Abstract
There are over half a billion people globally with Type 2 Diabetes (T2D), a disease linked to 5 million deaths annually. The development of T2D is associated with serious co-morbidities in which T2D is either directly or indirectly implicated including: obstructive sleep apnoea; fatty liver leading to cirrhosis; peripheral neuropathy; amputations and erectile dysfunction. Expenditure in the health sector related to T2D is estimated at US$966 billion worldwide in 2021. There is, therefore, an urgent need to explore alternative interventions to reduce the increasing prevalence of T2D and the resultant burden on the health system.Excessive weight gain is a key risk factor associated with the development of T2D. Lifestyle interventions such as diet and exercise are the preferred method to treat and manage overweight and obesity, yet for some individuals these interventions in isolation or combination are not efficacious. The processes of satiation and satiety are strongly associated with the regulation of energy intake and a better understanding of these may lead to improved interventions to prevent T2D. The first aim of this thesis was to investigate the potential to improve appetite responses through altered dietary composition, thereby possibly preventing or delaying the progression to T2D. The second aim of this thesis was to investigate the potential to improve the ability of the diabetes drug metformin to prevent or delay progression to T2D in pre-diabetics.
Two published systematic reviews, a published concept paper, and a pilot clinical trial were completed. This series of studies suggest adjustments to macronutrient composition may assist individuals to attain satiation at a reduced level of dietary energy intake. In individuals with the tendency to develop T2D and where diet and exercise have been shown not to be effective, the use of the oral anti-hyperglycaemic metformin offers an alternative pathway to potential prevention of T2D.
The meta-analysis carried out in Chapter 3 found no significant effects on hunger when a diet containing fat had an increased fibre content with no corresponding increase in fullness. However, the systematic review found evidence that the appetite response derived from fat may be variable, dependent on the other nutrients with which it is consumed. The meta-analysis carried out in Chapter 4 found that the digestive hormone Cholecystokinin (CCK) has a significant effect on satiation at both physiological and pharmacological levels in the blood plasma, confirming CCK’s key role in human appetite regulation. It was notable that eight of the ten studies included in the meta-analysis utilised some means to facilitate stomach distention, highlighting the importance of this additional stimulus to effectively deliver the sensation of satiation and reduce energy intake. The analysis in Chapter 5 using the dataset from the Diabetes Prevention Program demonstrated that metformin is effective at both lowering Fasting Plasma Glucose (FPG), especially in prediabetic persons with more pronounced Impaired Fasting Glucose (IFG) and also found that metformin maintained insulin sensitivity over four years. In Chapter 6, the author of the present thesis was able to propose a new hypothesis for the phenomenon of the slow and steady weight gain experienced by consumers worldwide in the context of the contemporary food environment. Chapter 7 was a first attempt to test this new hypothesis in the form of a pilot clinical trial.
Significant delay in the onset and possible prevention of T2D remains a viable prospect. The findings within this thesis propose both potential new avenues to prevent or delay progression to T2D and opportunities for future research.
| Date of Award | 2024 |
|---|---|
| Original language | English |
| Supervisor | Nenad NAUMOVSKI (Supervisor), Kate PUMPA (Supervisor) & Shawn SOMERSET (Supervisor) |