Dilek Yazici

Epicardial Fat Tissue Thickness Correlates with Endothelial Dysfunction and Other Cardiovascular Risk Factors in Patients with Metabolic Syndrome

BACKGROUND Epicardial adipose tissue has shown to be related to cardiovascular risk. The aim of this study is to investigate the relationship between epicardial adiposity and endothelial function in metabolic syndrome. METHODS Fifty patients with metabolic syndrome were recruited. Anthropometric measurements, fasting blood glucose, insulin, lipid profile, high-sensitivity C-reactive protein (hsCRP), fibrinogen, apolipoprotein A (Apo A), Apo B1, and lipoprotein (a) [Lp(a)] were determined. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Epicardial fat thickness was measured via two-dimensional M-mode echocardiography. Endothelial function was assessed as flow-mediated dilatation at the brachial artery. RESULTS Epicardial fat tissue thickness was shown to be correlated negatively with FMD and positively with age, diastolic blood pressure, hsCRP, fibrinogen, HOMA-IR, and lipid parameters. Multiple regression analysis showed epicardial fat tissue thickness to be an independent factor influencing the endothelial function. CONCLUSIONS Epicardial fat tissue may be a useful parameter in the assessment of patients with metabolic syndrome.

Association of Metabolic Syndrome Parameters with TT3 and FT3/FT4 Ratio in Obese Turkish Population

BACKGROUND Obesity and metabolic syndrome are major health problems worldwide, including Turkey. Recent studies have shown an association between thyroid function tests and metabolic syndrome parameters. In this study, we aimed to determine the frequency of metabolic syndrome in an obese Turkish population and the relationship between metabolic syndrome and thyroid functions. MATERIALS AND METHOD We recruited 211 patients (187 females/24 males; mean age, 39.7±11.7 years) with body mass index (BMI) >30 kg/m(2) and no other hormonal pathology that could cause obesity. Anthropometric evaluation was followed by measurement of fasting blood glucose (FBG), insulin, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free T3 (FT3), and free T4 (FT4). Metabolic syndrome was defined according to the 2005 revision of the National Cholesterol Education Program Adult Panel III (NCEP ATP III) criteria. Insulin resistance was calculated from homeostasis model assessment of insulin resistance (HOMA-IR) formula. The TSH cutoff value was set at 2.5 mU/L. RESULTS Metabolic syndrome was diagnosed in 122 patients (58%). Metabolic syndrome positive patients had significantly higher FBG, triglycerides, FT4, systolic (SBP) and diastolic blood pressure (DBP), and statistically lower HDL-C and FT3/FT4 ratio than metabolic syndrome negative patients. TSH decreased with age and was not related with any metabolic syndrome parameters. The FT3/FT4 ratio negatively correlated with FBG, triglycerides, SBP, and DBP (P=0.003, r=-38; P=0.02, r=-0.28; P=0.005, r=-0.35; and P=0.007, r=-0.34, respectively); TT3 positively correlated with HOMA-IR (P=0.006, r=0.40), FBG (P=0.009, r=0.38), and waist circumference (P=0.02, r=0.34). CONCLUSION Metabolic syndrome frequency was increased in our study population compared to the general population. Metabolic syndrome parameters (except HDL) correlated with TT3, FT4, and the FT3/FT4 ratio. FT4 levels were associated with obesity and metabolic syndrome independently of insulin resistance, whereas TT3 levels were associated with both insulin resistance and metabolic syndrome. This relationship can be explained by compensatory effects of TT3, and probably FT4, on energy expenditure and thermogenesis in obese people.

Circulating endothelial cells are elevated in patients with type 1 diabetes mellitus

OBJECTIVE Circulating endothelial cells (CECs) have emerged as vascular damage markers and are increased in type 2 diabetic patients. Since type 1 diabetes is associated with vascular damage, we hypothesized high CEC numbers in this patient population. METHODS Thirty-nine patients with type 1 diabetes and 39 controls were included. CECs were isolated using anti-CD146-coated Dynabeads, stained with Ulex lectin-1, and counted by fluorescence microscopy. Endothelial function was measured as flow-mediated dilation (FMD). Thiobarbituric acid reactive substances (TBARS), total glutathione levels (GSH), and paraoxonase (PON) activity levels were measured as oxidative stress markers. RESULTS Patients with type 1 diabetes mellitus had higher number of CECs (7.46+/-5.37 vs 2.13+/-1.13 cells/ml, P<0.001), lower FMD (7.87+/-2.19 vs 12.06+/-2.34%, P<0.001), higher TBARS (4.94+/-1.20 vs 3.07+/-0.75 nmol/MDA, P<0.001), lower GSH (206.12+/-98.06 vs 353.61+/-68.45 microM, P<0.001), and lower PON activity levels (89.10+/-17.82 vs 127.65+/-29.01 U/l, P<0.001) as compared to controls. There was positive correlation between CEC numbers and HbAlc levels (r=0.49, P=0.002). CECs and fasting glucose levels were not correlated. There was no correlation between the number of CECs and FMD. Furthermore, there were no correlations between the number of CECs and TBARS, GSH and PON activity levels. Multiple regression analysis showed that HbAlc levels (r(2)=0.40, P<0.009) were associated with CEC numbers. CONCLUSION CECs are elevated in patients with type 1 diabetes mellitus reflecting endothelial damage. This increase is dependent on long-term glucose control.

Insulin Resistance, Obesity and Lipotoxicity

Lipotoxicity , originally used to describe the destructive effects of excess fat accumulation on glucose metabolism, causes functional impairments in several metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. Lipotoxicity has roles in insulin resistance and pancreatic beta cell dysfunction. Increased circulating levels of lipids and the metabolic alterations in fatty acid utilization and intracellular signaling, have been related to insulin resistance in muscle and liver. Different pathways, like novel protein kinase c pathways and the JNK-1 pathway are involved as the mechanisms of how lipotoxicity leads to insulin resistance in nonadipose tissue organs, such as liver and muscle. Mitochondrial dysfunction plays a role in the pathogenesis of insulin resistance. Endoplasmic reticulum stress, through mainly increased oxidative stress, also plays important role in the etiology of insulin resistance, especially seen in non-alcoholic fatty liver disease. Visceral adiposity and insulin resistance both increase the cardiometabolic risk and lipotoxicity seems to play a crucial role in the pathophysiology of these associations.

Serum Adipokine Levels in Type 1 Diabetic Patients: Association with Carotid Intima Media Thickness

BACKGROUND Adipokines are markers of insulin resistance and play a role in the atherosclerotic process. The association of adipokines with the macrovascular complications of type 1 diabetes mellitus (DM) needs to be determined. The aim of this study was to measure serum adiponectin, leptin, and resistin levels in type 1 DM patients and investigate their relationship with carotid intima media thickness (CIMT), a clinical marker of atherosclerosis. METHODS Seventy-five type 1 DM patients and 115 sex and age-matched healthy controls were included in the study. Serum adiponectin, leptin, and resistin levels were measured by the enzyme-linked immunosorbent assay (ELISA method). CIMT was assessed by Doppler ultrasonography. RESULTS Adiponectin levels in diabetics were higher (25.8±14.8 μg/mL vs. 5.5±7.3 μg/mL; P<0.0001) and leptin levels were lower than controls (9.4±6.2 ng/mL vs. 12.8±8.6 ng/mL; P=0.01). Resistin levels were also higher in the diabetic group compared to controls (2.1±1.4 ng/mL vs. 1.6±0.8 ng/mL; P=0.04). Adiponectin was correlated negatively with CIMT (r=-0.24, P=0.03), age (r=-0.30, P=0.02), BMI (r=-0.33, P=0.02), waist-to-hip ratio (WHR) (r=-0.38, P=0.01) and positively with creatinine (r=0.44, P=0.004). Leptin levels were correlated with total cholesterol (r=0.53, P=0.01) and high-density lipoprotein (HDL) (r=0.67, P=0.001). Resistin was correlated with CIMT (r=0.24, P=0.03) and systolic blood pressure (r=0.48, P=0.009). Multivariate analysis revealed resistin and creatinine to be independent predictors of CIMT among adiponectin, leptin, resistin, WHR, glycosylated hemoglobin (HbA1c), and creatinine. CONCLUSIONS Increased adiponectin correlates negatively and resistin positively with CIMT in type 1 diabetic patients, but adjusting for other known predictors reveals only resistin to be associated with subclinical atherosclerosis in this group of patients.

Diurnal Blood Pressure Abnormalities Are Related to Endothelial Dysfunction in Patients with Non-Complicated Type 1 Diabetes

Patients with diabetes have an increased cardiovascular morbidity and mortality despite interventions to prevent these outcomes. Abnormalities in diurnal blood pressure patterns are also associated with excess cardiovascular mortality. The aim of this study was to determine the effects of diurnal blood pressure patterns on endothelial function and oxidative stress in patients with uncomplicated type 1 diabetes mellitus. Thirty-two normotensive and normoalbuminuric type 1 diabetic patients (21 dipper and 11 nondipper) and 37 healthy (27 dipper and 10 nondipper) volunteers underwent 24-h ambulatory blood pressure monitoring. Their endothelial functions were evaluated using flow mediated dilatation (FMD) and by measuring nitric oxide and thiobarbituric acid reactive substances (TBARS). Dippers were defined as subjects who exhibited an average reduction in both systolic and diastolic blood pressure of greater than 10% between day and night periods. Nondipper type 1 diabetic patients and controls had nighttime systolic and diastolic blood pressure values that were significantly higher than those of dipper diabetic patients (p<0.05) and dipper controls (p<0.01). Values of FMD for nondipper diabetic patients (5.12±2.2%) were significantly lower than those in dipper diabetic patients (10.19±2.5%, p<0.01), nondipper (10.08±2.9%, p<0.001) and dipper controls (11.76±3.8%, p<0.001). Additionally, levels of TBARS in the dipper diabetic group and dipper controls were significantly lower than those in the nondipper diabetic group (p<0.05). In conclusion, only type 1 diabetic patients with a nondipping pattern of blood pressure exhibited changes that may lead to endothelial dysfunction and atherosclerosis.

Erdheim-chester disease: Case report with testes involvement and review of literature

Histiocytosis is a group of rare diseases characterized by abnormal accumulation of macrophages, dendritic cells or monocyte-derived cells in different tissues causing various clinical findings.1 ECD is a rare, non-familial, non-Langerhans cell histiocytosis of unknown etiology with characteristic radiological and histological features, which was firstly described by Jakob Erdheim and William Chester in 1930.2 There have been up to 700 cases reported to date. Recently ECD has been recognised as an inflammatory myeloid neoplasia associated with oncogenic mutations of kinase signaling pathway including BRAF, NRAS, KRAS, MAP2K1, and PIK3CA in histiocytes.3 The recent studies have demonstrated BRAFV600E mutations in more than 50% cases. It is characterized