Gut hormones in patients with coeliac disease with and without diabetes mellitus

Background: Previous research indicated that coeliac disease (CD) is associated with type 1 diabetes mellitus (T1DM). However, the gut-brain axis peptide hormones secretion has not been evaluated so far in patients with CD prior to treatment initiation or under treatment, irrespective of patients having concomitant T1DM or not. The aim of the study was therefore to evaluate these gut hormones at the preprandial levels of patients with CD before and under treatment, irrespective of patients having concomitant T1DM or not.Methods: Forty-seven CD children, 12 untreated (UCD), 22 treated with gluten-free diet (TCD) and 13 treated CD with coexisting T1DM (DCD), and 18 healthy controls (HC) were enrolled. Preprandial active amylin, acylated ghrelin (AG), leptin, glucose-dependent-insulinotropic-polypeptide (GIP), glucagon-like-peptide-1 (GLP-1), pancreatic polypeptide (PP) and peptide-tyrosine-tyrosine (PYY) were determined with hormone-map-array technology. Results: We found in patients with CD compared with HC that the concentration of (i) amylin was remarkably reduced (P<0.01) in all patients with CD, (ii) AG was significantly decreased in patients with DCD (P<0.01), (iii) GIP was lower in patients with UCD (P=0.008), (iv) GLP-1 was reduced remarkably in all patients with CD (P=0.008), while (v) leptin, PP and PYY were not significantly different. GIP, GLP-1 and amylin levels correlated positively with insulin concentrations (P<0.001, P=0.004 and P<0.01, respectively) in all patients. Amylin and GIP levels were strongly associated with triglycerides concentrations (P<0.001, for both peptides) in children with CD.Conclusions: Our study revealed a different secretion pattern of gut-brain axis hormones in children with CD compared with HC. The alterations in the axis were more pronounced in children with both CD and T1DM.Εισαγωγή: Προηγούμενες έρευνες έδειξαν ότι η κοιλιοκάκη συνδέεται με τον σακχαρώδη διαβήτη τύπου 1 (ΣΔ1). Παρ’όλα αυτά, η έκκριση των πεπτιδικών ορμονών του άξονα γαστρεντερικού συστήματος-εγκεφάλου δεν έχει μελετηθεί μέχρι σήμερα σε ασθενείς με κοιλιοκάκη πριν από την έναρξη δίαιτας ή υπό δίαιτα, ανεξάρτητα από τη συνύπαρξη ΣΔ1 ή όχι. Επομένως, στόχος της μελέτης μας ήταν ο προσδιορισμός των προγευματικών επιπέδων αυτών των ορμονών του γαστρεντερικού συστήματος σε ασθενείς με κοιλιοκάκη πριν από την έναρξη δίαιτας και υπό δίαιτα, ανεξάρτητα από τη συνύπαρξη ΣΔ1 ή όχι.Μέθοδοι: Στη μελέτη συμπεριλήφθησαν σαράντα επτά παιδιά με κοιλιοκάκη, εκ των οποίων 12 ήταν πρωτοδιάγνωστα (ΠΚ), 22 ήταν υπό δίαιτα ελεύθερη γλουτένης (ΔΚ), 13 υπό δίαιτα και με ΣΔ1 συγχρόνως (ΚΣΔ) και 18 υγιείς μάρτυρες (Μ). Τα προγευματικά επίπεδα των ενεργής amylin, ακυλιωμένης ghrelin (AG), leptin, glucose-dependent-insulinotropic-polypeptide (GIP), glucagon-like-peptide-1 (GLP-1), pancreatic polypeptide (PP) και peptide-tyrosine-tyrosine (PYY) προσδιορίστηκαν με τεχνολογία hormone-map-array.Αποτελέσματα: Σε ασθενείς με κοιλιοκάκη συγκριτικά με τους υγιείς μάρτυρες παρατηρήσαμε ότι η συγκέντρωση (α) της amylin ήταν αξιοσημείωτα ελαττωμένη (P<0.01) σε όλους τους ασθενείς με κοιλιοκάκη, (β) της AG ήταν σημαντικά μειωμένη σε ασθενείς ΚΣΔ (P<0.01), (γ) του GIP ήταν μικρότερη στους ασθενείς ΠΚ (P=0.008), (δ) του GLP-1 ήταν αξιοσημείωτα μειωμένη σε όλους τους ασθενείς με κοιλιοκάκη (P=0.008), ενώ (ε) της leptin, του PP και του PYY δεν διέφεραν σημαντικά. Τα επίπεδα των GIP, GLP-1 και της amylin συσχετίστηκαν θετικά με τις συγκεντρώσεις της ινσουλίνης (P<0.001, P=0.004 και P<0.01, αντιστοίχως) σε όλους τους ασθενείς. Τα επίπεδα των amylin και GIP συσχετίστηκαν ισχυρά με τις συγκεντρώσεις των τριγλυκεριδίων (P<0.001 και για τα δύο πεπτίδια) σε παιδιά με κοιλιοκάκη. Συμπεράσματα: Η μελέτη μας αποκάλυψε ένα διαφορετικό πρότυπο έκκρισης των ορμονών του άξονα γαστρεντερικού συστήματος-εγκεφάλου σε παιδιά με κοιλιοκάκη συγκριτικά με τους μάρτυρες. Οι μεταβολές στον άξονα ήταν πιο έντονες στα παιδιά με κοιλιοκάκη και ΣΔ1 συγχρόνως

Evaluation of liver fibrosis in patients with thalassemia: The important role of hyaluronic acid

Patients with transfusion-dependent thalassemia major often develop liver fibrosis due to liver iron overload and/or hepatitis virus C (HCV) infection. Hyaluronic acid (HA) plays a prominent role in the pathogenesis of liver fibrosis and the elevation of serum HA concentration is due to either increased synthesis by inflammatory cells and hepatic stellate cells or impaired degradation by sinusoidal endothelial cells (SECs) and thus is proposed as a non-invasive biomarker of liver fibrosis either by itself and/or included in the Hepascore formula. In this study we evaluated prospectively a screening of liver fibrosis in 201 adult patients aged 19-54 years with transfusion-dependent thalassemia major, based on HA measurements. 41/201 patients were HCV-RNA (+). HA was measured with a turbidimetric assay applied on a clinical chemistry analyzer. The Hepascore was computed from the results by using the model previously published. The main results of the study showed that: a) HA levels were increased in 110/201 (55%) thalassemia patients 85.0 +/- 10.3 ng/ml, ranged from 15.0 to 1495.0 mu g/l, compared to 20.8 +/- 7.4 mu g/l reference laboratory values, p&lt;0.001, b) HA levels were significantly higher in HCV-RNA( +) compared to HCV-RNA(-) patients, 171.6 +/- 202 vs 53.8 +/- 35.5 mu g/l, p&lt;0.0001 c) no significant correlations were found between HA levels and/or Hepascore with ferritin and liver iron content (LIC) assessed with MRI (p&gt;0.324 and p&gt;0.270, respectively). Our findings indicate that hyaluronic acid measurements contribute to the assessment of liver fibrosis in patients with thalassemia and might be helpful for further evaluation of patients with liver biopsy if this is truly needed. Furthermore, liver fibrosis in thalassemia seems to be independent from liver siderosis. (C) 2010 Elsevier Inc. All rights reserved

Incretins, amylin and other gut-brain axis hormones in children with coeliac disease

Background Previous research indicated that coeliac disease (CD) is associated with type 1 diabetes mellitus (T1DM). However, the gut-brain axis peptide hormones secretion has not been evaluated so far in patients with CD prior to treatment initiation or under treatment, irrespective of patients having concomitant T1DM or not. The aim of the study was therefore to evaluate these gut hormones at the preprandial levels of patients with CD before and under treatment. Methods Of forty-seven CD children, 12 untreated (UCD), 22 treated with gluten-free diet (TCD) and 13 treated CD with coexisting T1DM (DCD), and 18 healthy controls (HC) were enrolled. Preprandial glucagon-like-peptide-1 (GLP-1), glucose-dependent-insulinotropic-polypeptide (GIP), active amylin, acylated ghrelin (AG), leptin, pancreatic polypeptide (PP) and peptide-tyrosine-tyrosine (PYY) were determined with hormone-map-array technology. Results We found in patients with CD compared with HC that the concentration of (i) GLP-1 was reduced remarkably in all patients with CD (P=0.008), (ii) GIP was lower in patients with UCD (P=0.008), (iii) amylin was remarkably reduced (P&lt;0.01) in all patients with CD, (iv) AG was significantly decreased in patients with DCD (P&lt;0.01), while (v) leptin, PP and PYY were not significantly different. GIP, GLP-1 and amylin levels correlated positively with insulin concentrations (P&lt;0.001, P=0.004 and P&lt;0.01, respectively) in all patients. Amylin and GIP levels were strongly associated with triglycerides concentrations (P&lt;0.001, for both peptides) in children with CD. Conclusions Our study revealed a different secretion pattern of gut-brain axis hormones in children with CD compared with HC. The alterations in the axis were more pronounced in children with both CD and T1DM

Absence of insulin resistance and low-grade inflammation despite early metabolic syndrome manifestations in children born after in vitro fertilization

Objective: 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. Design: Cross-sectional, case-control study. Setting: IVF Section of the First Department of Obstetrics and Gynecology and the First Department of Pediatrics of the University of Athens. Patient(s): One hundred six children conceived after classic IVF and 68 age-matched spontaneously conceived controls, aged 4-14 years. Intervention(s): Children underwent physical examination and morning fasting samples were collected. Main Outcome Measure(s): 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. Result(s): 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. Conclusion(s): 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. (Fertil Steril (R) 2010;94:1693-9. (C) 2010 by American Society for Reproductive Medicine.

Maternal-neonatal serum paraoxonase 1 activity in relation to the mode of delivery

Aim: To investigate the effect of the mode of labour and delivery on the total antioxidant status (TAS) and the paraoxonase 1 (PON 1) serum activity in mothers and their newborns. Subjects and methods: One hundred six women with normal pregnancy were divided into 4 groups: group A (n = 28) with normal labour and vaginal delivery (VG), group B (n = 25) with scheduled caesarean section (CS), group C (n = 26) with “emergency” CS and group D (n = 27) with prolonged labour + VG. Blood was obtained from the mothers at the beginning of the labour process and immediately after delivery (pre- and post-delivery) as well as from the umbilical cord (CB). PON I activity and blood chemistry were determined using the Bayer Advia 1650 Clinical Chemistry System, whereas TAS levels were measured spectrophotometrically at 450 min in microtiter plates. Results: TAS levels were similar pre-delivery and low in CB in all the groups. In contrast, TAS levels were remarkably reduced in group C and in group D post-delivery whereas they were nearly unchanged in group B and just lowered in group A, at the same time of study. PON 1 activity was practically unaltered in group A and group B pre- vs. post-delivery. Interestingly, the enzyme activity was remarkably decreased in group C (222 +/- 16 vs. 153 +/- 14 U/min/mL) and group D (216 +/- 16 vs. 135 +/- 15 U/min/mL, p &lt; 0.001) as compared with those of the other groups at the same time of study. Additionally, PON I activity was higher in the newborns of group A and group B than those in group C and group D. TAS and HDL positively correlated with PON 1 activity. Conclusions: The low TAS levels and the decreased PON 1 activity, which were found in groups C and D post-delivery, may be due to the increased production of free radicals, during long-lasting labour + VG and obstructive labour + CS. PON 1 activity was low in CB irrespectively of the mode of delivery, probably due to the low lipid levels in the serum of the umbilical cord. Neonates born with normal delivery or scheduled CS are benefited with a higher antiatherogenic enzyme activity perinatally. (c) 2006 The Canadian Society of Clinical Chemists. All rights reserved

Assessment of oxidative stress in patients with sickle cell disease: The glutathione system and the oxidant-antioxidant status

Continuous reactive oxygen species (ROS) production in individuals with sickle cell disease (SCD) may alter their overall redox status and cause tissue damage. The aim of this study was to evaluate oxidative stress in patients with SCD using two new assays, FORT (free oxygen radical test) and FORD (free oxygen radical defense) along with assessment of glutathione system including superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities, vitamins A C and E, malondialdehyde (MDA), non-transferrin bound iron (NTBI) and nitric oxide (NO) concentrations. A total of 40 patients with SCD and 25 apparently healthy volunteers (control group) were enrolled in the study. Components of glutathione system, vitamins A, C, and E, and malondialdehyde were determined with reverse-phase HPLC, non-transferrin bound iron (NTBI) was assessed with atomic absorption spectroscopy using graphite furnace, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities were determined spectrophotometrically in red cell lysates, nitric oxide (NO) was detected colorimetrically, while FORT and FORD using colorimetric assays, as two point-of-care tests. The findings revealed significant impairment of the glutathione system indicated by reduced GSH(total) (p&lt;0.00001), GSH(reduced) (p&lt;0.00001) and GSSG (p&gt;0.056) values of SCD patients compared to the control group. ROS expressed as FORT were significantly increased (p&lt;0.00001), while antioxidant defense expressed as FORD was significantly reduced (p&lt;0.02) in SCD group compared to the control group. Age and genotype of the patients as well as therapy of their disease appeared to play no role in their oxidative status. (C) 2011 Elsevier Inc. All rights reserved

Research update for articles published in EJCI in 2014

Our findings showed that p53 mRNA expression levels are upregulated in epicardial adipose tissue (EAT) from patients with heart failure (HF). This upregulation was also found in myocardium [2]. Our group have described its upregulation in EAT by sympathetic system