| Summary: | Type 2 diabetes mellitus is a chronic and debilitating disease whose prevalence continues to rise inexorably. Type 2 diabetes is usually preceded by a condition called prediabetes, which is characterised by impaired glucose regulation. Those with prediabetes have a significantly increased risk of developing type 2 diabetes compared to those with normal glucose control and therefore represent a key population in the prevention of type 2 diabetes. Physical inactivity is thought to be one of the key factors driving the increasing prevalence of prediabetes and type 2 diabetes and consequently forms a pivotal focus of initiatives aimed at their prevention. The principal aims of this thesis were to: 1) conduct a systematic review investigating the effectiveness of lifestyle and physical activity interventions at promoting physical activity in individuals with prediabetes and the effect of physical activity change on the risk of developing diabetes; 2) investigate the effect of walking activity on markers of chronic low grade inflammation; and 3) design and evaluate with objectively measured endpoints a physical activity intervention for adults at risk of developing type 2 diabetes that is suitable for implementation in a health care or community setting if found to be effective. The main findings are listed in the order of the stated aims. 1) Due to the dearth of controlled exercise training studies in those with prediabetes and the absence of evidence that previous diabetes prevention programmes have been successful at initiating clinically significant increases in physical activity, the evidence for the efficacy of physical activity behaviour change at prevention or delaying the progression to type 2 diabetes in those with prediabetes is equivocal. 2) Walking at levels that are consistent with the current physical activity recommendations is associated with reduced chronic low-grade inflammation, independent of other forms of physical activity. 3) The PREPARE programme, developed after a review of health behaviour theory and the current health care climate, is a theorydriven, group-based structured education programme designed to promote increased walking activity in individuals with prediabetes in a health care setting. A randomized controlled trial was conducted to test two versions of the PREPARE programme, a standard version and a pedometer version, against control conditions (advice leaflet). The standard version encouraged participants to set time-based goals based on generic exercise recommendations, whereas the pedometer version enabled participants to set personalized steps-per-day goals and to objectively self-monitor their daily physical activity levels using a pedometer. One hundred and three individuals were recruited to the study and follow-up was conducted at 3,6 and 12 months. At 12 months both intervention conditions were successful at achieving significant increases in objectively measured ambulatory activity; compared to the control group, those who received the pedometer version of the PREPARE programme increased their ambulatory activity by 1952 steps per day (95% CI 953 to 2951) and those who received the standard version by 1480 steps per day (95% CI 436 to 2522). However, significant improvements in glucose tolerance were only seen in the pedometer group, where 2-h glucose levels decreased by -0.94 mmol/l (95% Cl -1.79 to - 0.10) compared to control conditions, despite no significant change in body weight or waist circumference. This thesis has identified important limitations in the current evidence linking physical activity to the prevention of type 2 diabetes in those with prediabetes and has addressed several of these limitations by developing a theory-driven structured education programme which was shown to be successful at promoting physical activity and improving glucose tolerance in those with prediabetes to levels that are equal to or greater than previous multifactor diabetes prevention programmes. This is likely to have important implications for future diabetes prevention trials and clinical practice in the United Kingdom.
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