Fidelio
FIDELIO was a training network supported by a Horizon 2020 grant (Marie Skłodowska-Curie Action 860898) ran from October 2019 to March 2024. It involved more 14 European institutions, between university and industrial partners, and aimed enhance understanding of bone fragility in type 2 diabetes for the development of biomarkers for detection and treatment.
Rationale of FIDELIO
Diabetes mellitus has emerged as a novel risk factor for fragility fractures. While in type 1 diabetes the 3-fold overall relative risk for fractures may mostly derive from low bone mineral density (BMD) likely due to the lack of the bone-anabolic hormones, in type 2 diabetes, the fracture risk is increased about 2-fold, despite a normal or even higher BMD. This suggests that bone fragility in each form of diabetes develops by distinct mechanisms that to date remain largely unknown and may require an individualized approach for effective treatment. As the diabetes epidemic is increasing worldwide with aging, and the fractures that are associated with diabetes cause an increase in morbidity, mortality, and healthcare costs, diabetes-induced osteoporosis imposes a significant burden on our society and our healthcare system.
FIDELIO offers a comprehensive, multidisciplinary training program for Early Stage Researchers (ESRs) in this emerging field, unravelling i) the biological mechanisms that contribute to altered bone quality parameters with subsequent bone fragility in diabetes, ii) identify predictive markers for patient stratification and individualized interventions, and iii) develop novel imaging techniques to determine bone quality aspects. The research will employ well-defined patient cohorts, preclinical models of diabetic bone disease, in vitro studies, genetic databases, artificial intelligence, and cutting-edge imaging technologies in a highly collaborative and interdisciplinary environment. ESRs will be trained through individual research projects, secondments, residential courses, and webinars provided by a broad range of experts, including bone biologists, clinicians, epidemiologists, geneticists, engineers and entrepreneurs, as well as companies supporting this important area of research. The joint training programme will also develop transferable and entrepreneurial skills to help the ESRs succeed in their choice of professional future.
OUR ROLE IN FIDELIO
We trained two PhD students within this network, following the following projects
Genetics and biologic pathways underlying fracture risk in T2D (Samuel Gathan (does he have a page in the group to link))
Research of the genetics of diabetic bone disease in type 2 diabetes mellitus (T2D) in big datasets from population-based studies and clinical cohorts. Employment oof genetic scores in a Mendelian Randomization (MR) framework to assess causal relationships between potentially confounded risk factors shared by both conditions, with validation in the GWAS cohorts. Identification of the evidence derived from GWAS studies to identify possible plausible molecular pathways involved in both skeletal and glucose metabolism, with particular emphasis on the overlap of the biological underpinnings of T2D and fracture risk. We expect to identify new possible plausible molecular pathways that intersect between T2D and bone metabolism. Also, we expect the T2D allelic score to be causally related with either BMD or fracture.
Publications
Evaluating the relationship between glycemic control and bone fragility within the UK biobank: Observational and one-sample Mendelian randomization analyses. Samuel Ghatan, Fjorda Koromani, Katerina Trajanoska, Evert F.S. van Velsen, Maryam Kavousi, M Carola. Zillikens, Carolina Medina-Gomez, Ling Oei, Fernando Rivadeneira. medRxiv 2023.12.25.23300434; doi: https://doi.org/10.1101/2023.12.25.23300434
Ghatan S, van Rooij J, van Hoek M, Boer CG, Felix JF, Kavousi M, Jaddoe VW, Sijbrands EJG, Medina-Gomez C, Rivadeneira F, Oei L. Defining type 2 diabetes polygenic risk scores through colocalization and network-based clustering of metabolic trait genetic associations. Genome Med. 2024 Jan 10;16(1):10. doi: 10.1186/s13073-023-01255-7.
Li R, Shokri F, Rincon AL, Rivadeneira F, Medina-Gomez C, Ahmadizar F. Bi-Directional Interactions between Glucose-Lowering Medications and Gut Microbiome in Patients with Type 2 Diabetes Mellitus: A Systematic Review. Genes (Basel). 2023 Aug 1;14(8):1572. doi: 10.3390/genes14081572.
Li R, Medina-Gomez C, Rivadeneira F. 2022. Down-to-Earth Studies of the Gut Microbiome in Bone Health and Disease. J Bone Miner Res. Apr;37(4):595-596. Nazia Ayub , Malak Faraj , Sam Ghatan, Joannes A A Reijers, Nicola Napoli, Ling Oei. J Clin Med. 2021 Jul 5;10(13):3002. doi: 10.3390/jcm10133002.
Type 2 Diabetes Mellitus and Vertebral Fracture Risk. 2021. Fjorda Koromani, Samuel Ghatan, Mandy van Hoek, M. Carola Zillikens, Edwin H. G. Oei, Fernando Rivadeneira & Ling Oei. Curr Osteoporos Rep. 2021 Feb;19(1):50-57. doi: 10.1007/s11914-020-00646-8.
Microvascular Disease Associates with Larger Osteocyte Lacunae in Cortical Bone in Type 2 Diabetes Mellitus. Sebastian Zanner, Elliott Goff, Samuel Ghatan, Eva Maria Wölfel, Charlotte Ejersted, Gisela Kuhn, Ralph Müller and Morten Frost. JBMR Plus. 2023 Oct 27;7(11):e10832. doi: 10.1002/jbm4.10832. eCollection 2023 Nov