Danish healthcare data was analysed to determine the risk of fracture in diabetes by sex, age and site of fracture. Other studies examined whether the level of insulin sensitivity, and microvascular disease affect fracture risk in T2D. Studies of healthcare costs of fractures have revealed that treatment costs are higher for most fracture types in diabetes patients compared to those without diabetes.
The genetic basis of fracture risk in diabetes was investigated using data from population cohort and large genomic studies. Genetic sub-groups of T2D were classified, with disease duration identified as a major factor in fracture risk. This research provides new insights into the links between T2D and other metabolic conditions.
The potential role of the human gut microorganism population (microbiome) was also investigated in population cohort studies. Differences in microbiome profiles were found between healthy and less healthy people. Preliminary findings relating to musculoskeletal health are currently being validated.
Analysis of microRNAs in blood samples may be useful to predict fracture risk. In FIDELIO, microRNA analysis was performed in animal models and in patients, comparing to measurements of bone strength and quality. So far, none were confirmed to specifically indicate diabetic bone disease, but some microRNAs are of interest to study further in relation to diabetes or bone health in general.
A clinical study of T2D patients has examined the effects of a high fibre diet on bone. So far, this found a positive effect of the diet on metabolic health, but not on bone parameters. However, a study of the same diet in a T2D mouse model has observed interesting effects on bone that will be investigated further.
Bone samples were analysed for chemical changes due to high sugar levels in diabetes, and how these affect bone strength and quality. In T1D samples, effects on osteocytes, the most abundant bone cell, and damage to bone microstructure were observed. A computational model was developed that calculates bone strength, fracture properties and localised bone loading from patient scans. Scans from studies of diabetes patients has been analysed for their differences in bone microstructure. Bone formation and remodelling has been observed over repeated scans. Also an image processing tool has been developed correct for any motion of patients during scans. These tools are available for use by researchers and for eventual clinical applications.
Mouse models of diabetes have been characterised. The TallyHO model commonly used for T2D was found not to develop diabetic bone disease, while a study of the protein Dkk-1 in a T1D model suggest it has a role in regulating bone and fat metabolism. The role of mitochondrial dysfunction has been investigated with a focus on the Polg gene, in cells and an animal model, and in metabolic analysis of cells from patients. The effects of diabetes and exercise on osteocyte cells and bone properties have been studied in cells and in a T2D mouse model.
The FIDELIO training programme of residential courses, online training and secondments was implemented, with some modification due to the COVID-19 pandemic. ESRs received interdisciplinary scientific training including courses on imaging, animal models and bone biomechanics, while transferable skills training including scientific writing, video production and a professional development programme.
FIDELIO results are being disseminated in open access journal publications, available to the research and medical community for further research, development of new clinical guidelines and tools to improve patient care.
Videos about FIDELIO and each ESR project are available on YouTube, and lay summaries of publications are also available on the project website.
