Metabolic syndrome pathophysiology


 * Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [mailto:psingh@perfuse.org]

Overview
Metabolic syndrome are characterized by a cluster of conditions that greatly increases the risk of a person to develop heart diseases, diabetes and stroke. By definition one is said to have a metabolic syndrome if they have 3 of the following 5 conditions: high blood pressure (>130/85), abnormal fasting blood glucose > 100 mg/dl, increased weight around the waist (women > 35 inches, male > 40 inches), triglycerides > 150 mg/dl and a low HDL (female < 50, male < 40).

Pathophysiology

 * The cause of the metabolic syndrome is unknown.


 * The pathophysiology is extremely complex and has only been partially elucidated.


 * Most patients are older, obese, sedentary, and have a degree of insulin resistance.


 * The most important factors in order are 1) aging, 2) genetics and 3) lifestyle (i.e., decreased physical activity and excess caloric intake).


 * There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome or if it is a by-product of a more far-reaching metabolic derangement


 * Systemic inflammation: a number of inflammatory markers (including C-reactive protein) are often increased, as are fibrinogen, interleukin 6 (IL&minus;6), Tumor necrosis factor-alpha (TNFα) and others.


 * Some have pointed to oxidative stress due to a variety of causes including dietary fructose mediated increased uric acid levels.


 * Commonly, there is development of visceral fat followed by the adipocytes (fat cells) of the visceral fat increasing plasma levels of TNFα and altering levels of a number of other substances (e.g., adiponectin, resistin, PAI-1).


 * TNFα has been shown to not only cause the production of inflammatory cytokines, but may also trigger cell signaling by interaction with a TNFα receptor that may lead to insulin resistance.


 * An experiment with rats that were fed a diet one-third of which was sucrose has been proposed as a model for the development of the metabolic syndrome. The sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance . The progression from visceral fat to increased TNFα to insulin resistance has some parallels to human development of metabolic syndrome.

Associated Conditions

 * Polycystic ovarian syndrome
 * Hemochromatosis(iron overload)