Abstract
Multimorbidity, the co-existence of 2 or more conditions within a patient, is a significant problem for healthcare. Patients with type 2 diabetes (T2D) experience a significant burden from multimorbidity. There is a pressing need to identify patterns of multimorbidity as well as novel therapeutics that may improve the prevention, stratification, and treatment of multimorbid patients with T2D. We investigated multimorbidity patterns in the UK Biobank (UKB) cohort and found that there is a distinction within highly multimorbid patients between those with a high frequency of falls, injuries, and self-harm, and those with a high frequency of adverse drug reactions. We further investigated the mortality risk of subgroups of multimorbidity through a sex-stratified analysis of trajectories of diagnoses. We created rules based on the prior disease histories of patients for the triage of patients presenting with 63 common diseases and identified high-risk multimorbid subgroups. We subsequently performed an analysis of multimorbid patterns in the T2Dsubset of the UKB and found that patients with type 1 diabetes who go on to be diagnosed with T2D represent a high-risk subgroup with elevated levels of multimorbidity and mortality. We built a predictive model which may prove clinically useful in identifying these high-risk individuals earlier. We finally sought to identify novel therapeutic targets for the treatment of patients with T2D on high-risk disease trajectories to chronic kidney disease(CKD). We performed a genome-wide association study on high-risk CKD trajectories and found 19 gene variants associated with high-risk CKD trajectories. Through linkage with epigenomic databases, we identified 2 novel CKD-associated genes, NECAB1 andCLEC17A, that may be novel therapeutic targets for patients at a high risk of CKD development in disease backgrounds of hypertension and cataracts, respectively. We hope this work contributes to the improvement of care for patients with multimorbidity,T2D, and CKD.Thesis is embargoed until 30 June 2026
Date of Award | Jun 2024 |
---|---|
Original language | English |
Supervisor | Steven Watterson (Supervisor), Paula McClean (Supervisor), Priyank Shukla (Supervisor) & Joanna Sharman (Supervisor) |
Keywords
- multimorbidity
- UK Biobank
- diabetes
- trajectories
- genetics
- triage
- mortality