title: Potential of Polyphenols as Therapeutic Options in Type 2 Diabetes
Creators: name: Nikbakht Nasrabadi, Elham
Publisher: name: Griffith University
Year: 2018
Subjects: subject: Polyphenols
subject: Therapeutic options
subject: Type 2 diabetes
subject: Hyperglycemia
subject: ACN metabolites

description: Type 2 diabetes (T2D) is a complex phenotype mainly characterised by prolonged unsettled hyperglycemia caused by pancreatic beta cell [...] dysfunction and progressive insulin resistance. In addition, T2D is a well-recognised inflammatory disease due to the significant role of metabolic inflammation, triggered by over-nutrition, in [beta]-cell dysfunction initiation. The aetiology of T2D is influenced by the interactions of environmental and genetic factors. Although the exact mechanism by which diabetes-associated genes interact with each other and environmental influences is not fully understood, it has been indicated that several genes and lifestyle risk factors are involved in the development of T2D, each being a small contributor. The prevalence of diabetes is expected to rise in the adult population, affecting approximately 600 million by 2035. Untreated T2D is associated with long-term macrovascular and microvascular complications. In fact, there is a significant disability burden associated with T2D along with a considerable cost to the healthcare system. Annual healthcare costs of diabetes were estimated 245 billion US dollars in the United States in 2012 and 14.6 billion Australian dollars in Australia in the year 2010. With substantial treatment costs, the increasing prevalence of diabetes represents a significant social and economic issue. Thus, the development of novel therapeutic approaches for T2D and complications accompanying it, or prevention of diabetes in at-risk individuals is an essential component of future medical research strategies. Pharmacotherapy and lifestyle modifications are the primary therapeutic approaches for management of T2D. However, due to the side effects accompanying the use of medications, as well as the difficulty in maintaining health-related behaviour changes, non-pharmacological interventions are attracting scientific attention, with certain natural supplements and dietary components such as polyphenolic antioxidants showing promise as a replacement or complement to pharmacotherapy for T2D. The anti-diabetic effects of polyphenolic antioxidants such as anthocyanins (ACNs) have been demonstrated in several in vitro, in vivo, human interventional trials, and observational studies. ACNs are abundant in red to blue coloured fruits and vegetables as well as plant-derived beverages and are broadly distributed in the human diet. Polyphenolic compounds including ACNs are found to attenuate important hallmarks of T2D such as hyperglycaemia and hyperlipidaemia, in addition to having the ability to act as anti-inflammatory agents, hence potentially controlling obesity-induced inflammation and associated disorders. Moreover, various subclasses of polyphenols have demonstrated gene expression regulatory roles in different experimental models. As the overall aim, this doctoral study sought to investigate the potential of dietary polyphenols as therapeutic options for type 2 diabetic and pre-diabetic adults. The studies conducted as a part of this thesis were based on the hypothesised effects of polyphenolic antioxidants, including ACN, on physical measurements; biochemical parameters; pro-inflammatory biomarkers; and genetic signals including micro-RNAs (miRNAs) and associated messenger-RNAs (mRNAs), in T2D and pre-diabetic adults. This thesis incorporates a systematic review and meta-analysis followed by an intervention trial, with four main research questions being addressed in four studies presented in Chapters 3, 5, 6 and 7. [...]