Publications by authors named "Eirini Maratou"

50 Publications

The prognostic role of RBP-4 and adiponectin in patients with peripheral arterial disease undergoing lower limb endovascular revascularization.

Cardiovasc Diabetol 2021 11 10;20(1):221. Epub 2021 Nov 10.

2nd Department of Internal Medicine, Research Institute and Diabetes Centre, Athens University Medical School, Attikon University General Hospital, Athens, Greece.

Background: RBP4 is an adipokine with an established role in atherosclerosis, while adiponectin has unique anti-inflammatory properties. We investigated the association of RBP4 and adiponectin with the presence of symptomatic peripheral artery disease (PAD) and their possible prognostic role in major adverse cardiovascular events (MACE).

Methods: We enrolled 168 consecutive patients with symptomatic, established PAD, requiring revascularization by endovascular means of any or both of their lower limbs. 88 age- and sex-matched subjects with less than 2 classical cardiovascular risk factors served as controls. Clinical parameters, glycemic and lipid profile, RBP4 and adiponectin levels were assayed. The occurrence of MACE was recorded during the 6-month follow-up and patients were assigned to MACE and non-MACE subgroups.

Results: The presence of symptomatic PAD was significantly correlated with age, diabetes, hsCRP, RBP4 and low adiponectin levels (p < 0.05). After adjustment for age, RBP4 (β = 0.498, p < 0.001), and adiponectin (β = -0.288, p < 0.001) levels remained as independent predictors of PAD presence in the whole study cohort. At baseline, MACE subgroup appeared with higher RBP-4 and hsCRP serum levels than non-MACE subgroup (p < 0.001), but no differences were detected for adiponectin (p = 0.758). Serum RBP4 levels remained independent predictor of MACE (β = 0.455, p < 0.001) after adjustment for traditional cardiovascular risk factors.

Conclusions: High RBP4 and low adiponectin serum levels are independently associated with PAD presence. In addition, RBP4 is an independent predictor of MACE incidence in symptomatic PAD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-021-01411-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582224PMC
November 2021

Angiotensin-converting-enzyme insertion/deletion polymorphism, ACE activity, and COVID-19: A rather controversial hypothesis. A case-control study.

J Med Virol 2021 Oct 28. Epub 2021 Oct 28.

Department of Clinical Biochemistry, University General Hospital "ATTIKO," National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Accumulating data has shown a contribution of the renin-angiotensin system in COVID-19 pathogenesis. The role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism as a risk factor in developing COVID-19 disease comes from epidemiological data and is controversially discussed. We conducted a retrospective case-control study and assessed the impact of ACE I/D genotype in COVID-19 disease prevalence and severity. In 81 COVID-19 patients explicitly characterized and 316 controls, recruited during the first wave of COVID-19 pandemic, ACE I/D genotype, and ACE activity were determined. A generalized linear model was used and Poisson regression analysis estimated the risk ratios (RRs) of alleles and genotypes for disease severity. DD patients had almost 2.0-fold increased risk (RR: 1.886, confidence limit [CL] 95%: 1.266-2.810, p = 0.0018) of developing a more severe disease when contrasted to ID and II individuals, as did D allele carriers compared to I carriers (RR: 1.372; CL 95%: 1.051-1.791; p = 0.0201). ACE activity (expressed as arbitrary units, AU/L) was lower in patients (3.62 ± 0.26) than in controls (4.65 ± 0.13) (p < 0.0001), and this reduction was observed mainly among DD patients compared to DD controls (3.97 ± 0.29 vs. 5.38 ± 0.21; p = 0.0014). Our results demonstrate that ACE DD genotype may predispose to COVID-19 increased disease severity via a mechanism associated, at least in part, with the significant fall in their ACE activity. Our findings suggest a more complex pattern of synergy between this polymorphism and ACE activity in COVID-19 patients compared to healthy individuals and set the grounds for large-scale studies assessing ACE genotype-based optimized therapies with ACE inhibitors and angiotensin receptor blockers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.27417DOI Listing
October 2021

Plasma nesfatin-1 and DDP-4 levels in patients with coronary artery disease: Kozani study.

Cardiovasc Diabetol 2021 08 13;20(1):166. Epub 2021 Aug 13.

2nd Department of Internal Medicine, Research Institute and Diabetes Centre, Athens University Medical School, Attikon University General Hospital, Athens, Greece.

Background: Nesfatin-1, a novel adipokine and dipeptidyl peptidase-4 (DPP4), a mam malian serine protease, are potent factors of atherosclerosis. In the present cross-sectional study, we investigated whether the plasma nesfatin-1 and DPP4 is associated with the prevalence and severity of coronary artery disease (CAD) with and without diabetes mellitus (DM).

Methods: We consecutively enrolled a total of 240 patients with significant CAD (previous revascularization or angiographically-proven coronary artery stenosis > 50%) presented with either unstable angina (UA, N = 76) or stable chronic CAD (SCAD, N = 165). 85 patients with at least 2 classical cardiovascular risk factors but without significant CAD served as controls. The severity of CAD was assessed using coronary angiography by the Gensini score. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), nesfatin-1 and DPP4 levels were assayed.

Results: No differences were found for age, sex, hypertension and diabetes distribution between groups. Low nesfatin-1 levels were found in both CAD groups (UA & SCAD) with respect to controls. The difference between UA and SCAD groups was marginally non-significant. There was a significant increase of DPP4 along UA to SCAD and control groups. Differences between groups remained unchanged in non-diabetic participants. Nesfatin-1 significantly correlated to hsCRP (r = - 0.287, p = 0.036), HOMA-IR (r = - 0.587, p = 0.007) and hyperlipidemia (r = - 0.331, p = 0.034). DPP4 was significantly associated with hs-CRP (r = 0.353 p < 0.001) and FPG (r = 0.202, p = 0.020) in univariate analysis, but those correlations were lost in multiple regression analysis. There was a negative correlation between nesfatin-1 and the severity of CAD, quantified by the Gensini score (r = - 0.511, p < 0.001), but no association was found for DPP4.

Conclusions: Serum DPP4 levels are increased in patients with CAD, while serum nesfatin-1 levels have a negative association with both the incidence and the severity of CAD. These results are independent of the presence of diabetes mellitus. In addition, both peptides have a strong association with hsCRP. Trial registration ClinicalTrials.gov Identifier: NCT00306176.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-021-01355-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362239PMC
August 2021

Case Report: Metreleptin Treatment in a Patient With a Novel Mutation for Familial Partial Lipodystrophy Type 3, Presenting With Uncontrolled Diabetes and Insulin Resistance.

Front Endocrinol (Lausanne) 2021 8;12:684182. Epub 2021 Jun 8.

Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Oxford University Hospital Trusts, Oxford, United Kingdom.

Background: Familial partial lipodystrophy type 3 (FPLD3) is a very rare autosomal dominant genetic disorder which is caused by mutations in the peroxisome proliferator activated receptor gamma () gene. It is characterized by a partial loss of adipose tissue leading to subnormal leptin secretion and metabolic complications. Metreleptin, a synthetic analogue of human leptin, is an effective treatment for generalized lipodystrophies, but the evidence for efficacy in patients with FPLD3 is scarce.

Case Presentation: We present a 61-year-old woman, initially misdiagnosed as type 1 diabetes since the age of 29, with severe insulin resistance, who gradually displayed a more generalized form of lipoatrophy and extreme hypertriglyceridemia, hypertension and multiple manifestations of cardiovascular disease. She was found to carry a novel mutation leading to PPARG variant. After six months of metreleptin treatment, HbA1c decreased from 10 to 7.9% and fasting plasma triglycerides were dramatically reduced from 2.919 mg/dl to 198 mg/dl.

Conclusions: This case highlights the importance of early recognition of FPLD syndromes otherwise frequently observed as difficult-to-classify and manages diabetes cases, in order to prevent cardiovascular complications. Metreleptin may be an effective treatment for FPLD3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.684182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217860PMC
June 2021

Haemostatic profile of riboflavin-treated apheresis platelet concentrates.

Blood Transfus 2021 May 21. Epub 2021 May 21.

Laboratory of Haematology and Blood Bank Unit, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Background: The haemostatic activity of platelet concentrates (PCs) treated with pathogen reduction technology (PRT) remains a subject of debate. Our aim was to investigate the effect of Mirasol PRT on the haemostatic properties of PCs stored in plasma.

Material And Methods: Untreated and Mirasol-treated platelets stored in plasma and derived from ten split double-dose apheresis PCs were evaluated in vitro on days 1, 3 and 5 post collection for functionality, microparticle procoagulation activity (MPA), endogenous thrombin potential (ETP), and haemostatic profile using rotational thromboelastometry (ROTEM).

Results: P-selectin expression was significantly higher in Mirasol-treated platelets compared with untreated counterparts on days 3 and 5 (p=0.003 and p=0.002, respectively). Clot strength, as shown by EXTEM maximum clot firmness (MCF), was significantly lower in the Mirasol-treated platelets at all time points (days 1, 3, 5) than in untreated platelets (p=0.009, p<0.001, p<0.001, respectively). There was a considerable increase in MPA over time (p<0.001) and this was significantly higher in the Mirasol-treated platelets on day 5 (p=0.015). A notable acceleration of decrease in ETP values was observed for Mirasol-treated PCs over time (p<0.001), with significant differences between PRT-treated and untreated PCs on days 3 and 5 (p=0.038 and p=0.019, respectively). Clot strength attenuation was significantly associated with pH reduction (p<0.001, Spearman's rho: 0.84), increased microparticle procoagulant activity (p<0.001, Spearman's rho: -0.75), and with decreased ETP (p<0.032, Spearman's rho: 0.41).

Discussion: Increased platelet activation induced by PRT treatment leads to a decrease in in vitro haemostatic capacity as seen by reduced clot strength and thrombin generation capacity over time. The clinical relevance of this needs to be investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2450/2021.0089-21DOI Listing
May 2021

Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.

Nat Genet 2021 06 17;53(6):817-829. Epub 2021 May 17.

Department of Neuroscience, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-021-00857-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192451PMC
June 2021

Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach.

Nutrients 2021 Jan 6;13(1). Epub 2021 Jan 6.

Research Institute and Diabetes Center, 2nd Department of Internal Medicine, "Attikon" University Hospital, 1 Rimini Street, 12542 Haidari, Greece.

Glucose levels in blood must be constantly maintained within a tight physiological range to sustain anabolism. Insulin regulates glucose homeostasis via its effects on glucose production from the liver and kidneys and glucose disposal in peripheral tissues (mainly skeletal muscle). Blood levels of glucose are regulated simultaneously by insulin-mediated rates of glucose production from the liver (and kidneys) and removal from muscle; adipose tissue is a key partner in this scenario, providing nonesterified fatty acids (NEFA) as an alternative fuel for skeletal muscle and liver when blood glucose levels are depleted. During sleep at night, the gradual development of insulin resistance, due to growth hormone and cortisol surges, ensures that blood glucose levels will be maintained within normal levels by: (a) switching from glucose to NEFA oxidation in muscle; (b) modulating glucose production from the liver/kidneys. After meals, several mechanisms (sequence/composition of meals, gastric emptying/intestinal glucose absorption, gastrointestinal hormones, hyperglycemia mass action effects, insulin/glucagon secretion/action, de novo lipogenesis and glucose disposal) operate in concert for optimal regulation of postprandial glucose fluctuations. The contribution of the liver in postprandial glucose homeostasis is critical. The liver is preferentially used to dispose over 50% of the ingested glucose and restrict the acute increases of glucose and insulin in the bloodstream after meals, thus protecting the circulation and tissues from the adverse effects of marked hyperglycemia and hyperinsulinemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13010159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825450PMC
January 2021

The haemostatic profile in critically ill COVID-19 patients receiving therapeutic anticoagulant therapy: An observational study.

Medicine (Baltimore) 2020 Nov;99(47):e23365

Second Department of Critical Care, "Attikon" University Hospital, National and Kapodistrian University of Athens, Medical School.

Hypercoagulability and thrombosis remain a challenge in severe coronavirus disease 2019 (COVID-19) infections. Our aim is to investigate the hemostatic profile of critically ill COVID-19 patients on therapeutic anticoagulant treatment.Forty one patients were enrolled into the study. We recruited 11 consecutive, COVID-19, patients who received therapeutic anticoagulant treatment on intensive care unit (ICU) admission. Disease severity indexes, biochemical, hematological and haemostatic parameters, endogenous thrombin potential (ETP), plasminogen activator inhibitor-1 (PAI-1) activity and extrinsically activated rotational thromboelastometry assay (EXTEM) were recorded on days 1, 3, 7. We also enrolled 9 ICU non-COVID-19, 21 non-ICU COVID-19 patients and 20 healthy blood donors as control populations.Critically ill COVID-19 patients demonstrated a more hypercoagulable and hypofibrinolytic profile related to those with COVID-19 mild illness, based on EXTEM amplitude at 10 min (A10), maximum clot firmness (MCF) and lysis index at 60 min (LI60) variables (p = 0.020, 0.046 and 0.001, respectively). Similarly, a more hypercoagulable state was detected in COVID-19 ICU patients related to non-COVID-19 ICU patients based on A10 and MCF parameters (p = 0.03 and 0.04, respectively). On the contrary, ETP and EXTEM (clotting time) CT values were similar between patients with severe and mild form of the COVID-19 infection, probably due to anticoagulant treatment given.Critically ill COVID-19 patients showed a hypercoagulable profile despite the therapeutic anticoagulant doses given. Due to the small sample size and the study design, the prognostic role of the hypercoagulability in this clinical setting remains unknown and further research is required in order to be assessed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000023365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676559PMC
November 2020

Lessons from Wolfram Syndrome: Initiation of DDAVP Therapy Causes Renal Salt Wasting Due to Elevated ANP/BNP Levels, Rescued by Fludrocortisone Treatment.

Indian J Pediatr 2021 06 18;88(6):582-585. Epub 2020 Nov 18.

Department of Pediatric Endocrinology & Diabetes, Athens Medical Center, Athens, Greece.

Initiation of desmopressin acetate (DDAVP) for untreated diabetes insipidus (DI) in Wolfram syndrome (WS) causes abrupt volume expansion resulting in particularly high secretion of Atrial Natriuretic Peptide (ANP) and/or Brain Natriuretic Peptide (BNP), which in turn blocks all stimulators of zona glomerulosa steroidogenesis, resulting in secondary mineralocorticoid deficiency and acute hyponatremia, causing renal salt wasting (RSW). Two sisters, a 19-y-old girl (A) and a 7-y-old girl (B) with WS, presented with severe polyuria-polydipsia due to never treated DI. Both had neurogenic bladder and "B" had severe hydronephrosis secondary to untreated grade III bilateral vesicoureteral reflux. They initiated therapy with oral melt DDAVP which resulted in RSW. ANP was found ×50 and BNP ×2-4 fold elevated. Fludrocortisone 100-200 × 2 μg/d controlled natriuresis and restored electrolytes to normal within 48 h. Fludrocortisone treatment rescues otherwise potentially life-threatening hyponatremia due to RSW and the secondary mineralocorticoid deficiency driven by elevated ANP and/or BNP, caused by sudden volume expansion following DDAVP initiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12098-020-03538-yDOI Listing
June 2021

Association of Glycemic Indices (Hyperglycemia, Glucose Variability, and Hypoglycemia) with Oxidative Stress and Diabetic Complications.

J Diabetes Res 2020 12;2020:7489795. Epub 2020 Oct 12.

First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, Athens, Greece.

Oxidative stress (OS) is defined as a disturbance in the prooxidant-antioxidant balance of the cell, in favor of the former, which results in the antioxidant capacity of the cell to be overpowered. Excess reactive oxygen species (ROS) production is very harmful to cell constituents, especially proteins, lipids, and DNA, thus causing damage to the cell. Oxidative stress has been associated with a variety of pathologic conditions, including diabetes mellitus (DM), cancer, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and accelerated aging. Regarding DM specifically, previous experimental and clinical studies have pointed to the fact that oxidative stress probably plays a major role in the pathogenesis and development of diabetic complications. It is postulated that hyperglycemia induces free radicals and impairs endogenous antioxidant defense systems through several different mechanisms. In particular, hyperglycemia promotes the creation of advanced glycation end-products (AGEs), the activation of protein kinase C (PKC), and the hyperactivity of hexosamine and sorbitol pathways, leading to the development of insulin resistance, impaired insulin secretion, and endothelial dysfunction, by inducing excessive ROS production and OS. Furthermore, glucose variability has been associated with OS as well, and recent evidence suggests that also hypoglycemia may be playing an important role in favoring diabetic vascular complications through OS, inflammation, prothrombotic events, and endothelial dysfunction. The association of these diabetic parameters (i.e., hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress will be reviewed here.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/7489795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585656PMC
September 2021

Coagulation Profiles of Pulmonary Arterial Hypertension Patients, Assessed by Non-Conventional Hemostatic Tests and Markers of Platelet Activation and Endothelial Dysfunction.

Diagnostics (Basel) 2020 Sep 27;10(10). Epub 2020 Sep 27.

Second Department of Critical Care Medicine, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Rimini 1, 12462 Athens, Greece.

Many pathophysiologic processes of pulmonary arterial hypertension (PAH), namely, excess vasoconstriction, vascular remodeling and in situ thrombosis, involve the coagulation cascade, and more specifically, platelets. The aim of this study was to globally assess coagulation processes in PAH, by using non-conventional hemostatic tests, along with markers of platelet activation and endothelial dysfunction. We studied 44 new PAH patients (22 with idiopathic PAH and 22 with connective tissue disease) and 25 healthy controls. The following tests were performed: platelet function analyzer-100 (PFA-100), light transmission aggregometry (LTA), rotational thromboelastometry (ROTEM), endogenous thrombin potential (ETP), serotonin, thromboxane A2 and p-selectin plasma levels, and von Willebrand antigen (VWF:Ag) and activity (VWF:Ac). Our results showed that PAH patients had diminished platelet aggregation, presence of disaggregation, defective initiation of the clotting process and clot propagation, and diminished thrombin formation capacity. Serotonin, thromboxane A2 and p-selectin levels were increased, and VWF:Ag and VWF:Ac decreased in the same population. The results of this study suggest that the platelets of PAH patients are activated and present functional abnormalities. The procoagulant activity, in general, appears to be impaired probably due to a sustained and prolonged activation of the procoagulant processes. Larger observational studies are warranted to confirm these laboratory findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics10100758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601126PMC
September 2020

Prognostic impact of indoleamine 2,3-dioxygenase 1 mRNA expression on circulating tumour cells of patients with head and neck squamous cell carcinoma.

ESMO Open 2020 05;5(3):e000646

Second Department of Internal Medicine, Section of Medical Oncology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece. Electronic address:

Background: We sought to determine the prognostic role of indoleamine 2,3-dioxygenase 1 () by evaluating expression in circulating tumour cells (CTCs) at baseline and after completion of chemoradiotherapy in patients with locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) treated with curative intent.

Methods: In a prospective cohort of 113 patients with LA HNSCC, we evaluated expression of in the EpCAM+ CTC fraction at baseline and after cisplatin chemoradiation. The prognostic value of combined () and expression was assessed.

Results: was significantly overexpressed at baseline compared with the post-treatment counterparts (p=0.007). messenger RNA (mRNA) expression at baseline was associated with better survival in terms of progression-free survival (PFS) (HR=0.19, p=0.017). Post-treatment mRNA levels were correlated with unfavourable prognosis in terms of overall survival (OS) (HR=3.27, p=0.008). Patients with combined decreased expression levels of and after treatment exhibited superior PFS (p=0.043) and OS (p=0.021).

Conclusions: Our results strongly suggest that mRNA expression is an independent prognostic factor for clinical outcome. Our study provides useful information for future trials combining chemoradiation with immune checkpoint inhibitors and IDO1 inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/esmoopen-2019-000646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232623PMC
May 2020

Blood-based analysis of 84 microRNAs identifies molecules deregulated in individuals with type-2 diabetes, risk factors for the disease or metabolic syndrome.

Diabetes Res Clin Pract 2020 Jun 1;164:108187. Epub 2020 May 1.

Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK; Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia, Cyprus. Electronic address:

Aim: Micro-RNAs (miRNAs) are implicated in insulin-signaling and the development of type-2 diabetes (T2D). Their deregulated expression is mostly described in the pancreas, liver, skeletal muscle, or adipose tissue of diabetic animals. Relevant studies in humans are limited due to difficulties in accessing tissue-biopsies. Though, circulating miRNAs are indicators of organ-specific pathophysiological events and could potentially serve as disease biomarkers. We explored the profile of 84 T2D-related miRNAs in peripheral blood of subjects with or without the disease.

Methods: An RT-qPCR array screening 84 T2D-related miRNAs was applied in samples of T2D (n = 6) versus non-T2D (n = 6) subjects. The deregulated miRNAs were thereafter analyzed in peripheral blood samples of a validation cohort of 40 T2D and 37 non-T2D individuals [16 controls and 21 subjects with metabolic syndrome (Met-S) and/or T2D risk factors (T2D-RF)], using specific RT-qPCR assays. Correlations with clinicopathological parameters and risk factors were evaluated.

Results: Subjects with the disease displayed decreased levels of miR-214-3p, miR-24-3p and let-7f-5p, compared to those without. MiRNA levels correlated with serum insulin and HbA1c levels in individuals with T2D or Met-S/T2D-RF, and with higher BMI, dyslipidemia and family history in controls.

Conclusions: Blood levels of miR-214-3p, miR-24-3p and let-7f-5p are down-regulated in T2D- and Met-S/T2D-RF subjects. Future studies are needed to evaluate their potential as disease biomarkers and elucidate the associated tissue-specific pathogenetic mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diabres.2020.108187DOI Listing
June 2020

β-Amyloid and mitochondrial-derived peptide-c are additive predictors of adverse outcome to high-on-treatment platelet reactivity in type 2 diabetics with revascularized coronary artery disease.

J Thromb Thrombolysis 2020 Apr;49(3):365-376

Laboratory of Haematology & Blood Bank Unit, 'Attikon University Hospital', School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Background And Aims: Increased β-amyloid and decreased mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization.

Patients And Methods: In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: (a) maximum platelet aggregation to adenosine diphosphate (ADP) by light transmission aggregometry (LTAmax), (b) malondialdehyde (MDA), as oxidative stress marker, (c) MOTS-c, (d) β-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up.

Results: Out of 121 patients, 32 showed HPR (LTAmax > 48%,). At baseline, HPR was associated with β-amyloid > 51 pg/ml (p = 0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, β-amyloid > 51 pg/ml and MOTS-c < 167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p < 0.05) after adjusting for confounders and medication. There was significant interaction between HPR and β-amyloid or MOTS-c for the prediction of MACE (p < 0.05). Patients with HPR and β-amyloid > 51 mg/dl or HPR and MOTS-c concentration < 167 ng/ml had a fourfold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p < 0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD.

Conclusions: Increased β-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT04027712.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-020-02060-4DOI Listing
April 2020

Decreased expression of microRNAs targeting type-2 diabetes susceptibility genes in peripheral blood of patients and predisposed individuals.

Endocrine 2019 11 26;66(2):226-239. Epub 2019 Sep 26.

Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.

Aim: Certain microRNA molecules (miRNAs) that target genes involved in beta-cell growth and insulin resistance are found deregulated in patients with type-2 diabetes mellitus (T2D) and correlate with its complications. However, the expression profile of miRNAs that regulate genes bearing T2D-related single-nucleotide polymorphisms has been hardly studied. We recently reported that the mRNA patterns of specific T2D-susceptibility genes are impaired in patients, and associate with disease parameters and risk factors. The aim of this study was to explore the levels of miRNAs that target those genes, in peripheral blood of patients versus controls.

Methods: A panel of 14 miRNAs validated to target the CDKN2A, CDK5, IGF2BP2, KCNQ1, and TSPAN8 genes, was developed upon combined search throughout the DIANNA TarBase v7.0, miRTarBase, miRSearch v3.0-Exiqon, miRGator v3.0, and miRTarget Link Human algorithms. Specifically developed poly(A)polyadenylation(PAP)-reverse transcription(RT)-qPCR protocols were applied in peripheral blood RNA samples from patients and controls. Possible correlations with the disease, clinicopathological parameters and/or risk factors were evaluated.

Results: T2D patients expressed decreased levels of let-7b-5p, miR-1-3p, miR-24-3p, miR-34a-5p, miR-98-5p, and miR-133a-3p, compared with controls. Moreover, these levels correlated with certain disease features including insulin and % HbA1c levels in patients, as well as BMI, triglycerides' levels and family history in controls.

Conclusions: A T2D-specific expression profile of miRNAs that target disease-susceptibility genes is for the first time described. Future studies are needed to elucidate the associated transcription-regulatory mechanisms, perchance involved in T2D pathogenesis, and to evaluate the potential of these molecules as possible biomarkers for this disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-019-02062-0DOI Listing
November 2019

Prognostic Significance of IGF-1 Signalling Pathway in Patients With Advanced Non-small Cell Lung Cancer.

Anticancer Res 2019 Aug;39(8):4185-4190

Second Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Background/aim: Insulin-like growth factor 1 (IGF-1)-mediated molecular pathway has been implicated in non-small cell lung cancer (NSCLC) pathogenesis and progression. We aimed to evaluate serum levels of IGF-1, IGF-2 and IGF-binding protein 3 (IGF-BP3) before and after standard treatment in patients with advanced NSCLC and their prognostic and predictive correlations.

Patients And Methods: Seventy-three patients were prospectively included. Analysis and quantification of circulating levels of IGF1, IGF2, IGFBP3 were performed by total ELISA in peripheral blood samples at baseline and 3 months post-treatment.

Results: The median values of IGF-1 and IGF-1/IGF-BP3 ratios (125.82 vs. 133.4 ng/ml, p=0.087 and 0.01006 vs. 0.01252, p=0.011) were both decreased after treatment. Importantly, the post-treatment value of the ratio was significantly reduced only among responders to treatment (0.01044 from 0.01255, p=0.02).

Conclusion: Reduction of IGF-1/IGF-BP3 ratio was statistically significant only among patients with NSCLC who responded to first-line treatment. If validated in larger cohorts, IGF-1/IGFBP3 might be a useful predictive tool for response to chemotherapy in NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.13578DOI Listing
August 2019

Effects of Different Antidiabetic Medications on Endothelial Glycocalyx, Myocardial Function, and Vascular Function in Type 2 Diabetic Patients: One Year Follow-Up Study.

J Clin Med 2019 Jul 5;8(7). Epub 2019 Jul 5.

2nd Department of Cardiology, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, 12462 Athens, Greece.

Background: Poor glycaemic control affects myocardial function. We investigated changes in endothelial function and left ventricular (LV) myocardial deformation in poorly controlled type 2 diabetics before and after glycaemic control intensification.

Methods: In 100 poorly-controlled diabetic patients (age: 51 ± 12 years), we measured at baseline and at 12 months after intensified glycaemic control: (a) Pulse wave velocity (PWV, Complior); (b) flow-mediated dilatation (FMD, %) of the brachial artery; (c) perfused boundary region (PBR) of the sublingual arterial micro-vessels (side-view dark-field imaging, Glycocheck); (d) LV global longitudinal strain (GLS), peak twisting (pTw), peak twisting velocity (pTwVel), and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography, where the ratio of PWV/GLS was used as a marker of ventricular-arterial interaction; and (e) Malondialdehyde (MDA) and protein carbonyls (PCs) plasma levels.

Results: Intensified 12-month antidiabetic treatment reduced HbA1c (8.9 ± 1.8% (74 ± 24 mmol/mol) versus 7.1 ± 1.2% (54 ± 14 mmol/mol), = 0.001), PWV (12 ± 3 versus 10.8 ± 2 m/s), PBR (2.12 ± 0.3 versus 1.98 ± 0.2 μm), MDA, and PCs; meanwhile, the treatment improved GLS (-15.2 versus -16.9%), PWV/GLS, and FMD% ( < 0.05). By multi-variate analysis, incretin-based agents were associated with improved PWV ( = 0.029), GLS ( = 0.037), PBR ( = 0.047), and FMD% ( = 0.034), in addition to a reduction of HbA1c. The patients with a final HbA1c ≤ 7% (≤ 53 mmol/mol) had greater reduction in PWV, PBR, and markers of oxidative stress, with a parallel increase in FMD and GLS, compared to those who had HbA1c > 7% (> 53 mmol/mol).

Conclusions: Intensified glycaemic control, in addition to incretin-based treatment, improves arterial stiffness, endothelial glycocalyx, and myocardial deformation in type 2 diabetes after one year of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8070983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678085PMC
July 2019

Blood-based analysis of type-2 diabetes mellitus susceptibility genes identifies specific transcript variants with deregulated expression and association with disease risk.

Sci Rep 2019 02 6;9(1):1512. Epub 2019 Feb 6.

Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.

Despite significant progress by genome-wide association studies, the ability of genetic variants to conduce to the prediction or prognosis of type-2 diabetes (T2D) is weak. Expression analysis of the corresponding genes may suggest possible links between single-nucleotide polymorphisms and T2D phenotype and/or risk. Herein, we investigated the expression patterns of 24 T2D-susceptibility genes, and their individual transcript variants (tv), in peripheral blood of T2D patients and controls (CTs), applying RNA-seq and real-time qPCR methodologies, and explore possible associations with disease features. Our data revealed the deregulation of certain transcripts in T2D patients. Among them, the down-regulation of CAPN10 tv3 was confirmed as an independent predictor for T2D. In patients, increased expression of CDK5 tv2, CDKN2A tv3 or THADA tv5 correlated positively with serum insulin levels, of CDK5 tv1 positively with % HbA1c levels, while in controls, elevated levels of TSPAN8 were associated positively with the presence of T2D family history. Herein, a T2D-specific expression profile of specific transcripts of disease-susceptibility genes is for the first time described in human peripheral blood. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-37856-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365563PMC
February 2019

Using serum s100-β protein as a biomarker for comparing silent brain injury in carotid endarterectomy and carotid artery stenting.

Int Angiol 2019 Apr 16;38(2):136-142. Epub 2019 Jan 16.

Department of Vascular Surgery, Attikon University Hospital, Athens, Greece.

Background: S100-β protein has been introduced as a sensitive biomarker of silent cerebral injury. This study compares its serum levels before, during, and 24 hours after carotid artery stenting (CAS) and carotid endarterectomy (CEA).

Methods: We measured serum level of S100-β in arterial blood before (S100Ba), during (S100Bb), and 24 hours after (S100Bc) CAS and CEA. We assessed differences in S100-β levels using non-parametric tests. We analyzed the relationship between carotid plaque type (echolucency) and S100-β protein level. We also examined its relation to the oximetry results in the CEA group (ipsilateral and contralateral).

Results: Thirty patients were enrolled, including 15 CAS and 15 CEA patients, with no significant differences in baseline atherosclerotic characteristics. There was no significant difference in S100Ba or S100Bb levels between CAS and CEA patients. However, a significant difference was found in S100Bc: 331.3 pg/mL (IQ range 56.4-583.5) for CAS vs. 76.3 pg/mL (IQ range 29.7-117.4) for CEA (P=0.01). Type I and II plaques were associated with the higher S100Bc levels in CAS (P=0.048). S100Bc was higher in CEA patients when the contralateral cerebral hemisphere had oximetry values less than 60% (P=0.043).

Conclusions: Our study suggests that CAS might produce silent brain injury. Moreover, vulnerable plaques might be associated with higher levels of S100-β protein, especially in CAS. This pilot study demonstrates that S100-β is a useful biomarker for silent brain injury in carotid revascularization. Large scale studies are still needed to confirm these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0392-9590.19.04079-3DOI Listing
April 2019

Circulating adipokines and mRNA expression in adipose tissue and the placenta in women with gestational diabetes mellitus.

Peptides 2018 03 11;101:157-166. Epub 2018 Jan 11.

2nd Department of Internal Medicine, Research Institute and Diabetes Center, National and Kapodistrian University of Athens, Medical School, University General Hospital Attikon, Rimini 1, 12462 Haidari, Athens, Greece.

Maternal adipose tissue and the placenta secrete various molecules commonly called adipokines such as chemerin, omentin-1, visfatin, adiponectin, and leptin that are important players in the pathogenesis of insulin resistance. Gestational diabetes mellitus (GDM) is defined as a state of glucose intolerance characterized by β-cell dysfunction and insulin resistance. To examine whether circulating adipokines and their mRNA expression in the adipose tissue and the placenta are altered in GDM pregnancy, we compared 15 GDM women [obese (BMI > 30) and non-obese (BMI < 30)] to 23 NGT (normal glucose tolerance) women [obese and non-obese], at the time of the Cesarean section. Circulating chemerin and leptin were higher (p = 0.009 and p = 0.005, respectively) and circulating omentin-1, visfatin, as well as the adiponectin/leptin ratio were lower (p = 0.039, p = 0.007 and p = 0.011, respectively) in GDM-obese compared to NGT-non-obese women. Chemerin and leptin correlated positively with BMI and HOMA-IR and omentin-1 correlated negatively with BMI. Serum TNF-α was significantly elevated in all obese compared to non-obese pregnant women and correlated positively with BMI. Adiponectin levels were reduced -although not significantly- in GDM- and NGT-obese women compared to their non-obese counterparts. Resistin, RPB4 and IL-6 levels did not differ significantly between groups. Chemerin mRNA expression in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was significantly higher compared to placenta in all women (6-to 24-times, p < 0.05). Chemerin-VAT mRNA expression in GDM-obese tended to be significantly higher compared to NGT-non-obese women (3-times, p = 0.005). Omentin-1 mRNA expression was significantly higher in VAT compared to SAT (50- to 100-times, p < 0.01) and its expression in placenta was negligible in all women. Although, leptin was expressed significantly higher in SAT compared to VAT and the placenta in all women (5- to 46-times, p < 0.05), only its mRNA expression in VAT of obese (GDM and NGT) differed significantly when compared to NGT-non-obese women (3-times higher, p < 0.02). Visfatin mRNA expression was comparable in all tissues. In conclusion, chemerin and leptin are elevated and omentin-1 and visfatin levels are decreased in GDM women complicated by obesity. This finding together with the positive association of chemerin and leptin with markers of insulin resistance, suggests that these adipokines and more especially chemerin and leptin accompanied by their adipose tissue expression could contribute to the increased insulin resistance and low grade inflammation that characterizes GDM-obese women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.peptides.2018.01.005DOI Listing
March 2018

Empagliflozin Limits Myocardial Infarction and Cell Death : Role of STAT3, Mitochondria, and Redox Aspects.

Front Physiol 2017 19;8:1077. Epub 2017 Dec 19.

2nd University Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Empagliflozin (EMPA), a drug approved for type 2 diabetes management, reduced cardiovascular death but is unknown if it reduces myocardial infarction. We sought to investigate: (i) the effect of EMPA on myocardial function and infarct size after ischemia/reperfusion in mice fed with western diet (WD), (ii) the underlying signaling pathways, (iii) its effects on cell survival in rat embryonic-heart-derived cardiomyoblasts (H9C2) and endothelial cells (ECs). To facilitate the aforementioned aims, mice were initially randomized in Control and EMPA groups and were subjected to 30 min ischemia and 2 h reperfusion. EMPA reduced body weight, blood glucose levels, and mean arterial pressure. Cholesterol, triglyceride, and AGEs remained unchanged. Left ventricular fractional shortening was improved (43.97 ± 0.92 vs. 40.75 ± 0.61%) and infarct size reduced (33.2 ± 0.01 vs. 17.6 ± 0.02%). In a second series of experiments, mice were subjected to the above interventions up to the 10th min of reperfusion and myocardial biopsies were obtained for assessment of the signaling cascade. STAT3 was increased in parallel with reduced levels of malondialdehyde (MDA) and reduced expression of myocardial iNOS and interleukin-6. Cell viability and ATP content were increased in H9C2 and in ECs. While, STAT3 phosphorylation is known to bestow infarct sparing properties through interaction with mitochondria, we observed that EMPA did not directly alter the mitochondrial calcium retention capacity (CRC); therefore, its effect in reducing myocardial infarction is STAT3 dependent. In conclusion, EMPA improves myocardial function and reduces infarct size as well as improves redox regulation by decreasing iNOS expression and subsequently lipid peroxidation as shown by its surrogate marker MDA. The mechanisms of action implicate the activation of STAT3 anti-oxidant and anti-inflammatory properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2017.01077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742117PMC
December 2017

Effects of 6-month treatment with the glucagon like peptide-1 analogue liraglutide on arterial stiffness, left ventricular myocardial deformation and oxidative stress in subjects with newly diagnosed type 2 diabetes.

Cardiovasc Diabetol 2018 01 8;17(1). Epub 2018 Jan 8.

2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Rimini 1 str, Haidari, 12462, Athens, Greece.

Background: Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM.

Methods: We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months. We measured at baseline and after 6-month treatment: (a) carotid-femoral pulse wave velocity (PWV) (b) LV longitudinal strain (GLS), and strain rate (GLSR), peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography. LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO (%dpTw-Utw), at peak (%dpTw-Utw) and end of early LV diastolic filling (%dpTw-Utw) (c) Flow mediated dilatation (FMD) of the brachial artery and percentage difference of FMD (FMD%) (d) malondialdehyde (MDA), protein carbonyls (PCs) and NT-proBNP.

Results: After 6-months treatment, subjects that received liraglutide presented with a reduced PWV (11.8 ± 2.5 vs. 10.3 ± 3.3 m/s), MDA (0.92 [0.45-2.45] vs. 0.68 [0.43-2.08] nM/L) and NT-proBNP (p < 0.05) in parallel with an increase in GLS (- 15.4 ± 3 vs. - 16.6 ± 2.7), GLSR (0.77 ± 0.2 vs. 0.89 ± 0.2), pUtwVel (- 97 ± 49 vs. - 112 ± 52°, p < 0.05), %dpTw-Utw (31 ± 10 vs. 40 ± 14), %dpTw-Utw (43 ± 19 vs. 53 ± 22) and FMD% (8.9 ± 3 vs. 13.2 ± 6, p < 0.01). There were no statistically significant differences of the measured markers in subjects that received metformin except for an improvement in FMD. In all subjects, PCs levels at baseline were negatively related to the difference of GLS (r = - 0.53) post-treatment and the difference of MDA was associated with the difference of PWV (r = 0.52) (p < 0.05 for all associations) after 6-month treatment.

Conclusions: Six-month treatment with liraglutide improves arterial stiffness, LV myocardial strain, LV twisting and untwisting and NT-proBNP by reducing oxidative stress in subjects with newly diagnosed T2DM. ClinicalTrials.gov Identifier NCT03010683.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-017-0646-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759220PMC
January 2018

Exhaled Breath Condensate Acidification Occurs During Surgery for Abdominal Cancer.

Anticancer Res 2017 06;37(6):3315-3321

Second Pulmonary Medicine Department, School of Medicine, National and Kapodistrian, University of Athens, Attikon University Hospital, Haidari, Athens, Greece.

Background/aim: Acidification of exhaled breath condensate (EBC), reflecting airway inflammation and oxidative stress, has been reported in lung cancer patients undergoing lobectomy. We undertook this study to examine EBC pH changes during surgery for abdominal cancer.

Patients And Methods: EBC pH was measured from 20 patients undergoing abdominal cancer resection before and during surgery. Repeated-measures of ANOVA and random-effects linear models were applied to compare mean EBC pH values in samples collected at different times. Cox and linear regression models were used to determine the association of EBC pH with occurrence of acute bronchospasm intra-operatively and the duration of hospitalization.

Results: Significant acidification of EBC was observed during surgery (p=0.007) associated with 0.77% (95% confidence interval=-0.14-1.68, p-value=0.097) increase in the risk for developing acute bronchospasm, after adjustment for potential confounders.

Conclusion: EBC acidification occurs in patients undergoing abdominal cancer resection and is associated with the occurrence of acute bronchospasm intraoperatively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.11700DOI Listing
June 2017

Early detection of left ventricular dysfunction in first-degree relatives of diabetic patients by myocardial deformation imaging: The role of endothelial glycocalyx damage.

Int J Cardiol 2017 Apr 8;233:105-112. Epub 2017 Jan 8.

2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Greece.

Background: First-degree relatives of type-2 diabetes patients (FDR) present insulin resistance. We investigated whether FDR and dysglycaemic subjects demonstrate abnormal endothelial glycocalyx and LV deformation during postprandial hyperglycemia.

Methods: We studied 40 FDR with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic). At 0 and 120min of OGTT we measured: a) LV longitudinal strain (LS) of subendocardial, mid-myocardial and subepicardial layers, global LS (GLS), peak twisting (pTw), untwisting velocity (pUtwVel), by speckle tracking echocardiography b) perfused boundary region (PBR) of the sublingual arterial microvessels; high PBR values represent reduced glycocalyx thickness. Insulin resistance was evaluated using insulin sensitivity index (ISI).

Results: ISI was related with baseline PBR, GLS and pTw in all subjects (p<0.05). Compared to normoglycaemics, FDR and dysglycaemics had higher PBR, lower ISI, GLS (-18.4±2.6 and -16.8±2.0 vs. -19.2±2.4%), subendocardial LS (-19.0±4.2 and -17.9±3.0 vs. -20.1±3.4%), pTw (14.4±4.4 and 15.6±6.4 vs. 16.9±6.5deg) and pUtwVel (p<0.05 for all comparisons). A GLS<-18% identified FDR with LV dysfunction (p=0.016). Post-OGTT, GLS and the subendocardial LS decreased while pTw and pUtwVel increased in FDR and dysglycaemics (p<0.05) indicating prevalence of the motion of the subepicardial over a dysfunctioning subendocardial myocardial helix. Increased PBR was related with impaired deformation markers at baseline and 120min of OGTT (p<0.05).

Conclusion: First-degree relatives and dysglycaemics have reduced glycocalyx thickness related with impaired LV longitudinal, twisting-untwisting function. Postprandial hyperglycemia when combined with insulin resistance causes LV longitudinal dysfunction leading to increased LV twisting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2017.01.056DOI Listing
April 2017

Insulin resistance and acute glucose changes determine arterial elastic properties and coronary flow reserve in dysglycaemic and first-degree relatives of diabetic patients.

Atherosclerosis 2015 Aug 9;241(2):455-62. Epub 2015 Jun 9.

2nd Cardiology Department, Attikon Hospital, University of Athens, Greece.

Background: Insulin resistance is linked to endothelial dysfunction. We investigated whether first-degree relatives of type-2 diabetes patients (FDR) present differences in vascular function at baseline and during postprandial hyperglycemia compared to dysglycaemic or normoglycaemic subjects.

Methods: We studied 40 FDR with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic) with similar clinical characteristics. Glucose, insulin, pulse wave velocity (PWV), central systolic blood pressure (cSBP) and augmentation index (AI) were measured at 0, 30, 60, 90 and 120min during OGTT. Coronary flow reserve (CFR) was assessed using Doppler echocardiography at 0 and 120min after OGTT. Insulin sensitivity was evaluated using Matsuda and insulin sensitivity index (ISI).

Results: FDR and dysglycaemics had higher fasting insulin, reduced ISI, Matsuda index as well as reduced CFR (2.54 ± 0.5 vs. 2.45 ± 0.3 vs. 2.74 ± 0.5), increased PWV, (8.9 ± 1.1 vs. 10.3 ± 2.4vs. 8.0 ± 1.5 m/sec), AI (23.8 ± 13.6 vs. 26.5 ± 14.4vs.17.7  ±  14%) and cSBP than normoglycaemics (p < 0.05 for all comparisons). During OGTT, AI was similarly reduced in both normoglycaemic and FDR (p < 0.05) at peak insulin levels (60 min) though FDR had 2-fold higher insulin than normoglycaemics. AI was increased in dysglycaemics after peak glucose levels, at 120 min (p < 0.05). CFR was reduced by 10% and 15% at 120min in FDR and dysglycaemic respectively, while remained unchanged in normoglycaemics (p < 0.05). The percent reduction of CFR was related with the percent increase of glucose levels, ISI and Matsuda index(p < 0.05).

Conclusion: First-degree relatives and dysglycaemic patients have impaired arterial and coronary microcirculatory function. Insulin resistance determines acute vascular responses during postprandial hyperglycemia. CLINICALTRIALS.

Gov Identifier: NCT02244736.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2015.06.006DOI Listing
August 2015

Vinegar Consumption Increases Insulin-Stimulated Glucose Uptake by the Forearm Muscle in Humans with Type 2 Diabetes.

J Diabetes Res 2015 6;2015:175204. Epub 2015 May 6.

2nd Department of Internal Medicine and Research Institute, Athens University Medical School, Attikon University Hospital, 1 Rimini Street, 12462 Haidari, Greece.

Background And Aims: Vinegar has been shown to have a glucose-lowering effect in patients with glucose abnormalities. However, the mechanisms of this effect are still obscure. The aim of this randomised, crossover study was to investigate the effect of vinegar on glucose metabolism in muscle which is the most important tissue for insulin-stimulated glucose disposal.

Materials And Methods: Eleven subjects with DM2 consumed vinegar or placebo (at random order on two separate days, a week apart), before a mixed meal. Plasma glucose, insulin, triglycerides, nonesterified fatty acids (NEFA), and glycerol were measured preprandially and at 30-60 min for 300 min postprandially from the radial artery and from a forearm vein. Muscle blood flow was measured with strain-gauge plethysmography. Glucose uptake was calculated as the arteriovenous difference of glucose multiplied by blood flow.

Results: Vinegar compared to placebo (1) increased forearm glucose uptake (p = 0.0357), (2) decreased plasma glucose (p = 0.0279), insulin (p = 0.0457), and triglycerides (p = 0.0439), and (3) did not change NEFA and glycerol.

Conclusions: In DM2 vinegar reduces postprandial hyperglycaemia, hyperinsulinaemia, and hypertriglyceridaemia without affecting lipolysis. Vinegar's effect on carbohydrate metabolism may be partly accounted for by an increase in glucose uptake, demonstrating an improvement in insulin action in skeletal muscle. This trial is registered with Clinicaltrials.gov NCT02309424.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/175204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438142PMC
February 2016

Serum levels of retinol-binding protein-4 are associated with the presence and severity of coronary artery disease.

Cardiovasc Diabetol 2014 Aug 21;13:121. Epub 2014 Aug 21.

2nd Department of Internal Medicine, Research Institute and Diabetes Centre, Athens University Medical School, Attikon University General Hospital, 1st Rimini Street, Haidari, GR-12462, Greece.

Background: The interplay between the novel adipokine retinol-binding protein-4 (RBP4) and coronary artery disease (CAD) is still obscure. We investigated the relationship between RBP4 levels and the presence and severity of angiographically proven CAD and determined its possible role in acute myocardial infarction (AMI).

Methods: 305 individuals with angiographically proven CAD (CAD-patients), were classified into 2 subgroups: 1) acute myocardial infarction (AMI, n = 141), and 2) stable angina (SA, n = 164). Ninety-one age- and sex-matched individuals without CAD, but with at least 2 classical cardiovascular risk factors, served as controls (non-CAD group). RBP4 serum levels were measured at hospital admission and were analyzed in relation to the coronary severity stenosis, assessed by the Gensini-score and the number of coronary narrowed vessels. Other clinical parameters, including insulin levels, HOMA-IR, hsCRP, glycaemic and lipid profile, and left-ventricular ejection fraction were also assessed.

Results: Serum RBP4 levels were significantly elevated in patients with CAD compared to non-CAD patients (39.29 ± 11.72 mg/L vs. 24.83 ± 11.27 mg/L, p < 0.001). We did not observe a significant difference in RBP4 levels between AMI and SA subgroups (p = 0.734). Logistic regression analysis revealed an independent association of CAD presence with serum RBP4 (β = 0.163, p = 0.006), and hsCRP (β = 0.122, p = 0.022) levels, in the whole study group. Among variables, hsCRP (β = 0.220), HDL (β = -0.150), and RBP4 (β = 0.297), correlated in both univariate and multivariate analysis with CAD severity (R2 = 0.422, p < 0.001). Similarly, RBP4 concentrations increased with the number of coronary narrowed vessels (p < 0.05).

Conclusion: Patients with CAD, both SA and AMI, showed elevated RBP4 serum levels. Notably, increased RBP4 concentration seemed to independently correlate with CAD severity, but no with AMI.

Trial Registration: The ClinicalTrials.gov Identifier is: NCT00636766.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-014-0121-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156962PMC
August 2014

Effect of aliskiren on circulating endothelial progenitor cells and vascular function in patients with type 2 diabetes and essential hypertension.

Am J Hypertens 2015 Jan 3;28(1):22-9. Epub 2014 Jul 3.

2nd Department of Medicine-Propaedeutic Clinic, Research Institute, and Diabetes Centre, Athens University Medical School, Attikon University General Hospital, Haidari, Athens, Greece.

Background: The aim of this study was to investigate the effects of aliskiren on vascular function and endothelial progenitor cells (EPCs) in patients with type 2 diabetes and essential hypertension.

Methods: The study enrolled type 2 diabetic patients aged >50 years under stable glycemic control and first diagnosed mild essential hypertension. In phase A (n = 20), patients received aliskiren 150-300 mg daily for 3 months. In phase B (n = 12), hydrochlorothiazide (HCTZ) 12.5-25mg daily substituted for aliskiren for 3 more months. At baseline and at the end of each phase, we assessed (i) brachial blood pressure (BBP); (ii) central aortic systolic pressure (CSP), aortic augmentation index (Aix), and pulse wave velocity (PWV) as markers of arterial stiffness; (iii) brachial artery flow-mediated dilatation (FMD) as a marker of endothelial function; (iv) left ventricular (LV) twisting and untwisting as markers of LV function and (v) EPC numbers in culture of peripheral blood mononuclear cells.

Results: Aliskiren similarly reduced BBP and CSP, increased FMD (P < 0.001) and EPC numbers (P < 0.001), decreased PWV and Aix (P < 0.05), and improved LV twisting and untwisting (P < 0.05). Although substitution of HCTZ sustained BBP at similar levels, CSP and echocardiographic indices nearly returned at baseline levels, and the improvement of FMD, PWV, Aix, and EPC numbers was abolished.

Conclusions: Aliskiren had a favorable effect on endothelial function and EPCs, reduced arterial stiffness, and improved LV twisting and untwisting. These effects were independent of BBP lowering, as they were not observed after the achievement of similar values of BBP with HCTZ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajh/hpu119DOI Listing
January 2015

The relationship of novel adipokines, RBP4 and omentin-1, with carotid atherosclerosis severity and vulnerability.

Atherosclerosis 2014 Aug 8;235(2):606-12. Epub 2014 Jun 8.

Department of Vascular Surgery, Medical School, "Attikon" University General Hospital, Athens, Greece.

Objective: We investigated the relationship of circulating novel adipokines, retinol-binding protein 4 (RBP4) and omentin-1, with advanced carotid atherosclerosis and ultrasound indexes of severity (total plaque area-TPA) and plaque echogenicity and vulnerability (Gray-Scale median - GSM score).

Methods: We enrolled 225 patients with high-grade carotid stenosis (HGCS) who underwent carotid revascularization (73 Symptomatic patients, 152 asymptomatic patients) and 75 age- and sex-matched, asymptomatic individuals with low-grade (<50%) carotid stenosis (LGCS). Seventy-three individuals without current manifestations of atherosclerotic disease served as control group (COG). All participants underwent carotid ultrasound with TPA and GSM score assessment. Moreover, clinical parameters, metabolic profile, and circulating levels of hsCRP and adipokines were assessed.

Results: RBP4 was significantly elevated in HGCS (51.44 ± 16.23 mg/L) compared to LGCS (38.39 ± 8.85 mg/L), independent of symptoms existence, whereas RBP4 levels in COG were even lower (25.74 ± 10.72 mg/L, p < 0.001 compared to either HGCS or LGCS). Inversely, serum omentin-1 levels were significantly lower across HGCS (490.41 ± 172 ng/ml) and LGCS (603.20 ± 202.43 ng/ml) than COG (815.3 ± 185.32, p < 0.001). Moreover, the considerable difference between HGCS and LGCS (p < 0.001) was exclusively attributed to the excessive suppression of omentin-1 concentrations in symptomatic versus asymptomatic (p = 0.004) patients. HGCS and LGCS did not differ in the rest of clinical and biochemical parameters. In multiple regression analysis, RBP4 (beta = 0.232, p = 0.025) and hsCRP (beta = 0.300, p = 0.004) emerged as independent determinants of TPA in patients with carotid atherosclerosis. Low serum levels of omentin-1 correlated with GSM score and symptoms but that association was lost in multivariate analysis..

Conclusion: RBP4 serum levels were significantly elevated in patients with established carotid atherosclerosis and were positively associated with atherosclerosis severity. The association of low serum omentin-1 with carotid plaque echolucency requires further investigation.. ClinicalTrials.gov Identifier: NCT00636766.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2014.05.957DOI Listing
August 2014

Serum levels of novel adipokines in patients with acute ischemic stroke: potential contribution to diagnosis and prognosis.

Peptides 2014 Jul 24;57:12-6. Epub 2014 Apr 24.

Department of Vascular Surgery, Medical School, University of Athens, Greece.

This study evaluated serum levels of novel adipokines in acute ischemic stroke (AIS) and their association with prognosis. We enrolled 168 patients with AIS and 58 stroke-free age- and sex-matched individuals (controls). Clinical parameters, carotid ultrasound, metabolic profile, vaspin, apelin, visfatin, and ghrelin were assayed. Stroke-patients were sampled at hospital admission and were prospectively followed-up (median 16 months) for the cardiovascular endpoint (cardiovascular death/stroke/myocardial infarction). At admission, stroke-patients appeared with higher levels of systolic blood pressure, hsCRP and worse metabolic profile (p<0.05), (p>0.05). Compared to controls, AIS group had significantly higher serum concentrations of visfatin (22.92±9.72ng/ml vs 16.56±7.82ng/ml, p=0.006) and lower of vaspin (0.94±0.43ng/ml vs 1.84±0.82ng/ml, p=0.019) and ghrelin (3.47±1.44ng/ml vs 5.93±2.78ng/ml, p<0.001), while apelin did not differ between groups. Similar differences in adipokines were found between stroke subgroups with and without significant ipsilateral carotid stenosis (>50%) (p<0.05). In stepwise logistic regression analysis adjusted for diabetes, hypertension, dyslipidemia and age, visfatin (p=0.026) and ghrelin (p=0.012) proved to be independent predictors of AIS. During follow-up, 27 patients achieved cardiovascular endpoint. In addition to coronary artery disease and NIHSS score, visfatin serum levels was associated with cardiovascular endpoint (HR: 1.255, 95% CI: 1.025-1.576). Our results suggested the association of AIS with higher visfatin and lower vaspin and ghrelin serum levels. Visfatin levels can be a predictor of cardiovascular mortality and morbidity in AIS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.peptides.2014.04.008DOI Listing
July 2014
-->