Ridout Sean A, Vellanki Priyathama, Nemenman Ilya
Department of Physics, Emory University, Atlanta, United States.
Initiative in Theory and Modeling of Living Systems, Emory University, Atlanta, United States.
Elife. 2025 Jul 15;13:RP100193. doi: 10.7554/eLife.100193.
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.
酮症倾向型糖尿病（KPD）是2型糖尿病的一种亚型，其表现与1型糖尿病非常相似，伴有严重的高血糖和酮症酸中毒。虽然KPD患者最初依赖胰岛素，但经过几个月的胰岛素治疗后，大约70%的患者会出现近正常血糖缓解，并且可以像早期2型糖尿病或糖尿病前期患者一样，在不使用胰岛素的情况下维持血糖水平。在此，我们提出这些现象可以通过一种快速、可逆的糖毒性过程的存在来解释，这种过程可能存在于所有人中，但在易患KPD的人群中更为明显。我们建立了一个包含这一假设的KPD发病机制的简单数学模型，并表明它再现了KPD的现象学，包括患者实现和维持缓解能力的变化。这些结果表明，我们模型的一个变体可能能够定量描述KPD个体缓解过程中的变化。
