Syndrome X (metabolic) - Definition and Overview

Metabolic syndrome is a combination of medical disorders that affect a large number of people in a clustered fashion. In some studies, the prevalence in the USA is calculated as being up to 25% of the population.

Nomenclature

Other names for this syndrome are:

• Syndrome X;
• Metabolic syndrome X;
• Insulin resistance syndrome;
• Reaven's Syndrome, after Dr Gerald M. Reaven (who put the syndrome on the map in 1988 in the Banting lecture (http://diabetes.diabetesjournals.org/cgi/content/abstract/37/12/1595), named after Sir Frederick Banting).
• CHAOS (Australia)

It is not related to:

• Fragile X syndrome (a chromosomal abnormality);
• Cardiac syndrome X - this term is now mainly used for a type of angina pectoris where there is cardiac ischemia on exercise testing but no causative atherosclerosis on a coronary angiogram.

Signs and symptoms

Symptoms and features are:

• Diabetes mellitus type II (or impaired glucose tolerance or insulin resistance);
• High blood pressure;
• Central obesity and difficulty losing weight;
• High cholesterol (combined hyperlipidemia):
  • Elevated LDL;
  • Decreased HDL;
  • Elevated triglycerides;
• Fatty liver (especially in concurrent obesity).

Associated diseases are:

• Polycystic ovarian syndrome;
• Hemochromatosis (iron overload);
• Acanthosis nigricans (a skin condition featuring dark patches);
• Non-alcoholic steatohepatitis (extreme form of fatty liver).

Diagnosis

The above diseases are all diagnosed separately; please see the relevant articles. The Adult Treatment Panel III of the National Cholesterol Education Program defined the diagnosis as three or more of the following five:

• Increased waist circumference (>=102 cm in men and >=88 cm in women), indicating central obesity
• Elevated triglycerides (>=150 mg/dL or 1.7 mmol/l)
• Decreased HDL cholesterol (<40 mg/dL for men, <50 mg/dL for women)
• Blood pressure above 130/85 or active treatment for hypertension
• Glucose levels above 100 mg/dL

Pathophysiology

The causes of metabolic syndrome are extremely complex and have only been partially elucidated. Most patients have a degree of insulin resistance, but there is debate whether this is the cause of the metabolic syndrome or a byproduct of a more far-reaching metabolic derangement. There is a role for systemic inflammation, as a number of inflammatory markers (including C-reactive protein) is often increased, as are fibrinogen, IL-6, TNFα and others.

Therapy

Generally, the individual diseases that comprise Syndrome X are treated separately (e.g. diuretics and ACE inhibitors for hypertension). A remarkable finding is, however, that drugs that decrease insulin resistance (metformin and thiazolidinediones) not only reduce hyperglycemia but generally lead to in improvement in blood pressure and cholesterol (lipid profile) as well. Exercise and weight loss may be helpful, particularly in preventing progression to diabetes mellitus.

References

• Grundy SM. Obesity, Metabolic Syndrome and Cardiovascular Disease. J Clin Endocrinol Metab 2004;89:2595-600.