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Publication in JClinPharmacol supported by DDMoRe

Modeling of 24-Hour Glucose and Insulin Profiles in Patients With Type 2 Diabetes Mellitus Treated With Biphasic Insulin Aspart.

Rikke M. Røge, Søren Klim, Niels R. Kristensen, Steen H. Ingwersen, and Maria C. Kjellsson.


Insulin therapy for diabetes patients is designed to mimic the endogenous insulin response of healthy subjects and thereby generate normal blood glucose levels. In order to control the blood glucose in insulin-treated diabetes patients, it is important to be able to predict the effect of exogenous insulin on blood glucose. A pharmacokinetic/pharmacodynamic model for glucose homoeostasis describing the effect of exogenous insulin would facilitate such prediction. Thus the aim of this work was to extend the previously developed integrated glucose-insulin (IGI) model to predict 24-hour glucose profiles for patients with Type 2 diabetes following exogenous insulin administration. Clinical data from two trials were included in the analysis. In both trials, 24-hour meal tolerance tests were used as the experimental setup, where exogenous insulin (biphasic insulin aspart) was administered in relation to meals. The IGI model was successfully extended to include the effect of exogenous insulin. Circadian variations in glucose homeostasis were assessed on relevant parameters, and a significant improvement was achieved by including a circadian rhythm on the endogenous glucose production in the model. The extended model is a useful tool for clinical trial simulation and for elucidating the effect profile of new insulin product.

Work package: 

Associated members

Maria Kjellsson's picture
Maria Kjellsson
Uppsala Universitet
Niels Rode Kristensen's picture
Niels Rode Kris...
Novo Nordisk
Rikke Meldgaard Røge's picture
Rikke Meldgaard Røge
Novo Nordisk
Steen Hvass Ingwersen's picture
Steen Hvass Ing...
Novo Nordisk