Opening Keynote
Moderador / Chairperson : Manuel Serrano Ríos
Hospital Clínico San Carlos, Madrid, Spain

Síndrome Metabólico: Una actualización / Metabolic Syndrome: An Update
The metabolic syndrome, in addition to being a precursor to type 2 diabetes, is itself now recognised as an important risk factor for coronary heart disease (CHD). The recent consensus of the International Diabetes Federation (IDF) for a new definition of the metabolic syndrome will be reviewed in this presentation. This definition has central obesity as the core component based on waist measurement, with differing cut points for different ethnic groups. The patient must also have at least two abnormalities from: raised fasting glucose, hypertension, raised TG and lowered HDL-C. In addition, recommendations for the management of patients with the metabolic syndrome with lifestyle changes and drug therapy will be presented.

Norbert Stefan
Dept. Internal Medicine, Division of Endocrinology, Metabolism and Pathobiochemistry, University of Tübingen, Germany

Determinantes genéticos y ambientales de los lípidos intrahepáticos / Genetic and Environmental Determinants of Intrahepatic Lipids
There is increasing evidence that accumulation of lipids in the liver, the clinical disorder that is termed non-alcoholic fatty liver disease (NAFLD), is closely associated with the metabolic syndrome. It is currently under investigation which genetic and metabolic factors predispose to NAFLD. In a lifestyle intervention program, among others, an imbalance in plasma levels of adiponectin, and single nucleotide polymorphisms in the adiponectin receptor 1 gene were found to be regulators of NAFLD.

Giulio Marchesini
Servizio di Malattie del Metabolismo, "Alma Mater Studiorum", Universita di Bologna, Italy

Hábitos dietéticos, peso corporal y resistencia insulínica en el hígado graso no alcohólico / Dietary Habits, Body Weight and Insulin Resistance in Non-acoholic Fatty Liver Disease
Genetic and behavioral factors may contribute to the association of non-alcoholic fatty liver disease (NAFLD) with insulin resistance. In principles, genetic factors might have a primary role in lean, non-diabetic subjects, whereas eating habits and sedentary behaviors might promote hepatic steatosis in the presence of overweight or obesity. Excess body weight remains a major drive of disease and weight loss is a relevant clue to treatment. Qualitative aspects of food intake have been less convincingly associated with the extent of hepatic steatosis. The possibility that defects or abundance of specific dietary components may facilitate NAFLD and its progression should be addressed in future studies.

Cracterísticas clínicas, diagnóstico e historia natural del hígado graso no alcohólico / Clinical Features, Diagnosis and Natural History of Non-alcoholic Fatty Liver Disease
Non-alcoholic steatohepatitis (NASH), the most severe form of non-alcoholic fatty liver disease (NAFLD) is a progressive fibrotic disease in which cirrhosis and liver-related death occur in up to 20% and 12% respectively over a 10 year period. In contrast NAFLD has a benign clinical course.

The demographics of NAFLD and NASH include a wide spectrum of patient profile. Although the typical patient appears to be an obese, diabetic, hyperlipidemic middle age female, NAFLD/NASH can be present in any type of patient including children. The diagnosis can be problematic. Liver enzymes are not particularly helpful. A hepatic ultrasound is the most useful radiographic test but lacks sensitivity and cannot differentiate NAFLD from NASH.

NASH, the most severe form of NAFLD, have emerged as a common, clinically important type of chronic liver disease. The prevalence rates for NAFLD and NASH range between 17-33% for NAFLD and 6-17% for NASH.

Keith D. Lindor
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

Hígado graso no alcohólico: aproximación al tratamiento/ Non-alcoholic Fatty Fiver: Therapeutic Approach
In this discussion, various therapies for treating nonalcoholic fatty liver will be discussed, including attempts to reverse associated conditions such as obesity, hyperlipidemia, and hyperglycemia. Pharmacologic agents designed to address inflammation or oxidant stress will also be discussed, including insulin sensitizing agents, Betaine, Pentoxifylline, Vitamin E. Lessons learned from a large-scale randomized trial of ursodeoxycholic acid which provides information about the natural history of nonalcoholic fatty liver disease and points out some of the pitfalls in interpreting data from uncontrolled pilot studies will also be discussed.

Endotelio, trombosis y Síndrome Metabólico / Endothelium, Thrombosis and Metabolic Syndrome

Moderador / Chairperson: Diego Rodríguez Puyol
H. U. Príncipe de Asturias, Alcalá Henares, Madrid, Spain

José M. Fernández Real
Unit of Diabetes, Endocrinology and Nutrition, Hospital Universitari Girona, Spain

Resistencia insulínica y Síndrome inflamatorio cardiovascular crónico /Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome
In the last years, type 2 diabetes is increasingly recognized as an inflammatory state. Decreased insulin action was proposed as the triggering factor of the different components of the metabolic syndrome, which are directly linked to cardiovascular disease. Insulin resistance and cardiovascular disease share common pathophysiological mechanisms, as the chronic activation of the innate immune system. This system constitutes the first line of body's defense and is constituted by different barriers (epithelia, adipose tissue), and different blood and tissue components as macrophages, and neutrophils. Acute phase proteins and cytokines are produced in response to different aggressions as infections and traumatisms. The aim of this response is to eradicate these agents, to repair the harmed tissues, and, through increased insulin resistance, to optimize the energetic substrates.

Paresh Dandona
Millard Fillmore Hospital, University of Buffalo, New York, USA

Diabetes y Endotelio/ Diabetes and the Endothelium
Recent research has shown that insulin is a vasodilator and that it causes a secretion of NO from the endothelium. It has also been shown that insulin suppresses inflammatory mediators from the endothelium and circulating MNC. In addition, it suppresses atherogenesis in the apoEº mouse and that interference with its signal results in atherogenesis. Clearly, insulin has an anti-inflammatory and possibly an anti-atherogenic and cardioprotective effect. A re-interpretation of the metabolic (insulin resistance) syndrome in view of these novel actions of insulin would explain several clinical features of the metabolic syndrome related to its cardiovascular complications.

Marie Christine Alessi
Laboratoire d'ematologie, INSERM UMR626, UFR de Medecine, Universite de la Mediterranee, Marseille, France

Fibrinolisis y Síndrome Metabólico / Fibrinolysis and Metabolic Syndrome
ncreased plasma Plasminogen Activator Inhibitor type 1 (PAI-1) levels has, since a long time, been described in obese insulin resistant patients. This could be considered as a contributing factor to elevated risk of coronary heart disease in obese insulin resistant people. It appears likely, that the relationship between obesity, insulin resistance, and PAI-1 may depend at least in part on the increased production of PAI-1 by adipose tissue. PAI-1 is involved in tissue remodelling, therefore it has been speculated that the increased expression of PAI-1 in obesity influences the remodeling and expansion of adipose tissue. Finding using PAI-1 transgenic - suggest that PAI-1 produced by the adipose tissue could be directly involved in etiopathogenesis of obesity and insulin resistance.

Angelo Avogaro
Department of Clinical and Experimental Medicine, University of Padova, Italy

Disfunción endotelial en el Síndrome Metabólico / Endothelial Dysfunction in the Metabolic Syndrome
The aim is to describe the pathophysiology of endothelial dysfunction in the Metabolic Syndrome, and to outline the mechanisms that, in each component of the syndrome, lead to the endothelial damage.

Obesidad y Síndrome Metabólico / Obesity and Metabolic Syndrome
Moderador / Chairperson: Pedro González Santos
Hospital Clínico de Málaga. Spain

I Sadaf Farooqi
University Departments of Medicine and Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke's Hospital , Cambridge, UK

Susceptibilidad genética y obesidad / Genetic Susceptibility and Obesity
In the last few years, we and others have described six human disorders of energy balance that arise from genetic defects. The first monogenic human obesity syndrome we reported was congenital leptin deficiency which can be treated with recombinant human leptin. We have recruited over 1700 severely obese children to the Genetics of Obesity Study (GOOS). Using a candidate gene approach, we have identified loss of function mutations in the melanocortin 4 receptor (MC4R), which cause a dominantly inherited syndrome that accounts for up to 5% of patients with severe, early-onset obesity. These studies have highlighted the role of leptin and the melanocortin axis in humans and the characterization of these syndromes has shed light on the molecular and physiological mechanisms underlying the regulation of appetite and body weight.

Peter Arner
Department of Medicine at Karolinska Institute, Huddinge University Hospital, Sweden

Complicaciones metabólicas asociadas a la obesidad: un problema del tejido adiposo / Metabolic Complications Associated with Obesity: An Adipose Tissue Problem Adipose tissue secretes many molecules that may influence insulin sensitivity and cause a metabolic syndrome phenotype. Two adipocyte specif factors are adiponectin, which modulates insulin sensitivity and fatty acids which influence insulin action and secretion and also influence lipid and carbohydrate metabolism. The development of upper-body obesity leads to an inflammatory state of adipose tissue which increases fatty acid production and inhibits adiponectin production so that insulin resistance develops. An adipocyte-specific gene, CIDEA, protects adipose tissue from the inflammatory effects.

Miguel A. Rubio
Servicio de Endocrinología y Nutrición, Hospital Clínico San Carlos, Madrid, Spain

La experiencia del Estudio DRECE / The DRECE Study Experience
The Diet and Risk of Cardiovascular Diseases in Spain Study (DRECE) is a prospective study designed to evaluate the relation among life habits, mainly dietary, and cardiovascular diseases prevalence in Spain. More than 5000 persons, both sexes and age matched 5-59 years, representative of the Spanish population, are being followed from 1990. Results on Metabolic Syndrome prevalence among DRECE cohort will be commented. Also its correlation with other cardiovascular risk factors will be considered.

Closure Keynote
Moderador / Chairperson: José A. Gutiérrez Fuentes
Fundación Lilly, Spain

John Yudkin
Diabetes and Cardiovascular Disease Academic Unit, Department of Medicine, Royal Free and University College Medical School, London, UK

Nuevas formas de entender la relación entre el Síndrome Metabólico y la Enfermedad Cardiovascular/ New Understandings of the Links between Metabolic Syndrome and Vascular Disease
Insulin resistance is frequently associated with obesity, particularly an excess of central fat. Many of the features which have been ascribed to the metabolic syndrome are more common in obese subjects, including microalbuminunria and endothelial dysfunction. More recently, features of low-grade inflammation have been associated with obesity. Adipose tissue generation of adipocytokines such as tumour necrosis factor- a , may act predominantly in autocrine or paracrine fashion, others are released into the systemic circulation, acting as signalling molecules to remote tissues, including liver, skeletal muscle and endothelium. Perivascular fat may also contribute both to insulin resistance and to vascular disease.

Despedida / Farewell
José A Gutiérrez Fuentes
Manuel Serrano Ríos
Raffaele Carraro

José A Gutiérrez Fuentes
Manuel Serrano Ríos
Raffaele Carraro

Angelo Avogaro
I Sadaf Farooqi
Pedro González Santos
Peter Arner
Miguel A Rubio
José F. Caro
José A Gutiérrez Fuentes
John Yudkin
Juan Ascaso
Raffaele Carraro
Pedro Conthe