WITHDRAWN: Interventions for treating obesity in children.

BACKGROUND: Child and adolescent obesity is increasingly prevalent, and can be associated with significant short- and long-term health consequences. OBJECTIVES: To assess the efficacy of lifestyle, drug and surgical interventions for treating obesity in childhood. SEARCH METHODS: We searched CENTRAL on The Cochrane Library Issue 2 2008, MEDLINE, EMBASE, CINAHL, PsycINFO, ISI Web of Science, DARE and NHS EED. Searches were undertaken from 1985 to May 2008. References were checked. No language restrictions were applied. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of lifestyle (i.e. dietary, physical activity and/or behavioural therapy), drug and surgical interventions for treating obesity in children (mean age under 18 years) with or without the support of family members, with a minimum of six months follow up (three months for actual drug therapy). Interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data following the Cochrane Handbook. Where necessary authors were contacted for additional information. MAIN RESULTS: We included 64 RCTs (5230 participants). Lifestyle interventions focused on physical activity and sedentary behaviour in 12 studies, diet in 6 studies, and 36 concentrated on behaviorally orientated treatment programs. Three types of drug interventions (metformin, orlistat and sibutramine) were found in 10 studies. No surgical intervention was eligible for inclusion. The studies included varied greatly in intervention design, outcome measurements and methodological quality.Meta-analyses indicated a reduction in overweight at 6 and 12 months follow up in: i) lifestyle interventions involving children; and ii) lifestyle interventions in adolescents with or without the addition of orlistat or sibutramine. A range of adverse effects was noted in drug RCTs. AUTHORS' CONCLUSIONS: While there is limited quality data to recommend one treatment program to be favoured over another, this review shows that combined behavioural lifestyle interventions compared to standard care or self-help can produce a significant and clinically meaningful reduction in overweight in children and adolescents. In obese adolescents, consideration should be given to the use of either orlistat or sibutramine, as an adjunct to lifestyle interventions, although this approach needs to be carefully weighed up against the potential for adverse effects. Furthermore, high quality research that considers psychosocial determinants for behaviour change, strategies to improve clinician-family interaction, and cost-effective programs for primary and community care is required.

Later achievement of infant motor milestones is related to lower levels of physical activity during childhood: the GECKO Drenthe cohort.

BACKGROUND: The aim of this study is to investigate whether age of infant motor milestone achievement is related to levels of physical activity (PA), weight status and blood pressure at age 4-7 years of age. METHODS: In the Dutch GECKO (Groningen Expert Center of Kids with Obesity) Drenthe cohort, the age of achieving the motor milestone 'walking without support' was reported by parents. Weight status and blood pressure were assessed by trained health nurses and PA was measured using the Actigraph GT3X between age 4 and 7 years. RESULTS: Adjusted for children's age, sex and the mother's education level, infants who achieved walking without support at a later age, spent more time in sedentary behaviour during childhood and less time in moderate-to-vigorous PA. Later motor milestones achievement was not related to higher BMI Z-score, waist circumference Z-score, diastolic or systolic blood pressure. CONCLUSION: The results of this study indicate that a later age of achieving motor milestone within the normal range have a weak relation to lower PA levels at later age. It is not likely that this will have consequences for weight status or blood pressure at 4-7 years of age.

Long-term exposure to road traffic noise, ambient air pollution, and cardiovascular risk factors in the HUNT and lifelines cohorts.

AIMS: Blood biochemistry may provide information on associations between road traffic noise, air pollution, and cardiovascular disease risk. We evaluated this in two large European cohorts (HUNT3, Lifelines). METHODS AND RESULTS: Road traffic noise exposure was modelled for 2009 using a simplified version of the Common Noise Assessment Methods in Europe (CNOSSOS-EU). Annual ambient air pollution (PM10, NO2) at residence was estimated for 2007 using a Land Use Regression model. The statistical platform DataSHIELD was used to pool data from 144 082 participants aged ≥20 years to enable individual-level analysis. Generalized linear models were fitted to assess cross-sectional associations between pollutants and high-sensitivity C-reactive protein (hsCRP), blood lipids and for (Lifelines only) fasting blood glucose, for samples taken during recruitment in 2006-2013. Pooling both cohorts, an inter-quartile range (IQR) higher day-time noise (5.1 dB(A)) was associated with 1.1% [95% confidence interval (95% CI: 0.02-2.2%)] higher hsCRP, 0.7% (95% CI: 0.3-1.1%) higher triglycerides, and 0.5% (95% CI: 0.3-0.7%) higher high-density lipoprotein (HDL); only the association with HDL was robust to adjustment for air pollution. An IQR higher PM10 (2.0 µg/m3) or NO2 (7.4 µg/m3) was associated with higher triglycerides (1.9%, 95% CI: 1.5-2.4% and 2.2%, 95% CI: 1.6-2.7%), independent of adjustment for noise. Additionally for NO2, a significant association with hsCRP (1.9%, 95% CI: 0.5-3.3%) was seen. In Lifelines, an IQR higher noise (4.2 dB(A)) and PM10 (2.4 µg/m3) was associated with 0.2% (95% CI: 0.1-0.3%) and 0.6% (95% CI: 0.4-0.7%) higher fasting glucose respectively, with both remaining robust to adjustment for air/noise pollution. CONCLUSION: Long-term exposures to road traffic noise and ambient air pollution were associated with blood biochemistry, providing a possible link between road traffic noise/air pollution and cardio-metabolic disease risk.

Ambient air pollution, traffic noise and adult asthma prevalence: a BioSHaRE approach.

We investigated the effects of both ambient air pollution and traffic noise on adult asthma prevalence, using harmonised data from three European cohort studies established in 2006-2013 (HUNT3, Lifelines and UK Biobank).Residential exposures to ambient air pollution (particulate matter with aerodynamic diameter ≤10 µm (PM10) and nitrogen dioxide (NO2)) were estimated by a pan-European Land Use Regression model for 2007. Traffic noise for 2009 was modelled at home addresses by adapting a standardised noise assessment framework (CNOSSOS-EU). A cross-sectional analysis of 646 731 participants aged ≥20 years was undertaken using DataSHIELD to pool data for individual-level analysis via a "compute to the data" approach. Multivariate logistic regression models were fitted to assess the effects of each exposure on lifetime and current asthma prevalence.PM10 or NO2 higher by 10 µg·m-3 was associated with 12.8% (95% CI 9.5-16.3%) and 1.9% (95% CI 1.1-2.8%) higher lifetime asthma prevalence, respectively, independent of confounders. Effects were larger in those aged ≥50 years, ever-smokers and less educated. Noise exposure was not significantly associated with asthma prevalence.This study suggests that long-term ambient PM10 exposure is associated with asthma prevalence in western European adults. Traffic noise is not associated with asthma prevalence, but its potential to impact on asthma exacerbations needs further investigation.

Plasma N-terminal Prosomatostatin and Risk of Incident Cardiovascular Disease and All-Cause Mortality in a Prospective Observational Cohort: the PREVEND Study.

BACKGROUND: Somatostatin is a component of the well-known insulin-like growth factor-1/growth hormone (GH) longevity axis. There is observational evidence that increased GH is associated with an increased risk of cardiovascular disease (CVD). We aimed to investigate the potential association of plasma N-terminal fragment prosomatostatin (NT-proSST) with incident CVD and all-cause mortality in apparently healthy adults. METHODS: We studied 8134 participants without history of CVD (aged 28-75 years; women, 52.6%) from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study in Groningen, the Netherlands. Plasma NT-proSST was measured in baseline samples. Outcomes were incidence of CVD and all-cause mortality. RESULTS: In cross-sectional analyses, NT-proSST [mean (SD), 384.0 (169.3) pmol/L] was positively associated with male sex and age (both P < 0.001). During a median follow-up of 10.5 (Q1-Q3: 9.9-10.8) years, 708 (8.7%) participants developed CVD and 517 (6.4%) participants died. In univariable analyses, NT-proSST was associated with an increased risk of incident CVD and all-cause mortality (both P < 0.001). In multivariable analyses, these associations were independent of the Framingham risk factors, with hazard ratios (95% CI) per doubling of NT-proSST of 1.17 (1.03-1.34; P = 0.02) for incident CVD and of 1.28 (1.09-1.49; P = 0.002) for all-cause mortality. Addition of NT-proSST to the updated Framingham Risk Score improved reclassification (integrated discrimination improvement (P < 0.001); net reclassification improvement was 2.5% (P = 0.04)). CONCLUSIONS: Plasma NT-proSST is positively associated with increased risk of future CVD and all-cause mortality, partly independent of traditional CVD risk factors. Further research is needed to address the nature of associations.

Changing the obesogenic environment to improve cardiometabolic health in residential patients with a severe mental illness: cluster randomised controlled trial.

BackgroundFor patients with severe mental illness (SMI) in residential facilities, adopting a healthy lifestyle is hampered by the obesity promoting (obesogenic) environment.AimsTo determine the effectiveness of a 12-month lifestyle intervention addressing the obesogenic environment with respect to diet and physical activity to improve waist circumference and cardiometabolic risk factors v. care as usual (Dutch Trial Registry: NTR2720).MethodIn a multisite cluster randomised controlled pragmatic trial, 29 care teams were randomised into 15 intervention (365 patients) and 14 control teams (371 patients). Intervention staff were trained to improve the obesogenic environment.ResultsWaist circumference decreased 1.51 cm (95% CI -2.99 to -0.04) in the intervention v. control group after 3 months and metabolic syndrome z-score decreased 0.22 s.d. (95% CI -0.38 to -0.06). After 12 months, the decrease in waist circumference was no longer statistically significantly different (-1.28 cm, 95% CI -2.79 to 0.23, P=0.097).ConclusionsTargeting the obesogenic environment of residential patients with SMI has the potential to facilitate reduction of abdominal adiposity and cardiometabolic risk, but maintaining initial reductions over the longer term remains challenging.

Factors of physical activity among Chinese children and adolescents: a systematic review.

BACKGROUND: Lack of physical activity is a growing problem in China, due to the fast economic development and changing living environment over the past two decades. The aim of this review is to summarize the factors related to physical activity in Chinese children and adolescents during this distinct period of development. METHODS: A systematic search was finished on Jan 10th, 2017, and identified 2200 hits through PubMed and Web of Science. English-language published studies were included if they reported statistical associations between factors and physical activity. Adapted criteria from the Strengthening The Reporting of OBservational studies in Epidemiology (STROBE) statement and evaluation of the quality of prognosis studies in systematic reviews (QUIPS) were used to assess the risk of bias of the included studies. Related factors that were reported in at least three studies were summarized separately for children and adolescents using a semi-quantitative method. RESULTS: Forty two papers (published 2002-2016) were included. Most designs were cross-sectional (79%), and most studies used questionnaires to assess physical activity. Sample size was above 1000 in 18 papers (43%). Thirty seven studies (88%) showed acceptable quality by methodological quality assessment. Most studies reported a low level of physical activity. Boys were consistently more active than girls, the parental physical activity was positively associated with children and adolescents' physical activity, children in suburban/rural regions showed less activity than in urban regions, and, specifically in adolescents, self-efficacy was positively associated with physical activity. Family socioeconomic status and parental education were not associated with physical activity in children and adolescents. CONCLUSIONS: The studies included in this review were large but mostly of low quality in terms of study design (cross-sectional) and methods (questionnaires). Parental physical activity and self-efficacy are promising targets for future physical activity promotion programmes. The low level of physical activity raises concern, especially in suburban/rural regions. Future research is required to enhance our understanding of other influences, such as the physical environment, especially in early childhood.

The relationship between social functioning and subjective memory complaints in older persons: a population-based longitudinal cohort study.

OBJECTIVE: Poor social functioning is associated with cognitive decline in older adults. It is unclear whether social functioning is also associated with subjective memory complaints (SMC). We investigated the association between social functioning and incident SMC and SMC recovery. METHODS: A population-based sample of 8762 older adults (aged ≥65 years) with good objective cognitive functioning at baseline (MMSE ≥26) from the LifeLines Cohort Study were followed for 1.5 years. Self-reported SMC were measured at baseline and after 1.5 years follow-up. Aspects of social functioning included marital status, household composition, social network size, social activity, quality of social relationships, social support, affection, behavioral confirmation, and status. RESULTS: Thirteen percent (513/3963) developed SMC during follow-up (incident SMC). Multivariate logistic regression analyses (adjusted for age, gender, education level, physical activity, alcohol use, smoking status, depression, arrhythmia, myocardial infarction, heart failure, stroke) showed that participants with better feelings of affection, behavioral confirmation and stable good social support had a lower risk of incident SMC. Thirty-four percent (1632/4799) reported recovery. Participants with good social functioning at baseline on all determinants reported more SMC recovery. People who remained stable in a relationship, stable in good quality of social relationships or increased in quality of social relationships more often report SMC recovery. CONCLUSIONS: Good social functioning is associated with less incident SMC and more SMC recovery over a follow-up period of 1.5 years. Albeit future confirmative studies are needed, we argue for targeting also social functioning when designing multidomain interventions to prevent or slow down cognitive decline. Copyright © 2016 John Wiley & Sons, Ltd.

Association of Depressive and Anxiety Disorders With Diagnosed Versus Undiagnosed Diabetes: An Epidemiological Study of 90,686 Participants.

OBJECTIVE: To compare the odds of depressive and anxiety disorders for participants with diagnosed diabetes, participants with diabetes but unaware of this, and participants without diabetes. Such knowledge might improve etiological insight into psychopathology in diabetes. METHODS: Data of 90,686 participants (mean age = 45 years; 59% female) from the LifeLines cohort was used. Depressive and anxiety disorders were assessed by the Mini-International Neuropsychiatric Interview. The odds of depression and anxiety were assessed for three groups: a) diagnosed diabetes, diabetes medication use and/or self-reported "diabetes"; b) undiagnosed diabetes, fasting blood glucose ≥7.0 mmol/l, but no diabetes medication use and self-reported "no diabetes"; and c) no diabetes, fasting blood glucose <7.0 mmol/l and self-reported "no diabetes." Logistic regression was performed to compare the odds of depression and anxiety in these groups, adjusting for age, sex, diabetes-related diseases, comorbid depressive or anxiety disorders, and glycosylated hemoglobin. RESULTS: A total of 3002 (3.3%) participants were diagnosed as having depression and 9018 (9.9%) as having anxiety; 1781 (2.0%) had diagnosed and 786 (0.9%) had undiagnosed diabetes. Both diagnosed (odds ratio [OR] = 1.4:1.1-1.8, p = .006) and undiagnosed (OR = 1.8:1.3-2.6, p = .001) diabetes were independently associated with depression. The odds of depression did not differ between diagnosed and undiagnosed diabetes (OR = 0.7, p = .17). Diagnosed diabetes was independently associated with anxiety (OR = 1.4:1.2-1.7, p < .001), but undiagnosed diabetes was not (OR = 0.8:0.6-1.1, p = .20). The odds of anxiety were significantly higher in diagnosed compared with undiagnosed diabetes (1.68:1.23-2.31, p = .001). CONCLUSIONS: Depression was more prevalent in participants with diagnosed and undiagnosed diabetes, whereas anxiety was more prevalent only in participants who were aware of their diabetes. Longitudinal research is needed to assess the causal pathways of these associations.

Effect of diagnosis with a chronic disease on physical activity behavior in middle-aged women.

OBJECTIVE: Although regular physical activity is an effective secondary prevention strategy for patients with a chronic disease, it is unclear whether patients change their daily physical activity after being diagnosed. Therefore, the aims of this study were to (1) describe changes in levels of physical activity in middle-aged women before and after diagnosis with a chronic disease (heart disease, diabetes, asthma, breast cancer, arthritis, depression); and to (2) examine whether diagnosis with a chronic disease affects levels of physical activity in these women. METHODS: Data from 5 surveys (1998-2010) of the Australian Longitudinal Study on Women's Health (ALSWH) were used. Participants (N=4840, born 1946-1951) completed surveys every three years, with questions about diseases and leisure time physical activity. The main outcome measure was physical activity, categorized as: nil/sedentary, low active, moderately active, highly active. RESULTS: At each survey approximately half the middle-aged women did not meet the recommended level of physical activity. Between consecutive surveys, 41%-46% of the women did not change, 24%-30% decreased, and 24%-31% increased their physical activity level. These proportions of change were similar directly after diagnosis with a chronic disease, and in the years before or after diagnosis. Generalized estimating equations showed that there was no statistically significant effect of diagnosis with a chronic disease on levels of physical activity in women. CONCLUSION: Despite the importance of physical activity for the management of chronic diseases, most women did not increase their physical activity after diagnosis. This illustrates a need for tailored interventions to enhance physical activity in newly diagnosed patients.

Survey nonresponse among informal caregivers: effects on the presence and magnitude of associations with caregiver burden and satisfaction.

BACKGROUND: Informal caregiving is becoming more relevant with current trends such as population ageing. However, little is known about nonconsent and nonresponse bias in caregiving research. We investigated nonconsent and nonresponse bias in a sample of informal caregivers who participated in the LifeLines Cohort Study, and were invited for participation in an additional caregiving study. METHODS: We compared socio-demographic characteristics, caregiver health, caregiving situation, and caregiver outcomes of nonconsent and consent caregivers, and nonresponse and response caregivers, on LifeLines data, by using Chi-square tests, Independent Sample T-tests, and Mann-Whitney tests. Furthermore, we examined the influence of nonconsent and nonresponse on the presence and magnitude of the associations between caregiver characteristics and two commonly used caregiving outcomes (caregiver burden and satisfaction). We conducted multinomial logistic regression analyses, including interaction terms with nonconsent and nonresponse. RESULTS: Within a subcohort of 8443 caregivers, aged >18 years, 5095 caregivers (60 %) gave consent for participation in the caregiving study. Within the subgroup of 2002 caregivers who received the questionnaire, 965 (48 %) responded. Caregivers who were highly involved in caregiving (i.e. high time investment, high caregiver burden), gave more commonly consent to participate, and responded more often to the questionnaire. Nonconsent and nonresponse influenced the associations between caregiver characteristics and caregiver burden for only a few characteristics, mainly indicating the level of caregiving involvement (e.g. time investment, caregiving duration). Especially for caregiver burden, these indicators were stronger for consent and response caregivers than for nonconsent and nonresponse caregivers. CONCLUSIONS: Our findings are important for caregiving research, as they emphasized that participation might not be evenly distributed among caregivers, and that the possibility of nonconsent and nonresponse bias should be considered.

Neighborhood income and major depressive disorder in a large Dutch population: results from the LifeLines Cohort study.

BACKGROUND: Previous studies are inconclusive on whether poor socioeconomic conditions in the neighborhood are associated with major depressive disorder. Furthermore, conceptual models that relate neighborhood conditions to depressive disorder have not been evaluated using empirical data. In this study, we investigated whether neighborhood income is associated with major depressive episodes. We evaluated three conceptual models. Conceptual model 1: The association between neighborhood income and major depressive episodes is explained by diseases, lifestyle factors, stress and social participation. Conceptual model 2: A low individual income relative to the mean income in the neighborhood is associated with major depressive episodes. Conceptual model 3: A high income of the neighborhood buffers the effect of a low individual income on major depressive disorder. METHODS: We used adult baseline data from the LifeLines Cohort Study (N = 71,058) linked with data on the participants' neighborhoods from Statistics Netherlands. The current presence of a major depressive episode was assessed using the MINI neuropsychiatric interview. The association between neighborhood income and major depressive episodes was assessed using a mixed effect logistic regression model adjusted for age, sex, marital status, education and individual (equalized) income. This regression model was sequentially adjusted for lifestyle factors, chronic diseases, stress, and social participation to evaluate conceptual model 1. To evaluate conceptual models 2 and 3, an interaction term for neighborhood income*individual income was included. RESULTS: Multivariate regression analysis showed that a low neighborhood income is associated with major depressive episodes (OR (95 % CI): 0.82 (0.73;0.93)). Adjustment for diseases, lifestyle factors, stress, and social participation attenuated this association (ORs (95 % CI): 0.90 (0.79;1.01)). Low individual income was also associated with major depressive episodes (OR (95 % CI): 0.72 (0.68;0.76)). The interaction of individual income*neighborhood income on major depressive episodes was not significant (p = 0.173). CONCLUSIONS: Living in a low-income neighborhood is associated with major depressive episodes. Our results suggest that this association is partly explained by chronic diseases, lifestyle factors, stress and poor social participation, and thereby partly confirm conceptual model 1. Our results do not support conceptual model 2 and 3.

Dutch healthcare professionals inadequately perceived if three- and four-year-old preschool children were overweight.

AIM: We studied whether healthcare professionals adequately perceived if preschool children were overweight and whether this was influenced by their own body mass index (BMI). METHODS: We sent 716 Dutch healthcare professionals questionnaires containing seven pictures and seven sketches of three- and four-year-old children showing body weights from underweight to morbidly obese. The professionals rated the pictures on a five-point scale from too heavy to too light and chose the sketch that they felt best depicted the child's body shape. They also reported their own height and weight and their BMI was calculated. RESULTS: Of the 716 questionnaires, 346 (48.3%) were returned with complete information and analysed. Healthcare professionals mostly chose sketches that showed children as being lighter than they really were. Depending on their own BMI group, the overweight child was perceived as having a normal weight by 74-79% of the healthcare professionals. The obese children were rated correctly by 44-52% of the professionals, but 14-15% said their weight was normal. The morbidly obese child was adequately assessed by 93-98% of the professionals. CONCLUSION: Healthcare professionals inadequately perceived whether three- and four-year-old children were overweight and this may have hindered early interventions, leading to overweight children becoming overweight adolescents.

Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study.

AIMS/HYPOTHESIS: Oxidative stress plays a key role in the development of type 2 diabetes mellitus. We previously showed that the circulating antioxidant peroxiredoxin 4 (Prx4) is associated with cardiometabolic risk factors. We aimed to evaluate the association of Prx4 with type 2 diabetes risk in the general population. METHODS: We analysed data on 7,972 individuals from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (49% men, aged 28-75 years) with no diabetes at baseline. Logistic regression models adjusted for age, sex, smoking, waist circumference, hypertension and family history of diabetes were used to estimate the ORs for type 2 diabetes. RESULTS: During a median follow up of 7.7 years, 496 individuals (288 men; 58%) developed type 2 diabetes. The median (Q1-Q3) Prx4 level was 0.84 (0.53-1.40) U/l in individuals who developed type 2 diabetes and 0.68 (0.43-1.08) U/l in individuals who did not develop type 2 diabetes. For every doubling of Prx4 levels, the adjusted OR (95% CI) for type 2 diabetes was 1.16 (1.05-1.29) in the whole population; by sex, it was 1.31 (1.14-1.50) for men and 1.03 (0.87-1.21) for women. Further adjustment for other clinical measures did not materially change the results. The addition of Prx4 to a validated diabetes risk score significantly improved the prediction of type 2 diabetes in men (p = 0.002 for reclassification improvement). CONCLUSIONS/INTERPRETATION: Our findings suggest that elevated serum Prx4 levels are associated with a higher risk of incident type 2 diabetes. For men, taking Prx4 into consideration can improve type 2 diabetes prediction over a validated diabetes risk score; in contrast, there is no improvement in risk prediction for women.

Pleiotropic genes for metabolic syndrome and inflammation.

Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation.

Effect of obesity intervention programs on adipokines, insulin resistance, lipid profile, and low-grade inflammation in 3- to 5-y-old children.

BACKGROUND: Childhood obesity can cause the development of cardiovascular risk factors. We assessed the effect of a multidisciplinary intervention program on cardiovascular risk factors and compared this effect with a usual-care program in 3- to 5-y-old overweight or obese children. METHODS: Seventy-five children were randomly assigned to a multidisciplinary intervention or a usual-care program. Anthropometry, body composition, and abdominal adipose tissue were assessed at the start and end of a 16-wk program. Concurrently, fasting concentrations of serum lipids, glucose, insulin, HbA1c, leptin, adiponectin, high-sensitive C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were determined. RESULTS: In both groups, insulin sensitivity improved, demonstrated by decreased insulin concentrations and a decreased HOMA2-IR. In the multidisciplinary intervention group, there was also a decrease of HbA1c and TNF-α. In the usual-care group, an increase in glucose concentrations was found. Comparing both groups, changes over time were not different, besides trends in the decrease in total cholesterol and TNF-α, in favor of the multidisciplinary intervention group. Combining the results of both groups, a correlation was found between the decrease in body fat percentage (BF%), and both HOMA2-IR and triglyceride (TG) concentrations. CONCLUSION: In 3- to 5-y-old children, both obesity intervention programs improved insulin sensitivity, in parallel with a reduced BF%.

The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies.

BACKGROUND: Not all obese subjects have an adverse metabolic profile predisposing them to developing type 2 diabetes or cardiovascular disease. The BioSHaRE-EU Healthy Obese Project aims to gain insights into the consequences of (healthy) obesity using data on risk factors and phenotypes across several large-scale cohort studies. Aim of this study was to describe the prevalence of obesity, metabolic syndrome (MetS) and metabolically healthy obesity (MHO) in ten participating studies. METHODS: Ten different cohorts in seven countries were combined, using data transformed into a harmonized format. All participants were of European origin, with age 18-80 years. They had participated in a clinical examination for anthropometric and blood pressure measurements. Blood samples had been drawn for analysis of lipids and glucose. Presence of MetS was assessed in those with obesity (BMI ≥ 30 kg/m2) based on the 2001 NCEP ATP III criteria, as well as an adapted set of less strict criteria. MHO was defined as obesity, having none of the MetS components, and no previous diagnosis of cardiovascular disease. RESULTS: Data for 163,517 individuals were available; 17% were obese (11,465 men and 16,612 women). The prevalence of obesity varied from 11.6% in the Italian CHRIS cohort to 26.3% in the German KORA cohort. The age-standardized percentage of obese subjects with MetS ranged in women from 24% in CHRIS to 65% in the Finnish Health2000 cohort, and in men from 43% in CHRIS to 78% in the Finnish DILGOM cohort, with elevated blood pressure the most frequently occurring factor contributing to the prevalence of the metabolic syndrome. The age-standardized prevalence of MHO varied in women from 7% in Health2000 to 28% in NCDS, and in men from 2% in DILGOM to 19% in CHRIS. MHO was more prevalent in women than in men, and decreased with age in both sexes. CONCLUSIONS: Through a rigorous harmonization process, the BioSHaRE-EU consortium was able to compare key characteristics defining the metabolically healthy obese phenotype across ten cohort studies. There is considerable variability in the prevalence of healthy obesity across the different European populations studied, even when unified criteria were used to classify this phenotype.

Changing the obesogenic environment of severe mentally ill residential patients: ELIPS, a cluster randomised study design.

BACKGROUND: Severe mentally ill (SMI) patients have a reduced life expectancy of 13-30 years compared to the general population, largely due to an increased risk of cardiovascular mortality. Unhealthy lifestyle behaviours in SMI patients contribute to this increased risk. The obesogenic living environment of patients in residential facilities may even pose an extra risk. Although several studies have shown positive effects of lifestyle interventions on SMI patients' weight status, studies including residential patients and their obesogenic environment are scarce. This paper describes the Effectiveness of Lifestyle Interventions in PSychiatry trial (ELIPS). The goal of this trial is to improve cardiometabolic health in severe mentally ill residential patients by addressing the obesogenic environment. METHODS/DESIGN: The ELIPS study is a multi-site cluster randomised controlled trial (RCT) based on the principles of a pragmatic RCT. All residential and long-term clinical care teams of two large mental health care organisations in the North of the Netherlands serving SMI patients are invited to participate. The intervention is aimed at team level. Lifestyle coaches first develop a team specific lifestyle plan that tailors the ELIPS goals and protocol and then train teams on how to create a healthy environment and stimulate healthy behaviours in patients. After three months, teams take over the intervention after they have set out goals to achieve in the following nine months. In this phase, adherence to the lifestyle plan and pre-set goals is monitored. Patients in the control arm receive care as usual. Primary outcome measure is waist circumference at three and 12 months after baseline. DISCUSSION: ELIPS is different from previously published lifestyle intervention studies in three ways. First, it follows the principles of a pragmatic design, which enables the examination of effects in everyday practice. Second, by implementing the intervention at team level, we expect lifestyle activities to be maintained when interventionists leave. Last, by targeting the obesogenic environment we create a prerequisite for any sustainable health improvement, as patients can only make healthy choices in a healthy living environment. TRIAL REGISTRATION: Nederlands Trialregister NTR2720 (Dutch Trial Register, www.trialregister.nl). Registered 27 January 2011.

Daily physical activity in stable heart failure patients.

BACKGROUND: Physical activity is the only nonpharmacological therapy that is proven to be effective in heart failure (HF) patients in reducing morbidity. To date, little is known about the levels of daily physical activity in HF patients and about related factors. OBJECTIVE: The objectives of this study were to (a) describe performance-based daily physical activity in HF patients, (b) compare it with physical activity guidelines, and (c) identify related factors of daily physical activity. METHODS: The daily physical activity of 68 HF patients was measured using an accelerometer (SenseWear) for 48 hours. Psychological characteristics (self-efficacy, motivation, and depression) were measured using questionnaires. To have an indication how to interpret daily physical activity levels of the study sample, time spent on moderate- to vigorous-intensity physical activities was compared with the 30-minute activity guideline. Steps per day was compared with the criteria for healthy adults, in the absence of HF-specific criteria. Linear regression analyses were used to identify related factors of daily physical activity. RESULTS: Forty-four percent were active for less than 30 min/d, whereas 56% were active for more than 30 min/d. Fifty percent took fewer than 5000 steps per day, 35% took 5000 to 10 000 steps per day, and 15% took more than 10 000 steps per day. Linear regression models showed that New York Heart Association classification and self-efficacy were the most important factors explaining variance in daily physical activity. CONCLUSIONS: The variance in daily physical activity in HF patients is considerable. Approximately half of the patients had a sedentary lifestyle. Higher New York Heart Association classification and lower self-efficacy are associated with less daily physical activity. These findings contribute to the understanding of daily physical activity behavior of HF patients and can help healthcare providers to promote daily physical activity in sedentary HF patients.

Growth during infancy and childhood, and adiposity at age 16 years: ages 2 to 7 years are pivotal.

OBJECTIVE: To assess the period during infancy and childhood in which growth is most associated with adolescent adiposity and the metabolic syndrome (MS) and whether this differs depending on maternal smoking during pregnancy. STUDY DESIGN: A longitudinal population-based cohort study among 772 girls and 708 boys. RESULTS: Weight gains between ages 2-4 years and ages 4-7 years were most strongly associated with higher body mass index (BMI), sum of skinfold measurements, body fat percentage, and waist circumference at age 16. A one SD increase in weight between ages 2-4 and 4-7 years was associated with increases in outcome measures of +0.82 to +1.47 SDs (all P < .001), and with a less favorable MS score. In children whose mothers smoked during pregnancy, the association of relative weight gain during ages 2-4 years with adolescent BMI was stronger than in children whose mothers did not smoke. For adolescent BMI, the increase was 0.42 SD higher (P = .01). This was similar for the other adiposity measures. CONCLUSIONS: Large relative increases in weight from ages 2 to 7 years are associated with adolescent adiposity and MS. This is more pronounced in adolescents whose mothers smoked during pregnancy.