The onset of type 2 diabetes: Proposal for a multi-scale model

Filippo Castiglione, Paolo Tieri, Albert De Graaf, Claudio Franceschi, Pietro Liò, Ben Van Ommen, Claudia Mazzà, Alexander Tuchel, Massimo Bernaschi, Clare Samson, Teresa Colombo, Gastone C. Castellani, Miriam Capri, Paolo Garagnani, Stefano Salvioli, Viet Anh Nguyen, Ivana Bobeldijk-Pastorova, Shaji Krishnan, Aurelio Cappozzo, Massimo SacchettiMicaela Morettini, Marc Ernst

Research output: Contribution to journalArticlepeer-review


Background: Type 2 diabetes mellitus (T2D) is a common age-related disease, and is a major health concern, particularly in developed countries where the population is aging, including Europe. The multi-scale immune system simulator for the onset of type 2 diabetes (MISSION-T2D) is a European Union-funded project that aims to develop and validate an integrated, multilevel, and patient-specific model, incorporating genetic, metabolic, and nutritional data for the simulation and prediction of metabolic and inflammatory processes in the onset and progression of T2D. The project will ultimately provide a tool for diagnosis and clinical decision making that can estimate the risk of developing T2D and predict its progression in response to possible therapies. Recent data showed that T2D and its complications, specifically in the heart, kidney, retina, and feet, should be considered a systemic disease that is sustained by a pervasive, metabolically-driven state of inflammation. Accordingly, there is an urgent need (1) to understand the complex mechanisms underpinning the onset of this disease, and (2) to identify early patient-specific diagnostic parameters and related inflammatory indicators. Objective: We aim to accomplish this mission by setting up a multi-scale model to study the systemic interactions of the biological mechanisms involved in response to a variety of nutritional and metabolic stimuli and stressors. Methods: Specifically, we will be studying the biological mechanisms of immunological/inflammatory processes, energy intake/expenditure ratio, and cell cycle rate. The overall architecture of the model will exploit an already established immune system simulator as well as several discrete and continuous mathematical methods for modeling of the processes critically involved in the onset and progression of T2D. We aim to validate the predictions of our models using actual biological and clinical data. Results: This study was initiated in March 2013 and is expected to be completed by February 2016. Conclusions: MISSION-T2D aims to pave the way for translating validated multilevel immune-metabolic models into the clinical setting of T2D. This approach will eventually generate predictive biomarkers for this disease from the integration of clinical data with metabolic, nutritional, immune/inflammatory, genetic, and gut microbiota profiles. Eventually, it should prove possible to translate these into cost-effective and mobile-based diagnostic tools.

Original languageEnglish
Article number2854
JournalJournal of Medical Internet Research
Issue number10
Publication statusPublished - Oct 2013


  • Computational biology
  • Data integration
  • Metabolism
  • Metaflammation
  • Multiscale modeling
  • Physical activity
  • Simulation
  • Type 2 diabetes

ASJC Scopus subject areas

  • Health Informatics


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