Use of a novel double-antibody technique to describe the pharmacokinetics of rapid-acting insulin analogs.
OBJECTIVE
To measure the contribution of bedtime intermediate-acting human insulin on the morning plasma insulin profiles after injection of the rapid-acting insulin analogs lispro and aspart in patients with type 1 diabetes.


METHODS
A total of 14 patients with type 1 diabetes, aged 35 +/- 13 years (mean +/- SD), participated in this single-blind, randomized crossover study. After taking their usual injection of human intermediate-acting insulin the night before, they were given insulin aspart or insulin lispro (10 units) before a standardized breakfast. The contribution of continuing absorption of the human insulin was measured using a monoclonal antibody not cross-reacting with insulin aspart or lispro, whereas the contribution of the analogs was estimated by subtraction after measurement of all plasma free insulin using an antibody cross-reacting equally with human insulin and both analogs.


RESULTS
The correlation coefficient of the fasting free insulin concentrations measured with both insulin methods was 0.95. Fasting free insulin was 95 +/- 25 pmol/l before administration of insulin aspart, when determined with enzyme-linked immunosorbent assay detecting only human insulin, and 71 +/- 20 pmol/l before administration of insulin lispro (NS). Both insulin analogs gave marked peaks of free insulin concentrations, lispro at 40 +/- 3 min and aspart at 55 +/- 6 min after injection (P = 0.01). The later part of the profiles, from 4.5 to 5.5 h after injection, were similar and showed almost no contribution of the insulin analogs.


CONCLUSIONS
The combination of insulin assays that detect human insulin only or both human insulin and analogs provides a new tool for studying insulin pharmacokinetics. Using this technique, we showed that 4.5 h after administration of the rapid-acting insulin analogs lispro and aspart, the free insulin levels are almost only attributable to the intermediate-acting insulin given at bedtime.
Lindström
Torbjörn
T
Division of Internal Medicine, Department of Medicine and Care, University Hospital, Linköping University, Linköping, Sweden. torbjorn.lindstrom@lio.se
Hedman
Christina A
CA
Arnqvist
Hans J
HJ
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007328:Insulin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061267:Insulin Aspart; D061268:Insulin Lispro; D007700:Kinetics; D008297:Male; D016037:Single-Blind Method
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D061267:Insulin Aspart