In 1988, Dr. Gerald Reaven was awarded the Banting Medal for Scientific Research by the American Diabetes Association and introduced the term Syndrome X to the medical community. According to Dr. Reaven, “Syndrome X is a simple way to refer to a cluster of changes that encourage the onset and development of heart disease. ” (Reaven, 2000, pg. 40) The medical terms Syndrome X, Insulin Resistance (IR), or Metabolic Syndrome (MetS) have been used interchangeably in resent research and MetS will be used in further discussion.
The acquired risked factors that are included in the diagnoses of MetS will be discussed, as well as how they directly lead to heart disease. Cardiovascular disease is the medical outcome of this syndrome. Research estimates that 25 percent of American adults over the age of 20 and 45 percent over the age of 75 are affected by MetS, and those numbers are the proof of the prevalence of this syndrome (Reilly & Rader, 2003, p. 1546). It warrants the attention as a significant threat the health of Americans.
The relative newness of this diagnosis has left a short trail of research. Early studies suspect the pathogenesis of MetS has a genetic predisposition but lifestyle factors can’t be ignored. MetS has a unique set of symptoms that are not always felt by the patient. The liver, pancreas, and heart are all affected by the combination of risk factors. These cause the whole body to be negatively affected with insulin resistance, a constant prothrombotic and proinflammatory state, having atherogenic dyslipidemia, and most notably the increase in abdominal circumference.
The treatments of health style changes and possible medication additions are crucial to the patients’ chance of reducing risk of cardiovascular disease (CVD. ) What Could Be the Pathological Agent of Metabolic Syndrome? The International Diabetes Federation hosted members of the World Health Organization (WHO) and the National Cholesterol Education Program-Third Adult Treatment Panel (ATPIII) as well as members of other health professionals from five continents at a workshop in May of 2004 in London, UK.
The purpose of the workshop was to come to a consensus on the definition of MetS for the clinical diagnosis and research purposes (Alberti, Zimmet, & Shaw, 2006, p. 469). The pathogenesis of MetS was also discussed. The group’s pathogenic summary is much like that of Dr. Reaver: genetics, as well as a poor weight management, will lead the risk factors to develop (p. 86). Insulin resistance and central abdominal adipose fat tissue are the most prominent components of clinical pathogenesis. The Symptoms of Metabolic Syndrome and the Organs That Are Affected
The major symptoms of MetS are often not felt and may be unknown to the patient. Once the symptoms arise enough for the patient to be made aware of them, the chances are that a significant cardiovascular event (CVE) has already occurred. In order to identify the organs that are affected, the apparent clinical and laboratory signs must also be discussed. The most obvious outward sign of MetS is having excessive visceral adipose tissue (VAT). It is more centrally located in the belt area of the body. The body shape of an apple is more dangerous than a pear shape (Brand-Miller, et al. , 2007, p. 21).
This is more clearly defined as a waist circumference greater than 40 inches for men or 35 inches for women (Torpy & Glass, 2006). It should be noted that obviously the guidelines would be different depending on the nationality of the patient. For example, an Asian would be morbidly obese at the measurements given about. An eastern European may be able to have greater measurements and not be classified as at risk for MetS (Alberti, Zimmet, & Shaw, 2006, p. 476). Visceral adipose tissue (VAT) is acts as a metabolic organ. It plays a role in the homeostatic levels of hormones in the body (Choe, et al. , 2016).
The risk that VAT brings to the syndrome is that it is known to secrete cytokines that elevate the C-reactive protein levels in the blood (Grundy, et al. , 2004, p. 434). The increase in C-reactive proteins causes an inflammatory causative danger for CVD. Another secretion of adipose tissue is an adipokine called leptin, it is a relatively new discovery found in 1994 (Bonner, 2010). The role of leptin resistance is not completely agreed up by the scientific community and is being researched for its possible role in MetS. This is one example of how science is just beginning to understand the complexity of MetS.
The danger of having an increased abdominal circumference is that obesity contributes and aggravates all of the other risk factors. Obesity contributes to the risk of hypertension, hyperlipidemia, low HDL levels, high LDL levels, hyperglycemia and diabetes (Grundy et al. , 2004, p. 433, 434). The correlation between excessive VAT and having MetS is a visual sign that damage may be occurring. Dr. Reaver wrote in his book Syndrome X, “Obesity doesn’t cause insulin resistance. Not all obese people are insulin resistant and not everyone with syndrome X is obese” (pg. 87).
This is not to say that there isn’t a strong correlation to the obesity and insulin resistance in a MetS patient. It simply means that there isn’t a steadfast rule that makes it easy to diagnose in the clinic setting. Insulin resistance (IR) is the next most abundant risk factor characteristic of metabolic syndrome. The Collins Medical Dictionary defines it as: A state in which normal levels of insulin in the blood fail to produce the normal biological response. A feedback mechanism results in higher than normal levels of insulin and the blood sugars may be normal or raised (Youngson, 2005).
IR occurs when the pancreas is working correctly, but the body isn’t using the insulin in the normal ways. The body is overwhelmed with glucose and is forced to use it as the main source of energy instead of the body’s available fat. The fat has to go somewhere so it gets stored inside muscle cells, it remains in the blood as triglycerides and it may be stored in the liver. This cause the complication of a non-alcoholic fatty liver. The waist size will grow with adipose tissue as a result of IR. (Brand-Miller et al. , 2007, p. 27). The vicious cycle will continue.
Hyperinsulinemia can occur in patients with normal fasting glucose levels so the tests Homeostasis Model Assessment (HOMA0 and the Quantitative Insulin Sensitivity Check Index (QUICKI) or the hyperinsulinemic clamp method are needed to be run in order to properly diagnose IR (Reilly & Rader, 2003, p. 1548). IR is known to raise blood pressure. The increase in insulin makes the kidneys have to work harder than necessary. Sodium reabsorption in the kidneys occurs because of the excess glucose and thus the blood pressure rises (Zhou, Wang, & Yu, 2014).
Hyperinsulinemia occurs in as much as 50% of hypertensive patients as reported by Zhou et al. (2014) The two symptoms are inter-reliant on each other and create yet another perfect storm in the MetS patient. The MetS patient will also most like be shown to have atherogenic dyslipidemia: abnormally high triglycerides and low HDL (high-density lipoprotein) levels. A more extensive look at the blood panel can prove that often there are other abnormalities such as smaller than usual LDL and HDL particles which have been shown to be associate with heart disease (Reiley & Rader, 2003, p. 548. ) Increased remnant lipoproteins, and elevated apolipoprotein B levels are often detected in addition (Grundy et al. , 2004, p. 434).
The VAT is the source for the excess fatty acids that will storm the liver. When the liver processes those fatty acids, it creates triglycerides. If the patient is also IR, then the muscle cells are keeping insulin in the blood and encouraging the liver to over produce (Reaver, 2000, p. 52). Here is yet another organ that suffers from the effects of the risk factors of MetS.
This damage causes atherosclerosis or CVD. MetS has more interconnected risk factors. High triglyceride levels lead to elevated PAI-1 (plasminogen activator inhibitor-1) levels. The PAI-1 circulates in the body and slows the dissolving of blood clots. This is necessary to counteract the actions of the fibrinogen that the body creates when excessive bleeding occurs. The fibrinogen is also increased in the body that has a high C-reactive protein level. For example, when coronary arteries are damaged, a clot has to be made in the artery by fibrinogen.
When fibrinogen levels are too high, as they often are in MetS, then the level of PAI-1 must also be increased (Reaven, 2000, pp. 44, 135). This complex competition can cause an artery to become clogged and cause a heart attack. The body reacts by being in both a prothrombotic and proinflammatory condition. Treatments for Metabolic Syndrome The three organizations at the IDF summarized and agreed upon treatments for MetS (Alberti, Zimmet, & Shaw, 2006, p. 477). They agreed that the focus for lowering the risk of heart disease caused by MetS should be the overall loss of weight.
Weight loss of 5-10% of the body weight and significantly reduce the effects of obesity. Cholesterol levels will be improved. Blood pressure will show improvement, as well as overall cardiovascular health. Alberti et al. (2006) reports “observational studies have shown that moderate to vigorous physical activity for 180 min per week reduces the risk of the MetS by 50% and with more vigorous exercise only 60 min. is needed. ” Waist size measurements need to be within the acceptable range in order to reduce the negative effects of the visceral adipose tissue.
Exercise will not be as effective if it is not paired with an appropriate healthy diet. Body mass indexes (BMI) can indicate the level of need for weigh loss. Dr. Reaver suggests that the diet full of unsaturated fats can reduce LDL cholesterol levels and be doubly effective when paired with medications (2000). A specific medication therapy has not be designed yet. Medications may be used to target specific component symptoms in order to reduce the cardiovascular damage that they cause. Fibrates or niacin are being studied for effectiveness in MetS treatments.
Statins and fibrates together are showing promise, but the side effects can be worrisome (Grundy et al. , 2004, p. 437). Insulin resistance is becoming more intensely studied by of many of the drug companies. The diabetic medication Metformin and the insulin sensitizers are the focus of study but have yet been proven to lower the heart attack rates directly. (Grundy, et al. , p. 437) Aspirin given at the standard 81mg per day is being recommended as the way to lower the risk of CHD caused by inflammation (Grundy, et al. p. 437).
Hypertension is often treated clinically with diuretics and beta blockers, but Alberti et al. reports that those drugs “given in high doses can worsen insulin resistance and atherogenic dyslipidaemia. ” They also note that a patient who has diabetic shouldn’t be given beta blockers even though they provide protection for CHD. In those patients, exercise is just as useful in reducing the hypertension blood levels. Conclusion.
“Genetics may load the cannon, but human behavior pulls the trigger. – Frank Vinicor United States Centers for Disease Control and Prevention As America’s waist line increases, the amount of new MetS will continue to increase. The relative newness of the naming of the syndrome has put it behind in scientific research. The fact is that most medication treatments need to be studied for longer times before the can be conclusive in proving the reduction of cardiovascular disease. Lifestyle modifications are the cornerstone of treatments to decrease the cardiovascular risks that exist with MetS and should be viewed as a priority.
The complex and often inter-related associations of genetics, environmental factors (poor lifestyle choices) and the increase in insulin resistance sets up the patient for a potentially deadly cardiovascular event. See Table 1. Further research is needed in order to develop new targeted therapies for the unique combination of risk factors that create metabolic syndrome. The effective treatment of MetS, the rates and risks of heart disease will be significantly decreased.