REVIEW – September 2006

Metabolic syndrome – the nature and pathogenesis

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Abstract

Metabolic syndrome consists of several modifiable risk factors that may predispose people to type 2 diabetes and cardiovascular diseases. These abnormalities can, individually or in combination, increase the risk of diabetes and cardiovascular disorders. In 2005, the International Diabetes Federation (IDF) proposed a unified definition of the metabolic syndrome, convenient to use in clinical practice. According to this definition, abdominal obesity (increased waist circumference) is a prerequisite for the diagnosis. Additional criteria of metabolic syndrome include plasma triglyceride level > 1.7 mmol/l, lowered plasma HDL-cholesterol level < 1.03 mmol/l, increased blood pressure (systolic ≥ 130 mm Hg, diastolic ≥ 85 mm Hg) and increased fasting plasma glucose level ≥ 5.6 mmol/l. The diagnosis of metabolic syndrome is based on the coexistence of abdominal obesity with at least two additional criteria. Intraabdominal obesity plays a critical role in the development of a wide range of cardiometabolic risk factors. Visceral adipocytes, compared with subcutaneous fat cells, are active endocrine cells secreting several peptides actively involved in lipid and glycose metabolism. In response to signals from the sympathetic nervous system, visceral adipocytes secrete a larger amount of adipokines, including interleukin-6 and plasminogen activator inhibitor-1, which lead to intensive lipolysis of adipose cells and prodution of free fatty acids (FFA). In the liver, FFA inhibit insulin binding and degradation, which leads to the increased hepatic glycose production and hyperinsulinaemia. The FFA also affect hepatic lipid metabolism, stimulating production of triglycerides and LDL-cholesterol and reduction of HDLcholesterol synthesis in the liver. As metabolic syndrome is a growing problem, numerous agents have been developed to treat its individual components. If the condition involves more than a cluster of risk factors it would benefit from a comprehensive approach to treatment incorporating lifestyle changes and pharmacotherapy directed at the cause of the disease.
The Shape of Nations survey, conducted recently by the World Heart Federation and involving 16, 475 participants from 27 countries, summarized: on average 39 per cent of all persons visiting a primary care physician worldwide are overweight or obese. In North America this figure reaches 49%. Abdominal fat is recognized by 58% of physicians worldwide as a significant risk factor for heart disease. However, only a minority of patients are aware of increased waist size placing them at high risk of cardiovascular disease and only an average of 17% can expect to be measured by their physician.
These findings demonstrate the need for education and action to safeguard the health of patients worldwide.