The differentiating effect of COVID-19-associated stress on the morbidity of blood donors with symptoms of hidradenitis suppurativa, hyperhidrosis, or psoriasis.

PURPOSE: The burden of different skin diseases may vary leading individuals to have different sensitivity to stress. Therefore, we compared the health-related quality of life (HRQoL) and stress before and during the universal stress from the severe acute respiratory syndrome coronavirus-2-pandemic in individuals with and without hyperhidrosis, hidradenitis suppurativa, or psoriasis. METHODS: The study cohort was the Danish Blood Donor Study. Overall, 12,798 participants completed a baseline questionnaire before the pandemic, in 2018-2019, and a follow-up questionnaire during the pandemic, in 2020. Regression determined the association between the skin diseases and outcomes. Outcomes were the physical and mental component summary (MCS, PCS, respectively), which assess the mental and physical HRQoL, and the perceived stress scale, which assesses stress in the past four weeks. RESULTS: Overall, 1168 (9.1%) participants had hyperhidrosis, 363 (2.8%) had hidradenitis suppurativa, and 402 (3.1%) had psoriasis. At follow-up, the participants with hyperhidrosis had worse MCS (coefficient -0.59 [95% confidence interval (CI) -1.05, -0.13]) and higher odds of moderate-to-severe stress (odds ratio 1.37 [95% CI 1.13, 1.65]) and the participants with hidradenitis suppurativa worse PCS (coefficient -0.74 [95% CI -1.21, -0.27]) than the control groups. The associations were independent of baseline HRQoL, stress, the Connor-Davidson Resilience scale, and other covariables. Psoriasis was not associated with the outcomes. CONCLUSION: Individuals with hyperhidrosis or hidradenitis suppurativa experienced worse mental or physical well-being and individuals with hyperhidrosis also had higher stress during the pandemic compared to healthy individuals. This suggests that individuals with these skin diseases are particularly susceptible to external stress.

The temporal association of hyperhidrosis and its comorbidities - a nationwide hospital-based cohort study.

BACKGROUND: Research on hyperhidrosis comorbidities has documented the co-occurrence of diseases but has not provided information about temporal disease associations. OBJECTIVE: To investigate the temporal disease trajectories of individuals with hospital-diagnosed hyperhidrosis. METHODS: This is a hospital-based nationwide cohort study including all patients with a hospital contact in Denmark between 1994 and 2018. International Classification of Diseases version-10 diagnoses assigned to inpatients, outpatients and emergency department patients were collected from the Danish National Patient Register. The main outcome was the temporal disease associations occurring in individuals with hyperhidrosis, which was assessed by identifying morbidities significantly associated with hyperhidrosis and then examining whether there was a significant order of these diagnoses using binomial tests. RESULTS: Overall, 7 191 519 patients were included. Of these, 8758 (0.12%) patients had localized hyperhidrosis (5674 female sex [64.8%]; median age at first diagnosis 26.9 [interquartile range 21.3-36.1]) and 1102 (0.015%) generalized hyperhidrosis (606 female sex [59.9%]; median age at first diagnosis 40.9 [interquartile range 26.4-60.7]). The disease trajectories comprised pain complaints, stress, epilepsy, respiratory and psychiatric diseases. The most diagnosed morbidities for localized hyperhidrosis were abdominal pain (relative risk [RR] = 121.75; 95% Confidence Interval [CI] 121.14-122.35; P < 0.001), soft tissue disorders (RR = 151.19; 95% CI 149.58-152.80; P < 0.001) and dorsalgia (RR = 160.15; 95% CI 158.92-161.38; P < 0.001). The most diagnosed morbidities for generalized hyperhidrosis were dorsalgia (RR = 306.59; 95% CI 302.17-311.02; P < 0.001), angina pectoris (RR = 411.69; 95% CI 402.23-421.16; P < 0.001) and depression (RR = 207.92; 95% CI 202.21-213.62; P < 0.001). All these morbidities were diagnosed before hyperhidrosis. CONCLUSIONS: This paper ascertains which hospital-diagnosed morbidities precede hospital-diagnosed hyperhidrosis. As hyperhidrosis mainly is treated in the primary health care sector, the trajectories suggests that these morbidities may lead to a worse disease course of hyperhidrosis that necessitates treatment in hospitals. Treating these morbidities may improve the disease course of hyperhidrosis.

Incidence and remission rates of self-reported hidradenitis suppurativa - A prospective cohort study conducted in Danish blood donors.

BACKGROUND: A large discrepancy between physician-diagnosed and self-reported Hidradenitis suppurativa (HS) exists. Knowledge regarding incidence and remission rates of self-reported HS is missing, but may help bridge the gap in understanding between these two phenotypes. OBJECTIVES: To determine the incidence and remission rates of self-reported HS, and to what degree these are affected by sex, smoking and BMI. METHODS: A prospective cohort of 23 930 Danish blood donors. Information on self-reported HS, symptom-localisation, sex, age, BMI and smoking status was collected at baseline and study termination. Self-reported HS fulfilled clinical obligatory diagnostic criteria. Cox proportional hazards regression analyses were conducted for both incidence and remission rates providing a hazard ratio (HR) of risk for each variable in the regression. RESULTS: Incidence rate of self-reported HS was 10.8/1000 person-years (95% confidence interval (CI): 9.9-11.7), decreasing as a function of numbers of areas affected. Female BMI points above 25 (HR = 1.11, 95% CI: 1.09-1.13), male BMI points above 25 (HR = 1.07, 95% CI: 1.04-1.11), active smoking (HR = 1.72, 95% CI: 1.15-2.57), male sex (HR = 0.55, 95% CI: 0.45-0.67) and years of age above 25 (HR = 0.97, 95% CI: 0.96-0.97) were all statistically associated with the development of self-reported HS. Remission rate of self-reported HS was 256.7/1000 person-years (95% CI: 223.9-292.6), decreasing as a function of numbers of affected areas. Symptoms in ≥3 areas (HR = 0.54, 95% CI: 0.34-0.85), active smoking (HR = 0.49, 95% CI: 0.32-0.76) and female weight loss (every percentage drop in BMI: HR = 1.07, 95% CI: 1.05-1.11) all significantly affected the remission rate. CONCLUSIONS: Both incidence and remission rates of self-reported HS are high, indicating that many with self-reported HS are unlikely to be diagnosed, as they to a higher degree experience mild transient HS symptoms.

Full exome sequencing of 11 families with Hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is not a well-studied or easily treated disease. Genetic information is essential for advances in the understanding and treatment of HS. This study aims to examine mutations in the gamma-secretase complex, the Notch signalling pathway and to perform a Mendelian analysis of genetic variants that segregated with disease in a full exome sequencing of 11 families with HS. METHOD: Whole-exome sequencing and Mendelian analysis of 11 families with HS from Denmark. Patients with a clinical diagnosis of active HS and a positive family history of HS were recruited. Consenting family members were enrolled and examined for HS as well. We included 11 families, with a total of 51 participants, 24 with HS and 27 without. Whole-exome sequencing using HiSeq platform as paired-end 2 × 150 bases was used. RESULTS: We found mutations in the Notch pathway for all families. We found mutations in the PSENEN and APH1B of the gamma-secretase genes. We also report 161 variants of unknown significance that segregated with the disease within these families. CONCLUSIONS: We did not find causative mutation for each family in this study, supporting the theory that HS is rarely caused by single-gene mutations. We suggest that future genetic studies should be focused on genome-wide association with thousands of cases, as this technique is better suited for suspected polygenic diseases.

History of cardiovascular disease and cardiovascular biomarkers are associated with 30-day mortality in patients with hip fracture.

Hip fractures are associated with increased mortality and it is important to identify risk factors. This study demonstrates that preexisting cardiovascular disease as well as cardiovascular biomarkers that are associated with increased 30-day mortality. These findings can be used to identify high-risk patients who might benefit from specialized care. INTRODUCTION: This study investigates the association between cardiovascular disease (CVD), cardiovascular biomarkers, and 30-day mortality following a hip fracture. METHODS: The Danish National Patient Registry was used to investigate the association between CVD and mortality following hip fracture in a nationwide population-based cohort study. In a subset of the included patients (n = 355), blood samples were available from a local biobank. These samples were used for analyzing the association between specific biochemical markers and mortality. The primary outcome was 30-day mortality. RESULTS: A total of 113,211 patients were included in the population-based cohort study. Among these, heart failure was present in 9.4%, ischemic heart disease in 15.9%, and ischemic stroke in 12.0%. Within 30 days after the hip fracture, 11,488 patients died, resulting in an overall 30-day mortality of 10.1%. The 30-day mortality was significantly increased in individuals with preexisting CVD with multivariably adjusted odds ratios of 1.69 (95% confidence interval, 1.60-1.78) for heart failure, 1.23 (1.17-1.29) for ischemic heart disease, and 1.06 (1.00-1.12) for ischemic stroke. In the local database including 355 patients, 41 (11.5%) died within 30 days. The multivariably adjusted odds ratio for 30-day mortality increased with increasing NT-proBNP (2.36 [1.53-3.64] per quartile) and decreased with increasing HDL cholesterol (0.58 [0.41-0.82] per quartile). On this basis, we established a model for predicting the probability of death based on the biochemical markers. CONCLUSION: Preexisting CVD was associated with increased 30-day mortality after a hip fracture. Furthermore, high levels of NT-proBNP and low levels of HDL cholesterol were associated with increased 30-day mortality.

Prevalence of patients with self-reported hidradenitis suppurativa in a cohort of Danish blood donors: a cross-sectional study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent inflamed nodules. No pathognomonic test is available for HS; hence the diagnosis is based on three clinical criteria. OBJECTIVES: To estimate the cross-sectional prevalence and characterize patients with HS in the Danish Blood Donor Study cohort. METHODS: A questionnaire previously developed containing HS screening questions, the Major Depression Inventory, the Short Form-12, as well as questions about height, weight and drinking habits was answered by 27 765 blood donors. RESULTS: The prevalence of HS was 1·8% [95% confidence interval (CI) 1·6-2·0%] in the cohort of Danish blood donors. Donors with HS were on average 4·7 years younger (P < 0·001), had 1·3 kg m-2 higher mean body mass index (BMI) (P < 0·001) and were significantly more likely to smoke [odds ratio (OR) 1·44, 17·9% vs. 13·1%, P = 0·002] compared with donors without HS. Furthermore, significantly more donors with HS were classified as having moderate depression (3·2% vs. 0·7%, P < 0·001). Also, significantly more patients with HS were apprenticeship educated, received educational support and sickness or cash benefits. CONCLUSIONS: The prevalence of HS in the cohort of blood donors was estimated to 1·8% (95% CI 1·6-2·0%). Donors with HS reported characteristics similar to those reported for hospital-based patients with HS such as higher BMI, smoking rates and lower socioeconomic status than donors without HS.

Remitted affective disorders and high familial risk of affective disorders associate with aberrant intestinal microbiota.

OBJECTIVE: Affective disorders seem associated with aberrant intestinal microbiota but whether this pattern also occurs in individuals at increased heritable risk is unknown. We investigated associations between gut microbiota profiles and affective disorders by comparing monozygotic (MZ) twins concordant (affected twins with unipolar or bipolar disorder in remission) and discordant to affective disorders (high-risk) with MZ twins without affective disorders (low-risk). METHODS: Stool samples were collected from 128 MZ twins and the microbiome was profiled using 16S rDNA sequencing of the V3-V4 region. RESULTS: Affected twins had a lower diversity and an absence of a specific operational taxonomical unit (OTU) in comparison with low-risk twins. The high-risk twins exhibited the same pattern although the lower diversity was only at a trend level. The OTU belonged to the family Christensenellaceae. The findings were not explained by lifestyle factors (smoking, alcohol consumption, body mass index, or psychotropic medication). CONCLUSION: Affected twins in remission and high-risk twins presented aberrant gut microbiota with depletion of a specific OTU. If replicated, this reduced relative sequence absence may together with the globally altered microbiota composition act as a vulnerability marker by accentuating the effect of gene-environment interactions in individuals genetically disposed for an affective disorder.

Iron deficiency among blood donors: experience from the Danish Blood Donor Study and from the Copenhagen ferritin monitoring scheme.

Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark, is that routine ferritin measurements and iron supplementation are feasible and effective ways of reducing the proportion of donors with low haemoglobin levels.

The healthy donor effect impacts self-reported physical and mental health - results from the Danish Blood Donor Study (DBDS).

AIMS: This study aimed at quantifying the healthy donor effect by comparing self-perceived mental and physical health between blood donors and non-donors. BACKGROUND: In theory, the selection process known as the healthy donor effect should result in better self-perceived, health-related quality of life in donors than in non-donors. METHODS: The Short Form-12 data from the Danish Twin Registry (DTR) was compared with the data from the Danish Blood Donor Study (DBDS). Data on age, sex and smoking status were included in the analyses. The multivariable linear regression analysis was stratified by sex and age group intervals. Outcome variables were the mental component score (MCS) and the physical component score (PCS). RESULTS: A total of 28 982 and 36 913 participants from the DTR and the DBDS, respectively, were included in this study. Younger donors had higher MCS than non-donors, whereas MCS was only marginally high in older donors compared with non-donors. In contrast, PCS was almost similar for both young donors and non-donors. With the increase in age, non-donors had lower PCS than donors. CONCLUSIONS: Two selection patterns were revealed. Among young individuals, better self-perceived mental health was associated with a blood donor. With the increase in age, better self-perceived physical health was associated with blood donation.

Family recurrence risk of alopecia areata in the Faroe Islands.

BACKGROUND: Reports of a positive family history of alopecia areata (AA) have led to the assumption of a genetic component. The Faroe Islands population is small, has been isolated until the 20th century, and is served by only one dermatology clinic, making it highly suitable for genealogical studies. AIM: To determine the incidence of AA and to estimate the recurrence risk ratio (RRR) in five generations and in a nationwide dermatologist-based AA cohort using the Faroese genealogy database. METHODS: All registered cases of AA during the period 1973-2011 were identified from the Faroese national dermatology clinics. The AA cases were linked with the genealogy database covering the entire Faroese population, and the probability of AA among first-, second- and third-degree relatives was calculated. RESULTS: In total, 178 cases of AA were identified, giving a crude incidence of 10.1 per 100 000 person-years (10.9 for women and 9.4 for men). The cumulative incidence proportion over life was 0.8%. There was no apparent trend in the probabilities for AA in first-degree family members compared with second- and third-degree relatives. RRR was > 1 in second-degree family members only. CONCLUSION: A lower prevalence rate of AA was found than previously published. The genealogical study failed to identify any apparent trend in the RRR estimates, questioning the role of genetic factors in AA in the Faroe Islands. However, it is possible that the trend is masked by bias and low power; larger studies are therefore warranted to estimate the heritability of AA.

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization.

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC). METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or ß-estimates with 95% confidence interval (CI). RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: ß=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: ß=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2 higher BMI. CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

One-carbon metabolism markers are associated with cardiometabolic risk factors.

BACKGROUND AND AIMS: Alterations to one-carbon metabolism, especially elevated plasma homocysteine (Hcy), have been suggested to be both a cause and a consequence of the metabolic syndrome (MS). A deeper understanding of the role of other one-carbon metabolites in MS, including s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH), and the methylation capacity index (SAM:SAH ratio) is required. METHODS AND RESULTS: 118 men and women with MS-risk factors were included in this cross-sectional study and cardiometabolic outcomes along with markers of one-carbon metabolism, including fasting plasma SAM, SAH, Hcy and vitamin B12 concentrations, were analysed. Multiple linear regression models were also used to examine the association between plasma one-carbon metabolites and cardiometabolic health features. We found that fasting plasma concentrations of Hcy, SAM and SAH were all positively correlated with markers of adiposity, including BMI (increase in BMI per 1-SD increase in one-carbon metabolite: 0.92 kg/m2 95% CI (0.28; 1.56), p = 0.005; 0.81 (0.15; 1.47), p = 0.02; 0.67 (-0.01; 1.36), p = 0.05, respectively). Hcy, but not SAM, SAH or SAM:SAH ratio was associated with BMI and body fat percentage after mutual adjustments. SAM concentrations were associated with higher fasting insulin (9.5% 95% CI (0.3; 19.5) per SD increase in SAM, p = 0.04), HOMA-IR (10.8% (0.8; 21.9), p = 0.03) and TNF-α (11.8% (5.0; 19.0), p < 0.001). CONCLUSION: We found little evidence for associations between SAM:SAH ratio and cardiometabolic variables, but higher plasma concentrations of SAM, SAH and Hcy are related to an overall higher risk of metabolic dysfunctions. The studies were registered at www.clinicaltrials.gov (NCT01719913 &NCT01731366).

Low vs. high haemoglobin trigger for transfusion in vascular surgery: protocol for a randomised trial.

BACKGROUND: In patients with cardiovascular disease, guidelines for administration of red blood cells (RBC) are mainly based on studies outside the vascular surgical setting with the recommendation to use a haemoglobin (hb) trigger-level lower than by guidelines from The European Society for Vascular Surgery. Restricting RBC transfusion may affect blood O2 transport with a risk for development of tissue ischaemia and postoperative complications. METHODS: In a single-centre, open-label, assessor blinded trial, 58 vascular surgical patients (> 40 years of age) awaiting open surgery of the infrarenal aorta or infrainguinal arterial bypass surgery undergo a web-based randomisation to one of two groups: perioperative RBC transfusion triggered by hb < 8 g/dl or hb < 9.7 g/dl. Administration of fluid follows an individualised strategy by optimising cardiac stroke volume and near-infrared spectroscopy determines tissue oxygenation. Serious adverse event rates are: myocardial injury (troponin-I ≥ 45 ng/l or ischaemic electrocardiographic findings at day 30), acute kidney injury, death, stroke and severe transfusion reactions. A follow-up visit takes place 30 days after surgery and a follow-up of serious adverse events in the Danish National Patient Register within 90 days is pending. DISCUSSION: This trial is expected to determine whether a RBC transfusion triggered by hb < 9.7 g/dl compared with hb < 8 g/dl results in adequate separation of postoperative hb levels, transfusion of more RBC units and maintains a higher tissue oxygenation. The results will inform the design of a multicentre trial for evaluation of important postoperative outcomes.

Low-grade inflammation is associated with lower haemoglobin levels in healthy individuals: results from the Danish blood donor study.

BACKGROUND AND OBJECTIVES: Chronic inflammation can lead to anaemia of chronic disease due to the sequestration of iron caused by inflammatory cytokines and the protein hepcidin. However, the effect of low-grade inflammation (LGI) on haemoglobin among healthy individuals is not known. This study examines the effect of LGI on haemoglobin among Danish blood donors. MATERIALS AND METHODS: We performed multivariable linear regression to assess the effect of LGI (i.e. high-sensitivity C-reactive protein above 3 mg/l but below 10 mg/l) on haemoglobin in 17 322 Danish blood donors. We also performed multivariable logistic regression to evaluate the effect of LGI on the risk of having low haemoglobin (below the 10th percentile among men and women, respectively). We adjusted for donation activity, age, sex, low ferritin, oral contraceptives and menopause. All analyses were stratified by current smoking status. RESULTS: LGI was associated with lower haemoglobin (0·08 mm lower [0·12 g/dl], 95% confidence interval (CI): -0·11-0·05) and increased risk of low haemoglobin (OR = 1·22, 95% CI: 1·05-1·43) in non-smokers. Conversely, LGI was associated with higher haemoglobin in smokers (0·12 mm [0·19 g/dl], 95% CI: 0·06-0·18). CONCLUSION: In this first study of LGI and haemoglobin in healthy individuals, there was a negative association between LGI and haemoglobin in non-smokers. The association was positive in smokers, probably because smoking leads to both increased inflammation and increased haemoglobin through CO exposure.

Treatment with a GLP-1 receptor agonist diminishes the decrease in free plasma leptin during maintenance of weight loss.

BACKGROUND: Recent studies indicate that glucagon-like peptide (GLP)-1 inhibits appetite in part through regulation of soluble leptin receptors. Thus, during weight loss maintenance, GLP-1 receptor agonist (GLP-1RA) administration may inhibit weight loss-induced increases in soluble leptin receptors thereby preserving free leptin levels and preventing weight regain. METHODS: In a randomized controlled trial, 52 healthy obese individuals were, after a diet-induced 12% body weight loss, randomized to treatment with or without administration of the GLP-1RA liraglutide (1.2 mg per day). In case of weight gain, low-calorie diet products were allowed to replace up to two meals per day to achieve equal weight maintenance. Glucose tolerance and hormone responses were investigated before and after weight loss and after 52 weeks weight maintenance. Primary end points: increase in soluble leptin receptor plasma levels and decrease in free leptin index after 52 weeks weight loss maintenance. RESULTS: Soluble leptin receptor increase was 59% lower; 2.1±0.7 vs 5.1±0.8 ng ml(-1) (-3.0 (95% confidence interval (CI)=-0.5 to -5.5)), P<0.001 and free leptin index decrease was 43% smaller; -62±15 vs -109±20 (-47 (95% CI=-11 to -83)), P<0.05 with administration of GLP-1RA compared with control group. The 12% weight loss was successfully maintained in both the groups with no significant change in weight after 52 weeks follow-up. The GLP-1RA group had greater weight loss during the weight maintenance period (-2.3 kg (95% CI=-0.6 to -4.0)), and had fewer meal replacements per day compared with the control group (minus one meal per day (95% CI=-0.6 to -1)), P<0.001. Fasting glucose was decreased by an additional -0.2±0.1 mmol l(-1) in the GLP-1RA group in contrast to the control group, where glucose increased 0.3±0.1 mmol l(-1) to the level before weight loss (-0.5mmol l(-1) (95% CI=-0.1 to -0.9)), P<0.005. Meal response of peptide PYY3-36 was higher at week 52 in the GLP-1RA group compared with the control group, P<0.05. CONCLUSIONS: The weight maintaining effect of GLP-1RAs may be mediated by smaller decrease in free leptin and higher PYY3-36 response. Low dose GLP-1RA therapy maintained 12% weight loss for 1 year and may prevent pre-diabetes in obesity.

Prenatal exposure to systemic antibacterials and overweight and obesity in Danish schoolchildren: a prevalence study.

BACKGROUND/OBJECTIVE: Prenatal exposure to antibacterials may permanently dysregulate fetal metabolic patterns via epigenetic pathways or by altering maternal microbiota. We examined the association of prenatal exposure to systemic antibacterials with overweight and obesity in schoolchildren. SUBJECTS/METHODS: We conducted a prevalence study among Danish schoolchildren aged 7-16 years using data from routine school anthropometric evaluations conducted during 2002-2013. Prenatal exposure to antibacterials was ascertained by using maternal prescription dispensations and infection-related hospital admissions during pregnancy. We defined overweight and obesity among the children using standard age- and sex-specific cutoffs. We computed sex-specific adjusted prevalence ratios (aPRs) of overweight and obesity associated with exposure to prenatal antibacterials, adjusting for maternal age at delivery, marital status, smoking in pregnancy and multiple gestation; we also stratified the analyses by birth weight. RESULTS: Among 9886 schoolchildren, 3280 (33%) had prenatal exposure to antibacterials. aPRs associated with the exposure were 1.26 (95% confidence interval (CI): 1.10-1.45) for overweight and 1.29 (95% CI: 1.03-1.62) for obesity. Among girls, aPRs were 1.16 (95% CI: 0.95-1.42) for overweight and 1.27 (95% CI: 0.89 to 1.82) for obesity. Among boys, aPRs were 1.37 (95% CI: 1.13-1.66) for overweight and 1.29 (95% CI: 0.96-1.73) for obesity. The aPR for overweight was higher among schoolchildren with birth weight <3500 g (aPR: 1.30, 95% CI: 1.05-1.61) than in schoolchildren with birth weight ⩾3500 g (aPR: 1.18, 95% CI: 0.95-1.46). Inversely, the association for obesity was higher among schoolchildren with birth weight ⩾3500 g (aPR: 1.35, 95% CI: 1.00-1.81) than among those who were <3500 g at birth (aPR: 1.16, 95% CI: 0.82-1.65). CONCLUSIONS: Prenatal exposure to systemic antibacterials is associated with an increased risk of overweight and obesity at school age, and this association varies by birth weight.

Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and type 2 diabetes susceptibility.

AIMS: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic ß-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to type 2 diabetes in humans. METHODS: Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for type 2 diabetes susceptibility in up to 25 000 people (8148 with type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis. RESULTS: rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*104) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (P = 5.5*104) but again not in men (P = 0.34). CONCLUSION: The present data identify DRD2/ANKK1 as a potential sex-specific type 2 diabetes susceptibility gene.