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    المصدر: Hormone and Metabolic Research. 52:856-860

    الوصف: Diabetes is considered as a disease with a wide and continuous clinical spectrum, ranging from Type 1 (T1D) and Type 2 Diabetes (T2D) with complex multifactorial causes. In the last years, particular attention has been focused on the predictive value and therapeutic potential of single nucleotide polymorphisms (SNPs). SNPs can alter the seed-sequence in miRNA’s loci and miRNA target sites causing changes in the structure and influencing the binding function. Only few studies have investigated the clinical influence of SNPs, in particular potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ) gene variants in T1D population. The aim of the study is to investigate the occurrence and the possible metabolic significance of KCNJ polymorphism in a group of pediatric patients with T1D. The study was performed in a cohort of 90 Caucasian children and adolescents with T1D and 93 healthy subjects. Rs5210 polymorphism has been analyzed with a prevalence of the GG genotype in the patient group suggesting its association with T1D. Therefore, a relationship was found between GG genotype and body mass index (BMI) at diagnosis and insulin requirement (IR) after 6 months. The study suggested an action for rs5210 in determining the metabolic features of T1D pediatric patients, by showing some clues of insulin resistance in patients carrying that polymorphism.

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    المصدر: Experimental and Clinical Endocrinology & Diabetes. 128:104-110

    الوصف: Background Although diabetes is a common complication of acromegaly or Cushing´s disease, there are only few detailed studies with a focus on cardiovascular risk, metabolic control or diabetes therapy. Here, we provide a comprehensive characterization from the longitudinal DPV (Diabetes Patienten Verlaufsdokumentation) registry. Methods Patients from the registry≥18 years of age with diabetes and acromegaly or Cushing´s disease were compared to patients with type 1 diabetes or type 2 diabetes using the statistical software SAS 9.4. Results Patients with diabetes and acromegaly (n=52) or Cushing’s disease (n=15) were significantly younger at diabetes onset (median age 50.1 and 45.0 vs. 59.0 years in type 2 diabetes; both p Conclusion Patients with acromegaly are at a high risk for cardiovascular disease, reflected by dyslipidemia and hypertension. A high proportion of patients with diabetes in acromegaly or Cushing´s disease receives insulin. Based on a multicenter register, a sufficient number of patients with rare forms of diabetes can be analyzed.

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    المصدر: Experimental and Clinical Endocrinology & Diabetes. 128:745-751

    الوصف: Objective The aim of this systematic data analysis was to determine the prevalence of diabetic ketoacidosis (DKA) as well as hypoglycemic and hyperglycemic disorders during insulin pump therapy (CSII) in patients with type 1 diabetes. The main focus was to investigate whether CSII patients have more DKA than the general type 1 diabetes population. Subjects and Methods This retrospective study with patients who were treated in our treatment center from 2003 to 2016 includes data from 229 patients (52.4% male, 47.6% female, 37.2±16.3 years; DKA: 93, hypoglycemia: 66, hyperglycemia: 70). Results Intensified insulin therapy was the most common treatment regimen in the study cohort (73.4%), followed by CSII (24%). However, 32.3% of the patients with DKA were on CSII. This number of DKA cases among the insulin pump users in our study cohort was higher than the prevalence reported in a previously published study by Reichel et al. (2013; p Conclusions Our findings suggest that despite development of more sophisticated insulin pump devices, DKA is still more frequent with CSII than with other kinds of insulin treatment.

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    المصدر: Experimental and Clinical Endocrinology & Diabetes. 127:461-467

    الوصف: Objective The aim of this observational study was to analyse snacking pattern and satisfaction with snacking, and to associate snacking patterns with metabolic control and quality of life in people with diabetes type 1 and 2 on insulin therapy. Methods In 2017, 390 people with diabetes were interviewed in a university outpatient department: 132 diabetes type 1 (56.1y, diabetes duration 24.2y, HbA1c 7.0%), 89 diabetes type 2/biphasic insulin (72.8y, diabetes duration 22.0y, HbA1c 7.1%) and 169 diabetes type 2/prandial insulin (66.7y, diabetes duration 20.5y, HbA1c 7.0%). Standardised questionnaires were used to assess eating patterns, satisfaction with snacking, treatment satisfaction and quality of life. Results The far majority snacked regardless of diabetes type and type of insulin therapy (70.5% type 1, 80.9% type 2/biphasic insulin, 74.6% type 2/prandial insulin) and liked to do so or did not mind (type 1 diabetes 79.5%, type 2 diabetes/biphasic insulin 84.8%, type 2 diabetes/prandial insulin 83.5%). Snacking because of recommendations of healthcare professionals was rare (10.8% type 1 diabetes, 8.2% type 2 diabetes/biphasic insulin, 9.4% type 2 diabetes/prandial insulin). Snacking and not snacking participants did not differ in respect to HbA1c, quality of life or treatment satisfaction. Conclusions Snacking seems to be a common habit in individuals with diabetes and most of them like to snack. Snacking is not associated with better or worse metabolic control or quality of life. The decision to snack or not to snack can be left to the individual and integrated into the therapy without danger for the glycaemic control.

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    المصدر: Thrombosis and Haemostasis

    الوصف: SummaryGlucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only its metabolic effects but also the protective vascular actions. Since platelets exert a primary role in the pathogenesis of atherosclerosis, inflammation and vascular complications, we investigated whether GLP-1 directly influences platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute incubation with the native form GLP-1(7–36), the N-terminally truncated form GLP-1(9–36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation induced by collagen or arachidonic acid (AA); ii) platelet function under shear stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)-induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv) activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress. Experiments were repeated in the presence of the nitric oxide donor Na–nitroprusside. We found that platelets constitutively express GLP-1R and that, independently of GLP-1R, GLP-1(7–36), GLP-1(9–36) and Liraglutide exert platelet inhibitory effects as shown by: a) increased NO-antiaggregating effects, b) increased the activation of the cGMP/PKG/VASP pathway, c) reduced the activation of PI3-K/Akt and MAPK/ERK-2 pathways, d) reduced the AA-induced oxidative stress. When the experiments were repeated in the presence of the antagonist of GLP-1R Exendin(9–39), the platelet inhibitory effects were maintained, thus indicating a mechanism independent of GLP-1R. In conclusion, GLP-1(7–36), its degradation product GLP-1(9–36) and Liraglutide exert similar inhibitory effects on platelet activation, suggesting a potential protective effect on the cardiovascular system.

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    المصدر: Furio, Elena García-Fuster, María José Redón i Más, Josep Marques, Patrice Ortega, Rebeca Sanz, María Jesus Piqueras, Laura 2018 CX3CR1/CX3CL1 AXIS mediates platelet-leukocyte adhesion to arterial endothelium in younger patients with a history of idiopathic deep vein thrombosis. Thrombosis and Haemostasis 118 3 562 571
    RODERIC. Repositorio Institucional de la Universitat de Valéncia
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    الوصف: Mechanisms linking deep vein thrombosis (DVT) and subclinical atherosclerosis and risk of cardiovascular events are poorly understood. The aim of this study was to investigate the potential impact of CX3CR1/CX3CL1 axis in DVT-associated endothelial dysfunction. The study included 22 patients (age: 37.5 ± 8.2 years) with a history of idiopathic DVT and without known cardiovascular risk factors and 23 aged-matched control subjects (age: 34 ± 7.8 years). Flow cytometry was used to evaluate peripheral markers of platelet activation, leukocyte immunophenotypes and CX3CR1/CX3CL1 expression in both groups. A flow chamber assay was employed to measure leukocyte arrest under dynamic conditions. Platelet activation and the percentage of circulating CX3CR1-expressing platelets, CX3CR1-expressing platelet-bound monocytes and CD8+ lymphocytes were higher in patients with DVT than in controls. Additionally, patients with DVT had increased plasma levels of CX3CL1, soluble P-selectin and platelet factor 4/CXCL4. Interestingly, this correlated with enhanced platelet–leukocyte interaction and leukocyte adhesion to TNFα-stimulated arterial endothelial cells, which was partly dependent on endothelial CX3CL1 upregulation and increased CX3CR1 expression on platelets, monocytes and lymphocytes. In conclusion, increased CX3CR1 expression on circulating platelets may constitute a prognostic marker for long-term adverse cardiovascular events in patients with DVT. Blockade of CX3CL1/CX3CR1 axis may represent a new therapeutic strategy for the prevention of cardiovascular comorbidities associated with DVT.

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    المصدر: Experimental and Clinical Endocrinology & Diabetes. 124:140-147

    الوصف: Aims: While cytokines play a role in the etiology of type 1 diabetes, cytokines later in the disease are less understood. We therefore investigated associations of pro-inflammatory tumor necrosis factor-α levels measured at prolonged disease duration with C-peptide at diagnosis, long-term glycemic control, diabetes duration, clinical factors, and health behaviors. Methods: Data and blood were collected during an ancillary study to the longitudinal Wisconsin Diabetes Registry, a population-based cohort followed since diagnosis of type 1 diabetes. The ancillary study was conducted at 13–18 years diabetes duration, and enrolled premenopausal women age 18–45 years (n=87). Results: Higher tumor necrosis factor-α levels at 13–18 years diabetes duration were independently associated with longer duration (p=0.0004) and worse current renal function (p=0.02). Additionally, diabetes duration modified both of the positive associations of tumor necrosis factor-α levels (both interactions p≤0.01) with mean glycemic control during the previous 10 years (significant only in women with longer durations) and current daily caffeine intake (significant only in women with shorter durations). In women with C-peptide measured at diagnosis (n=50), higher tumor necrosis factor-α levels at 13–18 years duration were associated with lower C-peptide (p=0.01), independent of glycemic control during the previous 10 years. Conclusions: Lower residual C-peptide at diagnosis and poor long-term glycemic control independently predicted higher pro-inflammatory tumor necrosis factor-α levels years later. The novel relationship with C-peptide needs confirmation in a larger cohort. Given the association between tumor necrosis factor-α and diabetes complications, further longitudinal studies may help clarify the potentially complex associations between glycemic control, inflammatory cytokines, and complications.

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    المصدر: Experimental and Clinical Endocrinology & Diabetes. 125:322-326

    الوصف: As a transducer of PPARγ signaling, recent evidence supports that fibroblast growth factor 1 (FGF1) mediates adipose tissue remodeling and insulin sensitivity. This study is to assess the role of serum FGF1 in obesity. A hospital-based case-control study of 154 subjects was conducted. Serum level of FGF1 was measured by enzyme-linked immunosorbent assay. The serum level of FGF1 in the lean (119.0 [103.1–146.1] pg/ml) was higher than it in the subjects with overweight/obesity (111.9 [80.3–127.4] pg/ml, P=0.009). Binary logistic regression models found a reverse association between serum FGF1 level and the risk of overweight/obesity (adjusted odds ratio=0.990, 95% confidence interval [0.981–0.998], P=0.019). Furthermore, serum FGF1 reversely correlated with body mass index (r=−0.176, P=0.029), systolic blood pressure (r=−0.224, P=0.005), diastolic blood pressure (r=−0.185, P=0.022) and triglycerides (r=−0.162, P=0.044). Multiple stepwise linear regression analysis found serum level of FGF1 was dependent on anti-diabetic drugs, hemoglobin A1C, body mass index and sex. Serum level of FGF1 is associated with the decreased risk of obesity in human.

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    المصدر: Hormone and Metabolic Research. 49:36-42

    الوصف: 46,XY gonadal dysgenesis (GD) constitutes a rare group of disorders characterized by the presence of dysfunctional testes in genotypic males. The molecular etiology is not known in about 2 thirds of instances. The aim of this study was to identify the genetic cause in patients with 46,XY gonadal dysgenesis. Based on clinical, cytogenetic, and biochemical screening, 10 patients with 46,XY GD were recruited. Direct sequencing of SRY , NR5A1 , SOX9 , DAX1 , DHH , DMRT1 genes was carried out for molecular analysis. Among 10 patients, 5 were diagnosed with complete gonadal dysgenesis (CGD), 3 with partial gonadal dysgenesis (PGD), and 3 with testicular agenesis. Molecular analysis revealed 12 heterozygous genetic changes, 4 of which were novel. One (c.416T>A) was observed in evolutionary conserved region of DMRT1 gene in a patient with CGD and was found to be probably damaging on in silico analysis. Other 3 were identified in NR5A1 gene (c.990+22 C>A, c.1387+1403T>A and p.131P), but their association with gonadal dysgenesis is not evident from our study. These genetic changes were absent in parents and 50 healthy control samples, which were also studied. With targeted sequencing approach, a molecular diagnosis was made in only one patient with 46,XY GD. The application of new genomic technologies is required for the precise evaluation of these rare genetic defects.

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    المصدر: Thrombosis and Haemostasis. 113:312-318

    الوصف: SummaryThe increased risk of vascular complications in type 1 diabetes may in part be explained by changes in haemostatic function. In the present study, we investigated the fibrin clot properties in patients with type 1 diabetes in relation to sex and microvascular complications. The study included 236 patients (107 women) aged between 20–70 years and without any history of cardiovascular disease. Fibrin clot properties, assessed by determination of the permeability coefficient (Ks) and turbidimetric clotting and lysis assays, did not differ between men and women. Compared with men, women had worse glycaemic control as well as higher levels of prothrombin fragment 1+2 and peak thrombin generation in vitro, indicating increased thrombin generation both in vivo and in vitro. Subgroup analyses of patients younger than 30 years revealed less permeable fibrin clots and prolonged lysis time in females compared with age-matched men. Patients with microvascular complications had higher fibrinogen concentrations and denser and less permeable fibrin clots. Thus, we conclude that in vitro fibrin clot properties in patients with type 1 diabetes without cardiovascular disease are not different between the sexes, but associate with prevalence of microvascular complications. Tighter fibrin clot formation in younger women, as suggested by our results, may affect their future cardiovascular risk and should be investigated in a larger population.