Initiation of New Glucose-Lowering Therapies May Act to Reduce Physical Activity Levels: Pooled Analysis From Three Randomized Trials.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown. RESEARCH DESIGN AND METHODS: We pooled data (n = 148) from three randomized trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison with sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies, on accelerometer-assessed physical activity. RESULTS: Liraglutide (mean -1,144 steps/day; 95% CI -2,069 to -220), empagliflozin (-1,132 steps/day; -1,739, -524), and sitagliptin (-852 steps/day; -1,625, -78) resulted in reduced total daily physical activity after 6 months (P < 0.01 vs. control). Moderate- to vigorous-intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity. CONCLUSIONS: The initiation of all glucose-lowering therapies was associated with reduced physical activity, warranting further investigation.

Promoting physical activity in a multi-ethnic population at high risk of diabetes: the 48-month PROPELS randomised controlled trial.

BACKGROUND: Physical activity is associated with a reduced risk of type 2 diabetes and cardiovascular disease but limited evidence exists for the sustained promotion of increased physical activity within diabetes prevention trials. The aim of the study was to investigate the long-term effectiveness of the Walking Away programme, an established group-based behavioural physical activity intervention with pedometer use, when delivered alone or with a supporting mHealth intervention. METHODS: Those at risk of diabetes (nondiabetic hyperglycaemia) were recruited from primary care, 2013-2015, and randomised to (1) Control (information leaflet); (2) Walking Away (WA), a structured group education session followed by annual group-based support; or (3) Walking Away Plus (WAP), comprising WA annual group-based support and an mHealth intervention delivering tailored text messages supported by telephone calls. Follow-up was conducted at 12 and 48 months. The primary outcome was accelerometer measured ambulatory activity (steps/day). Change in primary outcome was analysed using analysis of covariance with adjustment for baseline, randomisation and stratification variables. RESULTS: One thousand three hundred sixty-six individuals were randomised (median age = 61 years, ambulatory activity = 6638 steps/day, women = 49%, ethnic minorities = 28%). Accelerometer data were available for 1017 (74%) individuals at 12 months and 993 (73%) at 48 months. At 12 months, WAP increased their ambulatory activity by 547 (97.5% CI 211, 882) steps/day compared to control and were 1.61 (97.5% CI 1.05, 2.45) times more likely to achieve 150 min/week of moderate-to-vigorous physical activity. Differences were not maintained at 48 months. WA was no different to control at 12 or 48 months. Secondary anthropometric and health outcomes were largely unaltered in both intervention groups apart from small reductions in body weight in WA (~ 1 kg) at 12- and 48-month follow-up. CONCLUSIONS: Combining a pragmatic group-based intervention with text messaging and telephone support resulted in modest changes to physical activity at 12 months, but changes were not maintained at 48 months. TRIAL REGISTRATION: ISRCTN 83465245 (registered on 14 June 2012).

Metabolic Effects of Breaking Prolonged Sitting With Standing or Light Walking in Older South Asians and White Europeans: A Randomized Acute Study.

BACKGROUND: Prolonged sitting is common in older adults and is associated with insulin resistance and poor cardiometabolic health. We investigate whether breaking prolonged sitting with regular short bouts of standing or light walking improves postprandial metabolism in older white European and South Asian adults and whether effects are modified by ethnic group. METHODS: Thirty South Asian (15 women) and 30 white European (14 women) older adults (aged 65-79 years) undertook three experimental conditions in random order. (a) Prolonged sitting: continuous sitting during an observation period if 7.5 hours consuming two standardized mixed meals. (b) Standing breaks: sitting interrupted with 5 minutes of standing every 30 minutes (accumulating 60 minutes of standing over the observation period). (c) Walking breaks: sitting interrupted with 5 minutes of self-paced light walking every 30 minutes (accumulating 60 minutes of walking). Blood samples (glucose, insulin, triglycerides) and blood pressure were sampled regularly throughout each condition. RESULTS: Compared with prolonged sitting, walking breaks lowered postprandial insulin by 16.3 mU/L, (95% CI: 19.7, 22.0) with greater reductions (p = .029) seen in South Asians (22.4 mU/L; 12.4, 32.4) than white Europeans (10.3 mU/L; 5.9, 14.7). Glucose (0.3 mmol/L; 0.1, 0.5) and blood pressure (4 mm Hg; 2, 6), but not triglycerides, were lower with walking breaks, with no ethnic differences. Standing breaks did not improve any outcome. CONCLUSIONS: Breaking prolonged sitting with short bouts of light walking, but not standing, resulted in clinically meaningful improvements in markers of metabolic health in older adults, with South Asians gaining a greater reduction in postprandial insulin. TRIAL REGISTRATION: NCT02453204.

The association between air pollution and type 2 diabetes in a large cross-sectional study in Leicester: The CHAMPIONS Study.

BACKGROUND: Observational evidence suggests there is an association between air pollution and type 2 diabetes; however, there is high risk of bias. OBJECTIVE: To investigate the association between air pollution and type 2 diabetes, while reducing bias due to exposure assessment, outcome assessment, and confounder assessment. METHODS: Data were collected from 10,443 participants in three diabetes screening studies in Leicestershire, UK. Exposure assessment included standard, prevailing estimates of outdoor nitrogen dioxide and particulate matter concentrations in a 1×1km area at the participant's home postcode. Three-year exposure was investigated in the primary analysis and one-year exposure in a sensitivity analysis. Outcome assessment included the oral glucose tolerance test for type 2 diabetes. Confounder assessment included demographic factors (age, sex, ethnicity, smoking, area social deprivation, urban or rural location), lifestyle factors (body mass index and physical activity), and neighbourhood green space. RESULTS: Nitrogen dioxide and particulate matter concentrations were associated with type 2 diabetes in unadjusted models. There was no statistically significant association between nitrogen dioxide concentration and type 2 diabetes after adjustment for demographic factors (odds: 1.08; 95% CI: 0.91, 1.29). The odds of type 2 diabetes was 1.10 (95% CI: 0.92, 1.32) after further adjustment for lifestyle factors and 0.91 (95% CI: 0.72, 1.16) after yet further adjustment for neighbourhood green space. The associations between particulate matter concentrations and type 2 diabetes were also explained away by demographic factors. There was no evidence of exposure definition bias. CONCLUSIONS: Demographic factors seemed to explain the association between air pollution and type 2 diabetes in this cross-sectional study. High-quality longitudinal studies are needed to improve our understanding of the association.

Associations of reallocating sitting time into standing or stepping with glucose, insulin and insulin sensitivity: a cross-sectional analysis of adults at risk of type 2 diabetes.

OBJECTIVE: To quantify associations between sitting time and glucose, insulin and insulin sensitivity by considering reallocation of time into standing or stepping. DESIGN: Cross-sectional. SETTING: Leicestershire, UK, 2013. PARTICIPANTS: Adults aged 30-75 years at high risk of impaired glucose regulation (IGR) or type 2 diabetes. 435 adults (age 66.8±7.4 years; 61.7% male; 89.2% white European) were included. METHODS: Participants wore an activPAL3 monitor 24 hours/day for 7 days to capture time spent sitting, standing and stepping. Fasting and 2-hour postchallenge glucose and insulin were assessed; insulin sensitivity was calculated by Homeostasis Model Assessment of Insulin Secretion (HOMA-IS) and Matsuda-Insulin Sensitivity Index (Matsuda-ISI). Isotemporal substitution regression modelling was used to quantify associations of substituting 30 min of waking sitting time (accumulated in prolonged (≥30 min) or short (<30 min) bouts) for standing or stepping on glucose regulation and insulin sensitivity. Interaction terms were fitted to assess whether the associations with measures of glucose regulation and insulin sensitivity was modified by sex or IGR status. RESULTS: After adjustment for confounders, including waist circumference, reallocation of prolonged sitting to short sitting time and to standing was associated with 4% lower fasting insulin and 4% higher HOMA-IS; reallocation of prolonged sitting to standing was also associated with a 5% higher Matsuda-ISI. Reallocation to stepping was associated with 5% lower 2-hour glucose, 7% lower fasting insulin, 13% lower 2-hour insulin and a 9% and 16% higher HOMA-IS and Matsuda-ISI, respectively. Reallocation of short sitting time to stepping was associated with 5% and 10% lower 2-hour glucose and 2-hour insulin and 12% higher Matsuda-ISI. Results were not modified by IGR status or sex. CONCLUSIONS: Reallocating a small amount of short or prolonged sitting time with standing or stepping may improve 2-hour glucose, fasting and 2-hour insulin and insulin sensitivity. Findings should be confirmed through prospective and intervention research. TRIAL REGISTRATION NUMBER: ISRCTN31392913, Post-results.

Differences in levels of physical activity between White and South Asian populations within a healthcare setting: impact of measurement type in a cross-sectional study.

OBJECTIVE: We investigate differences between White and South Asian (SA) populations in levels of objectively measured and self-reported physical activity. DESIGN: Cross-sectional study. SETTING: Leicestershire, UK, 2010-2011. PARTICIPANTS: Baseline data were pooled from two diabetes prevention trials that recruited a total of 4282 participants from primary care with a high risk score for type 2 diabetes. For this study, 2843 White (age=64±8, female=37%) and 243 SA (age=58±9, female=34%) participants had complete physical activity data and were included in the analysis. OUTCOME MEASURES: Moderate-intensity to vigorous-intensity physical activity (MVPA) and walking activity were measured using the International Physical Activity Questionnaire (IPAQ), and a combination of piezoelectric pedometer (NL-800) and accelerometer (Actigraph GT3X) were used to objectively measure physical activity. RESULTS: Compared to White participants, SA participants self-reported less MVPA (30 vs 51 min/day; p<0.001) and walking activity (11 vs 17 min/day; P=0.001). However, there was no difference in objectively measured ambulatory activity (5992 steps/day vs 6157 steps/day; p=0.75) or in time spent in MVPA (18.0 vs 21.5 min/day; p=0.23). Results were largely unaffected when adjusted for age, sex and social deprivation. Compared to accelerometer data, White participants overestimated their time in MVPA by 51 min/day and SA participants by 21 min/day. CONCLUSIONS: SA and White groups undertook similar levels of physical activity when measured objectively despite self-reported estimates being around 40% lower in the SA group. This emphasises the limitations of comparing self-reported lifestyle measures across different populations and ethnic groups. TRIAL REGISTRATION NUMBER: Reports baseline data from: Walking Away from Type 2 Diabetes (ISRCTN31392913) and Let's Prevent Diabetes (NCT00677937).

Bounding Quantum Contextuality with Lack of Third-Order Interference.

Recently, many simple principles have been proposed that can explain quantum limitations on possible sets of experimental probabilities in nonlocality and contextuality experiments. However, few implications between these principles are known. Here it is shown that the lack of irreducible third-order interference (a generalization of the idea that no probabilistic interference remains unaccounted for once we have taken into account interference between pairs of slits in a n-sit experiment) implies the principle known as the E principle or consistent exclusivity (that, if each pair of a set of experimental outcomes are exclusive alternatives in some measurement, then their probabilities are consistent with the existence of a further measurement in which they are all exclusive). This is a step towards a more unified understanding of quantum nonlocality and contextuality, which promises to allow derivations of important results from minimal, easily grasped assumptions. As one example, this result implies that lack of third-order interference bounds violation of the Clauser-Horne-Shimony-Holt-Bell inequality to 2.883.

Effect of physical activity measurement type on the association between walking activity and glucose regulation in a high-risk population recruited from primary care.

BACKGROUND: We investigate associations of self-reported and objectively assessed walking activity with measures of glucose regulation in a multi-ethnic population at high risk of type 2 diabetes. METHODS: This study reports data from a 2009-2011 screening programme for impaired glucose regulation (IGR) within a high-risk primary care population in Leicestershire, UK; 2532 participants (38% women, 8% South Asian) with a mean age of 64 ± 8 years and an average BMI of 32.1 ± 5.6 kg/m(2) were included. Walking activity was measured by self-report (International Physical Activity Questionnaire) and objectively (pedometer). Glucose regulation assessments included 2h post-challenge glucose, fasting glucose and HbA1c. RESULTS: Higher levels of self-reported walking activity and pedometer steps were associated with lower 2h post-challenge glucose after controlling for several known confounding variables, including BMI. Similarly, when categorized in tertiles, both measures were associated with a lower odds of having any form of IGR; odds ratio for lowest vs highest tertile was 0.64 (0.51-0.80) for self-report and 0.69 (0.55-0.87) for pedometer steps. There was no significant difference between self-reported and objective measures in the strength of associations with glucose regulation; associations with self-report were maintained when further adjusted for pedometer steps. Stronger associations between self-reported walking activity and glucose regulation were observed in South Asians compared with White Europeans. CONCLUSIONS: Self-reported and objectively measured walking activity were equally associated with indices of glucose regulation. Associations with self-reported walking activity were maintained when further adjusted for pedometer steps, suggesting that self-reported walking activity may measure facets of physical activity that are beyond total volume.

Association of sitting time and physical activity with CKD: a cross-sectional study in family practices.

BACKGROUND: Chronic kidney disease (CKD) represents a significant and growing health care burden globally. Lifestyle factors, such as physical activity and sitting-related sedentary behavior, have been hypothesized to be directly associated with CKD; however, epidemiologic research is limited. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: A population-level diabetes screening program conducted across 20 family practices in Leicester, United Kingdom, August 2004 to December 2007. PREDICTORS: Self-reported sitting time and physical activity, obtained using the International Physical Activity Questionnaire. OUTCOMES & MEASUREMENTS: CKD, defined using NKF-KDOQI (National Kidney Foundation's Kidney Disease Outcomes Quality Initiative) criteria. RESULTS: 6,379 (52% women) individuals were included. Lower levels of sitting time were associated with lower risk of CKD after controlling for physical activity, body mass index, and other potential confounding variables (OR, 0.74 [95% CI, 0.62-0.92] for lowest vs highest tertile). Interaction analysis showed that women trended toward a significantly higher risk of CKD with higher levels of sitting time compared with men. Participating in levels of physical activity that were at least consistent with the minimum recommendations for health was associated with lower risk of CKD. A significant interaction with sex was observed, with men showing a lower risk of CKD with high levels of physical activity compared with women. LIMITATIONS: Cross-sectional design, self-reported lifestyle data, CKD defined at a single time, and estimated glomerular filtration rate and microalbuminuria were the only measures used to define CKD. CONCLUSIONS: This study suggests that higher levels of physical activity and lower levels of sitting time are associated with a lower prevalence of CKD independently of each other and other risk factors. However, results may vary by sex, with sitting time being the more important factor in women and physical activity the more important factor in men. These results have important implications for future research.

Walking away from type 2 diabetes: trial protocol of a cluster randomised controlled trial evaluating a structured education programme in those at high risk of developing type 2 diabetes.

BACKGROUND: The prevention of type 2 diabetes is a recognised health care priority globally. Within the United Kingdom, there is a lack of research investigating optimal methods of translating diabetes prevention programmes, based on the promotion of a healthy lifestyle, into routine primary care. This study aims to establish the behavioural and clinical effectiveness of a structured educational programme designed to target perceptions and knowledge of diabetes risk and promote a healthily lifestyle, particularly increased walking activity, in a multi-ethnic population at a high risk of developing type 2 diabetes. DESIGN: Cluster randomised controlled trial undertaken at the level of primary care practices. Follow-up will be conducted at 12, 24 and 36 months. The primary outcome is change in objectively measured ambulatory activity. Secondary outcomes include progression to type 2 diabetes, biochemical variables (including fasting glucose, 2-h glucose, HbA1c and lipids), anthropometric variables, quality of life and depression. METHODS: 10 primary care practices will be recruited to the study (5 intervention, 5 control). Within each practice, individuals at high risk of impaired glucose regulation will be identified using an automated version of the Leicester Risk Assessment tool. Individuals scoring within the 90th percentile in each practice will be invited to take part in the study. Practices will be assigned to either the control group (advice leaflet) or the intervention group, in which participants will be invited to attend a 3 hour structured educational programme designed to promote physical activity and a healthy lifestyle. Participants in the intervention practices will also be invited to attend annual group-based maintenance workshops and will receive telephone contact halfway between annual sessions. The study will run from 2010-2014. DISCUSSION: This study will provide new evidence surrounding the long-term effectiveness of a diabetes prevention programme run within routine primary care in the United Kingdom. TRIAL REGISTRATION: ClinicalTrials.Gov identifier: NCT00941954.

Self-reported sitting time and markers of inflammation, insulin resistance, and adiposity.

BACKGROUND: Sedentary behavior is emerging as an independent risk factor for chronic disease; however, potential mechanisms underpinning these observations are not well understood. PURPOSE: This study aimed to investigate the association of self-reported weekday sitting time with biomarkers linked to chronic low-grade inflammation, insulin resistance, and adiposity. METHODS: This study reports data from individuals attending a diabetes screening program, United Kingdom, 2004-2007; analysis was conducted in 2010. Sitting time and physical activity were measured using the International Physical Activity Questionnaire; biochemical outcomes included fasting and 2-hour postchallenge glucose, fasting insulin, C-reactive protein (CRP), leptin, adiponectin, and interleukin-6 (IL-6). RESULTS: This study included 505 (female=46%; South-Asian ethnicity=19%, aged 59±10 years, BMI=29.5±4.7) individuals with valid sitting data. Increased sitting time was positively associated with fasting insulin, leptin, leptin/adiponectin ratio, CRP, and IL-6 in women, but not men, after adjustment for age, ethnicity, social deprivation, and smoking and medication status; interaction analysis revealed that the gender-specific differences were significant. The associations for women remained significant after additional adjustment for total moderate- to vigorous-intensity physical activity; however all associations were attenuated when further adjusted for BMI. There was no association between sitting time and glycemic status. CONCLUSIONS: Total self-reported weekday sitting time was associated with biomarkers linked to chronic low-grade inflammation and poor metabolic health in women, but not men, independent of physical activity.