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Abstract Background Chronic obstructive pulmonary disease (COPD) is a common disease associated with premature death. Tobacco exposure is the main risk factor, but lower socioeconomic status, early life insults, and occupational exposures are also important risk factors. Socially marginalized people, facing homelessness, substance use disorder, and mental illness, are likely to have a higher risk of developing COPD, and, furthermore, experience barriers to healthcare access and consequently poorer outcomes. Objective This study aims to assess COPD prevalence and the impact of opportunistic screening among hospitalized patients who are in contact with hospital social nurses. These patients constitute a group of patients with a high prevalence of psychiatric and somatic diseases, substance use, low life expectancy, and are socially marginalized. Methods The present prospective longitudinal study includes a clinical examination at baseline. Participants will have spirometry done and be interviewed regarding risk factors, socioeconomic conditions, and respiratory symptoms. The 5-year follow-up assessment incorporates data from baseline and register data over the 5 years, including information on morbidity, use of COPD medication, hospital contacts, mortality, and socioeconomic factors. Anticipated results Referral for further diagnostic work-up and management after the screening, including COPD treatment and smoking cessation support, is expected to improve survival rates. The study is still enrolling patients. Trial registration The study is registered at ClinicalTrials.gov , NCT04754308 with study status: “enrolling”.

Abstract Background National comprehensive smoke-free legislation has been found to decrease the incidence of several smoking-related diseases. In 2007, Denmark introduced a national smoking ban, which banned smoking indoor in workplaces and public places, although only partial restrictions were applied in certain settings. We examined the impact of the smoking ban on smoking-related diseases and whether this differed across socioeconomic groups. Methods Interrupted time series analyses of nationwide register data were performed using Poisson regression models to examine the differential impact of the smoking ban on monthly incidence rates of acute myocardial infarction, chronic obstructive pulmonary disease, and smoking-related cancers from 2002 to 2015. Immediate changes in incidence rates after the smoking ban and long-term changes in disease trends were estimated by comparing data from the pre- and post-ban period. Models were stratified by socioeconomic position. Results Overall, we found neither immediate changes in rates of acute myocardial infarction, chronic obstructive pulmonary disease, and smoking-related cancers following the smoking ban nor long-term post-ban changes in disease trends as compared to before the ban. Results did not differ across socioeconomic groups. A pronounced socioeconomic gradient in incidence rates was observed for all outcomes both before and after the smoking ban. Conclusion The national smoking ban was not associated with a lower incidence of smoking-related diseases in the post-ban period compared to pre-ban levels and no differences between socioeconomic groups were observed. Future tobacco control in Denmark should consider which measures most effectively target the low socioeconomic groups to decrease the current strong socioeconomic inequality in health.

The smoking prevalence among vocational education and training (VET) students is high. This paper describes the development and feasibility test of a multicomponent intervention designed to promote non-smoking behaviour at VET schools. We applied the Behaviour Change Wheel (BCW) stages and the capability, opportunity, and motivation for behaviour (COM-B) model to develop the intervention components based on theory, evidence, and a thorough needs-assessment study. Moreover, we feasibility-tested the preliminary ideas. All in all, our study was based on the literature, survey data, fieldwork, workshops, and expert and stakeholder involvement. The final intervention programme targets VET students’ smoking behaviour at the school, class, and individual levels through (a) a comprehensive tobacco policy to limit the physical and social opportunities to smoke, supplemented with a two-day staff course in conversations about smoking and an edutainment session (a lecture that both educates and entertains) to support a smoke-free environment; (b) classroom curricular with teaching materials to increase knowledge and social support, along with a quit-and-win competition to increase motivation; and (c) the national Quitline adapted to VET students to increase access to cessation support. The BCW model enabled a systematic and comprehensive development of an intervention, which demonstrates relevant techniques and delivery options to have the potential to reduce smoking in VET schools.

Abstract Background Hospital visits constitute a ‘window of opportunity’ for initiating smoking cessation attempts, and healthcare providers (HCPs) play an important role in supporting patients to stop smoking. Yet, the current practices of supporting smoking cessation in the hospital setting are largely unexplored. The aim of this study was to explore practices of smoking cessation support among hospital-based HCPs. Methods HCPs working in a large hospital in the secondary care sector completed an online, cross-sectional survey, including sociodemographic and work-related factors as well as 21 questions assessing practices of smoking cessation support based on the “five As” framework. Descriptive statistics were computed, and predictors of HCPs giving patients advice to stop smoking were explored using logistic regression analysis. Results All employees (N = 3998) in the hospital received a survey link; 1645 (41.1%) HCPs with daily patient contact completed the survey. Smoking cessation support in the hospital setting was limited with regard to assessment of smoking; providing information and advice; planning and referral for further support; and follow-up on smoking cessation attempts. Almost half (44.8%) of participating HCPs with daily patient contact never or rarely advise their patients to stop smoking. Physicians were more likely than nurses to advice patients to stop smoking, and HCPs in outpatient clinics were more likely to give advice than inpatient clinic HCPs. Conclusion Smoking cessation support is very limited in the hospital-based healthcare setting. This is problematic, as hospital visits can be windows of opportunity to help patients change their health behaviour. An intensified focus on the implementation of hospital-based smoking cessation support is needed.

Objectives Public health interventions are designed to improve specific health-related outcomes; however, they may also produce negative side effects, such as substitution use, psychological or social harms. Knowledge about the unintended effects of school-based smoking preventive interventions is sparse. Hence, this study examined these potential unintended effects of the smoking-reducing intervention, Focus, among students in the vocational education and training setting.Design Cluster randomised controlled trial stratified by school type with 5 months follow-up.Setting and participants Across Denmark, eight schools were randomised to the intervention group (n=844 students, response proportion 76%) and six schools to the control group (n=815 students, response proportion 75%). This study focused solely on students who smoked at baseline (N=491).Interventions The intervention was developed systematically based on theory and a thoroughly mixed-methods needs assessment. Intervention components included a comprehensive school tobacco policy (smoke-free school hours) supported by a 3-day course for school staff and launched by an edutainment session for students; class-based lessons and a quit-and-win competition; and individual telephone smoking cessation support.Outcomes Alternative tobacco and nicotine products (regular use of smokeless tobacco, hookah and e-cigarettes), regular cannabis use, boredom and loneliness at school, stress and perceived stigmatisation among smokers.Results We found no statistically significant unintended effects of the intervention. Nonetheless, insignificant findings indicated that students in the intervention group were less likely to be bored during school hours (OR 0.59, 95% CI 0.32 to 1.10) and experience stress (OR 0.62, 95% CI 0.35 to 1.10), but more likely to report feeling stigmatised compared with the control group (OR 1.55, 95% CI 0.71 to 3.40).Conclusions Overall, findings suggested no unintended effects of the Focus trial with respect to substitution use, psychological, nor group or social harms. Future research is encouraged to report potential harmful outcomes of smoking preventive interventions, and interventions should be aware of the possible stigmatisation of smokers.Trial registration number ISRCTN16455577.

Abstract Background Social inequality in smoking remains an important public health issue. Upper secondary schools offering vocational education and training (VET) comprise more students from lower socioeconomic backgrounds and have higher smoking prevalence than general high schools. This study examined the effects of a school-based multi-component intervention on students’ smoking. Methods A cluster randomized controlled trial. Eligible participants were schools offering VET basic courses or preparatory basic education in Denmark, and their students. Schools were stratified by subject area and eight schools were randomly allocated to intervention (1,160 invited students; 844 analyzed) and six schools to control (1,093 invited students; 815 analyzed). The intervention program comprised smoke-free school hours, class-based activities, and access to smoking cessation support. The control group was encouraged to continue with normal practice. Primary outcomes were daily cigarette consumption and daily smoking status at student level. Secondary outcomes were determinants expected to impact smoking behavior. Outcomes were assessed in students at five-month follow-up. Analyses were by intention-to-treat and per protocol (i.e., whether the intervention was delivered as intended), adjusted for covariates measured at baseline. Moreover, subgroup analyses defined by school type, gender, age, and smoking status at baseline were performed. Multilevel regression models were used to account for the cluster design. Missing data were imputed using multiple imputations. Participants and the research team were not blinded to allocation. Results Intention-to-treat analyses showed no intervention effect on daily cigarette consumption and daily smoking. Pre-planned subgroup analyses showed statistically significant reduction in daily smoking among girls compared with their counterparts in the control group (OR = 0.39, 95% CI: 0.16, 0.98). Per-protocol analysis suggested that schools with full intervention had higher benefits compared with the control group (daily smoking: OR = 0.44, 95% CI: 0.19, 1.02), while no marked differences were seen among schools with partial intervention. Conclusion This study was among the first to test whether a complex, multicomponent intervention could reduce smoking in schools with high smoking risk. Results showed no overall effects. There is a great need to develop programs for this target group and it is important that they are fully implemented if an effect is to be achieved. Trial registration https://www.isrctn.com/ISRCTN16455577 , date of registration 14/06/2018.

Abstract The subjective indicator of health self-rated health (SRH) and the chronic inflammation biomarker soluble urokinase plasminogen activator receptor (suPAR) are both robust predictors of healthcare use and mortality. However, the possible relationship between SRH and suPAR in the assessment of hospitalization and mortality risk is unknown. We used data from the Danish population-based Inter99 cohort to examine the association between SRH and suPAR and test their individual and combined associations with 2-year risk of acute hospitalization and 5- and 15-year mortality. SRH and serum suPAR levels were measured in 5490 participants (median age 45.1 years, 48.7% men). Poorer SRH was associated with elevated suPAR. In unadjusted analyses, SRH and suPAR were individually associated with higher risks of acute hospitalization and mortality, and both measures remained independently associated with higher risks of hospitalization and 15-year mortality after mutual adjustments. The association of suPAR with mortality was stronger in poorer SRH categories, and when combined, SRH and suPAR could identify different groups of individuals with increased risk of acute hospitalization and mortality. Both SRH and suPAR were independently associated with risk of acute hospitalization and mortality, and different combinations of the two measures could identify different groups of individuals at increased risk.

Abstract Background Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and it contributes to the development of many other serious diseases. Smoking cessation in COPD patients is known to improve survival and reduce the number of hospitalization-requiring acute exacerbations of COPD. However, smoking cessation interventions in these patients have only been successful for approximately 15–20% for consistent smoking abstinence in 12 months. Thus, more effective interventions are needed for this patient group. The aim of this study is to determine whether a high-intensity intervention compared to a low-intensity intervention can increase the proportion of persistent (> 12 months) anamnestic and biochemical smoking cessation in active smokers with COPD. Methods This study is a randomized controlled trial. A total of 600 active smokers with COPD will be randomly assigned 1:1 to either a standard treatment (guideline-based municipal smoking cessation program, “low intensity” group) or an intervention (“high-intensity” group) group, which consists of group sessions, telephone consultations, behavior design, hotline, and “buddy-matching” (smoker matched with COPD patient who has ceased smoking). Both groups will receive pharmacological smoking cessation. The primary endpoint is anamnestic and biochemical (cotinine analysis in urine) validated smoking cessation after 12 months. Discussion The potential benefit of this project is to improve smoking cessation rates and thereby reduce smoking-related exacerbations of COPD. In addition, the project can potentially benefit from increasing the quality of life and longevity of COPD patients and reducing the risk of other smoking-related diseases. Trial registration ClinicalTrials.gov NCT04088942 . Registered on 13 September 2019

Abstract Background The plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is a strong predictor of disease development and premature mortality in the general population. Unhealthy lifestyle habits such as smoking or unhealthy eating is known to elevate the suPAR level. We aimed to investigate whether change in lifestyle habits impact on the suPAR level, and whether the resultant levels are associated with mortality. Results Paired suPAR measurements from baseline- and the 5-year visit of the population-based Inter99 study were compared with the habits of diet, smoking, alcohol consumption, and physical activity. Paired suPAR measurements for 3225 individuals were analyzed by linear regression, adjusted for demographics and lifestyle habits. Compared to individuals with a healthy lifestyle, an unhealthy diet, low physical activity, and daily smoking were associated with a 5.9, 12.8, and 17.6% higher 5-year suPAR, respectively. During 6.1 years of follow-up after the 5-year visit, 1.6% of those with a low suPAR (mean 2.93 ng/ml) died compared with 3.8% of individuals with a high suPAR (mean 4.73 ng/ml), P

Introduction Smoke-free school hours (SFSHs) entails a smoking ban during school hours and might be an effective intervention to reduce the high smoking prevalence in vocational schools. For SFSH to be effective, the policy must be adequately implemented and enforced; this challenge for schools constitutes a research gap. The ‘Smoke-Free Vocational Schools’ research and intervention project has been developed to facilitate schools’ implementation of SFSH. It is scheduled to run from 2018 to 2022, with SFSH being implemented in 11 Danish vocational schools. This study protocol describes the intervention project and evaluation design of the research and intervention project.Methods and analysis The intervention project aims to develop an evidence-based model for implementing SFSH in vocational schools and similar settings. The project is developed in a collaboration between research and practice. Two public health NGOs are responsible for delivering the intervention activities in schools, while the research partner evaluates what works, for whom, and under what circumstances. The intervention lasts one year per school, targeting different socioecological levels. During the first 6 months, activities are delivered to stimulate organisational readiness to implement SFSH. Then, SFSH is established, and during the next 6 months, activities are delivered to stimulate implementation of SFSH into routine practice. The epistemological foundation is realistic evaluation. The evaluation focuses on both implementation and outcomes. Process evaluation will determine the level of implementation and explore what hinders or enables SFSH becoming part of routine practice using qualitative and quantitative methods. Outcomes evaluation will quantitively assess the intervention’s effectiveness, with the primary outcome measure being changes in smoking during school hours.Ethics and dissemination Informed consent will be obtained from study participants according to the General Data Protection Regulation (GDPR) and Danish data protection law. The study adheres to Danish ethics procedures. Study findings will be disseminated at conferences and further published in open-access peer-reviewed journals.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P

Background and challenges to implementation World-wide shelter users have an alarmingly high smoking prevalence; more than 70% of homeless people smoke. The burden of tobacco related diseases as cancer, heart disease and chronic obstructive disease is very high in this population. The aim of this study was to develop systematic smoking cessation activities in the shelters of Copenhagen, Denmark and thereby improve the health of shelter users. Intervention or response All available (n=13) shelters in Copenhagen were included. There was a development/test period and a period with implementation of the revised intervention. Shelter-staff completed a questionnaire at up-start meetings. Municipal smoking cessation counsellors were trained to work with shelter users. Three types of smoking cessation activities were developed -these should be tailored, flexible and on-site. Results and lessons learnt The mean smoking prevalence was 79% among users of shelters. The level of smoking control in shelters varied and only two shelters had smoking cessation activities at baseline. All shelters implemented at least two out of three offered smoking cessation activities (1. participation in a house-meeting 2. quit smoking café with individual counselling, and 3. tailored group-based smoking cessation with free nicotine replacement therapy). All but one shelter implemented the group-based intervention: approx. 13% of smokers signed up and 26% of those who signed up were abstinent after approx. 12 weeks, as confirmed by staff. Conclusions and key recommendations Smoking cessation activities in shelters are wanted by staff and users, they are feasible and even very vulnerable persons are able to quit. Based on experiences from all shelters in the Capital of Denmark, we propose a systematic approach for future smoking cessation initiatives, where the smoking activities should be driven by the municipality, be pro-active, on-site, tailored and flexible, and the smoking cessation counsellors should be trained to work with the target group.

Background and Objectives. Approximately one in five ex-smokers reduces or maintains weight after smoking cessation but little is known about who succeeds to avoid weight gain. The purpose of this study was to identify predictors of weight reduction after long-term smoking cessation in a general population. Methods. Data was obtained from two Danish population-based cohorts (the Inter99 and the Helbred2006 study). Anthropometric measurements were performed by trained research staff. Out of 3.577 daily smokers at baseline 317 participants had quit smoking at the five-year follow-up for at least one year. Multiple logistic regression analysis was performed to determine predictors of weight reduction. Results. Thirteen percent reduced weight by at least 1 kg and 4% maintained their weight. Quitters with obesity had more than seven times higher odds than normal weight quitters to lose weight (OR 7.13 (95% CI 2.76–19.71)), and they had the largest median weight loss of 4.45 kg. The only other significant predictor of weight reduction was low tobacco consumption at baseline. Conclusions. Predictors of weight reduction after smoking cessation were high body mass index and low tobacco consumption at baseline. This study might motivate smokers with obesity to quit smoking and health professionals to give them support.

The objective of this trial was to assess the long-term effect of the CHANGE lifestyle coaching intervention for 428 people with abdominal obesity and schizophrenia spectrum disorders on cardiovascular risk. In this randomized, superiority, multi-center clinical trial, participants were randomized to 12 months of either lifestyle coaching plus care coordination (N = 138), care coordination alone, (N = 142) or treatment as usual (N = 148). There was no effect after 12 months, but we hypothesized that there might have been a delayed treatment effect. Our primary outcome at two-year follow-up was 10-year risk of cardiovascular disease standardized to 60 years of age. After two-years the mean 10-year cardiovascular-disease risk was 8.7% (95% confidence interval (CI) 7.6-9.9%) in the CHANGE group, 7.7% (95% CI 6.5-8.9%) in the care coordination group, and 8.9% (95% CI 6.9-9.2%) in the treatment as usual group (P = 0.24). Also, there were no intervention effects for any secondary or exploratory outcomes, including cardiorespiratory fitness, weight, physical activity, diet and smoking. No reported adverse events could be ascribed to the intervention. We conclude that there was neither any direct nor any long-term effect of individual lifestyle coaching or care coordination on cardiovascular risk factors in people with abdominal obesity and schizophrenia spectrum disorders. The trial was approved by the Ethics Committee of Capitol Region Copenhagen, Denmark (registration number: H-4-2012-051) and the Danish Data Protection Agency (registration number: 01689 RHP-2012-007). The trial was funded by the Mental Health Services of the Capital Region of Denmark, the Lundbeck Foundation, the Tryg Foundation, the Danish Ministry of Health, and the Dæhnfeldts Foundation.

We sought to examine whether neighborhood deprivation is associated with participation in a large population-based health check. Such analyses will help answer the question whether health checks, which are designed to meet the needs of residents in deprived neighborhoods, may increase participation and prove to be more effective in preventing disease. In Europe, no study has previously looked at the association between neighborhood deprivation and participation in a population-based health check.The study population comprised 12,768 persons invited for a health check including screening for ischemic heart disease and lifestyle counseling. The study population was randomly drawn from a population of 179,097 persons living in 73 neighborhoods in Denmark. Data on neighborhood deprivation (percentage with basic education, with low income and not in work) and individual socioeconomic position were retrieved from national administrative registers. Multilevel regression analyses with log links and binary distributions were conducted to obtain relative risks, intraclass correlation coefficients and proportional change in variance.Large differences between neighborhoods existed in both deprivation levels and neighborhood health check participation rate (mean 53%; range 35-84%). In multilevel analyses adjusted for age and sex, higher levels of all three indicators of neighborhood deprivation and a deprivation score were associated with lower participation in a dose-response fashion. Persons living in the most deprived neighborhoods had up to 37% decreased probability of participating compared to those living in the least deprived neighborhoods. Inclusion of individual socioeconomic position in the model attenuated the neighborhood deprivation coefficients, but all except for income deprivation remained statistically significant.Neighborhood deprivation was associated with participation in a population-based health check in a dose-response manner, in which increasing neighborhood deprivation was associated with decreasing participation. This suggests the need to develop preventive health checks tailored to deprived neighborhoods.

ObjectivesVitamin D deficiency is common among persons with chronic obstructive pulmonary disease (COPD). Whether vitamin D affects the development and deterioration of COPD or is a consequence of the disease lacks clarity. We investigated the association between vitamin D status and prevalent and incident COPD in the general population.MethodsWe included a total of 12,041 individuals from three general population studies conducted in 1993-94, 1999-2001, and 2006-2008, respectively, with vitamin D measurements. Information on COPD was obtained from the Danish National Patient Register and The Danish Registry of Causes of Death.ResultsThere were 85 prevalent and 463 incident cases of COPD (median follow-up 9.7 years). We found a statistically significant inverse association between vitamin D status and prevalent COPD with odds ratio = 0.89 (95% confidence interval, CI: 0.79, 1.0), but no statistically significant association with incident COPD with a hazard ratio = 0.98 (95% CI: 0.94, 1.0), respectively, per 10 nmol/l higher vitamin D status, when adjusted for possible confounders.ConclusionsWe found a statistically significant inverse cross-sectional association between vitamin D status and COPD, but no association between vitamin D status and incident COPD.

Urine albumin creatinine ratio, UACR, is positively associated with all-cause mortality, cardiovascular disease and diabetes in observational studies. Whether a high UACR is also associated with other causes of death is unclear. We investigated the association between UACR and cause-specific mortality.We included a total of 9,125 individuals from two population-based studies, Monica10 and Inter99, conducted in 1993-94 and 1999-2001, respectively. Urine albumin creatinine ratio was measured from spot urine samples by standard methods. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2010. There were a total of 920 deaths, and the median follow-up was 11.3 years.Multivariable Cox regression analyses with age as underlying time axis showed statistically significant positive associations between UACR status and risk of all-cause mortality, endocrine nutritional and metabolic diseases, mental and behavioural disorders, diseases of the circulatory system, and diseases of the respiratory system with hazard ratios 1.56, 6.98, 2.34, 2.03, and 1.91, for the fourth UACR compared with the first, respectively. Using UACR as a continuous variable, we also found a statistically significant positive association with risk of death caused by diseases of the digestive system with a hazard ratio of 1.02 per 10 mg/g higher UACR.We found statistically significant positive associations between baseline UACR and death from all-cause mortality, endocrine nutritional and metabolic diseases, and diseases of the circulatory system and possibly mental and behavioural disorders, and diseases of the respiratory and digestive system.

BackgroundVitamin D deficiency is associated with increased cardiovascular disease risk in observational studies. Whether these associations are causal is not clear. Loss-of-function mutations in the filaggrin gene result in up to 10% higher serum vitamin D concentrations, supposedly due to a decreased UV-protection of the keratinocytes. We used a Mendelian randomization approach to estimate the causal effect of vitamin D status on serum lipids, blood pressure, body mass index, waist circumference, and the metabolic syndrome.MethodsThree population based studies were included, Monica10 (2,656 individuals aged 40-71 years), Inter99 (6,784 individuals aged 30-60 years), and Health2006 (3,471 individuals aged 18-69 years) conducted in 1993-94, 1999-2001, and 2006-2008, respectively. Participants were genotyped for the two most common filaggrin gene mutations in European descendants R501X and 2282del4, in all three studies and further for the R2447X mutation in the Inter99 and Health2006 studies. Filaggrin genotype was used as instrumental variable for vitamin D status. Baseline measurements of serum 25-hydroxyvitamin D were performed in all three studies.ResultsInstrumental variable analyses showed a 23.8% (95% confidence interval, CI 3.0, 48.6) higher HDL cholesterol level and a 30.5% (95% CI: 0.8, 51.3) lower serum level of triglycerides per doubling of vitamin D. These associations were, however, not statistically significant when applying the Bonferroni adjusted significance level. The remaining lipids showed non-significant changes in a favorable direction. Doubling of vitamin D gave a non-significantly lower odds ratio = 0.26 (95% CI: 0.06, 1.17) of the metabolic syndrome. There were no statistically significant causal effects of vitamin D status on blood pressure, body mass index, or waist circumference.ConclusionOur results support a causal effect of higher vitamin D status on a more favorable lipid profile, although more studies in other populations are needed to confirm our results.

Vitamin D deficiency is associated with an increased risk of all-cause mortality in observational studies. The specific causes of death underlying this association lack clarity. We investigated the association between vitamin D status and cause-specific mortality.We included a total of 9,146 individuals from the two population-based studies, Monica10 and Inter99, conducted in 1993-94 and 1999-2001, respectively. Vitamin D status was assessed as serum 25-hydroxyvitamin D. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2009. There were a total of 832 deaths (median follow-up 10.3 years).Multivariable Cox regression analyses with age as underlying time axis and vitamin D quartiles showed significant associations between vitamin D status and death caused by diseases of the respiratory system, the digestive system, and endocrine, nutritional and metabolic diseases with hazard ratios (HRs) 0.26 (p(trend) = 0.0042), 0.28 (p(trend) = 0.0040), and 0.21 (p(trend) = 0.035), respectively, for the fourth vitamin D quartile compared to the first. We found non-significantly lower HRs for death caused by mental and behavioural diseases and diseases of the nervous system, but no association between vitamin D status and death caused by neoplasms or diseases of the circulatory system.The associations of vitamin D status and cause-specific mortality suggest that we also look elsewhere (than to cardiovascular disease and cancer) to explain the inverse association between vitamin D status and mortality.

BACKGROUND AND AIM:The first genome-wide association study on birth weight was recently published and the most significant associated birth weight lowering variant was the rs900400 C-allele located near LEKR1 and CCNL1. We aimed to replicate the association with birth weight in the Danish Inter99 study and furthermore to evaluate associations between rs900400 and indices of insulin secretion and insulin sensitivity obtained by oral glucose tolerance tests in adults from the Danish Inter99 study and the Finnish, Metabolic Syndrome in Men (METSIM) sample. METHODS:For 4,744 of 6,784 Inter99 participants, midwife journals were traced through the Danish State Archives and association of rs900400 with birth weight was examined. Associations between rs900400 and fasting serum insulin, fasting plasma glucose, insulinogenic index, homeostasis model assessment of insulin resistance (HOMA-IR) and disposition index were studied in 5,484 Danish and 6,915 Finnish non-diabetic individuals and combined in meta-analyses. RESULTS:The C-allele of rs900400 was associated with a 22.1 g lower birth weight ([-41.3;-3.0], P = 0.024) per allele. Moreover, in combined analyses of the Danish Inter99 study and the Finnish METSIM study we found that the birth weight lowering allele was associated with increased insulin release measured by the insulinogenic index (β = 2.25% [0.59; 3.91], P = 0.008) and with an increased disposition index (β = 1.76% [0.04; 3.49], P = 0.05). CONCLUSION:The birth weight lowering effect of the C-allele of rs900400 located near LEKR1 and CCNL1 was replicated in the Danish population. Furthermore the C-allele was associated with increased insulin response following oral glucose stimulation in a meta-analysis based on Danish and Finnish non-diabetic individuals.

Several obesity risk alleles affecting adult adiposity have been identified by the recent wave of genome wide association studies. We aimed to examine the potential effect of these variants on fetal body composition by investigating the variants in relation to birth weight and ponderal index of the newborn.Midwife records from the Danish State Archives provided information on mother's age, parity, as well as birth weight, birth length and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. Twenty-four risk alleles showing genome-wide associations with adult BMI and/or waist circumference were genotyped. None of the 24 risk variants tested showed an association with birth weight or ponderal index after correction for multiple testing. Birth weight was divided into three categories low (≤10(th) percentile), normal (10(th)-90(th) percentile) and high birth weight (≥90th percentile) to allow for non-linear associations. There was no difference in the number of risk alleles between the groups (p = 0.57). No interactions between each risk allele and birth weight in the prediction of adult BMI were observed. An obesity risk score was created by summing up risk alleles. The risk score did not associate with fetal body composition. Moreover there was no interaction between the risk score and birth weight/ponderal index in the prediction of adult BMI.24 common variants associated with adult adiposity did not affect or interact with birth weight among Danes suggesting that the effects of these variants predominantly arise in the post-natal life.

The growth hormone secretagogue receptor (GHSR) is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites.In a population-based study sample of 15,854 unrelated, middle-aged Danes, seven variants were genotyped to capture common variation in an 11 kbp region including GHSR. These were investigated for their individual and haplotypic association with obesity. None of these analyses revealed consistent association with measures of obesity. A -151C/T promoter mutation in the GHSR was found in two unrelated obese patients. One family presented with complete co-segregation, but the other with incomplete co-segregation. The mutation resulted in an increased transcriptional activity (p0.05) could be shown.In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related traits. A rare functional GHSR promoter mutation variant was identified, yet there was no consistent relationship with obesity in neither family- nor population-based studies.

BackgroundPolymorphisms in the potassium channel, voltage-gated, KQT-like subfamily, member 1 (KCNQ1) have recently been reported to associate with type 2 diabetes. The primary aim of the present study was to investigate the putative impact of these KCNQ1 polymorphisms (rs2283228, rs2237892, rs2237895, and rs2237897) on estimates of glucose stimulated insulin release.Methodology/principal findingsGenotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT) in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses. Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean+/-SD: (CC) 277+/-160 vs. (AC) 280+/-164 vs. (AA) 299+/-200 pmol/l, p = 0.008) after an oral glucose load, insulinogenic index (29.6+/-17.4 vs. 30.2+/-18.7vs. 32.2+/-22.1, p = 0.007), incremental area under the insulin curve (20,477+/-12,491 vs. 20,503+/-12,386 vs. 21,810+/-14,685, p = 0.02) among the 4,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified for the less common diabetes risk alleles of rs2237892, rs2237897, or rs2283228.ConclusionThe minor C-allele of rs2237895 of KCNQ1, which has a prevalence of about 42% among Caucasians was associated with reduced measures of insulin release following an oral glucose load suggesting that the increased risk of type 2 diabetes, previously reported for this variant, likely is mediated through an impaired beta cell function.