A mathematical model for ketosis-prone diabetes suggests the existence of multiple pancreatic β-cell inactivation mechanisms
Ketosis-prone diabetes mellitus (KPD) is a subtype of type 2 diabetes, which presents much like type 1 diabetes, with dramatic hyperglycemia and ketoacidosis. Although KPD patients are initially insulin-dependent, after a few months of insulin treatment, roughly 70% undergo near-normoglycemia remiss...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-07-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/100193 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849469696738328576 |
|---|---|
| author | Sean A Ridout Priyathama Vellanki Ilya Nemenman |
| author_facet | Sean A Ridout Priyathama Vellanki Ilya Nemenman |
| author_sort | Sean A Ridout |
| collection | DOAJ |
| description | Ketosis-prone diabetes mellitus (KPD) is a subtype of type 2 diabetes, which presents much like type 1 diabetes, with dramatic hyperglycemia and ketoacidosis. Although KPD patients are initially insulin-dependent, after a few months of insulin treatment, roughly 70% undergo near-normoglycemia remission and can maintain blood glucose without insulin, as in early type 2 diabetes or prediabetes. Here, we propose that these phenomena can be explained by the existence of a fast, reversible glucotoxicity process, which may exist in all people but be more pronounced in those susceptible to KPD. We develop a simple mathematical model of the pathogenesis of KPD, which incorporates this assumption, and show that it reproduces the phenomenology of KPD, including variations in the ability for patients to achieve and sustain remission. These results suggest that a variation of our model may be able to quantitatively describe variations in the course of remission among individuals with KPD. |
| format | Article |
| id | doaj-art-8d397b2c1d3c4ce0a919833414de7230 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-8d397b2c1d3c4ce0a919833414de72302025-08-20T03:25:23ZengeLife Sciences Publications LtdeLife2050-084X2025-07-011310.7554/eLife.100193A mathematical model for ketosis-prone diabetes suggests the existence of multiple pancreatic β-cell inactivation mechanismsSean A Ridout0https://orcid.org/0000-0003-2387-8361Priyathama Vellanki1https://orcid.org/0000-0002-6544-015XIlya Nemenman2https://orcid.org/0000-0003-3024-4244Department of Physics, Emory University, Atlanta, United States; Initiative in Theory and Modeling of Living Systems, Emory University, Atlanta, United StatesDepartment of Internal Medicine, Division of Endocrinology, Emory University School of Medicine, Emory University, Atlanta, United States; Grady Health System, Atlanta, United StatesDepartment of Physics, Emory University, Atlanta, United States; Initiative in Theory and Modeling of Living Systems, Emory University, Atlanta, United States; Department of Biology, Emory University, Atlanta, United StatesKetosis-prone diabetes mellitus (KPD) is a subtype of type 2 diabetes, which presents much like type 1 diabetes, with dramatic hyperglycemia and ketoacidosis. Although KPD patients are initially insulin-dependent, after a few months of insulin treatment, roughly 70% undergo near-normoglycemia remission and can maintain blood glucose without insulin, as in early type 2 diabetes or prediabetes. Here, we propose that these phenomena can be explained by the existence of a fast, reversible glucotoxicity process, which may exist in all people but be more pronounced in those susceptible to KPD. We develop a simple mathematical model of the pathogenesis of KPD, which incorporates this assumption, and show that it reproduces the phenomenology of KPD, including variations in the ability for patients to achieve and sustain remission. These results suggest that a variation of our model may be able to quantitatively describe variations in the course of remission among individuals with KPD.https://elifesciences.org/articles/100193ketosis-prone diabetes mellitusdiabetes remissiondiabetes pathogenesismathematical modelingglucotoxicity |
| spellingShingle | Sean A Ridout Priyathama Vellanki Ilya Nemenman A mathematical model for ketosis-prone diabetes suggests the existence of multiple pancreatic β-cell inactivation mechanisms eLife ketosis-prone diabetes mellitus diabetes remission diabetes pathogenesis mathematical modeling glucotoxicity |
| title | A mathematical model for ketosis-prone diabetes suggests the existence of multiple pancreatic β-cell inactivation mechanisms |
| title_full | A mathematical model for ketosis-prone diabetes suggests the existence of multiple pancreatic β-cell inactivation mechanisms |
| title_fullStr | A mathematical model for ketosis-prone diabetes suggests the existence of multiple pancreatic β-cell inactivation mechanisms |
| title_full_unstemmed | A mathematical model for ketosis-prone diabetes suggests the existence of multiple pancreatic β-cell inactivation mechanisms |
| title_short | A mathematical model for ketosis-prone diabetes suggests the existence of multiple pancreatic β-cell inactivation mechanisms |
| title_sort | mathematical model for ketosis prone diabetes suggests the existence of multiple pancreatic β cell inactivation mechanisms |
| topic | ketosis-prone diabetes mellitus diabetes remission diabetes pathogenesis mathematical modeling glucotoxicity |
| url | https://elifesciences.org/articles/100193 |
| work_keys_str_mv | AT seanaridout amathematicalmodelforketosispronediabetessuggeststheexistenceofmultiplepancreaticbcellinactivationmechanisms AT priyathamavellanki amathematicalmodelforketosispronediabetessuggeststheexistenceofmultiplepancreaticbcellinactivationmechanisms AT ilyanemenman amathematicalmodelforketosispronediabetessuggeststheexistenceofmultiplepancreaticbcellinactivationmechanisms AT seanaridout mathematicalmodelforketosispronediabetessuggeststheexistenceofmultiplepancreaticbcellinactivationmechanisms AT priyathamavellanki mathematicalmodelforketosispronediabetessuggeststheexistenceofmultiplepancreaticbcellinactivationmechanisms AT ilyanemenman mathematicalmodelforketosispronediabetessuggeststheexistenceofmultiplepancreaticbcellinactivationmechanisms |