Effects of diabetes family history and exercise training on the expression of adiponectin and leptin and their receptors

The daughters of patients with diabetes have reduced insulin sensitivity index (ISI) scores compared with women with no family history of diabetes, but their ISI increase more in response to exercise training(1). The present study aimed to determine whether differences between these groups in exercise-induced changes in circulating adiponectin and leptin concentrations and expression of their genes and receptors in subcutaneous adipose tissue (SAT), could explain differences in the exercise-induced changes in ISI between women with and without a family history of diabetes

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

The impact of confounding on the associations of different adiposity measures with the incidence of cardiovascular disease: a cohort study of 296 535 adults of white European descent

Aims: The data regarding the associations of body mass index (BMI) with cardiovascular (CVD) risk, especially for those at the low categories of BMI, are conflicting. The aim of our study was to examine the associations of body composition (assessed by five different measures) with incident CVD outcomes in healthy individuals. Methods and results: A total of 296 535 participants (57.8% women) of white European descent without CVD at baseline from the UK biobank were included. Exposures were five different measures of adiposity. Fatal and non-fatal CVD events were the primary outcome. Low BMI (≤18.5 kg m−2) was associated with higher incidence of CVD and the lowest CVD risk was exhibited at BMI of 22–23 kg m−2 beyond, which the risk of CVD increased. This J-shaped association attenuated substantially in subgroup analyses, when we excluded participants with comorbidities. In contrast, the associations for the remaining adiposity measures were more linear; 1 SD increase in waist circumference was associated with a hazard ratio of 1.16 [95% confidence interval (CI) 1.13–1.19] for women and 1.10 (95% CI 1.08–1.13) for men with similar magnitude of associations for 1 SD increase in waist-to-hip ratio, waist-to-height ratio, and percentage body fat mass. Conclusion: Increasing adiposity has a detrimental association with CVD health in middle-aged men and women. The association of BMI with CVD appears more susceptible to confounding due to pre-existing comorbidities when compared with other adiposity measures. Any public misconception of a potential ‘protective’ effect of fat on CVD risk should be challenged

Reliability, minimal detectable change and responsiveness to change: indicators to select the best method to measure sedentary behaviour in older adults in different study designs

Introduction : Prolonged sedentary behaviour (SB) is associated with poor health. It is unclear which SB measure is most appropriate for interventions and population surveillance to measure and interpret change in behaviour in older adults. The aims of this study: to examine the relative and absolute reliability, Minimal Detectable Change (MDC) and responsiveness to change of subjective and objective methods of measuring SB in older adults and give recommendations of use for different study designs. Methods : SB of 18 older adults (aged 71 (IQR 7) years) was assessed using a systematic set of six subjective tools, derived from the TAxonomy of Self report Sedentary behaviour Tools (TASST), and one objective tool (activPAL3c), over 14 days. Relative reliability (Intra Class Correlation coefficients-ICC), absolute reliability (SEM), MDC, and the relative responsiveness (Cohen's d effect size (ES) and Guyatt's Responsiveness coefficient (GR)) were calculated for each of the different tools and ranked for different study designs. Results : ICC ranged from 0.414 to 0.946, SEM from 36.03 to 137.01 min, MDC from 1.66 to 8.42 hours, ES from 0.017 to 0.259 and GR from 0.024 to 0.485. Objective average day per week measurement ranked as most responsive in a clinical practice setting, whereas a one day measurement ranked highest in quasi-experimental, longitudinal and controlled trial study designs. TV viewing Previous Week Recall (PWR) ranked as most responsive subjective measure in all study designs. Conclusions : The reliability, Minimal Detectable Change and responsiveness to change of subjective and objective methods of measuring SB is context dependent. Although TV viewing-PWR is the more reliable and responsive subjective method in most situations, it may have limitations as a reliable measure of total SB. Results of this study can be used to guide choice of tools for detecting change in sedentary behaviour in older adults in the contexts of population surveillance, intervention evaluation and individual care

Associations between diabetes and both cardiovascular disease and all-cause mortality are modified by grip strength: evidence from UK Biobank, a prospective population-based cohort study

OBJECTIVE Grip strength and diabetes are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to predispose to adverse health outcomes is unknown. This study determined the interactions between diabetes and grip strength and their association with health outcomes. RESEARCH DESIGN AND METHODS We undertook a prospective, general population cohort study by using UK Biobank. Cox proportional hazards models were used to explore the associations between both grip strength and diabetes and the outcomes of all-cause mortality and CVD incidence/mortality as well as to test for interactions between diabetes and grip strength. RESULTS 347,130 UK Biobank participants with full data available (mean age 55.9 years, BMI 27.2 kg/m2, 54.2% women) were included in the analysis, of which 13,373 (4.0%) had diabetes. Over a median follow-up of 4.9 years (range 3.3–7.8 years), 6,209 died (594 as a result of CVD), and 4,301 developed CVD. Participants with diabetes were at higher risk of all-cause and CVD mortality and CVD incidence. Significant interactions (P < 0.05) existed whereby the risk of CVD mortality was higher in participants with diabetes with low (hazard ratio [HR] 4.05 [95% CI 2.72, 5.80]) versus high (HR 1.46 [0.87, 2.46]) grip strength. Similar results were observed for all-cause mortality and CVD incidence. CONCLUSIONS Risk of adverse health outcomes among people with diabetes is lower in those with high grip strength. Low grip strength may be useful to identify a higher-risk subgroup of patients with diabetes. Intervention studies are required to determine whether resistance exercise can reduce risk

Individual responsiveness to exercise-induced fat loss is associated with change in resting substrate utilization

Fat loss in response to exercise training varies between individuals, even when differences in compliance to the exercise program are accounted for. The purpose of this study was to investigate whether individual variation in change in fasting respiratory quotient (RQ) after exercise training contributes to this interindividual variability. Fifty-five premenopausal women participated in a 7-week endurance-type exercise training program; and fitness, body composition, and resting substrate utilization and metabolic rate in the fasted state were assessed at baseline and postintervention. Total net energy expenditure of the exercise intervention (exEE) was determined from heart rate obtained in all exercise sessions and individualized calibration of the heart rate vs oxygen uptake relationship. Dietary intake and physical activity (by constant heart rate monitoring) were assessed at baseline and during the final week of the intervention. Mean change in fat mass for the group was −0.97 kg (range, +2.1 to −5.3 kg). The strongest correlate of change in fat mass was exEE (r = 0.60, P < .0005). Change in fasting RQ correlated significantly (r = −0.26, P = .05) with the residual for change in fat mass after adjusting for the effects of both exEE and change in energy intake, explaining 7% of the variance. In multiple regression analysis, exEE (P < .0005) and change in fasting RQ (P = .02) were the only statistically significant independent predictors of change in fat mass, together explaining 40.2% of the variance. Thus, fat loss in response to exercise training depends not only on exercise energy expenditure but also on exercise training–induced changes in RQ at rest. This suggests that development of strategies to maximize the change in resting fat oxidation in response to an exercise training program may help individuals to maximize exercise-induced fat loss

PCSK9 genetic variants and cognitive abilities:a large-scale Mendelian randomization study

Introduction: PCSK9 inhibitors lower low-density lipoprotein (LDL) cholesterol and are efficacious at reducing vascular disease, however questions remain about potential effects on cognitive function. Methods: We examined the association of genetic variants in PCSK9 with continuous measures of cognitive ability in UK Biobank. Six independent polymorphisms in PCSK9 were used in up to 337,348 individuals. Results: The PCSK9 allele score was associated with a lower risk of CHD, and weakly with worse log reaction time. Conclusions: We are unable to rule out meaningful associations of PCSK9 genetic variants with cognition, emphasising the potential need for continued pharmacovigilance for patients currently treated with PCSK9 inhibitors

Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants

Objective: To investigate the association of grip strength with disease specific incidence and mortality and whether grip strength enhances the prediction ability of an established office based risk score. Design: Prospective population based study. Setting: UK Biobank. Participants: 502 293 participants (54% women) aged 40-69 years. Main outcome measures: All cause mortality as well as incidence of and mortality from cardiovascular disease, respiratory disease, chronic obstructive pulmonary disease, and cancer (all cancer, colorectal, lung, breast, and prostate). Results: Of the participants included in analyses, 13 322 (2.7%) died over a mean of 7.1 (range 5.3-9.9) years’ follow-up. In women and men, respectively, hazard ratios per 5 kg lower grip strength were higher (all at P&lt;0.05) for all cause mortality (1.20, 95% confidence interval 1.17 to 1.23, and 1.16, 1.15 to 1.17) and cause specific mortality from cardiovascular disease (1.19, 1.13 to 1.25, and 1.22, 1.18 to 1.26), all respiratory disease (1.31, 1.22 to 1.40, and 1.24, 1.20 to 1.28), chronic obstructive pulmonary disease (1.24, 1.05 to 1.47, and 1.19, 1.09 to 1.30), all cancer (1.17, 1.13 to 1.21, 1.10, 1.07 to 1.13), colorectal cancer (1.17, 1.04 to 1.32, and 1.18, 1.09 to 1.27), lung cancer (1.17, 1.07 to 1.27, and 1.08, 1.03 to 1.13), and breast cancer (1.24, 1.10 to 1.39) but not prostate cancer (1.05, 0.96 to 1.15). Several of these relations had higher hazard ratios in the younger age group. Muscle weakness (defined as grip strength &lt;26 kg for men and &lt;16 kg for women) was associated with a higher hazard for all health outcomes, except colon cancer in women and prostate cancer and lung cancer in both men and women. The addition of handgrip strength improved the prediction ability, based on C index change, of an office based risk score (age, sex, diabetes diagnosed, body mass index, systolic blood pressure, and smoking) for all cause (0.013) and cardiovascular mortality (0.012) and incidence of cardiovascular disease (0.009). Conclusion: Higher grip strength was associated with a range of health outcomes and improved prediction of an office based risk score. Further work on the use of grip strength in risk scores or risk screening is needed to establish its potential clinical utility

Developing a realist informed framework for cultural adaptation of lifestyle interventions for the prevention of type 2 diabetes in South Asian populations in Europe

Aims Selected lifestyle interventions proven effective for White-European populations have been culturally adapted for South Asian populations living in Europe, who are at higher risk of type 2 diabetes. However, a limited theoretical basis underpins how cultural adaptations are believed to augment intervention effectiveness. We undertook a realist review to synthesise existing literature on culturally adapted type 2 diabetes prevention interventions, to develop a framework that shows ‘how’ cultural adaptation works, for ‘whom’ and in ‘what contexts’. Methods We followed the stepped methodological approach of realist review. Our work concluded a European-wide project (EuroDHYAN), and core studies were identified from the preceding EuroDHYAN reviews. Data were extracted, coded into themes and synthesised to create ‘Context–Mechanism–Outcome’ configurations and to generate a refined explanatory framework. Results We identified eight core intervention papers. From this evidence, and supporting literature, we examined the ‘Team’ domain of cultural adaptation and identified a mechanism of shared cultural identity which we theorised as contributing to strong team-participant relationships. We also identified four key contexts which influenced intervention outcomes: ‘research setting’ and ‘heterogeneous populations’ (intrinsic to the intervention) and ‘broader environment’ and ‘socio-cultural stress’ (extrinsic barriers). Conclusions This work instigates research into the mechanisms of cultural adaptation which, if pursued, will allow a more nuanced understanding of how to apply adaptations, and for whom. In practice we recommend greater consideration of heterogeneous and intersecting population characteristics; how intervention design can safeguard sustainability; and how the four key contexts identified influence how, and whether, these interventions work