Publications (11)23.11 Total impact
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Article: Insulin Resistant Phenotype of Polycystic Ovary Syndrome does not Seem to be Caused by Variation in FTO.
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ABSTRACT: Genetic variation in the FTO gene is associated with increased body weight and reduced insulin sensitivity. We investigated whether genetic variation in FTO is associated with polycystic ovary syndrome (PCOS), a condition also characterized by insulin resistance. Furthermore, we tested whether insulin resistance is specifically associated with genetic variation in FTO in women with PCOS. Sixty-two nondiabetic patients with PCOS defined by the Rotterdam criteria were compared to BMI and age-matched women. Each PCOS case was matched to 2 controls. All participants underwent an oral glucose tolerance test and were genotyped for the single nucleotide polymorphism rs8050136 in the FTO gene. There was no difference in the frequency of FTO genotypes between the PCOS and the non-PCOS groups. In non-PCOS participants, genetic variation in FTO is associated with insulin sensitivity (p=0.03). This association remained significant after adjustment for age and/or BMI (p<= 0.03). In subjects with PCOS, however, FTO did not associate with insulin sensitivity (p=0.67). Genetic variation in FTO does not have an impact on insulin sensitivity in women with PCOS and is therefore not involved in the pathogenesis of the insulin resistant phenotype seen in patients with PCOS.Hormone and Metabolic Research 07/2012; 44(11):810-3. · 2.19 Impact Factor -
Article: Can Internet surveys help us understanding allergic disorders? - results from a large survey in urticaria in Greece.
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ABSTRACT: Urticaria is often underdiagnosed and/or undertreated. We have conducted an Internet-based study to record epidemiological and clinical features as well as therapeutic interventions for urticaria in a large sample of patients in Greece. A standard anonymous questionnaire was posted for a 3-month period on 'http://www.in.gr', a Greek popular Internet portal. Each individual participated only once. Participants were screened for the presence or history of urticaria by two key questions and were then asked to provide information on symptomatology and management. A total of 12 396 subjects voluntarily responded to the survey, of which 8440 (5136 females) who reported to have or had urticaria, were finally analysed. A total of 4780 (56.6%) had experienced weals only, 507 (6.0%) angio-oedema only and 3018 (35.8%) both. Weals and angio-oedema were found to be more common in women; 2761(57.8%) and 277(54.6%), respectively. Age of onset significantly correlated with disease duration; a 1% higher possibility of longer duration of urticaria exists (more than 6 weeks compared with less than 6 weeks) for each additional year of age of onset after controlling for gender. Patients with chronic urticaria had increased mean age compared with those reporting the acute form (35.04 vs. 33.88 years, P < 0.001). Dermatologists were the most frequently visited specialists and the most common treatments were antihistamines and topical preparations. The self-reported eliciting factors of urticaria were as follows: physical stimuli (approximately 25%), psychological distress (17.2%), direct contact to metals or chemicals (14.5%), foods and drugs (10%), whereas a third of the participants could not identify any trigger. Internet surveys can be a useful tool for screening the general population for common allergic disorders, such as urticaria.Journal of the European Academy of Dermatology and Venereology 05/2011; 25(5):532-7. · 2.98 Impact Factor -
Article: Effect of hyperthyroidism on clearance and secretion of glucagon in man.
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ABSTRACT: Glucagon has been proposed to contribute to the increased glucose production found in hyperthyroidism. However, fasting plasma glucagon levels are not increased in hyperthyroidism suggesting that the activity of the α-cell is normal. Nevertheless, an increase in the clearance rate of glucagon may mask increased glucagon secretion. This study was designed to examine the effects of hyperthyroidism on the kinetics of glucagon. A primed-continuous infusion of glucagon was administered to 9 euthyroid and 9 hyperthyroid subjects at 3 sequential rates (1,200, 3,000 and 6,000 pg/kg/min, each given for 2 h). Arterialized blood was drawn at 15-30 min intervals for determination of glucagon. Fasting plasma glucagon levels were comparable in euthyroids (195±8 pg/ml) and hyperthyroids (231±16 pg/ml). During infusions (1,200, 3,000 and 6,000 pg/kg/min), plasma glucagon increased to 387±19, 624±44 and 977±51 pg/ml in euthyroids and to 348±23, 597±42 and 938±56 pg/ml in hyperthyroids respectively. At these infusion rates, metabolic clearance of glucagon (ml/kg/min) was 6.6±0.5, 7.4±0.6 and 7.9±0.5 in euthyroids and 12.6±2, 8.9±1 and 8.8±0.6 in hyperthyroids, respectively. Metabolic clearance of glucagon differed between hyperthyroids and euthyroids at 1 200 pg/kg/min infusion rate (p=0.001). The basal delivery rate of glucagon (ng/kg/min) was 1.3±0.1 in euthyroids and 2.9±0.6 in hyperthyroids (p=0.0005). In hyperthyroidism, the secretion and metabolic clearance rates of glucagon are increased. These effects may explain the changes in plasma glucagon levels observed in hyperthyroidism and support the important role of glucagon in increasing endogenous glucose production in this condition.Experimental and Clinical Endocrinology & Diabetes 01/2011; 119(4):214-7. · 1.69 Impact Factor -
Article: Correlation between intracellular interferon-gamma (IFN-gamma) production by CD4+ and CD8+ lymphocytes and IFN-gamma gene polymorphism in patients with type 2 diabetes mellitus and latent autoimmune diabetes of adults (LADA).
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ABSTRACT: IFN-gamma is considered to be involved in the pathogenesis of diabetes mellitus. In this study, the presence of T/A mutation at position -874 in IFN-gamma gene was assessed in patients with latent autoimmune diabetes of adults (LADA), in patients with type 2 diabetes and in healthy individuals. Subsequently, an attempt was made to correlate the presence of this mutation with the ability of CD4+ or CD8+ lymphocytes from these individuals to release IFN-gamma following mitogenic stimulation. There were no significant differences in the distribution of genotypes and haplotypes in the three study groups. However, the frequency of the low IFN-gamma production allele (IFN-gamma 874( *)A) was significantly higher in type 2 diabetics compared to controls. CD4+ and CD8+ cells obtained from type 2 diabetics released significantly lower amounts of IFN-gamma in the intracellular space, compared to those released by cells obtained from LADA patients and healthy volunteers. Furthermore, even CD4+ and CD8+ from type 2 diabetics bearing the TT genotype (high producers) released significantly lower amounts of IFN-gamma than LADA patients carrying the same genotype, probably due to the activity of molecules directly or indirectly inhibiting IFN-gamma production. The results of this study indicate that IFN-gamma may contribute to the development of type 2 diabetes, based on a combination of molecular and immunological observations.Cytokine 08/2005; 31(2):135-41. · 3.02 Impact Factor -
Article: TNF-alpha, TGF-beta1, IL-10, IL-6, gene polymorphisms in latent autoimmune diabetes of adults (LADA) and type 2 diabetes mellitus.
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ABSTRACT: Abundant evidence suggests that cytokines involve in the pathogenesis of latent autoimmune diabetes of adults (LADA). This is a slowly progressive form of type 1 diabetes, which is initially diagnosed as type 2 diabetes. In this study, healthy individuals LADA and type 2 diabetic patients were genotyped for IL-6-174G/C, TNF-alpha-308A/G, TGF-beta1-codon10T/C, TGF-beta1-codon25G/C, IL-10-1082A/G, IL-10-819T/C, IL-10-592A/C gene polymorphisms, by sequence-specific-primer polymerase chain reaction methodology. A significant difference in the frequencies of -1082A/G IL-10 alleles was observed, with the -1082*A allele (known to be associated with low IL-10 production), predominating in LADA diabetics than type 2 diabetics (p=0.036). No significant differences of genotypes, phenotypes, or haplotype frequencies in the remaining cytokine polymorphisms were observed. Analysis of allele combinations revealed a significant involvement of the low and high in vitro production IL-10 alleles in the development of LADA and type 2 diabetes, respectively. These results suggest that the G/A mutation at position -1082 of IL-10 promoter gene region might be one of the factors participating to the pathogenesis of LADA diabetes and that identification of cytokine gene polymorphisms might contribute to the characterization of the different types of diabetes mellitus.Journal of Clinical Immunology 12/2004; 24(6):591-9. · 3.08 Impact Factor -
Article: Intracellular IFN-gamma production and IL-12 serum levels in latent autoimmune diabetes of adults (LADA) and in type 2 diabetes.
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ABSTRACT: Th1 cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), and Th1-inducing cytokines, such as IL-12, are involved in the pathogenesis of various organ-specific autoimmune diseases, including autoimmune diabetes. In this study, we investigated intracellular IFN-gamma release by T lymphocytes and IL-12 serum levels in 48 type 2 and 36 latent autoimmune diabetes of adults (LADA) diabetics and 25 control subjects in an attempt to evaluate their role in the pathogenesis of these clinical entities. Ionomycin (ION) and phorbol-12-myristate-13-acetate (PMA)-activated peripheral blood mononuclear cells (PBMCs) were stained with anti-CD4-FITC or anti-CD8-FITC and anti-IFN-gamma phycoerythrin (PE) monoclonal antibodies (mAbs) and analyzed by flow cytometry. IL-12 serum levels were determined by enzyme-linked immunosorbent assay (ELISA). In all study groups, IFN-gamma content of CD4(+) and CD8(+) lymphocytes was significantly upregulated by stimulation. Furthermore, it was observed that CD4(+) and CD8(+) lymphocytes from type 2 diabetics produced significantly lower levels of IFN-gamma compared with LADA patients and controls. However, the percentages of CD4(+)/IFN-gamma(+) and CD8(+)/IFN-gamma(+) cells from type 2 diabetics were significantly higher compared with controls. The flow cytometric picture of intracellular IFN-gamma release in LADA patients did not differ from that observed in controls. However, IL-12 serum levels in type 2 and LADA diabetics were lower than in controls. Because Th1 cytokines have been associated with the pathogenesis of autoimmune diabetes, these results preclude Th1 involvement in the autoimmune phenomena observed in LADA patients. In contrast, the low IFN-gamma levels observed in type 2 diabetics in combination with the low IL-12 serum levels might be a contributing factor in the frequently observed chronic complications in these patients.Journal of Interferon & Cytokine Research 08/2004; 24(7):381-7. · 3.06 Impact Factor -
Article: Flow cytometric detection of intracellular IL-12 release: in vitro effect of widely used immunosuppressants.
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ABSTRACT: Interleukin 12 (IL-12) is a potent regulator of the Th1/Th2 pathway, enhancing alloantigen-specific immune functions. In the present study, we developed a flow cytometric assay detecting intracellular IL-12 production by human CD14+ monocytes in order to assess the in vitro effects of widely used immunosuppressants, such as cyclosporine (CsA), sirolimus (SRL) and dexamethasone (DXM). For the purpose of the study, a two-step activation procedure was developed involving the preactivation of peripheral blood mononuclear cells (PBMC) with interferon-gamma (IFN-gamma) and reactivation with IFN-gamma and lipopolysaccharide (LPS). All immunosuppressive agents were added at the initiation of the preactivation or the reactivation step. Following this activation protocol, a fourfold to fivefold up-regulation of the percentage of CD14+/IL-12+ cells and of the mean fluorescence intensity was observed. CsA did not significantly affect the intracellular IL-12 release by CD14+ cells, independent of the time point of the addition. SRL exerted an up-regulatory effect when added at the initiation of the IFN-gamma pre-incubation, and this was manifested as a significant increase in the percentage of CD14+/IL-12+ cells. In contrast, DXM effectively repressed both the percentage and the fluorescence intensity of IL-12-producing CD14+ cells when added at the initiation of the reactivation step. Since only the steroid preparation was shown to down-regulate the intracellular release of IL-12, it is tempting to assume that steroid addition in immunosuppressive schemes is beneficial for the suppression of Th1-inducing cytokine production, as well as for the compensation of possible up-regulation induced by other immunosuppressive agents administered concurrently.International Immunopharmacology 12/2002; 2(12):1713-20. · 2.38 Impact Factor -
Article: Comparative effects of glimepiride and glibenclamide on blood glucose, C-peptide and insulin concentrations in the fasting and postprandial state in normal man.
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ABSTRACT: A single-center, randomised, placebo- controlled, cross-over study was conducted to characterize the new sulfonylurea glimepiride and to compare its profile of action with the second generation sulfonylurea glibenclamide. The total duration of each experiment was 5 hours. At zero time an i.v. injection of 2 and 4 mg glimepiride, 1 mg glibenclamide or placebo was given i.v. to 24 healthy volunteers. Blood samples were collected for three hours after the injection (0-3 hours, preprandial experiment). At 3 hours, a standard mixed meal was given (20%, of a 30 Kcal/Kg Body Weight diet) and blood samples were collected for 2 more hours (postprandial experiment). Pre-prandially (0-3 hrs) blood glucose (expressed as the area under the curve divided by the time) was significantly lower (p < 0.0001) after the administration of 2 and 4 mg glimepiride (3.8 +/- 0.22 and 3.5 +/- 0.3 mM respectively) compared to placebo (4.63 +/- 0.31 mM), but not compared to glibenclamide. Insulin and C-peptide were not different after glimepiride or glibenclamide. Both glimepiride and glibenclamide had similar effects on insulin secretion. Post-prandially (3-5 hrs) blood glucose was significantly higher after glibenclamide (6.54 +/- 0.8 mM) (p < 0.0001) than after 2 mg glimepiride (5.75 +/- 0.5 mM). Despite this C-peptide was significantly higher (p < 0.002) glibenclamide (5.7 +/- 1.5 ng/ml) compared to glimepiride (5.1 +/- 1.3 ng/ml); the trend was the same for insulin but the results were not significantly different (p = 0.06) In conclusion, in the fasting state, glimepiride and glibenclamide had similar effects on the changes in blood glucose levels after i.v. administration. After the meal, less pronounced hyperglycemia and lower insulin and C-peptide levels following glimepiride (2 mg) suggests either that glimepiride induces insulin secretion through a pathway which is different from that of glibenclamide or that glimepiride facilitates insulin action through extrapancreatic effects.Experimental and Clinical Endocrinology & Diabetes 01/1999; 107(6):350-5. · 1.69 Impact Factor -
Article: Effects of prolonged administration of two new alpha-glucosidase inhibitors on blood glucose control, insulin requirements and breath hydrogen excretion in patients with insulin-dependent diabetes mellitus.
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ABSTRACT: Alpha-glucosidase inhibitors delay carbohydrate absorption. In order to study the effects of two new alpha-glucosidase inhibitors with long (BAYo1248) and short (BAYm1099) duration of action on glycaemic control, seventeen insulin-dependent diabetics were connected to the Biostator for 24 h and postprandial hyperglycaemia, insulin requirements and breath H2 concentrations were assessed under three conditions: (a) before administration of any alpha-glucosidase inhibitor (control experiments), (b) after administration of BAYo1248 (40 mg before breakfast, nine patients) or BAYm1099 (100 mg before breakfast and dinner, eight patients) for 1 month, (c) after 1-month administration of placebo (double-blind crossover study). All patients were on standard diets (30 kcal kg-1, 45% carbohydrate, 35% fat, 20% protein). BAYo1248 reduced postprandial hyperglycaemia and insulin requirements (vs. values in control and placebo experiments) after breakfast (124 +/- 8 vs. 159 +/- 8 and 158 +/- 8 mg dl-1, 16 +/- 2 vs. 24 +/- 4 and 23 +/- 3 units, P less than 0.01) and lunch (138 +/- 7 vs. 155 +/- 11 and 162 +/- 13 mg dl-1, 19 +/- 3 vs. 24 +/- 3 and 23 +/- 3 units, P less than 0.01) whereas BAYm1099 reduced postprandial hyperglycaemia and insulin requirements after breakfast (127 +/- 4 vs. 167 +/- 12 and 159 +/- 6 mg dl-1, 15 +/- 3 vs. 24 +/- 4 and 21 +/- 3 units, P less than 0.02) and dinner (128 +/- 4 vs. 169 +/- 7 and 157 +/- 10 mg dl-1, 19 +/- 2 vs. 28 +/- 3 and 25 +/- 2 units, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)European Journal of Clinical Investigation 03/1988; 18(1):33-8. · 3.02 Impact Factor -
Article: Effects of two new alpha-glucosidase inhibitors on glycemic control in patients with insulin-dependent diabetes mellitus.
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ABSTRACT: BAYo1248 and BAYm1099 are two new alpha-glucosidase inhibitors. Postprandial glucose tolerance was significantly improved and postprandial insulin requirements were significantly reduced as compared to placebo after breakfast and lunch when 20 mg BAYo1248 were administered prior to breakfast and after breakfast, lunch and dinner when 50 mg BAYm1099 were given prior to all three main meals. Postprandial breath H2 concentrations were mildly increased when these alpha-glucosidase inhibitors were given and no patient complained of any adverse effects (such as flatulence, abdominal pain or diarrhea). BAYo1248 and BAYm1099 might be useful adjuncts to insulin in the treatment of patients with insulin-dependent diabetes mellitus.Klinische Wochenschrift 06/1986; 64(9):405-10. -
Article: IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies
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ABSTRACT: Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, –174G>C (rs1800795) and –573G>C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 –174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 –573G>C and type 2 diabetes. The observed association of the IL6 –174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding.Huth, C. and Heid, I.M. and Vollmert, C. and Gieger, C. and Grallert, H. and Wolford, J.K. and Langer, B. and Thorand, B. and Klopp, N. and Hamid, Y.H. and Pedersen, O. and Hansen, T. and Lyssenko, V. and Groop, L. and Meisinger, C. and Döring, A. and Löwel, H. and Lieb, W. and Hengstenberg, C. and Rathmann, W. and Martin, S. and Stephens, J.W. and Ireland, H. and Mather, H. and Miller, G.J. and Stringham, H.M. and Boehnke, M. and Tuomilehto, J. and Boeing, H. and Möhlig, M. and Spranger, J. and Pfeiffer, A. and Wernstedt, I. and Niklason, A. and López-Bermejo, A. and Fernández-Real, J.-M. and Hanson, R.L. and Gallart, L. and Vendrell, J. and Tsiavou, A. and Hatziagelaki, E. and Humphries, S.E. and Wichmann, H.-E. and Herder, C. and Illig, T. (2006) IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies. Diabetes, 55 (10). pp. 2915-2921. ISSN 00121797.
Top co-authors
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Institutions
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2011–2012
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Attikon University Hospital
Athens, Attiki, Greece
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2004–2005
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Onassis Cardiac Surgery Center
Kallithéa, Attiki, Greece
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