Individualisation of HbA1c targets and treatment strategies in people with diabetes: real-world observational studies
Publication Date
July 17, 2024
Creator
Abstract
All forms of diabetes are associated with increased risks of vascular complications and all-cause mortality. Although often considered a single condition, it is by its nature heterogenous, even within current type classifications. There is increasing focus on individualising the management of type 2 diabetes with an emphasis on collaborative goal setting and increasing emphasis on the role of real-world observational data to support findings from randomised controlled trials.
Chapter 1 gives a general overview of the pathophysiology of diabetes, with a focus on type 2 diabetes, and explores the heterogeneity of phenotypes within this diagnostic umbrella. It also reviews the current guidelines for treatment. It then goes on to explore the evidence underpinning these recommendations and situations where alternative approaches, including precision medicine, may aid clinicians in future.
Chapter 2 gives a broad overview of observational study methodologies and where they fit in the overall landscape of research evidence. It then details some of the key methods utilised in my main studies (Chapter 3 and 5) and the developmental work that led to their final methodologies.
Chapter 3 presents the results from the HbA1c individualisation study and explores the association between HbA1c, all-cause mortality, and macrovascular complications.
The thesis then moves on to frailty, starting with the systematic review and meta-analysis in chapter 4 which synthesises currently published work on intensive glycaemic control in individuals in older age groups across multiple outcomes and highlights the paucity of research in this area. Chapter 5 then presents data aimed to fill this gap and to my knowledge is the first diabetes study to assess and then utilise electronic frailty index scores within its design. It shares important insights into optimal HbA1c levels using a recognised definition of frailty rather than using age as a proxy – the first study of its kind.
The final two results chapters share outcomes from two real-world observational studies as examples of the impact this work can have in translating randomised control trial evidence into a clinical context. Chapter 6 contains results from a clinical audit assessment of injectable semaglutide and highlights individuals who may benefit the most which may be important information for clinicians in view of medication shortages.
Chapter 7 focuses on hybrid-closed loop therapy in type 1 diabetes. This real-world observational work has had significant impact in informing national policy positions and recent technology appraisals by the National Institute of Health and Care Excellence and is a good example of the power real-world studies can have.
Item Type
ethesis
Thesis Type
PhD
Subjects (LC)
Associated Schools / Departments
School of Medicine
eprints ID
78316
UoN Repository URI
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