Bile Acid Diarrhea Is Associated With an Increased Incidence of Gastrointestinal Cancers.

INTRODUCTION: Bile acid diarrhea (BAD) is an underrecognized and socially debilitating disease caused by high concentrations of bile acids in the colon. Bile acids directly and indirectly promote carcinogenesis. In this article, we investigated whether individuals with BAD have an increased risk of gastrointestinal (GI) cancers. METHODS: By using the Danish health registries, adult individuals with BAD were identified by International Classification of Diseases 10th revision code K90.8 or referral to the diagnostic 75selenium-homotaurocholic acid test followed by prescription of a bile acid sequestrant within 365 days (n = 5,245). Age- and sex-matched individuals without BAD were included for comparison (n = 52,450). We analyzed the cumulative incidence of GI cancers after BAD diagnosis and the odds ratios (ORs) of GI cancer 8 and 15 years before BAD diagnosis/matching. RESULTS: Cumulative incidence of GI cancer 6 years after BAD diagnosis/matching was 1.6% in the BAD group and 1.1% in controls ( P = 0.01). The ORs of total GI cancer 8 and 15 years before BAD diagnosis were 6.16 (5.08-7.48) and 5.19 (4.28-6.29), respectively. Furthermore, 47 individuals with BAD (0.9%) and 250 (0.5%) controls died of GI cancer. DISCUSSION: This nationwide cohort study indicates an association between BAD and GI cancers. We found both a higher incidence of GI cancer after BAD diagnosis compared with controls and increased OR of GI cancer before BAD diagnosis. Bearing in mind the underdiagnosis of BAD, the delay of BAD diagnosis, and the carcinogenic effect of bile acids, these findings warrant further investigations of the risk of GI cancer in individuals with BAD.

Population-based epidemiology: The Glostrup Population Studies 1964-2021.

The Glostrup Population Studies are population-based cohorts undertaken in the south-western part of Greater Copenhagen since 1964. The participants were randomly selected from the adult general population. The first cohort was established to assess cardiovascular risk factors and, since, the objectives have been broadened to describe and analyse the health of the general population. The studies are health-examination studies with clinical and biochemical data in addition to data from self-administered questionnaires and, in some studies, interviews. Fasting blood and urine samples were collected and stored in our biobank for further studies. Several of the cohorts were performed according to standardized methods in international consortia, hence data have been pooled with other, both Danish and international, cohorts. To date more than 30,000 individuals, both men and women, aged 15-85 years, have participated in The Glostrup Population Studies and participants have been re-examined up to eight times. The data can be used for disease-specific epidemiology, social epidemiology, genetic epidemiology, ageing, lifestyle and health interventions nested within the cohorts. The Glostrup Population Studies represent a great resource; the possibility of merging the different cohorts enables large datasets, as well as trends over time. Furthermore, the long follow-up in both the national registers and with follow-up examinations is unique. The purpose of this commentary is to inform about The Glostrup Population Studies and to invite collaborations to continue utilizing this great resource to combat current and future challenges within health promotion and disease prevention.

Regional and temporal differences in the associations between cardiovascular disease and its classic risk factors: an analysis of 49 cohorts from 11 European countries.

AIMS: The regional and temporal differences in the associations between cardiovascular disease (CVD) and its classic risk factors are unknown. The current study examined these associations in different European regions over a 30-year period. METHODS AND RESULTS: The study sample comprised 553 818 individuals from 49 cohorts in 11 European countries (baseline: 1982-2012) who were followed up for a maximum of 10 years. Risk factors [sex, smoking, diabetes, non-HDL cholesterol, systolic blood pressure (BP), and body mass index (BMI)] and CVD events (coronary heart disease or stroke) were harmonized across cohorts. Risk factor-outcome associations were analysed using multivariable-adjusted Cox regression models, and differences in associations were assessed using meta-regression. The differences in the risk factor-CVD associations between central Europe, northern Europe, southern Europe, and the UK were generally small. Men had a slightly higher hazard ratio (HR) in southern Europe (P = 0.043 for overall difference), and those with diabetes had a slightly lower HR in central Europe (P = 0.022 for overall difference) compared with the other regions. Of the six CVD risk factors, minor HR decreases per decade were observed for non-HDL cholesterol [7% per mmol/L; 95% confidence interval (CI), 3-10%] and systolic BP (4% per 20 mmHg; 95% CI, 1-8%), while a minor HR increase per decade was observed for BMI (7% per 10 kg/m2; 95% CI, 1-13%). CONCLUSION: The results demonstrate that all classic CVD risk factors are still relevant in Europe, irrespective of regional area. Preventive strategies should focus on risk factors with the greatest population attributable risk.

All classic cardiovascular disease (CVD) risk factors are still relevant in Europe, irrespective of regional area. The differences in the associations of CVD risk factors with overt CVD between regions of Europe are generally small. Minor temporal hazard decreases were observed for non-HDL cholesterol and systolic blood pressure, while a minor hazard increase was observed for body mass index.

The Epidemiology of Bile Acid Diarrhea in Denmark.

Objective: Bile acid diarrhea (BAD) is a socially debilitating disease with frequent bowel movements, urgency, and fecal incontinence as the main symptoms. It is caused by excessive bile acid levels in the colon and is most commonly treated with bile acid sequestrants. It is estimated that 1-2% of the population suffers from the disease, but only a fraction of these are properly diagnosed with the gold standard 75selenium-homotaurocholic acid (SeHCAT) test. Here, we use nationwide registries to describe the demographic characteristics of individuals suffering from BAD in Denmark. Methods: Since the International Classification of Diseases diagnosis code for BAD was not used until 2021, we identified the BAD population by referral to SeHCAT testing followed by a prescription of a bile acid sequestrant (colestyramine, colestipol or colesevelam) within 365 days. The study period was from 2003 to 2021. Results: During the study period, a total of 5264 individuals with BAD were identified with large differences between the five regions in Denmark. The number of prescriptions of colestyramine and colesevelam, the number of SeHCAT tests, and the number of individuals diagnosed with BAD increased during the study period. The BAD population had more co-morbidities and more health care contacts as well as lower levels of education and income compared with age- and sex-matched controls from the general population. Conclusion: Using the Danish registries, we identified a BAD population, which seems to be inferior in health care and socio-economic parameters compared with the Danish general population.

Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.

Symptoms and biomarkers associated with celiac disease: evaluation of a population-based screening program in adults.

OBJECTIVES: To identify possible early predictors (symptoms and biomarkers) of celiac disease, compare symptoms before and after screening, and evaluate the diagnostic efficacy of serologic screening for celiac disease in an adult Danish population. METHODS: This cross-sectional population-based study was based on the 5-year follow-up of the Health2006 cohort, where 2297 individuals were screened for celiac disease; 56 were antibody positive and thus invited to clinical evaluation. Eight were diagnosed with biopsy-verified celiac disease. A follow-up questionnaire was sent to antibody-positive individuals 19 months after the clinical evaluation to obtain information on their symptoms and their experience with participation in the screening. RESULTS: Before screening, participants subsequently diagnosed with celiac disease did not differ from the rest of the population with respect to symptoms, but had significantly lower total cholesterol. Tissue transglutaminase IgA antibodies with a cut-off of 10 U/ml had a positive predictive value of 88%. The majority of participants were satisfied with their participation in the screening program. Individuals with celiac disease were generally satisfied with having been diagnosed and 71% felt better on a gluten-free diet. CONCLUSION: There were no differences in the prevalence of symptoms between participants with and without screening-detected celiac disease, confirming that risk stratification in a general population by symptoms is difficult. The majority of participants diagnosed with celiac disease felt better on a gluten-free diet despite not reporting abdominal symptoms before diagnosis and participants in the clinical evaluation were generally satisfied with participation in the screening program.