Incorporating a generic model of subcutaneous insulin absorption into the AIDA v4 diabetes simulator. 3. Early plasma insulin determinations.

INTRODUCTION: AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described. METHODS: This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done. RESULTS: Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as well as for insulin doses up to 50 IU. DISCUSSION: The methodology to be adopted for implementing the generic absorption model within AIDA has been overviewed, and the first plasma insulin profiles based on this approach have been demonstrated. Ideas for future work and development are discussed. It is expected that an updated release of AIDA (v4.5), based on this collaborative approach, will become available for free--in due course--via the www.2aida.org Web site. Readers who wish to be informed when the new software is launched can join the very low volume AIDA announcement list by sending a blank email note to subscribe@2aida.org.

Incorporating a generic model of subcutaneous insulin absorption into the AIDA v4 diabetes simulator: 1. a prospective collaborative development plan.

INTRODUCTION: AIDA v4 is an interactive educational diabetes simulator that has been made available, for over a decade, without charge via the Internet. The software is currently freely accessible at http://www.2aida.org. This report sets out a collaborative development plan to enhance the program with a new model of subcutaneous insulin absorption, which permits the simulation of rapidly acting and very long-acting insulin analogues, as well as insulin injection doses larger than 40 units. METHODS: A novel, generic, physiological subcutaneous insulin absorption model is overviewed and a methodology is proposed by which this can be substituted in place of the previously adopted insulin absorption model utilized within AIDA v4.3a. Apart from this substitution it is proposed to retain the existing model of the glucoregulatory system currently used in AIDA v4.3a. RESULTS: Initial simulation results based on bench testing of this approach using MATLAB are presented for the exogenous insulin flow profile (I(ex)) following subcutaneous injections of a rapidly acting insulin analogue, a short-acting (regular) insulin preparation, intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue. DISCUSSION: It is proposed to implement this collaborative development plan-first by bench testing the approach in MATLAB and then by integrating the generic subcutaneous insulin absorption I(ex) model into the AIDA simulator in Pascal. The aim is to provide enhanced functionality and educational simulations of regimens utilizing novel insulin analogues, as well as injections larger than 40 units of insulin.

Incorporating a generic model of subcutaneous insulin absorption into the AIDA v4 diabetes simulator: 2. preliminary bench testing.

BACKGROUND: The AIDA interactive educational diabetes simulator has been available without charge for over a decade via the Internet (see www.2aida.org). Part 1 of this report [J Diabetes Sci Technol. 2007;1(3):423-35] described the model components to be integrated to enhance the utility of the software, with the aim being to provide enhanced functionality and educational simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 units. This report provides some preliminary subcutaneous insulin absorption bench testing results for the updated modeling prototype. METHODS: An analysis has been done of the spatial distribution of insulin in the region of the injection site for different classes of insulin preparations and times after the administration of a set insulin injection. Demonstrations of the proportion of residual insulin in depot versus time after a subcutaneous bolus have also been simulated for different insulin injection volumes and concentrations, as well as to show the proportions of hexameric, dimeric, and bound insulin over time after an injection. RESULTS: Some early bench testing results are highlighted following subcutaneous injections of a rapidly acting insulin analogue (such as lispro/Humalog or aspart/NovoLog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (such as glargine/Lantus). The transformation, dissociation/association, and absorption processes by which insulin moves from the subcutaneous injection site to the plasma are also illustrated. DISCUSSION: This report demonstrates how enhanced capabilities may be added to AIDA once a new model of subcutaneous insulin absorption is incorporated. The revised approach, once fully implemented, should permit the simulation of plasma insulin profiles for rapidly acting and very long-acting insulin analogues, as well as insulin injections greater than 40 units.