This article was last reviewed on
This article waslast modified on
21 September 2017.
What is it?

Metabolic syndrome is a set of cardiovascular risk factors that includes: central abdominal obesity, a decreased ability to process glucose (increased blood glucose and/or insulin resistance), dyslipidaemia, and hypertension. Patients who have this syndrome have been shown to be at an increased risk of developing cardiovascular disease and/or type 2 diabetes. Metabolic syndrome is a common condition that goes by many other names (dysmetabolic syndrome, syndrome X, insulin resistance syndrome, obesity syndrome, and Reaven’s syndrome). Most people identified as having this syndrome have been educated about the importance of checking their lipid levels, watching for symptoms of diabetes, having their blood pressure monitored, and exercising – but there has been little to tie all of these factors together except pursuit of a "healthier lifestyle."  

It is estimated that around 25% of adults in the Western World have metabolic syndrome. It can affect anyone at any age, but it is most frequently seen in those who are significantly overweight - with most of their excess fat in the central abdominal area - and physically inactive.

While several national and international organisations use certain criteria to define metabolic syndrome, others, including the American Diabetes Association (ADA), question the value of the specific diagnosis of metabolic syndrome. They point out that the criteria, taken together, are no more useful at predicting risk of cardiovascular disease or diabetes than the individual criteria considered separately. The science needs to be clearer, suggests the ADA, before metabolic syndrome be considered a definable syndrome. There is therefore an ongoing debate about the scientific validity of the term ‘metabolic syndrome’. However, most clinicians are agreed that it is a clinically useful term as it alerts the clinic to the increased cardiovascular risk and risk of the patient developing diabetes.

The World Health Organization (WHO) was the first to publish an internationally accepted definition for metabolic syndrome in 1998, but the criteria that have received the most widespread acceptance and use in the United States are those established as guidelines in the ATP III (the third report of the National Cholesterol Education Program expert panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults).

The American Heart Association (AHA) in conjunction with the NHLBI also released a scientific statement regarding metabolic syndrome that includes a set of criteria that defines the condition. The table below summarizes the three sets of criteria:

Criteria for Clinical Diagnosis of Metabolic Syndrome

clinical measure WHO1 ATP III2 AHA/NHLBI3
Waist Circumference   ≥102 cm in men,
≥88 cm in women
Same as ATP III
BMI BMI >30 kg/m2    
Triglycerides ≥1.64mmol/L Same as WHO Same as WHO
HDL-C <0.9mmol/L in men,
<1.0mmol/L in women
<1.0mmol/L in men,
<1.2mmol/L in women
Same as ATP III
Blood Pressure ≥140/90 mm Hg ≥130/85 mm Hg Same as ATP III
Glucose IGT, IFG, or T2D Fasting >6.1mmol/L (IFG) Fasting >5.6mmol/L (IFG)
Insulin Resistance YES NO NO
Microalbuminuria YES NO NO
References:

1. Alberti KG, Zimmet PZ. Diabet Med 1998;15:539–553.

2. National Cholesterol Education Program (NCEP) Adult Treatment Panel III final report. Circulation 2002;106:3143–3421.

3. Grundy, SM, et al. Circulation 2005;112:2735–2752.

Notes: WHO requires insulin resistance plus two additional risk factors for diagnosis; ATP III requires three of five risk factors for diagnosis. AHA/NHLBI recommends that triglycerides, HDL-C, and blood pressure should be considered abnormal when drug treatment is prescribed.

Abbreviations: BMI=Body mass index; IGT=Impaired Glucose Tolerance; IFG=Impaired Fasting Glucose; T2D=Type 2 Diabetes

Adapted from: Pizzi, R.,  Agreeing to Disagree: ADA, AHA Publish Opposing Views on Metabolic Syndrome, Clincal Laboratory News, January 2006 Volume 32, No. 1

Also frequently seen with metabolic syndrome but not included in the ATP III criteria are pro-thrombotic (blood clotting) and pro-inflammatory tendencies. While overt disease symptoms may be absent, these features are a warning of an increased likelihood of clogged arteries, heart disease, stroke, diabetes, kidney disease, and even premature death. If left untreated, complications from diseases associated with untreated metabolic syndrome can develop in as few as 15 years. Those patients who have metabolic syndrome and also smoke tend to have an even poorer prognosis.

Another feature commonly present in metabolic syndrome but not included in the diagnostic criteria is hyperuricaemia (an increased level of uric acid in the blood). In many patients this does not cause any symptoms but excessive amounts of uric acid can be associated with gout.

The root cause of most cases of metabolic syndrome can be traced back to poor eating habits and a sedentary lifestyle. Some cases occur in those already diagnosed with hypertension and in those with poorly controlled diabetes; a few are thought to be linked to genetic factors that are still being researched.

All of the factors associated with metabolic syndrome are interrelated. Obesity and lack of exercise tend to lead to insulin resistance. Insulin resistance has a negative effect on lipid production, increasing VLDL (very low-density lipoprotein), LDL (low-density lipoprotein – the “bad” cholesterol), and triglyceride levels in the bloodstream and decreasing HDL (high-density lipoprotein – the “good” cholesterol). This can lead to fatty plaque deposits in the arteries which, over time, can lead to cardiovascular disease and strokes. Insulin resistance also leads to increased insulin and glucose levels in the blood. Excess insulin increases sodium retention by the kidneys, which increases blood pressure and can lead to hypertension. Chronically elevated glucose levels in turn damage blood vessels and organs, such as the kidneys.

 

Accordion Title
About Metabolic Syndrome
  • Tests

    A doctor may suspect that a patient has metabolic syndrome if he has central/abdominal obesity and a sedentary lifestyle. In order to make a diagnosis of metabolic syndrome the criteria in the above table must be met therefore both laboratory and non-laboratory tests are important in establishing the diagnosis. Recommended laboratory tests include:

    Laboratory Tests

    • Glucose. Usually a fasting glucose test is performed but, in some cases, a doctor may also order a post prandial glucose (after a meal) or a GTT (glucose tolerance test – several glucose tests that are taken before and at timed intervals after a glucose drink. The commonest form of the test involves a fasting level and another glucose level 2 hours after the glucose drink). The goal of glucose testing is to determine whether a patient has an impaired response to glucose resulting in elevated blood glucose concentrations.
    • Lipid profile. Measures total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. If the triglycerides are significantly elevated, a DLDL (direct measurement of the LDL cholesterol) may need to be done.

    There are other laboratory tests that are not recommended for diagnosing metabolic syndrome but that may requested by some doctors to provide additional information. They include:

    • C-peptide. A reliable indicator of endogenous (by the body itself) insulin production.
    • Urine albumin : creatinine ratio. An early indicator of kidney disease, this test is used to help monitor patients with diabetes and is recommended under the WHO criteria.
    • hs-CRP (highly sensitive C-reactive protein). A measure of low levels of inflammation that may be tested as part of an evaluation of cardiovascular risk. This test is not performed by many laboratories.
    • sdLDL. A measurement of the number of small dense LDL particles a patient has. LDL particles vary in size, and the smaller denser ones, which tend to form when elevated triglycerides and VLDL are present in the blood, are thought to be more aggressive in causing atherosclerosis. This test is not performed by many laboratories and is not requested frequently. Its ultimate clinical utility has yet to be determined. May be evaluated in a lipoprotein subfractionation test.
    • Insulin. The fasting insulin test is considered too variable to be clinically useful in diagnosing metabolic syndrome and is not currently recommended by guidelines for this purpose.  However, if measured it will usually be elevated in those affected.

    Tests for which the clinical utility in diagnosing metabolic syndrome has not yet been established include plasminogen activator inhibitor-1 (PAI-1) and proinsulin.

    Non-Laboratory Tests

    • Blood pressure. To check for hypertension
    • Weight and waist circumference. To document abdominal obesity
    • BMI (Body Mass Index). An alternate measure of obesity that is used by many doctors. It is calculated by taking: (Weight in pounds X 705) / (height in inches squared); for example: (150 pounds X 705) / (67 inches X 67 inches) = a BMI of 23.5. If you prefer to use kilograms for weight and metres for height BMI can be calculated by (weight in kilograms)/(height in metres squared); for example: (62kg)/(1.70m x 1.70m) = 21.5 kg/m2. An adult with a BMI greater than 30 kg/m2 is considered obese. This calculation does not, however, describe where the excess weight is on the body.

     

  • Treatments

    The primary “treatments” for metabolic syndrome are for patients to lose excess weight, exercise regularly, and stop smoking. Weight reduction and exercise can:

    Drug treatment may be necessary to address hypertension and high cholesterol and triglyceride levels. Some doctors also recommend aspirin to decrease the risk of clotting, and a few doctors prescribe medications to increase insulin sensitivity (although there is not widespread agreement on this).

    Patients with metabolic syndrome should work with their doctor and develop an individualised treatment plan and to monitor its effectiveness.

     

  • More details

    Insulin is a hormone that causes glucose to move into tissue cells, where is it is used for energy production. Insulin then prompts the liver to either store the remaining excess blood glucose as glycogen (for short-term energy storage) and/or to use it to produce fatty acids which then become triglycerides (fat). In patients with insulin resistance, additional insulin must be released by the pancreas to overcome the tissue cells' resistance and allow glucose to enter the cells. This resistance and response to resistance can lead to increased insulin and glucose concentrations in the bloodstream. Over time, increased glucose levels can harm blood vessels and organs such as the kidneys. Increased insulin levels can increase sodium retention by the kidneys, resulting in increases in blood pressure (which can lead to hypertension).

    The liver uses triglycerides, cholesterol, and protein to make triglyceride-rich very low-density lipoproteins (VLDL). In the bloodstream, an enzyme removes triglycerides from VLDL to first produce intermediate density lipoproteins (IDL) and then low-density lipoproteins (LDL - the "bad" cholesterol). LDL is not all bad; it is an essential part of lipid metabolism and is necessary for the integrity of cell walls and for sex hormone and steroid production. However, in excess, LDL can oxidize and accumulate, eventually leading to fatty deposits in artery walls and to hardening and scarring of the blood vessels (and to cardiovascular disease and blood clots).

    LDL particles are heterogeneous; they are produced in a variety of sizes. Small dense LDL (sdLDL) are thought to be more prone to have their cholesterol deposited in artery walls than their larger counterparts. In obese and/or insulin resistant patients, excessive amounts of VLDL and triglycerides remain in the blood stream and lead to increases in the number of sdLDL produced.

    High-density lipoprotein (HDL – the “good” cholesterol) ordinarily transports excess cholesterol from the tissues back to the liver. This is called reverse cholesterol transport. In the liver, the cholesterol is either recycled for future use or excreted into bile. HDL’s reverse transport is the only way that cells can get rid of excess cholesterol. It helps protect the arteries and, if there is enough HDL present, it can even reverse the build up of fatty plaques in the arteries. When there are excessive amounts of VLDL and triglyceride present, however, HDL concentrations in the blood decrease.