Nutritionist-Dietitians' Association of the Philippines

The concept of metabolic syndrome was introduced as early as the 1950s by a clinician, Jean Vague, in Marseille, France. He noticed that women exhibiting abdominal obesity were more frequently suffering from diabetes, hypertension and cardiovascular complications. The pioneering work of Prof. Gerald Reaven in the 1980s, however, opened the doors to a better understanding of atherosclerosis. He described the clustering of glucose intolerance, hypertension, dyslipidemia and obesity and termed it Syndrome X with insulin resistance as the unifying underlying etiological factor. An explosion of studies and publications followed with the syndrome. It was given a variety of names with a wide range of variables being added to the list of abnormalities. The metabolic syndrome has proven to be the most durable and popular of the names.

Before the initial publication of the WHO definition of metabolic syndrome in 1998, those describing the prevalence of metabolic syndrome used their own definitions and measures of a component as well as their own number and composition of the various components used to define the syndrome. Metabolic syndrome defines a phenotype characterized by central obesity, insulin resistance, atherogenic dyslipidemia (low HDL, high triglyceride, small dense LDL particles, and markers of vascular inflammation), and impaired glucose homeostasis that together confer increased risk for the development of cardiovascular disease and type 2 diabetes. Yet, insulin resistance is not necessarily accompanied by metabolic syndrome, and central obesity is not universally associated with insulin resistance or other hallmarks of metabolic syndrome.

The three most widely recognized definitions of metabolic syndrome include the WHO report from 1999, the European Group for the Study of Insulin Resistance (EGIR) also in 1999, and the National Cholesterol Education program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in adults (ATP III) in 2001. Most recently, the International Diabetes Federation (IDF) proposed a definition that can be used worldwide both clinically and epidemiologically with central obesity as an important and central part of the syndrome with ethnic-specific cut-off points. Although obesity plays a critical role in the development of metabolic syndrome, not all overweight and obese persons develop the syndrome. Metabolic syndrome is believed to develop only in genetically susceptible individuals. The pattern of metabolic syndrome varies considerably among individuals and populations with the South Asians exhibiting a high prevalence of metabolic syndrome even in the presence of mild obesity, suggesting the role of genetic variability in the regulation of the different risk components in different groups. The regulation of the pathways underlying the metabolic risk factors is highly complex and susceptible to genetic variability.

Many studies show that obesity is associated with all of the risk factors of the metabolic syndrome. The precise mechanisms behind these associations, however, have not been determined fully. Ongoing research revealed several possible connections, which seem to be mediated by products released by adipose tissue. Among those most intensely studied are the nonesterified fatty acid (NEFA), inflammatory cytokines, PAI-1, adiponectin, resistin and leptin. The role and association of these different cytokines and products in metabolic syndrome will be presented and discussed.

The increased influx of NEFA into the liver is perhaps the most important factor responsible for lipoprotein overproduction. The primary abnormality of atherogenic dyslipidemia characteristic of metabolic syndrome seems to be an increased influx of apo-B lipoprotein into the circulation. The increased synthesis of hepatic lipase and the normal action of cholesterol-ester transfer protein are two other important factors that lead to the multiple lipoprotein abnormalities characteristic of atherogenic dyslipidemia. The low HDL-C characteristic of metabolic syndrome reduces the capacity to counter the cholesterol accumulation in macrophages, a decreased ability to prevent the oxidation of small dense LDL-C and a reduced inhibition of the pro-atherogenic expression of endothelial adhesion proteins and chemokines. The loss of the protection normally provided by HDL has the capacity to amplify the already powerful pro-atherogenic forces that exist in the metabolic syndrome.

Treatment of metabolic syndrome should therefore be directed toward the management of the different components of the syndrome. Much emphasis has been placed, however, on lifestyle change with focus on weight management and visceral fat reduction, which significantly play a central role in the treatment of the syndrome.

WHO definition of the metabolic syndrome (1999), diabetes or impaired fasting glycemia or impaired glucose tolerance or insulin resistance (under euglycemic conditions, glucose uptake in the lowest 25%) plus 2 or more of the following: 1) obesity: BMI >30 kg/m2 or waist to hip ratio >0.9 (male) or 0.85 (female); 2) dyslipidemia: triglyceride >1.7 mmol/L or HDL-C <0.9 (male) or <1.0 (female); 3) hypertension: BP > 140/90 mmHg; 4) microalbuminuria: albumin excretion > 20μg/min.

European Group for the Study of Insulin Resistance (1999), insulin resistance (defined as hyperinsulinemia, top 25% of fasting insulin values among the nondiabetic population) plus 2 or more of the following: 1) central obesity: waist circumference > 94 cm (male) or >80 cm (female); 2) dyslipidemia: triglycerides >2.0 mmol/L or HDL-C <1.0; 3) hypertension: BP >140/90 mmHg and / or medication; 4) fasting plasma glucose >6.1 mmol/L

ATP-III 2001, three or more of the following: 1) central obesity: waist circumference >102 cm (male) or >88 cm (female); 2) hypertriglyceridemia: triglyceride >1.7 mmol/L; 3) low HDL-C <1.0 mmol/l (male) or 1.3 mmol/l (female); 4) hypertension: BP >150/85 mmHg or medication; 5) fasting plasma glucose >6.1 mmol/L.

International Diabetes Federation definition 2005, central obesity: ethnic-specific, i.e. Europids >94 cm (male) 80 cm (female), South Asians >90 cm (male) 80 cm (female), Chinese >90 cm (male) 80 cm (female), Japanese >85 cm (male) 90 cm (female), plus any 2 of the following: 1) hypertriglyceridemia: triglyceride >1.7 mmol/L; 2) low HDL-C <0.9 (male); 3) hypertension BP> 130/85 mmHg on treatment; 3) increased FBS or pre-existing DM or pre-existing IGT >5.6.

Some references:

4. Lamarche et al. Hypertriglycedemic waist: a marker of the atherogenic triad (hyerinsulinemic; hyperapolipoprotein B, small dense LDL in men? Circulation 2000; 102: 179-84.

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