title: Determination of personalized diabetes treatment plans using a two-delay model.
abstract: Diabetes cases worldwide have risen steadily over the past few decades, lending urgency to the search for more efficient, effective, and personalized ways to treat the disease. Current treatment strategies, however, may fail to maintain oscillations in blood glucose concentration that naturally occur multiple times per day, an important element of normal human physiology. Building upon recent successes in mathematical modeling of the human glucose-insulin system, we show that both food intake and insulin therapy likely demand increasingly precise control over insulin sensitivity if oscillations at a healthy average glucose concentration are to be maintained. We then model and describe personalized treatment options for patients with diabetes that maintain these oscillations. We predict that for a person with type II diabetes, both blood glucose levels can be controlled and healthy oscillations maintained when the patient gets an hour of daily exercise and is placed on a combination of Metformin and sulfonylurea drugs. We note that insulin therapy and an additional hour of exercise will reduce the patient׳s need for sulfonylureas. Results of a modeling analysis suggest that, with constant nutrition and controlled exercise, the blood glucose levels of a person with type I diabetes can be properly controlled with insulin infusion between 0.45 and 0.7μU/mlmin. Lastly, we note that all suggested strategies rely on existing clinical techniques and established treatment measures, and so could potentially be of immediate use in the design of an artificial pancreas.
authors.affiliation: Department of Applied Mathematics, University of Colorado, Boulder, CO 80309-0526, USA. Electronic address: Stephen.Kissler@colorado.edu.
authors.forename: S M
authors.initials: SM
authors.lastname: Kissler
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA. Electronic address: cody.cichowitz@jhmi.edu.
authors.forename: C
authors.initials: C
authors.lastname: Cichowitz
authors.affiliation: Department of Computer Science, University of Colorado, Boulder, CO 80309-0430, USA. Electronic address: srirams@colorado.edu.
authors.forename: S
authors.initials: S
authors.lastname: Sankaranarayanan
authors.affiliation: Department of Applied Mathematics, University of Colorado, Boulder, CO 80309-0526, USA. Electronic address: dmbortz@colorado.edu.
authors.forename: D M
authors.initials: DM
authors.lastname: Bortz
mesh_terms: D001683:Biological Clocks / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D008687:Metformin / Q000008:administration & dosage; D066230:Patient-Specific Modeling; D057285:Precision Medicine / Q000379:methods*; D013453:Sulfonylurea Compounds / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013453:Sulfonylurea Compounds; D008687:Metformin
keywords: Artificial pancreas; Blood glucose; Insulin sensitivity; Personalized medicine; Ultradian oscillations