Research Programme Image Programme Our overarching aim is to improve the understanding of the pathogenesis of diabetes and its complications and to contribute to the development of new treatments and management strategies for diabetes. Approach and Progress Our research programme uses large scale population based approaches to further our understanding of the pathogenesis and means of prevention of diabetes complications. Our approach harnesses the increasing availability of e-health record data and new technologies for acquiring high dimensional molecular ‘omics data. Our research programme comprises three inter-related workstreams: 1) Discovery of genetic, proteomic, metabolomic and lipidomic correlates and predictors of complications in diabetes using biobanks linked to e-health care record data. This workstream involves using biobanks from large Scottish cohorts of people with type 1 diabetes (the SDRNT1BIO) and type 2 diabetes (Go-DARTs) to carry out genome wide association studies, and ‘omic biomarker studies. This workstream aims to discover new pathways leading to disease and to maximise the predictive potential of genetic and non genetic biomarkers. It involves collaborations combining data from Scotland with data internationally. Current research includes: Genome wide association studies of genetic determinants of type 1 diabetes and related phenotypes using the SDRNT1BIO and Generation Scotland cohort as control. Genome wide association studies of diabetes complications including nephropathy, retinopathy, CVD and peripheral vascular disease. Large scale biomarker studies using Mass spectrometry and multiplexed ELISA and other technologies for predicting rapid progression of nephropathy in type 2 diabetes in the EU IMI SUMMIT programme, and in the JDRF Diabetic Nephropathy Biomarker Discovery and Validation collaboration programme. Evaluation of N-glycans as potential biomarkers of complications. Examination of genetic and other determinants of variation in C-peptide persistence in type 1 diabetes. Combining genetic and other biomarkers for complications to elucidate novel pathways involved in complications pathogenesis. 2) Epidemiology of diabetes, its complications and treatment using e-health record data This workstream involves building platforms for the efficient safe use of anonymised e-health record data in a secure data environment. Using these data we then quantify current rates of complications and trends in complications, explore the determinants of complications and build predictive models. Models are validated in collaboration with international collaborators. We aim in the future to have such models incorporated into software tools for clinical and self management use. The outputs of this research are also useful for health service planning. We also evaluate aspects of the efficacy and safety of current management of diabetes. Current research includes: Quantifying current rates of and building predictive models of CVD incidence in type 1 and type 2 diabetes. Examining retinopathy progression so as to optimise screening intervals in type 1 and type 2 diabetes. Exploring unintended adverse consequences of established and new diabetes drugs. This includes developing and applying appropriate methods in pharmacoepidemiology. 3) Clinical trials of drugs in diabetes Professor Colhoun’s current clinical trial involvement includes REMOVAL study: REducing with MetfOrmin Vascular Adverse Lesions in type 1 diabetes. Co-Principal Investigator. The Effect of Dulaglutide on Major Cardiovascular Events in Patients With Type 2 Diabetes: an academically led CVD endpoint trial of n=10,000, funded by Eli-Lilly. Steering and Operations Committee member. The ODYSSEY programme for Alirocumab, a new monoclonal antibody to PCSK9 being developed by Sanofi-Regeneron. Steering Committee member. This article was published on 2024-09-23
