INTERCEPT-T2D

Until recently, diabetes was classified into two main forms, type 1 and type 2 diabetes, a classification that does not adequately reflect the complexity of type 2 diabetes in terms of etiologies, differing clinical manifestations and potential complications. In a complex study published in 2018, Ahlqvist et al. analyzed diabetes characteristics in a large Swedish cohort, and three other Scandinavian groups. Five subgroups were distinguished: Severe Autoimmune Diabetes, Severe Insulin Deficient Diabetes, Severe Insulin Resistant Diabetes, Mild Obesity-related Diabetes and Mild Age-related Diabetes. The data-driven cluster analysis was based on easily measurable clinical parameters: GAD antibodies, BMI, HbA1c, age at diabetes onset, HOMA-2 estimates of b-cell function and insulin resistance. The novel subgroups were validated in the German Diabetes Study (GDS) and in the Verona Newly Diagnosed T2D Study-VNDS (partners of the project). In these studies, the subgroups had distinct progression trajectories of diabetes-related complications which were associated with different clinical, metabolic and genetic traits. Both diabetes and its comorbidities have in common that inflammation-related processes are involved in their development. A cross-sectional analysis of the data of 414 individuals with recent adult-onset diabetes from the GDS showed multiple differences in 23 biomarkers of inflammation in the novel diabetes subgroups as described by Ahlqvist et al. A comprehensive multi-omics analysis of metabolically profiled pancreatectomized living human donors showed that patients with diabetes and prediabetes display upregulation of islet genes that were functionally related to cell-extracellular matrix interaction, immune response and signaling pathways. The heterogeneity of immune cells and biomarkers of inflammation raises the question about the role of immune-inflammatory mechanisms in the apparent differences between patients with diabetes regarding the glycemic continuum and risk of developing diabetes-related complications and comorbidities. We believe that the inflammatory component of diabetes plays a crucial role in guiding the trajectory of the disease: deterioration of insulin sensitivity and b-cell function and the progression of micro- and macrovascular comorbidities. The global objective of the network is to redefine the classification of diabetes and set up a clustering of the disease based on in-depth targeted immune-inflammatory phenotyping of individuals, and subsequently a personalized therapy course. In this context, the INTERCEPT-T2D (Improving Type 2 Diabetes Care through Personalized Inflammation-Based Interceptive Medicine) consortium will address two key goals: > Establish novel subgroups of diabetes based on immune-inflammatory profiles of patients > Elucidate the role of the identified subgroups/trajectories in diabetes-related outcomes The project ambition is to develop and utilize algorithms and sensors of immune-inflammatory metabolites to dynamically monitor diabetes status and to identify inflammation indicators correlative to the uncomplicated-to-complicated diabetes transition (“health-to-disease”). The overarching vision of the INTERCEPT-T2D Consortium is to provide a framework for personalized medicine in diabetes. To support its formalisation, evolution, works and goals reaching, INTERCEPT-T2D is aiming for the European call for projects HORIZON-HLTH-2022-STAYHLTH-02-01 : Personalised blue print of chronic inflammation in health-to-disease transition.