Postprandial Triglyceride, Glucose and Insulin Levels 10 Years After Bariatric Surgery in Women With Severe Obesity - A Pilot Study: Part 1 - Laparoscopic Greater Curvature Plication.

The long-term effects of bariatric surgery on postprandial profiles in patients with obesity and type 2 diabetes (T2D) have not yet been investigated. Therefore, this study examined postprandial profiles before laparoscopic greater curvature plication (LGCP), and then at 2 and 10 years after surgery.The studied cohort included 10 women (mean age= 54.4±5 years) with obesity (mean BMI= 42.5±7.8 kg/m?) and T2D who underwent LGCP. All subjects underwent a standardized liquid mixed-meal test. For statistical evaluation, ANOVA with Bonferroni multiple comparison was used. Mean postprandial levels were significantly decreased 2 years after surgery. Responses 10 years after the surgery also remained significantly lower than before surgery. Changes observed during the follow-up were significant: glucose: F=34.5, p<0.001; insulin: F=49.3, p<0.001; triglycerides F=9.2, p<0.001. The long-term favorable effects of bariatric surgery on cardiometabolic health may be partly mediated by reductions in postprandial glucose, insulin, and triglyceride levels.

Postprandial Triglyceride, Glucose and Insulin Levels 10 Years After Bariatric Surgery in Women With Severe Obesity - A Pilot Study: Part 2 - Biliopancreatic Diversion.

Obesity significantly increases the risk of developing metabolic and cardiovascular diseases. The most effective management tool for both obesity and type 2 diabetes (T2D) is bariatric/metabolic surgery. Delayed postprandial plasma triglyceride clearance contributes to the development of atherosclerosis in patients with T2D. Biliopancreatic diversion (BPD) was shown to be the most effective procedure in long-term T2D remission. However, the effect of BPD on postprandial metabolic profile has not been studied so far. In this pilot study, we therefore examined the changes in postprandial glucose, insulin, and triglyceride in women with severe obesity and T2D before surgery and then two and ten years after BPD. The studied cohort included 7 women (mean age at baseline=49.3±8.2 years) with severe obesity (mean BMI= 45.7±2.9 kg/m?) and T2D. A standardized liquid mixed-meal test was carried out in all subjects and the mean postprandial levels of plasma glucose, insulin, and triglyceride were analyzed by standard laboratory procedures. For statistical evaluation, ANOVA with Bonferroni multiple comparisons was used. Ten years after BPD not only a significant reduction of an average BMI (F=32.9, p<0.001) but also significant declines in mean postprandial plasma levels of glucose (F=155.3, p<0.001), insulin (F=69.8, p<0.001), and triglyceride (F=139.9, p<0.001) were demonstrated. The observed changes in postprandial metabolic profile may contribute to improved cardiometabolic health after bariatric surgery.

Endocrine disruptors, obesity, and cytokines - how relevant are they to PCOS?

As environmental and genetic components contribute to the PCOS expression, we compared levels of endocrine disruptors, steroid hormones, cytokines, and metabolic parameters in twenty healthy, nine normal-weight PCOS women, and ten obese PCOS women. Steroid hormones, bisphenols (BPA, BPS, BPF, BPAF) and parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-parabens) were measured by liquid chromatography-tandem mass spectrometry. Differences between the groups were assessed using the Mann-Whitney U test. Spearman correlation coefficients were calculated for the individual parameters relationship. Significantly higher levels of BPA, anti-Müllerain hormone, lutropine, lutropine/folitropine ratio, testosterone, androstenedione, 7beta-OH-epiandrosterone, and cytokines (IL-6, VEGF, PDGF-bb), were found in normal-weight PCOS women compared to controls. Between normal-weight and obese PCOS women, there were no differences in hormonal, but in metabolic parameters. Obese PCOS women had significantly higher insulin resistance, fatty-liver index, triglycerides, cytokines (IL-2, IL-13, IFN-gamma). In healthy, but not in PCOS, women, there was a positive correlation of BPA with testosterone, SHBG with lutropine, and folitropine, while testosterone negatively correlated with SHBG. In obese women with PCOS, insulin resistance negatively correlated with SHBG and estradiol. No differences were observed in the paraben exposure. Levels of BPA were higher in PCOS women, indicating its role in the etiology. Obesity significantly worsens the symptoms.

The gold standard of thyroid nodule examination? Prospective validation of the ACR TI-RADS in a secondary referral center.

The aim of this prospective study was the validation of the risk stratification of thyroid nodules using ultrasonography with the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) and partly in comparison to American Thyroid Association (ATA) guidelines in a secondary referral center. Fine needle aspiration biopsy (FNA) (n=605) and histological examinations (n=63) were the reference standards for the statistical analysis. ACR TI-RADS cut-off value: TR4 with sensitivity 85.7 %, specificity 54.1 %, PPV 58.5 %, accuracy 67.7 % (AUC 0.738; p<0.001). ATA cut-off value: "high suspicion" with sensitivity 80 %, specificity 83.3 %, PPV 80 %, accuracy 81.8 % (AUC 0.800; p=0.0025). 18.4 % nodules (3 malignant) could not be assigned to a proper ATA US pattern group (p<0.0001). Both ACR TI-RADS and ATA have allowed fair selection of nodules requiring FNA with superiority of ACR TI-RADS according to classification of all thyroid nodules to the proper group. According to ACR TI-RADS almost one third of the patients were incorrectly classified with 17.9 % missed thyroid carcinomas, exclusively micropapillary carcinomas, even though, the amount of FNA would be reduced to 48 %.

Diagnostic pitfalls in ovarian androgen-secreting (Leydig cell) tumours: case series.

Leydig cell tumours of the ovary are rare and represent a diagnostic challenge not only due to their sporadic incidence but also due to the seemingly normal imaging. We present three cases of pre- and postmenopausal women who were presented with severe clinical signs of hyperandogenism where modern imaging modalities (including computed tomography (CT), magnetic resonance imaging (MRI) and positron-emission tomography combined with computed tomography (PET-CT)) failed to identify the tumour. Two patients underwent non-expert ultrasound, CT and MRI examination with uniform conclusion that ovaries are of normal appearance. One of the two patients even had a PET-CT performed, which was inconclusive. Our case reports show the importance of examination by specialists with established skills in gynaecologic ultrasonography in the diagnosis of the Leydig cell tumours. The most useful diagnostic tool seems to be the combination of age (postmenopause), symptoms (onset of hirsutism and virilisation), high total testosterone plasma values and expert sonography. On ultrasound, these tumours are unilateral, usually small, solid intraovarian nodules of a slightly increased echogenicity in contrast to the surrounding ovarian tissue, delineated by abundant perfusion with an enhanced vascularity. The appropriate setting of the sensitive colour Doppler is crucial for the detection of intraovarian Leydig cell tumour. Impact statement What is already known on this subject? A diagnosis of Leydig cell tumours is based on ultrasound performed by a trained examiner or by MRI. CT or PET/CT are not among the primary methods of choice. According to the results of imaging investigations surgical treatment is planned. Because these tumours are usually benign and have a good prognosis the unilateral salpingo-oophorectomy is a standard procedure. What do the results of this study add? Our case series show how difficult it can be to establish the diagnosis of Leydig cell tumours by imaging, including transvaginal ultrasound, the most frequently recommended diagnostic tool. We demonstrate in three cases how easily a small hyperechogenic tumour can be overseen or interchanged for a different gynaecological pathology if transvaginal scan is not performed by an experienced examiner trained in sonographic features of gynaecologic neoplasms. What are the implications of these findings for clinical practice and/or further research? This case series demonstrate how important it is to see the patient in the whole complexity with their medical history, proper clinical symptoms evaluation, laboratory test and not to rely solely just on sophisticated high-end investigations, such as the PET-CT, a CT and an MRI. It also emphasises the importance of specialists with established skills in gynaecologic ultrasonography. Further effort should be made to define the resources for the appropriate training of such sonographers.

Genetic predictors of the development and recurrence of Graves' disease.

Graves' disease affects approximately 3 % of women and 0.5 % of men. The first-choice therapy is based on the administration of thyrostatic drugs. However, approximately half of patients relapse within two years of discontinuation. These patients must then decide whether to re-initiate thyrostatics, which may have serious side effects, or to undergo surgery or radioiodine treatment. Familial forms of Graves' disease indicate a significant genetic component, with twin studies demonstrating a contribution of genetic factors up to 70-80 %. The autoimmune nature of the disease involves the human leukocyte antigen (HLA) complex, which has a decisive impact on each individual's immune response. Within HLA, some variants of the DRB1, DQA1 and DQB1 genes appear to be possible predictors of the development and recurrence of Graves' disease. Outside the HLA region, many variants of immunocompetent genes have also been identified as potential Graves' disease predictors. Apart from the immune system, some thyroid-specific genes have been described in relation to the disease. Here, we present current knowledge regarding the genetic components involved in the development and recurrence of Graves' disease. Further, we present original pilot results from a cohort of Czech Graves' disease patients regarding the HLA variants.

Distinct response of fat and gastrointestinal tissue to glucose in gestational diabetes mellitus and polycystic ovary syndrome.

Gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS) are distinct pathologies with impaired insulin sensitivity as a common feature. The aim of this study was to evaluate the response of fat tissue adipokines and gastrointestinal incretins to glucose load in patients diagnosed with one of the two disorders and to compare it with healthy controls. Oral glucose tolerance test (oGTT) was performed in 77 lean young women: 22 had positive history of GDM, 19 were PCOS patients, and 36 were healthy controls. Hormones were evaluated in fasting and in 60 min intervals during the 3 h oGTT using Bio-Plex ProHuman Diabetes 10-Plex Assay for C-peptide, ghrelin, GIP, GLP1, glucagon, insulin, leptin, total PAI1, resistin, visfatin and Bio-Plex ProHuman Diabetes Adipsin and Adiponectin Assays (Bio-Rad). Despite lean body composition, both PCOS and GDM women were more insulin resistant than controls. Significant postchallenge differences between the GDM and PCOS groups were observed in secretion of adipsin, leptin, glucagon, visfatin, ghrelin, GIP, and also GLP1 with higher levels in GDM. Conversely, PCOS was associated with the highest resistin, C-peptide, and PAI1 levels. Our data suggest that decreased insulin sensitivity observed in lean women with GDM and PCOS is associated with distinct hormonal response of fat and gastrointestinal tissue to glucose load.

Fatty acid composition of adipose tissue triglycerides in obese diabetic women after bariatric surgery: a 2-year follow up.

Bariatric surgery is the most effective method in the treatment of obesity and type 2 diabetes (T2DM). The aim of this study was to evaluate the effects of different types of bariatric procedures on remission of T2DM and on the fatty acid composition in subcutaneous adipose tissue. Patients included obese diabetic women who underwent bariatric surgery: biliopancreatic diversion (BPD), n=8, laparoscopic gastric banding (LAGB), n=9 or laparoscopic greater curvature plication (LGCP), n=12. Anthropometric characteristics and fatty acid composition of adipose tissue (FA AT) were analyzed before surgery, then 6 months and 2 years after surgery. FA AT was analyzed by gas chromatography. Diabetes remission was estimated. BPD was most efficient in inducing a remission of diabetes (p=0.004). Significantly higher increases in lauric (12:0), myristoleic (14:1n-5) and palmitoleic (16:1n-7) acids and delta-9 desaturase were found two years after BPD, suggesting higher lipogenesis in adipose tissue. Docosatetraenoic acid (22:4n-6) increased significantly after BPD, while docosapentaenoic acid (22:5n-3) decreased 6 months after BPD and increased after 2 years. No changes were found after LAGB and LGCP after 2 years. Bariatric surgery led to significant changes in the fatty acid composition of subcutaneous adipose tissue in severely obese diabetic women after six months and two years, and was partly influenced by the type of surgery used.

T2D risk haplotypes of the TCF7L2 gene in the Czech population sample: the association with free fatty acids composition.

The association of transcription factor 7-like 2 (TCF7L2) gene variants with the pathogenesis of T2D, gestational diabetes and polycystic ovary syndrome (PCOS) was examined. The study involved 1460 individuals: 347 T2D patients (D); 261 gestational diabetics (G); 147 offspring of T2D (O); 329 women with PCOS, and 376 controls (C). The SNPs: rs7901695; rs7903146; rs12255372 in the TCF7L2 gene were genotyped. Anthropometric and biochemical parameters, oGTT derived indices were assessed. In addition, free fatty acids (FFAs) were evaluated in 183 non-diabetic women. The CTT haplotype showed the strongest association with T2D with OR 1.57, p=0.0003. The frequency of the CTT/CTT haplotype was decreasing in following order: D 10.6, O 9.5, G 6.1, C 5.3 and PCOS 4.9 [%]. Among CTT carriers, significantly decreased levels of oGTT-stimulated insulin and C-peptide as well as proportions of fasting PUFAs were observed. The carriership of CTG/TCG was associated with gestational diabetes, OR 2.59, p=0.036. The association of TCF7L2 haplotypes with T2D and gestational diabetes but not with PCOS was confirmed. Novel association of TCF7L2 with FFAs composition was found.

[A recommended approach to evaluate cardiovascular risk and to prevent cardiovascular diseases and type 2 diabetes mellitus in women with polycystic ovary syndrome]. / Doporucený postup k posouzení kardiovaskulárního rizika a prevenci kardiovaskulárních onemocnení a diabetes mellitus 2. typu u zen se syndromem polycystických ovarií

Polycystic ovary syndrome is one of the most common endocrinopathy in women of fertile age. It is commnoly accompanied by an increased occurence of cardiovascular risk factors. This association led to a consensus statement of Androgen Excess Society for screening of cardiovascular risk factors. We present the recommendations of Czech Endocrine and Czech Diabetological Societies for the screening and primary prevention of cardiovascular diseases and diabetes mellitus.

[Extremely low SHBG level in consequence of Pro156Leu SHBG polymorphism--case reports of two women with polycystic ovary syndrome]. / Extrémne nízké hladiny SHBG jako dusledek polymorfizmu Pro156Leu v genu pro SHBG-- kazuistiky dvou zen se syndromem polycystických ovarií.

Presented case reports illustrate clinical manifestations of two women with polycystic ovary syndrome who had extremely low serum SHBG levels (Sex Hormone Binding Globulin) due to homozygote carriership of the rare Pro156Leu SHBG polymorphism.

Fasting insulin pulsatile secretion in lean women with polycystic ovary syndrome.

The aim of our study was to evaluate rapid insulin pulses and insulin secretion regularity in fasting state in lean women with polycystic ovary syndrome (PCOS) in comparison to lean healthy women. PCOS (n=8) and controls (n=7) underwent every minute blood sampling for 60 min. Insulin pulsatility was assessed by deconvolution and insulin secretion regularity by approximate entropy methodology. PCOS had higher testosterone (p<0.02), prolactin (p<0.05) and lower sex hormone binding globulin (SHBG) (p<0.0006) levels than controls. Approximate entropy, insulin pulse frequency, mass, amplitude and interpulse interval did not differ between PCOS and controls. PCOS had broader insulin peaks determined by a common half-duration (p<0.07). Burst mass correlated positively with testosterone (p<0.05) and negatively with SHBG (p 0.0004) and common half-duration correlated positively with prolactin (p<0.008) and cortisol levels (p<0.03). Approximate entropy positively correlated with BMI (p<0.04) and prolactin (p<0.03). Lean PCOS patients tended to have broader insulin peaks in comparison to healthy controls. Prolactin, androgens and cortisol might participate in alteration of insulin secretion in PCOS-affected women. Body weight and prolactin levels could influence insulin secretion regularity.

Family history of diabetes mellitus determines insulin sensitivity and beta cell function in polycystic ovary syndrome.

OBJECTIVE: To examine the impact of family history of diabetes mellitus 2 (DM 2) on insulin sensitivity and secretion in lean women with polycystic ovary syndrome (PCOS). Thirteen healthy women (C), 14 PCOS without family history of DM 2 (FH-) and 8 PCOS with family history of DM 2 (FH+) were examined using euglycemic hyperinsulinemic clamp and an arginine secretion test (insulin and glucagon at fasting glycemia (AIR(FG) and AGR(FG)) and at hyperglycemia (AIR(14) and AGR(14)). FH+ women were more insulin resistant than FH- with lower insulin sensitivity index corrected per lean body mass (p 0.05). They had significantly higher triglycerides (p 0.05) and lower HDL-cholesterol (p 0.05) than C or FH- women. Concerning insulin secretion, AIR(FG) was increased in FH+ women comparing FH- women (p 0.05). Disposition indices derived from AIR(FG) or AIR(14) and insulin sensitivity index did not differ between FH+ or FH-. Thus, women with PCOS with the concomitant family history of DM 2 have lower insulin sensitivity than healthy control women. Insulin resistance observed in these women with PCOS is compensated by increased insulin secretion.

The identification and simultaneous quantification of neuroactive androstane steroids and their polar conjugates in the serum of adult men, using gas chromatography-mass spectrometry.

Certain androstane steroids (AS) modulate ionotropic receptors, as do the pregnane steroids. Whereas women produce significant amounts of neuroactive progesterone metabolites, the steroid neuromodulators in men originate mainly from the 3-oxo-4-ene C(19)-steroids, which are converted to their 3alpha- and 3beta-hydroxy-5alpha/5beta-reduced metabolites. The neuromodulating effects of AS prompted us to monitor circulating levels of the steroids to estimate metabolic pathways in the periphery that may influence brain concentrations of AS. Hence, the serum levels of 20 steroids and 16 steroid polar conjugates including 17-oxo- and 17beta-hydroxy-derivatives of 5alpha/beta-androstane-3alpha/beta-hydroxy-androstane steroids were quantified in 15 men (16-62 years of age) using GC-MS. The conjugated AS for the most part reached micromolar concentrations, these being two or three orders of magnitude higher than those of the free steroids. The ratios of conjugates to free steroids were one to two orders of magnitude higher than the values for the corresponding pregnane steroids. This data suggested that conjugation may considerably restrain the transport of free AS from the periphery into the central nervous system.

[Study of the genetic causes of polygeneticallv determined endocrinopathies--patience can bring success]. / Studium genetických prícin polygenne determinovaných endokrinopatií - aneb trpelivostí k úispechu.

Complex endocrinopathies, such as diabetes mellitus, obesity, polycystic ovary syndrome and osteoporosis belong to the most common diseases but their pathogenesis is still not fully explained. Environmental fadors along with genetic factors contribute to their occurrence and development. The study of genetic background is based on different strategies, mostly on linkage analysis and candidate gene approach. The common forms of these endocrinopathies do not seem to be the result of a defect of one or several major genes but the search for complex gene-gene, gene-environment interactions is needed. The article gives a short review of the recent knowledge together with our own experience in the field of study of the genetic background of polygenic diseases.

[Polycystic ovary syndrome in 2006]. / Syndrom polycystických ovarií v roce 2006.

Polycystic ovary syndrome was defined as the combination of anovulation and hyperandrogenaemia (NIH 1990). Another definition used the combination of ultrasonographic appearance of polycystic ovaries and/or anovulation and/or hyperandrogenaemia or cutaneous manifestations of hyperandrogenism (Rotterdam). The population defined according to NIH is probably in greater risk of insulin resistance and obesity. Pathogenesis of PCOS is not clear till now. Dysregulation of ovarian steroidogenesis could be one of the causes of the full-blown syndrome. Up-regulation of steroidogenic enzymes, probably due to the exaggerated expression of transcription factors such as GATA-6 or retinoids could be involved. Insulin sensitisators are now widely used in the therapy. They could beneficially modify not only insulin resistance and dyslipidaemia, but also ovarian and adrenal steroidogenesis. Metformin and glitazones improve anovulation however the studies conducted till now were not representative concerning the point of successful pregnancy.

[Diabetes mellitus in adult patients with type I diabetes shows immunological, functional and clinical differences depending on the presence of autoimmune thyroiditis]. / Diabetes mellitus dospelých diabetiku 1. typu v závislosti na prítomné autoimunitní tyroiditide vykazuje imunologické, funkcní a klinické odlisnosti.

BACKGROUND: Autoimmune diabetes is usually accompanied by other autoimmune endocrinopathies, most often by autoimmune thyroiditis (AIT), but it is not clear whether diabetes in these patients differs from diabetes without AIT. METHODS AND RESULTS: Eleven-year follow-up of 47 young adult Type 1 diabetic patients with respect to the presence of AIT (group I - positive antibodies against microsomal peroxidase, antiTPO, and tyreoglobulin, antiTgl, group II - only positive antiTPO, group III - without AIT) showed: a) cessation of endogenous insulin secretion (Cpeptide <0.03 nmol/l) in 100 % of patients with AIT (in group I between year 2 and 9, in group II between year 3 and 11, p<0.05), while in group III without AIT only in 55 % of patients (I,II vs. II, p<0.001); b) higher prevalence of antiGAD values > 5 U/ml in group I when compared to patients without AIT (I vs III, p<0.05); c) tendency toward higher doses of insulin needed for diabetes compensation in patients without AIT; d) the highest prevalence of organ-specific and systemic autoantibodies in group I with the most distinct manifestations of AIT, and the lowest prevalence in group III without AIT (statistically significant). CONCLUSIONS: Autoimmune diabetes in adults with AIT compared to diabetes occurring isolated showed differences in the area of autoimmunity against islets of Langerhans, Langerhans islets' function and in the clinical course of the disease.

[Incretins]. / Inkretiny.

Insulin secretion is greater after peroral challenge than after intravenous glucose administration due to so-called incretin effect. The major incretins are glucagon-like peptide 1 and glucose-dependent-insulinotropic peptide. Physiology, pathophysiology and therapeutic implications of incretins in diabetes, neurodegenerative disorders and stress-induced hyperglycemia are concerned.

Weight change and androgen levels during contraceptive treatment of women affected by polycystic ovary.

OBJECTIVE: The aim of this study was to investigate the effect of oral contraceptive Diane 35 (ethinylestradiol + cyproteroneacetate EE/CPA) which is widely used in the treatment of PCOS in Europe, on body weight, lipid levels and endocrine parameters in non-obese women with PCOS. SUBJECTS AND METHODS: Nineteen PCOS women were examined in the early follicular phase of menstrual cycle, blood samples for the estimation of cholesterol (C), HDL cholesterol (HDL-C), triglycerides (TG), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were taken before the start of treatment with Diane 35 and again after 7 +/- 3.8 months of treatment with Diane 35. Body weight (W) was recorded at the time of both examinations. RESULTS: After the treatment with Diane 35 the levels of W (p<0.05), total C (p<0.05), TG (p<0.004) and SHBG (p<0.0001) increased significantly. In addition, significant negative correlation between SHBG levels before treatment and increase of W after Diane 35 was found (r= -0.56; p<0.02). Increase of W correlated negatively with T before treatment (r= 0.58; p< .02) and positively with the change in T level after treatment (r=0.50; p<0.05). CONCLUSIONS: Increase of body weight in a significant number of PCOS-affected women was seen after treatment with Diane 35 and it is assumed to blunt ameliorating effects of this treatment on androgen levels. Considering our findings, we conclude that the treatment with CPA/EE can result in significant weight gain ameliorating positive effects of the treatment on androgen levels. These findings could underline the necessity of the finding new therapeutical options for PCOS, besides contraception. Studies concerning body composition during contraceptive treatment in PCOS would be also useful in the future.