Lack of association between PCK1 polymorphisms and obesity, physical activity, and fitness in European Youth Heart Study (EYHS)

Phosphoenolpyruvate carboxykinase-1 (PCK1) is the rate-limiting enzyme in the hepatic gluconeogenic pathway. Studies have shown that overexpression of Pck1 in mice results in obesity-related traits and higher levels of physical activity (PA). Therefore, our aims were to investigate whether common genetic variation in the PCK1 gene influences obesity-related traits, PA, and fitness, and to examine whether PA and fitness attenuate the influence of the PCK1 polymorphisms on obesity in children. Analyses were undertaken on data from Danish and Estonian children (958 boys and 1,104 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of children (mean ± s.d. age: 9.6 ± 0.4 years) and adolescents (15.5 ± 0.5 years). We genotyped eight polymorphisms that captured the common genetic variations in the PCK1 gene. The association between the PCK1 polymorphisms and BMI, waist circumference (WC), sum of four skinfolds, PA, and fitness was tested using an additive model adjusted for age, age-group, gender, maturity, and country. Interactions were tested by including interaction terms in the model. None of the polymorphisms were significantly associated with BMI, WC, sum of four skinfolds, PA, and fitness, and also with the risk of being overweight or obese (P > 0.05). The interactions between the polymorphisms and age-group, gender, PA, and fitness were not statistically significant. This is the first study to comprehensively examine the association of PCK1 polymorphisms with obesity, PA, and fitness. Despite strong evidence from animal studies, our study in the EYHS cohort failed to identify an association of PCK1 polymorphisms with obesity, PA, and fitness

Objective measurement of sedentary behaviour using accelerometers

Background: Sedentary behaviour (SB) is an important risk factor for a number of chronic diseases. Although gaps remain in our knowledge of the elements of SB most associated with reduced health outcomes, measuring SB is important, especially in less active patient populations where treatment-related changes may be seen first in changes in SB.Methods: We review current published work in the measurement of SB to make recommendations for SB measurement in clinical studies.Results: To help move our understanding of the area forward, we propose a set of derived measures of SB that can be easily understood and interpreted.Conclusion: Although there is more work required to determine and validate the most clinically relevant and sensitive measures of SB, there is enough understanding of how to measure SB to enable its inclusion in study protocols

Managing sedentary behavior to reduce the risk of diabetes and cardiovascular disease

Modern human environments are vastly different from those of our forebears. Rapidly advancing technology in transportation, communications, workplaces, and home entertainment confer a wealth of benefits, but increasingly come with costs to human health. Sedentary behavior—too much sitting as distinct from too little physical activity—contributes adversely to cardiometabolic health outcomes and premature mortality. Findings from observational epidemiology have been synthesized in meta-analyses, and evidence is now shifting into the realm of experimental trials with the aim of identifying novel mechanisms and potential causal relationships. We discuss recent observational and experimental evidence that makes a compelling case for reducing and breaking up prolonged sitting time in both the primary prevention and disease management contexts. We also highlight future research needs, the opportunities for developing targeted interventions, and the potential of population-wide initiatives designed to address too much sitting as a health risk

“Keeping Moving”: factors associated with sedentary behaviour among older people recruited to an exercise promotion trial in general practice

Background Sedentary behaviour is detrimental to health, even in those who achieve recommended levels of physical activity. Efforts to increase physical activity in older people so that they reach beneficial levels have been disappointing. Reducing sedentary behaviour may improve health and be less demanding of older people, but it is not clear how to achieve this. We explored the characteristics of sedentary older people enrolled into an exercise promotion trial to gain insights about those who were sedentary but wanted to increase activity. Method Participants in the ProAct65+ trial (2009–2013) were categorised as sedentary or not using a self-report questionnaire. Demographic data, health status, self-rated function and physical test performance were examined for each group. 1104 participants aged 65 & over were included in the secondary analysis of trial data from older people recruited via general practice. Results were analysed using logistic regression with stepwise backward elimination. Results Three hundred eighty seven (35 %) of the study sample were characterised as sedentary. The likelihood of being categorised as sedentary increased with an abnormal BMI (25 kg/m2) (Odds Ratio 1.740, CI 1.248–2.425), ever smoking (OR 1.420, CI 1.042–1.934) and with every additional medication prescribed (OR 1.069, CI 1.016–1.124). Participants reporting better self-rated physical health (SF-12) were less likely to be sedentary; (OR 0.961, 0.936–0.987). Participants’ sedentary behaviour was not associated with gender, age, income, education, falls, functional fitness, quality of life or number of co-morbidities. Conclusion Some sedentary older adults will respond positively to an invitation to join an exercise study. Those who did so in this study had poor self-rated health, abnormal BMI, a history of smoking, and multiple medication use, and are therefore likely to benefit from an exercise intervention

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants

BACKGROUND: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. METHODS: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence—defined as fasting plasma glucose of 7·0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs—in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. FINDINGS: We used data from 751 studies including 4 372 000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4·3% (95% credible interval 2·4–7·0) in 1980 to 9·0% (7·2–11·1) in 2014 in men, and from 5·0% (2·9–7·9) to 7·9% (6·4–9·7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28·5% due to the rise in prevalence, 39·7% due to population growth and ageing, and 31·8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. INTERPRETATION: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. FUNDING: Wellcome Trust

Genetic Susceptibility to Obesity and Related Traits in Childhood and Adolescence: Influence of Loci Identified by Genome-Wide Association Studies

Large-scale genome-wide association (GWA) studies have thus far identified 16 loci incontrovertibly associated with obesity-related traits in adults. We examined associations of variants in these loci with anthropometric traits in children and adolescents

Longitudinal patterns in objective physical activity and sedentary time in a multi-ethnic sample of children from the UK

Background: Children of South Asian decent born in the UK display lower levels of physical activity than British Caucasians although no longitudinal data are available. Objectives: We aimed to investigate change in activity levels over 1 year in a diverse ethnic sample of children residing in London, UK. Methods: Children were categorized into ethnic groups (Caucasian/mixed, Black, South Asian). At baseline and 1-year follow-up, children’s objective physical activity was monitored (Actigraph accelerometer) for at least 1 day. Mixed models were employed to investigate differences in change in activity levels between ethnic groups. Results: A total of 281 children were included in the analyses. South Asians had a significantly greater increase in time spent sedentary at follow-up than those of a Caucasian/mixed ethnicity (B [ratio sedentary/wear time] = 0.024; 95% confidence interval 0.003, 0.046). South Asian children recorded lower moderate to vigorous physical activity at baseline (B = 6.5, 95% confidence interval, 11.1, 1.9 min d1, p = 0.006) although levels remained relatively stable over follow-up and changes did not differ across ethnic group. Conclusions: In a diverse ethnic sample of children from inner city London, those of a South Asian ethnicity exhibited a significantly greater increase in sedentary time over a period of 12 months in comparison with Caucasian/mixed and Black children

DNA-Induced Unfolding of the Thyroid Hormone Receptor a A/B Domain through Allostery

The A/B domains of nuclear receptors such as thyroid receptor a (TRa) are considered to be conformationally flexible and can potentially adopt multiple structural conformations. We used intrinsic tryptophan fluorescence quenching and circular dichroism spectroscopy to characterize the unfolding of this A/B domain upon DNA binding to the contiguous DNA binding domain (DBD). We propose that this allosteric change in A/B domain conformation can allow it to make the multiple interactions with distinct molecular factors of the transcriptional preinitiation complex. We further suggest that by influencing the affinity of the DBD for DNA, A/B domain can fine-tune the recognition of promotor DNA by TRa