Childhood maltreatment is not associated with atopic dermatitis in adults: results from a cross-sectional population-based cohort study.

BACKGROUND: Childhood maltreatment (CM) is related to poor physical and mental health outcomes in adults. Knowledge on the impact of CM on skin diseases is limited, and no study has previously addressed the association of CM with atopic dermatitis (AD) in adult age. OBJECTIVES: To analyse the prevalence of CM in individuals with physician-diagnosed AD, and to examine the relationship between different types of CM with physician-diagnosed AD in a general population sample of German adults. METHODS: Data from 2973 participants from the cross-sectional population-based Study of Health in Pomerania (SHIP) TREND-0 were analysed (aged 20 to 83 years; 51.4% female). We administered the Childhood Trauma Questionnaire (CTQ) assessing emotional, physical and sexual abuse, and emotional and physical neglect. AD was diagnosed by dermatologists in a standardized clinical examination. We conducted logistic regression analyses adjusted for age, sex and school education to investigate the association of CM types with AD. RESULTS: Among all individuals with AD, 20.6% reported to have experienced at least one type of moderate or severe CM. Emotional and physical neglect were the most frequently reported CM types. Overall, the prevalence of CM types among individuals with AD did not differ from those among individuals without AD. We found no association of CM type with AD. CONCLUSIONS: This is the first study investigating the association of CM with AD in adults. CM was common in the present general population sample, emphasizing that CM is an important public health problem. Our findings suggest that CM is not a risk factor for AD. It might be hypothesized that AD severity is a crucial outcome, and that CM history is a factor with impact on disease severity and course rather than a risk factor for the development of AD. Longitudinal studies are required to address this question.

Whole-body R2∗ mapping to quantify tissue iron in iron storage organs: reference values and a genotype.

AIM: To define reference values for the transverse relaxation rate (R2∗) in iron storage organs and to investigate the role of human haemochromatosis protein (HFE) genotype on iron storage. MATERIALS AND METHODS: Whole-body magnetic resonance imaging (MRI) including a five-echo gradient-echo sequence was performed in 483 volunteers (269 men, mean age 59.3 ± 12.2 years) without clinical evidence of an iron storage disease at 1.5 T. R2∗ values were assessed for liver, spleen, pancreas, heart, bones, and brain parenchyma. The HFE genotype was determined regarding the single nucleotide polymorphisms (SNPs) rs74315324, rs1799945, rs41303501, rs1800562, rs1800730. R2∗ values were compared among participants without and with at least one mutation. R2∗ reference values were defined using volunteers without any mutation. RESULTS: Three hundred and one participants had no mutations in any HFE SNP, 182 had at least one mutation. HFE gene mutations were distributed as (heterozygous/homozygous) rs1799945:132/9, rs1800562:33/1, and rs1800730:11/0. Mean R2∗ values ± SD (per second) in the group without mutation were: liver: 33.4 ± 12.7, spleen: 24.1 ± 13.8, pancreas: 27.2 ± 6.6, heart: 32.7 ± 11.8, bone: 69.3 ± 21.0, brain parenchyma: 13.9 ± 1.2. No significant difference in R2∗ values were found between participants with and without the HFE gene mutation for any examined iron storage organ (pliver=0.09, pspleen=0.36, ppancreas = 0.08, pheart = 0.36, pbone = 0.98, pbrain=0.74). CONCLUSION: Reference values of R2∗ in iron storage organs are feasible to support the diagnosis of iron storage diseases. Non-specific mutations in HFE SNPs appear not to affect the phenotype of tissue iron accumulation.

Reference Values for Pulmonary Single-Breath Diffusing Capacity - Results of the "Study of Health in Pomerania".

OBJECTIVES: The assessment of pulmonary single-breath diffusing capacity is a frequently performed diagnostic procedure and considered as an important tool in medical surveillance examinations of pulmonary diseases.The aim of this study was to establish reference equations for pulmonary single-breath diffusing capacity parameters in a representative adult-population across a wide age range and to compare the normative values from this sample with previous ones. METHODS: Diffusing capacity measurement was carried out in 3566 participants (1811 males) of a cross-sectional, population-based survey ("Study of Health in Pomerania - SHIP"). RESULTS: Individuals with cardiopulmonary disorders and current smoking habits were excluded, resulting in 1786 healthy individuals (923 males), aged 20 - 84 years. Prediction equations for both sexes were established by quantile regression analyses, taking into consideration the influence of age, height, weight and former smoking. CONCLUSION: The study provides a novel set of prediction equations for pulmonary single-breath diffusing capacity in an adult Caucasian population. The results are comparable to previously reported equations, underline their importance and draw attention to the need for up-to-date reference equations that adequately take into account both the subjects' origin, age, anthropometric characteristics and the equipment used.

Accuracy of ultrasonography in the assessment of liver fat compared with MRI.

AIM: To investigate the accuracy of ultrasonography in the assessment of hepatic steatosis using magnetic resonance imaging (MRI) as standard of reference and to explore the influence of additional hepatic iron overload. MATERIAL AND METHODS: A total of 2,783 volunteers (1,442 women, 1,341 men; mean age, 52.3±13.8 years) underwent confounder-corrected chemical-shift-encoded MRI of the liver at 1.5 T. Proton-density fat fraction (PDFF) and transverse relaxation rate (R2*) were calculated to estimate hepatic steatosis and liver iron overload, respectively. In addition, the presence of hepatic steatosis was assessed by B-mode ultrasonography. The sensitivity, specificity, and accuracy of hepatic ultrasonography were determined for different degrees of hepatic steatosis and different amounts of liver iron. RESULTS: MRI revealed hepatic steatosis in 40% of participants (n=1,112), which was mild in 68.9% (n=766), moderate in 26.7% (n=297), and severe in 4.4% (n=49) of patients. Ultrasonography detected hepatic steatosis in 37.8% (n=1,052), corresponding to 74.5% sensitivity and 86.6% specificity. The sensitivity of ultrasound increased with the amount of hepatic fat present and was 65.1%, 95%, and 96% for low, moderate, and high fat content; whereas the specificity was constantly high at 86.6%. The diagnostic accuracy of ultrasound for detection of hepatic steatosis did not vary significantly with the amount of liver iron present. CONCLUSION: Ultrasonography is an excellent tool to assess hepatic steatosis in the clinical setting with some limitations in patients with a low liver fat content. The detection of hepatic steatosis by ultrasonography is not influenced by liver iron.

Abdominal fat deposits determined by magnetic resonance imaging in relation to leptin and vaspin levels as well as insulin resistance in the general adult population.

BACKGROUND: Various fat depots including visceral (VAT), subcutaneous adipose tissue (SAT) or liver fat content (LFC) were supposed to have different influences on various entities including adipokine levels as well as insulin resistance/sensitivity. Therefore, the aim of the study was to investigate the associations of SAT, VAT and LFC with the levels of leptin and vaspin as well as insulin resistance in a general non-diabetic population. METHODS: In total, 1825 participants of the Study of Health in Pomerania were characterized according to body fat compartments and LFC determined by magnetic resonance imaging. Of those subjects, insulin resistance (HOMA-IR) and insulin sensitivity ([ISI(comp)) were determined in 981 participants and adipokines were assessed in 698 using enzyme-linked immunosorbent assay. Analyses of variance and linear regression models adjusted for age, sex, smoking, height, physical inactivity and alcohol consumption were used for analysis. RESULTS: Using the residual method to assess independently the effect of the various fat depots, a strong positive association of SAT (beta per standard deviation (s.d.) increase 0.54 (95% confidence interval (CI) 0.47-0.60)) but not VAT (beta 0.01 (95% CI -0.08 to 0.09)) and LFC (beta 0.01 (95% CI -0.06 to 0.08)) with log2-leptin levels was found independent of the HOMA-IR status. Moreover, a positive association of LFC (beta 0.17 (95% CI 0.07-0.26)) with log2-vaspin levels becomes apparent, which were mostly driven by subjects with a low HOMA-IR. With respect to HOMA-IR and ISI(comp) index, pronounced positive and inverse associations to all fat markers were revealed, respectively, with the strongest relation found for SAT and LFC. CONCLUSIONS: SAT and LFC were identified as predominant sites associated with leptin and vaspin levels, respectively. Residual analysis pointed towards a general adverse effect of disproportional triglyceride storage across physiological despots, in particular in ectopic sides such as the liver, with markers of insulin resistance.

Associations of insulin-like growth factor-I and insulin-like growth factor binding protein-3 with bone quality in the general adult population.

OBJECTIVE: Growth hormone (GH) and its main mediator, insulin-like growth factor-I (IGF-I), play a significant role in bone metabolism. The relations between IGF-I and bone mineral density (BMD) or osteoporosis have been assessed in previous studies but whether the associations are sex-specific remains uncertain. Moreover, only a few studies examined bone quality assessed by quantitative ultrasound (QUS). We aimed to investigate these associations in the general population of north-east Germany. DESIGN AND MEASUREMENTS: Data from 1759 men and 1784 women who participated in the baseline examination of the Study of Health in Pomerania (SHIP)-Trend were used. IGF-I and IGF-binding protein-3 (IGFBP-3) concentrations were measured on the IDS-iSYS multidiscipline automated analyser (Immunodiagnostic Systems Limited). QUS measurements were performed at the heel (Achilles InSight, GE Healthcare). Sex-specific linear and multinomial logistic regression models adjusted for potential confounders were calculated. RESULTS: Linear regression analyses revealed significant positive associations between IGF-I and IGF-I/IGFBP-3 ratio, a marker for free IGF-I, with all QUS parameters in men. Among women, we found an inverse association between IGF-I and the QUS-based fracture risk but no association with any other QUS parameter. There was no association between IGFBP-3 and the QUS-based fracture risk. CONCLUSIONS: Our data suggest an important role of IGF-I on bone quality in men. The observed association of IGF-I with the QUS-based stiffness index and QUS-based fracture risk in this study might animate clinicians to refer patients with low IGF-I levels, particularly men, to a further evaluation of risk factors for osteoporosis and a detailed examination of the skeletal system.

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization.

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC). METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or ß-estimates with 95% confidence interval (CI). RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: ß=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: ß=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2 higher BMI. CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

No calcitonin change in a person taking dulaglutide diagnosed with pre-existing medullary thyroid cancer.

BACKGROUND: Glucagon-like peptide-1 receptor agonists, such as dulaglutide, exenatide and liraglutide, are approved to treat Type 2 diabetes mellitus. Although these drugs provide substantial glycaemic control, studies in rodents have prompted concerns about the development of medullary thyroid carcinoma. These data are reflected in the US package insert, with boxed warnings and product labelling noting the occurrence of these tumours after clinically relevant exposures in rodents, and contraindicating glucagon-like peptide-1 receptor agonist use in people with a personal or family history of medullary thyroid carcinoma, or in people with multiple endocrine neoplasia type 2. However, there are substantial differences between rodent and human responses to glucagon-like peptide-1 receptor agonists. This report presents the case of a woman with pre-existing medullary thyroid carcinoma who exhibited no significant changes in serum calcitonin levels despite treatment with dulaglutide 2.0 mg for 6 months in the Assessment of Weekly AdministRation of LY2189265 [dulaglutide] in Diabetes-5 clinical study (NCT00734474). CASE REPORT: Elevated serum calcitonin was noted in a 56-year-old woman with Type 2 diabetes mellitus at the 6-month discontinuation visit in a study of long-term dulaglutide therapy. Retroactive assessment of serum collected before study treatment yielded an elevated calcitonin level. At 3 months post-study, calcitonin level remained elevated; ultrasonography revealed multiple bilateral thyroid nodules. Eventually, medullary thyroid carcinoma was diagnosed; the woman was heterozygous positive for a germline RET proto-oncogene mutation. CONCLUSION: The tumour was not considered stimulated by dulaglutide therapy because calcitonin remained stable throughout.

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Hyperthyroxinemia is positively associated with prevalent and incident type 2 diabetes mellitus in two population-based samples from Northeast Germany and Denmark.

BACKGROUND AND AIMS: A potential causal relationship between thyroid function and type 2 diabetes mellitus is currently under debate, but the current state of research is limited. Our aim was to investigate the association of thyroid hormone levels with prevalent and incident type 2 diabetes mellitus (T2DM) in two representative studies. METHODS AND RESULTS: Analyses are based on data from the Study of Health in Pomerania (SHIP), a German population based cohort with 4308 individuals at baseline and 3300 individuals at a five-year follow-up, and from INTER99, a Danish population-based randomized controlled trial with 6784 individuals at baseline and 4516 individuals at the five-year-follow-up. Serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) concentrations were measured in both studies, while free triiodothyronine was measured in SHIP only. T2DM was defined by self report or intake of anti-diabetic medication. Neither in SHIP nor in INTER99 we detected significant associations of serum TSH levels with prevalent or incident T2DM. Serum fT4 levels were significantly positively associated with prevalent T2DM in SHIP and INTER99. In longitudinal analyses baseline levels of fT4 were significantly positively associated with incident T2DM in SHIP (RR per pmol/L = 1.07; 95%-CI = 1.05-1.10), while this association barely missed statistical significance in INTER99 (RR per pmol/L = 1.03; 95%-CI = 0.99-1.06). In SHIP baseline fT3 levels were significantly associated with incident T2DM (RR per pmol/L = 1.21; 95%-CI = 1.16-1.27). CONCLUSION: We demonstrated positive associations of thyroid hormones with prevalent and incident type 2 diabetes mellitus suggesting that hyperthyroxinemia may contribute to the pathogenesis of this condition.

Prediabetes is associated with microalbuminuria, reduced kidney function and chronic kidney disease in the general population: The KORA (Cooperative Health Research in the Augsburg Region) F4-Study.

BACKGROUND AND AIMS: We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose tolerance categories were analyzed for association with ACR and eGFR in multivariable adjusted linear and median regression models, and with isolated microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic regression models. Among the 2713 study participants, 28% revealed prediabetes (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or both by American Diabetes Association definition), 4.2% had unknown type 2 diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR) were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for individuals with IFG + IGT. CONCLUSION: Our findings suggest that prediabetes might have harmful effects on the kidney.

Cardiopulmonary fitness is strongly associated with body cell mass and fat-free mass: The Study of Health in Pomerania (SHIP).

Peak oxygen uptake (VO2peak) is commonly indexed by total body weight (TBW) to determine cardiopulmonary fitness (CPF). This approach may lead to misinterpretation, particularly in obese subjects. We investigated the normalization of VO2peak by different body composition markers. We analyzed combined data of 3848 subjects (1914 women; 49.7%), aged 20-90, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-2 and SHIP-TREND). VO2peak was assessed by cardiopulmonary exercise testing. Body cell mass (BCM), fat-free mass (FFM), and fat mass (FM) were determined by bioelectrical impedance analysis. The suitability of the different markers as a normalization variable was evaluated by taking into account correlation coefficients (r) and intercept (α-coefficient) values from linear regression models. A combination of high r and low α values was considered as preferable for normalization purposes. BCM was the best normalization variable for VO2peak (r = .72; P ≤ .001; α-coefficient = 63.3 mL/min; 95% confidence interval [CI]: 3.48-123) followed by FFM (r = .63; P ≤ .001; α-coefficient = 19.6 mL/min; 95% CI: -57.9-97.0). On the other hand, a much weaker correlation and a markedly higher intercept were found for TBW (r = .42; P ≤ .001; α-coefficient = 579 mL/min; 95% CI: 483 to 675). Likewise, FM was also identified as a poor normalization variable (r = .10; P ≤ .001; α-coefficient = 2133; 95% CI: 2074-2191). Sex-stratified analyses confirmed the above order for the different normalization variables. Our results suggest that BCM, followed by FFM, might be the most appropriate marker for the normalization of VO2peak when comparing CPF between subjects with different body shape.

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Prediabetes is associated with lower brain gray matter volume in the general population. The Study of Health in Pomerania (SHIP).

BACKGROUND AND AIMS: We investigated the associations of fasting (FG) and 2-h postload (2HG) plasma glucose from oral glucose tolerance test (OGTT) with gray (GMV) and white (WMV) matter volume. METHODS AND RESULTS: We analyzed data from 1330 subjects without known diabetes mellitus, aged 21 to 81, from the second cohort (SHIP-Trend-0) of the population-based Study of Health in Pomerania (SHIP). Following the OGTT, individuals were classified in five groups (according to the American Diabetes Association criteria): normal glucose tolerance (NGT), isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT) and unknown type 2 diabetes mellitus (UDM). GMV and WMV were determined by magnetic resonance imaging. FG, 2HG and OGTT groups were associated with GMV and WMV by linear regression models adjusted for confounders. FG and 2HG were inversely associated with GMV. The adjusted mean GMV, when compared with the NGT group (584 ml [95% CI: 581 to 587]), was significantly lower in the groups i-IFG (578 ml [95% CI: 573 to 582]; p = 0.035) and UDM (562 ml [95% CI: 551 to 573]; p < 0.001), but not different in the i-IGT (586 ml [95% CI: 576 to 596]; p = 0.688) and IFG + IGT (579 ml [95% CI: 571 to 586]; p = 0.209) groups. There were no associations of FG, 2HG and OGTT parameters with WMV. CONCLUSION: Our findings suggest that elevated FG levels, even within the prediabetic range, might already have some harmful effects on GMV.

[Lung Health Data of the Study of Health in Pomerania - a Review of Samples, Methods and First Results]. / Pneumologisch relevante Daten aus der "Study of Health in Pomerania" (SHIP) ­ eine Übersicht zu den Kohorten, Methoden und ersten Ergebnissen.

Investigating reasons for differing life expectancy and prevalence of cardiovascular risk factors between old and new states of the Federal Republic of Germany an epidemiological study in Western Pomerania - the population-based project Study of Health in Pomerania (SHIP) - was planned.Prevalence and incidence of common risk factors, subclinical disorders and clinical diseases have been assessed since 1997 in five-year intervals. The third follow up (SHIP-3) was assessed between 2014 and 2016. In addition, an independent representative population sample was investigated between 2008 - 2012 (SHIP-TREND). Recently, the first follow up of this cohort has been started (SHIP-TREND-1). This paper reports the methodological approaches for detecting pneumological relevant morbidities in this population-based study. It aims to offer insights for potential cooperation with interested research groups.

Thyrotropin serum levels are differentially associated with biochemical markers of bone turnover and stiffness in women and men: results from the SHIP cohorts.

UNLABELLED: In two large German population-based cohorts, we showed positive associations between serum thyrotropin (TSH) concentrations and the Fracture Risk Assessment score (FRAX) in men and positive associations between TSH concentrations and bone turnover markers in women. INTRODUCTION: The role of thyroid hormones on bone stiffness and turnover is poorly defined. Existing studies are confounded by differences in design and small sample size. We assessed the association between TSH serum concentrations and bone stiffness and turnover in the SHIP cohorts, which are two population-based cohorts from a region in Northern Germany comprising 2654 men and women and 3261 men and women, respectively. METHODS: We calculated the bone stiffness index using quantitative ultrasound (QUS) at the calcaneus, employed FRAX score for assessment of major osteoporotic fractures, and measured bone turnover markers, N-terminal propeptide of type I procollagen (P1NP), bone-specific alkaline phosphatase (BAP), osteocalcin, and type I collagen cross-linked C-telopeptide (CTX) in all subjects and sclerostin in a representative subgroup. RESULTS: There was no association between TSH concentrations and the stiffness index in both genders. In men, TSH correlated positively with the FRAX score both over the whole TSH range (p < 0.01) and within the reference TSH range (p < 0.01). There were positive associations between TSH concentrations and P1NP, BAP, osteocalcin, and CTX (p < 0.01) in women but not in men. There was no significant association between TSH and sclerostin levels. CONCLUSIONS: TSH serum concentrations are associated with gender-specific changes in bone turnover and stiffness.

Multimodal imaging of a tescalcin (TESC)-regulating polymorphism (rs7294919)-specific effects on hippocampal gray matter structure.

In two large genome-wide association studies, an intergenic single-nucleotide polymorphism (SNP; rs7294919) involved in TESC gene regulation has been associated with hippocampus volume. Further characterization of neurobiological effects of the TESC gene is warranted using multimodal brain-wide structural and functional imaging. Voxel-based morphometry (VBM8) was used in two large, well-characterized samples of healthy individuals of West-European ancestry (Münster sample, N=503; SHIP-TREND, N=721) to analyze associations between rs7294919 and local gray matter volume. In subsamples, white matter fiber structure was investigated using diffusion tensor imaging (DTI) and limbic responsiveness was measured by means of functional magnetic resonance imaging (fMRI) during facial emotion processing (N=220 and N=264, respectively). Furthermore, gene x environment (G × E) interaction and gene x gene interaction with SNPs from genes previously found to be associated with hippocampal size (FKBP5, Reelin, IL-6, TNF-α, BDNF and 5-HTTLPR/rs25531) were explored. We demonstrated highly significant effects of rs7294919 on hippocampal gray matter volumes in both samples. In whole-brain analyses, no other brain areas except the hippocampal formation and adjacent temporal structures were associated with rs7294919. There were no genotype effects on DTI and fMRI results, including functional connectivity measures. No G × E interaction with childhood maltreatment was found in both samples. However, an interaction between rs7294919 and rs2299403 in the Reelin gene was found that withstood correction for multiple comparisons. We conclude that rs7294919 exerts highly robust and regionally specific effects on hippocampal gray matter structures, but not on other neuropsychiatrically relevant imaging markers. The biological interaction between TESC and RELN pointing to a neurodevelopmental origin of the observed findings warrants further mechanistic investigations.

Association of neighbourhood unemployment rate with incident Type 2 diabetes mellitus in five German regions.

AIM: To analyse the association of neighbourhood unemployment with incident self-reported physician-diagnosed Type 2 diabetes in a population aged 45-74 years from five German regions. METHODS: Study participants were linked via their addresses at baseline to particular neighbourhoods. Individual-level data from five population-based studies were pooled and combined with contextual data on neighbourhood unemployment. Type 2 diabetes was assessed according to a self-reported physician diagnosis of diabetes. We estimated proportional hazard models (Weibull distribution) in order to obtain hazard ratios and 95% CIs of Type 2 diabetes mellitus, taking into account interval-censoring and clustering. RESULTS: We included 7250 participants residing in 228 inner city neighbourhoods in five German regions in our analysis. The incidence rate was 12.6 per 1000 person-years (95% CI 11.4-13.8). The risk of Type 2 diabetes mellitus was higher in men [hazard ratio 1.79 (95% CI 1.47-2.18)] than in women and higher in people with a low education level [hazard ratio 1.55 (95% CI 1.18-2.02)] than in those with a high education level. Independently of individual-level characteristics, we found a higher risk of Type 2 diabetes mellitus in neighbourhoods with high levels of unemployment [quintile 5; hazard ratio 1.72 (95% CI 1.23-2.42)] than in neighbourhoods with low unemployment (quintile 1). CONCLUSIONS: Low education level and high neighbourhood unemployment were independently associated with an elevated risk of Type 2 diabetes mellitus. Studies examining the impact of the residential environment on Type 2 diabetes mellitus will provide knowledge that is essential for the identification of high-risk populations.

Lower bone turnover markers in metabolic syndrome and diabetes: the population-based Study of Health in Pomerania.

BACKGROUND AND AIMS: Accumulating evidence demonstrates an important interaction between bone and energy metabolism. We aimed to study the associations of three bone turnover markers (BTM: osteocalcin, beta-crosslaps, procollagen type 1 N-terminal propeptide) as well as of 25-hydroxyvitamin D and parathyroid hormone with metabolic syndrome (MetS) or type 2 diabetes mellitus (T2DM) in a large population-based cohort. METHODS AND RESULTS: This cross-sectional study comprised 2671 adult men and women participating in the first follow-up of the population-based Study of Health in Pomerania (SHIP-1). Multivariable logistic regression analyses were performed to assess sex-specific associations between the BTMs, 25-hydroxyvitamin D or parathyroid hormone and metabolic disease. All models were adjusted for age, body mass index, smoking status, physical activity, estimated glomerular filtration rate and month of blood sampling. The models for women were further adjusted for menopausal status. Higher BTM or 25-hydroxyvitamin D concentrations were associated with significantly lower odds for metabolic disease, while there was no association between parathyroid hormone and MetS or T2DM. CONCLUSION: Our results contribute to the accumulating evidence of a cross-sectional association between high BTM or 25-hydroxyvitamin D concentrations and a lower prevalence of MetS or T2DM. Further research is necessary to evaluate the mechanisms underlying these results.

Trends of barriers to eye care among adults with diagnosed diabetes in Germany, 1997-2012.

BACKGROUND AND AIMS: To study trends of barriers to receiving recommended eye care among subjects with diabetes aged 20-81 years in northeast Germany. METHODS AND RESULTS: We analyzed population-based data from two repeated cross-sectional surveys conducted in 1997-2001 and 2008-2012 (Ns of 4308 and 4402). Andersen's Behavioral Model of Health Services Utilization was used to identify individual-level demographic, financial and health-related barriers to annual eye-care utilization in subjects with a self-reported physician's diabetes and to examine population trends in these barriers. The prevalence of diabetes increased from 6.5% to 11.4%. The prevalence of annual eye-care utilization among persons with diabetes decreased from 69.4% to 56.0% (adjusted relative risk = 0.77, p < 0.001). The decline of eye care utilization over the past decade in eye-care use was more pronounced in groups at risk for diabetes-related complications (i.e., lower socio-economic status, >5 years since diagnosis of diabetes, poor glycemic control, obesity, smoking, lack of physical activity, co-existing diseases). We identified relevant predictors of missed annual eye-care use among diabetics. CONCLUSION: The increase of diabetes prevalence and downward trend of eye-care visits at the recommended level call for development, implementation and evaluation of continued efforts to improve access to eye specialists, particularly among those with poor diabetic control, co-existing diabetic complications, and comorbidities.