Inflammation, metabolic disorders and incident type 2 diabetes
Date of Award
2024
Document Type
Thesis - ECU Access Only
Publisher
Edith Cowan University
Degree Name
Doctor of Philosophy
School
School of Medical and Health Sciences
First Supervisor
Wei Wang
Second Supervisor
Lois Balmer
Third Supervisor
Manshu Song
Fourth Supervisor
Xingang Li
Abstract
Type 2 diabetes (T2D) is a major health threat of our era and has become a health priority worldwide. Emerging evidence suggests that T2D is a main post-COVID-19 metabolic sequela, further exacerbating its epidemic. Inflammation and metabolic disorders are two hallmarks of T2D, and both have been shown to heighten the risk of incident diabetes.
However, there are significant heterogeneities in the risks of incident diabetes with exposure to each of them. Notably, accumulated evidence suggests a closely intertwined biological process between them. It is unknown whether elevated inflammation could interact with metabolic disorders acting on diabetogenesis and explain the diabetic risk heterogeneity in metabolic disorders.
Furthermore, different levels of inflammation have distinct sources. Low-grade systemic inflammation commonly results from metabolic disorders, whereas highgrade inflammation is indicative of an acute phase response, mainly initiated from acute infectious processes and acute stress. Currently, mainstream knowledge excludes highgrade inflammation for addressing the risk of cardiometabolic diseases and has seldom linked it to the pathophysiology of diabetes. Nonetheless, the alarmingly high incidence of T2D postacute SARS-CoV-2 infections has awakened a need to link infectious diseases to the development of T2D.
This thesis aims to provide data-based epidemiological insights into the combined effect of different sources and levels of inflammation with a wide range of metabolic disorders on the development of diabetes and specifically considers the potential interactive effects between them.
This thesis is composed of nine chapters: an overview of the thesis (Chapter 1); a comprehensive literature review (Chapter 2); six results chapters (Chapters 3–8); and a final chapter with a general discussion of the main findings and future directions (Chapter 9).
The first chapter of the thesis includes an introduction and overview of the entire thesis. This is then followed by a thorough review of the literature on inflammation, metabolic disorders and T2D (Chapter 2). Based on data from a real-world, large-scale, prospective cohort (Kailuan study) in China, I first investigated the effect of elevated inflammation on incident T2D among individuals with different levels of adiposity (Chapter 3). Followed by an investigation into whether elevated inflammation had a role in driving the progression to diabetes from prediabetes and explored the diabetespreventive potential of currently available anti-inflammatory treatments (Chapter 4). In Chapter 5, I examined the temporal relationship between inflammation and atherogenic dyslipidemia (a hallmark of diabetes-specific dyslipidemia, also an alternative indicator of insulin resistance) and their joint effect on incident T2D. Furthermore, I specifically addressed the age-specific association between co-exposure to chronic inflammation and dyslipidemia and incident diabetes and their age-related interactions (Chapter 6). Thereafter, I examined the role of high-grade inflammation/acute phase response in incident T2D. In Chapter 7, I specifically investigated the impact of high-grade inflammation, transient or cumulative, on incident diabetes, especially among participants with different levels of dyslipidemia. In Chapter 8, I evaluated the role of transient acute phase response/suspected infection in incident T2D considering the interactions with increased body mass. Chapter 9 is a comprehensive discussion of the studies covered in this thesis.
Access Note
Access to this thesis is embargoed until 20th May 2029.
Recommended Citation
Lan, Y. (2024). Inflammation, metabolic disorders and incident type 2 diabetes. Edith Cowan University. Retrieved from https://ro.ecu.edu.au/theses/2778