Publications by authors named "Christine Dalgård"

48 Publications

Increased serum SP-D in identification of high-risk smokers at high risk of COPD.

Am J Physiol Lung Cell Mol Physiol 2021 06 24;320(6):L1005-L1010. Epub 2021 Mar 24.

Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

Pulmonary surfactant protein D (SP-D) is an important component of the pulmonary innate immune system with the ability to dampen cigarette smoke-induced lung inflammation. However, cigarette smoking mediates translocation of SP-D from the lung to the blood, and serum SP-D (sSP-D) has therefore previously been suggested as marker for smoke-induced lung injury. In support of this notion, associations between high sSP-D and low lung function measurements have previously been demonstrated in smokers and in chronic obstructive lung disease (COPD). The present investigations employ a 12-yr longitudinal Danish twin study to test the hypothesis that baseline sSP-D variation has the capacity to identify smokers with normal baseline lung function who are at high risk of significant future smoke-induced lung function decline. We find that sSP-D is significantly increased in those with normal lung function at baseline who develop lung function decline during follow-up compared with those who stay lung healthy. Moreover, we demonstrate that it is the smoke-induced baseline sSP-D level, and not the constitutional level, which has capacity as biomarker, and which is linearly increased with the decline in lung function during follow-up. In conclusion, we here present first observation of increased sSP-D for identification of high-risk smokers.
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http://dx.doi.org/10.1152/ajplung.00604.2020DOI Listing
June 2021

Disentangling the relationship between bone turnover and glucose homeostasis: A prospective, population-based twin study.

Bone Rep 2021 Jun 5;14:100752. Epub 2021 Feb 5.

Department of Endocrinology, Odense University Hospital, Denmark.

Background: Biochemical markers of bone turnover are lower in patients with type 2 diabetes, which may be explained by genetic variants being associated with type 2 diabetes and bone turnover as well as environmental factors. We hypothesized that bone turnover markers associate with and predict changes in glucose homeostasis after control for genetics and shared environment.

Methods: 1071 healthy, non-diabetic (at baseline, 1997-2000) adult mono- and dizygotic twins participating in the prospective study GEMINAKAR were reassessed between 2010 and 2012 with clinical evaluation, biochemical tests and oral glucose tolerance test. Fasting bone turnover markers (CTX, P1NP and osteocalcin) were measured. The association between bone turnover, glucose homeostasis and the ability of bone turnover markers to predict changes in glucose homeostasis were assessed in cross-sectional and longitudinal analyses. Analyses were performed both at an individual level and adjusted for shared environmental and genetic factors.

Results: Glucose levels increased with age, and 33 (3%) participants had developed type 2 diabetes at follow-up. In women, bone turnover markers increased with age, whereas for men only osteocalcin increased with age. Bone turnover markers were not associated with fasting glucose, insulin, or HOMA-IR at baseline or follow-up before or after adjustment for age, sex, BMI, smoking, and use of medication at baseline. Variation in bone turnover markers was mainly explained by unique environmental factors, 70%, 70% and 55% for CTX, P1NP and osteocalcin, respectively, whereas additive genetic factors explained 7%, 13% and 45% of the variation in CTX, P1NP and osteocalcin.

Conclusions: Bone turnover markers were not associated with baseline plasma glucose levels and did not predict changes in glucose homeostasis. Variation in bone turnover markers is mainly explained by environmental factors, however, compared to CTX and P1NP, genetic factors have a larger impact on osteocalcin levels.
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http://dx.doi.org/10.1016/j.bonr.2021.100752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900018PMC
June 2021

Bone mineral density at age 7 years does not associate with adherence to vitamin D supplementation guidelines in infancy or vitamin D status in pregnancy and childhood: an Odense Child Cohort study.

Br J Nutr 2021 Nov 26;126(10):1466-1477. Epub 2021 Jan 26.

Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense C, Denmark.

Vitamin D supplementation in infancy is recommended to prevent rickets. At the population level, its effects on bone mineralisation are largely unknown. We aimed to explore whether adherence to national vitamin D supplementation guidelines (10 µg/d up to the age of 2 years), supplementation at the ages of 5 and 7 years, and serum 25-hydroxyvitamin D (s-25(OH)D) at various time points associated with bone mineral density (BMD) at the age of 7 years in the Odense Child Cohort, Denmark (n 1194). High adherence was defined as supplementation with 10 µg of vitamin D 6-7 times per week during ≥80 % of the observation time. s-25(OH)D was analysed using LC-MS/MS. Total-body-less-head (TBLH) BMD was measured by dual-energy X-ray absorptiometry. At the median age of 18·1 months, 53·9 % (n 475/881) reported high adherence. The median s-25(OH)D was 64·7, 78·8, 46·0 and 71·8 nmol/l in early pregnancy, late pregnancy, cord blood and at 5 years, respectively. The mean TBLH BMD at the median age of 7·1 years was 0·613 (SD 0·049) g/cm2 (z-score +0·363 (SD 0·824)). In adjusted analyses, vitamin D supplementation up to 18 months, and at 5 and 7 years, was not associated with TBLH BMD. Similarly, no robust associations were found between TBLH BMD and s-25(OH)D at any time point. No associations were found for TBLH bone mineral concentration or bone area. In this population with relatively high s-25(OH)D concentrations, no consistent associations were found between adherence to vitamin D supplementation recommendations or vitamin D status in pregnancy or childhood, and bone mineralisation at the age of 7 years.
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http://dx.doi.org/10.1017/S0007114521000301DOI Listing
November 2021

Prenatal Exposures to Perfluoroalkyl Acids and Associations with Markers of Adiposity and Plasma Lipids in Infancy: An Odense Child Cohort Study.

Environ Health Perspect 2020 07 6;128(7):77001. Epub 2020 Jul 6.

Department of Environmental Medicine, University of Southern Denmark, Odense, Denmark.

Background: Perfluoroalkyl acids (PFAA) are repellants that cross the placental barrier, enabling interference with fetal programming. Maternal PFAA concentrations have been associated with offspring obesity and dyslipidemia in childhood and adulthood, but this association has not been studied in infancy.

Objectives: We investigated associations between maternal PFAA concentrations and repeated markers of adiposity and lipid metabolism in infancy.

Methods: In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAA: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 649 women. Offspring were examined at birth () and at 3 months () and 18 months () of age. Total cholesterol, LDL, HDL, and triglyceride were evaluated at 3 months () and 18 months () of age. Mixed effects linear regression models estimated associations between PFAA and standardized (SDS) body mass index (BMI), ponderal index, and waist circumference. Associations between PFAA and body fat% (BF%) and plasma lipids SDS at 3 months and 18 months of age were investigated with linear regression models.

Results: PFNA and PFDA were associated with higher BMI SDS [adjusted ; 95% confidence interval (CI): 0.03, 0.49 and ; 95% CI: , 1.19, respectively, for increases] and ponderal index SDS (; 95% CI: 0.13, 0.59 and ; 95% CI: 0.40, 1.64, respectively) at 3 and 18 months of age (pooled) in girls. Corresponding estimates for boys were closer to the null but not significantly different from estimates for girls. In boys and girls (combined), PFNA and PFDA were associated with BF% at age 3 months (for PFDA, ; 95% CI: 0.04, 0.75), and PFDA was associated with total cholesterol SDS at 18 months (; 95% CI: 0.08, 2.03) ().

Discussion: Prenatal PFAA were positively associated with longitudinal markers of adiposity and higher total cholesterol in infancy. These findings deserve attention in light of rising rates of childhood overweight conditions and dyslipidemia. https://doi.org/10.1289/EHP5184.
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http://dx.doi.org/10.1289/EHP5184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338787PMC
July 2020

Heritability of Curve Patterns in Oral Glucose Tolerance Test.

Twin Res Hum Genet 2020 02 21;23(1):39-44. Epub 2020 Feb 21.

Department of Clinical Research and The Danish Twin Registry, University of Southern Denmark and Odense Patient Data Explorative Network (OPEN), Odense University Hospital, Odense C, Denmark.

Type 2 diabetes, which is caused by both genetic and environmental factors, may be diagnosed using the oral glucose tolerance test (OGTT). Recent studies demonstrated specific patterns in glucose curves during OGTT associated with cardiometabolic risk profiles. As the relative contribution of genetic and environmental influences on glucose curve patterns is unknown, we aimed to investigate the heritability of these patterns. We studied twins from the Danish GEMINAKAR cohort aged 18-67 years and free from diabetes at baseline during 1997-2000; glucose concentrations were measured three times during a 2-h OGTT. Heterogeneity of the glucose response during OGTT was examined with latent class mixed-effects models, evaluating goodness of fit by Bayes information criterion. The genetic influence on curve patterns was estimated using quantitative genetic modeling based on linear structural equations. Overall, 1455 twins (41% monozygotic) had valid glucose concentrations measured from the OGTT, and four latent classes with different glucose response patterns were identified. Statistical modeling demonstrated genetic influence for belonging to a specific class or not, with heritability estimated to be between 45% and 67%. During ∼12 years of follow-up, the four classes were each associated with different incidence of type 2 diabetes. Hence, glucose response curve patterns associated with type 2 diabetes risk appear to be moderately to highly heritable.
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http://dx.doi.org/10.1017/thg.2020.3DOI Listing
February 2020

Associations of Fish Oil Supplement Use With Testicular Function in Young Men.

JAMA Netw Open 2020 01 3;3(1):e1919462. Epub 2020 Jan 3.

Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Importance: Many young men have poor semen quality, and the causes are often unknown. Supplement intake of ω-3 polyunsaturated fatty acid has been found to improve semen quality among men with infertility, but the association with semen quality among healthy men is unknown.

Objective: To determine if intake of ω-3 fatty acid supplements is associated with testicular function as measured by semen quality and reproductive hormone levels among healthy men.

Design, Setting, And Participants: This cross-sectional study included young Danish men from the general population recruited between January 1, 2012, and December 31, 2017, at compulsory examinations to determine their fitness for military service. Young unselected men were approached after the examination and invited to participate in a study of reproductive function, regardless of their fitness for military service. Data analysis was conducted from September 1, 2018, to June 30, 2019.

Exposures: Intake of supplements, including fish oil, during the past 3 months.

Main Outcomes And Measures: Semen quality, measured as volume, concentration, total sperm count, percentage of morphologically normal spermatozoa, and motility, and serum reproductive hormone levels, measured as follicle-stimulating hormone, luteinizing hormone, testosterone, free testosterone, and inhibin B levels.

Results: Among 1679 young Danish men (median [interquartile range] age, 18.9 [18.7-19.4] years) recruited to participate, 98 men (5.8%) reported use of fish oil supplements during the past 3 months, of whom 53 (54.1%) reported intake on 60 or more days. After adjustment and compared with men with no supplement intake, men with fish oil supplement intake on fewer than 60 days had semen volume that was 0.38 (95% CI, -0.03 to 0.80) mL higher, and men with fish oil supplement intake on 60 or more days had semen volume that was 0.64 (95% CI, 0.15 to 1.12) mL higher (P for trend < .001). Similarly, testicular size in men with supplement intake on fewer than 60 days was 0.8 (95% CI, -0.2 to 1.9) mL larger and in men with fish oil supplement intake on 60 or more days was 1.5 (95% CI, 0.2 to 2.8) mL larger compared with men with no supplement intake (P for trend = .007). After adjustment, men with fish oil supplement intake had a 20% (95% CI, 9%-31%) lower follicle-stimulating hormone level and 16% (95% CI, 8%-24%) lower luteinizing hormone level compared with men with no supplement intake. There were no associations of intake of other supplements with measures of testicular function.

Conclusions And Relevance: These findings suggest that intake of fish oil supplements was associated with better testicular function, which is less likely to be due to confounding by indication, as no associations of intake of other supplements with testicular function were found. This cross-sectional study did not examine the actual content of ω-3 fatty acids in the supplements; therefore, these findings need confirmation in well-designed randomized clinical trials among unselected men.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.19462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991322PMC
January 2020

Twin Family Registries Worldwide: An Important Resource for Scientific Research.

Twin Res Hum Genet 2019 12 15;22(6):427-437. Epub 2020 Jan 15.

Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.

Much progress has been made in twin research since our last special issue on twin registries (Hur, Y.-M., & Craig, J. M. (2013). Twin Research and Human Genetics, 16, 1-12.). This special issue provides an update on the state of twin family registries around the world. This issue includes 61 papers on twin family registries from 25 countries, of which 3 describe consortia based on collaborations of several twin family registries. The articles included in this issue discuss the establishment and maintenance of twin registries, recruitment strategies, methods of zygosity assessment, research aims and major findings from twin family cohorts, as well as other important topics related to twin studies. The papers amount to approximately 1.3 million monozygotic, dizygotic twins and higher order multiples and their family members who participate in twin studies around the world. Nine new twin family registries have been established across the world since our last issue, which demonstrates that twin registers are increasingly important in studies of the determinants and correlates of complex traits from disease susceptibility to healthy development.
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http://dx.doi.org/10.1017/thg.2019.121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301690PMC
December 2019

Child behaviour and subsequent changes in body weight, composition and shape.

PLoS One 2019 19;14(12):e0226003. Epub 2019 Dec 19.

Research Unit for Dietary Studies at The Parker Institute and Institute of Preventive Medicine, The Capital Region, Copenhagen, Denmark.

Objective: Studies have found an association between child behavioural problems and overweight, but the existing evidence for this relationship is inconsistent, and results from longitudinal studies are sparse. Thus, we examined the association between behavioural problems and subsequent changes in body mass index (BMI) and anthropometry over a follow-up period of 1.3 years among children aged 2-6 years.

Design: The study was based on a total of 345 children from The Healthy Start Study; all children were healthy weight but predisposed to develop overweight. The Danish version of the Strengths and Difficulties Questionnaire (SDQ), classified as SDQ Total Difficulties (SDQ-TD) and SDQ Prosocial Behaviour (SDQ-PSB), was used to assess child behaviour. Linear regression analyses were used to examine associations between SDQ scores and subsequent change in BMI z-score, body fat percentage, waist circumference and waist-hip ratio, while taking possible confounding factors into account.

Results: We found an association between SDQ-PSB and subsequent change in BMI z-score (β: 0.040 [95% CI: 0.010; 0.071, p = 0.009]). However, there was no evidence of an association between SDQ-PSB and measures of body composition or body shape.

Conclusions: Among 2 to 6 years old children predisposed to overweight, the association between SDQ-scores and weight gain is either absent or marginal. The SDQ-PSB score may be associated with subsequent increases in BMI z-score, but this association does not seem driven by an increased relative fat accumulation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226003PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922444PMC
March 2020

The Danish Twin Registry: An Updated Overview.

Twin Res Hum Genet 2019 12 23;22(6):499-507. Epub 2019 Sep 23.

The Danish Twin Registry, Department of Public Health, University of Southern Denmark, Odense, Denmark.

The Danish Twin Registry (DTR) was established in the 1950s, when twins born from 1870 to 1910 were ascertained, and has since been extended to include twins from birth cohorts until 2009. The DTR currently comprises of more than 175,000 twins from the 140 birth cohorts. This makes the DTR the oldest nationwide twin register and among the largest in the world. The combination of data from several surveys, including biological samples and repeated measurements on the same individuals, and data from Danish national registers provides a unique resource for a wide range of twin studies. This article provides an updated overview of the data in the DTR: First, we provide a summary of the establishment of the register, the different ascertainment methods and the twins included; then follows an overview of major surveys conducted in the DTR since 1994 and a description of the DTR biobank, including a description of the molecular data created so far; finally, a short description is given of the linkage to Danish national registers at Statistics Denmark and some recent examples of studies using the various data resources in the DTR are highlighted.
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http://dx.doi.org/10.1017/thg.2019.72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039015PMC
December 2019

Pregnancy or cord 25-hydroxyvitamin D is not associated with measures of body fat or adiposity in children from three months to three years of age. An Odense Child Cohort study.

Clin Nutr 2020 06 8;39(6):1832-1839. Epub 2019 Aug 8.

Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark. Electronic address:

Background & Aims: The susceptibility to overweight in adults born during winter season may suggest foetal programming of prenatal vitamin D levels on adiposity. We investigated whether cord or pregnancy serum 25-hydroxyvitamin D (s-25OHD) was associated with infant and child body fat measures in a Danish population-based prospective cohort.

Methods: In the Odense Child Cohort, 1905 singletons had cord s-25OHD and data on waist circumference (WC), weight, body mass index (BMI), and sum of skin folds (SSF) at median 3.7 months, 18.9 months and three years' age. Early and late pregnancy samples of s-25OHD (mean gestational age 12 and 29 weeks) were chosen as secondary exposures. Multiple linear and logistic regression as well as linear mixed models was applied testing the relation between cord and pregnancy s-25OHD and body fat outcomes and their Z-scores by use of updated national reference populations. Models were adjusted for maternal educational level, maternal ethnicity, pre-gestational BMI and season of birth, a priori stratified by sex.

Results: The median [IQR] cord s-25OHD was 45.5 [31.1; 60.9] nmol/L. Cord s-25OHD <50 nmol/L was found in 57.5%; values < 25 nmol/L in 16.3%. The mean Z-scores of body fat measures at all ages were in the range of -0.32 to +0.42. No consistent associations were found between s-25OHD in cord, early pregnancy or late pregnancy and WC, weight, BMI, SSF, or their Z-scores at ages 3.7 months, 18.9 months, or 3 years. Neither did a computed composite outcome (WC, SSF, BMI, or weight >90th vs. ≤90 percentile) associate with cord or pregnancy s-25OHD.

Conclusion: Cord or pregnancy s-25OHD was not associated with measures of body fat or adiposity in children up to three years of age. Our data suggested no programming effect of maternal s-25OHD on offspring obesity in a relatively lean and healthy population of mothers.
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http://dx.doi.org/10.1016/j.clnu.2019.07.023DOI Listing
June 2020

Blood pressure in 3-year-old girls associates inversely with umbilical cord serum 25-hydroxyvitamin D: an Odense Child Cohort study.

Endocr Connect 2018 Dec;7(12):1236-1244

Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.

Background Low foetal vitamin D status may be associated with higher blood pressure (BP) in later life. Objective To examine whether serum 25-hydroxyvitamin D2+3 (s-25OHD) in cord and pregnancy associates with systolic and diastolic BP (SBP; DBP) in children up to 3 years of age. Design Prospective, population-based cohort study. Methods We included 1594 singletons from the Odense Child Cohort with available cord s-25OHD and BP data at median age 3.7 months (48% girls), 18.9 months (44% girls) or 3 years (48% girls). Maternal s-25OHD was also assessed at gestational ages 12 and 29 weeks. Multiple regression models were stratified by sex a priori and adjusted for maternal educational level, season of birth and child height, weight and age. Results In 3-year-old girls, SBP decreased with -0.7 mmHg (95% CI -1.1; -0.3, P = 0.001) and DBP with -0.4 mmHg (95% CI -0.7; -0.1, P = 0.016) for every 10 nmol/L increase in cord s-25OHD in adjusted analyses. Moreover, the adjusted odds of having SBP >90th percentile were reduced by 30% for every 10 nmol/L increase in cord s-25OHD (P = 0.004) and by 64% for cord s-25OHD above the median 45.1 nmol/L (P = 0.02). Similar findings were observed between pregnancy s-25OHD and 3-year SBP, cord s-25OHD and SBP at 18.9 months, and cord s-25OHD and DBP at 3 years. No consistent associations were observed between s-25OHD and BP in boys. Conclusion Cord s-25OHD was inversely associated with SBP and DBP in young girls, but not in boys. Higher vitamin D status in foetal life may modulate BP in young girls. The sex difference remains unexplained.
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http://dx.doi.org/10.1530/EC-18-0308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240151PMC
December 2018

A novel inverse association between cord 25-hydroxyvitamin D and leg length in boys up to three years. An Odense Child Cohort study.

PLoS One 2018 11;13(6):e0198724. Epub 2018 Jun 11.

Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.

Background And Aim: Long standing vitamin D deficiency in children causes rickets with growth impairment. We investigated whether sub-ischial leg length (SLL) is shorter, and cephalo-caudal length:length (CCL:L) ratio and sitting height:height (SH:H) ratio larger, with lower cord s-25-hydroxyvitamin D (25OHD) in the population-based prospective Odense Child Cohort, Denmark.

Methods: We included healthy singletons born to term with available measures of cord 25OHD and anthropometrics up to three years' age. Linear regression was stratified by sex a priori and adjusted for maternal ethnicity, pre-pregnancy body mass index and smoking during pregnancy, season of blood sampling and child age.

Results: Median (IQR) cord 25OHD was 48.0 (34.0-62.4) nmol/L. At mean age 19.1 months, n = 504, mean (SD) SLL was 31.7 (1.7) cm; CCL:L-ratio 0.62 (0.01). At 36.3 months, n = 956, mean SLL was 42.9 (2.0) cm; SH:H-ratio 0.56 (0.01). No participants had rickets. In adjusted analyses, 19-months-old boys had 0.1 cm shorter SLL (p = 0.009) and 0.1% higher CCL:L-ratio (p = 0.04) with every 10 nmol/L increase in cord 25OHD. Similar findings were seen for late pregnancy 25OHD. In the highest cord 25OHD quartile (>60.7 nmol/L), SLL was 0.8 cm shorter (95% C.I.: 1.36;-0.29, linear trend, p = 0.004), and CCL:L-ratio 0.8% higher (95% C.I. 8.0x10-05;0.01, linear trend, p = 0.01), compared to lowest quartile (<30.7 nmol/L). Similar associations with cord 25OHD were observed in 3-year-old boys. No consistent associations between 25OHD and anthropometrics were seen in girls at either age.

Conclusion: No leg shortening was found with decreasing cord s-25OHD in a healthy population of infants. A small, yet significant inverse association between cord 25OHD and SLL in boys 1½-3 years warrants further investigations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198724PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995352PMC
December 2018

Prenatal pesticide exposure associated with glycated haemoglobin and markers of metabolic dysfunction in adolescents.

Environ Res 2018 10 4;166:71-77. Epub 2018 Jun 4.

Department of Growth and Reproduction, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.

Background: Pesticide exposure has been associated with increased risk of diabetes mellitus in adults, but potential effects of prenatal exposure on glucose regulation have not been investigated. The aim of this study was to investigate if maternal occupational pesticide exposure in pregnancy was associated with glycated haemoglobin A1c (HbA1c) in adolescents and whether an association was modified by sex and paraoxonase-1 (PON1) Q192R polymorphism.

Methods: A prospective cohort study of children whose mothers were either occupationally exposed or unexposed to pesticides in early pregnancy. At age 10-to-16 years, the children (n = 168) underwent clinical examinations including pubertal stage assessment (accepted by 141 children) and blood sampling. PON1 Q192R genotype was available for 139 children and 103 mothers. The main outcome measure was HbA1c but other relevant biomarkers were also included.

Results: Prenatal pesticide exposure was associated with a 5.0% (95% confidence interval: 1.8; 8.2) higher HbA1c compared to unexposed children after adjustment for confounders. After stratification, the association remained significant for girls (6.2% (1.6; 11.1)) and if the child or the mother had the PON1 192R-allele (6.1% (1.6; 10.8) and 7.1% (2.0; 12.6), respectively). Besides, an exposure-related increase was seen for the leptin-to-adiponectin ratio, for plasminogen activator inhibitor type-1 in girls, and for interleukin-6 in children whose mothers had the R-allele.

Conclusion: Prenatal pesticide exposure was associated with higher HbA1c and changes in related biomarkers in adolescents. Our results suggest an adverse effect on glucose homeostasis and support previous findings from this cohort of an exposure-associated metabolic risk profile with higher susceptibility related to female sex and the PON1 192R-allele.
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http://dx.doi.org/10.1016/j.envres.2018.05.032DOI Listing
October 2018

S-25OHD Is Associated With Hand Grip Strength and Myopathy at 5 Years in Girls: An Odense Child Cohort Study.

J Clin Endocrinol Metab 2018 07;103(7):2630-2639

Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense C, Denmark.

Context: Severe vitamin D deficiency may lead to myopathy in adults. Little is known about vitamin D and muscle strength in children.

Objective: To test whether hand grip strength (HGS) in 5-year-old children is associated with serum 25-hydroxyvitamin D (S-25OHD).

Design: Observational study in the population-based Odense Child Cohort, Denmark. At 5 years, anthropometrics, body fat percentage by skinfold measurements, HGS (n = 881), and S-25OHD2+3 (n = 499) were obtained.

Results: Mean (SD) HGS was higher for boys compared with girls [8.76 (1.76) vs 8.1 (1.64) kg, P < 0.001]. Mean (SD) 5-year S-25OHD was 70.7 (24.5) nmol/L. HGS was directly associated with height in girls and with weight (directly) and body fat percentage (inversely) in both sexes (P < 0.01 for all). In girls, 5-year S-25OHD was associated with HGS, adjusting for height, weight, and body fat percentage [β = 0.011 (95% CI: 0.004; 0.019), P = 0.003]. S-25OHD ≥75 nmol/L was associated with higher HGS compared with values <50 nmol/L [adjusted β = 0.783 (95% CI: 0.325; 1.241), P = 0.001]. The odds of having myopathy (HGS <10th percentile) were reduced by approximately 70% for S-25OHD ≥50 vs <50 nmol/L [adjusted OR: 0.310 (95% CI: 0.126; 0.762), P = 0.011]. No associations were seen for boys. Pregnancy or umbilical cord S-25OHD did not associate with 5-year HGS.

Conclusions: Five-year S-25OHD was independently associated with HGS and myopathy in girls but not in boys. Muscle strength may be dependent on vitamin D status even in the higher range in preschool girls. The sex difference remains unexplained.
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http://dx.doi.org/10.1210/jc.2018-00281DOI Listing
July 2018

Gestational diabetes and offspring birth size at elevated environmental pollutant exposures.

Environ Int 2017 10 25;107:205-215. Epub 2017 Jul 25.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.

Background: Gestational diabetes mellitus (GDM) is associated with increased availability of glucose and macronutrients in fetal circulation and macrosomia. Therefore, the role of GDM in the association between metabolism-disrupting chemicals and birth size deserves attention.

Objective: We examined whether GDM may mediate or modify the associations between maternal environmental pollutant exposures and offspring birth size measures.

Methods: We analyzed 604 Faroese pregnant women and their offsprings born in 1997-2000. Maternal pregnancy serum concentrations of organochlorine compounds (OCs: polychlorinated biphenyl (PCB) congeners and dichlorodiphenyldichloroethylene (DDE)), and five perfluoroalkyl substances (PFASs), and hair and cord blood mercury concentrations were measured. We used regression (single-pollutants) and structural equation models (SEMs) (multiple-pollutant analyses using latent constructs of OCs, PFASs and mercury) to estimate the associations with GDM and birth size measures, accounting for mediation and/or effect modification by GDM.

Results: Serum-DDE and hair-mercury concentrations were associated with GDM (adjusted OR per concentration doubling: 1.29; 95% CI: 0.94, 1.77 for DDE, and 0.79; 95% CI: 0.62, 0.99 for mercury), but in multiple pollutant-adjusted SEMs only a positive association between OC exposure and GDM remained significant (change in GDM odds per OC doubling: 0.45; 95% CI: 0.05, 0.86). PCB and overall OC exposure were positively associated with head circumference (SEM; mean change per OC doubling: 0.13cm; 95% CI, 0.01. 0.25). Overall PFAS exposure was inversely associated with birth weight (SEM; mean change per PFAS doubling: -169g; 95% CI: -359, 21), and for many single-PFASs we found a pattern of inverse associations with birth weight and head circumference in boys, and positive or null associations in girls. None of the environmental pollutants was associated with offspring length. GDM neither modified nor mediated the associations with birth size measures.

Conclusions: We found associations with GDM and offspring birth size to be specific to the environmental pollutant or pollutant group. Associations with birth size measures appear to be independent of GDM occurrence.
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http://dx.doi.org/10.1016/j.envint.2017.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584560PMC
October 2017

High insulin-like growth factor-binding protein-1 (IGFBP-1) is associated with low relative muscle mass in older women.

Metabolism 2017 08 1;73:36-42. Epub 2017 May 1.

Unit of Nutritional Epidemiology, The National Institute for Environmental Medicine, Karolinska Institutet, Box 210, 171 77, Stockholm, Sweden. Electronic address:

Objective: Skeletal muscles serve several important roles in maintaining good health. Insulin-like growth factor-1 (IGF-1) is a promoter of protein synthesis in skeletal muscle. Its binding protein, Insulin-like growth factor-binding protein-1 (IGFBP-1) can be one determinant of IGF-1 activity. In the present study we investigate the association between serum IGFBP-1 and muscle mass.

Design: Cross-sectional analysis of 4908 women, between 55 and 85years old, participating in the Swedish Mammography Cohort-Clinical.

Methods: We defined low relative muscle mass (LRMM) as an appendicular lean mass divided by height squared of less than 5.45 (kg/m), assessed by dual energy x-ray absorptiometry. IGFBP-1 was measured by radioimmunoassay. Logistic regression was used to calculate odds-ratios of LRMM across quartiles of IGFBP-1.

Results: The odds of LRMM increased across quartiles of IGFBP-1. In the age-adjusted model the odds-ratio (OR) of LRMM was 3.41 (95% CI: 2.55-4.56), comparing the highest to the lowest quartile. This estimate was attenuated in multivariate models (OR: 1.84, 95% CI: 1.34-2.53), mainly due to inclusion of fat mass index.

Conclusion: Women with higher IGFBP-1 were more likely to have a low relative muscle mass. High IGFBP-1 may be a marker of a catabolic state.
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http://dx.doi.org/10.1016/j.metabol.2017.04.013DOI Listing
August 2017

Quality of life correlates with muscle strength in patients with dermato- or polymyositis.

Clin Rheumatol 2017 Oct 6;36(10):2289-2295. Epub 2017 Jun 6.

Department of Rheumatology, Odense University Hospital, Sønder Boulevard 29, 5000, Odense, Denmark.

The aim of this study was to compare health-related quality of life (HQoL) in adults with dermatomyositis (DM) or polymyositis (PM) with a healthy control group and to assess whether muscle strength was associated with HQoL in patients with DM or PM. A cross-sectional study was performed and included 75 patients with DM or PM and 48 healthy controls. HQoL was assessed by the Short Form 36 questionnaire (SF-36). Muscle strength of the patients was assessed using the Manual Muscle Test-8 (MMT8). Covariables and possible confounding factors were collected by validated tools. Associations were determined in multiple linear regression models. The patients had significantly lower HQoL than the control group in both the physical component summary score (PCS) and the mental component summary score (MCS). Thus, the PCS-difference between groups was 32% (p < 0.001), whereas the MCS-difference was 14% (p < 0.001). Muscle strength was associated with one domain in the patients; Physical Function (β = 1.2; 95% confidence interval 0.37 to 2.1). No statistically significant associations were found between muscle strength and HQoL in the remaining domains. Patients with DM or PM have reduced HQoL compared to healthy controls. Notably, muscle strength was associated with scores of the domain reflecting perceived physical function in patients. These findings corroborate the validity of including selected patient reported outcomes in the evaluation and monitoring of patients with DM or PM.
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http://dx.doi.org/10.1007/s10067-017-3706-6DOI Listing
October 2017

Telomeres and the natural lifespan limit in humans.

Aging (Albany NY) 2017 04;9(4):1130-1142

Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.

An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends in life expectancy should confront a biological limit due to crossing the telomeric brink.
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http://dx.doi.org/10.18632/aging.101216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425118PMC
April 2017

Cardiorespiratory Fitness and Adiposity as Determinants of Metabolic Health-Pooled Analysis of Two Twin Cohorts.

J Clin Endocrinol Metab 2017 05;102(5):1520-1528

Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, 00290 Helsinki, Finland.

Context: The joint effects of cardiorespiratory fitness (CRF) and body composition on metabolic health are not well known.

Objective: To examine the associations of CRF, fat-free mass index (FFMI), and fat mass index (FMI) with metabolic health in individual twins and controlling for genetic and shared environmental effects by studying monozygotic intrapair differences.

Design, Setting, And Participants: Two cross-sectional samples of healthy adult monozygotic and dizygotic twins were drawn from population-based Danish and Finnish national twin registries (n = 996 and n = 309).

Main Measures: CRF was defined as VO2max divided by fat-free mass. Insulin sensitivity and acute insulin response indices were derived from an oral glucose tolerance test. A continuous metabolic syndrome score was calculated. Visceral and liver fat were measured in the Finnish sample. Associations were analyzed separately in both cohorts with multivariate linear regression and aggregated with meta-analytic methods.

Results: Insulin sensitivity, acute insulin response, metabolic syndrome score, visceral, and liver fat amount had strong and statistically significant associations with FMI (|β| 0.53 to 0.79), whereas their associations with CRF and FFMI were at most weak (|β| 0.02 to 0.15). The results of the monozygotic intrapair differences analysis showed the same pattern.

Conclusions: Although FMI is strongly associated with worsening of metabolic health traits, even after controlling for genetic and shared environmental factors, there was little evidence for the effects of CRF or FFMI on metabolic health. This suggests that changing FMI rather than CRF or FFMI may affect metabolic health irrespective of genetic or early environmental determinants.
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http://dx.doi.org/10.1210/jc.2016-3435DOI Listing
May 2017

Inverse associations between cord vitamin D and attention deficit hyperactivity disorder symptoms: A child cohort study.

Aust N Z J Psychiatry 2017 Jul 30;51(7):703-710. Epub 2016 Sep 30.

1 Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.

Objective: To examine the association between cord 25-hydroxyvitamin D (25(OH)D) and attention deficit hyperactivity disorder symptoms in toddlers, using Child Behaviour Checklist for ages 1.5-5.

Method: In a population-based birth cohort, a Child Behaviour Checklist for ages 1.5-5 questionnaire was returned from parents of 1233 infants with mean age 2.7 (standard deviation 0.6) years. Adjusted associations between cord 25(OH)D and Child Behaviour Checklist-based attention deficit hyperactivity disorder problems were analysed by multiple regression. Results The median cord 25(OH)D was 44.1 (range: 1.5-127.1) nmol/L. Mean attention deficit hyperactivity disorder problem score was 2.7 (standard deviation 2.1). In adjusted analyses, cord 25(OH)D levels >25 nmol/L and >30 nmol/L were associated with lower attention deficit hyperactivity disorder scores compared to levels ⩽25 nmol/L ( p = 0.035) and ⩽30 nmol/L ( p = 0.043), respectively. The adjusted odds of scoring above the 90th percentile on the Child Behaviour Checklist-based attention deficit hyperactivity disorder problem scale decreased by 11% per 10 nmol/L increase in cord 25(OH)D.

Conclusion: An inverse association between cord 25(OH)D and attention deficit hyperactivity disorder symptoms in toddlers was found, suggesting a protective effect of prenatal vitamin D.
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http://dx.doi.org/10.1177/0004867416670013DOI Listing
July 2017

Longitudinal Investigation into Genetics in the Conservation of Metabolic Phenotypes in Danish and Chinese Twins.

PLoS One 2016 12;11(9):e0162805. Epub 2016 Sep 12.

Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.

Longitudinal twin studies on long term conservation of individual metabolic phenotypes can help to explore the genetic and environmental basis in maintaining metabolic homeostasis and metabolic health. We performed a longitudinal twin study on 12 metabolic phenotypes from Danish twins followed up for 12 years and Chinese twins traced for 7 years. The study covered a relatively large sample of 502 pairs of Danish adult twins with a mean age at intake of 38 years and a total of 181 Chinese adult twin pairs with a mean baseline age of 39.5 years. Bivariate twin models were fitted to the longitudinal measurements taken at two time points (at baseline and follow-up) to estimate the genetic and environmental contributions to phenotype variation and correlation at and between the two time points. High genetic components in the regulation of intra-individual phenotype correlation or stability over time were estimated in both Danish (h2>0.75 except fasting blood glucose) and Chinese (h2>0.72 except blood pressure) twins; moderate to high genetic contribution to phenotype variation at the two time points were also estimated except for the low genetic regulation on glucose in Danish and on blood pressure in Chinese twins. Meanwhile the bivariate twin models estimated shared environmental contributions to the variance and covariance in fasting blood glucose in Danish twins, and in systolic and diastolic blood pressure, low and high density lipoprotein cholesterol in Chinese twins. Overall, our longitudinal twin study on long-term stability of metabolic phenotypes in Danish and Chinese twins identified a common pattern of high genetic control over phenotype conservation, and at the same time revealed population-specific patterns of genetic and common environmental regulation on the variance as well as covariance of glucose and blood pressure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162805PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019416PMC
August 2017

Umbilical Cord Serum 25-Hydroxyvitamin D Concentrations and Relation to Birthweight, Head Circumference and Infant Length at Age 14 Days.

Paediatr Perinat Epidemiol 2016 May 24;30(3):238-45. Epub 2016 Feb 24.

Department of Public Health, Environmental Medicine, University of Southern Denmark, Odense C, Denmark.

Background: Insufficient supply of vitamin D during early development may negatively affect offspring growth.

Methods: We examined the association between umbilical cord (UC) serum 25-hydroxyvitamin D (25(OH)D) concentrations and infant size in a study of two Faroese birth cohorts of 1038 singleton infants. In the third trimester, the pregnant women completed questionnaires, and clinical examination included birthweight, head circumference, and infant length at age 14 days.

Results: Fifty-three percent of the newborn population had UC 25(OH)D < 25 nmol/L as determined by LC-MS/MS. Using multiple linear regression models with adjustment for pre-pregnancy BMI, sex, parity, gestational age, or infant age at examination, season of birth, smoking, gestational diabetes, examiner, and cohort identity, we found no relationship between birthweight or head circumference and UC 25(OH)D. However, infants with vitamin D status <12 nmol/L had a 0.49 (95% confidence interval 0.05, 0.93) cm lower length than infants with vitamin D status >50 nmol/L in models further adjusted for birthweight.

Conclusion: Our data suggest that umbilical cord serum 25(OH)D concentrations are positively associated with infant length but not with birthweight and head circumference. Although the paediatric relevance of the observed association is unclear, the possible long-term consequences of late-pregnancy hypovitaminosis D deserve attention.
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http://dx.doi.org/10.1111/ppe.12288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172952PMC
May 2016

A short leucocyte telomere length is associated with development of insulin resistance.

Diabetologia 2016 06 28;59(6):1258-65. Epub 2016 Mar 28.

INSERM, U1116, Vandoeuvre-les-Nancy, France.

Aims/hypothesis: A number of studies have shown that leucocyte telomere length (LTL) is inversely associated with insulin resistance and type 2 diabetes mellitus. The aim of the present longitudinal cohort study, utilising a twin design, was to assess whether shorter LTL predicts insulin resistance or is a consequence thereof.

Methods: Participants were recruited between 1997 and 2000 through the population-based national Danish Twin Registry to participate in the GEMINAKAR study, a longitudinal evaluation of metabolic disorders and cardiovascular risk factors. Baseline and follow-up measurements of LTL and insulin resistance over an average of 12 years were performed in a subset of the Registry consisting of 338 (184 monozygotic and 154 dizygotic) same-sex twin pairs.

Results: Age at baseline examination was 37.4 ± 9.6 (mean ± SD) years. Baseline insulin resistance was not associated with age-dependent changes in LTL (attrition) over the follow-up period, whereas baseline LTL was associated with changes in insulin resistance during this period. The shorter the LTL at baseline, the more pronounced was the increase in insulin resistance over the follow-up period (p < 0.001); this effect was additive to that of BMI. The co-twin with the shorter baseline LTL displayed higher insulin resistance at follow-up than the co-twin with the longer LTL.

Conclusions/interpretation: These findings suggest that individuals with short LTL are more likely to develop insulin resistance later in life. By contrast, presence of insulin resistance does not accelerate LTL attrition.
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http://dx.doi.org/10.1007/s00125-016-3915-6DOI Listing
June 2016

Genetic and Environmental Regulation on Longitudinal Change of Metabolic Phenotypes in Danish and Chinese Adult Twins.

PLoS One 2016 10;11(2):e0148396. Epub 2016 Feb 10.

Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.

Objective: The rate of change in metabolic phenotypes can be highly indicative of metabolic disorders and disorder-related modifications. We analyzed data from longitudinal twin studies on multiple metabolic phenotypes in Danish and Chinese twins representing two populations of distinct ethnic, cultural, social-economic backgrounds and geographical environments.

Materials And Methods: The study covered a relatively large sample of 502 pairs of Danish adult twins followed up for a long period of 12 years with a mean age at intake of 38 years (range: 18-65) and a total of 181 Chinese adult twin pairs traced for about 7 years with a mean baseline age of 39.5 years (range: 23-64). The classical twin models were fitted to the longitudinal change in each phenotype (Δphenotype) to estimate the genetic and environmental contributions to the variation in Δphenotype.

Results: Moderate to high contributions by the unique environment were estimated for all phenotypes in both Danish (from 0.51 for low density lipoprotein cholesterol up to 0.72 for triglycerides) and Chinese (from 0.41 for triglycerides up to 0.73 for diastolic blood pressure) twins; low to moderate genetic components were estimated for long-term change in most of the phenotypes in Danish twins except for triglycerides and hip circumference. Compared with Danish twins, the Chinese twins tended to have higher genetic control over the longitudinal changes in lipids (except high density lipoprotein cholesterol) and glucose, higher unique environmental contribution to blood pressure but no genetic contribution to longitudinal change in body mass traits.

Conclusion: Our results emphasize the major contribution of unique environment to the observed intra-individual variation in all metabolic phenotypes in both samples, and meanwhile reveal differential patterns of genetic and common environmental regulation on changes over time in metabolic phenotypes across the two samples.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148396PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749287PMC
July 2016

The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium.

Twin Res Hum Genet 2015 Dec;18(6):762-71

Department of Twin Research & Genetic Epidemiology,King's College London,London,UK.

Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.
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http://dx.doi.org/10.1017/thg.2015.83DOI Listing
December 2015

Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomization Meta-Analysis in the CARTA Consortium.

Circ Cardiovasc Genet 2015 Dec 4;8(6):832-41. Epub 2015 Nov 4.

Background: Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood.

Methods And Results: Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day.

Conclusions: This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.
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http://dx.doi.org/10.1161/CIRCGENETICS.115.001225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684098PMC
December 2015

Leukocyte telomere length dynamics in women and men: menopause vs age effects.

Int J Epidemiol 2015 Oct 18;44(5):1688-95. Epub 2015 Sep 18.

Center of Human Development and Aging, Rutgers, State University of New Jersey, Newark, NJ, USA and

Background: A longer leukocyte telomere length (LTL) in women than men has been attributed to a slow rate of LTL attrition in women, perhaps due to high estrogen exposure during the premenopausal period.

Methods: To test this premise we performed a longitudinal study (an average follow-up of 12 years) in a subset of the population-based Danish National Twin Registry. Participants consisted of 405 women, aged 37.5 (range 18.0-64.3) years, and 329 men, aged 38.8 (range 18.0-58.5) years, at baseline examination.

Results: Women showed a longer LTL [kb ± standard error(SE)] than men (baseline: 7.01 ± 0.03 vs 6.87 ± 0.04; follow-up: 6.79 ± 0.03 vs 6.65 ± 0.03; both P = 0.005). Women displayed deceleration of LTL attrition (bp/years ± SE), as they transitioned from the premenopausal period (20.6 ± 1.0) through the perimenopausal period (16.5 ± 1.3) to the postmenopausal period (15.1 ± 1.7). Age was not associated with LTL attrition in women after statistical control for menopausal status. Men, in contrast, displayed a trend for age-dependent increase in the rate of LTL attrition, which differed significantly from the pattern in women (P for interaction = 0.01).

Conclusions: Results indicate that the premenopausal period is expressed in a higher rate of LTL attrition than the postmenopausal period. They further suggest that the sex gap in LTL stems from earlier ages-the period of growth and development. The higher rate of LTL attrition in premenopausal women, we propose, might relate to estrogen-mediated increased turnover of erythrocytes, menstrual bleeding or both.
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http://dx.doi.org/10.1093/ije/dyv165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681111PMC
October 2015

Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium.

BMJ Open 2015 Aug 11;5(8):e008808. Epub 2015 Aug 11.

School of Social and Community Medicine, University of Bristol, Bristol, UK MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, University of Bristol, Bristol, UK.

Objectives: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity.

Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes.

Participants: 148,731 current, former and never-smokers of European ancestry aged ≥ 16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).

Primary Outcome Measures: Waist and hip circumferences, and waist-hip ratio.

Results: The data included up to 66,809 never-smokers, 43,009 former smokers and 38,913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele.

Conclusions: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.
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http://dx.doi.org/10.1136/bmjopen-2015-008808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538266PMC
August 2015

Vitamin D insufficiency is associated with increased risk of first-trimester miscarriage in the Odense Child Cohort.

Am J Clin Nutr 2015 Sep 15;102(3):633-8. Epub 2015 Jul 15.

Institute for Clinical Research and Hans Christian Andersen Children's Hospital,

Background: Miscarriage is the most common negative outcome of pregnancy, and identification of modifiable risk factors is potentially of great importance for public health. Low vitamin D concentrations in pregnancy are widespread worldwide, and vitamin D deficiency is implicated in immune cell regulation at the feto-maternal interface and several diseases of pregnancy.

Objective: We investigated whether 25-hydroxyvitamin D serum concentration was a modifiable risk factor for early miscarriage.

Design: In a prospective cohort study of 1683 pregnant women donating serum before gestational week 22, we investigated the association between maternal serum concentrations of serum 25-hydroxyvitamin D [25(OH)D] and the risk of subsequent miscarriage (n = 58).

Results: The adjusted hazard of first-trimester miscarriage was lower with higher 25(OH)D concentrations (HR: 0.98; 95% CI: 0.96, 0.99). Concentrations of 25(OH)D <50 nmol/L were associated with a >2-fold increased adjusted HR for miscarriage (HR: 2.50; 95% CI: 1.10, 5.69). Concentrations of 25(OH)D were not associated with an increased risk of second-trimester miscarriage.

Conclusions: We found an association between 25(OH)D and first-trimester miscarriages, suggesting vitamin D as a modifiable risk factor for miscarriage. To test this hypothesis, randomized controlled trials should investigate the possible effect of vitamin D supplementation to increase 25(OH)D concentrations in early pregnancy, or before conception, to decrease risk of miscarriage. This trial was registered at clinicaltrials.gov as NCT02434900.
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http://dx.doi.org/10.3945/ajcn.114.103655DOI Listing
September 2015

Paternal age and telomere length in twins: the germ stem cell selection paradigm.

Aging Cell 2015 Aug 10;14(4):701-3. Epub 2015 Apr 10.

Center of Human Development and Aging, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, 07103, USA.

Telomere length, a highly heritable trait, is longer in offspring of older fathers. This perplexing feature has been attributed to the longer telomeres in sperm of older men and it might be an 'epigenetic' mechanism through which paternal age plays a role in telomere length regulation in humans. Based on two independent (discovery and replication) twin studies, comprising 889 twin pairs, we show an increase in the resemblance of leukocyte telomere length between dizygotic twins of older fathers, which is not seen in monozygotic twins. This phenomenon might result from a paternal age-dependent germ stem cell selection process, whereby the selected stem cells have longer telomeres, are more homogenous with respect to telomere length, and share resistance to aging.
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http://dx.doi.org/10.1111/acel.12334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531084PMC
August 2015
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