RESUMEN
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.
Asunto(s)
Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Insulina , Laparoscopía , Obesidad Mórbida , Femenino , Humanos , Persona de Mediana Edad , Glucemia , Diabetes Mellitus Tipo 2/cirugía , Glucosa , Insulina/sangre , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Proyectos Piloto , Periodo Posprandial , TriglicéridosRESUMEN
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.
Asunto(s)
Cirugía Bariátrica , Desviación Biliopancreática , Diabetes Mellitus Tipo 2 , Obesidad Mórbida , Humanos , Femenino , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Desviación Biliopancreática/métodos , Glucosa , Proyectos Piloto , Diabetes Mellitus Tipo 2/cirugía , Triglicéridos , Obesidad/cirugía , Insulina , Cirugía Bariátrica/métodos , Glucemia/metabolismoRESUMEN
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.
Asunto(s)
Citocinas/sangre , Disruptores Endocrinos/sangre , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/epidemiología , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , República Checa/epidemiología , Estrógenos/sangre , Femenino , Humanos , Resistencia a la Insulina , Obesidad/sangre , Obesidad/epidemiología , Obesidad/patología , Síndrome del Ovario Poliquístico/patología , Testosterona/sangreRESUMEN
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 %.
Asunto(s)
Centros de Atención Secundaria/normas , Glándula Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Nódulo Tiroideo/diagnóstico , Ultrasonografía/métodos , Biopsia con Aguja Fina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estándares de Referencia , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/cirugíaRESUMEN
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.
Asunto(s)
Tumor de Células de Leydig/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen , Amenorrea/etiología , Femenino , Hirsutismo/etiología , Humanos , Histerectomía Vaginal , Tumor de Células de Leydig/patología , Tumor de Células de Leydig/cirugía , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Ovariectomía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Testosterona/sangre , Ultrasonografía Doppler en Color , Virilismo/etiologíaRESUMEN
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.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Enfermedad de Graves/diagnóstico , Enfermedad de Graves/genética , Antígenos HLA/genética , Estudios de Cohortes , República Checa/epidemiología , Predisposición Genética a la Enfermedad/epidemiología , Enfermedad de Graves/epidemiología , Humanos , Proyectos Piloto , Valor Predictivo de las Pruebas , Recurrencia , Glándula Tiroides/patología , Glándula Tiroides/fisiologíaRESUMEN
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.
Asunto(s)
Tejido Adiposo/metabolismo , Glucemia/metabolismo , Diabetes Gestacional/metabolismo , Tracto Gastrointestinal/metabolismo , Hormonas/sangre , Insulina/sangre , Síndrome del Ovario Poliquístico/metabolismo , Adulto , Ayuno/metabolismo , Femenino , Humanos , Resistencia a la Insulina , EmbarazoRESUMEN
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.
Asunto(s)
Tejido Adiposo/metabolismo , Cirugía Bariátrica/tendencias , Diabetes Mellitus Tipo 2/sangre , Ácidos Grasos/sangre , Obesidad Mórbida/sangre , Triglicéridos/sangre , Adulto , Anciano , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/cirugía , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Obesidad Mórbida/epidemiología , Obesidad Mórbida/cirugíaRESUMEN
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.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Ácidos Grasos no Esterificados/sangre , Haplotipos , Proteína 2 Similar al Factor de Transcripción 7/genética , Adulto , Anciano , Análisis de Varianza , Biomarcadores/sangre , Distribución de Chi-Cuadrado , República Checa/epidemiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Gestacional/sangre , Diabetes Gestacional/epidemiología , Diabetes Gestacional/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/epidemiología , Síndrome del Ovario Poliquístico/genética , Polimorfismo de Nucleótido Simple , Embarazo , Medición de Riesgo , Factores de RiesgoRESUMEN
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.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/prevención & control , Síndrome del Ovario Poliquístico/complicaciones , Enfermedades Cardiovasculares/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Medición de RiesgoRESUMEN
Cortisone acetate test was performed in twelve young adult patients with diabetes mellitus type 1, after dexamethasone administration to suppress endogenous cortisol production. Previous screening revealed that all of the subjects had peak cortisol responses in the range from subnormal to normal, as determined by a low-dose Synacthen test. The aim was to find out whether these patients would exhibit different conversion of cortisone to cortisol by 11beta-hydroxysteroid dehydrogenase. Using multifactorial ANOVA the following significant relationships were obtained between cortisol or cortisol/cortisone ratio measured during the test and other parameters examined a) before dexamethasone suppression and b) during the test: a) Cortisol at 120(th) minute negatively correlated with daily insulin dose and positively with basal aldosterone. Cortisol/cortisone ratio at 60(th), 120(th), 180(th), and 240(th) minute negatively correlated with basal aldosterone/plasma renin activity ratio, urinary free cortisol/24 hours and positively with basal dehydroepindrosterone sulphate. b) Cortisol at 120(th) minute negatively correlated with suppressed basal serum glycemia; cortisol/cortisone ratio during the whole test negatively correlated with supressed basal ACTH. The examination of peripheral metabolism of cortisol using cortisone acetate test in patients with diabetes mellitus type 1 showed adaptive changes of 11beta-hydroxysteroid dehydrogenace activity associated with altered cortisol tissue supply.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasas/metabolismo , Cortisona/análogos & derivados , Diabetes Mellitus Tipo 1/enzimología , Hidrocortisona/biosíntesis , Hígado/enzimología , Adulto , Aldosterona/sangre , Sulfato de Deshidroepiandrosterona/sangre , Dexametasona , Femenino , Humanos , Hidrocortisona/sangre , Hidrocortisona/orina , Insulina/uso terapéutico , Masculino , Renina/sangreRESUMEN
Epilepsy is associated with various reproductive disorders and some antiepileptic drugs also influence the steroid metabolism. There is only limited data concerning the role of steroid sulphates in human epilepsy. Moreover, the substitution treatment with therapeutic substances also improves cognitive functions in humans. Therefore, we evaluated the balance between free and Delta5 sulphated steroids in women with epilepsy on various antiepileptic drugs. The study included 28 patients (17.0-51.0 years), with generalized (n=16) or catamenial epilepsy (n=12) followed in the follicular (FP) and luteal (LP) phases of menstrual cycle. Fifteen patients were on monotherapy and 13 were on polytherapy with 2 or 3 drugs. RIA was used for the steroid analyses. Statistical evaluation was done by Mann-Whitney tests and multivariate regression with reduction of dimensionality (Orthogonal Projections to Latent Structures, O2PLS). The final O2PLS model found a single significant predictive component extracting the variability shared between carbamazepine therapy, age of the subjects, and steroid levels and correlating with the variables as follows pregnenolone sulphate (PregS)-FP: R= -0.844, p<0.01; DHEAS-FP: R= -0.923, p<0.01; PregS-LP: R= -0.876, p<0.01; DHEAS-LP: R= -0.902, p<0.01; carbamazepine therapy: R=0.441, p<0.01; age of the participants (R=0.584, p<0.01). Carbamazepine significantly decreased DHEAS in both FP (p=0.02) and LP (p=0.003) and PregS in LP (p=0.03) and tended to decrease the PregS levels in FP (p=0.10), while primidone decreased DHEAS in both FP and LP (both p=0.05) and did not significantly change the levels of PregS. In conclusion, carbamazepine and primidone therapies significantly suppressed the sulphated steroids in serum.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Sulfato de Deshidroepiandrosterona/sangre , Epilepsia/sangre , Pregnenolona/sangre , Adolescente , Adulto , Epilepsia/tratamiento farmacológico , Femenino , Fase Folicular , Humanos , Fase Luteínica , Persona de Mediana Edad , Adulto JovenAsunto(s)
Enfermedades Autoinmunes , Síndrome del Ovario Poliquístico/inmunología , Artritis Reumatoide/complicaciones , Autoanticuerpos/análisis , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Síndrome del Ovario Poliquístico/complicaciones , Tiroiditis Autoinmune/complicacionesRESUMEN
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.
Asunto(s)
Síndrome del Ovario Poliquístico/genética , Polimorfismo Genético , Globulina de Unión a Hormona Sexual/genética , Adulto , Femenino , Homocigoto , Humanos , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/diagnóstico , Globulina de Unión a Hormona Sexual/análisis , Adulto JovenRESUMEN
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.
Asunto(s)
Peso Corporal/fisiología , Insulina/sangre , Insulina/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Adulto , Diabetes Mellitus Tipo 2/metabolismo , Ayuno , Femenino , Humanos , Hidrocortisona/sangre , Resistencia a la Insulina/fisiología , Secreción de Insulina , Prolactina/sangre , Flujo Pulsátil , Globulina de Unión a Hormona Sexual/metabolismo , Testosterona/sangreRESUMEN
Free fatty acids (FFAs) are natural ligands of the PPARgamma2 receptor. FFA plasma concentration and composition may represent one of the factors accounting for high heterogeneity of conclusions concerning the effect of the Pro12Ala on BMI, insulin sensitivity or diabetes type 2 (DM2) susceptibility. Our objective was to investigate the relation and possible interactions between the Pro12Ala polymorphism and FFA status, metabolic markers, and body composition in 324 lean nondiabetic subjects (M/F: 99/225; age 32+/-11 years; BMI 23.9+/-4.0 kg/m(2)) with and without family history of DM2. Family history of DM2 was associated with lower % PUFA and slightly higher % MUFA. The presence of Pro12Ala polymorphism was not associated with fasting plasma FFA concentration or composition, anthropometric or metabolic markers of glucose and lipid metabolism in tested population. However, the interaction of carriership status with FFA levels influenced the basal glucose levels, insulin sensitivity and disposition indices, triglycerides, HDL-cholesterol and leptin levels, especially in women. The metabolic effects of 12Ala carriership were influenced by FFA levels - the beneficial role of 12Ala was seen only in the presence of low concentration of plasma FFA. Surprisingly, a high PUFA/SFA ratio was associated with lower insulin sensitivity, the protective effect of 12Ala allele was apparent in subjects with family history of DM2. On the basis of our findings and published data we recommend the genotyping of diabetic patients for Pro12Ala polymorphism of the PPARgamma2 gene before treatment with thiazolidinediones and education of subjects regarding diet and physical activity, which modulate metabolic outcomes.
Asunto(s)
Peso Corporal/genética , Diabetes Mellitus Tipo 2/genética , Ácidos Grasos no Esterificados/sangre , PPAR gamma/genética , Polimorfismo Genético , Adulto , Glucemia/metabolismo , Composición Corporal/genética , República Checa , Metabolismo Energético/genética , Salud de la Familia , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Células Secretoras de Insulina/fisiología , Masculino , Receptor de InsulinaRESUMEN
This study aimed to examine relationships between DHEA(S), anthropometric parameters, oral glucose tolerance test derived data and lipid spectra in a Czech non-diabetic population. 380 healthy volunteers both with and without a family history of diabetes type 2 (DM2) were enrolled into the study (women: n=235, age 28.9+/-9.4 years, BMI 22.3+/-4.5 kg/m(2), men: n=145, age 32.3+/-10.0 years, BMI 24.7+/-3.6 kg/m(2)). Spearman's correlations (both without and with the adjustment for age, age and BMI), as well as ANCOVA were used. Non-adjusted data showed many "beneficial" correlations between DHEA(S) and both anthropometric and metabolic variables. Statistical analysis revealed that almost all correlations of DHEA(S) to adiposity and fat distribution in men as well as in women disappeared after the adjustment. There are, however, differences between men and women in the correlation of DHEA(S) to insulin sensitivity and lipid levels. The use of hormonal contraceptives (COC) is also an important factor in this relationship. In men and also in women using COC, DHEA-S after adjustment correlated positively with fasting and stimulated glucose, insulin and C-peptide, and negatively with insulin sensitivity. In this respect, the benefit of DHEA(S) supplementation seems -- at least in terms of its alleged antiobesity and antidiabetogenic effects -- to be more than controversial.
Asunto(s)
Tejido Adiposo/metabolismo , Glucemia/metabolismo , Sulfato de Deshidroepiandrosterona/sangre , Deshidroepiandrosterona/sangre , Intolerancia a la Glucosa/metabolismo , Lípidos/sangre , Adulto , Índice de Masa Corporal , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Anticonceptivos Femeninos/uso terapéutico , República Checa , Ácidos Grasos no Esterificados/sangre , Femenino , Humanos , Resistencia a la Insulina , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Globulina de Unión a Hormona Sexual/metabolismoRESUMEN
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.
Asunto(s)
Diabetes Mellitus/genética , Diabetes Mellitus/fisiopatología , Resistencia a la Insulina/genética , Células Secretoras de Insulina/fisiología , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/fisiopatología , Adulto , Antropometría , Arginina/metabolismo , Glucemia/metabolismo , Presión Sanguínea/fisiología , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/genética , Femenino , Células Secretoras de Glucagón/fisiología , Técnica de Clampeo de la Glucosa , Homeostasis , Hormonas/sangre , HumanosRESUMEN
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.
Asunto(s)
Androstanos/sangre , Cromatografía de Gases y Espectrometría de Masas/métodos , Adolescente , Adulto , Androstanos/química , Androstenodiona/química , Humanos , Masculino , Persona de Mediana Edad , Pregnanos/sangre , Presión , Temperatura , Testosterona/química , Compuestos de Trimetilsililo/análisisRESUMEN
OBJECTIVE: To summarize available data concerning adrenal hyperandrogenemia caused by 21-hydroxylase deficiency, non-classic adrenal hyperplasia (NCAH). DESIGN: Review article. SETTING: Department of Gynecology and Obstetrics, General Faculty Hospital and 1st Medical Faculty, Prague. METHODS: Compilation of published data from scientific literature. CONCLUSION: Although 21-hydroxylase deficiency is one of the most frequent autosomal recessive genetic disorders, prevalence of NCAH in the whole population and among hyperandrogenic women is very low. The measurement of 17OH-progesterone should be incorporated into the standard evaluation of all hyperandrogenic patients to establish or exclude the diagnosis of NCAH. There is no typical clinical sign of NCAH, and clinical symptoms are to similar to patients with PCOS. Corticoid substitution as a treatment modality of NCAH is derived from therapy of classic congenital adrenal hyperplasia (CAH). Anti-androgen therapy is effective in skin disorders (hirsutism). Due to normal cortisol value there is to use of combined oral contraceptives in the treatment of choice. An improvement of clinical symptoms is a key parameter for the evaluation of treatment effectiveness. There are no data about risk of late metabolic complications in NCAH patients.