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Endocrine disorders including hypothyroidism and hypercortisolism are considered as causes of secondary obesity. However, several hormonal abnormalities can also be found in individuals with primary (simple) obesity. Part of them results from the adipose tissue dysfunction that, via secreted adipokines, modulates the function of endocrine organs and can be reversed with weight loss. However, part of them correspond to the real endocrine disorder and require appropriate treatment. Therefore in the management of obese patients, it is essential to distinguish between obesity-related abnormal results of hormonal tests and underlying endocrine disorder. This chapter presents pathophysiological concepts of obesity-related changes in the endocrine system and briefly reviews diagnostic algorithms helpful in distinguishing them from the co-existing endocrine disorders.

Sirtuins (silent information regulators, sirts) via modification of histones, as well as transcription factors and co-regulators, control expression of other genes, particularly those involved in the organism response to stress. Detection of sirtuin expression in adipocytes initiated interest in their role in adipose tissue development and metabolism. This chapter presents how sirtuins control the critical steps of preadipocytes’ differentiation and proliferation, as well as the process of adipose tissue browning. Moreover, it shows in vitro and in vivo data proving that sirtuins are involved in the regulation of lipogenesis, lipolysis, and secretory activity of adipose tissue. Due to all these reasons, sirtuins may constitute potential targets in the treatment of obesity and related complications.

Obesity-related changes in the composition of the body interfere with the proper functioning of the thyrotropic axis, leading to its disturbances and changes in the structure of the thyroid gland. Distinguishing what is related to obesity and what constitutes pathological changes is crucial for the proper treatment of patients. In this paper authors present a case of a patient with a diet-induced obesity, whose only abnormalities in thyroid assessment included an elevated level of thyroid stimulating hormone (TSH) and hypoechoic thyroid gland on ultrasound. Based on this clinical situation, we reviewed literature in order to establish rules regarding management of thyroid disorders in obese individuals. The most common obesity-related thyroid abnormality is an isolated increase of TSH, without clinical symptoms of hypothyroidism, defined as hyperthyrotropinaemia. In obese adults, autoimmune thyroid disease is found equally often as in the normal-weight population. Thyroid enlargement, increased risk of nodules, and decreased echogenicity, not related to autoimmunity, is frequent among obese individuals. Weight loss leads to the normalisation of TSH levels and thyroid echogenicity. Excessive weight can influence both the TSH level and ultrasound image of the thyroid gland; however, these findings can be reversed by weight reduction. Therefore, in asymptomatic obese patients elevated TSH should not be treated with thyroid hormone replacement.

Long-term outcomes of children with nephrotic syndrome have not been well described in the literature. Cross-sectional study data analysis of n = 43 patients with steroid-sensitive (SSNS) and n = 7 patients with steroid-resistant (SRNS) nephrotic syndrome were retrospectively collected; patients were clinically examined at a follow-up visit (FUV), on average 30 years after onset, there was the longest follow-up period to date. The mean age at FUV was 33.6 years (14.4–50.8 years, n = 41). The mean age of patients with SSNS at onset was 4.7 years (median 3.8 years (1.2–14.5 years), the mean number of relapses was 5.8 (0 to 29 relapses). Seven patients (16.3%) had no relapses. Eleven patients were “frequent relapsers” (25.6%) and four patients still had relapses beyond the age of 18 years. Except of cataracts and arterial hypertension, there were no negative long-term outcomes and only one patient was using immunosuppressant therapy at FUV. 55% of patients suffered from allergies and 47.5% had hypercholesterolemia. Two patients suffered a heart attack in adulthood. A younger age at onset (

Non-invasive brain stimulation (NBS) techniques can induce neuroplastic changes similar to those associated with motor learning and there is evidence for the involvement of common mechanisms. Whether there are correlations between the changes induced by NBS and those associated with motor learning remains unclear. We investigated whether there was any relationship between an individual's neuroplastic responses to several different NBS protocols (continuous theta-burst stimulation (cTBS); intermittenttheta-burst stimulation (iTBS); facilitatory paired associative stimulation (PAS: inter-stimulus interval25 ms)) and whether these responses correlated with the neuroplastic response associated with a motortraining (MT)task involving repeated fast-as-possible thumb abductions.Changes in motor evoked potential(MEP) amplitude were used to assess the neuroplastic response to each protocol. MEP amplitude decreased significantly following cTBS,however there was no significant change in MEP amplitude following iTBS, PAS or MT. There were no significant correlations between individuals' neuroplastic responses to any of the NBS protocols tested or between individuals' neuroplastic responses to the NBS protocols and motor learning. These results provide no support for an association between individuals' neuroplastic responses to several plasticity-inducing protocols. Although there is evidence for involvement of common mechanisms in the neuroplastic changes induced by NBS and motor learning, the results of this study suggest (1) the mechanisms mediating TBS-, PAS-, and MT-induced plasticity may only partially overlap, and (2) additional factors, including large intra and inter-subject response variability, may makethe demonstration of associations between neuroplastic responses to the various protocols difficult. Refereed/Peer-reviewed

Excess adiposity is associated with chronic inflammation, which takes part in the development of obesity-related complications. The aim of this study was to establish whether subcutaneous (SAT) or visceral (VAT) adipose tissue plays a major role in synthesis of pro-inflammatory cytokines. Concentrations of interleukins (IL): 1β, 6, 8 and 15 were measured at the protein level by an ELISA-based method and on the mRNA level by real-time PCR in VAT and SAT samples obtained from 49 obese (BMI &gt, 40 kg/m2) and 16 normal-weight (BMI 20–24.9 kg/m2) controls. IL-6 and IL-15 protein concentrations were higher in SAT than in VAT for both obese (p = 0.003 and p &lt, 0.0001, respectively) and control individuals (p = 0.004 and p = 0.001, respectively), while for IL-1β this was observed only in obese subjects (p = 0.047). What characterized obese individuals was the higher expression of IL-6 and IL-15 at the protein level in VAT compared to normal-weight controls (p = 0.047 and p = 0.016, respectively). Additionally, obese individuals with metabolic syndrome had higher IL-1β levels in VAT than did obese individuals without this syndrome (p = 0.003). In conclusion, concentrations of some pro-inflammatory cytokines were higher in SAT than in VAT, but it was the increased pro-inflammatory activity of VAT that was associated with obesity and metabolic syndrome.

Preterm-born children commonly experience motor, cognitive, and learning difficulties that may be accompanied by altered brain microstructure, connectivity, and neurochemistry. However, the mechanisms linking the altered neurophysiology with the behavioral outcomes are unknown. Here we provide the first physiological evidence that human adolescents born preterm at or before 37 weeks of completed gestation have a significantly reduced capacity for cortical neuroplasticity, the key overall mechanism underlying learning and memory. We examined motor cortex neuroplasticity in three groups of adolescents who were born after gestations of ≤32 completed weeks (early preterm), 33–37 weeks (late preterm), and 38 – 41 weeks (term) using a noninvasive transcranial magnetic brain stimulation technique to induce long-term depression (LTD)-like neuroplasticity. Compared with term-born adolescents, both early and late preterm adolescents had reduced LTD-like neuroplasticity in response to brain stimulation that was also associated with low salivary cortisol levels. We also compared neuroplasticity in term-born adolescents with that in term-born young adults, finding that the motor cortex retains a relatively enhanced neuroplastic capacity in adolescence. These findings provide a possible mechanistic link between the altered brain physiology of preterm birth and the subsequent associated behavioral deficits, particularly in learning and memory. They also suggest that altered hypothalamic–pituitary– adrenal axis function due to preterm birth may be a significant modulator of this altered neuroplasticity. This latter finding may offer options in the development of possible therapeutic interventions. Refereed/Peer-reviewed

Background The interplay between adiponectin and resistin, the two adipokines of opposite effects, may determine the metabolic profile of obese individuals and development of obesity-related complications. The current study was conducted to assess how adiponectin/resistin interplay in sera and adipose tissues may influence the metabolic profile of obese and normal-weight subjects. Methods Concentrations of adiponectin and resistin were measured on protein level by immunoassay in visceral and subcutaneous adipose tissues from 50 obese (body mass index > 40 kg/m2) and 28 normal-weight (body mass index 20–24.9 kg/m2) individuals. Simultaneously expression of ADIPOQ and RETN (encoding adiponectin and resistin, respectively) was assessed on mRNA level by real-time PCR. Results ADIPOQ mRNA (P = 0.0001) and adiponectin protein (P = 0.0013) levels were lower, while RETN mRNA (P = 0.0338) and resistin (P

Both obesity and weight loss may cause molecular changes in adipose tissue. This study aimed to characterize changes in adipose tissue miRNome in order to identify molecular pathways affected by obesity and weight changes. Next generation sequencing (NGS) was applied to identify microRNAs (miRNAs) differentially expressed in 47 samples of visceral (VAT) and subcutaneous (SAT) adipose tissues from normal-weight (N), obese (O) and obese after surgery-induced weight loss (PO) individuals. Subsequently miRNA expression was validated by real-time PCR in 197 adipose tissues and bioinformatics analysis performed to identify molecular pathways affected by obesity-related changes in miRNA expression. NGS identified 344 miRNAs expressed in adipose tissues with ≥5 reads per million. Using >2 and

Basal serum 17OHP measurement remains the first screening step for nonclassic congenital adrenal hyperplasia (NCCAH) and the accuracy of the test is of high value. The aim of this study was to compare the accuracy of immunoassays to LC-MS/MS in the assessment of serum 17OHP and androgens concentration in women with hyperandrogenism and controls. 17OHP, total testosterone, androstendione and DHEA-S were measured in 39 women with clinically and/or biochemically evident hyperandrogenism and in 29 age-matched controls without clinical hyperandrogenism. 17OHP and androgens were measured by immunoassays and by LC-MS/MS. In patients group median 17OHP level measured by immunoassays was significantly higher compared to LC-MS/MS (5.49 nmol/l-ELISA NovaTec® and 3.57 nmol/l-ELISA DRG® versus 1.56 nmol/l-LC-MS/MS p 0.0001) as well as in the control group (2.58 nmol/l-ELISA DRG® versus 1.14 nmol/l-LC-MS/MS p 0.0001). Additional, unnecessary diagnostic procedures explaining elevated 17OHP level were undertaken in 85% of patients when NovaTec® test was used, in 50% when ELISA DRG® and in none when LC-MS/MS method was applied. Total testosterone, androstendione and DHEA-S concentrations in the patients and the controls assessed by the immunoassays were also significantly higher compared to LC-MS/MS. LC-MS/MS is more reliable diagnostic tool in the measurement of serum 17OHP and androgens concentrations compared to immunoassays in women with hyperandrogenism.

Here we describe for the first time the synthesis of colloidally stable, brightly luminescent perfluorodecyl-capped silicon nanocrystals and compare the properties of solutions and films made from them with those of their perhydrodecyl-capped relatives. The perfluorodecyl capping group compared to the perhydrodecyl capping group yields superior hydrophobicity and much greater resistance to air oxidation, the enhanced electron-withdrawing character induces blue shifts in the wavelength of photoluminescence, and the lower-frequency carbon-fluorine stretching modes disfavor non-radiative relaxation pathways and boost the absolute photoluminescence quantum yield. Together these attributes bode well for advanced materials and biomedical applications founded upon perfluorodecyl-protected silicon nanocrystals.

Aim Aging is usually associated with hyperleptinemia and leptin resistance, both increasing the risk of age-related diseases. It was relevant to establish if healthily aging, non-obese individuals develop changes in leptin, the soluble leptin receptor (OB-Re), free leptin index (FLI), in methylation of the leptin receptor gene (LEPR) promoter, and in the expression of long (OB-Rb) and short (OB-Ra) leptin receptor isoforms. Methods We analyzed these parameters in 38 young (aged 26.8 ± 3.6 years), 37 elderly (aged 64.7 ± 3.1 years) and 39 long-lived (aged 94.2 ± 3.7 years) healthy, non-obese Polish Caucasians. Results In elderly men, the median concentration of leptin and the median FLI were significantly higher than in young men (P = 0.009 and P = 0.007, respectively), which was probably partly due to a higher mean body mass index of the elderly study participants. In peripheral blood mononuclear cells, the expression of functionally active OB-Rb did not depend on age or sex, whereas the expression of OB-Ra was lower in the elderly and long-lived groups than in the young group (P

Wstep: Dlugowieczności czesto towarzyszy dobry stan zdrowia, opoźnione zachorowanie na „choroby związane z wiekiem”, ktorych przebieg jest zwykle lagodny. Leptyna (LEP) znacząco wplywa na metabolizm oraz na inne funkcje organizmu. Aby sprawdzic, czy ekstremalna dlugowiecznośc i jej fenotyp są powiązane z odmianami genow leptyny i receptora leptyny (LEPR), przebadaliśmy czestośc wystepowania polimorfizmow –2548 G/A i +19 G/A genu LEP oraz K109R, Q223R, i K656N genu LEPR u stulatkow i w grupach kontrolnych. Material i metody: Czestośc wystepowania polimorfizmow genow LEP i LEPR badano metodą analizy dlugości fragmentow restrykcyjnych u 128 stulatkow, 414 mlodych kontroli (Y), 226 pacjentow z zawalem serca (MI) i u 190 pacjentow z cukrzycą 2 typu (DM2). Wyniki: Genotyp GG polimorfizmu –2548 G/A genu LEP byl znamiennie czestszy u stulatkow niz w grupach Y, MI i DM2 (odpowiednio p = 0,048, p = 0,003 i p = 0,049). Genotyp AA polimorfizmu K109R genu LEPR byl znamiennie rzadszy u stulatkow niz w grupach Y, MI i DM2 (odpowiednio p = 0,026, p = 0,013 i p = 0,001). Wnioski: Sugerujemy, ze szlak oddzialywan leptyny bierze udzial w regulowaniu dlugości zycia, byc moze poprzez modulowanie ryzyka zachorowania na MI i DM2. (Endokrynol Pol 2014; 65 (1): 11–16)

Background: Given the role that vitamin D (VD) plays in the regulation of the inflammatory activity of adipocytes, we aimed to assess whether obesity changes the expression of VD-related genes in adipose tissue and, if so, to investigate whether this phenomenon depends on microRNA interference and how it may influence the local inflammatory milieu. Methods: The expression of genes encoding VD 1&alpha, hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and receptor (VDR), selected interleukins and microRNAs was evaluated by real-time PCR in visceral (VAT) and in subcutaneous (SAT) adipose tissues of 55 obese (BMI &gt, 40 kg/m2) and 31 normal-weight (BMI 20&ndash, 24.9 kg/m2) individuals. Results: VDR mRNA levels were higher, while CYP27B1 levels were lower in adipose tissues of obese patients than in those of normal-weight controls (VAT: P = 0.04, SAT: P &lt, 0.0001 and VAT: P = 0.004, SAT: P = 0.016, respectively). The expression of VDR in VAT of obese subjects correlated negatively with levels of miR-125a-5p (P = 0.0006, rs = &minus, 0.525), miR-125b-5p (P = 0.001, rs = &minus, 0.495), and miR-214-3p (P = 0.009, rs = &minus, 0.379). Additionally, VDR mRNA concentrations in visceral adipose tissues of obese subjects correlated positively with mRNA levels of interleukins: 1&beta, 6 and 8. Conclusions: We observed obesity-associated up-regulation of VDR and down-regulation of CYP27B mRNA levels in adipose tissue. VDR expression correlates with the expression of pro-inflammatory cytokines and may be regulated by miRNAs.

The number of years of education an individual completes is related to their future morbidity and mortality. There are obvious drivers for educational attainment such as childhood intellect, parental intelligence, and education attainment, as well as socioeconomic status; and associations may be age dependent. We investigated associations between intelligence across childhood (collected at 2, 4, 7, and between 11 and 13 years) and educational attainment (total years) by the late 20s in the Port Pirie Cohort Study, South Australia (n = 388), taking into account maternal intelligence, parental schooling, and occupational prestige. A structural equation model showed that paternal schooling and intelligence at 7 years were significantly related to educational attainment by the late 20s. Maternal intelligence was strongly associated with early life but not adolescent intelligence within the model. These findings highlight the complex intergenerational transmission of social advantages and substantiate the independent effects of education and intelligence on later morbidly and mortality. Refereed/Peer-reviewed

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the developed world. Simple hepatic steatosis is mild, but the coexistence of steatohepatitis (NASH) and fibrosis increases the risk of hepatocellular carcinoma. Proper dietary and pharmacological treatment is essential for preventing NAFLD progression. The first-line treatment should include dietary intervention and increased physical activity. The diet should be based on the food pyramid, with a choice of products with low glycemic index, complex carbohydrates in the form of low-processed cereal products, vegetables, and protein-rich products. Usage of insulin-sensitizing substances, pro- and prebiotics, and vitamins should also be considered. Such a therapeutic process is intended to support both liver disease and obesity-related pathologies, including insulin resistance, diabetes, dyslipidemia, and blood hypertension. In the pharmacological treatment of NAFLD, apart from pioglitazone, there are new classes of antidiabetic drugs that are of value, such as glucagon-like peptide 1 analogs and sodium/glucose cotransporter 2 antagonists, while several other compounds that target different pathogenic pathways are currently being tested in clinical trials. Liver biopsies should only be considered when there is a lack of decline in liver enzymes after 6 months of the abovementioned treatment. Dietary intervention is recommended in all patients with NAFLD, while pharmacological treatment is recommended especially for those with NASH and showing significant fibrosis in a biopsy.

The brain is dependent on the cerebrovascular system, particularly microvasculature, for a consistent blood supply; however, age-related changes in this system affect neuronal and therefore cognitive function. Structural vascular markers and vascular disease appear to preferentially affect fluid cognitive abilities, sparing crystallized abilities. We sought to investigate the relationships between cerebrovascular function and cognitive domains. Fifty individuals between 60 and 75 years of age (31 women, 19 men) underwent cognitive testing: Wechsler Vocabulary and Matrix Reasoning subtests (crystallized and fluid ability measures, respectively Wechsler, 2011), and the Addenbrooke's Cognitive Examination-Revised (ACE-R; general cognitive ability; Mioshi, Dawson, Mitchell, Arnold, & Hodges, 2006). Transcranial Doppler (TCD) measures were also collected at rest and during a cognitive word-generation task, from which a lateralization index was calculated. Lower pulsatility index at rest, and greater left lateralization during the TCD cognitive task were associated with better performance on the Matrix Reasoning but not the Vocabulary test; these effects were independent from each other and from any vascular comorbidity burden. These functional findings confirm previous structural studies, which revealed that fluid abilities are more vulnerable to cerebrovascular dysfunction than crystallized abilities, and identify two (likely related) mechanisms: degraded cerebrovascular integrity (indexed by pulsatility index) and a delateralization of function. Cerebrovascular dysfunction is a key contributor to cognitive aging that deserves further attention, particularly in relation to early diagnostic markers of impairment and monitoring of vascular (e.g., physical activity) interventions.

Objectives: Total testosterone/dihydrotestosterone ratio (TT/DHT) was found to determine metabolic risk in polycystic ovary syndrome (PCOS). The aim of this study was to analyze whether (TT/DHT) may be helpful in predicting metabolic risk not only in PCOS patients but also in healthy women. Material and methods: Total testosterone (TT), dihydrotestosterone (DHT), androstendione and dehydroepiandrosterone sulphate (DHEA-S) were measured by LC-MS/MS in 36 women with PCOS and in 29 age-matched controls without clinical hyperandrogenism. In all participants, anthropometric data, lipids, adipose tissue percent (%fat), HOMA-IR were also assessed. Results: The studied groups were not different in terms of age, BMI, waist circumference, %fat and HOMA-IR. In the patients group, mean TT and androstendione levels were significantly higher as compared to controls (1.4 nmol/L vs . 1.0 nmol/L, P < 0.001) and (6.6 nmol/L vs. 4.9 nmol/L, P < 0.01), respectively. In the patients group, mean TT/DHT ratio was significantly higher compared to controls (3.6 vs. 2.7, P < 0.01) and correlated with BMI (r = 0.37, P < 0.05), waist circumference (r = 0.44, P < 0.01), %fat (r = 0.30, P < 0.05), as well as with insulin levels (r = 0.38, P < 0.05) and HOMA-IR (r = 0.44, P < 0.05). The association between TT/DHT ratio and unfavorable metabolic parameters was also seen in controls. Conclusion: Total testosterone/dihydrotestosterone ratio assessed by LC-MS/MS correlates with a worse metabolic profile not only in PCOS patients, but also in healthy women.

Most of the available non-invasive medical therapies for obesity are non-efficient in a long-term evaluation; therefore there is a constant need for new methods of treatment. Research on calorie restriction has led to the discovery of sirtuins (silent information regulators, SIRTs), enzymes regulating different cellular pathways that may constitute potential targets in the treatment of obesity. This review paper presents the role of SIRTs in the regulation of glucose and lipid metabolism as well as in the differentiation of adipocytes. How disturbances of SIRTs’ expression and activity may lead to the development of obesity and related complications is discussed. A special emphasis is placed on polymorphisms in genes encoding SIRTs and their possible association with susceptibility to obesity and metabolic complications, as well as on data regarding altered expression of SIRTs in human obesity. Finally, the therapeutic potential of SIRTs-targeted strategies in the treatment of obesity and related disorders is discussed.

The influence of surface geometry on adsorbed proteins offers new possibilities for controlling quaternary structure by manipulating protein-protein interactions at a surface, with applications that are relevant to protein aggregation, fibrillation, ligand binding, and surface catalysis. To understand the effect of surface curvature on the structure of the surface-bound protein β-lactoglobulin (β-LG), we have used a combination of polystyrene (PS) nanoparticles (NPs) and ultrathin PS films to fabricate chemically pure, hydrophobic surfaces that have nanoscale curvature and are stable in aqueous buffer. We have used single molecule force spectroscopy to measure the detachment contour lengths L(c) for β-LG adsorbed on the highly curved PS surfaces, and we compare these values in situ to those measured for β-LG adsorbed on flat PS surfaces on the same samples. The L(c) distributions measured on all flat PS surfaces show a large monomer peak near 60 nm and a smaller dimer peak at 120 nm. For 190 and 100 nm diameter NPs, which are effectively flat on the scale of the β-LG molecules, there is no measurable difference between the L(c) distributions obtained for the flat and curved surfaces. However, for 60 nm diameter NPs the dimer peak is smaller, and for 25 nm diameter NPs the dimer peak is absent, indicating that the number of surface-bound dimers is significantly reduced by an increase in the curvature of the underlying surface. These results indicate that surface curvature provides a new method of manipulating protein-protein interactions and controlling the quaternary structure of adsorbed proteins.

Although autoimmune diseases are relatively common, mechanisms that lead to their development remain largely unknown. Nuclear factor-kappaB (NF-kappaB), as a key transcription factor involved in the regulation of immune responses and apoptosis, appears to be a good candidate for studies on the pathogenesis of autoimmunity. This review presents how perturbations of the NF-kappaB signaling pathway may contribute to self-tolerance failure, initiation of autoimmune inflammatory response as well as its persistent maintenance and therefore to the development of common autoimmune diseases including rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, thyroid autoimmune diseases, systemic lupus erythematosus as well as inflammatory bowel diseases and psoriasis. A special emphasis is put on the genetic variations in the NF-kappaB related genes and their possible association with susceptibility to autoimmune diseases, as well as on the therapeutic potential of the NF-kappaB targeted strategies in the treatment of autoimmunity.

OBJECTIVE The aim of the present study was to verify whether selected functional single nucleotide polymorphisms in LEP, LEPR, and ADIPOQ loci are associated with the development of obesity and serum levels of the respective adipokines in prepubertal white children with obesity. METHODS Frequencies of -2548G>A LEP (rs7799039), Q223R (rs1137101) and K656N (rs8129183) LEPR, and -11377C>G (rs266729) and -11426A>G (rs16861194) ADIPOQ polymorphisms were analyzed by restriction fragment length polymorphism in 101 obese (standard deviation score [SDS]-body mass index [BMI] >2) and 67 normal-weight (SDS-BMI ) children. Serum adipokine concentrations were measured using the enzyme-linked immunosorbent assay method. RESULTS The GC/GG genotypes of -11377C>G ADIPOQ polymorphism were associated with a higher risk of obesity (P = 0.022, odds ratio 2.08 [95% confidence interval 1.11-3.90]). Individuals carrying the GG genotype had a higher leptin/total adiponectin ratio by 25% than CC homozygotes (P trend = 0.05). In the multivariate linear regression model, we found differences among particular genotypes of this polymorphism in concentrations of high molecular weight (HMW) adiponectin (P trend = 0.043) and HMW/total adiponectin ratio (P trend = 0.048), with the lowest values in GG homozygotes. Positive correlations between SDS-BMI and dietary reference intake percentage were observed in individuals homozygous for allele C (r = 0.403, P = 0.01) and CG heterozygotes (r = 0.428, P = 0.004). No significant correlations between both parameters were found in the GG homozygotes. CONCLUSIONS Among the analyzed polymorphisms, only -11377C>G ADIPOQ single nucleotide polymorphism was associated with obesity during the prepubertal period. Adipokine abnormalities coexisting with the lack of relations between SDS-BMI and dietary intake may predict a higher risk of future obesity-related disorders in obese children carrying the GG genotype than in those with other genotypes.

The diagnosis of celiac disease (CD) in patients with different autoimmune diseases including Graves disease (GD) remains a challenge. The aims of our study were to: (1) assess the prevalence of CD in Polish patients with GD and (2) evaluate the prevalence of CD in the subgroups of patients with GD divided on the basis of clinical and human leukocyte antigen (HLA) typing criteria.The prospective study was conducted at an academic referral center. The study groups consisted of consecutive, euthyroid patients with GD (n = 232) and healthy volunteers without autoimmune thyroid diseases (n = 122). The diagnosis of CD was based on elevated immunoglobulin A autoantibodies to the enzyme tissue transglutaminase (IgA-TTG) and small intestine biopsy findings.CD was diagnosed in 8 patients with GD (3.4%) and 1 healthy volunteer (0.8%). The development of CD in patients with GD was strongly associated with HLA-DQ2 haplotype (as predicted from linkage disequilibria, 14.6% vs. 1.5%, P = .009; odds ratio [OR] = 11.3; 95% confidence interval [CI] 1.3-252.7): 6 patients with CD carried HLA-DRB1(*)03, 1 carried an HLA-DRB1(*)04 allele, and 1 had an HLA-DRB1(*)07/(*)11 genotype. Multivariate analysis showed independent associations between CD and early GD onset (P = .014, OR = 9.6), autoimmunity in family (P = .029, OR = 6.3) and gastroenterologic symptoms (P = .031, OR = 8.1).The results of our study suggest that serologic screening for CD may be considered in GD patients (1) with the HLA alleles typical for CD, (2) with an early onset of GD, or (3) a family history of autoimmunity. Moreover, the diagnosis of CD should be explored in euthyroid GD patients with nonspecific gastrointestinal symptoms.

OBJECTIVE As nonclassic congenital adrenal hyperplasia (NCCAH) needs to be taken into account in women with hyperandrogenism, we aimed to assess whether the recommended level of poststimulated 17OHP ≥30 nmol/l confirms NCCAH. PATIENTS AND METHODS Forty, consecutive women with biochemical and/or clinical hyperandrogenism (aged 25·4, 18-38) suspected of having NCCAH were recruited to the study. In patients with 17OHP level between 5·1 and 29·9 nmol/l an ACTH stimulation test was performed. In patients with basal or poststimulated 17OHP ≥30 nmol/l, twenty-four-hour urinary steroid profile (USP) analysis was performed and CYP21A2 mutation was assessed. In selected patients with poststimulated 17OHP

OBJECTIVE Vitamin D-binding protein (DBP) genetic variants have an influence on vitamin D status and, therefore, they may contribute to the development of autoimmune diseases. In this case-control study, we investigated the association of DBP gene polymorphisms with susceptibility to Graves' disease (GD) in a Polish population. Furthermore, we analyzed the distribution of DBP genotypes in GD patients divided according to the clinical (gender, age of onset, ophthalmopathy, family history, smoking habits) and genetic parameters (CTLA4 49G and HLA-DRB1*03 alleles), as well as the vitamin D serum levels. METHODS 332 polish patients with GD and 185 healthy controls were genotyped for the DBP gene single nucleotide polymorphisms (SNPs) at codon 420 ACG --> AAG (Thr --> Lys) and at codon 416 GAT --> GAG (Asp --> Glu) by the PCR-RFLP method. The variable (TAAA)N repeat polymorphism in the intron 8 was analyzed in 332 patients and 164 controls by the PCR amplification followed by the PAGE. In addition, 25(OH)D3 serum levels were measured in 110 patients. RESULTS In patients with GD, the frequency of the Lys allele (34.2% vs. 25.7%, p = 0.005; OR = 1.50; 95% CI: 1.13-1.99) at codon 420 was significantly higher compared to controls. The distribution of codon 420 genotypes also differed significantly (p = 0.01), with the frequency of the Lys/Lys homozygotes (9.3% vs. 5.9%; OR = 1.63; 95% CI: 0.80-3.32) being higher in GD. The distribution of codon 416 alleles and genotypes did not differ in both studied groups (p = 0.59 and p = 0.81, respectively). Analysis of the intron 8 (TAAA)N repeat polymorphism led to the identification of a novel variant in the Polish population, described as 7 repeats, but no association between the intron 8 alleles and GD was observed. The 420 Lys allele was associated with lower 25(OH)D3 serum levels (p = 0.01). No correlation between the DBP genotypes and other susceptibility alleles or the GD clinical phenotype was observed. CONCLUSIONS (i) The DBP gene Lys allele at codon 420 confers susceptibility to GD in the Polish population, (ii) the codon 416 alleles and intron 8 (TAAA)N variants are not associated with susceptibility to and clinical phenotype of GD, and (iii) the codon 420 Lys allele correlates with lower 25(OH)D3 serum concentration.

To study interactions between the two most widely confirmed Graves' disease (GD) loci: HLA-DRB1 and CTLA-4. HLA-DRB1*03 (risk allele) and DRB1*07 (protective allele) were analyzed in this aspect, the linked TNF G(-308)A polymorphism was also considered.A case-control study of 429 patients with GD compared to 308 healthy subjects. The impact of genes and their interactions were analyzed by stepwise logistic regression.The independent effects of DRB1*03 and DRB1*07 were confirmed in our study both by stratification studies and logistic regression. CTLA-4 did not appear to be associated with GD when the interactions with other genes were considered. By logistic regression we observed a significant interaction between DRB1*07 and CTLA-4 and revealed that CTLA-4 49G attenuated the DRB1*07-related protection, the effect noticed also in three-way stratification studies. We confirmed that the TNF G(-308)A polymorphism is only a marker of the DRB1 status.Our results stress the importance of complex gene interactions in the multigene predisposition to GD. The interactions between two predisposing loci, DRB1 and CTLA-4, are exerted rather by DRB1*07 than DRB1*03 allele: CTLA-4 acts via switching off the protective DRB1*07 influence, whereas the effect of DRB1*03 is independent.

Recently, a functional polymorphism in the CD40 gene at position -1, C to T change (C-1T) has been identified and the C/C genotype has been reported to be associated with Graves' disease (GD).We performed a case-control, replication study on 556 patients with GD and 611 healthy subjects in a Polish population. Furthermore, we analyzed the distribution of CD40 genotypes in subgroups of patients with GD divided according to age of onset, gender, family history, tobacco smoking, ophthalmopathy, and genetic parameters (CTLA4 49G, PTPN22/LYP 1858T or HLA-DRB1*03 alleles).Although the frequency of C/C genotype was increased in GD compared to controls, the difference was not significant (60.5% versus 55.8%, p = 0.062, odds ratio [OR] = 1.21, 95% confidence interval [CI]: 0.96-1.53). Because our study was underpowered to detect such a modest association, we performed a meta-analysis with the data from previous studies. The combined OR for the C/C genotype as a risk factor for GD was 1.22 (95% CI: 1.08-1.38, p = 0.001). We failed to find an interaction between CD40 genotypes and other GD susceptibility alleles. No significant genotype-phenotype associations were found.Our results support the notion that CD40 C-1T polymorphism has a modest effect on genetic susceptibility to sporadic GD.

Summary objective In patients with Graves’ disease (GD), an elevation of serum immunoglobulin E (IgE) has been recently reported to be associated with the severity of hyperthyroidism and ophthalmopathy. Interleukin 13 (IL-13) is a major cytokine involved in IgE synthesis and therefore may be a potential candidate gene contributing to the development of GD or influencing the clinical course of the disease. design In a case–control study, we examined IL-13 gene single-nucleotide polymorphisms in the 5′ promoter region at position −1112 (C to T change, termed as C−1112T) and in exon 4 at position 2044 (G to A change, G2044A, which results in an amino acid exchange Arg130Gln) in 261 patients with GD. The control groups consisted of healthy young subjects (n = 168) and subjects over 100 years old with no history of autoimmune or allergic diseases recruited from the Polish Centenarians Project (n = 50). measurements C−1112T and G2044A polymorphisms were defined by fluorescent single-strand conformational polymorphism and by restriction fragment length polymorphism analysis, respectively. results In patients with GD, the distribution of IL-13 alleles (−1112T 31%; 2044A 25%) and genotypes (−1112T/T 10%; 2044A/A 7%) did not differ significantly compared to control groups. Subdividing GD patients according to clinically evident ophthalmopathy (NOSPECS class III or higher, n = 93) revealed no significant differences in the frequencies of −1112T allele (33%vs. 29%; P = 0·4), −1112T/T genotype (13%vs. 8%; P = 0·3), 2044A allele (27%vs. 24%; P = 0·5) and 2044A/A genotype (9%vs. 7%; P = 0·7) between GD patients with and without eye involvement. In order to analyse the association with the severity of hyperthyroidism, we examined patients with a first onset of GD treated with antithyroid drugs (n = 32). IL-13 genotypes were not associated with the laboratory findings at diagnosis (thyroid volume, serum levels of FT4, TRAb, TPOAb, TGAb) and with the outcome of antithyroid drug treatment. conclusions Our results suggest that IL-13 gene polymorphisms at positions −1112 (C → T) and 2044 (G → A): (1) do not confer genetic susceptibility to Graves’ disease; (2) do not contribute to the development of clinically evident ophthalmopathy; (3) are not associated with severity of hyperthyroidism.