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Variability of the metabolic effect of soluble insulin and the rapid-acting insulin analog insulin aspart.

  1. L Heinemann,
  2. C Weyer,
  3. M Rauhaus,
  4. S Heinrichs and
  5. T Heise
  1. Department of Metabolic Diseases and Nutrition, WHO Collaborating Centre for Diabetes, Heinrich-Heine University, Düsseldorf, Germany. lutz.heinemann@uni-duesseldorf.de
    Diabetes Care 1998 Nov; 21(11): 1910-1914. https://doi.org/10.2337/diacare.21.11.1910
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    Abstract

    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 AND 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.

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    November 1998, 21(11)
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    Variability of the metabolic effect of soluble insulin and the rapid-acting insulin analog insulin aspart.
    L Heinemann, C Weyer, M Rauhaus, S Heinrichs, T Heise
    Diabetes Care Nov 1998, 21 (11) 1910-1914; DOI: 10.2337/diacare.21.11.1910

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    Variability of the metabolic effect of soluble insulin and the rapid-acting insulin analog insulin aspart.
    L Heinemann, C Weyer, M Rauhaus, S Heinrichs, T Heise
    Diabetes Care Nov 1998, 21 (11) 1910-1914; DOI: 10.2337/diacare.21.11.1910
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