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ABSTRACT: OBJECTIVE: Maturity-Onset Diabetes of the Young (MODY) is the most common type of monogenic diabetes accounting for 1-2% of the population with diabetes. The relative incidence of HNF1A-MODY (MODY3) is high in European countries; however, data are not available for the Greek population. The aims of this study were to determine the relative frequency of MODY3 in Greece, the type of the mutations observed, and their relation to the phenotype of the patients. DESIGN AND METHODS: Three hundred ninety-five patients were referred to our center because of suspected MODY during a period of 15 yr. The use of Denaturing Gradient Gel Electrophoresis of polymerase chain reaction amplified DNA revealed 72 patients carrying Glucokinase gene mutations (MODY2) and 8 patients carrying HNF1A gene mutations (MODY3). After using strict criteria, 54 patients were selected to be further evaluated by direct sequencing or by multiplex ligation probe amplification (MLPA) for the presence of HNF1A gene mutations. RESULTS: In 16 unrelated patients and 13 of their relatives, 15 mutations were identified in the HNF1A gene. Eight of these mutations were previously reported, whereas seven were novel. Clinical features, such as age of diabetes at diagnosis or severity of hyperglycemia, were not related to the mutation type or location. CONCLUSIONS: In our cohort of patients fulfilling strict clinical criteria for MODY, 12% carried an HNF1A gene mutation, suggesting that defects of this gene are responsible for a significant proportion of monogenic diabetes in the Greek population. No clear phenotype-genotype correlations were identified.
Pediatric Diabetes 03/2013; · 2.16 Impact Factor
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ABSTRACT: Context:Holoprosencephaly (HPE) is a developmental defect characterized by wide phenotypic variability, ranging from minor midline malformations (eg, single central incisor) to severe deformities. In 10-15% of HPE patients, mutations in specific genes have been identified (eg, SHH, TGIF, SIX3). Pituitary stalk interruption syndrome (PSIS) constitutes a distinct abnormality of unknown pathogenesis, whereas isolated pituitary hypoplasia (IPH) has been linked to various developmental genes.Objective:Three of our patients with PSIS had a single central incisor, a malformation encountered in some HPE cases. Based on this observation, we initiated a search for mutations in HPE-associated genes in 30 patients with PSIS or IPH.Design and Participants:The entire coding region of the TGIF, SHH, and SIX3 genes was sequenced in patients with combined pituitary hormone deficiency associated with either PSIS or IPH and in healthy controls.Results:Two novel mutations in the HPE-related genes were detected (ie, c.799 C>T, p.Q267X in the TGIF gene, and c.1279G>A, p.G427R in the SHH gene) in 2 of our patients. The overall incidence of HPE-related gene mutations in our nonsyndromic and nonchromosomal patients was 6.6%. No molecular defect in the SIX3 gene was detected in our cohort.Conclusions:The data suggest that HPE-related gene mutations are implicated in the etiology of isolated pituitary defects (PSIS or IPH). Alternatively, PSIS or IPH may constitute mild forms of an expanded HPE spectrum.
The Journal of clinical endocrinology and metabolism 03/2013; · 6.50 Impact Factor
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ABSTRACT: BACKGROUND: In vitro fertilisation (IVF) has been widely used during the last decades. Recent studies demonstrated some alterations in IVF children's metabolic profile compared with controls. The recently reported lipocalins retinol-binding protein 4 (RBP-4) and neutrophil gelatinase-associated lipocalin (NGAL), as well as visfatin, which are associated with glucose intolerance and could help in the early detection of metabolic abnormalities, have not been studied in IVF children as yet. We studied the lipocalins RBP-4 and NGAL as well as visfatin in children born after IVF. SUBJECTS AND METHODS: A total of 100 children born after IVF (47 boys) and 60 controls born after normal conception (30 boys), aged 4-14 year, were studied cross-sectionally. All children had a physical examination, their fasting glucose, insulin, lipid profile, RBP-4, NGAL, and visfatin were determined and their homoeostasis model assessment (HOMA) index was calculated. RESULTS: Children born after IVF had significantly higher RBP-4 (P = 0·009) and NGAL (P = 0·028) levels than controls. When divided by gender, RBP-4 remained higher in IVF girls (P = 0·002), whereas NGAL was higher in IVF boys (P = 0·021). Linear regression analysis had revealed that the differences are attributed to the IVF procedure per se. CONCLUSIONS: In our study, IVF children had significantly higher RBP-4 and NGAL levels than controls, suggesting early metabolic derangements that could be attributed to an epigenetic phenomenon. These results are in accordance with our earlier findings of higher blood pressure and triglycerides in IVF children than controls. Further prospective studies in IVF children will determine the natural course of their metabolic profile.
European Journal of Clinical Investigation 02/2013; · 3.02 Impact Factor
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ABSTRACT: CONTEXT: StAR gene mutations lead to adrenal and gonadal failure. Interesting, though as yet unexplained features are the formation of ovarian cysts and the potential presence of Central Nervous System (CNS) findings. Objective: To report biochemical, genetic and long-term clinical data in five Greek patients from four different families with StAR gene defects (three 46,XX and two 46,XY). Methods and results: All patients presented in early infancy with adrenal insufficiency. The StAR gene mutation c.834del11bp, detected in three of our patients, completely alters the carboxyl end of the StAR protein and has not thus far been described in other population groups. These three patients belong to three separate families, possibly genetically related, as they live in different villages located in a small region of a Greek island. However their interrelation has not been proven. A second mutation, p.W250X, detected in our fourth family, was previously described only in two Serbian patients. Ovarian cysts were detected ultrasonographically in our 46,XX patients and seem to respond to low dose of a contraceptive. The histology of an excised ovarian cyst was diagnosed as a corpus luteum cyst. In two out of the four patients who had brain magnetic resonance imaging, asymptomatic Chiari-1 malformation was observed. Conclusions: The occurrence of StAR gene mutation c.834del11bp in three families living in a restricted geographic region could indicate either a founder effect or simply reflect a spread of this defect in a highly related population. The ovarian histological findings suggest that ovarian cysts detected ultrasonographically in 46,XX individuals with StAR gene defects may be corpus luteum cysts. The Chiari-1 malformation in two of our patients may be part of the StAR gene-mutation phenotype. Nevertheless, more data are needed to confirm or disprove the existence of specific CNS pathology in patients with StAR gene mutations.
European Journal of Endocrinology 12/2012; · 3.42 Impact Factor
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ABSTRACT: Frasier syndrome (FS) phenotype in 46,XY patients usually consists of female external genitalia, gonadal dysgenesis, high risk of gonadoblastoma and the development of end stage renal failure usually in the second decade of life. FS is caused by heterozygous de novo intronic splice site mutations of the Wilms' tumor suppressor gene 1 (WT1), although a few cases with typical exonic WT1 Denys-Drash mutations that resemble an FS phenotype have been described. The aim of this study was to present further data on the spectrum of FS phenotypes through the evaluation of a 29-year-old patient with a predominantly male phenotype and coexistence of Sertoli cell tumor and gonadoblastoma.
Genetic analysis using standard methods for DNA sequencing confirmed FS due to a WT1 gene mutation, IVS9+4C>T.
This very rare case illustrates the natural course of FS over many years due to the neglect by the patient to address his need for follow-up, while adding further data on the spectrum of FS phenotypes associated with IVS9+4 C>T mutations. The coexistence of the rare Sertoli cell tumor and gonadoblastoma emphasizes that early clinical recognition and molecular identification facilitates appropriate patient management, especially with respect to the high risk of gonadal malignancy.
Hormones (Athens, Greece) 07/2012; 11(3):361-7. · 2.44 Impact Factor
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ABSTRACT: Obesity is highly co-morbid with anxiety and/or depression in children, conditions that may further worsen the metabolic and cardiovascular risks for obese individuals. Dysregulation of the hypothalamic-pituitary-adrenal axis is involved in the pathophysiology of anxiety disorders, depression, and obesity, and diverse cortisol concentrations may be found in obese children, depending on their degree of psychological distress. The aim of this study was to examine cortisol profiles among obese children with or without symptoms of anxiety and depression. A group of 128 children (53% females; mean age ± SD: 11.2 ± 2.2 years) derived from a pediatric obesity clinic were studied. Anxiety and depressive symptomatology were assessed with appropriate instruments. Morning serum and five diurnal salivary cortisol concentrations were measured. Obese children were 3.1/2.3 times more likely to report state and trait anxiety, respectively, and 3.6 times more likely to report depressive symptoms than children of the same age group, from a contemporary Greek sample. Trait anxiety and noon salivary cortisol concentrations were significantly positively correlated (p = 0.002). Overall, salivary cortisol concentrations were increased in children with anxiety or depression symptomatology compared to obese children without any affective morbidity (p = 0.02) and to those with anxiety and depression co-morbidity (p = 0.02). In conclusion, in obese children, emotional distress expressed by symptoms of anxiety and/or depression is associated with circadian cortisol profiles reflecting a potential pathway for further morbidity. Longitudinal studies may reveal a role of cortisol in linking obesity, anxiety, and depression to the development of further psychological and physical morbidity.
Stress (Amsterdam, Netherlands) 04/2012; · 3.21 Impact Factor
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ABSTRACT: Introduction: Dilated cardiomyopathy associated with vitamin D deficiency has been reported in infants. Purpose: To assess myocardial functions in infants with nutritional vitamin D deficiency rickets using tissue velocity imaging (TVI), Strain (S) and Strain rate (SR). Material: This study included 40 infants (mean age 15.3 ± 3.2 months) with active vitamin D deficiency rick-ets and 40 age and sex matched controls. Patients had no cardiac symptoms or signs. Methods: M mode, 2D echocardiography, TVI [early systolic (S') and early diastolic (E') waves of the mitral lateral and septal annulus], S and SR than controls, S and SR were performed to all patients and controls. Patients were treated with vitamin D 600 000 IU as a single IM dose and oral elemental calcium 1 gm/day for 6 weeks. Patients were reevaluated after clinical and radiological healing of rickets and return of laboratory values to normal. Results: Before treatment, patients showed significant increase in the interventricular septal thickness in diastole (IVSd), left ventricular dimension at end systole (LVIDd) (P < 0.05) and significant decrease in ejection fraction (EF) and TVI indices (P < 0.05). TDI, S and SR values showed significant positive correlation with serum calcium. Following treatment there was a significant decrease in IVSd and increase in EF and significant decrease (P < 0.001) in TVI values. These post treatment values were not significantly different than those of the control group (P > 0.05). However, S and SR remained signifi-cantly decreased post treatment when compared to the control group (P < 0.05). Conclusions: Infants with active nutritional rickets show subclinical myocardial dysfunction as detected by M-mode, TVI, S and SR. Treatment was associated by nor-malization of M-mode and TVI but not S and SR values. Increased dose or duration of treatment might be needed for some indices of myocardial function to reach normal values. Introduction: In young children, the etiology of heart failure consists of congenital heart malformations (CHM) whose therapeutic solution is surgical correction. The bi-omarkers derived from compensation neurohumoral acti-vation such as natriuretic peptides are biomarkers in congestive heart failure (CHF). Purpose: The aim of our study was to compare serum NT-proBNP levels in children with CHF secondary to CHM, with and without heart surgery. Material: Two groups of patients aged between 0–48 months with CHF secondary to CHM were studied. The first group included 32 patients with unoperated heart malformations and the second group, 21 patients within 24 h after surgery for the correction of the heart malformation. The control group included 18 subjects with normal ventricular systolic function, aged 0– 48 months. Methods: NT-proBNP levels were assessed by ELISA method, (Enzyme-Linked Immunoabsorbent Assay), using a standardized kit containing monoclonal antibod-ies that recognize epitopes located in the NT-proBNP portion. Results: The mean NT-proBNP value was 212 mol/mL in patients with operated CHM, 68.2 fmol/mL in patients with unoperated CHM, and 17.9 fmol/mL in the control group. There were significant differences in NT-proBNP values between the control group and the group of patients with CHF and unoperated congenital malformations, P = 0.0005, as well as between the control group and the group of patients with CHF and operated congenital mal-formations, P = 0.00001.
Acta Paediatrica 11/2011; 100(s463):44. · 2.07 Impact Factor
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ABSTRACT: Few studies have thus far assessed body composition by dual energy X-ray absorptrometry (DXA) in children with HIV, primarily because reference data for normally growing children and adolescents are not available. Our study aimed at evaluating body composition in children with HIV and their relatiοn to serum lipids and glucose homeostasis.
Body composition was assessed by DXA in 17 HIV-1 infected children at entrance to the study and after 12 months and in one hundred fifty nine age, gender, body mass index (BMI), and Tanner stage matched healthy subjects who served as controls. Lipodystrophy was diagnosed if the trunk/leg fat ratio was out of the range of the expected mean ± 1SD of the controls.
At study entry, 10 patients (7 girls) had developed lipohypertrophy, whereas all remaining patients had lipoatrophy. Lipohypertrophy was associated with older age (p=0.027). Lipodystrophic phenotype was stable in all patients except in one over the 12-month period of follow-up while on continuous antiretroviral therapy (ART). 80% and 70% of patients with lipohypertrophy had triglycerides and cholesterol levels, respectively above the 75th percentile, while 57% and 43% of patients with lipoatrophy had triglycerides and cholesterol, respectively greater than the 75th percentile. High triglycerides were associated with the use of protease inhibitors (p=0.028). Basal fasting glucose and homeostasis model assessment (HOMA) values were within normal limits.
HIV-infected paediatric patients on continuous ART developed significant and persistent body composition changes which were associated with dyslipidemia without overt abnormalities of glucose metabolism.
Hormones (Athens, Greece) 04/2011; 10(2):149-55. · 2.44 Impact Factor
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ABSTRACT: To investigate the metabolic profile, traditional adipokines, and indices of insulin resistance and low-grade inflammation in children born as a result of IVF compared with spontaneously conceived controls.
Cross-sectional, case-control study.
IVF Section of the First Department of Obstetrics and Gynecology and the First Department of Pediatrics of the University of Athens.
One hundred six children conceived after classic IVF and 68 age-matched spontaneously conceived controls, aged 4-14 years.
Children underwent physical examination and morning fasting samples were collected.
Lipid profile, circulating fasting glucose, insulin, leptin, adiponectin, high-sensitivity interleukin-6, and high-sensitivity C-reactive protein were determined and the fasting glucose-to-insulin ratio was calculated.
Children born as a result of classic IVF had significantly higher systolic and diastolic blood pressures (BP) and triglycerides than controls. These BP differences remained significant even after correction for birth size and multiple births. No significant differences in biochemical indices of insulin resistance, circulating adipokines, and inflammatory markers were detected before or after these same corrections.
Despite an increase of BP, children born as a result of IVF have no biochemical evidence of insulin resistance, including fasting glucose-to-insulin ratio and circulating adipokines, or low-grade chronic inflammation. However, the long-term impact of periconceptual manipulations should be closely monitored.
Fertility and sterility 10/2010; 94(5):1693-9. · 3.97 Impact Factor
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Christina Kanaka-Gantenbein
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ABSTRACT: According to the fetal origin of adult diseases hypothesis, the intrauterine environment through developmental plasticity may permanently influence long-term health and disease. Therefore, intrauterine growth restriction (IUGR), due either to maternal, placental, or genetic factors, may permanently alter the endocrine-metabolic status of the fetus, driving an insulin resistance state that can promote survival at the short term but that facilitates the development of type 2 diabetes mellitus and metabolic syndrome in adult life, especially when the intrauterine nutrient restriction is followed by a postnatal obesogenic environment. Furthermore, an energy-rich environment during fetal programming may also drive the development of excess abdominal fat and type 2 diabetes in later life, demonstrating that both intrauterine nutrient restriction as well as intrauterine nutrient excessive supply may predispose for the development of adult diabetes.
Annals of the New York Academy of Sciences 09/2010; 1205:99-105. · 3.15 Impact Factor
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ABSTRACT: In our neonatal program, a number of infants with congenital hypothyroidism (CH) had escaped diagnosis, when a spot RIA-TSH value of 20 mU/liter whole blood was used as a cutoff point.
The objective of the study was to find out prospectively the additional number of newborns with CH if the TSH cutoff point is lowered to 10 mU/liter.
The study included 311,390 screened newborns. The children with CH were followed up for a period of 3 yr.
Twenty-eight percent of infants diagnosed with CH had neonatal TSH values between 10 and 20 mU/liter (56 of 200). Forty of 47 infants, who were reevaluated later on (85.1%), suffered permanent CH. A thyroid scintiscan and/or echogram revealed that eight of 40 children (20.0%) had a structural defect, and the remaining (32 of 40) had a functional defect of the thyroid gland without anatomical abnormality; 14 of 32 cases were familial. Eighteen of the 47 reevaluated infants were prematurely born (38.3%) and 15 of these 18 had permanent CH (83.3%). The lowering of TSH cutoff point from 20 to 10 mU/liter resulted in a 10-fold increase of recall rate.
A significant number of cases with permanent CH are missed when a TSH threshold of 20 mU/liter is applied. Almost 40% of the missed CH cases were premature. A mild increase of TSH at screening is not a predictor of transient CH. The increase in recall rate constitutes a serious drawback and should be balanced against the possible consequences of thyroid dysfunction at this important developmental stage.
The Journal of clinical endocrinology and metabolism 09/2010; 95(9):4283-90. · 6.50 Impact Factor
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ABSTRACT: We aimed to investigate possible alterations in circulating levels of the perinatal stress markers high sensitivity (hs)-CRP, PAI-1, and S100B--probably reflecting brain and adipose tissue inflammation--in intrauterine growth-restricted-(IUGR) and appropriate-for-gestational-age-(AGA) pregnancies, given that these groups differ in fat mass and metabolic mechanisms involving aseptic inflammation. Serum hs-CRP, PAI-1, and S100B levels were measured in 40 mothers, and their 20 AGA and 20 IUGR full-term fetuses and neonates on postnatal days 1 and 4. hs-CRP, PAI-1, and S100B levels did not differ at all time points between AGA and IUGR groups. We conclude that the lack of difference in hs-CRP, PAI-1 and S100B levels, between IUGR and AGA fetuses/neonates--despite the lower birth weight, reflecting reduced fat mass in the former--might indicate more intense adipose tissue and nervous system inflammation in IUGRs. However, implication of other inflammation-related mechanisms, common in the IUGR state (e.g. preeclampsia), cannot be excluded.
Mediators of Inflammation 01/2010; 2010:790605. · 3.26 Impact Factor
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ABSTRACT: Background: Obesity and hypertension are often comorbid, but the pathophysiologic mechanisms that link them are not fully understood. Natriuretic peptides might play a role in this association. The majority of studies show lower brain natriuretic peptide (BNP) concentrations as well as lower concentrations of the N-terminal of the prohormone (NT-proBNP) in obese than normal body mass index (BMI) adults and higher BNP concentrations in hypertensive than in normotensive individuals. In children, there are no studies examining the relations between NT-proBNP, BMI and blood pressure. Materials and Methods: Ninety-six children, 24 obese/25 normal BMI boys, and 23 obese/24 normal BMI girls, aged 10-16 years, were studied. Plasma NT-proBNP was measured using electrochemiluminescence. Results: In males, NT-proBNP concentrations were lower in the obese than the normal BMI group but higher in the obese hypertensive than the obese normotensive group (p = 0.04). In addition, a significant positive correlation was noted between plasma NT-proBNP and blood pressure (p = 0.03) only in obese males. In females, no correlations were detected between NT-proBNP, BMI and systolic or diastolic blood pressure. Conclusions: Longitudinal studies are needed to define the role of NT-proBNP as a screening biomarker in obese children, particularly males, to determine their risk for developing arterial hypertension.
Hormone Research in Paediatrics 01/2010; 73(5):341-8.
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ABSTRACT: Assisted reproductive technologies (ARTs) have been widely used during the last three decades and progressively more children are born with the help of such methods. There is now evidence that ARTs may be associated with slight epigenetic modifications in the expression of several genes that could have a long-term impact on the health of the offspring. Also, a clear association between such techniques and genomic imprinting abnormalities has been reported. The neuroendocrine impact of ART on the offspring includes slight elevations of systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as increased circulating triglyceride concentrations, in children born after ART, especially in those with rapid catch-up growth in weight during early childhood. However, the postnatal growth of most children after ART is normal and no increased incidence of the full metabolic syndrome has been observed in these children and adolescents. Moreover, the pace and timing of puberty of such children is normal and no increased incidence of premature adrenarche could be discerned in ART children in the absence of restricted fetal growth. Finally, a slight modification of the set point of thyroid stimulating hormone sensitivity was observed in ART children, without an apparent impact on thyroid hormone secretion. This has been attributed to epigenetic changes. Questions remain to be answered regarding the future reproductive capacity of children born after ART, as well as their cardiovascular risk in later adult life. Long-term prospective studies should be performed to provide robust evidence.
Progress in brain research 01/2010; 182:161-74. · 3.04 Impact Factor
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Maria Alexandra Magiakou,
Despoina Manousaki,
Marina Papadaki,
Dimitrios Hadjidakis,
Georgia Levidou,
Marina Vakaki,
Athanassios Papaefstathiou,
Niki Lalioti, Christina Kanaka-Gantenbein,
George Piaditis,
George P Chrousos,
Catherine Dacou-Voutetakis
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ABSTRACT: The objective of the study was to evaluate the long-term effect of GnRH analog (GnRHa) treatment on final height (FH), body mass index (BMI), body composition, bone mineral density (BMD), and ovarian function.
Ninety-two females, evaluated in adulthood, were categorized as follows: group A, 47 girls with idiopathic central precocious puberty (33 GnRHa treated and 14 nontreated); group B, 24 girls with isolated GH deficiency (15 GnRHa and GH treated and nine GH treated); group C, 21 girls with idiopathic short stature (seven GnRHa and GH treated, seven GnRHa treated, and seven nontreated).
FH, BMD, and percent fat mass of GnRHa-treated patients in all three groups were comparable with those of the respective nontreated subjects. BMI values of GnRHa-treated and nontreated subjects in groups A and C were comparable, whereas in group B, a higher BMI was found in subjects treated only with GH. Nontreated patients with ICPP had greater maximal ovarian volumes, higher LH and LH to FSH ratio, and more severe hirsutism than GnRHa-treated ones. Menstrual cycle characteristics were not different between treated and nontreated subjects. The prevalence of polycystic ovary syndrome in treated and untreated girls with ICPP was comparable, whereas in the entire cohort, it was 11.1% in GnRHa treated and 32.1% in the untreated (P = 0.02).
Girls treated in childhood with GnRHa have normal BMI, BMD, body composition, and ovarian function in early adulthood. FH is not increased in girls with ICPP in whom GnRHa was initiated at about 8 yr. There is no evidence that GnRHa treatment predisposes to polycystic ovary syndrome or menstrual irregularities.
The Journal of clinical endocrinology and metabolism 11/2009; 95(1):109-17. · 6.50 Impact Factor
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ABSTRACT: The role of insulin-like growth factor 1 (IGF-1) and ghrelin in intrauterine growth restricted (IUGR) neonates in comparison to appropriate for gestational age (AGA) ones was investigated. Levels of IGF-1/insulin-like growth factor binding protein 3 (IGFBP3), ghrelin, insulin, and cortisol were determined in 20 singleton, full-term IUGR and 20 respective AGA neonates at birth (umbilical cord-UC), on days 1 (d1) and 4 (d4) postnatally. The ratio of IGF-1 to birth weight was higher in IUGR than in AGA in both UC (18.2 +/- 1.2 vs14.4 +/- 0.9, P = .05) and d1 (9.6 +/- 0.5 vs 6.8 +/- 0.3, P = .05). A significant positive correlation was found between IGF-1 and ghrelin levels and a negative one between IGFBP3 and ghrelin only in IUGR. In both groups, fetal IGF-1 levels negatively correlated with fetal cortisol levels. Intrauterine growth restricted neonates demonstrate a relative IGF-1 resistance in an attempt to drive energy toward survival on the expense of growth. The observed correlations between ghrelin and IGF-1/IGFBP3 postnatally indicate that ghrelin might play a role in the compensation of intrauterine undernutrition, promoting postnatal growth.
Reproductive sciences (Thousand Oaks, Calif.) 09/2009; 16(12):1193-200. · 2.31 Impact Factor
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ABSTRACT: We investigated the actions of growth-differentiation factor (GDF)-15, endoglin and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in 15 male athletes who participated in the ultradistance foot race of the 246 km 'Sparthathlon'. Measurements were performed before (phase I), at the end of the race (phase II) and 48 h post-race (phase III). GDF-15 and endoglin serum concentrations were determined with enzyme-linked immunosorbent assay and NT-pro-BNP plasma levels by electrochemiluminescence. GDF-15 levels were increased from phase I (563.9 +/- 57.1 pg ml(-1)) to phase II (2311.1 +/- 462.3 pg ml(-1)) and decreased at phase III (862.0 +/- 158.0 pg ml(-1)) (p < 0.0002). NT-pro-BNP levels followed a similar pattern to that of GDF-15 from 38.1 +/- 4.8 pg ml(-1) at phase I to 1280.6 +/- 259.0 pg ml(-1) at phase II and 89.8 +/- 13.6 pg ml(-1) at phase III (p < 0.0001) and at the same time points, endoglin levels were 4.7 +/- 0.2 ng ml(-1) at phase I, 5.8 +/- 0.2 ng ml(-1) at phase II and 4.3 +/- 0.2 ng ml(-1) at phase III (p < 0.002). These findings indicate that circulating GDF-15, endoglin and NT-pro-BNP levels reflect a transient endothelial dysfunction in these athletes who participated in a foot race consisting of continuous, prolonged and brisk exercise.
Biomarkers 07/2009; 14(6):418-22. · 2.21 Impact Factor
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Sarantis Livadas,
Maria Dracopoulou,
Karmen Vasileiadi,
Christina Lazaropoulou,
Maria-Alexandra Magiakou,
Paraskevi Xekouki,
Antonis Voutetakis, Christina Kanaka-Gantenbein,
Ioannis Papassotiriou,
Christodoulos Stefanadis,
George P Chrousos,
Catherine Dacou-Voutetakis
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ABSTRACT: Females with a history of premature adrenarche are at high risk of developing polycystic ovary syndrome (PCOS) and features of the metabolic syndrome later in life. Coagulation disorders, subclinical inflammation, and oxidative stress have been reported in patients with PCOS and metabolic syndrome. These factors were studied in a group of adolescents with a history of premature adrenarche. This is a cross-sectional study that determined the biochemical-hormonal profile and indices of inflammation, coagulation, and oxidative stress in 45 adolescent girls with a history of premature adrenarche and 19 age- and body mass index-matched controls. Girls with premature adrenarche had hyperandrogenism and higher indices of insulin resistance than controls. They also had significantly higher C-reactive protein (0.76 +/- 0.65 vs 0.41 +/- 0.31 mg/L, P = .0001) and plasminogen activator inhibitor 1 (37.6 +/- 24.7 vs 24.47 +/- 4.6 ng/mL, P = .034), and lower tissue plasminogen activator values in comparison with controls (3.5 +/- 1.5 vs 5.2 +/- 2.12 ng/mL, P = .0019). Both C-reactive protein(r = 0.545, P = .0001) and plasminogen activator inhibitor 1 (r = 0.36, P = .04) were positively correlated with oxidative stress, whereas tissue plasminogen activator was positively correlated (r = 0.37, P = .02) with total antioxidant status. None of these factors was correlated with androgens or indices of insulin resistance. Adolescent girls with a history of premature adrenarche display metabolic deviations usually encountered in subjects with PCOS and metabolic syndrome, such as subclinical inflammation and fibrinolytic abnormalities.
Metabolism: clinical and experimental 05/2009; 58(4):576-81. · 2.59 Impact Factor
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ABSTRACT: Assisted reproduction techniques are now commonly used. Although classic in vitro fertilization (IVF) started almost 30 yr ago, few long-term systematic prospective studies of children conceived with assisted reproduction have been performed.
Our objective was to investigate thyroid function in children conceived after IVF vs. naturally conceived controls.
A total of 106 children conceived after classic IVF and 68 naturally conceived controls, aged 4-14 yr, were studied. All children were thoroughly examined, and serum T(3), T(4), TSH, anti-thyroid peroxidase, and anti-thyroglobulin antibodies were measured. A second TSH determination and a thyroid ultrasound were performed for TSH higher than 5 microIU/ml, and children were considered to have persistent hyperthyrotropinemia, if the TSH elevation was confirmed.
Seven IVF children but none of the controls had persistent elevations of circulating TSH, suggesting euthyroid hyperthyrotropinemia or subclinical primary hypothyroidism (P = 0.044). TSH was significantly higher in the IVF group than in controls (P = 0.046), whereas no significant differences in the concentrations of T(3) or T(4) were observed. None of the children had detectable circulating antithyroid antibodies in either group.
A significant elevation of serum TSH compatible with a mild TSH resistance of the thyroid were found in IVF children compared with controls. This was not due to the presence of antithyroid autoantibodies. We suggest that this might represent a slight epigenetic developmental abnormality related to the preimplantation manipulation of the embryo. Further studies are needed to confirm these findings and to better determine their etiopathogenesis and clinical significance.
The Journal of clinical endocrinology and metabolism 02/2009; 94(4):1338-41. · 6.50 Impact Factor
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ABSTRACT: although there is much evidence regarding the physiologic and pathogenic roles of the newly described adipokines retinol-binding protein 4 (RBP4) and lipocalin-2 as potential promoters of insulin resistance in obese adults, relatively little information exists regarding their roles in obese children.
we investigated the circulating concentrations of RBP4 and lipocalin-2 in 80 obese girls (ages 9- 15 years) and their relationships with high-sensitivity C-reactive protein (hs-CRP) and the adipokines leptin and adiponectin. We divided participants by their body mass index standard deviation scores (BMI SDSs) into 4 groups of 20 girls each: overweight [mean BMI SDS (SD), 1.8 (0.4)], obese [2.2 (0.4)], morbidly obese [3.6 (0.4)], and lean controls [-0.11 (0.4)]. We measured plasma-soluble RBP4, the RBP4-binding protein transthyretin, lipocalin-2, hs-CRP, leptin, and adiponectin and calculated the homeostatic assessment model (HOMA) index from fasting glucose and insulin concentrations.
unexpectedly, plasma RBP4 and lipocalin-2 concentrations were correlated negatively with BMI SDS values (P = 0.005, and P < 0.03, respectively). These results were different from those of adults and were not correlated with the HOMA index. In contrast, hs-CRP and leptin concentrations were positively correlated with BMI SDS values (P < 0.0001, and P < 0.00001, respectively), as expected, whereas the adiponectin concentration was negatively correlated (P = 0.008).
although the correlations of leptin, adiponectin, and hs-CRP concentrations with BMI in children are similar to those of adults, the correlations of RBP4 and lipocalin-2 with BMI in children are the inverse of those observed in adults. Thus, although systemic inflammation and mild insulin resistance are present in childhood obesity, RBP4 and lipocalin-2 concentrations are not increased in children as they are in obese adults with long-standing severe insulin resistance and type 2 diabetes.
Clinical Chemistry 07/2008; 54(7):1176-82. · 7.91 Impact Factor
