The Impact of Elevated Risk of Poor Glucoregulation on Cognition: Comparing Neurophysiological, Glucoregulatory and Cardiovascular Factors in Non-diabetic Healthy Young Adults Vs Non-Diabetic, Potentially At-Risk Young Adults.

The global prevalence of metabolic syndrome, which is predominantly characterised by insulin resistance and is a precursor to type two diabetes mellitus (T2DM), is a major health concern. In 2018 it was estimated that 1 in 3 older adults aged 50 or over in the UK were affected by metabolic syndrome. The global prevalence of type two diabetes mellitus (T2DM), and its co-presenting cognitive impairment, is alarming. With 171 million afflicted individuals in 2000 and expectations that this will rise to 366 million, by the year 2037. Known risk factors for the development of T2DM, are obesity, poor glucoregulatory control, normal ageing, high-blood pressure, smoking, physical inactivity, and other negative lifestyle choices such as an unhealthy high carbohydrate diet.

Using a novel combination of methodologies, this thesis aimed to validate theories of memory recognition and glucose enhancement effects to achieve an understanding of the mechanisms involved in memory impairment, often co-morbid with T2DM. Glucose and glucoregulation have been shown to mediate cognitive functioning, although inconsistent results are reported. Chapters 2 and 3 investigated whether these anomalies may be a result of differential treatment ingredients being used by research centres, with a view to establishing best practice for experimental and placebo treatment composition. Some ingredients were not cognitively inert, potentially suggesting some inconsistencies in the glucose enhancement literature may be influenced by treatment ingredients rather than a direct glucose effect.

Chapters 4 and 5 explored the impact of glucose ingestion and early sub-clinical deficits in glucoregulatory control, on episodic memory in young, non-diabetic adults. EEG was used and nuanced memory differences were indeed visible in this population, offering important insight into early cognitive and structural changes underpinning glucoregulation linked cognitive decline. Also investigated, was cardiovascular health which is implicated in T2DM. Ingested glucose accelerated heart rate for both better and poorer regulators, and although only a trend, poorer regulators had globally higher heart rate than better regulators. Chapter 5 explored the potential of a questionnaire, based on known T2DM risk factors alongside glucoregulation measures, as a means of identifying a T2DM risk profile. This section provided evidence suggesting that these known associable T2DM risk factors have a significant positive relationship with blood glucose measures (iAUC) taken via an oral glucose tolerance test. Heart rate variability, which is also implicated in T2DM, was also found to be correlated with T2DM risk scores, blood glucose levels, and baseline heart rate, with more widespread effects being seen in poorer glucoregulators. As these effects have been observed in this population, the relationship between these measures provides evidence for the efficacy of this risk assessment model as a preventative intervention which could lead to lifestyle changes being put into place prior to the onset of T2DM.

Further exploration of the methodologies employed here, comparing populations of different age groups and pathologies, would help to gain further knowledge of the mechanistic pathways which mediate memory impairment, and give more insight into cognitive decrements associated with impaired glucoregulatory control and T2DM.