Can we out-walk the type 2 diabetes mellitus epidemic?

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

Can we out-walk the type 2 diabetes mellitus epidemic?

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.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study

Objectives: While bidirectional relationships exist between body weight and physical activity, direction of causality remains uncertain and previous studies have been limited by self-reported activity or weight and small sample size. We investigated the prospective relationships between weight and physical activity. Design: Observational analysis of data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study, a double-blinded randomised clinical trial of nateglinide and valsartan, respectively. Setting Multinational study of 9306 participants. Participants: Participants with biochemically confirmed impaired glucose tolerance had annual measurements of both weight and step count using research grade pedometers, worn for 7 days consecutively. Along with randomisation to valsartan or placebo plus nateglinide or placebo, participants took part in a lifestyle modification programme. Outcome measures: Longitudinal regression using weight as response value and physical activity as predictor value was conducted, adjusted for baseline covariates. Analysis was then repeated with physical activity as response value and weight as predictor value. Only participants with a response value preceded by at least three annual response values were included. Results: Adequate data were available for 2811 (30%) of NAVIGATOR participants. Previous weight (χ2=16.8; p<0.0001), but not change in weight (χ2=0.1; p=0.71) was inversely associated with subsequent step count, indicating lower subsequent levels of physical activity in heavier individuals. Change in step count (χ2=5.9; p=0.02) but not previous step count (χ2=0.9; p=0.34) was inversely associated with subsequent weight. However, in the context of trajectories already established for weight (χ2 for previous weight measurements 747.3; p<0.0001) and physical activity (χ2 for previous step count 432.6; p<0.0001), these effects were of limited clinical importance. Conclusions: While a prospective bidirectional relationship was observed between weight and physical activity, the magnitude of any effect was very small in the context of natural trajectories already established for these variables

Association of after school sedentary behaviour in adolescence with mental wellbeing in adulthood

Sedentary behaviour is associated with poorer mental health in adolescence but no studies have followed participants into mid-life. We investigated the association between after-school sedentary behaviours (screen time and homework) in adolescence with mental wellbeing in adulthood when participants were aged 42.Participants (n=2038, 59.2% female) were drawn from The 1970 British Cohort Study (BCS70). At age 16 respondents were asked separate questions about how long they spent in three types of screen based activities (TV, video films, computer games) and homework 'after school yesterday'. Mental well-being and psychological distress were assessed at the age 42 sweep in 2012 using the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) and Malaise Inventory, respectively.After adjustment for all covariates, participants reporting more than 3hrs of after school screen time as an adolescent had -1.74 (95% CI, -2.65, -0.83) points on the WEMWBS compared with adults reporting less than 1 hr screen time as an adolescent. Participants that reported high screen time both at age 16 (≥3hrs/d) and age 42 (≥3hrs/d TV viewing) demonstrated even lower scores (-2.91; -4.12, -1.69). Homework was unrelated to wellbeing after adjustment for covariates. The longitudinal association between adolescent screen time and adult psychological distress was attenuated to the null after adjustment for covariates.Screen time in adolescence was inversely associated with mental wellbeing in adulthood

The effect of sacubitril/valsartan compared to olmesartan on cardiovascular remodelling in subjects with essential hypertension: the results of a randomized, double-blind, active-controlled study

Aims: Progressive aortic stiffening eventually leads to left ventricular (LV) hypertrophy and heart failure if left untreated. Anti-hypertensive agents have been shown to reverse this to some extent. The effects of sacubitril/valsartan (LCZ696), a dual-action angiotensin receptor blocker (ARB), and neprilysin inhibitor, on arterial stiffness and LV remodelling have not been investigated. Methods and results: This was a randomized, multi-centre, double-blind, double-dummy, active-controlled, parallel group, study to compare the effects on cardiovascular remodelling of sacubitril/valsartan with those of olmesartan in patients with hypertension and elevated pulse pressure. Magnetic resonance imaging scans were used to assess LV mass and local aortic distensibility, at baseline and at 12 and 52 weeks after initiation of treatment. Central pulse and systolic pressure were determined using a SphymoCor® XCEL device at each time point. A total of 114 patients were included, with 57 in each treatment group. The mean age was 59.8 years, and 67.5% were male. Demographic characteristics did not vary between the two sets of patients. Left ventricular mass index decreased to a greater extent in the sacubitril/valsartan group compared to the olmesartan group from baseline to 12 weeks (−6.36 vs. −2.32 g/m2; P = 0.039) and from baseline to 52 weeks (−6.83 vs. −3.55 g/m2; P = 0.029). These differences remained significant after adjustment for systolic blood pressure (SBP) at follow-up (P = 0.036 and 0.019 at 12 and 52 weeks, respectively) and similar signals (though formally non-significant) were observed after adjusting for changes in SBP (P = 0.0612 and P = 0.0529, respectively). There were no significant differences in local distensibility changes from baseline to 12 or 52 weeks between the two groups; however, there was a larger reduction in central pulse pressure for the sacubitril/valsartan group compared to the olmesartan group (P = 0.010). Conclusion: Since LV mass change correlates with cardiovascular prognosis, the greater reductions in LV mass indicate valuable advantages of sacubitril/valsartan compared to olmesartan. The finding that LV mass index decrease might be to some extent independent of SBP suggests that the effect of the dual-acting agent may go beyond those due to its BP-lowering ability

Co-production of an educational package for the universal human papillomavirus (HPV) vaccination programme tailored for schools with low uptake:A participatory study protocol

AIM: To co-produce with young people an educational package about the human papillomavirus (HPV) vaccine that is tailored to increase vaccine uptake in schools and populations with lower uptake. INTRODUCTION: Persistent infection with HPV can result in cancers affecting men and especially women. From September 2019, the English-schools-based HPV vaccination programme was expanded to include young men (in addition to young women) aged 12-13 years. Some young people attending schools with lower uptake of the vaccine have unmet information needs. We hypothesise that mechanisms to address information needs and increase young people's autonomy in consent procedures will result in higher uptake. METHODS AND ANALYSIS: The Medical Research Council's framework for development and evaluation of complex interventions will inform intervention development. Recruitment of young people aged 12-15 years and key stakeholders (National Health Service commissioners, school staff, immunisation nurses and youth workers/practitioners) will be facilitated through existing links with healthcare organisations, schools and youth organisations in areas with lower uptake of the HPV vaccination programme. The proposed research will comprise three phases: (1) a rapid review of adolescent immunisation materials and preliminary qualitative interviews with young people and key stakeholders, (2) theory development and co-production of HPV vaccine communication materials through an iterative process with young people and (iii) testing delivery mechanisms and acceptability of the educational package in four schools with lower uptake. ETHICS AND DISSEMINATION: The University of Bristol's Faculty of Health Sciences and London School of Hygiene and Tropical Medicine's Research Ethics Committees provided approvals for the study. A dissemination event for young people and key stakeholders and webinar with the National Immunisation Network will be organised. The study findings will be published in peer-reviewed journals and presented at conferences. Recommendations for a future larger scale study will be made

Effect of exercise intensity on circulating hepatokine concentrations in healthy men

Fibroblast growth factor 21 (FGF21), follistatin and leukocyte cell-derived chemotaxin 2 (LECT2) are novel hepatokines which are modulated by metabolic stresses. This study investigated whether exercise intensity modulates the hepatokine response to acute exercise. Ten young, healthy men undertook three 8-h experimental trials: moderate-intensity exercise (MOD; 55% V̇O2 peak), high-intensity exercise (HIGH; 75% V̇O2 peak) and control (CON; rest), in a randomised, counterbalanced order. Exercise trials commenced with a treadmill run of varied duration to match gross exercise energy expenditure between trials (MOD vs HIGH; 2475 ± 70 vs 2488 ± 58 kJ). Circulating FGF21, follistatin, LECT2, glucagon, insulin, glucose and non-esterified fatty acids (NEFA) were measured before exercise and at 0, 1, 2, 4 and 7 h post-exercise. Plasma FGF21 concentrations were increased up to 4 h post-exercise compared to CON (P ≤ 0.022) with greater increases observed at 1, 2 and 4 h post-exercise during HIGH vs MOD (P ≤ 0.025). Irrespective of intensity (P ≥ 0.606), plasma follistatin concentrations were elevated at 4 and 7 h post-exercise (P ≤ 0.053). Plasma LECT2 concentrations were increased immediately post-exercise (P ≤ 0.046) but were not significant after correcting for plasma volume shifts. Plasma glucagon (1 h; P = 0.032) and NEFA (4 and 7 h; P ≤ 0.029) responses to exercise were accentuated in HIGH vs MOD. These findings demonstrate that acute exercise augments circulating FGF21 and follistatin. Exercise-induced changes in FGF21 are intensity-dependent and may support the greater metabolic benefit of high-intensity exercise

Devices for self-monitoring sedentary time or physical activity: a scoping review.

It is well documented that meeting the guideline levels (150 minutes per week) of moderate-to-vigorous physical activity (PA) is protective against chronic disease. Conversely, emerging evidence indicates the deleterious effects of prolonged sitting. Therefore, there is a need to change both behaviors. Self-monitoring of behavior is one of the most robust behavior-change techniques available. The growing number of technologies in the consumer electronics sector provides a unique opportunity for individuals to self-monitor their behavior.The aim of this study is to review the characteristics and measurement properties of currently available self-monitoring devices for sedentary time and/or PA.To identify technologies, four scientific databases were systematically searched using key terms related to behavior, measurement, and population. Articles published through October 2015 were identified. To identify technologies from the consumer electronic sector, systematic searches of three Internet search engines were also performed through to October 1, 2015.The initial database searches identified 46 devices and the Internet search engines identified 100 devices yielding a total of 146 technologies. Of these, 64 were further removed because they were currently unavailable for purchase or there was no evidence that they were designed for, had been used in, or could readily be modified for self-monitoring purposes. The remaining 82 technologies were included in this review (73 devices self-monitored PA, 9 devices self-monitored sedentary time). Of the 82 devices included, this review identified no published articles in which these devices were used for the purpose of self-monitoring PA and/or sedentary behavior; however, a number of technologies were found via Internet searches that matched the criteria for self-monitoring and provided immediate feedback on PA (ActiGraph Link, Microsoft Band, and Garmin Vivofit) and sedentary time (activPAL VT, the Lumo Back, and Darma).There are a large number of devices that self-monitor PA; however, there is a greater need for the development of tools to self-monitor sedentary time. The novelty of these devices means they have yet to be used in behavior change interventions, although the growing field of wearable technology may facilitate this to change

Associations of objectively measured moderate-to-vigorous-intensity physical activity and sedentary time with all-cause mortality in a population of adults at high risk of type 2 diabetes mellitus

The relationships of physical activity and sedentary time with all-cause mortality in those at high risk of type 2 diabetes mellitus (T2DM) are unexplored. To address this gap in knowledge,we examined the associations of objectively measured moderate-to-vigorous-intensity physical activity (MVPA) and sedentary time with all-cause mortality in a population of adults at high risk of T2DM. In 2010–2011, 712 adults (Leicestershire, U.K.), identified as being at high risk of T2DM, consented to be followed up for mortality.MVPA and sedentary time were assessed by accelerometer; those with valid data (≥10 hours of wear-time/day with ≥4 days of data) were included. Cox proportional hazards regression models, adjusted for potential confounders, were used to investigate the independent associations of MVPA and sedentary time with all-cause mortality. 683 participants (250 females (36.6%)) were included and during a mean follow-up period of 5.7 years, 26 deaths were registered. Every 10% increase in MVPA time/day was associated with a 5% lower risk of all-cause mortality [Hazard Ratio (HR): 0.95 (95% Confidence Interval (95% CI): 0.91, 0.98); p=0.004]; indicating that for the average adult in this cohort undertaking approximately 27.5 minutes of MVPA/day, this benefit would be associated with only 2.75 additional minutes of MVPA/day. Conversely, sedentary time showed no association with all-cause mortality [HR (every 10-minute increase in sedentary time/day): 0.99 (95% CI: 0.95, 1.03); p=0.589]. These data support the importance of MVPA in adults at high risk of T2DM. The association between sedentary time and mortality in this population needs further investigation