Background, History & Definition of Metabolic Syndrome

Annie Sawyer, Ph. D. 

 

Metabolic syndrome is not considered a disease. It is named a syndrome (a combination of different symptoms), or a cluster of disorders of human body's metabolism — including high blood pressure, increased insulin levels, excess body weight, and abnormal levels of cholesterol (dyslipidemia), that lead to many other degenerative diseases. Each of these disorders is by itself a risk factor for other diseases and in combination; these disorders dramatically boost chances of developing potentially life-threatening illnesses as heart attack, stroke, diabetes 2, gout, kidney failure and even Alzheimer.

Although the metabolic syndrome is identified as a major cause of diabetes 2 and cardiovascular disease, it is well known that it increases death and disabilities from all causes, and underlies female reproductive disorders, polycystic ovary syndrome, non-alcoholic fatty-liver disease, non-alcoholic steatohepatitis, gout, calculi, with terminal kidney failure, diabetes mellitus 2, and even certain cancers. However the refinement in the clustering is lost when factors are all packaged together. In an analysis of the West of Scotland Coronary Prevention Study (WOSCOPS), risk prediction increased with the number of metabolic abnormalities (Sattar et al., 2003).

Risk factors as genetics, advanced age, excessive dietary intake of refined sugar, lack of active lifestyle or exercise, genetic tendencies, environmental factors, stress, low socio-economic status and other adverse reasons contribute variably to the pathogenesis of metabolic syndrome. It has been argued, though, that the combination of risk factors does not add up to a more significant or higher cardiovascular risk than the individual components (Kahn et al., 2005).

Stern M.P.(1995) have long hypothesized that there are links between the metabolic derangements of insulin resistance syndrome, pre-diabetes or type 2 diabetes and the development and progression of atherosclerosis. People with metabolic syndrome have a 5-fold greater risk of developing type-2 diabetes if not already present (Stern et al., 2004). This puts metabolic syndrome and diabetes way ahead of HIV/AIDS in morbidity and mortality terms, yet the problem is not as well recognized.

Ridker P.M. at al. (2000), have similarly concluded that IL-6 and CRP are associated with hyperglycemia, insulin resistance, type 2 diabetes, and both are strong predictors of cardiovascular disease in apparently healthy people. In a 10-year observational study 21 of Dutch adults without diabetes or coronary heart disease (CHD) at baseline, the presence of the metabolic syndrome imparted a twofold increased risk for cardiovascular events. The above collection of cardiovascular disease (CVD) risk factors-including hypertension and dyslipidemia, type 2 diabetes, and their association with insulin resistance led establishment of investigators to propose the existence of a distinct entity called “metabolic syndrome”, which has been defined by reputable organizations and assigned its own code in the World Health Organization’s (WHO). With or without C-reactive protein metabolic syndrome is a predictor of coronary heart disease, and diabetes 2 (Sattar et al., 2003). 

As the name suggests, metabolic syndrome is tied to the metabolism of the body, possibly to a condition named ‘insulin resistance’. Total metabolism is the rate at which the energy is used (measured in calories) when one is exercising or doing anything else including resting or sleeping. Resting energy expenditure is the rate at which the calories are burned when a person is not being physically active. Resting energy expenditure varies from person to person and is affected a person’s age, gender, genetic make-up, psychological state, and level of physical activity. Pregnancies as well as illness tend to increase resting energy usage. Both total metabolism and resting energy expenditure influence the person’s weight by affecting how many calories one is burning in the course of a day. 

Metabolic syndrome is also known as a “pre-diabetic” state characterized by dyslipidemia, insulin resistance, obesity, and hypertension. Type 2 diabetes and pre-diabetes (lesser degrees of glucose intoler­ance) are also associated with insulin resistance, central obesity, hyperten­sion, and dyslipidemia. The term metabolic syndrome describes the same constellation, with or without glucose intolerance.

Metabolic syndrome, also known as Syndrome X or insulin resistance syndrome (IRS), is defined as having three or more of the associated symptoms, which include elevated blood pressure, abdominal obesity (increased abdominal fat), insulin resistance (high fasting glucose levels), dyslipidemia( disrupted lipid profile) and elevated C-reactive protein (CRP) levels(one of the major inflammatory markets). It is obvious that metabolic syndrome comprises a conglomeration or accumulation of different and mutually intensifying diseases and risk factors, which mostly share the same causes: a/ Age is seen as factor in approximately 35% (using ATP III criteria) to approximately 40% (using IDF criteria), depending on the definition of impaired fasting glucose (Ford 2005); b/ Race; c/ Gender; e/ Life style (Panagiotakos DB 2004); f/ Stress and depression; j/ Diet. It is a strong predictor, linked to an increased risk of cardiovascular disease, stroke, gout, and type 2 diabetes. It is known that if three of the five criteria are met, some of which include high blood pressure, low HDL (“good” cholesterol) levels, or elevated triglycerides with increased risk of clotting, apple type of obesity or abdominal (visceral) fat the metabolic syndrome is well established.            

Allopathic medicine believes that some people are genetically predisposed to insulin resistance and the tendency may be partly inherited. But being overweight, aged or inactive are also major contributors. The prevalence of metabolic syndrome increases with age, affecting less than 10% of people in their 20s and 40% of people in their 60s. Thus with aging physical activity should consist of a minimum of 30 minutes of moderate-intensity physical activity most days of the week. It has been shown that physical activity can heal metabolic syndrome. In a study of 621 healthy adults with metabolic syndrome, 30.5% of the participants were no longer classified with metabolic syndrome after 40 weeks of aerobic exercise training. Another study of white women showed that leisure-time physical activity levels are inversely associated with the prevalence of metabolic syndrome (JOPERD, 2002)

The connection metabolic syndrome -- mortality is shown in a study published by Farmer A. in Br. Med J (2006). Some of the main complications resulting from metabolic syndrome include cardiovascular disease and diabetes 2. Doctors believe that the underlying cause of this cluster of risk factors is resistance to insulin— a hormone produced by the pancreas that helps regulate the amount of sugar in your body. Normally, the digestive system breaks down some of the food into sugar (glucose). Then the human body uses insulin to transport the glucose into the cells, where it is converted to energy to fuel body processes. If that body becomes resistant to the action of insulin, glucose processing is impaired and reacts by producing more and more insulin in an effort to help glucose enter its cells. This extra insulin helps maintain normal glucose levels in the blood for a while, but eventually the pancreas is unable to overcome insulin resistance. (Nathaniel, 2004). As a result, glucose accumulates in the blood, ultimately leading to type 2 diabetes-- the most common form of diabetes, formerly called noninsulin-dependent diabetes or adult-onset diabetes.

Metabolic syndrome occurs before this point. Glucose levels in the blood are abnormally high, although not high enough to be classified as diabetic, but still high enough so that the excess insulin in the body system opens the door of a risk for other health consequences. The levels of cholesterol and triglycerides in the bloodstream may increase, causing damage to the coronary arteries. At the end excessively high insulin levels may interfere with the kidneys' ability to process salt, which can raise the blood pressure (Nathaniel, 2004) The macrophages and the liver are an integral factor in the development of cardiovascular (CVD) disease and diabetes 2. Macrophages exposed to high blood lipids become foam cells and contribute to heart disease by imbedding into vessel walls leading to fatty streaks, plaque formation, and atherosclerosis. The liver is the main site of glucose and lipid metabolism and has a major impact on the overall metabolic homeostasis of the body.     

History of Metabolic Syndrome

An association between certain metabolic disorders and cardiovascular disease has been known since the late 1950s, but comes into common usage in the 1970-1980s.The question of clustering of the cardiovascular risk factors has been talked about for at least 35 years. The concept was developed by an Italian group in the late 1960s, and in the 1970s there were a variety of papers on the subject (a group in East Germany led by Hanefeld talked about clustering of cardiovascular risk factors and insulin resistance). Reaven was the first who began the discussion about an insulin resistant syndrome, calling it Syndrome X (Diabetes 1987), and Ferrannini (Diabetologia 1991), Haffner (Diabetes 1992) added to this.

Metabolic syndrome is a term coined by the Stanford University physician– Prof. in endocrinology Dr. Gerald Reaven, that describes a cluster or a group of symptoms including high blood pressure, abdominal fat (obesity), insulin resistance, increased levels of triglycerides and low levels of HDL ("good" cholesterol) (Reaven, 1988). Thus the term “Reaven syndrome” refers to the name of Gerald M. Reaven who first describes the syndrome at the 1988 Banting Lecture of the annual meeting of the American Diabetes Association (ADA). He proposed insulin resistance as the underlying factor and named the constellation of abnormalities while naming it- ‘Syndrome X’, but he did not include abdominal obesity, which has also been hypothesized as the underlying factor, as part of the condition. It was defined as a cluster of metabolic risk factors that come together in a single individual. In more current times, the term metabolic syndrome is found throughout medical literature and in the lay press as well. 

Definition of Metabolic syndrome

Attempts have been made to assemble the various fea­tures of the metabolic syndrome into a single all-purpose definition, for which diagnostic, prognostic, and therapeutic value has been claimed. However, the definition of metabolic syndrome depends on which group of experts is doing the defining. There are various definitions of the metabolic syndrome.Building on the earlier definitions, the new consensus definition proposed by the International Diabetes Federation (IDF) in April 2005 is mainly based on abdominal obesity as a central core of the syndrome. It avoids the need for measurements that may only be available in research settings. For a person to be defined as having metabolic syndrome, the new definition requires the presence of central obesity, plus two of the following four additional factors: raised triglycerides, reduced high-density lipoprotein cholesterol (HDL-C), raised blood pressure, or raised fasting plasma glucose level. Gender and, for the first time, ethnicity-specific cut-points for central obesity as measured by waist circumference are included.

Two of the major definitions of the syndrome have been proposed: the first one by the World Health Organization (WHO) (Alberti, Zimmet & Shaw, 1998), and the second by the US National Cholesterol Education Program (NCEP) in 2001- (NCEP 2001). Both definitions share the essential components: glucose intolerance, obesity, hypertension, and dyslipidemia. They do differ, however, in detail and criteria. According to the World Health Organization (WHO) criteria, there is: 1/dysglycemia (diabetes 2, impaired fasting glucose, or impaired glucose tolerance) plus two of the following: 2/ high body mass index (BMI); 3/ some markers of dyslipidemia, elevated blood pressure; or the current marker of vascular dysfunction, which is microalbuminuria (small amounts of protein in urine).

Based on the guidelines from the 2001 National Cholesterol Education Program Adult Treatment Plan (ATPIII), any three of the following traits in the same individual meet the criteria for metabolic syndrome: a/ abdominal obesity-- a waist circumference over 102 cm (40 in) in men and over 88 cm (35in) in women; b/ serum triglycerides 150 mg/dl or above; c/ Low HDL cholesterol—40 mg/dl or lower in men and 50 mg/dl or lower in women. d/ High LDL cholesterol- above 150 mg/dl; e/ Blood pressure of 130/85 or more; f/ fasting blood glucose of 100 (110) mg/dl or above or fasting plasma glucose of at least 6.1 mmol/l. An attempt to harmonize the definition of metabolic syndrome on background of a comparison of the criteria of ATPIII and IDF in US and EU populations is offered by Assman L. (1982).

The revised NCEP and IDF definitions of metabolic syndrome are very similar and it can be expected that they will identify many of the same individuals as having metabolic syndrome. The two differences are that IDF excludes any subject without increased waist circumference, while in the NCEP definition metabolic syndrome can be diagnosed based on other criteria and the IDF uses geography-specific cut points for waist circumference, while NCEP uses only one set of cut points for waist circumference regardless of geography. These two definitions are much closer to each other than the original NCEP and WHO definitions.     

Although not all experts agree on the definition of metabolic syndrome or whether it even exists as a distinct medical condition, they have discussed about this constellation of risk factors for years and have called it many names, including syndrome X or insulin resistance syndrome (IRS). Whatever name or term it is used, and however it is defined, this cluster of risk factors is apparently becoming seriously prevalent in the 21st century. While not all experts agree on the definition of metabolic syndrome as a syndrome or a disease, they do all agree on how serious and prevalent metabolic syndrome is becoming around the Globe. Despite no consensus has been reached as to the definition of metabolic syndrome- the abnormal insulin or glucose intolerance regulation, dyslipidemia, visceral adiposity or abdominal obesity, and hypertension are mostly included in the most widely accepted definition on the syndrome.