Modeling Subcutaneous Absorption of Long-Acting Insulin Glargine in Type 1 Diabetes
| Autor: | Chiara Dalla Man, Claudio Cobelli, Roberto Visentin, Clemens Giegerich, Thomas Klabunde, Michele Schiavon |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male medicine.medical_specialty Long acting insulin medicine.medical_treatment 0206 medical engineering Biomedical Engineering Insulin Glargine 02 engineering and technology Models Biological Text mining Subcutaneous Absorption Diabetes mellitus Internal medicine medicine Humans Insulin Computer Simulation Absorption (logic) Randomized Controlled Trials as Topic Type 1 diabetes Insulin glargine business.industry Chemistry nutritional and metabolic diseases Middle Aged medicine.disease 020601 biomedical engineering Diabetes Mellitus Type 1 Endocrinology Female business medicine.drug |
| Zdroj: | IEEE Transactions on Biomedical Engineering. 67:624-631 |
| ISSN: | 1558-2531 0018-9294 |
| Popis: | Objective: Subcutaneous (sc) administration of long-acting insulin analogs is often employed in multiple daily injection (MDI) therapy of type 1 diabetes (T1D) to cover patient's basal insulin needs. Among these, insulin glargine 100 U/mL (Gla-100) and 300 U/mL (Gla-300) are formulations indicated for once daily sc administration in MDI therapy of T1D. A few semi-mechanistic models of sc absorption of insulin glargine have been proposed in the literature, but were not quantitatively assessed on a large dataset. The aim of this paper is to propose a model of sc absorption of insulin glargine able to describe the data and provide precise model parameters estimates with a clear physiological interpretation. Methods: Three candidate models were identified on a total of 47 and 77 insulin profiles of T1D subjects receiving a single or repeated sc administration of Gla-100 or Gla-300, respectively. Model comparison and selection were performed on the basis of their ability to describe the data and numerical identifiability. Results: The most parsimonious model is linear two-compartment and accounts for the insulin distribution between the two compartments after sc administration through parameter k . Between the two formulations, we report a lower fraction of insulin in the first versus second compartment ( k = 86% versus 94% in Gla-100 versus Gla-300, p $k_{sp}= \text{0.0013}$ versus 0.0008 min−1 in Gla-100 versus Gla-300, p $k_{a}= \text{0.0018}$ versus 0.0016 min−1 in Gla-100 versus Gla-300, p = NS), in accordance with the mechanisms of insulin glargine protraction. Conclusions: The proposed model is able to both accurately describe plasma insulin data after sc administration and precisely estimate physiologically plausible parameters. Significance: The model can be incorporated in simulation platforms potentially usable for optimizing basal insulin treatment strategies. |
| Databáze: | OpenAIRE |
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