A trial-validated model of diabetes

  1. David M. Eddy, MD, PHD1 and
  2. Leonard Schlessinger, PHD2
  1. 1Kaiser Permanente Southern California, Pasadena, California
  2. 2Care Management Institute, Kaiser Permanente, Oakland, California
  1. Address correspondence and reprint requests to David M. Eddy, 1426 Crystal Lake Rd., Aspen, CO 81611. E-mail: eddyaspen{at}


OBJECTIVE—To build a mathematical model of the anatomy, pathophysiology, tests, treatments, and outcomes pertaining to diabetes that could be applied to a wide variety of clinical and administrative problems and that could be validated.

RESEARCH DESIGN AND METHODS—We used an object-oriented approach, differential equations, and a construct we call “features.” The level of detail and realism was determined by what clinicians considered important, by the need to distinguish clinically relevant variables, and by the level of detail used in the conduct of clinical trials.

RESULTS—The model includes the pertinent organ systems, more than 50 continuously interacting biological variables, and the major symptoms, tests, treatments, and outcomes. The level of detail corresponds to that found in general medical textbooks, patient charts, clinical practice guidelines, and designs of clinical trials. The model is continuous in time and represents biological variables continuously. As demonstrated in a companion article, the equations can simulate a variety of clinical trials and reproduce their results with good accuracy.

CONCLUSIONS—It is possible to build a mathematical model that replicates the pathophysiology of diabetes at a high level of biological and clinical detail and that can be tested by simulating clinical trials.


  • Additional information for this article can be found in an online appendix at

    L.S. holds stock in Merck and Pfizer.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    See accompanying editorial, p. 3182.

    • Accepted July 24, 2003.
    • Received February 24, 2003.
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