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Metabolic Syndrome

“The combination of metabolic disturbances now known as the metabolic syndrome (MetS) was first described by Kylin in the 1920s as the clustering of hypertension, hyperglycemia and gout. Two decades later, Vague noted that upper body adiposity (android or male-type obesity) was the type most often associated with the metabolic abnormalities seen with diabetes and cardiovascular disease (CVD). During the 1988 Banting Lecture, Reaven used the term ‘Syndrome X’ and firmly established the clinical importance of this syndrome, although obesity was not included. In 1989, Kaplan renamed it ‘The Deadly Quartet’ and others then coined the term ‘The Insulin Resistance Syndrome’. It is now agreed that the well-established term ‘metabolic syndrome’ remains the most useful and widely accepted description of this cluster of metabolically related cardiovascular risk factors which also predict a high risk of developing diabetes (if not already present).”1 

“Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity — the most prevalent manifestation of metabolic syndrome — is a marker of ‘dysfunctional adipose tissue’, and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.”2

Metabolic syndrome is a set of abnormal biochemical processes gone awry which increases the risk of many widespread diseases, most prominently, cardiovascular disease and Type 2 Diabetes.  Like many diseases, metabolic syndrome is also known by other names such as syndrome x, insulin resistance syndrome and prediabetes. There are five physiological conditions that are used to identify Metabolic Syndrome but only three of them must be present at the same time for a confirmed diagnosis:

  • Abdominal obesity.
  • High blood pressure
  • Increased blood glucose due to insulin resistance
  • Elevated triglyceride levels
  • Low HDL levels (this is the good kind of fat that gets rid of bad fats)

Factors that favor metabolic syndrome development

The main factor is abdominal obesity as both a cause and a symptom. When excessive adipose tissue is accumulated in the abdomen with a correspondingly low abdominal muscle bulk, a high waist to hip ratio develops. The following contribute to metabolic syndrome:

  • Sedentarism
  • Age
  • Race
  • Lipodystrophy
  • Increased free fatty acids in the liver
  • A higher presence of fatty tissue in muscle cells
  • Insulin resistance sets in due to excess amounts of insulin in circulation (hyperinsulinemia)
  • Breakdown of glucose is impaired due to insulin resistance which increases the risk of diabetes type 2
  • Increase in the plasma levels of cholesterol and/or triglycerides.
  • Low levels of high-density lipoproteins (HDL, good cholesterol)
  • Atherosclerosis – fatty plaque deposits in the blood vessel walls. This reduces the size of the arterial lumen resulting in decreased blood flow.
  • Hypertension.
  • Hyperuricemia
  • Increased blood coagulation with arterial hyper-inflammation which further destroys the state of blood vessels

 

All about Metabolic Syndrome
The lipid overflow–ectopic fat model

 

“The lipid overflow–ectopic fat model. Excess visceral fat accumulation might be causally related to the features of insulin resistance, but might also be a marker of a dysfunctional adipose tissue being unable to appropriately store the energy excess. According to this model, the body’s ability to cope with the surplus of calories (resulting from excess caloric consumption, a sedentary lifestyle or, as is often the case, a combination of both factors) might, ultimately, determine the individual’s susceptibility to developing metabolic syndrome. There is evidence suggesting that if the extra energy is channeled into insulin-sensitive subcutaneous adipose tissue, the individual, although in positive energy balance, will be protected against the development of the metabolic syndrome. However, in cases in which adipose tissue is absent, deficient or insulin-resistant with a limited ability to store the energy excess, the triacylglycerol surplus will be deposited at undesirable sites such as the liver, the heart, the skeletal muscle and in visceral adipose tissue — a phenomenon described as ectopic fat deposition. Factors associated with a preferential accumulation of visceral fat and with features of insulin resistance include, among others, smoking, the well documented genetic susceptibility to visceral obesity and a neuroendocrine profile related to a maladaptive response to stress. The resulting metabolic consequences of this ‘defect’ in energy partitioning include visceral obesity, insulin resistance, atherogenic dyslipidemia, and a prothrombotic, inflammatory profile. These are defining features of metabolic syndrome. This constellation of abnormalities can be detected by the clinical criteria for metabolic syndrome, the two simplest being the simultaneous presence of increased waist girth and fasting triacylglycerol levels, a condition that has been described as ‘hypertriglyceridemic waist’.”3   

If not managed in time, metabolic syndrome can lead to chronic conditions such as:

  • Steatohepatitis (non-alcoholic) – Hepatic deposits of adipose tissue and liver inflammation. This condition can progress to become liver cirrhosis
  • Renal pathologies
  • Polycystic Ovarian Syndrome in women.
  • Sexual disorders in men
  • Low testosterone levels
  • Cardiovascular disease

In most cases, the symptoms seen are those of the complications of metabolic syndrome.

 

Factors contributing to global cardiometabolic risk
Factors contributing to global cardiometabolic risk

 

Factors contributing to global cardiometabolic risk

“Cardiometabolic risk is the overall risk of CVD (cardiovascular disease) resulting from the presence of metabolic syndrome but also of traditional risk factors such as lipids (LDL and HDL), hypertension, diabetes, age, male gender, smoking and other unknown risk factors (including genetic factors that cannot be assessed in clinical practice most of the time). According to this model, metabolic syndrome does not replace the need to assess global CVD risk, but may eventually have to be considered in global risk assessment. Whether metabolic syndrome is an independent factor that adds significantly to the global CVD risk as assessed with traditional risk factors is uncertain and much debated in the literature. The controversy over its added value is highlighted by the question mark.”4  

How is metabolic syndrome diagnosed?

The main diagnostic factor is the size of the waist. The risk differs in people of different races but a woman with central obesity and a waist above 28 inches is at risk. For men, the risk begins from a waist measuring 31 inches together with large abdominal fat deposits. Other considerations include:

  • History of blood glucose (fasting) level above 100 mg/dl
  • Blood pressure consistently higher than 130 mmHg/85 mmHg
  • Elevated triglyceride levels during fasting (above 150 mg/dl)
  • Levels of high-density lipoprotein (HDL) below 50 mg/dl in women

ATPIII (Adult Treatment Panel III) definition

“Any three or more of the following criteria:

  1. Waist circumference: >102 cm in men and >88 cm in women
  2. Serum triglycerides: >1.7 mmol/l
  3. Blood pressure: >130/85 mmHg
  4. HDL-cholesterol: <1.0 mmol/l in men and <1.3 mmol/l in women
  5. Serum glucose: >6.1 mmol/l (>5.6 mmol/l may be applicable)

WHO (World Health Organization) definition

Diabetes or IFG or IGT or insulin resistance (assessed by clamp studies), plus at least two of the following criteria:

  1. Waist-to-hip ratio >0.90 in men or >0.85 in women
  2. Serum triglycerides >1.7 mmol/l or HDL-cholesterol <0.9 mmol/l in men and <1.0 mmol/l in women
  3. Blood pressure >140/90 mmHg
  4. Urinary albumin excretion rate >20 μg/min or albumin: creatinine ratio >30 mg/g.”5

“Many investigations confirm that multiple cardiovascular risk factors of endogenous origin commonly aggregate in one individual. Although this aggregation was originally observed many years ago, more recently, several terms have been proposed to describe this clustering: metabolic syndrome, syndrome X, the “deadly quartet,” insulin-resistance syndrome and hypertriglyceridemic waist. The term metabolic syndrome is most commonly used in the cardiovascular field. Although the metabolic syndrome is often referred to as a discrete entity, it is important to recognize, as noted earlier, that it is a syndrome and not a defined uniform entity. No single pathogenesis has been elucidated, nor may one exist. Thus, the syndrome could range from a cluster of unrelated risk factors to a constellation of risk factors linked through a common underlying mechanism. From a clinical standpoint, presence of the metabolic syndrome identifies a person at increased risk for ASCVD (Atherosclerotic Cardiovascular Disease) and/or type 2 diabetes mellitus. Eventually, a better understanding of the specific cause(s) of the syndrome may provide an improved estimate of risk of developing ASCVD or type 2 diabetes mellitus for individuals. For now, however, the presence of the syndrome is a more general indicator of higher risk for these conditions. Because of a documented high relative risk for ASCVD events and type 2 diabetes mellitus, the metabolic syndrome undoubtedly carries a relatively high lifetime risk for these disorders even when shorter-term (10-year) risk is in the low-to-moderate range.”6  

Treatment of metabolic syndrome

There are two major ways of treating this condition:

Lifestyle changes

It is paramount to reduce the waistline by eliminating abdominal fat. Some of the ways to do this include:

  • Exercise and an active lifestyle. This will take you a long way on the road to recovering.
  • A healthy diet. – This, only when combined with an active lifestyle, is the most potent tool in your management/prevention arsenal.
  • Reduction of alcohol consumption
  • Cessation of smoking.

Medications

Appropriate drugs are given to treat problems accompanying the metabolic syndrome. Common ones used include:

  • Anti-insulin resistance medications such as metformin or drugs in the group of thiazolidinediones
  • Management of cardiovascular disorders. This includes medications for high blood pressure and others that lower the levels of triglycerides in the blood.

The treatment regime is determined by the presence of any other complication which must be managed independently in an effort to reverse metabolic syndrome.

“Once a diagnosis of the MetS (Metabolic Syndrome) is made, individuals should receive increased attention with the aim of reducing the risk for CVD (cardiovascular disease) and Type 2 diabetes. They should undergo a full cardiovascular risk assessment, which would include smoking status. Primary management for the MetS is healthy lifestyle promotion. This includes:

  • Moderate calorie restriction (to achieve a 5–10% loss of body weight in the first year)
  • Moderate increases in physical activity
  • Change dietary composition to reduce saturated fat and total intake, increase fiber and, if appropriate, reduce salt intake. 

“Whenever possible, a normal BMI and/or normal waist circumference ought to be a long-term target of lifestyle intervention. The results of the Finnish and American prevention of diabetes studies have, however, both shown the marked clinical benefits associated with a small weight loss in terms of preventing (or at least delaying by several years) the conversion to Type 2 diabetes among high-risk individuals with glucose intolerance who were, on average, obese. Moreover, observational studies have shown that moderate to vigorous physical activity for 180 min per week reduces the risk of the MetS (Metabolic Syndrome) by 50%—with more vigorous exercise only 60 min is needed. In addition, an improvement in all lipid parameters has been observed with increased physical activity. Similar clinical trial data showing the impact of exercise on the development of CVD (Cardiovascular Disease) and diabetes are, however, lacking for people presenting with MetS.”7 

 

References:

(1, 7) Metabolic syndrome—a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Alberti, M., Zimmet, P. & Shaw, J. Diabetic Medicine. 2006. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1464-5491.2006.01858.x 

(2, 3, 4) Abdominal obesity and metabolic syndrome. Després J.P. & Lemieux, I. Nature. 2006. https://www.researchgate.net/publication/6633458_Abdominal_obesity_and_metabolic_syndromeJ 

(5, 6) The metabolic syndrome: time for a critical appraisal. Kahn, R., Buse, J., Ferrannini, E. &  Stern, M. Diabetología. 2005. https://link.springer.com/article/10.1007/s00125-005-1876-2 

 

María Laura Márquez
13 October, 2018

Written by

María Laura Márquez, general doctor graduated from The University of Oriente in 2018, Venezuela. My interests in the world of medicine and science, is focused on surgery and its greatest advances. Nowadays I practice my...read more:

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