Abstract
In this paper, we investigate the disruption of the glucose homeostasis at the whole-body level by the presence of cancer disease. Of particular interest are the potentially different responses of patients with or without hyperglycemia (including diabetes mellitus) to the cancer challenge, and how tumor growth, in turn, responds to hyperglycemia and its medical management. We propose a mathematical model that describes the competition between cancer cells and glucose-dependent healthy cells for a shared glucose resource. We also include the metabolic reprogramming of healthy cells by cancer-cell-initiated mechanism to reflect the interplay between the two cell populations. We parametrize this model and carry out numerical simulations of various scenarios, with growth of tumor mass and loss of healthy body mass as endpoints. We report sets of cancer characteristics that show plausible disease histories. We investigate parameters that change cancer cells’ aggressiveness, and we exhibit differing responses in diabetic and non-diabetic, in the absence or presence of glycemic control. Our model predictions are in line with observations of weight loss in cancer patients and the increased growth (or earlier onset) of tumor in diabetic individuals. The model will also aid future studies on countermeasures such as the reduction of circulating glucose in cancer patients.
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Acknowledgements
Jonathan Doria and Chinh Nguyen received awards from the Support for Undergraduate Research Fellows (SURF) program at the University of Wisconsin—Milwaukee. Noah Salentine was supported by the Ronald E. McNair Postbaccalaureate Achievement Program at the University of Wisconsin—Milwaukee. Shizhen Emily Wang was partially supported by the National Institutes of Health grants R01CA218140 and R01CA266486. The funding bodies had no influence on study design, collection, analysis and interpretation of results. We thank Dr. Wei Ying (University of California San Diego) and two unknown readers for valuable comments.
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Dedicated to Professor Glenn Webb in honor of his 80th birthday.
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Salentine, N., Doria, J., Nguyen, C. et al. A Mathematical Model of the Disruption of Glucose Homeostasis in Cancer Patients. Bull Math Biol 85, 58 (2023). https://doi.org/10.1007/s11538-023-01146-3
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DOI: https://doi.org/10.1007/s11538-023-01146-3