heise
T
T
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061267:Insulin Aspart; D008297:Male; D015203:Reproducibility of Results; D012995:Solubility
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart