Anne-Marie Ellegaard,1 Martin L Kårhus,1 Filip K Knop,1-3 Line L Kårhus4 1Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark; 2Steno ...Diabetes Center Copenhagen, Herlev, Denmark; 3Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark; 4Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Frederiksberg, DenmarkCorrespondence: Anne-Marie Ellegaard, Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Gentofte Hospitalsvej 7, 3rd floor, Hellerup, DK-2900, Denmark, Email anne.marie.gade.ellegaard@regionh.dk
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.
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.
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.
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.
Martin L Kårhus,1 Anne-Marie Ellegaard,1 Filip K Knop,1-3 Line L Kårhus4 1Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark; 2Steno ...Diabetes Center Copenhagen, Herlev, Denmark; 3Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark; 4Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Frederiksberg, DenmarkCorrespondence: Anne-Marie Ellegaard, Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Gentofte Hospitalsvej 7, 3rd floor, Hellerup, DK-2900, Denmark, Email anne.marie.gade.ellegaard@regionh.dk
Diagnosed celiac disease (CD) is associated with lymphoproliferative malignancy and gastrointestinal cancer, but little is known about the long-term consequences of undiagnosed CD. We aimed to ...investigate long-term consequences of undiagnosed CD for mortality and incidence of cancer and other chronic diseases.
We screened biobank serum samples for immunoglobulin (Ig) A and IgG tissue transglutaminase (TTG) and IgG deamidated gliadin peptide in a study of 8 population-based cohort studies comprising 16,776 participants examined during 1976-2012 and followed with >99% complete follow-up in Danish nationwide registries until December 31, 2017, regarding vital status and incidence of diseases. Undiagnosed CD was defined as antibody positivity (IgA-TTG or IgG-TTG ≥ 7 U/mL and/or IgG deamidated gliadin peptide ≥ 10 U/mL) in individuals without a diagnosis of CD recorded in the National Patient Register. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox regression analyses with age as the underlying time scale.
The prevalence of undiagnosed CD was 1.0% with no statistically significant increase over time. Undiagnosed CD was associated with increased risk of cancer overall (HR, 1.57; 95% CI, 1.16-2.11), gastrointestinal cancer (HR, 2.33; 95% CI, 1.35-4.04), cancer of the uterus (HR, 3.95; 95% CI, 1.46-10.69), breast cancer (HR, 1.98; 95% CI, 1.02-3.82), head and neck cancer (HR, 3.12; 95% CI, 1.15-8.43), and cardiovascular disease (HR, 1.37; 95% CI, 1.01-1.85). We found no statistically significant association between undiagnosed CD and mortality (HR, 1.19; 95% CI, 0.87-1.61).
Undiagnosed CD was associated with increased risk of cardiovascular disease and cancer suggesting that untreated CD has serious long-term health consequences not only affecting the gastrointestinal tract (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/AJG/B566).
To investigate possible biochemical abnormalities associated with celiac disease (CD) antibody positivity in a primary health care setting and thereby identify predictors that could potentially ...reduce diagnostic delay and underdiagnosis of CD. This observational cohort study included measurements of CD antibodies in the Copenhagen Primary Care Laboratory (CopLab) database from 2000 to 2015; CD antibody positivity was defined as tissue transglutaminase antibody IgA or IgG ≥ 7 kU/L and/or deamidated gliadin peptide antibody IgG ≥ 10 kU/L. Individuals with a prior diagnosis of CD were excluded. We examined differences between individuals with positive and negative CD antibody tests regarding the results of biochemical tests performed six months before and one month after the date of the CD antibody test. We identified 76,265 measurements of CD antibodies during 2000-2015, and 57,061 individuals met the inclusion criteria (706 antibody-positive and 56,355 antibody-negative). We found lower ferritin, hemoglobin, cobalamin and folic acid levels and higher levels of transferrin, ALAT (alanine transaminase), and alkaline phosphate among individuals with a positive CD antibody test. Furthermore, we illustrated more measurements below the sex-specific reference intervals for hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), ferritin, cobalamin and folic acid among individuals with a positive CD antibody test. This study identified several biochemical abnormalities associated with CD antibody positivity among individuals referred to CD antibody testing. The pattern of abnormalities suggested that micronutrient deficiencies were prevalent among CD antibody-positive individuals, confirming malabsorption as a sign of CD. These findings illustrate the possibility of reducing diagnostic delay and underdiagnosis of CD.
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.
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%).
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.
Abstract
Context
Supraphysiological serum insulin-like growth factor-I (IGF-I) concentrations have been a matter of concern in children treated with GH because high IGF-I levels were associated with ...risk of later disease in former epidemiological studies.
Objective
To determine whether a single IGF-I measurement reliably reflects lifetime IGF-I exposure we evaluated intraindividual longitudinal tracking of IGF-I and IGF-binding protein-3 (IGFBP-3) levels and we estimated cumulative lifetime exposure to IGF-I in healthy and GH-treated individuals.
Methods
We included 6459 healthy participants (cross-sectional = 5326; longitudinal = 1133) aged 0-76 years (9963 serum samples) and 9 patients born small-for-gestational-age (SGA) with 238 serum samples during GH treatment. Intraindividual tracking of IGF-I and IGFBP-3 (SD score SDS) was determined by intraclass correlation coefficients (ICCs). Cumulative lifetime IGF-I exposure was estimated by area under the curve of the predicted SDS trajectory from 0 to 76 years.
Results
For IGF-I (SDS), ICCs were 0.50 (95% CI, 0.47-0.53) for male and 0.53 (0.50-0.56) for female participants. Lifetime IGF-I exposure was significantly higher in female (mean 12 723 ± 3691 SD) than in male participants (12 563 ± 3393); P = 0.02. In SGA children, treatment with GH increased the lifetime exposure to IGF-I from 9512 ± 1889 to 11 271 ± 1689, corresponding to an increase in lifetime IGF-I trajectory from −0.89 SD ± 0.57 to −0.35 SD ± 0.49.
Conclusion
Because IGF-I and IGFBP-3 levels track throughout life, a single measurement reliably reflects lifetime exposure. GH therapy increased the lifetime exposure to IGF-I only slightly and it remained below the average lifetime exposure in the reference population.
Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD ...GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.
Objective
The incidence of hypothyroidism is not expected to differ by socioeconomic factors. However, the decision to test and initiate treatment may differ. We aimed to examine whether educational ...level influences the probability of thyroid stimulation hormone (TSH)‐measurement and initiation of levothyroxine treatment.
Design
Citizens in the greater Copenhagen Area during 2001‐2015 were included. Individual‐level data on educational level, diagnoses, GP‐contact, TSH‐measurement and medication were derived from administrative and healthcare registers. The relative risks (RR) between educational levels of annual TSH‐measurement and treatment initiation following a TSH‐measurement were analysed in Poisson regression models with generalized estimation equations.
Results
A TSH‐measurement was performed in 19% of 9,390,052 person years. The probability of TSH‐measurement was higher with short (RR 1.16 95% CI 1.15–1.16) and medium (RR 1.11 95% CI 1.06–1.12) compared with long education.
Treatment was initiated after 0.8% of 2,049,888 TSH‐measurements. For TSH < 5 mIU/L, RR for treatment initiation ranged between 0.47 (95%CI 0.39–0.57) and 0.78 (95%CI 0.67–0.91) for short and medium compared with long education. For TSH 5–10 mIU/L, there was no statistically significant difference. For TSH > 10 mIU/L, RR was 1.07 (95% CI 1.02–1.12) for short and 1.08 (95% CI 1.03–1.13) for medium compared with long education.
Conclusion
The probability of TSH‐measurement was higher with shorter education, and the probability of treatment initiation with TSH > 10 mIU/L was marginally higher with short‐medium education compared with long education. However, the probability of treatment initiation with TSH < 5 mIU/L, that is treatment incongruous with guidelines, was substantially higher in persons with long education.
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