Andreas Hiemisch

Effects of obesity on human sexual development

Puberty is a period of physical and psychological maturation, with long-term effects on health. During the 20th century, a secular trend towards earlier puberty occurred in association with improvements in nutrition. The worldwide pandemic of childhood obesity has renewed interest in the relationship between body composition in childhood and the timing and tempo of puberty. Limited evidence suggests that earlier puberty is associated with a tendency towards central fat deposition; therefore, pubertal status needs to be carefully considered in the categorization of childhood and adolescent overweight and obesity. In the other direction, rapid early weight gain is associated with advanced puberty in both sexes, and a clear association exists between increasing BMI and earlier pubertal development in girls. Evidence in boys is less clear, with the majority of studies showing obesity to be associated with earlier puberty and voice break, although a subgroup of boys with obesity exhibits late puberty, perhaps as a variation of constitutional delay in growth and puberty. The possible mechanisms linking adiposity with pubertal timing are numerous, but leptin, adipocytokines and gut peptides are central players. Other possible mediators include genetic variation and environmental factors such as endocrine disrupting chemicals. This Review presents current evidence on this topic, highlighting inconsistencies and opportunities for future research.

The LIFE child study: a life course approach to disease and health

BackgroundProfound knowledge about child growth, development, health, and disease in contemporary children and adolescents is still rare. Epidemiological studies together with new powerful research technologies present exciting opportunities to the elucidation of risk factor-outcome associations with potentially major consequences for prevention, diagnosis and treatment.AimTo conduct a unique prospective longitudinal cohort study in order to assess how environmental, metabolic and genetic factors affect growth, development and health from fetal life to adulthood.MethodsThe ‘Leipzig Research Centre for Civilization Diseases (LIFE) Child Study’ focuses on two main research objectives: (1) monitoring of normal growth, development and health; (2) non-communicable diseases such as childhood obesity and its co-morbidities, atopy and mental health problems. Detailed assessments will be conducted alongside long-term storage of biological samples in 2,000 pregnant women and more than 10,000 children and their families.ResultsClose coordination and engagement of a multidisciplinary team in the LIFE Child study successfully established procedures and systems for balancing many competing study and ethical needs. Full participant recruitment and complete data collection started in July 2011. Early data indicate a high acceptance rate of the study program, successful recruitment strategies and the establishment of a representative cohort for the population of Leipzig. A series of subprojects are ongoing, and analyses and publications are on their way.DiscussionThis paper addresses key elements in the design and implementation of the new prospective longitudinal cohort study LIFE Child. Given the recognized need for long-term data on adverse effects on health and protective factors, our study data collection should provide magnificent opportunities to examine complex interactions that govern the emergence of non-communicable diseases.

The LIFE Child study: a population-based perinatal and pediatric cohort in Germany

The LIFE Child study is a large population-based longitudinal childhood cohort study conducted in the city of Leipzig, Germany. As a part of LIFE, a research project conducted at the Leipzig Research Center for Civilization Diseases, it aims to monitor healthy child development from birth to adulthood and to understand the development of lifestyle diseases such as obesity. The study consists of three interrelated cohorts; the birth cohort, the health cohort, and the obesity cohort. Depending on age and cohort, the comprehensive study program comprises different medical, psychological, and sociodemographic assessments as well as the collection of biological samples. Optimal data acquisition, process management, and data analysis are guaranteed by a professional team of physicians, certified study assistants, quality managers, scientists and statisticians. Due to the high popularity of the study, more than 3000 children have already participated until the end of 2015, and two-thirds of them participate continuously. The large quantity of acquired data allows LIFE Child to gain profound knowledge on the development of children growing up in the twenty-first century. This article reports the number of available and analyzable data and demonstrates the high relevance and potential of the study.

Pediatric reference data of serum lipids and prevalence of dyslipidemia: Results from a population-based cohort in Germany.

BACKGROUND Serum lipid concentrations are thought to be risk factors for the development of cardiovascular disease. The present study aims to investigate the prevalence of dyslipidemia and provide sex- and age-related reference values for triglycerides, total cholesterol, LDL and HDL cholesterol as well as apolipoproteins A1 and B by using modern analytical approaches. MATERIALS AND METHODS Venous blood and anthropometric data were collected from 2571 subjects of the LIFE Child study, aged between 0.5 and 16years. Age- and gender-related reference intervals (3rd and 97th percentiles) were established by using Coles LMS method. RESULTS Serum concentrations of TC, LDL-C, TG and ApoB were higher in girls than in boys. In girls TC reached peak levels two years earlier than in boys. Triglyceride levels initially declined until the school age. Until early adolescence there was a steady increase. The LDL-C concentrations in girls and boys followed similar patterns to that of TC. Up to the age of 8years, a continuous increase in HDL levels for both sexes was found. Due to the strong correlation between HDL-C and ApoA1 (r=0.87) or rather between LDL-C and ApoB (r=0.93), the respective percentiles showed very similar patterns. Dyslipidemia prevalence were as follows: increased TC 7.8%, increased LDL 6.1%, increased TG 0-9years 22.1%, increased TG 10-16years 11.7%, and decreased HDL 8.0%. CONCLUSION Age- and sex-related trends for all parameters are similar to those of the German KIGGS study. With the exception of HDL cholesterol, the prevalence of dyslipidemias in the German LIFE Child cohort are similar to the US-American prevalence.

Evaluation of hair cortisol and cortisone change during pregnancy and the association with self-reported depression, somatization, and stress symptoms

Abstract Hair cortisol levels are used to measure long-term stress, while its inactive metabolite cortisone is often not assessed. We measured hair cortisol concentrations (HCC) and hair cortisone concentrations (HCNC) via liquid chromatography quadrupole linear ion trap mass spectrometry (LC-MS3) in 62 pregnant women who participated in the LIFE CHILD STUDY in their 2nd and 3rd trimester between 12/2011 and 11/2014. Sociodemographic factors, pregnancy-related factors, and hair characteristics were assessed. Degree of severity of depression, somatization, and stress were evaluated in both trimesters with a self-reported Patient Health Questionnaire (PHQ). Multivariate regression analyses were conducted between HCC and potential influencing factors, as well as with subscales of the PHQ, with HCNC and with the ratio of HCNC to HCC. Spearman correlation coefficients were calculated between steroid concentrations and subscale scores of the PHQ, as well as between the log2-fold change in HCC and HCNC and the change in PHQ subscale scores. HCC increased 1.3-fold and HCNC increased 1.5-fold by the 3rd trimester. HCNC was more than three times higher than HCC in both trimesters. We found significant associations of PHQ subscores with HCNC. The PHQ depression score was negatively correlated with HCNC in the 2nd trimester (p < .05). The PHQ stress score change was negatively correlated with the fold change of HCNC (p < .05) and with the change in the ratio of HCNC to HCC (p < .001). Our study suggests an association of cortisol/cortisone metabolism with self-reported stress in the 2nd and 3rd trimester of pregnancy. Since associations with PHQ subscores were only found with cortisone or the ratio of cortisone to cortisol, but not with cortisol alone, both cortisone and cortisol should be used as a marker for stress in pregnant woman.

The hyporeactivity of salivary cortisol at stress test (TSST-C) in children with internalizing or externalizing disorders is contrastively associated with α-amylase

BACKGROUND Stress biomarkers of the autonomic nervous system and hypothalamic-pituitary-adrenal axis (HPA-axis) can be measured via alpha-amylase (AA) and cortisol and cortisone in saliva. Objectives were to determine 1) the response patterns of cortisol, cortisone, and AA under both circadian conditions and the Trier Social Stress Test for Children (TSST-C), 2) which reactivity index is most suitable to differentiate internalizing or externalizing disorders from controls, and to explore 3) the interaction between AA and cortisol in the presence of internalizing or externalizing disorders. METHODS Saliva samples (n = 2893) from children with internalizing (n = 55) or externalizing disorders (n = 33) and healthy children (n = 81) were analyzed for cortisol, cortisone, and AA under circadian conditions and TSST-C. RESULTS Circadian rhythm of three biomarkers did not differ between diagnostic groups. Age and gender were significant predictors for cortisol and awakening time influenced all three biomarkers significantly. TSST-C responses appeared sequentially in the order of AA, cortisol, and cortisone. Trajectories of cortisol and cortisone responses, not in AA, were significantly lower in children with internalizing or externalizing disorders than in healthy children. Cortisol percentage increase appeared to be the most suitable reactivity index to detect the difference between the diagnostic groups. Internalizing disorders had a negative association between AA decrease and cortisol increase (β = -.199, p < .05, R(2) = .304). Externalizing disorders had a positive association between AA baseline and cortisol increase (β = .229, p < .05, R(2) = .304). CONCLUSION An altered HPA-axis response during stress might result from chronic allostatic load in internalizing disorders and underaroused stress response system in externalizing disorders.

Association between IgE-mediated allergies and diabetes mellitus type 1 in children and adolescents.

Type 1 diabetes mellitus (T1DM) is characterized by an immunological reaction that is dominated by type‐1 T helper (Th1) cells, whereas immunoglobulin E (IgE)‐mediated allergies are associated with Th2 cell. According to the Th1/Th2‐hypothesis, the immune system is said to either develop into the direction of Th1 or Th2 cells. This would mean that a child developing T1DM is unlikely to develop an IgE‐mediated allergy and vice versa.

Nocturnal levels of chemerin and progranulin in adolescents: influence of sex, body mass index, glucose metabolism and sleep.

Abstract Background: Adipokines have been implicated in obesity, insulin resistance and sleep regulation. However, the role of chemerin and progranulin, two recently described adipokines, in the context of sleep remains unclear. The aim of this study was to compare nocturnal serum chemerin and progranulin levels between overweight/obese and normal-weight adolescents and to assess variations by sex, across different sleep stages and in relation to glucose metabolism. Methods: The study sample included 34 overweight/obese and 32 normal-weight adolescents from secondary schools and the Leipzig Research Center for Civilization Diseases (LIFE) Child study cohort. We obtained longitudinal serum adipokine levels during in-laboratory polysomnography followed by an oral glucose tolerance test. Results: Overweight/obese adolescents had significantly higher mean nocturnal serum chemerin area under the curve (AUC) levels (348.2±133.3 vs. 241.7±67.7 vs. ng/mL×h, p<0.001) compared to normal-weight controls. In detail, higher chemerin AUC levels in obese/overweight subjects were exclusively due to increased levels in females. No overall difference for serum progranulin AUC was found between the groups. However, when assessing sex-specific levels, serum progranulin AUC levels were ~30% higher in overweight/obese males compared to overweight/obese females. Of note, nocturnal serum chemerin and progranulin AUC did not exhibit a correlation with markers of glucose metabolism or sleep stages. Conclusions: Collectively, we report a sexual dimorphism in nocturnal progranulin and chemerin levels, which may help explain underlying differences in energy balance and body composition between males and females in the context of obesity.

The acceptance of the K‐SADS‐PL – potential predictors for the overall satisfaction of parents and interviewers

The presented study investigated the interviewee (parents) and interviewer acceptance of the semi‐structured diagnostic interview Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children Present Lifetime version (KSADS‐PL; German version). Seventeen certified interviewers conducted 231 interviews (interviewers conducted several interviews; interviewees were only questioned once). Interviewees and interviewers anonymously rated their acceptance right after the interview was finished. The nested data structure was analysed regarding an individual interviewer bias and potential predictors of overall satisfaction. Therefore, factors improvable by interviewer training were included, as well as fixed factors which cannot be improved by professional training. The overall satisfaction was evaluated as highly positive with significant higher interviewee and interviewer ratings in the research as compared to the clinical recruitment setting. An individual bias of the interviewer on his or her own acceptance over time, but not on the evaluation of the corresponding interviewee was found. Neither the professional background nor the gender of the interviewer had a significant contribution in predicting these differences. The interviewer model showed no significant change over time and only the interview duration and the interviewee acceptance were significant predictors for interviewer overall satisfaction. Regarding the interviewee model, just the interviewer acceptance was a significant predictor. Copyright Copyright

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.