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Purpose We compared the sexual function in women with classic forms of congenital adrenal hyperplasia (CAH) and polycystic ovary syndrome (PCOS) to find if the cause of androgen excess determines sexual functioning. Methods Hundred and four women (21 with CAH, 63 with PCOS and 20 healthy controls) aged 18–40 years were included into the study. All participants completed a questionnaire regarding their sociodemographic background and underwent anthropometric and basic biochemical measurements. Plasma levels of total testosterone, androstenedione, and 17-hydroxyprogesterone were measured with immunoassay. To assess the sexual functions, the Female Sexual Function Index (FSFI) questionnaire was applied. Results Apart from the higher physical activity in PCOS patients (P = 0.017), we found no significant sociodemographic differences between the studied groups. In clinical assessment, women with CAH had a lower incidence of acne (P = 0.006). Their plasma levels of 17OHP (P = 0.005) and insulin resistance index (P = 0.0248) were higher, while total testosterone (P = 0.0495) and glucose (P = 0.0061) was lower compared to the PCOS group. Significantly more women with CAH were homosexual (P = 0.003) and bisexual (P = 0.006). CAH group showed a lower total FSFI score (P = 0.0043) and lower scores in three domains: lubrication (P = 0.0131), sexual satisfaction (P = 0.0006), and dyspareunia (P P = 0.009) and scores in the domain of desire (P = 0.034) and sexual satisfaction (P = 0.01), while in CAH women apart from the total score (P = 0.03) and sexual satisfaction (P = 0.002) also in the domains of orgasm (P = 0.005), and pain (P = 0.03). Conclusions CAH women present more often homosexual and bisexual orientation, while their sexual functions are impaired compared to PCOS patients.

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.

Given the growing number of type 2 diabetic individuals and the substantial social and financial costs associated with diabetes management, every effort should be made to improve its prevention and treatment methods. There is an ongoing search for natural dietary compounds that could be used for this purpose. This narrative review focuses on the therapeutic potential of isoflavones in diabetes prevention and treatment. This review summarizes (i) the molecular mechanisms of isoflavones action that are critical to their anti-diabetic properties; (ii) preclinical (in vitro and in vivo) studies evaluating the influence of isoflavones on the function of key organs involved in the pathogenesis of diabetes; and (iii) epidemiological studies and clinical trials that assessed the effectiveness of isoflavones in the prevention and treatment of type 2 diabetes in humans. Apart from discussing the effects of isoflavones on the function of organs “classically” associated with the pathogenesis of diabetes (pancreas, liver, muscles, and adipose tissue), the impact of these compounds on other organs that contribute to the glucose homeostasis (gastrointestinal tract, kidneys, and brain) is also reviewed.

In recent years, there has been a large amount of evidence on the role of microRNA (miRNA) in regulating adipose tissue physiology. Indeed, miRNAs control critical steps in adipocyte differentiation, proliferation and browning, as well as lipolysis, lipogenesis and adipokine secretion. Overnutrition leads to a significant change in the adipocyte miRNOME, resulting in adipose tissue dysfunction. Moreover, via secreted mediators, dysfunctional adipocytes may impair the function of other organs and tissues. However, given their potential to control cell and whole-body energy expenditure, miRNAs also represent critical therapeutic targets for treating obesity and related metabolic complications. This review attempts to integrate present concepts on the role miRNAs play in adipose tissue physiology and obesity-related dysfunction and data from pre-clinical and clinical studies on the diagnostic or therapeutic potential of miRNA in obesity and its related complications.

Purpose/Aim: So far no research concerning the omentin-1 (ITLN1) rs2274907 and vaspin (SERPINA12) rs2236242 polymorphisms has been carried out in a healthy pediatric population. We analyzed...

Introduction Polymorphism of the glucocorticoid receptor gene (NR3C1) may modify protein abundance or function and therefore disturb human homeostasis. Methods Variant frequencies of the three NR3C1 polymorphisms, rs2963154, rs10515522 and rs2918418, selected in silico as associated with longevity, was analyzed in 552 DNA samples from 95 to 106-year-old individuals and in 284 samples of cord blood DNA from newborns. Results Frequencies of the TT genotypes of rs2963154 and rs10515522, and of the rs291841 CC genotype, were higher in the long-lived study subjects (p = 0.002, p = 0.016 and p = 0.028, respectively). In the long-lived cohort, the rs2963154 CC genotype was associated with higher concentrations of total (p = 0.007) and high-density cholesterol (p = 0.039). The rs10515522 CC genotype was associated with a higher concentration of total cholesterol (p = 0.049). The rs2918418 GG genotype was associated with higher concentrations of total (p = 0.03) and low-density cholesterol (p = 0.03). None of the polymorphisms was associated with fasting glucose, C-reactive protein levels and white blood count, prevalence of diabetes, stroke, myocardial infarction, or cognitive function. However, carriers of the rs10515522 minor allele had significantly better survival rates than carriers of other genotypes. Conclusion NR3C1 polymorphisms modify cholesterol levels, and may affect the survival rates of individuals in their tenth and eleventh decades of life.

Skin aging is associated with the accumulation of senescent cells and is related to many pathological changes, including decreased protection against pathogens, increased susceptibility to irritation, delayed wound healing, and increased cancer susceptibility. Senescent cells secrete a specific set of pro-inflammatory mediators, referred to as a senescence-associated secretory phenotype (SASP), which can cause profound changes in tissue structure and function. Thus, drugs that selectively eliminate senescent cells (senolytics) or neutralize SASP (senostatics) represent an attractive therapeutic strategy for age-associated skin deterioration. There is growing evidence that plant-derived compounds (flavonoids) can slow down or even prevent aging-associated deterioration of skin appearance and function by targeting cellular pathways crucial for regulating cellular senescence and SASP. This review summarizes the senostatic and senolytic potential of flavonoids in the context of preventing skin aging.

Introduction: Type 2 diabetes is one of the most common diseases in the aging population; however, data concerning correlates of diabetes in age-advanced individuals are limited. The study aimed to identify the socioeconomic correlates of diabetes in representative groups of oldest-old (≥ 85 years) and younger (65 to 84 years) Polish Caucasian seniors. Material and methods: PolSenior is a multicentre, population-based study conducted in Poland. Fasting plasma glucose levels and data from detailed medical questionnaires were obtained from 2128 male and 1961 female study participants aged ≥ 65 years. Multivariate logistic regression was used to identify significant socioeconomic risk factors for diabetes and undiagnosed diabetes. Results: The overall prevalence of diabetes in the study group was 21.9% (24.0% in women vs. 19.9% in men, p = 0.002), with an estimated weighted prevalence for all older Poles of 23.1%. Nearly one-fifth of cases were previously undiagnosed. Diabetes was more common in the younger elderly (65–84 years) than in the oldest-old (≥ 85 years) (23.4% vs. 18.6%, p < 0.001). The frequency of diabetes was higher in women than in men (24.0% vs. 19.9%, p < 0.002); however, men remained undiagnosed more commonly than women (4.7% vs. 3.3%, p = 0.029). The frequency of diabetes was higher among urban than rural dwellers (23% vs. 20.4%, p = 0.048). It was also related to marital status in women (p = 0.036) and occupation in men (p = 0.015). Multivariate logistic regression analysis revealed that the independent risk factors for diabetes were body mass index (BMI) and marital status in women, while in men it was solely BMI. Undiagnosed diabetes was more frequent among rural than city dwellers (4.8% vs. 3.5%, p = 0.03). In multivariate logistic regression analysis, only BMI and place of residence remained significant risk factors for being undiagnosed. Conclusions: The prevalence of diabetes in the ≥ 65-year-old population exceeds 20% but is lower in the oldest-old than in the younger elderly and is modified by socioeconomic factors. Many elderly individuals remain undiagnosed and do not benefit from the currently available therapy.

In the assessment of the health risk of an obese individual, both the amount of adipose tissue and its distribution and metabolic activity are essential. In adults, the distribution of adipose tissue differs in a gender-dependent manner and is regulated by sex steroids, especially estrogens. Estrogens affect adipocyte differentiation but are also involved in the regulation of the lipid metabolism, insulin resistance, and inflammatory activity of the adipose tissue. Their deficiency results in unfavorable changes in body composition and increases the risk of metabolic complications, which can be partially reversed by hormone replacement therapy. Therefore, the idea of the supplementation of estrogen-like compounds to counteract obesity and related complications is compelling. Phytoestrogens are natural plant-derived dietary compounds that resemble human estrogens in their chemical structure and biological activity. Supplementation with phytoestrogens may confer a range of beneficial effects. However, results of studies on the influence of phytoestrogens on body composition and prevalence of obesity are inconsistent. In this review, we present data from in vitro, animal, and human studies regarding the role of phytoestrogens in adipose tissue development and function in the context of their potential application in the prevention of visceral obesity and related complications.

AIM The diagnosis of biochemical hyperandrogenism is still challenging because a set of appropriate, recommended diagnostic tests has not been established. In our study, we aimed to answer the question of whether salivary testosterone is a reliable test to establish the diagnosis of biochemical hyperandrogenism as compared to serum total testosterone (TT) measured either by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay and to assess which set of biochemical tests would be the most appropriate for the identification of biochemical hyperandrogenism. METHODS A total of 39 women, aged 18-45 years, with clinical or biochemical hyperandrogenism and 41 healthy individuals, aged 19-45 years, were enrolled in the study. Salivary testosterone was measured using the Salimetrics test. Serum TT was measured either using the LC-MS/MS method or immunoassay, and dehydroepiandrosterone sulphate (DHEA-S) and androstenedione were measured using LC-MS/MS. RESULTS In 15 of 17 (88%) patients with elevated serum TT measured by LC-MS/MS and in 14 of 16 (87%) measured with immunoassay, salivary testosterone showed normal levels. In 11 of 39 women (28%) with normal serum testosterone levels, DHEA-S was elevated. All patients with elevated androstenedione presented with an elevated concentration of either serum testosterone or DHEA-S. CONCLUSION Salivary testosterone measurement may lead to the underdiagnosis of biochemical hyperandrogenism. Both serum testosterone and DHEA-S should be measured in the endocrine work-up toward biochemical hyperandrogenism.

Objectives To investigate the influence of overweight and obesity on general performance and mortality in seniors. Design Cross-sectional multidisciplinary study on ageing of the Polish population. Setting Community-dwelling individuals aged 65 years or older, selected using three-stage stratified, proportional draw. Participants 4944 Polish Caucasian seniors, aged 65 years or older recruited between October 2007 and October 2010. Measurements All study subjects underwent measurement of body mass index (BMI), waist circumference (WC), and arm circumference (AC). The physical and cognitive performance was evaluated using the Katz Activities of Daily Living (ADL) score and Mini-Mental State Examination (MMSE), respectively. Morbidity data were obtained from a medical questionnaire. Mortality data were obtained from the Population Register of Poland between October 2015 and October 2018. Results Increasing age was associated with a decreased prevalence of obesity (all p Conclusions Overweight and obesity in Caucasian seniors are not associated with deterioration of physical and cognitive function or with increased mortality.

The aim of the study was to investigate the possible role of coagulation factor XIII (FXIII) plasma activity and its gene (F13A1) Val34Leu variant as well as thrombospondin-2 gene (THBS2) T/G 3′UTR and thrombospondin-4 gene (THBS4) Ala387Pro variants in the development of myocardial infarction (MI) in young patients. The studied group consisted of 158 patients aged

One of the concepts explaining the coincidence of obesity and type 2 diabetes (T2D) is the metaflammation theory. This chronic, low-grade inflammatory state originating from metabolic cells in response to excess nutrients, contributes to the development of T2D by increasing insulin resistance in peripheral tissues (mainly in the liver, muscles, and adipose tissue) and by targeting pancreatic islets and in this way impairing insulin secretion. Given the role of this not related to infection inflammation in the development of both: insulin resistance and insulitis, anti-inflammatory strategies could be helpful not only to control T2D symptoms but also to treat its causes. This review presents current concepts regarding the role of metaflammation in the development of T2D in obese individuals as well as data concerning possible application of different anti-inflammatory strategies (including lifestyle interventions, the extra-glycemic potential of classical antidiabetic compounds, nonsteroidal anti-inflammatory drugs, immunomodulatory therapies, and bariatric surgery) in the management of T2D.

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.

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.

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

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.

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

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.

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.

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.

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

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.

Tumor necrosis factor (TNF)-alpha plays a central role in the development of ophthalmopathy in patients with Graves' disease (GD). The aim of this study was to investigate the association of TNF promoter polymorphisms at positions -1031 (T-1031C), -863 (C-863A), -857 (C-857T), -308 (G-308A), and -238 (G-238A) with Graves' ophthalmopathy (GO). We studied the distribution of TNF and human leukocyte antigen (HLA) DRB1 alleles in 228 Polish white patients with GD, 106 of whom had ophthalmopathy (NOSPECS class > or = III) and 248 healthy subjects. TNF -308A and HLA-DRB1*03 alleles were significantly increased in patients with GD compared with healthy subjects. Stratification analysis revealed no independent association of -308A with GD when the DRB1*03 status was considered. Subdividing GD according to eye involvement revealed that the distribution of TNF promoter haplotypes differed significantly in patients with or without ophthalmopathy. The haplotype containing the -238A allele was absent in GO. The association of G-238A with GO was independent of DRB1 alleles. These results indicate that TNF G-308A is associated with susceptibility to GD (however, this association is not independent of HLA-DRB1*03) and that TNF G-238A is associated with the development of ophthalmopathy, suggesting that G-238A or a gene in linkage disequilibrium may be disease modifying in 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.

The worldwide epidemic of obesity and the limited effectiveness of the available treatments led to a renewed interest in developing therapeutic approaches which would reduce obesity by increasing energy expenditure. Knowledge of the mechanism involved in the regulation of thermogenesis in mammals has led to the belief that compounds activating adrenergic receptors beta and/or thyroid hormone receptors may be effective in obesity treatment. However, the translation of the results obtained in the in vitro and in animal studies on humans occurred to be not as direct and effective as expected. This mini-review discusses the potential role of thermogenesis impairment in development of human obesity as well as possible limitations in the application of thermogenic compounds in obesity treatment.

During the last decade a growing interest in vitamin D-related problems can be observed and a few thousands of scientific publications are dedicated to this task every year. The alarming statistical data regarding propagation of vitamin D deficiency in all continents and our developing knowledge about novel, non-calcemic actions of vitamin D seem to be two main causes of this phenomenon. Indeed, recent epidemiological studies suggest that worldwide prevalence of inadequate vitamin D status is higher than expected, however it may result from different factors, including geographical location and cultural background. Since vitamin D skin synthesis, which takes place under the influence of the sun’s ultraviolet B (UVB) radiation, covers as much as 90% of total body needs, inadequate radiation or insufficient cutaneous absorption of UVB are regarded as major causes of vitamin D deficiency. Air pollution is a chief factor determining the extent of solar UVB that reaches earth surface and several epidemiological data, which represents different populations living in different geographic latitudes, indicate that atmospheric pollution (especially high tropospheric ozone content) may play a significant independent role in the development of vitamin D deficiency. As a result prevalence of D hypovitaminosis among urban residents can be more than twice higher than that of rural inhabitants. The problem of vitamin D insufficiency has been underestimated for many years and it has been predominantly associated only with bone diseases. Discovery of vitamin D receptor and its identification in a wide number of tissues other than bones led to the designation of novel, so-called “non-calcemic” (e.g. antiproliferative and immunomodulatory), actions of cholecalciferol. Subsequently, there is a growing number of diseases and conditions, development and/or progression of which can be associated with inadequate vitamin D status, including different types of cancers, autoimmune disorders as well as cardiovascular events. Interestingly, prevalence of many of these diseases also positively correlates with the intensity of air pollution. Therefore one can conclude that with the increasing atmospheric pollution grows a number of people in the world who are vitamin D deficient or insufficient and indirectly exposed to several poor health outcomes. This chapter gives an overview of the literature on this topic and assesses the available data about the association between air pollution, vitamin D status and prevalence of so-called civilization-related diseases. A general information regarding vitamin D metabolism is

Diverse genes are candidates for susceptibility to Graves' disease, including the vitamin D receptor (VDR), which regulates the transcription of target genes in response to the active metabolite 1,25(OH)(2)D(3). We analyzed four polymorphisms of the VDR gene (ApaI, TaqI, BsmI, and FokI) in patients with Graves' disease (n = 789) and healthy controls (n = 823) from three European populations (German, Polish, and Serbian). The VDR ApaI (rs7975232) and TaqI (rs731236) polymorphisms showed no significant difference in any population. The BsmI (rs1544410) variant "b" was associated with Graves' disease in the Polish population (p = 0.0070). The FokI (rs10735810) variant "f " was found to be associated with Graves' disease in Germans and "F" in Polish patients (p = 0.0024 and 0.0049, respectively). Construction of haplotypes for TaqI, ApaI, and BsmI showed the haplotype "Tab" to be the most frequent in the German and Polish population as well as in the Serbian patients, while "tAB" in Serbian controls. Our results show an association of VDR gene polymorphisms in the German and Polish population but not in the Serbian. Furthermore, the VDR polymorphisms are differentially distributed in the three populations. Therefore, VDR polymorphisms analysis needs to be stratified according to the population background.

Interleukin-6 (IL-6) may play an important role in the pathogenesis of Graves' ophthalmopathy (GO). The aim of this study was to analyze the association of IL-6 gene promoter polymorphism, at position - 174 (G --> C, termed as G-174C), which may affect IL-6 production, with the development of GO. The G-174C polymorphism was determined in 279 Polish-Caucasian patients with Graves' disease (GD), of which 108 had clinically evident ophthalmopathy (NOSPECS class III or higher) and 186 healthy Polish adults. In patients with GD, the frequencies of the C allele (45 vs 42%; P = 0.35) and C/C genotype (20 vs 15%; P = 0.13) were not significantly different compared to controls. Subdividing patients with GD for the presence of eye disease revealed that the C allele (44 vs 45%; P = 0.76) and C/C genotype (20 vs 20%; P = 0.92) were equally distributed in patients with or without ophthalmopathy. There was also no association between the G-174C polymorphism and the severity of eye changes. Finally, IL-6 genotypes were not associated with laboratory findings (thyroid volume, serum IL-6 and thyroid autoantibodies levels) in patients with GD at diagnosis. Our results suggest that G-174C polymorphism of the IL-6 gene does not contribute to the development and severity of GO.

Background Genes related to the nuclear factor-κB (NF-κB), a key transcription factor involved in regulation of immune responses, are interesting candidates for association studies in autoimmune disorders. The aim of this study was to investigate an association of polymorphisms in two genes encoding NF-κB inhibitors: IKBL (encoding inhibitor of κB-like) and NFKBIA (encoding κB inhibitor α), withsusceptibility to and phenotype of Graves' disease (GD). Methods A population-based, case-control association study comprising 481 patients with GD and 455 healthy controls was performed. We analyzed 3 single nucleotide polymorphisms (SNPs) in IKBL [promoter region -62T/A substitution (rs2071592), intron 1 C/T substitution (rs2071591) and exon 4 T/C substitution (rs3130062)] and 3 SNPs in NFKBIA [G/A substitution in 3' untranslated region (rs696) and two promoter region polymorphisms -297C/T (rs2233409) and -826C/T (rs2233406)] by the PCR-restriction fragment length polymorphism (RFLP) method. Results The two SNPs in IKBL (rs2071592 and rs2071591) were in a strong linkage disequilibrium (D' = 0.835) and the AT haplotype was associated with susceptibility to GD (p < 10-4, OR = 1.61 [95%CI:1.21-2.14]). Moreover subgroup analysis revealed a gen-gen interaction between the investigated IKBL haplotype and HLA-DRB1*03 allele (p < 10-4). The investigated NFKBIA SNPs were not associated with susceptibility to GD. However, when correlated with phenotype, the -297T (rs2233409) and -826T (rs2233406) alleles were associated with the development of clinically evident ophthalmophaty (p = 0.004, pc = 0.07, OR = 1.65 [95%CI: 1.18-2.38] and p = 0.002, pc = 0.036, OR = 1.67 [95%CI: 1.20-2.36], respectively). Conclusion Our results suggest that SNPs in genes encoding NF-κB inhibitors may contribute to the development and clinical phenotype of GD.