title: The onset of type 2 diabetes: proposal for a multi-scale model.
abstract: 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.
authors.affiliation: Consiglio Nazionale delle Ricerche, Istituto per le Applicazioni del Calcolo "Mauro Picone", Roma, Italy. f.castiglione@iac.cnr.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Castiglione
authors.forename: Paolo
authors.initials: P
authors.lastname: Tieri
authors.forename: Albert
authors.initials: A
authors.lastname: De Graaf
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Pietro
authors.initials: P
authors.lastname: Liò
authors.forename: Ben
authors.initials: B
authors.lastname: Van Ommen
authors.forename: Claudia
authors.initials: C
authors.lastname: Mazzà
authors.forename: Alexander
authors.initials: A
authors.lastname: Tuchel
authors.forename: Massimo
authors.initials: M
authors.lastname: Bernaschi
authors.forename: Clare
authors.initials: C
authors.lastname: Samson
authors.forename: Teresa
authors.initials: T
authors.lastname: Colombo
authors.forename: Gastone C
authors.initials: GC
authors.lastname: Castellani
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.forename: Paolo
authors.initials: P
authors.lastname: Garagnani
authors.forename: Stefano
authors.initials: S
authors.lastname: Salvioli
authors.forename: Viet Anh
authors.initials: VA
authors.lastname: Nguyen
authors.forename: Ivana
authors.initials: I
authors.lastname: Bobeldijk-Pastorova
authors.forename: Shaji
authors.initials: S
authors.lastname: Krishnan
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cappozzo
authors.forename: Massimo
authors.initials: M
authors.lastname: Sacchetti
authors.forename: Micaela
authors.initials: M
authors.lastname: Morettini
authors.forename: Marc
authors.initials: M
authors.lastname: Ernst
keywords: computational biology; data integration; metabolism; metaflammation; multiscale modeling; physical activity; simulation; type 2 diabetes