Danish Individuals Research Articles

Use of genetic testing for hypolactasia trait in the North Denmark Region

Objective Lactose intolerance (LI) may be considered in patients with unspecific gastrointestinal symptoms, but there is no clear consensus on when and how to diagnose the disorder. The LCT-13910 CC genotype is associated with acquired primary lactase deficiency (adult-type hypolactasia; ATH). We aimed to describe the number of tests and test results in the North Denmark Region considering patient age, geographical origin and repeated testing. Methods Retrospective evaluation of the polymerase chain reaction-based LCT-13910 genotype tests registered in the clinical laboratory information system (LABKA II) with data linkage to Danish nationwide registers. Results Between 18 May 2007 and 31 December 2018, a total of 23,560 individuals were tested. There was a sevenfold increase in the number of tests performed during the study period. About 9.8% of the tests performed in 2018 were repeated testing in the same individuals. Overall, 8.8% of tested individuals were younger than 5 years, 90.7% were of Danish origin and 5.5% originated from outside of Europe. The LCT-13910 CC genotype was identified in 13.3% of all tested individuals, in 16.0% of children younger than 5 years, in 6.8% of Danish individuals and in 90.9% originating from outside of Europe. Conclusions In the North Denmark Region, a marked increase in the use of genetic testing for hypolactasia was observed and repeated testing was frequent. Furthermore, the use of the test and the test results were dependent on patient age and geographical origin. Results inform the debate on when and how to use genetic testing in the diagnosing of LI.

Long-term employment, education, and healthcare costs of childhood and adolescent onset of epilepsy

ObjectiveChildhood- and adolescent-onset epilepsy may have a significant impact on long-term educational and vocational status, which in turn has consequences for individuals' socioeconomic status. We estimated the factual long-term socioeconomic consequences and healthcare costs of individuals with diagnosed epilepsy. MethodsThe prospective cohort study included Danish individuals with epilepsy onset before the age of 18 years, diagnosed between 2002 and 2016. Healthcare costs and socioeconomic data were obtained from nationwide administrative and health registers. The prediction was made with a general estimating equation (GEE). A total of 15,329 individuals were found with the diagnosis during this period and were followed until the age of 30 years. These were compared with 31,414 controls. We used 30 years as this represent an age where most has finalized their education, and as such represent the final educational level. Patients and their controls were subdivided into debut age groups of 0–5 and 6–18 years. Individuals were matched for age, gender, and residential location. ResultsCompared with control groups, patients with epilepsy at the age of 30 years tended to have the following: 1) parents with lower educational attainment; 2) a significantly lower educational level when controlling for parental education attainment; 3) lower grade-point averages; 4) a lower probability of being in employment and lower income, even when transfer payments were considered; and 5) elevated healthcare costs, including those for psychiatric care. It was also noted that the long-term educational consequences for patients with epilepsy were associated with parental educational level. Differences were more pronounced for those with early (0–5 years) rather than later (6–18 years) onset epilepsy. ConclusionsEpilepsy is associated with severe long-term socioeconomic consequences: lower educational level, school grades, employment status, and earned income. The presence of epilepsy is associated with parental educational level. Limitations1.Register-based study; epilepsy based on diagnosis within the hospital sector; patients found with diagnosis in general practice were not included.2.Some patients treated in the primary sector may not have been identified.3.Parental education level may have risen after the index date when the patient was first included. Significant outcomes•Childhood and adolescent epilepsy are associated with long-term negative impacts on educational level, employment status, and earned income.•Childhood and adolescent epilepsy are associated with long-term healthcare uses, especially for those with early disease onset.•Childhood and adolescent epilepsy are related to lower levels of parental education.

Laboratory Diagnostics of Rickettsia Infections in Denmark 2008-2015.

Rickettsiosis is a vector-borne disease caused by bacterial species in the genus Rickettsia. Ticks in Scandinavia are reported to be infected with Rickettsia, yet only a few Scandinavian human cases are described, and rickettsiosis is poorly understood. The aim of this study was to determine the prevalence of rickettsiosis in Denmark based on laboratory findings. We found that in the Danish individuals who tested positive for Rickettsia by serology, the majority (86%; 484/561) of the infections belonged to the spotted fever group. In contrast, we could confirm 13 of 41 (32%) PCR-positive individuals by sequencing and identified all of these as R. africae, indicating infections after travel exposure. These 13 samples were collected from wound/skin material. In Denmark, approximately 85 individuals test positive for Rickettsia spp. annually, giving an estimated 26% (561/2147) annual prevalence among those suspected of rickettsiosis after tick bites. However, without clinical data and a history of travel exposure, a true estimation of rickettsiosis acquired endemically by tick bites cannot be made. Therefore, we recommend that both clinical data and specific travel exposure be included in a surveillance system of Rickettsia infections.

Mutational analysis of TSC1 and TSC2 in Danish patients with tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in the skin and other organs, including brain, heart, lung, kidney and bones. TSC is caused by mutations in TSC1 and TSC2. Here, we present the TSC1 and TSC2 variants identified in 168 Danish individuals out of a cohort of 327 individuals suspected of TSC. A total of 137 predicted pathogenic or likely pathogenic variants were identified: 33 different TSC1 variants in 42 patients, and 104 different TSC2 variants in 126 patients. In 40 cases (24%), the identified predicted pathogenic variant had not been described previously. In total, 33 novel variants in TSC2 and 7 novel variants in TSC1 were identified. To assist in the classification of 11 TSC2 variants, we investigated the effects of these variants in an in vitro functional assay. Based on the functional results, as well as population and genetic data, we classified 8 variants as likely to be pathogenic and 3 as likely to be benign.

P0036THE EFFECT OF CKD ASSOCIATED SNPS ON THE PROGRESSION OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Abstract Background and Aims Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent, inherited, cystic kidney disease. It is characterized by formation and growth of renal cysts obstructing normal tubules leading to a decline in renal function and eventually end stage renal disease (ESRD). The disease is mainly caused by mutations in either PKD1 or PKD2. Both the involved genes and the type of mutation have been shown to provide significant prognostic information in relation to the risk of early progression to ESRD. However, even within families, progression of disease varies widely between individuals with the same disease causing mutation. This variation might be explained by other genetic components. Previous studies have suggested genetic components affect the progression of Chronic Kidney Disease (CKD) and ESRD. To explain the variation in disease progression, not accounted for by the disease causing gene, 15 Single Nucleotide Variants (SNPs) associated to CKD and/or ESRD were chosen for further analysis. In addition, 3 SNPs within CFTR was included, since variants within this gene is known to affect the progression of ADPKD. Method A cohort of 120 Danish individuals suffering from ADPKD was sequenced using targeted Next Generation Sequencing (NGS). The targeted NGS panel included PKD1, PKD2, rs13538, rs12460876, rs17319721, rs10109414, rs653178, rs267734, rs1260326, rs347685, rs11959928, rs6420094, rs7805747, rs4744712, rs626277, rs881858, rs12917707, rs213950, rs213965, rs1042180. If no causative variant was identified using the NGS panel, Multiplex Ligation-dependent Probe Amplification was performed to identify larger deletions and duplications. In addition, clinical information was obtained to divide patients into two established or predicted progression groups; fast or slow. Results Based on clinical information we identified 39 patients with established or predicted fast progression and 81 with slow progression. The distribution of SNPs in the fast progression group was compared to the distribution within a European population. Out of 18 SNPs, one was significantly different distributed among the fast progressive ADPKD patients, rs13538 (p=0.01); however, in contrast to expected the frequency of the SNP was lower in the fast progression group compared to the European population. To examine if the shift could be associated to a specific disease causing mutation type, the distribution of each SNP within different mutation types were analysed. The mutations were divided into three groups; PKD1 truncating, PKD1 nontruncating and PKD2. A significant difference was observed in all three groups. Conclusion A single SNP associated to progression of CKD was observed to have a different distribution in the fast progressive ADPKD patients. The distribution differed for all analysed mutation types, thus no specific mutation type or gene could explain the shift in distribution alone. Hence, none of the analysed SNPs seem to influence the rate of progression in the analysed cohort of ADPKD patients.

Risk of Lifetime Psychiatric Morbidity in Adults With Atrial Septal Defect (from a Nation-Wide Cohort)

In this nation-wide cohort study we report the first long-term results of the association between having a atrial septal defects (ASD) on psychiatric disorders and use of psychotropic agents. Through population-based registries we included Danish individuals born before 1994 who received an ASD diagnosis between 1959and 2013. We used Cox proportional hazards regression and Fine and Grey competing risk regression to estimate the risk of receiving a psychiatric diagnosis and use of psychotropic medicine compared with a gender and age matched background population cohort. In 2,277 patients with a median follow-up from ASD diagnosis of 23.4 years (range 0.2 to 59.3 years) we found ASD patients to have a higher risk of psychiatric disorders (adjusted hazard ratio [HR]: 3.9; 95% confidence interval [CI] 3.4 to 4.5) compared with the comparison cohort and a cumulative incidence of using psychotropic agents 30 years after the ASD diagnosis of 47.4% (95% CI: 40.3 to 55.1) in the ASD patients and 25.5%, (95% CI: 23.5 to 27.8) in the comparison cohort. Diagnosis of the ASD before the age of 15 years (adjusted HR: 3.4; 95% confidence interval: 2.0 to 4.0) and surgical correction of the defect (HR: 1.5 (95% CI: 1.2 to 1.8), p <0.0001) had a higher risk than those with an ASD diagnosis after the age of 15 years and those with transcatheter closure of the defect. In conclusion, ASD patients had increased long-term risk of psychiatric disorder and use of psychotropic agents compared with a gender and age matched general population controls.

Morbidity and mortality in carriers of the cystic fibrosis mutation CFTR Phe508del in the general population.

Cystic fibrosis (CF) is caused by autosomal-recessive inheritance of a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR), up to 90% due to Phe508del mutation in the CFTR gene. We tested the hypothesis that CFTR Phe508del carriers have increased morbidity and mortality versus non-carriers in the general population.We genotyped 108 035 randomly selected white Danish individuals from the Copenhagen General Population Study (aged from 20-100 years) for CFTR Phe508del mutation (rs113993960). Risk of chronic bronchitis and airflow limitation was assessed cross-sectionally. Overall survival and risk of bronchiectasis, lung cancer, pneumonia, chronic rhinosinusitis, airway bleeding, spontaneous pneumothorax, respiratory failure, acute and chronic pancreatitis, liver cirrhosis, ileus, gastric and colorectal cancer, and male infertility were assessed prospectively during up to 15 years of follow-up (median: 9 years). A single individual was excluded due to homozygosity for CFTR Phe508del and known CF. No other individuals had diagnosed CF at baseline examination or during follow-up.Among the resulting 108 034 individuals, 105 176 (97%) were non-carriers and 2858 (3%) were carriers (i.e. were heterozygous for CFTR Phe508del). Overall survival was similar between carriers and non-carriers. Compared to non-carriers and with multivariable adjustment, carriers had an odds ratio (OR) of 1.31 (95% CI 1.16-1.48) for chronic bronchitis, a hazard ratio (HR) of 1.88 (95% CI 1.03-3.45) for bronchiectasis and 1.52 (95% CI 1.12-2.08) for lung cancer. Carriers did not differ from non-carriers concerning lung function or any other morbidity outcomes as mentioned above.In the general population, carriers of CFTR Phe508del have a normal lifespan but an increased risk of chronic bronchitis (1.3-fold), bronchiectasis (1.9-fold) and lung cancer (1.5-fold).

Association and Familial Coaggregation of Type 1 Diabetes and Eating Disorders: A Register-Based Cohort Study in Denmark and Sweden.

OBJECTIVETo ascertain the association and coaggregation of eating disorders and childhood-onset type 1 diabetes in families.RESEARCH DESIGN AND METHODSUsing population samples from national registers in Sweden (n = 2,517,277) and Demark (n = 1,825,920), we investigated the within-individual association between type 1 diabetes and eating disorders and their familial coaggregation among full siblings, half siblings, full cousins, and half cousins. On the basis of clinical diagnoses, we classified eating disorders into any eating disorder (AED), anorexia nervosa (AN) and atypical AN, and other eating disorder (OED). Associations were determined with hazard ratios (HRs) with 95% CIs from Cox regressions.RESULTSSwedish and Danish individuals with a type 1 diabetes diagnosis had a greater risk of receiving an eating disorder diagnosis (HR [95% CI] Sweden: AED 2.02 [1.80–2.27], AN 1.63 [1.36–1.96], OED 2.34 [2.07–2.63]; Denmark: AED 2.19 [1.84–2.61], AN 1.78 [1.36–2.33], OED 2.65 [2.20–3.21]). We also meta-analyzed the results: AED 2.07 (1.88–2.28), AN 1.68 (1.44–1.95), OED 2.44 (2.17–2.72). There was an increased risk of receiving an eating disorder diagnosis in full siblings in the Swedish cohort (AED 1.25 [1.07–1.46], AN 1.28 [1.04–1.57], OED 1.28 [1.07–1.52]); these results were nonsignificant in the Danish cohort.CONCLUSIONSPatients with type 1 diabetes are at a higher risk of subsequent eating disorders; however, there is conflicting support for the relationship between having a sibling with type 1 diabetes and an eating disorder diagnosis. Diabetes health care teams should be vigilant about disordered eating behaviors in children and adolescents with type 1 diabetes.

Associations of health literacy with socioeconomic position, health risk behavior, and health status: a large national population-based survey among Danish adults

BackgroundHealth literacy concerns the ability of citizens to meet the complex demands of health in modern society. Data on the distribution of health literacy in general populations and how health literacy impacts health behavior and general health remains scarce. The present study aims to investigate the prevalence of health literacy levels and associations of health literacy with socioeconomic position, health risk behavior, and health status at a population level.MethodsA nationwide cross-sectional survey linked to administrative registry data was applied to a randomly selected sample of 15,728 Danish individuals aged ≥25 years. By the short form HLS-EU-Q16 health literacy was measured for the domains of healthcare, disease prevention, and health promotion. Adjusted multinomial logistic regression analyses were used to estimate associations of health literacy with demographic and socioeconomic characteristics, health risk behavior (physical activity, smoking, alcohol consumption, body weight), and health status (sickness benefits, self-assessed health).ResultsOverall, 9007 (57.3%) individuals responded to the survey. Nearly 4 in 10 respondents faced difficulties in accessing, understanding, appraising, and applying health information. Notably, 8.18% presented with inadequate health literacy and 30.94% with problematic health literacy. Adjusted for potential confounders, regression analyses showed that males, younger individuals, immigrants, individuals with basic education or income below the national average, and individuals receiving social benefits had substantially higher odds of inadequate health literacy. Among health behavior factors (smoking, high alcohol consumption, and inactivity), only physical behavior [sedentary: OR: 2.31 (95% CI: 1.81; 2.95)] was associated with inadequate health literacy in the adjusted models. The long-term health risk indicator body-weight showed that individuals with obesity [OR: 1.78 (95% CI: 1.39; 2.28)] had significantly higher odds of lower health literacy scores. Poor self-assessed health [OR: 4.03 (95% CI: 3.26; 5.00)] and payments of sickness absence compensation benefits [OR: 1.74 (95% CI: 1.35; 2.23)] were associated with lower health literacy scores.ConclusionsDespite a relatively highly educated population, the prevalence of inadequate health literacy is high. Inadequate health literacy is strongly associated with a low socioeconomic position, poor health status, inactivity, and overweight, but to a lesser extent with health behavior factors such as smoking and high alcohol consumption.

A large population-based investigation into the genetics of susceptibility to gastrointestinal infections and the link between gastrointestinal infections and mental illness

Gastrointestinal infections can be life threatening, but not much is known about the host’s genetic contribution to susceptibility to gastrointestinal infections or the latter’s association with psychiatric disorders. We utilized iPSYCH, a genotyped population-based sample of individuals born between 1981 and 2005 comprising 65,534 unrelated Danish individuals (45,889 diagnosed with mental disorders and 19,645 controls from a random population sample) in which all individuals were linked utilizing nationwide population-based registers to estimate the genetic contribution to susceptibility to gastrointestinal infections, identify genetic variants associated with gastrointestinal infections, and examine the link between gastrointestinal infections and psychiatric and neurodevelopmental disorders. The SNP heritability of susceptibility to gastrointestinal infections ranged from 3.7% to 6.4% on the liability scale. Significant correlations were found between gastrointestinal infections and the combined group of mental disorders (OR = 2.09; 95% CI: 1.82–2.4, P = 1.87 × 10–25). Correlations with autism spectrum disorder, attention deficit hyperactivity disorder, and depression were also significant. We identified a genome-wide significant locus associated with susceptibility to gastrointestinal infections (OR = 1.13; 95% CI: 1.08–1.18, P = 2.9 × 10–8), where the top SNP was an eQTL for the ABO gene. The risk allele was associated with reduced ABO expression, providing, for the first time, genetic evidence to support previous studies linking the O blood group to gastrointestinal infections. This study also highlights the importance of integrative work in genetics, psychiatry, infection, and epidemiology on the road to translational medicine.

Impact of Glucose Level on Micro- and Macrovascular Disease in the General Population: A Mendelian Randomization Study.

To evaluate whether high glucose levels in the normoglycemic range and higher have a causal genetic effect on risk of retinopathy, neuropathy, nephropathy, chronic kidney disease (CKD), peripheral arterial disease (PAD), and myocardial infarction (MI; positive control) in the general population. This study applied observational and one-sample Mendelian randomization (MR) analyses to individual-level data from 117,193 Danish individuals, and validation by two-sample MR analyses on summary-level data from 133,010 individuals from the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC), 117,165 from the CKDGen Consortium, and 452,264 from the UK Biobank. Observationally, glucose levels in the normoglycemic range and higher were associated with high risks of retinopathy, neuropathy, diabetic nephropathy, PAD, and MI (all P for trend <0.001). In genetic causal analyses, the risk ratio for a 1 mmol/L higher glucose level was 2.01 (95% CI 1.18-3.41) for retinopathy, 2.15 (1.38-3.35) for neuropathy, 1.58 (1.04-2.40) for diabetic nephropathy, 0.97 (0.84-1.12) for estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, 1.19 (0.90-1.58) for PAD, and 1.49 (1.02-2.17) for MI. Summary-level data from the MAGIC, the CKDGen Consortium, and the UK Biobank gave a genetic risk ratio of 4.55 (95% CI 2.26-9.15) for retinopathy, 1.48 (0.83-2.66) for peripheral neuropathy, 0.98 (0.94-1.01) for eGFR <60 mL/min/1.73 m2, and 1.23 (0.57-2.67) for PAD per 1 mmol/L higher glucose level. Glucose levels in the normoglycemic range and higher were prospectively associated with a high risk of retinopathy, neuropathy, diabetic nephropathy, eGFR <60 mL/min/1.73 m2, PAD, and MI. These associations were confirmed in genetic causal analyses for retinopathy, neuropathy, diabetic nephropathy, and MI, but they could not be confirmed for PAD and seemed to be refuted for eGFR <60 mL/min/1.73 m2.

Solitary confinement placement and post-release mortality risk among formerly incarcerated individuals: a population-based study

With more than 10 million people incarcerated worldwide, some of whom will have experienced solitary confinement, a better understanding of health and mortality after release is needed. The aim of this study was to assess the relationship between placement in solitary confinement and mortality in the 5 years following release among formerly incarcerated individuals. In this population-based study we used data from Danish administrative registers and administrative dataset from the Danish Prison and Probation Service. We linked information on all Danish individuals who had been incarcerated for more than 7 days during 2006-11, with information on mortality for the 60 months following release. We used Cox proportional hazards models to estimate the association between being placed in solitary confinement and mortality (death and cause of death) among formerly incarcerated Danish individuals, controlling for several possible confounders (prison security level, release year, sentence length, reason for conviction, age at admission, sex, ethnic minority background, and education level) and using a reference group of incarcerated Danish individuals who had been sanctioned for in-prison infractions but not placed in solitary confinement in some models. Our study included 13 776 individuals, which translated to 812 374 person-months of exposure to the risk of mortality up to Dec 31, 2016. Formerly incarcerated Danish individuals who spent time in solitary confinement had higher overall mortality 5 years after release (4·5%) than did those who had not spent time in solitary confinement (2·8%; p<0·0001). After adjusting for possible confounders, our results suggested an association between solitary confinement and elevated mortality due to non-natural causes (hazard ratio 2·342, 95% CI 1·527-3·592). We did not identify a significant association with natural causes. The results from these analyses indicate that solitary confinement placement might be a key moderator of the association between a history of incarceration and post-release outcomes. Our findings suggest that incarcerated individuals ever placed in solitary confinement are a vulnerable population in need of interventions. ROCKWOOL Foundation.

Long-term health and socioeconomic consequences of childhood and adolescent-onset of narcolepsy

ObjectivesThere is limited information about the long-term consequences of childhood- and adolescent-onset narcolepsy on educational and social factors. Here, we estimate the long-term socioeconomic consequences and health care costs of narcolepsy. MethodsThe prospective cohort study included Danish individuals with narcolepsy onset in childhood or adolescence, diagnosed between 1994 and 2015. Health care costs and socioeconomic data were obtained from nationwide administrative and health registers. One hundred seventy-one patients were compared with 680 controls (mean index age, 15.2 years; SD, 3.4 years) matched for age, gender, and other sociodemographic characteristics. ResultsComparing the narcolepsy patient and control groups at age 20 years we found: (1) no differences in parental educational level; (2) patients had a significantly lower educational level than controls; (3) patients had significantly lower grade-point averages; (4) patients had a lower employment rate and lower-income, even when transfer payments were considered; and (5) patients' initial health care costs were higher. Patients had a higher mortality rate than controls, although the difference was not statistically significant. ConclusionNarcolepsy is associated with a significant influence on educational level, grading, social outcome, and welfare consequences. The development of narcolepsy is independent of parental social level.

Pregnancy outcome in women with atrial septal defect: associated with in vitro fertilisation and pre-eclampsia

ObjectiveTo investigate in vitro fertilisation (IVF) in women with atrial septal defect (ASD), and to examine the maternal characteristics and outcome of pregnancy, as well as the fetal outcome of...

Burden of disease of heavy metals in population clusters: towards targeted public health strategies

Abstract Background Humans are exposed to heavy metals from certain foods, thus specific dietary patterns may lead to high burden of disease (BoD). By identifying diet, lifestyle and socio-demographic characteristics of population groups with highest BoD, targeted preventive strategies can be developed. We aimed at identifying clusters and characteristics of Danish individuals with highest BoD due to food exposure to three heavy metals: methylmercury (MeHg), cadmium and inorganic arsenic. Methods We collected diet, lifestyle and socio-demographic information of 3,946 individuals in the Danish National Survey of Diet and Physical Activity. Occurrence of heavy metals in food was obtained from Danish food monitoring. We applied machine learning self-organizing maps to group individuals according to similarities in diet, lifestyle and socio-demographics, and estimated BoD due to metal exposure in terms of Disease-Adjusted Life Years (DALY). We will present calculation steps of our approach in a tutorial-like way and demonstrate its applicability to other cases. Results We identified 13 population subgroups with distinct dietary and lifestyle characteristics. The estimated BoD varied largely between subgroups, with five subgroups experiencing a BoD &amp;gt; 10 DALY/100,000. The cluster bearing the highest BoD (26.2 (95% uncertainty interval (UI): 10.3, 50.6) DALY/100,000) was significantly different from the cluster with the lowest BoD (5.1 (95% UI: 2.5, 9.2) DALY/100,000) (preliminary). BoD was higher in subgroups with diet and lifestyle considered healthy. Most of the BoD was due to MeHg, particularly in female-dominant subgroups. Conclusions Linking machine learning, exposure assessment and burden of disease metrics, this novel approach identified population subgroups with higher BoD due to exposure to three heavy metals. It can be expanded to estimate BoD of other chemicals, and used to develop targeted preventive strategies to reduce BoD in more affected subgroups.

Greater glucagon-like peptide-1 responses to oral glucose are associated with lower central and peripheral blood pressures

Background and aimCardiovascular diseases (CVDs) are globally the leading cause of death and hypertension is a significant risk factor. Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists has been associated with decreases in blood pressure and CVD risk. Our aim was to investigate the association between endogenous GLP-1 responses to oral glucose and peripheral and central haemodynamic measures in a population at risk of diabetes and CVD.MethodsThis cross-sectional study included 837 Danish individuals from the ADDITION-PRO cohort (52% men, median (interquartile range) age 65.5 (59.8 to 70.7) years, BMI 26.1 (23.4 to 28.5) kg/m2, without antihypertensive treatment and known diabetes). All participants received an oral glucose tolerance test with measurements of GLP-1 at 0, 30 and 120 min. Aortic stiffness was assessed by pulse wave velocity (PWV). The associations between GLP-1 response and central and brachial blood pressure (BP) and PWV were assessed in linear regression models adjusting for age and sex.ResultsA greater GLP-1 response was associated with lower central systolic and diastolic BP of − 1.17 mmHg (95% confidence interval (CI) − 2.07 to − 0.27 mmHg, P = 0.011) and − 0.74 mmHg (95% CI − 1.29 to − 0.18 mmHg, P = 0.009), respectively, as well as lower brachial systolic and diastolic BP of − 1.27 mmHg (95% CI − 2.20 to − 0.33 mmHg, P = 0.008) and − 1.00 (95% CI − 1.56 to − 0.44 mmHg, P = 0.001), respectively. PWV was not associated with GLP-1 release (P = 0.3). Individuals with the greatest quartile of GLP-1 response had clinically relevant lower BP measures compared to individuals with the lowest quartile of GLP-1 response (central systolic BP: − 4.94 (95% CI − 8.56 to − 1.31) mmHg, central diastolic BP: − 3.05 (95% CI − 5.29 to − 0.80) mmHg, brachial systolic BP: − 5.18 (95% CI − 8.94 to − 1.42) mmHg, and brachial diastolic BP: − 2.96 (95% CI − 5.26 to − 0.67) mmHg).ConclusionGreater glucose-stimulated GLP-1 responses were associated with clinically relevant lower central and peripheral blood pressures, consistent with beneficial effects on the cardiovascular system and reduced risk of CVD and mortality.Trial registration ClinicalTrials.gov Identifier: NCT00237549. Retrospectively registered 10 October 2005

Psychosocial working conditions and depressive disorder: disentangling effects of job control from socioeconomic status using a life-course approach

PurposeJob control, the combination of skill discretion and decision authority, is considered a central component of the psychosocial working environment. This longitudinal study examines the relation between job control and risk of incident depressive disorder using a life-course approach.MethodsWe analyze data from The Danish Work Life Course Cohort study, including all Danish individuals aged 15–30 who entered the Danish labor market during 1995–2009 and were free from depressive disorder at entry (955,573 individuals). We measured job control using a job exposure matrix. Depressive disorders were measured using information from nationwide registers of psychiatric in- and outpatient admissions. Using Cox regression models we estimated the prospective association between job control and risk of incident depressive disorders. Analyses accounted for a range of potential confounders prior to workforce entry including socioeconomic status in adolescence and parental psychiatric and somatic diagnoses prior to labor market entry, together with potential confounders in adulthood including income, education, and demographics.ResultsLower levels of past year job control were associated with a higher risk of depressive disorder after adjustment for all covariates (HR = 1.27, 95% CI 1.16–1.38). Results stratified by gender showed associations for both men (HR = 1.38, 95% CI 1.19–1.61) and women (HR = 1.19, 95% CI 1.08–1.32). Conclusions: Our findings suggest that the level of job control at work affects the risk of clinically diagnosed depressive disorder, and that this association is not due to confounding by socioeconomic status.

Impact of LDL Cholesterol on Microvascular Versus Macrovascular Disease: A Mendelian Randomization Study

BackgroundLow-density lipoprotein cholesterol (LDL-C) is causally associated with a high risk of coronary artery disease. Whether this also holds for a spectrum of peripheral vascular diseases is unknown. ObjectivesThe purpose of this study was to determine whether high LDL-C causally relates to risk of retinopathy, neuropathy, chronic kidney disease (CKD), and peripheral arterial disease (PAD) in the general population. MethodsOne-sample Mendelian randomization (MR) of 116,419 Danish individuals, 2-sample MR on summary-level data from the Global Lipid Genetics Consortium (GLGC) (n = 94,595) and the UK Biobank (n = 408,455), and meta-analysis of randomized statin trials (n = 64,134) were performed. ResultsObservationally, high LDL-C did not associate with high risk of retinopathy or neuropathy. There were stepwise increases in risk of CKD and PAD with higher LDL-C (both p for trend <0.001), with hazard ratios of 1.05 (95% confidence interval [CI]: 0.97 to 1.13) for CKD, and 1.41 (95% CI: 1.23 to 1.62) for PAD in individuals with LDL-C above the 95th percentile versus below the 50th percentile. In genetic, causal analyses in the Copenhagen studies, the risk ratio of disease for a 1 mmol/l higher LDL-C was 1.06 (95% CI: 0.24 to 4.58) for retinopathy, 1.05 (95% CI: 0.64 to 1.72) for neuropathy, 3.83 (95% CI: 2.00 to 7.34) for CKD, and 2.09 (95% CI: 1.30 to 2.38) for PAD. Summary-level data from the GLGC and the UK Biobank for retinopathy, neuropathy, and PAD gave similar results. For CKD, a 1-mmol/l lower LDL-C conferred a higher eGFR of 1.95 ml/min/1.73 m2 (95% CI: 1.88 to 2.02 ml/min/1.73 m2) observationally, 5.92 ml/min/1.73 m2 (95% CI: 4.97 to 6.86 ml/min/1.73 m2) genetically, and 2.69 ml/min/1.73 m2 (95% CI: 1.48 to 3.94 ml/min/1.73 m2) through statin therapy. ConclusionsHigh LDL-C was not causally associated with risk of retinopathy and neuropathy; however, high LDL-C was observationally and genetically associated with high risks of PAD and CKD, suggesting that LDL-C is causally involved in the pathogenesis of these diseases.

Histological age-at-death estimation in white South Africans using stereology.

Various methods are available for estimating age from skeletal remains, amongst them the use of histomorphometry. It is generally argued that age estimation standards are population specific, but this in itself creates problems as the reference samples used are often not large enough and/or lack substantial representation of all age cohorts. Traditional age methods have been shown to suffer from problems such as age mimicry. This paper aims at establishing histological age-at-death standards for the white South African population by supplementing the available sample (lacking an adequate number of young adults) with another sample of European descent to avoid over-estimation of age in younger individuals caused by age mimicry. Bone microstructures related to the number of osteons and fragments, osteon size and Haversian canal size that change with advancing age were used for the development of regression formulae. A histomorphometric assessment of the anterior cortex of the femur was done using stereology for the estimation of age at death. All sections were analysed using the optical fractionator and nucleator probes. A sample of 94 bone sections (n = 50 male, n = 44 females) of white South African individuals were used. A sample of Danish individuals (n = 14 males, n = 16 females) was combined with the South African sample to create a normal age distribution for the reference sample. Single and multiple regression equations were developed after randomly selecting a hold-out sample (n = 14) for validation. Osteon size (average length, surface area and volume) showed the highest correlation with age, followed by the number of osteons and fragments per grid area. Haversian canal size showed inconsistent changes with advancing age. Using the regression equations, predicted ages were obtained for the 14 individuals. RMSE values ranged between 14 and 17years, which we deemed acceptable.

Large diversity in Danish health literacy profiles: perspectives for care of long-term illness and multimorbidity.

Health literacy is an important, modifiable, social determinant of health. This study aims to explore health literacy challenges of people with long-term illness or multimorbidity and provide detailed profiles revealing health literacy strengths and weaknesses within a Danish population. In this cross-sectional study among Danish individuals (n = 490), health literacy was assessed using the nine-scale Health Literacy Questionnaire (HLQ). Using multiple logistic regression and hierarchical cluster analysis, we estimated the association between HLQ scale scores and the likelihood of long-term illness and multimorbidity, and identified socio-demographic and health characteristics related to profiles of health literacy strengths and weaknesses. An increase in 'actively managing my health' and 'social support for health' decreased the odds of having a long-term illness [odds ratio, OR 0.53 (0.31-0.9); OR 0.43 (0.24-0.74)] and multimorbidity [OR 0.51 (0.26-0.98); OR 0.33 (0.17-0.62)], respectively. Conversely, an increase in 'healthcare provider support' increased the odds of having long-term illness [OR 2.97 (1.78-5.08)] and multimorbidity [OR 2.94 (1.53-5.87)], respectively. Five profiles were identified based on the cluster analysis. Each cluster was characterized by specific health characteristics, e.g. Cluster A by better health status (χ2 = 39.976 (4), P < 0.001) and well-being (χ2 = 28.832 (4), P < 0.001) and Cluster D by poor health status (χ2 = 39.976 (4), P < 0.001) and increased likelihood of long-term illness (χ2 = 18.641 (4), P < 0.001). The association of health literacy with long-term illness and multimorbidity in combination with the health literacy profiling based on cluster analysis provides a comprehensive needs assessment and a promising starting point for the development of health literacy responsive interventions.