[Symptoms, Comorbidities and Therapy of Children and Adolescents with Gender Dysphoria]. / Symptome, Komorbiditäten und Therapie von Kindern und Jugendlichen mit Geschlechtsdysphorie.

INTRODUCTION: Gender dysphoria (GD) in childhood and adolescence is characterized by an incongruence between sex at birth and gender identity, which usually increases during puberty. Gender dysphoric children and adolescents often suffer from psychological comorbidities such as depression. The purpose of our study is to give an overview of the patients treated in our clinic. METHODS: We analyzed data of 66 patients who presented with GD at our outpatient clinic between 2005 and 2018. RESULTS: We noted a rise of presentations with one or no patient with GD per year between 2005 and 2008 up to 18 patients in 2018, although the percentage of all 14.339 endocrinological outpatients (2005-2018) is low. 54 patients were assigned as female and 12 as male at birth resulting in a ratio of 4.5:1. The mean age at their first appointment was 13.6 years. 49 patients (74%) had reached tanner stadium P3/B3 or P3/G3. 30 (45%) showed symptoms of a comorbidity related to GD. 48 (73%) showed symptoms of GD before puberty. 15 patients (23%) experienced a negative response regarding their outing and 17 (26%) were victims of mobbing in school. CONCLUSION: The number of patients increased in the last years. About half of the patients suffered from a psychological comorbidity. They often experienced negative response regarding their GD in the family. The variability of appearance and the comorbidities pose the challenge in the treatment of gender dysphoric children and adolescents.

An MRM-Based Multiplexed Quantification Assay for Human Adipokines and Apolipoproteins.

Adipokines and apolipoproteins are key regulators and potential biomarkers in obesity and associated diseases and their quantitative assessment is crucial for functional analyses to understand disease mechanisms. Compared to routinely used ELISAs, multiple reaction monitoring (MRM)-based mass spectrometry allows multiplexing and detection of proteins for which antibodies are not available. Thus, we established an MRM method to quantify 9 adipokines and 10 apolipoproteins in human serum. We optimized sample preparation by depleting the two most abundant serum proteins for improved detectability of low abundant proteins. Intra-day and inter-day imprecision were below 16.5%, demonstrating a high accuracy. In 50 serum samples from participants with either normal weight or obesity, we quantified 8 adipokines and 10 apolipoproteins. Significantly different abundances were observed for five adipokines (adipsin, adiponectin, chemerin, leptin, vaspin) and four apolipoproteins (apo-B100/-C2/-C4/-D) between the body mass index (BMI) groups. Additionally, we applied our MRM assay to serum samples from normal weight children and human adipocyte cell culture supernatants to proof the feasibility for large cohort studies and distinct biological matrices. In summary, this multiplexed assay facilitated the investigation of relationships between adipokines or apolipoproteins and phenotypes or clinical parameters in large cohorts, which may contribute to disease prediction approaches in the future.

Validity and intraobserver reliability of three-dimensional scanning compared with conventional anthropometry for children and adolescents from a population-based cohort study.

BACKGROUND: Conventional anthropometric measurements are time consuming and require well trained medical staff. To use three-dimensional whole body laser scanning in daily clinical work, validity, and reliability have to be confirmed. METHODS: We compared a whole body laser scanner with conventional anthropometry in a group of 473 children and adolescents from the Leipzig Research Centre for Civilization Diseases (LIFE-Child). Concordance correlation coefficients (CCC) were calculated separately for sex, weight, and age to assess validity. Overall CCC (OCCC) was used to analyze intraobserver reliability. RESULTS: Body height and the circumferences of waist, hip, upper arm, and calf had an "excellent" (CCC ≥ 0.9); neck and thigh circumference, a "good" (CCC ≥ 0.7); and head circumference, a "low" (CCC < 0.5) degree of concordance over the complete study population. We observed dependencies of validity on sex, weight, and age. Intraobserver reliability of both techniques is "excellent" (OCCC ≥ 0.9). CONCLUSION: Scanning is faster, requires less intensive staff training and provides more information. It can be used in an epidemiologic setting with children and adolescents but some measurements should be considered with caution due to reduced agreement with conventional anthropometry.

Sixteen-week multicentre randomised controlled trial to study the effect of the consumption of an oat beta-glucan-enriched bread versus a whole-grain wheat bread on glycaemic control among persons with pre-diabetes: a study protocol of the CarbHealth study.

INTRODUCTION: In 2012, the estimated global prevalence of pre-diabetes was 280 million, and the prevalence is expected to rise to 400 million by 2030. Oat-based foods are a good source of beta-glucans, which have been shown to lower postprandial blood glucose. Studies to evaluate the effectiveness of the long-term intake of beta-glucan-enriched bread as part of a habitual diet among individuals with pre-diabetes are needed. Therefore, we designed a multicentre intervention study in adults with pre-diabetes to investigate the effects of consumption of an oat-derived beta-glucan-enriched bread as part of a normal diet on glycated haemoglobin (HbA1c) in comparison to consumption of whole-grain wheat bread. METHODS AND ANALYSIS: The CarbHealth trial is a multicentre double-blind randomised controlled 16-week dietary intervention trial in participants 40-70 years of age with a body mass index of ≥27 kg/m2 and HbA1c of 35-50 mmol/mol. The study is conducted at four universities located in Norway, Sweden and Germany and uses intervention breads specifically designed for the trial by Nofima AS. The aim is to recruit 250 participants. The primary outcome is the difference in HbA1c between the intervention and the control groups. The main analysis will include intervention group, study centre and baseline HbA1c as independent variables in an analysis of covariance model. ETHICS AND DISSEMINATION: The study protocol was approved by respective ethical authorities in participating countries. The results of the study will be communicated through publication in international scientific journals and presentations at (inter)national conferences. TRIAL REGISTRATION NUMBER: NCT04994327.

Pediatric Reference Intervals for Thyrotropin, Free Triiodothyronine, and Free Thyroxine and the Relevance of Body Mass Index and Puberty in Measurement Interpretation.

Background: The present study aimed to establish age- and sex-specific reference intervals for serum concentrations of thyrotropin (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) in healthy children and adolescents. Additionally, we investigated the association of TSH, fT3, and fT4 with putative influencing factors, such as sex, body mass index (BMI), and puberty. Methods: A total of 9404 blood serum samples from 3140 children and adolescents without thyroid affecting diseases were included in determining TSH, fT3, and fT4 levels and age- and sex-specific reference ranges. To investigate the association of TSH, fT3, and fT4 with age, sex, weight status, and the role of puberty-based changes, the hormone levels and BMI values were converted to standard deviation scores (SDS). Results: In general, TSH, fT3, and fT4 were found to be age- and sex-dependent. Puberty was accompanied by decreased TSH, decreased fT3 with a temporary peak in males, and a temporary nadir of fT4 in Tanner stage 3 for both sexes. BMI-SDS was positively associated with TSH-SDS (ß = 0.081, p < 0.001); the effect was more pronounced in overweight subjects (ß = 0.142, p < 0.01) and insignificantly negative in underweight subjects (ß = -0.047, p > 0.05). BMI-SDS was positively associated with fT3-SDS (ß = 0.066, p < 0.001) and negatively associated with fT4-SDS (ß = -0.135, p < 0.001), with the effect insignificantly less negative in overweight children (ß = -0.055, p > 0.05). Conclusions: Age- and sex-specific reference intervals are important for the interpretation of measurements of TSH, fT3, and fT4 in children and adolescents. Influencing factors such as BMI and puberty should be taken into consideration when using measurements of TSH and thyroid hormones in the diagnosis, treatment, and monitoring of thyroid diseases. Clinical Trial Registration number: NCT02550236.

Age- and Sex-Related Percentiles of Skinfold Thickness, Waist and Hip Circumference, Waist-to-Hip Ratio and Waist-to-Height Ratio: Results from a Population-Based Pediatric Cohort in Germany (LIFE Child).

BACKGROUND: Skinfold thickness (ST), waist circumference (WC) and hip circumference (HC) measurements are simple methods for assessing fat tissue at defined body parts. We examined these parameters in a cohort of healthy children and adolescents in Leipzig. Our study provides current percentile curves for biceps, triceps, subscapular and iliac crest ST, plus WC, HC, waist-to-hip ratio and waist-to-height ratio. METHODS: 6,344 visits were recorded involving 2,363 individuals from 3 to 16 years in age. Continuous age- and gender-related percentiles (3rd, 10th, median, 90th, 97th percentiles) were estimated using Cole's LMS method. RESULTS: For biceps and triceps ST, boys show a peak at the beginning of adolescence with a subsequent decrease, while percentile values among girls rise across the age range. Subscapular and iliac crest percentiles also show increasing curves with disproportionately high values for P90 and P97. Boys show higher values of WC, girls have higher levels of HC. WC and HC median percentiles constantly increase in both sexes with a plateau at the age of 16 for girls. CONCLUSION: Trends for all parameters of body fat are in line with other national and international studies. Unlike the KiGGS study, our study provides circumference data across the whole of our age range, i.e. from 3 to 16 years.

Leptin inhibits cell growth of human vascular smooth muscle cells.

Elevated leptin levels are thought to contribute to the individual cardiovascular risk, however, the role of leptin in the pathogenesis of atherosclerosis remains unclear. The aim of our study was to elucidate the effects of leptin on growth of human vascular smooth muscle cells (VSMC) and leptin receptor expression. By establishing a new quantitative real-time PCR for leptin receptor (ObR) isoforms we showed that the short isoforms of ObR were expressed in a 10- to 27-fold excess compared to the long isoform in cultured human VSMCs. Incubation of VSMCs with 100 ng/ml leptin downregulated the short isoforms significantly, whereas the long isoform was not influenced. Increasing leptin concentrations of 50 and 100 ng/ml significantly reduced the cell number of VSMCs compared to untreated controls. Our findings suggest a role for leptin in vascular smooth muscle cell growth, associated to a downregulation of leptin receptor isoforms.

Adipocytokines: leptin--the classical, resistin--the controversical, adiponectin--the promising, and more to come.

With the growing prevalence of obesity, scientific interest in the biology of adipose tissue has been extended to the secretory products of adipocytes, since they are increasingly shown to affect several aspects in the pathogenesis of obesity-related diseases. The cloning of the ob gene is consistent with this concept and suggests that body fat content in adult rodents is regulated by a negative feedback loop centred in the hypothalamus. In recent years, a number of additional signalling molecules secreted by adipose tissue have been discovered, commonly referred to as 'adipocytokines'. Among these, adiponectin is perhaps the most interesting and promising compound for the clinician since it has profound protective actions in the pathogenesis of diabetes and cardiovascular disease. Adiponectin is low in obese subjects and, in particular, insulin-resistant patients. In contrast, resistin seems to be of greater relevance in relation to the immune stress response than in the regulation of glucose homeostasis. However, inflammatory processes have recently been connected with the development of atherosclerosis. Finally, little is known regarding the clinical relevance of visfatin. Recent research has revealed many functions of adipocytokines extending far beyond metabolism, such as immunity, cancer and bone formation. This report aims to review some of the recent topics of adipocytokine research that may be of particular importance.