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OBJECTIVE: We sought to assess body mass index trajectories of children with genetic obesity to identify optimal early age of onset of obesity (AoO) cut-offs for genetic screening. STUDY DESIGN: This longitudinal, observational study included growth measurements from birth onward of children with nonsyndromic and syndromic genetic obesity and control children with obesity from a population-based cohort. Diagnostic performance of AoO was evaluated. RESULTS: We describe the body mass index trajectories of 62 children with genetic obesity (29 nonsyndromic, 33 syndromic) and 298 controls. Median AoO was 1.2 years in nonsyndromic genetic obesity (0.4 and 0.6 years in biallelic LEPR and MC4R; 1.7 in heterozygous MC4R); 2.0 years in syndromic genetic obesity (0.9, 2.3, 4.3, and 6.8 years in pseudohypoparathyroidism, Bardet-Biedl syndrome, 16p11.2del syndrome, and Temple syndrome, respectively); and 3.8 years in controls. The optimal AoO cut-off was ≤3.9 years (sensitivity, 0.83; specificity, 0.49; area under the curve, 0.79; P < .001) for nonsyndromic and ≤4.7 years (sensitivity, 0.82; specificity, 0.37; area under the curve, 0.68; P = .001) for syndromic genetic obesity. CONCLUSIONS: Optimal AoO cut-off as single parameter to determine which children should undergo genetic testing was ≤3.9 years. In case of older AoO, additional features indicative of genetic obesity should be present to warrant genetic testing. Optimal cut-offs might differ across different races and ethnicities.
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Testes Genéticos , Obesidade , Humanos , Criança , Índice de Massa Corporal , Idade de Início , Obesidade/epidemiologia , Obesidade/genética , Heterozigoto , Receptor Tipo 4 de Melanocortina/genéticaRESUMO
BACKGROUND: It is unknown whether weight class is associated with impairment of health-related quality of life (HRQOL) for children in the Netherlands. The aim of this study was to explore generic and weight-specific HRQOL in a clinical cohort of children with overweight, obesity or severe obesity aged 5-19 years in the Netherlands. METHODS: 803 children from three clinical cohorts participated: mean age 11.5 (SD 2.9) years, 61.1% girls. The influence of weight class was explored in a subgroup of 425 children (25.2% with overweight, 32.5% obesity and 42.3% severe obesity), of whom the exact International Obesity Task Force (IOTF) BMI class was known. Generic HRQOL was measured by the PedsQL child report. Weight-specific HRQOL was measured by the IWQOL-Kids child or parent report. Average total, subscale and item scores were reported and the influence of the IOTF BMI class analyzed by multiple linear regression, corrected for age and sex. RESULTS: Children with severe obesity had lower generic and weight-specific HRQOL scores than those with obesity or overweight. IOTF BMI class was negatively associated with item scores from all subscales, especially physical, social and emotional functioning. Children with overweight reported similar HRQOL total, subscale and item scores to children with obesity. CONCLUSIONS: In the Netherlands, children treated for overweight, obesity or severe obesity experience problems on the majority of items within all subscales of generic and weight-specific HRQOL. Children with severe obesity especially report significantly more challenges due to their weight than children with obesity or overweight.
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Obesidade Mórbida , Sobrepeso , Feminino , Criança , Humanos , Masculino , Sobrepeso/terapia , Sobrepeso/psicologia , Qualidade de Vida/psicologia , Obesidade Mórbida/terapia , Estudos Transversais , Países Baixos , Índice de Massa Corporal , Obesidade/psicologiaRESUMO
INTRODUCTION: Corticosteroids are widely prescribed and their use has been linked to adverse cardiometabolic outcomes. A pivotal role in the action of corticosteroids is reserved for the glucocorticoid receptor (GR). Here, we assessed the relationship of glucocorticoid sensitivity-altering GR polymorphisms with anthropometrics and metabolic syndrome (MetS) in corticosteroid users. METHODS: In this population-based cohort study (Lifelines), we genotyped 10,621 adult participants for GR hypersensitive (1/2 copies BclI and/or N363S) and GR resistant (1/2 copies ER22/23EK and/or 9ß) variants. We assessed the relationship between functional GR polymorphisms with BMI, waist circumference (WC), and MetS in users of corticosteroids. RESULTS: Overall corticosteroid use was associated with a significantly higher BMI and WC in GR wild-type (WT) users (BMI, +0.63 kg/m2 [0.09-1.16], p = 0.022; WC, +2.03 cm [0.61-3.44], p = 0.005) and GR hypersensitive (BMI, +0.66 kg/m2 [95% CI, 0.31-1.01]; WC, +2.06 cm [1.13-2.98], both p < 0.001) but not in GR resistant users. Significantly higher WC in GR resistant carriers was observed only for inhaled corticosteroid users. With respect to MetS, again only GR WT users (odds ratio [OR] 1.44 [1.07-1.94], p = 0.017) and GR hypersensitives (OR 1.23 [95% CI, 1.00-1.50], p = 0.046) were more likely to have MetS; even more pronounced in only inhaled corticosteroid users (GR WT users, OR 1.64 [1.06-2.55], p = 0.027; GR hypersensitive users, OR 1.43 [1.08-1.91], p = 0.013). CONCLUSIONS: Polymorphisms associated with increased GR sensitivity and WT GR are related to increased BMI, WC, and an increased MetS presence in corticosteroid users, especially of the inhaled types, when compared to nonusers. The adverse effects of corticosteroid use are less pronounced in users harboring GR resistant polymorphisms.
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Corticosteroides/efeitos adversos , Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Síndrome Metabólica/induzido quimicamente , Receptores de Glucocorticoides/genética , Circunferência da Cintura , Corticosteroides/administração & dosagem , Adulto , Idoso , Antropometria , Estudos de Coortes , Feminino , Humanos , Masculino , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Polimorfismo Genético , Circunferência da Cintura/fisiologiaRESUMO
Human donor milk is the feeding of choice for preterm infants, when own mother's milk is not available. Holder pasteurization is necessary to secure the safety of donor milk, although it can affect milk quality by reduction of nutritional and bioactive components. Recently, research has focused on the potential role of breast milk glucocorticoids for infant development. At this moment, it is unknown whether pasteurization affects milk glucocorticoid levels. Therefore, we assessed whether Holder pasteurization, the most frequently used method nowadays, reduces breast milk cortisol and cortisone levels, using breast milk samples from 30 women who delivered at term. We found tight correlations between pre- and postpasteurization levels of cortisol (Râ=â0.99) and cortisone (Râ=â0.98), and good agreement in Passing and Bablok regression analysis. In conclusion, cortisol and cortisone in human term breast milk are not significantly affected by Holder pasteurization.
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Cortisona/análise , Hidrocortisona/análise , Leite Humano/química , Pasteurização , Cortisona/química , Feminino , Glucocorticoides/análise , Humanos , Hidrocortisona/química , Lactente , Recém-Nascido , Bancos de Leite HumanoRESUMO
BACKGROUND: Many very preterm (i.e., <32 weeks of gestation) newborns fail to mount an adequate adrenocortical response to stress or illness, termed relative adrenal insufficiency. Conversely, later in life these infants show features of increased glucocorticoid bioactivity, such as abdominal adiposity, insulin resistance, raised blood pressure, shorter stature and internalizing problem behavior. SUMMARY: Studies suggested that very preterm newborns have impairments along multiple levels of the hypothalamus-pituitary-adrenal (HPA) axis. Among the impairment were defects in: (1) the pituitary responsiveness to exogenous corticotropin-releasing hormone, (2) 11ß-hydroxylase activity, and (3) the interconversion between cortisol and inert cortisone. There is some evidence suggesting that later in life these infants have an increased basal secretion rate of cortisol and adrenal hyperandrogenism. However, the response to acute (psychosocial) stress was blunted rather than enhanced in them. The mechanisms explaining this switch in HPA axis activity are complex and not yet fully understood. Key Messages: Very preterm newborns have several impairments along the HPA axis that could impede an adequate adrenocortical response to stress or illness. Later in life, these infants are predisposed to increased HPA axis activity, which could partially explain their phenotype.
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Sistema Hipotálamo-Hipofisário/anormalidades , Lactente Extremamente Prematuro/fisiologia , Sistema Hipófise-Suprarrenal/anormalidades , Feminino , Humanos , Recém-Nascido , Masculino , Fenótipo , Estresse Fisiológico/fisiologiaRESUMO
BACKGROUND: Very preterm infants often receive donor milk from mothers who deliver at term, but its composition differs from that of their own mother's milk. Because breast-milk glucocorticoids can support developing neonates, we explored concentration variability within and between mothers. OBJECTIVE: We hypothesized that breast-milk glucocorticoid concentrations would be higher after very preterm delivery [gestational age (GA) <32 wk; study 1] and would follow the diurnal rhythm of maternal adrenocortical activity (study 2). METHODS: Study 1 assessed differences in milk cortisol, cortisone, and the cortisone-to-(cortisol+cortisone) ratio of mothers who delivered at (median) GA: 28.6 wk or at term weekly during the first month postpartum. Study 2 assessed variations in milk cortisol, cortisone, and the cortisone-to-(cortisol+cortisone) ratio over 24 h, and tested Pearson correlations between milk and salivary concentrations in mothers who delivered at term (median GA: 38.9 wk) during week 4 postpartum. In these studies, foremilk glucocorticoids were measured by liquid chromatography-tandem mass spectrometry. Associations of milk cortisol, milk cortisone, and the milk cortisone-to-(cortisol+cortisone) ratio with prematurity (study 1) or collection time (study 2) were studied with longitudinal data analyses. RESULTS: In study 1, giving birth to a very preterm infant was associated with reductions in milk cortisol and cortisone concentrations of 50% (ß: 0.50; 95% CI: 0.26, 0.99; P = 0.05) and 53% (ß: 0.53; 95% CI: 0.30, 0.93; P = 0.03), respectively, when adjusted for collection time. In study 2, concentrations of milk cortisol and cortisone were associated with collection time (both P < 0.01), peaking at â¼0700. Milk and salivary concentrations of cortisol (r = 0.92, P < 0.01) and cortisone (r = 0.93, P < 0.01) as well as the cortisone-to-(cortisol+cortisone) ratio (r = 0.64, P < 0.01) were correlated with one another. CONCLUSIONS: Breast-milk glucocorticoid concentrations follow the diurnal rhythm of maternal hypothalamus-pituitary-adrenal axis activity and are lower in mothers who deliver very preterm.
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Cortisona/metabolismo , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Leite Humano/química , Sistema Hipófise-Suprarrenal/fisiologia , Adulto , Ritmo Circadiano/fisiologia , Cortisona/química , Feminino , Humanos , Hidrocortisona/química , Recém-Nascido , Nascimento PrematuroRESUMO
AIM: The aim of this study was to provide an overview of foetal/neonatal alloimmune neutropenia (FNAIN), together with advice on the clinical management. METHODS: Neutrophil serology in the Netherlands is centralised at Sanquin Diagnostic Services. We examined FNAIN cases between January 1, 1991, and July 1, 2013, to determine the number of cases diagnosed, the relationship with human neutrophil antigen (HNA) antibody, the clinical presentation and therapeutic interventions. RESULTS: We identified 35 FNAIN cases. The detected HNA antibodies were as follows: anti-HNA-1a (n = 7), anti-HNA-1b (n = 12), anti-HNA-1c (n = 2), anti-HNA-2 (n = 8), anti-HNA-3a (n = 1), anti-HNA-5a (n = 1) and anti-FcγRIIIb (n = 4). No infections were diagnosed in 14 neonates, and the other 21 neonates suffered from omphalitis (n = 6), urinary tract infection (n = 1), candida mucositis (n = 1), fever of unknown origin (n = 6) and sepsis (n = 7, 20%). Parity, gestational age, birthweight, neutrophil counts and antibody specificity were not significantly different for cases with, and without, infections. All the infected children were treated with antibiotics. No children died. CONCLUSION: More than half (21) of the 35 cases of FNAIN presented with infections and most implicated were HNA-1a, HNA-1b and HNA-2. Treatment with antibiotics seemed adequate. A neonatal neutropenia workflow model for use in neonatal intensive care units is presented.
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Doenças Fetais/imunologia , Neutropenia/congênito , Neutropenia/imunologia , Árvores de Decisões , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/terapia , Humanos , Recém-Nascido , Isoantígenos , Masculino , Neutropenia/complicações , Neutropenia/diagnóstico , Neutropenia/terapia , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Dutch healthcare workers experience the highest workload and absenteeism rates compared to all other professions. This has been associated with a more unhealthy diet. Nudging strategies in the workplace have been shown to improve food choices. We studied the potential of a combination of evidence and practice-based nudging strategies; determined their feasibility in a real-life setting; and explored their effectiveness on healthier purchases over a two-month period in a hospital workplace cafeteria. METHODS: We conducted an explorative, prospective field study. Based on information gathered through a literature search and a qualitative field study, we selected the potentially most effective and feasible nudges. These were subsequently implemented in a commercial workplace cafeteria of a Dutch academic medical centre. The selected nudging strategies included product placement, increasing the ratio of healthy to unhealthy product options, and providing nutritional information and motivational statements. Data on the products purchased was collected using photographs of the lunch trays of healthcare workers, with the products then labelled and their nutritional value calculated. Effects were evaluated after one and two months. Chi-square analyses were used to analyse differences over time. RESULTS: A total of 905 photographs of lunches were analysed (approximately 300 at each time point). The nudging strategies implemented resulted in a 41% increase in the purchase of whole-wheat products at the expense of non-whole-wheat products, between baseline and final measurement (p = 0.012). The purchases of healthy and unhealthy bread fillings and beverages did not significantly change during the study period. CONCLUSION: This explorative study showed that a combination of three nudging strategies partly improved healthy food choices for lunch in a Dutch healthcare setting. These results may help guide other professionals to implement nudging strategies to improve employee food choices. Future research should evaluate the effect over a longer period of time, thereby identifying the most effective combination of nudging strategies and investigate how these effect the health of hospital employees.
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Dieta , Preferências Alimentares , Humanos , Local de Trabalho , Almoço , Pessoal de SaúdeRESUMO
Little is known about the prevalence of negative weight-biased attitudes among Dutch healthcare professionals (HCPs) when treating children and adolescents with obesity and whether interdisciplinary differences are present. Accordingly, we asked Dutch HCPs that treat pediatric patients with obesity to complete a validated 22-item self-report questionnaire about their weight-biased attitudes. In total, 555 HCPs participated from seven different disciplines: 41 general practitioners (GPs), 40 pediatricians, 132 youth healthcare physicians, 223 youth healthcare nurses, 40 physiotherapists, 40 dieticians, and 39 mental health professionals. HCPs from all disciplines reported to experience negative weight-biased attitudes among themselves. Pediatricians and GPs scored highest on negative weight-biased attitudes, including frustrations in treating children with obesity, and feeling less confident and prepared to treat children with obesity. Dieticians scored the least negative weight-biased attitudes. Participants from all groups perceived weight bias expressed by their colleagues, toward children with obesity. These findings are comparable to results reported by adult HCPs from other countries. Interdisciplinary differences were found and underscore the need for more research on contributing factors that impact explicit weight bias among pediatric HCPs.
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Obesidade Infantil , Preconceito de Peso , Adulto , Adolescente , Humanos , Criança , Obesidade/terapia , Obesidade/psicologia , Pessoal de Saúde , Atenção à Saúde , Atitude , Atitude do Pessoal de Saúde , Obesidade Infantil/terapiaRESUMO
Disrupted hormonal appetite signaling plays a crucial role in obesity as it may lead to uncontrolled reward-related eating. Such disturbances can be induced not only by weight gain itself but also by glucocorticoid overexposure, for example, due to chronic stress, disease, or medication use. However, the exact pathways are just starting to be understood. Here, we present a conceptual framework of how glucocorticoid excess may impair hormonal appetite signaling and, consequently, eating control in the context of obesity. The evidence we present suggests that counteracting glucocorticoid excess can lead to improvements in appetite signaling and may therefore pose a crucial target for obesity prevention and treatment. In turn, targeting hormonal appetite signals may not only improve weight management and eating behavior but may also decrease detrimental effects of glucocorticoid excess on cardio-metabolic outcomes and mood. We conclude that gaining a better understanding of the relationship between glucocorticoid excess and circulating appetite signals will contribute greatly to improvements in personalized obesity prevention and treatment.
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Apetite , Glucocorticoides , Humanos , Apetite/fisiologia , Glucocorticoides/efeitos adversos , Comportamento Alimentar/fisiologia , Obesidade , Aumento de Peso , Ingestão de Alimentos/fisiologiaRESUMO
Background: Obesity is a multifactorial, chronic, progressive disease associated with decreased health-related quality of life, comorbidities, and increased mortality risk. Lifestyle interventions, focusing on dietetics, physical exercise, and behavioral therapy, are a cornerstone of therapy. Despite this very multidisciplinary treatment approach, the definition of treatment success is often based only on a weight loss of ≥ 5%. However, the heterogeneous nature of obesity may necessitate a more comprehensive approach to assessing treatment effects. Objectives: Here, we describe changes in physiological, psychological, and behavioral health after a multidisciplinary combined lifestyle intervention (CLI). Additionally, we investigated whether these changes were related to weight loss. Methods: This prospective observational longitudinal study comprised 96 adults with obesity (73 women, 81 Caucasian) participating in a CLI at the Obesity Center CGG, Erasmus University Medical Center, Rotterdam, the Netherlands. The 1.5-year intervention comprised multidisciplinary professional guidance towards a healthy diet, increased physical activity, and included cognitive behavioral therapy. Physiological health outcomes, psychological well-being, eating behavior, and physical activity were assessed after ten weeks and 1.5 years and compared to baseline. Results: An average of 5.2% weight loss (-6.0 kg) was accompanied by a mean 9.8% decrease in fat mass (-5.9 kg; both P < 0.001) and significant improvements in metabolism, hormonal status, and immune parameters (all P < 0.05). Moreover, we observed decreased psychopathology, increased quality of life, and decreased disordered eating (all P < 0.05). Weight loss correlated with most metabolic changes (all P < 0.05) but not with most psychological/behavioral changes. Conclusions: Combined lifestyle intervention in patients with obesity was accompanied by significant improvements in body weight and body composition along with cardiometabolic, endocrine, immunological, psychological, and behavioral improvements. Interestingly, most changes in psychological and behavioral health occurred independently of weight loss. Obesity treatment success should be evaluated based on a combination of physical and patient-reported outcomes rather than weight loss alone.
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Increasing evidence points to a relation between increased glucocorticoid (GC) exposure and weight gain. In support, long-term cortisol measurements using hair analysis revealed that many individuals with obesity appear to have cortisol values in the high physiological range. The mechanisms behind this relationship need to be determined in order to develop targeted therapy to reach sustainable weight loss in these subgroups. The effect of GCs is not only determined by the plasma concentration of GCs but also by individual differences in GC sensitivity and the target tissue, which can be analyzed by functional GC assays. GC sensitivity is influenced by multiple genetic and acquired (e.g., disease-related) factors, including intracellular GC availability, hormone binding affinity, and expression levels of the GC receptors and their isoforms, as well as factors involved in the modulation of gene transcription. Interindividual differences in GC sensitivity also play a role in the response to exogenous GCs, with respect to both therapeutic and adverse effects. Accordingly, in this review, we summarize current knowledge on mechanisms that influence GC sensitivity and their relationships with obesity and discuss personalized treatment options targeting the GC receptor.
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Glucocorticoides , Hidrocortisona , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Obesidade/genética , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Long-term glucocorticoids (HairGC) measured in scalp hair have been associated with body mass index (BMI), waist circumference (WC), and waist-hip-ratio (WHR) in several cross-sectional studies. We aimed to investigate the magnitude, strength, and clinical relevance of these relations across all ages. METHODS: We performed a systematic review and meta-analysis (PROSPERO registration CRD42020205187) searching for articles relating HairGC to measures of obesity. Main outcomes were bivariate correlation coefficients and unadjusted simple linear regression coefficients relating hair cortisol (HairF) and hair cortisone (HairE) to BMI, WC, and WHR. RESULTS: We included k = 146 cohorts (n = 34,342 individuals). HairGC were positively related to all anthropometric measurements. The strongest correlation and largest effect size were seen for HairE-WC: pooled correlation 0.18 (95%CI 0.11-0.24; k = 7; n = 3,158; I2 = 45.7%) and pooled regression coefficient 11.0 cm increase in WC per point increase in 10-log-transformed HairE (pg/mg) on liquid-chromatography-(tandem) mass spectrometry (LC-MS) (95%CI 10.1-11.9 cm; k = 6; n = 3,102). Pooled correlation for HairF-BMI was 0.10 (95%CI 0.08-0.13; k = 122; n = 26,527; I2 = 51.2%) and pooled regression coefficient 0.049 kg/m2 per point increase in 10-log-transformed HairF (pg/mg) on LC-MS (95%CI 0.045-0.054 kg/m2 ; k = 26; n = 11,635). DISCUSSION: There is a consistent positive association between HairGC and BMI, WC, and WHR, most prominently and clinically relevant for HairE-WC. These findings overall suggest an altered setpoint of the hypothalamic-pituitary-adrenal axis with increasing central adiposity.
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Glucocorticoides , Sistema Hipotálamo-Hipofisário , Índice de Massa Corporal , Estudos Transversais , Glucocorticoides/análise , Cabelo/química , Humanos , Obesidade/complicações , Sistema Hipófise-Suprarrenal/química , Fatores de Risco , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
Background: Pediatric obesity is a multifactorial disease which can be caused by underlying medical disorders arising from disruptions in the hypothalamic leptin-melanocortin pathway, which regulates satiety and energy expenditure. Aim: To investigate and compare resting energy expenditure (REE) and body composition characteristics of children and adolescents with severe obesity with or without underlying medical causes. Methods: This prospective observational study included pediatric patients who underwent an extensive diagnostic workup in our academic centre that evaluated endocrine, non-syndromic and syndromic genetic, hypothalamic, and medication-induced causes of obesity. REE was assessed by indirect calorimetry; body composition by air displacement plethysmography. The ratio between measured REE (mREE) and predicted REE (Schofield equations), REE%, was calculated, with decreased mREE defined as REE% ≤90% and elevated mREE ≥110%. Additionally, the influence of fat-free-mass (FFM) on mREE was evaluated using multiple linear regression. Results: We included 292 patients (146 [50%] with body composition measurements), of which 218 (75%) patients had multifactorial obesity and 74 (25%) an underlying medical cause: non-syndromic and syndromic genetic (n= 29 and 28, respectively), hypothalamic (n= 10), and medication-induced (n= 7) obesity. Mean age was 10.8 ± 4.3 years, 59% were female, mean BMI SDS was 3.8 ± 1.1, indicating severe obesity. Mean REE% was higher in children with non-syndromic genetic obesity (107.4% ± 12.7) and lower in children with hypothalamic obesity (87.6% ± 14.2) compared to multifactorial obesity (100.5% ± 12.6, both p<0.01). In 9 children with pseudohypoparathyroidism type 1a, mean REE% was similar (100.4 ± 5.1). Across all patients, mREE was decreased in 60 (21%) patients and elevated in 69 (24%) patients. After adjustment for FFM, mREE did not differ between patients within each of the subgroups of underlying medical causes compared to multifactorial obesity (all p>0.05). Conclusions: In this cohort of children with severe obesity due to various etiologies, large inter-individual differences in mREE were found. Consistent with previous studies, almost half of patients had decreased or elevated mREE. This knowledge is important for patient-tailored treatment, e.g. personalized dietary and physical activity interventions and consideration of pharmacotherapy affecting central energy expenditure regulation in children with decreased mREE.
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Obesidade Mórbida , Obesidade Infantil , Adolescente , Composição Corporal , Calorimetria Indireta , Criança , Metabolismo Energético/genética , Feminino , Humanos , Masculino , Obesidade Infantil/genéticaRESUMO
Objective: Childhood obesity is associated with alterations in hypothalamus-pituitary-adrenal axis activity. We tested the hypothesis that multiple alterations in the metabolism of glucocorticoids are required for the development of hypertension in children who become overweight. Methods: Spot urine for targeted gas chromatography-mass spectrometry steroid metabolome analysis was collected from (1) overweight/hypertensive children (n = 38), (2) overweight/non-hypertensive children (n = 83), and (3) non-overweight/non-hypertensive children (n = 56). Results: The mean (± s.d.) age of participants was 10.4 ± 3.4 years, and 53% of them were male. Group 1 and group 2 had higher excretion rates of cortisol and corticosterone metabolites than group 3 (869 (interquartile range: 631-1352) vs 839 (609-1123) vs 608 (439-834) µg/mmol creatinine × m2 body surface area, P < 0.01, for the sum of cortisol metabolites), and group 1 had a higher excretion rate of naive cortisol than group 3. Furthermore, groups differed in cortisol metabolism, in particular in the activities of 11ß-hydroxysteroid dehydrogenases, as assessed from the ratio of cortisol:cortisone metabolites (group 2 < group 3), 5α-reductase (group 1 > group 2 or 3), and CYP3A4 activity (group 1 < group 2 or 3). Discussion: The sequence of events leading to obesity-associated hypertension in children may involve an increase in the production of glucocorticoids, downregulation of 11ß-hydroxysteroid dehydrogenase type 1 activity, and upregulation of 5α-reductase activity, along with a decrease in CYP3A4 activity and an increase in bioavailable cortisol.
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INTRODUCTION: COVID-19 lockdown measures have large impact on lifestyle behaviors and well-being of children. The aim of this mixed-methods study was to investigate the impact of COVID-19 lockdown measures on eating styles and behaviors, physical activity (PA), screen time, and health-related quality of life (HRQoL) in children (0-18 years) with severe obesity. METHODS: During the first COVID-19 wave (April 2020), validated questionnaires were completed and semi-structured telephone interviews were conducted with parents of children with severe obesity (adult body mass index [BMI]-equivalent ≥35 kg/m2) and/or with the children themselves. Changes in pre-pandemic versus lockdown scores of the Dutch Eating Behavior Questionnaire Children, Pediatric Quality of Life Inventory, and Dutch PA Questionnaire were assessed. Qualitative analyses were performed according to the Grounded Theory. RESULTS: Ninety families were approached of which 83 families were included. Characteristics of the included children were: mean age 11.2 ± 4.6 years, 52% female, mean BMI SD-score +3.8 ± 1.0. Emotional, restrained, and external eating styles, HRQoL, and (noneducational) screen time did not change on group level (all p > 0.05). However, weekly PA decreased (mean difference -1.9 h/week, p = 0.02) mostly in adolescents. In the majority of children, mean weekly PA decreased to ≤2 h/week. Children with high emotional or external eating scores during lockdown or pre-existent psychosocial problems had the lowest HRQoL (p < 0.01). Qualitative analyses revealed an increased demand for food in a significant proportion of children (n = 21), mostly in children <10 years (19/21). This was often attributed to loss of daily structure and perceived stress. Families who reported no changes (n = 15) or improved eating behaviors (n = 11) attributed this to already existing strict eating schemes that they kept adhering to during lockdown. CONCLUSION: This study shows differing responses to COVID-19 lockdown measures in children with severe obesity. On group level, PA significantly decreased and in substantial minorities eating styles and HRQoL deteriorated. Children with pre-existent psychosocial problems or pre-pandemic high external or emotional eating scores were most at risk. These children and their families should be targeted by health care professionals to minimize negative physical and mental health consequences.
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COVID-19 , Obesidade Mórbida , Adolescente , Adulto , COVID-19/prevenção & controle , Criança , Controle de Doenças Transmissíveis , Feminino , Humanos , Estilo de Vida , Masculino , Pandemias/prevenção & controle , Qualidade de Vida , SARS-CoV-2RESUMO
OBJECTIVE: Patients with pro-opiomelanocortin (POMC) defects generally present with early-onset obesity, hyperphagia, hypopigmentation and adrenocorticotropin (ACTH) deficiency. Rodent models suggest that adequate cleavage of ACTH to α-melanocortin-stimulating hormone (α-MSH) and desacetyl-α-melanocortin-stimulating hormone (d-α-MSH) by prohormone convertase 2 at the KKRR region is required for regulating food intake and energy balance. METHODS: We present 2 sisters with a novel POMC gene variant, leading to an ACTH defect at the prohormone convertase 2 cleavage site, and performed functional studies of this variant. RESULTS: The patients had obesity, hyperphagia and hypocortisolism, with markerly raised levels of ACTH but unaffected pigmentation. Their ACTH has reduced potency to stimulate the melanocortin (MC) 2 receptor, explaining their hypocortisolism. CONCLUSION: The hyperphagia and obesity support evidence that adequate cleavage of ACTH to α-MSH and d-α-MSH is also required in humans for feeding control.
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Hormônio Adrenocorticotrópico , Pró-Opiomelanocortina , Insuficiência Adrenal , Humanos , Hiperfagia/genética , Obesidade/genética , Pró-Opiomelanocortina/genética , Pró-Proteína Convertase 2 , alfa-MSHRESUMO
BACKGROUND: Chronic stress is often accompanied by alterations in the diurnal rhythm of hypothalamus-pituitary-adrenal activity. However, there are limited data on the diurnal rhythmicity of breast milk glucocorticoids (GCs) among women with psychological distress. We compared mothers who sought consultation at an expertise center for pregnant women with an increased risk of psychological distress with control mothers for GC diurnal rhythmicity in milk and saliva obtained at the same time. METHODS: We included 19 mothers who sought consultation at the psychiatry-obstetric-pediatric (POP) outpatient clinic and 44 control mothers. One month postpartum, mothers collected on average eight paired milk and saliva samples during a 24 h period. GC levels were measured using liquid chromatography-tandem mass spectrometry. GC rhythmicity parameters were determined with specialized software. RESULTS: For both milk and saliva, no group differences regarding GC rhythms were found. Milk cortisol area under the curve with respect to the ground was lower in the POP group than in the control group (p = 0.02). GC levels in human milk and saliva were highly correlated within each group (p < 0.001). CONCLUSION: Although there were no differences between groups in GC rhythmicity, the total amount of milk cortisol was lower in the POP group. Long-term follow-up is needed to address the impact of vertical transmission of breast milk GCs.
Assuntos
Ritmo Circadiano , Glucocorticoides/análise , Leite Humano/química , Estresse Psicológico , Adulto , Feminino , Humanos , Hidrocortisona/análise , Mães/psicologia , Gravidez , Gestantes , Psicopatologia , Saliva/químicaRESUMO
OBJECTIVE: Sex-specific differences in hypothalamic-pituitary-adrenal axis activity might explain why male preterm infants are at higher risk of neonatal mortality and morbidity than their female counterparts. We examined whether male and female preterm infants differed in cortisol production and metabolism at 10 days post-partum. DESIGN AND METHODS: This prospective study included 36 preterm born infants (18 boys) with a very low birth weight (VLBW) (<1.500 g). At 10 days postnatal age, urine was collected over a 4- to 6-h period. Glucocorticoid metabolites were measured using gas chromatography-mass spectrometry. Main outcome measures were: (1) cortisol excretion rate, (2) sum of all glucocorticoid metabolites, as an index of corticosteroid excretion rate, and (3) ratio of 11-OH/11-OXO metabolites, as an estimate of 11B-hydroxysteroid dehydrogenase (11B-HSD) activity. Differences between sexes, including interaction with Score of Neonatal Acute Physiology Perinatal Extension-II (SNAPPE II), sepsis and bronchopulmonary dysplasia (BPD), were assessed. RESULTS: No differences between sexes were found for cortisol excretion rate, corticosteroid excretion rate or 11B-HSD activity. Interaction was observed between: sex and SNAPPE II score on 11B-HSD activity (P = 0.04) and sex and BPD on cortisol excretion rate (P = 0.04). CONCLUSION: This study did not provide evidence for sex-specific differences in adrenocortical function in preterm VLBW infants on a group level. However, in an interaction model, sex differences became manifest under stressful circumstances. These patterns might provide clues for the male disadvantage in neonatal mortality and morbidity following preterm birth. However, due to the small sample size, the data should be seen as hypothesis generating.
RESUMO
Obesity is highly prevalent and comes with serious health burden. In a minority, a genetic cause is present which often results in therapy-resistant obesity. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue, which has beneficial effects on satiety and weight in common obesity. We present the effects of GLP-1 analogues in adults with a molecularly proven genetic cause of their overweight or obesity. All patients were treated with liraglutide 3.0 mg daily, in addition to intensive supportive lifestyle treatment. Anthropometrics, metabolic parameters, resting energy expenditure (REE), side effects, and subjectively reported satiety and quality of life were assessed. Two patients with 16p11.2 deletion syndrome and two patients with heterozygous pathogenic melanocortin-4 receptor variants were treated. At baseline, their age ranged between 21 and 32 years and body mass index (BMI) ranged between 28.1 and 55.7 kg/m2 . At follow-up (ranges 43 weeks-12 years), a mean change in BMI and waist circumference was observed of -5.7 ± 3.8 kg/m2 and -15.2 ± 21.1 cm, respectively. All patients achieved ≥5% weight loss, three of them lost ≥10% of their body weight. All patients reported improved quality of life and three of them reported ameliorated satiety. Moreover, improvement of glycaemic control and dyslipidaemia were seen. In two patients, REE before and during treatment was measured, which either increased (+26% of predicted REE) or decreased (-18% of predicted REE). Two patients experienced mild side effects for a brief period. In conclusion, our case series shows beneficial effects of GLP-1 analogues on weight, metabolic parameters and quality of life in all four patients with genetic obesity.