Metabolic syndrome is related to multiple cardiovascular risk factors. Visceral adipose tissue (VAT) plays a key role in metabolic syndrome. Easy detection of VAT could be an important tool to increase knowledge of metabolic syndrome. The objective of this study was to study the relationship of echocardiographic epicardial adipose tissue to anthropometric and clinical parameters of metabolic syndrome. We selected 72 consecutive subjects, 46.5 ؎ 17. M ETABOLIC SYNDROME IS related to multiple cardiovascular risk factors (1-3). There are no wellaccepted criteria for the diagnosis of metabolic syndrome. Nevertheless, it is identified by the presence of three or more metabolic alterations, such as abdominal obesity, hypertension, impaired fasting glucose or glucose intolerance, high levels of triglycerides, low levels of high-density lipoprotein cholesterol, and insulin resistance (4). Plasma adiponectin and C-reactive protein (CRP) have also been proposed to be related to central adiposity and cardiovascular risk (5-7).Visceral obesity seems to play a key role in the development of all features of metabolic syndrome (8 -15). Hence, detection of visceral adipose tissue (VAT), the fat deposited around the internal organs, might be important for risk stratification of metabolic syndrome. Nevertheless, it is difficult to obtain an accurate measurement and characterization of VAT. Several methods are applied as surrogates for estimation of VAT. Anthropometric measurements are the most used, but are frequently imprecise. However, waist circumference is widely accepted as a good predictor of intraabdominal fat mass (16, 17). Imaging techniques are certainly more precise and reliable than anthropometric measurements. Magnetic resonance imaging (MRI), the gold standard technique, estimates VAT accurately, but unfortunately it is costly (18). Recently, we have proposed and validated a new method to estimate VAT by echocardiographic epicardial adipose tissue measurement (19). Epicardial adipose tissue is a true visceral fat deposited around the heart with characteristics of a high insulin-resistant tissue. Epicardial adipose tissue measurement could be an important tool to increase knowledge of metabolic syndrome on epidemiological basis.The aim of this work was to study the relationship of echocardiographic epicardial adipose tissue to anthropometric, metabolic, and cardiac parameters of metabolic syndrome. Subjects and Methods SubjectsWe selected 72 consecutive subjects (Caucasian; 36 females and 36 males), 46.5 Ϯ 17.4 yr of age, with a body mass index (BMI) between 22 and 47 kg/m 2 (median, 34). Echocardiographic measurements were performed in all subjects during routine examinations. Metabolic syndrome was identified by the presence of three or more of the following parameters: BMI greater than 30 kg/m 2 , predominant truncal/abdominal fat distribution (value of waist circumference Ͼ88 cm in women and Ͼ102 cm in men), impaired fasting glucose (fasting glucose Ͼ110 mg/ dl), hypertension (systolic arterial blood pressure Ͼ13...

Research Methods and Procedures:We selected 60 healthy subjects (29 women, 31 men, 49.5 Ϯ 16.2 years) with a wide range of body mass indexes. Each subject underwent transthoracic echocardiogram and magnetic resonance imaging (MRI) to measure epicardial fat thickness on the right ventricle. Measurements of epicardial adipose tissue thickness were obtained from the same echocardiographic and MRI views and points. MRI was also used to measure VAT cross-sectional areas at the level of L4 to L5. Anthropometric indexes were also measured. Results: Subjects with predominant visceral fat accumulation showed higher epicardial adipose tissue thickness than subjects with predominant peripheral fat distribution: 9.97 Ϯ 2.88 vs. 4.34 Ϯ 1.98 (p ϭ 0.005) and 7.19 Ϯ 2.74 vs. 3.43 Ϯ 1.64 (p ϭ 0.004) in men and women, respectively. Simple linear regression analysis showed an excellent correlation between epicardial adipose tissue and waist circumference (r ϭ 0.895, p ϭ 0.01) and MRI abdominal VAT (r ϭ 0.864, p ϭ 0.01). Multiple regression analysis showed that epicardial adipose tissue thickness (r 2 ϭ 0.442, p ϭ 0.02) was the strongest independent variable correlated to MRI VAT. Bland test confirmed the good agreement between the two methods. Discussion: Epicardial adipose tissue showed a strong correlation with anthropometric and imaging measurements of VAT. Hence, transthoracic echocardiography could be an easy and reliable imaging method for VAT prediction.

In an effort to better understand the phenomenon of lipotoxicity in human ␤-cells, we evaluated the effects of 48-h preculture with 1.0 or 2.0 mmol/l free fatty acid (FFA) (2:1 oleate to palmitate) on the function and survival of isolated human islets and investigated some of the possible mechanisms. Compared with control islets, triglyceride content was significantly increased and insulin content and glucose-stimulated insulin release were significantly reduced in islets precultured with increased FFA concentrations. These changes were accompanied by a significant reduction of glucose utilization and oxidation. By cell death detection techniques, it was observed that exposure to FFAs induced a significant increase of the amount of dead cells. Electron microscopy showed the involvement of ␤-cells, with morphological appearance compatible with the presence of apoptotic phenomena. FFA-induced islet cell death was blocked by inhibition of upstream caspases and partially prevented by inhibiton of ceramide synthesis or serine protease activity, whereas inhibition of nitric oxide synthesis had no effect. RT-PCR studies revealed no major change of iNOS and Bax mRNA expression and a marked decrease of Bcl-2 mRNA expression in the islets cultured with FFA. Thus, prolonged exposure to FFAs has cytostatic and proapoptotic effects on human pancreatic ␤-cells. The cytostatic action is likely to be due to the FFA-induced reduction of intraislet glucose metabolism, and the proapoptotic effects are mostly caspase mediated, partially dependent on ceramide pathway, and possibly Bcl-2 regulated.

The peptide hormone, glucagon-like peptide 1 (GLP-1), has been shown to increase glucose-dependent insulin secretion, enhance insulin gene transcription, expand islet cell mass, and inhibit beta-cell apoptosis in animal models of diabetes. The aim of the present study was to evaluate whether GLP-1 could improve function and inhibit apoptosis in freshly isolated human islets. Human islets were cultured for 5 d in the presence, or absence, of GLP-1 (10 nm, added every 12 h) and studied for viability and expression of proapoptotic (caspase-3) and antiapoptotic factors (bcl-2) as well as glucose-dependent insulin production. We observed better-preserved three-dimensional islet morphology in the GLP-1-treated islets, compared with controls. Nuclear condensation, a feature of cell apoptosis, was inhibited by GLP-1. The reduction in the number of apoptotic cells in GLP-1-treated islets was particularly evident at d 3 (6.1% apoptotic nuclei in treated cultures vs. 15.5% in controls; P < 0.01) and at d 5 (8.9 vs. 18.9%; P < 0.01). The antiapoptotic effect of GLP-1 was associated with the down-regulation of active caspase-3 (P < 0.001) and the up-regulation of bcl-2 (P < 0.01). The effect of GLP-1 on the intracellular levels of bcl-2 and caspase-3 was observed at the mRNA and protein levels. Intracellular insulin content was markedly enhanced in islets cultured with GLP-1 vs. control (P < 0.001, at d 5), and there was a parallel GLP-1-dependent potentiation of glucose-dependent insulin secretion (P < 0.01 at d 3; P < 0.05 at d 5). Our findings provide evidence that GLP-1 added to freshly isolated human islets preserves morphology and function and inhibits cell apoptosis.