Henriette A Delemarre-van de Waal

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (11)30.24 Total impact

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    ABSTRACT: Recently, the fat mass and obesity-associated gene (FTO) has been identified as a genetic risk factor for developing obesity. The underlying mechanisms remain speculative. SNPs within FTO have been associated with brain atrophy in frontal and occipital regions, suggesting that FTO might affect body weight through cerebral pathways. Behavioral studies suggested a relationship between FTO and the reward-related behavioral traits. Therefore the relationship between the FTO risk allele rs9939609A and volumes of reward-related brain structures has been investigated. Four hundred and ninety-two Dutch individuals (56% males, age: 70-82 years) participating in the PROSPER study underwent a 3D-T1-weighted MRI to assess the volumes of reward-related brain structures (e.g., amygdala, nucleus accumbens) and of gray matter and white matter. Linear regression analysis was performed to test for the association of subcortical and cortical structures with rs9939609A. rs9939609A is associated with lower volumes of the nucleus accumbens (p=0.03) and trended toward lower cortical gray matter volumes (p=0.08). This association is independent of gender, age, and BMI, FDR corrected. The FTO risk allele is associated with lower nucleus accumbens volumes, suggesting that the higher body weight of risk-allele carriers might be due to changes within reward-related brain structures. © 2015 The Obesity Society.
    Full-text · Article · Sep 2015 · Obesity
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    Carla L. van der Wijden · Henriette A. Delemarre-van de Waal · Willem van Mechelen · Mireille NM Poppel
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    ABSTRACT: ContextChildbearing is considered to be a significant risk factor for developing overweight and obesity. Physical activity might influence weight change via hormonal changes.Objective To test the hypothesis that higher levels of moderate to vigorous intensity physical activity (MVPA) are positively associated with maternal insulin sensitivity, and reduce IGF-1, IGFBP-3, leptin levels, bodyweight gain/retention and birth weight.Methods In healthy nulliparous women weight measurements were carried out and blood was collected during pregnancy in the 15th, 25th, and 35th week, and after delivery at 6, 26, and 52 weeks. At 15 and 35 weeks of pregnancy and 26 weeks postpartum MVPA was measured using accelerometers. In linear regression models, the relationship between MVPA below or above the median with metabolic and weight outcomes was assessed, adjusted for maternal BMI, age and smoking.ResultsMVPA decreased significantly during pregnancy, but was very low already in early pregnancy. Insulin resistance and leptin levels increased during pregnancy and decreased significantly after delivery (all p<0,05). After adjustment, insulin, IGFBP-3 and BMI were significantly lower at 15 weeks of pregnancy in women with MVPA above the median compared to those with MVPA below the median. After 15 weeks of pregnancy, no significant associations were observed between hormonal levels and MVPA. MVPA was neither related to weight retention, nor to birth weight.Conclusion Except in early pregnancy, MPVA was not related to metabolic outcomes. In addition MVPA during pregnancy was not related to weight retention or birth weight.This article is protected by copyright. All rights reserved.
    Full-text · Article · Aug 2014 · Clinical Endocrinology
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    ABSTRACT: Context and Objective: Information on the correlation of normative reproductive hormone levels with physical development (Tanner stages) during puberty and on the influences of genes and environment on variation in these hormones and Tanner stages is limited. Design, Setting, and Participants: One hundred twelve healthy 9-year-old twin pairs (n = 224) took part in a longitudinal study, of which 89 pairs participated again at age 12 years (n = 178). Main Outcome Measures: Morning urinary LH, FSH, estradiol, and salivary testosterone levels, determined by competitive immunoassays, were measured. Tanner stages were determined through physical examination. Results: Over the 3-year interval, all hormone levels showed a 2- to 9-fold increase. LH and FSH at age 9 years predicted sex-specific Tanner stages at age 12 years in both boys and girls. Most of the associations between hormone levels at age 9 years and physical development at 12 years were explained by genetic influences. FSH in 9-year-old boys correlated with all hormone levels and Tanner stages at age 12 years. Moderate to high heritability estimates were found for hormone levels at both ages and in both sexes. In girls a shift from environmental (age 9 years) to genetic influences (age 12 years) was found for estradiol and pubic hair development, and for breast development a shift in the opposite direction was seen. Conclusions: During development LH and FSH (and testosterone in boys) levels predict secondary sexual characteristics in boys and girls 3 years later. These correlations are largely due to genes that are involved in both early pubertal hormone levels and subsequent physical development.
    Full-text · Article · Mar 2013 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: The Sixth Evian Annual Reproduction (EVAR) Workshop Group Meeting was held to evaluate the impact of IVF/intracytoplasmic sperm injection on the health of assisted-conception children. Epidemiologists, reproductive endocrinologists, embryologists and geneticists presented data from published literature and ongoing research on the incidence of genetic and epigenetic abnormalities and congenital malformations in assisted-conception versus naturally conceived children to reach a consensus on the reasons for potential differences in outcomes between these two groups. IVF-conceived children have lower birthweights and higher peripheral fat, blood pressure and fasting glucose concentrations than controls. Growth, development and cognitive function in assisted-conception children are similar to controls. The absolute risk of imprinting disorders after assisted reproduction is less than 1%. A direct link between assisted reproduction and health-related outcomes in assisted-conception children could not be established. Women undergoing assisted reproduction are often older, increasing the chances of obtaining abnormal gametes that may cause deviations in outcomes between assisted-conception and naturally conceived children. However, after taking into account these factors, it is not clear to what extent poorer outcomes are due to the assisted reproduction procedures themselves. Large-scale, multicentre, prospective epidemiological studies are needed to investigate this further and to confirm long-term health consequences in assisted-conception children.
    Full-text · Article · Jan 2013 · Reproductive biomedicine online
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    ABSTRACT: Introduction: In our hospital, female-to-male (FtM) transgender adolescents from the age of 16 are treated with two- or four-weekly intra-muscular injections of testosterone-esters. Some patients treated with four-weekly injections have complaints of fatigue and experience mood swings towards the end of the inter-injection period, which calls for an evaluation of the time-course of testosterone levels between injections. Evaluation of salivary testosterone is a practical approach for sequential measurements. Since only ∼2% of total serum testosterone is present in saliva, a sensitive assay is necessary. The objective was to develop an isotope dilution-liquid chromatography-tandem mass spectrometry method (ID-LC-MS/MS) for salivary testosterone measurements and to evaluate the testosterone profiles after testosterone-ester mixture injections in FtM-adolescents. Experimental: FtM treated with 125 mg/2 weeks or with 250 mg/4 weeks depots of testosterone-ester mixture collected saliva at different time intervals. Salivary testosterone was measured by a thoroughly validated ID-LC-MS/MS assay. Results: An ID-LC-MS/MS method for measuring salivary testosterone was developed with adequate accuracy and specificity. The reference range was established at 135-400 pmol/L. Testosterone levels peaked supra-physiologically immediately post-injection, and decreased to levels within the male reference range after nine days in all patients. 250 mg/4 weeks depots resulted in values below the reference range at the end of the 4 weeks. Discussion: The development of an adequate ID-LC-MS/MS method for measuring salivary testosterone allowed us to investigate the testosterone profile in FtM-adolescents after testosterone-esters mixture injections. These injections lead to extreme concentrations which may affect the wellbeing of the patients.
    No preview · Article · Nov 2012 · Steroids
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    Linda van den Berg · Miriam Glorie-Docter · Erica van den Akker · Henriette A Delemarre-van de Waal
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    ABSTRACT: Obesity is usually the result of a combination of genetic and lifestyle factors. In monogenic obesity, overweight is caused by a single gene mutation. The most frequent form of monogenic obesity is caused by mutations in the gene that codes for the melanocortin-4 receptor (MC4R gene). Approximately 2% of Dutch children with obesity have a mutation in the MC4R gene. Children with homozygous and 'compound' heterozygous MC4R mutations have a phenotype distinguished by extreme overweight at an early age and hyperphagia. Children with heterozygous MC4R mutations have a more subtle phenotype and are difficult to distinguish clinically from obese children without this mutation. MC4R mutations can be identified by DNA diagnostics.- Drug treatment is not yet available for this condition.
    Full-text · Article · Aug 2012 · Nederlands tijdschrift voor geneeskunde
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    ABSTRACT: In short children, a low IGF-I and normal GH secretion may be associated with various monogenic causes, but their prevalence is unknown. We aimed at testing GH1, GHR, STAT5B, IGF1, and IGFALS in children with GH insensitivity. Subjects and Patients were divided into three groups: group 1 (height SDS <-2.5, IGF-I <-2 SDS, n = 9), group 2 (height SDS -2.5 to -1.9, IGF-I <-2 SDS, n = 6) and group 3 (height SDS <-1.9, IGF-I -2 to 0 SDS, n = 21). An IGF-I generation test was performed in 11 patients. Genomic DNA was used for direct sequencing, multiplex ligation-dependent probe amplification and whole-genome SNP array analysis. Three patients in group 1 had two novel heterozygous STAT5B mutations, in two combined with novel IGFALS variants. In groups 2 and 3 the association between genetic variants and short stature was uncertain. The IGF-I generation test was not predictive for the growth response to GH treatment. In severely short children with IGF-I deficiency, genetic assessment is advised. Heterozygous STAT5B mutations, with or without heterozygous IGFALS defects, may be associated with GH insensitivity. In children with less severe short stature or IGF-I deficiency, functional variants are rare.
    Full-text · Article · Jun 2012 · Hormone Research in Paediatrics
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    ABSTRACT: The quality and quantity of food intake affect body weight, but little is known about the genetics of such human dietary intake patterns in relation to the genetics of BMI. We aimed to estimate the heritability of dietary intake patterns and genetic correlation with BMI in participants of the Erasmus Rucphen Family study. The study included 1,690 individuals (42 % men; age range, 19–92), of whom 41.4 % were overweight and 15.9 % were obese. Self-report questionnaires were used to assess the number of days (0–7) on which participants consumed vegetables, fruit, fruit juice, fish, unhealthy snacks, fastfood, and soft drinks. Principal component analysis was applied to examine the correlations between the questionnaire items and to generate dietary intake pattern scores. Heritability and the shared genetic and shared non-genetic (environmental) correlations were estimated using the family structure of the cohort. Principal component analysis suggested that the questionnaire items could be grouped in a healthy and unhealthy dietary intake pattern, explaining 22 and 18 % of the phenotypic variance, respectively. The dietary intake patterns had a heritability of 0.32 for the healthy and 0.27 for the unhealthy pattern. Genetic correlations between the dietary intake patterns and BMI were not significant, but we found a significant environmental correlation between the unhealthy dietary intake pattern and BMI. Specific dietary intake patterns are associated with the risk of obesity and are heritable traits. The genetic factors that determine specific dietary intake patterns do not significantly overlap with the genetic factors that determine BMI. Electronic supplementary material The online version of this article (doi:10.1007/s00592-012-0387-0) contains supplementary material, which is available to authorized users.
    Full-text · Article · Mar 2012 · Acta Diabetologica
  • L van den Berg · K Pieterse · J A Malik · M Luman · K. Willems van Dijk · J Oosterlaan · H A Delemarre-van de Waal
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    ABSTRACT: Childhood obesity is a major health problem. An association between children's body mass index (BMI) and overeating has been established, but mechanisms leading to overeating are poorly understood. The personality characteristics impulsivity and reward responsiveness may be involved in the tendency to overeat. Impulsivity might relate to overeating through poor inhibition of food intake; reward responsiveness through the rewarding value of food. This study aimed to reveal the relationships between impulsivity, reward responsiveness, overeating and BMI in a sample of 346 Dutch children aged 6-13 years. The BMI distribution in the sample was representative of the BMI distribution in the Dutch pediatric population. Impulsivity and reward responsiveness were measured with the Dutch version of the parent-report Sensitivity to Punishment and Sensitivity to Reward Questionnaire for children. Overeating was assessed with the Dutch translation of the parent-report Children's Eating Behaviour Questionnaire. Overeating, impulsivity and reward responsiveness were significantly associated with childhood BMI. Mediation analysis revealed that impulsivity and reward responsiveness equally and significantly predicted BMI indirectly through overeating. The personality characteristics impulsivity and reward responsiveness predict childhood BMI indirectly through overeating. This suggests that these personality characteristics are risk factors for obesity.
    No preview · Article · Jun 2011 · International journal of obesity (2005)

  • No preview · Article · Oct 2010 · Animal Genetics

  • No preview · Article · Jan 2010

Publication Stats

103 Citations
30.24 Total Impact Points


  • 2012-2015
    • Leiden University Medical Centre
      • Department of Pediatrics
      Leyden, South Holland, Netherlands
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2010-2013
    • Leiden University
      Leyden, South Holland, Netherlands