What is metabolic syndrome?

Causes and Symptoms

Metabolic syndrome is a complex medical disorder. According to guidelines issued by the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III), diagnosis of metabolic syndrome is made when an individual displays at least three of the following risk factors: abdominal obesity, elevated triglycerides, low levels of the high-density lipoprotein (HDL) type of cholesterol, high blood pressure, and the presence of more than 100 milligrams per deciliter (mg/dL) of glucose in the blood after fasting.

The National Heart, Lung, and Blood Institute (NHLBI) estimates that as many as forty-seven million adults in the United States suffer from metabolic syndrome, which is around 25 percent of the total adult population. A study published in National Health Statistics Reports in May 2009 reported that 34 percent of the study's 3,423 adults aged twenty and older met the criteria for metabolic syndrome. Age plays a large role in metabolic syndrome, with the likelihood of being diagnosed increasing as an individual gets older. Total body weight is also an indicator of the likelihood of the metabolic syndrome criteria being met. Males who are overweight are six times as likely as normal-weight males to be diagnosed with metabolic syndrome, and those who are obese are thirty-two times as likely.

In females, being overweight leads to a fivefold increase in the chances of being diagnosed with metabolic syndrome and obesity a seventeen-fold increase, compared to women of normal weight. Disturbingly, metabolic syndrome is now being recognized in children and adolescents; this is probably related to the increase in obesity and type 2 diabetes mellitus
seen in this age group over recent years. There is also evidence to demonstrate a genetic component to metabolic syndrome; further research will clarify this.

Key aspects of the metabolic syndrome are an energy imbalance and resultant altered metabolic pathways. The abnormal metabolic reactions seen in metabolic syndrome confer an increased risk for type 2 diabetes mellitus and cardiovascular
disease (CVD). Several other diseases—colon
cancer, Nonalcoholic steatohepatitis (NASH), polycystic ovary disease, and chronic renal failure—can also be a consequence of this syndrome.

The National Health and Nutrition Examination Survey determined that the most prevalent risk factor displayed by individuals with metabolic syndrome is abdominal obesity.
This is when fat is stored in the abdominal region of the body as opposed to in the buttocks and thighs. People with abdominally stored fat are often said to have “apple” type bodies; those with fat stored lower, in the buttocks and thighs, are said to be “pear” shaped. Men are typically apples and women are pears. Cortisol is a stress response hormone that promotes fat deposition in the abdominal area in individuals with chronic stress. Nearly all cases of overweight and obesity, including abdominal obesity, are due to excess calorific intake (overeating) combined with a sedentary lifestyle. In the United States, around one-third of the adult population is obese. Obesity greatly increases the risk for type 2 diabetes and cardiovascular disease.

Abnormal levels of fats in the blood is called dyslipidemia. In people who are overweight or obese, the levels of lipids in the body are so high that the pathways involved in fat synthesis and breakdown cannot keep up, and chronically high blood lipids are seen.

In addition, due to impaired insulin action and incorrect handling of glucose by their cells, individuals with type 2 diabetes tend to have high levels of blood triglyceride and low HDL cholesterol levels. This puts type 2 diabetics and obese individuals at high risk for CVD.

The second most prevalent factor seen in patients diagnosed with metabolic syndrome is hypertension, or high blood pressure. One in four Americans suffers from hypertension. If untreated, it can lead to CVD and kidney failure. The atherosclerotic process is accelerated in the metabolic syndrome and in type 2 diabetes because of the presence of multiple metabolic abnormalities. In insulin resistance, plaque formation may be enhanced because of the increased expression of adhesion molecules on endothelial cells and an increased rate of monocyte adhesion to endothelial cells. Circulating plasminogen is also more likely activated, which typically leads to increased clotting. In addition, hypertension may contribute to an increased risk of stroke in those with the metabolic syndrome.

The third most prevalent factor is hyperglycemia, or impaired fasting glucose. To satisfy the criterion for metabolic syndrome the glucose level in the blood after fasting must be over 100 mg/dl. A person with 100 to 125 mg/dl would be considered prediabetic, and diabetes is diagnosed when the fasting level of glucose is 126 mg/dl or above. Increases in blood glucose are indicative of a phenomenon called insulin resistance. Here, the cells of the body do not respond properly to insulin, and as a result glucose cannot enter the cells for use or storage so it remains in the circulating blood. Chronically elevated blood glucose concentration permits glucose molecules to combine with diverse proteins in the body, including hemoglobin within red blood cells, by a process known as glycation or glycosylation. Glycation also leads to blood vessels becoming rigid, a factor that contributes to CVD.

Any one of the risk factors listed on the NCEP/ATP III guidelines can cause chronic health problems, specifically type 2 diabetes mellitus and CVD. Diagnosis of metabolic syndrome requires that at least three out of the five criteria are met. This translates into a vastly increased risk for these chronic health problems; the reason why the life span of individuals diagnosed with metabolic syndrome is an average of fourteen years shorter than those without the disease.

Treatment and Therapy

Treatment strategies for the metabolic syndrome focus on weight loss through a comprehensive program utilizing behavioral changes, including improved nutrition and an increase in physical activities. The long-term goal of therapy is a better balance between the intake of food energy sources and energy expenditure, so that a healthier body weight can be achieved. Dietary treatment typically requires the involvement of nutritionists and registered dieticians to provide educational information and institute changes in food selection.

Physicians provide overall care, and concomitant with lifestyle changes use the prescription of medications for one or more of the components of metabolic syndrome. Metformin is a drug used to treat type 2 diabetes mellitus; it works by improving insulin action, and has also been shown to stop the development of impaired fasting glucose to type 2 diabetes in patients with metabolic syndrome. Angiotensin-converting enzyme (ACE) inhibitors are used in the treatment of hypertension. They are successful in treating hypertension and, in addition, have a beneficial effect on insulin resistance in metabolic syndrome. Another class of drugs is the statins, which are used to improve cholesterol levels in people with metabolic syndrome. Statins also appear to cause a reduction in inflammation seen in metabolic syndrome, leading to a reduction in CVD.

Since the emerging epidemic of the metabolic syndrome is expected to continue, both preventive and treatment strategies are needed. Prevention aimed toward reducing the development of this syndrome in children and adolescents should involve schools and community agencies.

Perspective and Prospects

Recognition of the metabolic syndrome essentially paralleled the increases in overweight and obesity in the United States in the early 1990’s. Physicians were diagnosing many overweight and obese patients with the major components of the metabolic syndrome without linking them to a major health trend. Other countries of affluence were also reporting cases.

The metabolic syndrome was first defined in 1998 by the World Health Organization (WHO). The WHO criteria included a BMI of more than thirty; a blood triglyceride level greater than or equal to 150 mg/dl; HDL cholesterol level under 35 mg/dl in men and 39 mg/dl in women; blood pressure over 140/90 mm Hg; impaired glucose tolerance, insulin tolerance or type 2 diabetes; insulin resistance; and microalbuminuria (protein in the urine). In 2001 the NCEP/ATP III released their guidelines for the diagnosis of metabolic syndrome, which quickly became the most widely accepted. These differed from the WHO guidelines in several ways. Firstly, BMI measurement was replaced with waist circumference measurement when it became clear that it was not necessarily the total body fat content, but the way in which it is deposited in the body that is important to pathogenesis. A waist circumference of over forty inches for men and over thirty-five inches for women is considered a risk factor for metabolic syndrome. Secondly, the HDL values were changed to less than 40 mg/dl for men and 50 mg/dl for women, and blood pressure limit was lowered to 130/85 mm Hg. A fasting glucose level of
over 110 mg/dl was defined as a risk for metabolic syndrome. Finally, insulin resistance and microalbumiuria were removed from the criteria. In 2005 the guidelines were updated by American Heart Association (AHA) and NHLBI; the fasting blood glucose level was lowered to 100 mg/dl. These are the currently used criteria for the diagnosis of metabolic syndrome.

The metabolic syndrome has deadly consequences because of the nature of the chronic diseases that it spawns. This problem will worsen in the future in the United States because excessive calorific intake, eating the wrong kinds of food (for example highly processed food containing high fructose corn syrup, trans fats, or too much salt), and too little physical activity continue to dominate society. The epidemic nature of this syndrome requires that new public health measures be initiated and implemented as soon as possible. Preventive strategies need to be instituted to reduce the enormous impact of this syndrome anticipated in the United States in the coming decades. The overall cost of treatment will be enormous.

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