The Demand-Control Model as a Predictor of Depressive Symptoms-Interaction and Differential Subscale Effects: Prospective Analyses of 2212 German Employees.

Testing assumptions of the widely used demand-control (DC) model in occupational psychosocial epidemiology, we investigated (a) interaction, i.e., whether the combined effect of low job control and high psychological demands on depressive symptoms was stronger than the sum of their single effects (i.e., superadditivity) and (b) whether subscales of psychological demands and job control had similar associations with depressive symptoms. Logistic longitudinal regression analyses of the 5-year cohort of the German Study of Mental Health at Work (S-MGA) 2011/12-2017 of 2212 employees were conducted. The observed combined effect of low job control and high psychological demands on depressive symptoms did not indicate interaction (RERI = -0.26, 95% CI = -0.91; 0.40). When dichotomizing subscales at the median, differential effects of subscales were not found. When dividing subscales into categories based on value ranges, differential effects for job control subscales (namely, decision authority and skill discretion) were found (p = 0.04). This study does not support all assumptions of the DC model: (1) it corroborates previous studies not finding an interaction of psychological demands and job control; and (2) signs of differential subscale effects were found regarding job control. Too few prospective studies have been carried out regarding differential subscale effects.

Home-Based Telework and Presenteeism Across Europe.

OBJECTIVE: Flexible work arrangements such as telework are gaining importance. Although telework is accompanied by advantages for employees such as increased flexibility, current research reveals associations between home-based telework and self-endangering behavior such as sickness presenteeism. As empirical evidence is still scarce, we explore the relationship between home-based telework and sickness presenteeism across Europe. METHODS: We perform multilevel analyses including 25,465 individuals who responded to the 6th wave of the European Working Conditions Survey 2015. RESULTS: Home-based telework is positively related to sickness presenteeism. The results are quite robust across different measures of sickness presenteeism and to several sensitivity analyses. CONCLUSION: Although sickness presenteeism can be functional for specific illnesses, organizations should be aware of possible risks related to home-based telework. They should design telework in a way that it reduces triggers for self-endangering behavior.

[Neuroenhancement in four occupations in Germany]. / Neuroenhancement in Deutschland am Beispiel von vier Berufsgruppen.

OBJECTIVE: The aim of this study was to assess the prevalence of pharmacological neuroenhancement in 4 occupations and to investigate its association with psychosocial working conditions and mental health. METHODS: In the study on "Neuroenhancement Behaviour in the Context of Stressful Workload - empirical Studies on Employees", 4166 employed physicians, advertising experts, publishers and software developers were surveyed with computer-assisted personal interviews. Lifetime, 12 months and 4 weeks prevalence rates with corresponding confidence intervals were calculated. The association of neuroenhancement with psychosocial working conditions and mental health were estimated in Poisson regression models. RESULTS: The lifetime prevalence of pharmacological neuroenhancement was 8.4%, the 12 months prevalence 2.9% and the 4 weeks prevalence 1.3%. Advertising experts and female software developers showed elevated prevalence rates for neuroenhancement. Psychosocial working conditions, such as support from colleagues, role clarity, emotional demands and job insecurity were associated with neuroenhancement in men. Burnout and depressive symptoms were related to an increase in neuroenhancement. CONCLUSIONS: Compared to samples from the general population or the overall working population, the estimated prevalence rates among the investigated occupations were slightly elevated. Burnout and depressive symptoms might operate as potential risk factors or consequences of pharmacological neuroenhancement.

[Working Conditions and Mental Health Among Salaried Physicians: A Nationwide Comparison With a Representative Sample of Employees]. / Arbeitsbedingungen und psychische Gesundheit bei sozialversicherungspflichtig beschäftigten Ärzten: Ein bundesweiter Vergleich mit einer repräsentativen Beschäftigtenstichprobe.

AIM: Do the amount of workload, strain and the association between both differ between employed physician and other employees subject to social security contributions? This is investigated in this present study by comparing two representative samples. METHODS: Psycho-social working conditions were by assessed computer-assisted personal interviews and supplemented by questions about burnout and depressive symptoms. The associations were investigated by linear regression analysis including moderating effects due to differences between occupations. RESULTS: The score for depressive symptoms was lower among male and female physicians than in the comparison groups. Moreover, male physician had higher scores for burnout. Quantitative demands and job insecurity were associated with an increase of scores for burnout and depressive symptoms. Higher quality of leadership, role clarity, and decision latitude contributed to a decrease of both scores. Additional effects were found for hours worked per week (females) and number of night shifts (males). The moderating effect of occupational group was detected for quantitative demands and decision latitude. CONCLUSION: The associations of working conditions with mental health indicators are similar in the compared groups. There is a higher workload and higher level of burnout among physicians but there is no indication for more depressive symptoms.

Work-Related Determinants of Burnout in a Nationally Representative Sample of German Employees: Results From the Study on Mental Health at Work.

OBJECTIVE: The aim of the study was to present first representative data on burnout measured as exhaustion in German employees. METHODS: Data were taken from the Study on Mental Health at Work (n = 4058). Computer-assisted personal interviews were conducted in 2011 to 2012. Multiple linear regression models were estimated to investigate the association between work-related and personal variables and burnout. RESULTS: Severe burnout was detected in nearly 3% of employees. Job demands were associated with higher burnout scores, more resources with lower scores. Independent of personal factors, higher quantitative demands (men: regression coefficient [ß] = 0.19; 95% confidence interval [CI], 0.16 to 0.23; women: ß = 0.24; 95% CI, 0.20 to 0.27) was identified as the strongest predictor of burnout measured as exhaustion. The model explained 28% to 33% of the total variance. CONCLUSIONS: Quantitative demands seem to be important risk factors for burnout independent of critical life events and general self-efficacy.

12-month trajectories of depressive symptoms among nurses-Contribution of personality, job characteristics, coping, and burnout.

BACKGROUND: Job related factors have been associated with higher risk for developing depression, but past studies lacked full consideration of individual factors such as personality and coping. We sought to evaluate associations of personality, coping, job characteristics, and burnout with 12-month trajectories of depressive symptoms among nursing workers. METHODS: Cohort of nursing workers (N = 281) in a private hospital system, with baseline assessments of personality, job characteristics, and coping. Burnout and depression were measured at baseline and during monthly follow-ups. Linear mixed modeling was used to examine contributions to between- and within-individual variation in monthly depressive symptoms. RESULTS: Personality trait of negative affectivity accounted for 36% of between-individual variation in depressive symptoms over 12 months, while job characteristics and coping explained an additional 5% and 8% of this variation, respectively. Exhaustion dimension of burnout was associated with between-individual variation in depressive symptoms (fixed effect ß coefficient 2.44, p < 0.001), but not with within-individual variation in symptoms. Disengagement dimension of burnout was not associated with between-individual variation in depressive symptoms, but contributed to within-individual variation in depressive symptoms over time (fixed effect ß coefficient 0.52, p = 0.01). LIMITATIONS: Participants were nursing workers within a single hospital system. Participants who were excluded due to missing baseline data were more likely of non-white race, which may also limit the generalizability of our results. We used latent variables to represent certain job and coping characteristics, which may make our results less comparable with other studies examining the role of these factors in work-associated depression. CONCLUSIONS: Future interventions to prevent depression in healthcare workers should consider multiple job and individual factors. Potential components include strategies to manage negative affectivity and reduce avoidant coping, such as cognitive reframing and mindfulness-based techniques, and organizational approaches to address burnout through augmentation of job resources.

Inner-city green space and its association with body mass index and prevalent type 2 diabetes: a cross-sectional study in an urban German city.

OBJECTIVE: The accessibility of green space is an important aspect of the urban residential environment and has been found to be beneficial for health and well-being. This study investigates the association between different indicators of green space and the outcomes body mass index (BMI) and prevalent type 2 diabetes in an urban population. DESIGN: Population-based cross-sectional study. SETTING: Dortmund, a city located in the industrial Ruhr area in Western Germany. PARTICIPANTS: 1312 participants aged 25-74 years from the Dortmund Health Study. METHODS: The participants' addresses were geocoded and shapefiles of statistical districts, road network and land use, as well as data on neighbourhood characteristics were obtained at baseline. Three indicators of green space were constructed using geographical information systems: proportion of green space, recreation location quotient (RLQ) weighted by population and distance to the next park or forest. Multilevel linear and logistic regression analyses on the association of green space with BMI and type 2 diabetes were performed, adjusted by individual-level characteristics and neighbourhood unemployment rate. RESULTS: The multilevel regression analyses showed no association between green space and BMI. In contrast, the three indicators of green space were significantly associated with type 2 diabetes. Residents of neighbourhoods with a low RLQ had a 2.44 (95% CI 1.01 to 5.93) times higher odds to have type 2 diabetes compared with residents of high RLQ neighbourhoods. Likewise, residing more than 0.8 km away from the nearest park or forest increased the odds of type 2 diabetes (OR 1.71, 95% CI 1.05 to 2.77). CONCLUSIONS: This study indicates that green space and its spatial accessibility might play a role in the development of type 2 diabetes. Further research is needed to clarify this association.

Exploring the putative self-binding property of the human farnesyltransferase alpha-subunit.

Farnesylation is an important post-translational protein modification in eukaryotes. Farnesylation is performed by protein farnesyltransferase, a heterodimer composed of an α- (FTα) and a ß-subunit. Recently, homodimerization of truncated rat and yeast FTα has been detected, suggesting a new role for FTα homodimers in signal transduction. We investigated the putative dimerization behaviour of human and rat FTα. Different in vitro and in vivo approaches revealed no self-dimerization and a presumably artificial formation of homotrimers and higher homo-oligomers in vitro. Our study contributes to the clarification of the physiological features of FTase in different species and may be important for the ongoing development of FTase inhibitors.

The Study on Mental Health at Work: Design and sampling.

AIMS: The Study on Mental Health at Work (S-MGA) generates the first nationwide representative survey enabling the exploration of the relationship between working conditions, mental health and functioning. This paper describes the study design, sampling procedures and data collection, and presents a summary of the sample characteristics. METHODS: S-MGA is a representative study of German employees aged 31-60 years subject to social security contributions. The sample was drawn from the employment register based on a two-stage cluster sampling procedure. Firstly, 206 municipalities were randomly selected from a pool of 12,227 municipalities in Germany. Secondly, 13,590 addresses were drawn from the selected municipalities for the purpose of conducting 4500 face-to-face interviews. The questionnaire covers psychosocial working and employment conditions, measures of mental health, work ability and functioning. Data from personal interviews were combined with employment histories from register data. Descriptive statistics of socio-demographic characteristics and logistic regressions analyses were used for comparing population, gross sample and respondents. RESULTS: In total, 4511 face-to-face interviews were conducted. A test for sampling bias revealed that individuals in older cohorts participated more often, while individuals with an unknown educational level, residing in major cities or with a non-German ethnic background were slightly underrepresented. CONCLUSIONS: There is no indication of major deviations in characteristics between the basic population and the sample of respondents. Hence, S-MGA provides representative data for research on work and health, designed as a cohort study with plans to rerun the survey 5 years after the first assessment.

Anthropometric markers and their association with incident type 2 diabetes mellitus: which marker is best for prediction? Pooled analysis of four German population-based cohort studies and comparison with a nationwide cohort study.

OBJECTIVE: To compare the association between different anthropometric measurements and incident type 2 diabetes mellitus (T2DM) and to assess their predictive ability in different regions of Germany. METHODS: Data of 10,258 participants from 4 prospective population-based cohorts were pooled to assess the association of body weight, body mass index (BMI), waist circumference (WC), waist-to-hip-ratio (WHR) and waist-to-height-ratio (WHtR) with incident T2DM by calculating HRs of the crude, adjusted and standardised markers, as well as providing receiver operator characteristic (ROC) curves. Differences between HRs and ROCs for the different anthropometric markers were calculated to compare their predictive ability. In addition, data of 3105 participants from the nationwide survey were analysed separately using the same methods to provide a nationally representative comparison. RESULTS: Strong associations were found for each anthropometric marker and incidence of T2DM. Among the standardised anthropometric measures, we found the strongest effect on incident T2DM for WC and WHtR in the pooled sample (HR for 1 SD difference in WC 1.97, 95% CI 1.75 to 2.22, HR for WHtR 1.93, 95% CI 1.71 to 2.17 in women) and in female DEGS participants (HR for WC 2.24, 95% CI 1.91 to 2.63, HR for WHtR 2.10, 95% CI 1.81 to 2.44), whereas the strongest association in men was found for WHR among DEGS participants (HR 2.29, 95% CI 1.89 to 2.78). ROC analysis showed WHtR to be the strongest predictor for incident T2DM. Differences in HR and ROCs between the different markers confirmed WC and WHtR to be the best predictors of incident T2DM. Findings were consistent across study regions and age groups (<65 vs ≥ 65 years). CONCLUSIONS: We found stronger associations between anthropometric markers that reflect abdominal obesity (ie, WC and WHtR) and incident T2DM than for BMI and weight. The use of these measurements in risk prediction should be encouraged.

Association of Change of Anthropometric Measurements With Incident Type 2 Diabetes Mellitus: A Pooled Analysis of the Prospective Population-Based CARLA and SHIP Cohort Studies.

Our objective was to investigate the association of change of anthropometric measurements and the incidence of type 2 diabetes mellitus (T2DM) within a pooled sample of 2 population-based cohorts.A final sample of 1324 women and 1278 men aged 31 to 83 years from 2 prospective cohorts in Germany, the CARLA (Cardiovascular Disease - Living and Ageing in Halle) and the SHIP study (Study of Health in Pomerania), were pooled. The association of change of body weight and waist circumference (WC) with incidence of T2DM was assessed by calculating sex-specific hazard ratios (HRs). We investigated the absolute change of markers of obesity as well as change relative to the baseline value and estimated crude and adjusted HRs. Furthermore, we conducted the analyses stratified by obesity status and age (<60 vs ≥60 years) at baseline.Associations were found for both change of body weight and WC and incidence of T2DM in the crude and adjusted analyses. In the stratified study sample, those participants with a body mass index of <30 kg/m at baseline showed considerably lower HRs compared with obese women and men for both weight and WC. In the age-stratified analysis, we still found associations between change of weight and WC and incident T2DM with only marginal differences between the age groups.Our study showed associations of change of weight and WC as markers of obesity with incidence of T2DM. Keeping a healthy and primarily stable weight should be the goal for preventing the development of T2DM.

Regional differences in the incidence of self-reported type 2 diabetes in Germany: results from five population-based studies in Germany (DIAB-CORE Consortium).

BACKGROUND: Population-based data are paramount to investigate the long-term course of diabetes, for planning in healthcare and to evaluate the cost-effectiveness of primary prevention. We analysed regional differences in the incidence of self-reported type 2 diabetes mellitus in Germany. METHODS: Data of participants (baseline age 45-74 years) from five regional population-based studies conducted between 1997 and 2010 were included (mean follow-up 2.2-7.1 years). The incidence of self-reported type 2 diabetes mellitus at follow-up was compared. The incidence rates per 1000 person-years (95% CI) and the cumulative incidence (95% CI) from regional studies were directly standardised to the German population (31 December 2007) and weighted by inverse probability weights for losses to follow-up. RESULTS: Of 8787 participants, 521 (5.9%) developed type 2 diabetes mellitus corresponding to an incidence rate of 11.8/1000 person-years (95% CI 10.8 to 12.9). The regional incidence was highest in the East and lowest in the South of Germany with 16.9 (95% CI 13.3 to 21.8) vs 9.3 (95% CI 7.4 to 11.1)/1000 person-years, respectively. The incidence increased with age and was higher in men than in women. CONCLUSIONS: The incidence of self-reported type 2 diabetes mellitus shows regional differences within Germany. Prevention measures need to consider sex-specific differences and probably can be more efficiently introduced toward those regions in need.

Gender differences in the association of individual social class and neighbourhood unemployment rate with prevalent type 2 diabetes mellitus: a cross-sectional study from the DIAB-CORE consortium.

OBJECTIVE: To analyse gender differences in the relationship of individual social class, employment status and neighbourhood unemployment rate with present type 2 diabetes mellitus (T2DM). DESIGN: Five cross-sectional studies. SETTING: Studies were conducted in five regions of Germany from 1997 to 2006. PARTICIPANTS: The sample consisted of 8871 individuals residing in 226 neighbourhoods from five urban regions. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalent T2DM. RESULTS: We found significant multiplicative interactions between gender and the individual variables--social class and employment status. Social class was statistically significantly associated with T2DM in men and women, whereby this association was stronger in women (lower vs higher social class: OR 2.68 (95% CIs 1.66 to 4.34)) than men (lower vs higher social class: OR 1.78 (95% CI 1.22 to 2.58)). Significant associations of employment status and T2DM were only found in women (unemployed vs employed: OR 1.73 (95% CI 1.02 to 2.92); retired vs employed: OR 1.77 (95% CI 1.10 to 2.84); others vs employed: OR 1.64 (95% CI 1.01 to 2.67)). Neighbourhood unemployment rate was associated with T2DM in men (high vs low tertile: OR 1.52 (95% CI 1.18 to 1.96)). Between-study and between-neighbourhood variations in T2DM prevalence were more pronounced in women. The considered covariates helped to explain statistically the variation in T2DM prevalence among men, but not among women. CONCLUSIONS: Social class was inversely associated with T2DM in both men and women, whereby the association was more pronounced in women. Employment status only affected T2DM in women. Neighbourhood unemployment rate is an important predictor of T2DM in men, but not in women.

Regional and neighborhood disparities in the odds of type 2 diabetes: results from 5 population-based studies in Germany (DIAB-CORE consortium).

The objective of this study was to investigate the association between residential environment and type 2 diabetes. We pooled cross-sectional data from 5 population-based German studies (1997-2006): the Cardiovascular Disease, Living and Ageing in Halle Study, the Dortmund Health Study, the Heinz Nixdorf Recall Study, the Cooperative Health Research in the Region of Augsburg Study, and the Study of Health in Pomerania. The outcome of interest was the presence of self-reported type 2 diabetes. We conducted mixed logistic regression models in a hierarchical data set with 8,879 individuals aged 45-74 years on level 1; 226 neighborhoods on level 2; and 5 study regions on level 3. The analyses were adjusted for age, sex, social class, and employment status. The odds ratio for type 2 diabetes was highest in eastern Germany (odds ratio = 1.98, 95% confidence interval: 1.81, 2.14) and northeastern Germany (odds ratio = 1.58, 95% confidence interval: 1.40, 1.77) and lowest in southern Germany (reference) after adjustment for individual variables. Neighborhood unemployment rates explained a large proportion of regional differences. Individuals residing in neighborhoods with high unemployment rates had elevated odds of type 2 diabetes (odds ratio = 1.62, 95% confidence interval: 1.25, 2.09). The diverging levels of unemployment in neighborhoods and regions are an independent source of disparities in type 2 diabetes.

Personal attributes that influence the adequate management of hypertension and dyslipidemia in patients with type 2 diabetes. Results from the DIAB-CORE Cooperation.

BACKGROUND: Hypertension and dyslipidemia are often insufficiently controlled in persons with type 2 diabetes (T2D) in Germany. In the current study we evaluated individual characteristics that are assumed to influence the adequate treatment and control of hypertension and dyslipidemia and aimed to identify the patient group with the most urgent need for improved health care. METHODS: The analysis was based on the DIAB-CORE project in which cross-sectional data from five regional population-based studies and one nationwide German study, conducted between 1997 and 2006, were pooled. We compared the frequencies of socio-economic and lifestyle factors along with comorbidities in hypertensive participants with or without the blood pressure target of<140/90 mmHg. Similar studies were also performed in participants with dyslipidemia with and without the target of total cholesterol/HDL cholesterol ratio<5. Furthermore, we compared participants who received antihypertensive/lipid lowering treatment with those who were untreated. Univariable and multivariable logistic regression models were used to assess the odds of potentially influential factors. RESULTS: We included 1287 participants with T2D of whom n=1048 had hypertension and n=636 had dyslipidemia. Uncontrolled blood pressure was associated with male sex, low body mass index (BMI), no history of myocardial infarction (MI) and study site. Uncontrolled blood lipid levels were associated with male sex, no history of MI and study site. The odds of receiving no pharmacotherapy for hypertension were significantly greater in men, younger participants, those with BMI<30 kg/m(2) and those without previous MI or stroke. Participants with dyslipidemia received lipid lowering medication less frequently if they were male and had not previously had an MI. The more recent studies HNR and CARLA had the greatest numbers of well controlled and treated participants. CONCLUSION: In the DIAB-CORE study, the patient group with the greatest odds of uncontrolled co-morbidities and no pharmacotherapy was more likely comprised of younger men with low BMI and no history of cardiovascular disease.

Blood pressure and lipid management fall far short in persons with type 2 diabetes: results from the DIAB-CORE Consortium including six German population-based studies.

BACKGROUND: Although most deaths among patients with type 2 diabetes (T2D) are attributable to cardiovascular disease, modifiable cardiovascular risk factors appear to be inadequately treated in medical practice. The aim of this study was to describe hypertension, dyslipidemia and medical treatment of these conditions in a large population-based sample. METHODS: The present analysis was based on the DIAB-CORE project, in which data from five regional population-based studies and one nationwide German study were pooled. All studies were conducted between 1997 and 2006. We assessed the frequencies of risk factors and co-morbidities, especially hypertension and dyslipidemia, in participants with and without T2D. The odds of no or insufficient treatment and the odds of pharmacotherapy were computed using multivariable logistic regression models. Types of medication regimens were described. RESULTS: The pooled data set comprised individual data of 15, 071 participants aged 45-74 years, including 1287 (8.5%) participants with T2D. Subjects with T2D were significantly more likely to have untreated or insufficiently treated hypertension, i.e. blood pressure of > = 140/90 mmHg (OR = 1.43, 95% CI 1.26-1.61) and dyslipidemia i.e. a total cholesterol/HDL-cholesterol ratio > = 5 (OR = 1.80, 95% CI 1.59-2.04) than participants without T2D. Untreated or insufficiently treated blood pressure was observed in 48.9% of participants without T2D and in 63.6% of participants with T2D. In this latter group, 28.0% did not receive anti-hypertensive medication and 72.0% were insufficiently treated. In non-T2D participants, 28.8% had untreated or insufficiently treated dyslipidemia. Of all participants with T2D 42.5% had currently elevated lipids, 80.3% of these were untreated and 19.7% were insufficiently treated. CONCLUSIONS: Blood pressure and lipid management fall short especially in persons with T2D across Germany. The importance of sufficient risk factor control besides blood glucose monitoring in diabetes care needs to be emphasized in order to prevent cardiovascular sequelae and premature death.

Prevalence of obesity and elevated blood pressure as well as onset of puberty in German school children attending different educational tracks.

BACKGROUND: Obesity and associated comorbidities are increasingly evident in adolescents. This cross-sectional study investigates the relationship between educational level and prevalence of obesity, comorbidities, and onset of puberty in German schoolchildren. SUBJECTS AND METHODS: 1,488 children from Leipzig attending different types of schools ('Hauptschule' or 'Realschule', HR, vs. 'Gymnasium', GYM) were examined for indices of obesity, pubertal stage and blood pressure. RESULTS: Subjects attending HR had markedly increased body fat compared to age- and gender-matched peers attending GYM. Higher BMIs seen in children attending HR were associated with an earlier onset of puberty. The differences in body fat mass persisted after adjustment for puberty. In addition, children attending HR had higher systolic blood pressure compared to their age- and gender matched peers. This effect vanished when adjusting for BMI. CONCLUSION: Educational level affects the risk to develop obesity and associated comorbidities already at school age. The strong relationship between the educational track attended and increased BMI as well as elevated blood pressure in schoolchildren implies that comprehensive prevention activities should start already in school age and should be implemented in all educational establishments to target the increasing epidemic of childhood obesity.

Characterization of missense mutations and large deletions in the ALPL gene by sequencing and quantitative multiplex PCR of short fragments.

Hypophosphatasia is a rare inherited bone disorder characterized by defective bone and dental mineralization and deficiency of serum and liver/bone/kidney alkaline phosphatase activity. The disease is due to mutations in the alkaline phosphatase liver-type (ALPL) gene. Gross deletions or insertions have not previously been reported in this gene. We report here the characterization of nine novel ALPL gene mutations in a series of 8 patients affected by various forms of hypophosphatasia. The newly discovered mutations included five missense mutations (c.368C --> A, c.814C--> T, c.1196C--> T, c.1199C--> T, c.1283G--> C), two small deletions (c.797_802del, c.1044_1055del), and two large deletions. The large deletions were detected by quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments (QMPSF). We conclude that QMPSF slightly reduces the proportion of undetected mutations in hypophosphatasia and improves genetic counselling in the affected families.

Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels.

Adiponectin is an adipocytokine with profound antidiabetic and antiatherogenic effects that is decreased in obesity. With the increasing prevalence of obesity and the emergence of related disorders, including type 2 diabetes in children, the regulation of adiponectin and its relationship to childhood obesity is of great interest. In this study we aimed to elucidate the impact of gender, pubertal development, and obesity on adiponectin levels in children. We investigated two phenotypically characterized cohorts of 200 normal weight and 135 obese children and adolescents covering a wide range of age (3.4-17.9 yr) and body mass index (-2.1 to +4.8 sd score). In healthy lean boys, adiponectin levels significantly declined in parallel with physical and pubertal development, subsequently leading to significantly reduced adiponectin levels in adolescent boys compared with girls (5.6 +/- 0.5 vs. 7.1 +/- 0.5 mg/liter; P = 0.03). This decline was inversely related to testosterone (r = -0.42; P < 0.0001) and dehydroepiandrosterone sulfate (r = -0.20; P = 0.0068) serum concentrations and may account for the gender differences seen in adults. Using a stepwise forward multiple regression model, pubertal stage was the strongest independent predictor of adiponectin (r(2) = 0.206; P < 0.0001), with additional influences of body mass index sd score and testosterone. Adiponectin levels were decreased in obese children and adolescents compared with lean peers of corresponding age and pubertal stage (5.18 vs. 7.13 mg/liter; P = 0.015). In obese children, adiponectin levels were closely associated with parameters related to the metabolic syndrome, such as insulin resistance, hyperinsulinemia, blood pressure, and uric acid, in univariate and multivariate analyses, with the insulin sensitivity index being the strongest independent parameter identified by stepwise forward multiple regression (r(2) = 0.226; P < 0.0001). Hence, there is a strong association of adiponectin serum concentrations with obesity, pubertal development, and metabolic parameters in children indicating epidemiological and pathophysiological relevance already in childhood.

Impact of metabolic control and serum lipids on the concentration of advanced glycation end products in the serum of children and adolescents with type 1 diabetes, as determined by fluorescence spectroscopy and nepsilon-(carboxymethyl)lysine ELISA.

OBJECTIVE: Advanced glycation end products (AGEs) are a complex and heterogenous group of proteins that are formed by nonenzymatic glycation in a series of reactions. It is hypothesized that they may play a role in the pathogenesis of diabetes-related complications; at present, however, their exact biological role is scarcely understood. Clinical studies so far have shown that serum levels of AGEs are correlated with clinical stages of diabetes complications such as retinopathy and nephropathy. This study was performed in children and adolescents with type 1 diabetes to examine the putative role of serum AGEs in respect to metabolic control and diabetes complications in relation to a number of clinical and laboratory parameters. RESEARCH DESIGN AND METHODS: We studied 99 children and adolescents up to the age of 20 years with type 1 diabetes and 60 control subjects. Serum levels of AGEs were measured with two different methods [fluorescence spectroscopy and Nepsilon-(carboxymethyl)lysine (CML) enzyme-linked immunosorbent assay] and correlated with clinical data, such as age, diabetes duration, BMI, and long-term metabolic control determined by HbA(1c), and laboratory parameters, such as serum lipids. RESULTS: Serum levels of fluorescent AGEs, but not of CML-AGEs, in children and adolescents with type 1 diabetes were significantly higher compared with control subjects. There was an age-dependent increase of fluorescent AGEs in children and adolescents with diabetes that was not seen in healthy children and adolescents. Levels of fluorescent AGEs in patients with diabetes between 13 and 16 years of age correlated positively with HbA(1c) levels. No significant association between levels of AGEs and diabetes duration was found. Children and adolescents with diabetes and high serum triglycerides had significantly higher serum levels of fluorescent AGEs. Children and adolescents with diabetes between the age of 13 and 16 years with high levels of LDL had significantly higher levels of fluorescent AGEs. CONCLUSIONS: In this study we demonstrated a clear age-dependent increase of fluorescent AGEs but not of CML-AGEs in children and adolescents with diabetes type 1. Moreover we showed a strong association between serum AGEs and serum triglycerides and cholesterol. The observed effect may be caused by a loss of optimal regulation of lipid metabolism. It could suggest a link between triglycerides and formation of AGEs. This new and interesting finding and its impact on metabolic control and the development of diabetes complications should be examined in the future.