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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/E1462    most recent 90444.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by De Gaetano, A. Articles by Pørksen, N. Search for Related Content PubMed PubMed Citation Articles by De Gaetano, A. Articles by Pørksen, N.

Mathematical models of diabetes progression

¹Consiglio Nazionale delle Ricerche, Istituto di Analisi dei Sistemi ed Informatica "A. Ruberti," Rome, Italy; ²Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana; and ³Axiosis Sprl, Bousval, Belgium

Submitted 16 May 2008 ; accepted in final form 24 August 2008

Few attempts have been made to model mathematically the progression of type 2 diabetes. A realistic representation of the long-term physiological adaptation to developing insulin resistance is necessary for effectively designing clinical trials and evaluating diabetes prevention or disease modification therapies. Writing a good model for diabetes progression is difficult because the long time span of the disease makes experimental verification of modeling hypotheses extremely awkward. In this context, it is of primary importance that the assumptions underlying the model equations properly reflect established physiology and that the mathematical formulation of the model give rise only to physically plausible behavior of the solutions. In the present work, a model of the pancreatic islet compensation is formulated, its physiological assumptions are presented, some fundamental qualitative characteristics of its solutions are established, the numerical values assigned to its parameters are extensively discussed (also with reference to available cross-sectional epidemiologic data), and its performance over the span of a lifetime is simulated under various conditions, including worsening insulin resistance and primary replication defects. The differences with respect to two previously proposed models of diabetes progression are highlighted, and therefore, the model is proposed as a realistic, robust description of the evolution of the compensation of the glucose-insulin system in healthy and diabetic individuals. Model simulations can be run from the authors' web page.

glucose; insulin resistance; β-cell mass; mathematical models; type 2 diabetes mellitus