SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function
Abstract Modelling insulin-glucose homeostasis may provide novel functional insights. In particular, simple models are clinically useful if they yield diagnostic methods. Examples include the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). However,...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-10-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22531-3 |
| _version_ | 1811336188220407808 |
|---|---|
| author | Johannes W. Dietrich Riddhi Dasgupta Shajith Anoop Felix Jebasingh Mathews E. Kurian Mercy Inbakumari Bernhard O. Boehm Nihal Thomas |
| author_facet | Johannes W. Dietrich Riddhi Dasgupta Shajith Anoop Felix Jebasingh Mathews E. Kurian Mercy Inbakumari Bernhard O. Boehm Nihal Thomas |
| author_sort | Johannes W. Dietrich |
| collection | DOAJ |
| description | Abstract Modelling insulin-glucose homeostasis may provide novel functional insights. In particular, simple models are clinically useful if they yield diagnostic methods. Examples include the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). However, limitations of these approaches have been criticised. Moreover, recent advances in physiological and biochemical research prompt further refinement in this area. We have developed a nonlinear model based on fundamental physiological motifs, including saturation kinetics, non-competitive inhibition, and pharmacokinetics. This model explains the evolution of insulin and glucose concentrations from perturbation to steady-state. Additionally, it lays the foundation of a structure parameter inference approach (SPINA), providing novel biomarkers of carbohydrate homeostasis, namely the secretory capacity of beta-cells (SPINA-GBeta) and insulin receptor gain (SPINA-GR). These markers correlate with central parameters of glucose metabolism, including average glucose infusion rate in hyperinsulinemic glucose clamp studies, response to oral glucose tolerance testing and HbA1c. Moreover, they mirror multiple measures of body composition. Compared to normal controls, SPINA-GR is significantly reduced in subjects with diabetes and prediabetes. The new model explains important physiological phenomena of insulin-glucose homeostasis. Clinical validation suggests that it may provide an efficient biomarker panel for screening purposes and clinical research. |
| first_indexed | 2024-04-13T17:35:50Z |
| format | Article |
| id | doaj.art-1df77cd608df4a5c94db768118ef7837 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T17:35:50Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1df77cd608df4a5c94db768118ef78372022-12-22T02:37:21ZengNature PortfolioScientific Reports2045-23222022-10-0112111310.1038/s41598-022-22531-3SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell functionJohannes W. Dietrich0Riddhi Dasgupta1Shajith Anoop2Felix Jebasingh3Mathews E. Kurian4Mercy Inbakumari5Bernhard O. Boehm6Nihal Thomas7Diabetes, Endocrinology and Metabolism Section, Department of Internal Medicine I, St. Josef Hospital, Ruhr University Bochum, NRWDepartment of Endocrinology, Diabetes and Metabolism, Christian Medical CollegeDepartment of Endocrinology, Diabetes and Metabolism, Christian Medical CollegeDepartment of Endocrinology, Diabetes and Metabolism, Christian Medical CollegeDepartment of Endocrinology, Diabetes and Metabolism, Christian Medical CollegeDepartment of Endocrinology, Diabetes and Metabolism, Christian Medical CollegeLee Kong Chian School of Medicine, Nanyang Technological University SingaporeDepartment of Endocrinology, Diabetes and Metabolism, Christian Medical CollegeAbstract Modelling insulin-glucose homeostasis may provide novel functional insights. In particular, simple models are clinically useful if they yield diagnostic methods. Examples include the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). However, limitations of these approaches have been criticised. Moreover, recent advances in physiological and biochemical research prompt further refinement in this area. We have developed a nonlinear model based on fundamental physiological motifs, including saturation kinetics, non-competitive inhibition, and pharmacokinetics. This model explains the evolution of insulin and glucose concentrations from perturbation to steady-state. Additionally, it lays the foundation of a structure parameter inference approach (SPINA), providing novel biomarkers of carbohydrate homeostasis, namely the secretory capacity of beta-cells (SPINA-GBeta) and insulin receptor gain (SPINA-GR). These markers correlate with central parameters of glucose metabolism, including average glucose infusion rate in hyperinsulinemic glucose clamp studies, response to oral glucose tolerance testing and HbA1c. Moreover, they mirror multiple measures of body composition. Compared to normal controls, SPINA-GR is significantly reduced in subjects with diabetes and prediabetes. The new model explains important physiological phenomena of insulin-glucose homeostasis. Clinical validation suggests that it may provide an efficient biomarker panel for screening purposes and clinical research.https://doi.org/10.1038/s41598-022-22531-3 |
| spellingShingle | Johannes W. Dietrich Riddhi Dasgupta Shajith Anoop Felix Jebasingh Mathews E. Kurian Mercy Inbakumari Bernhard O. Boehm Nihal Thomas SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function Scientific Reports |
| title | SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function |
| title_full | SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function |
| title_fullStr | SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function |
| title_full_unstemmed | SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function |
| title_short | SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function |
| title_sort | spina carb a simple mathematical model supporting fast in vivo estimation of insulin sensitivity and beta cell function |
| url | https://doi.org/10.1038/s41598-022-22531-3 |
| work_keys_str_mv | AT johanneswdietrich spinacarbasimplemathematicalmodelsupportingfastinvivoestimationofinsulinsensitivityandbetacellfunction AT riddhidasgupta spinacarbasimplemathematicalmodelsupportingfastinvivoestimationofinsulinsensitivityandbetacellfunction AT shajithanoop spinacarbasimplemathematicalmodelsupportingfastinvivoestimationofinsulinsensitivityandbetacellfunction AT felixjebasingh spinacarbasimplemathematicalmodelsupportingfastinvivoestimationofinsulinsensitivityandbetacellfunction AT mathewsekurian spinacarbasimplemathematicalmodelsupportingfastinvivoestimationofinsulinsensitivityandbetacellfunction AT mercyinbakumari spinacarbasimplemathematicalmodelsupportingfastinvivoestimationofinsulinsensitivityandbetacellfunction AT bernhardoboehm spinacarbasimplemathematicalmodelsupportingfastinvivoestimationofinsulinsensitivityandbetacellfunction AT nihalthomas spinacarbasimplemathematicalmodelsupportingfastinvivoestimationofinsulinsensitivityandbetacellfunction |