Sindrome Metabolico y Disfuncion Endotelial

The Metabolic Syndrome and Endothelial Dysfunction: Common Highway to Type 2 Diabetes and CVD?
Michaela Diamant, MD, PhD, and Maarten E. Tushuizen, MD

Corresponding author Michaela Diamant, MD, PhD Department of Endocrinology/Diabetes Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: m.diamant@vumc.nl
Current Diabetes Reports 2006, 6:279 –286Current Science Inc. ISSN 1534-4827 Copyright © 2006 by Current Science Inc.

Due to global lifestyle changes, obesity (the main driver of type 2 diabetes [T2D] and cardiovascular disease [CVD]) is reaching pandemic proportions. The metabolic syndrome, which is regarded as a prediabetic state, is characterized by a concurrence of interrelated cardiovascular risk factors, including abdominal obesity,insulin resistance, hypertension, dyslipidemia, and glucose intolerance. Endothelial dysfunction (ED) is common in the metabolic syndrome and is associated with increased risk for T2D and CVD. This review focuses on the mechanisms linking ED to the metabolic syndrome, T2D, and CVD, and the possible therapies that may improve ED and reduce T2D and CVD risk.

Introduction
Overweight and obesityare reaching pandemic proportions and the projected increase for the coming decades will occur predominantly in the densely populated developing parts of the world [1]. Concomitantly, using modest assumptions about future growth, the number of people with type 2 diabetes (T2D) will increase from 175 million in 2000 to 353 million in 2030, with the biggest increases expected in India (25 to 59million) and China (14 to 25 million) [1,2]. The excess global mortality attributable to diabetes in the year 2000 was estimated to be 2.9 million deaths, equivalent to 5.2% of all deaths, which is similar in magnitude to numbers reported for HIV and AIDS in the same year [2]. Development of diabetes is related to that of atherosclerotic cardiovascular disease (CVD) [3].

The etiologicinterrelationship of T2D with CVD suggests that both arise from a common antecedent, which was described earlier as the metabolic syndrome of insulin resistance [4]. Although the notion of the existence of “a diminished ability of the tissue to utilization of glucose” as the essential lesion in diabetes already existed in the 30s of the past century [5••], the insulin resistance syndrome or syndrome X was firstdescribed by Reaven in 1988 [4]. It was defined as insulin resistance, compensatory hyperinsulinemia, varying degrees of glucose tolerance, hypertriglyceridemia, and low plasma high-density lipoprotein (HDL) cholesterol concentration [4]. Ever since, assuming as a premise that insulin resistance increases CVD risk, many experimental data have led to the expansion and modification of this concept[5••]. Thus, in addition to insulin resistance, glucose intolerance, dyslipidemia, central adiposity, hypertension, a procoagulant state, inflammation, hyperuricemia, hyperhomocysteinemia, and endothelial dysfunction (ED) have been added [5••]. Today, for reasons of unification and clinical use, the most used working definition of the metabolic syndrome is that proposed by the National CholesterolEducation Program Adult Treatment Panel III, characterized by central obesity, hypertriglyceridemia, low plasma HDL cholesterol, hypertension, subclinical inflammation, and insulin resistance (Table 1) [6]. The syndrome increases the risk for both T2D and CVD, but the specific unifying mechanisms that underlie these seemingly diverse pathophysiologic effects remain unclear. ED is a mechanism that mayunify the etiology of T2D and CVD: vascular ED may contribute to insulin resistance and the development of diabetes, whereas ED is a consistent antecedent of CVD [7–9].

Endothelial Dysfunction
The vascular endothelium, consisting of approximately 1014 cells in the human body and when spread as a monolayer, able to cover an area of numerous tennis courts, regulates many different processes,...