Metabolic syndrome



Last Review Date: October 25, 2018


What is it?

Metabolic syndrome is a set of risk factors that includes: abdominal obesity, a decreased ability to process glucose (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 names (dysmetabolic syndrome, syndrome X, insulin resistance syndrome and obesity syndrome) but few outside the medical community have heard of it. Most patients have been educated about the importance of checking their cholesterol levels, watching for signs 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'.

According to the AusDiab Study which was reported in 2012 found that the prevalence of the metabolic syndrome was 31.0% in Australia with an annual rate of occurrence of new cases in 2.6% of men and 1.7% of women. The rate of occurrence of new cases of the metabolic syndrome between the ages of 25 and 64 was higher in men than in women. However, after the age of 65 years, the rate of occurrence of new cases of the metabolic syndrome was higher in women than in men. The rate of occurrence of new cases was found to increase with age and with increasing waist circumference.

Various diagnostic criteria have been proposed by different organizations over the past twenty years

The World Health Organization (WHO) was the first to publish an internationally accepted definition for metabolic syndrome in 1998. Subsequently a number of other groups produced their own slightly different definitions.
In order to provide more consistency in both patient care and research, the International Diabetes Federation,  The National Heart, Lung and Blood Institute (NHLBI), the American Heart Association (AHA), World Heart Federation, and the International Association for the Study of Obesity published a joint statement in 2009 that describes a "harmonized" definition of metabolic syndrome which is widely used in Australia. The presence of any 3 of 5 risk factors listed below constitutes a diagnosis of metabolic syndrome.

Table 1. Criteria for clinical diagnosis of the metabolic syndrome according to the Joint Statement on the metabolic syndrome.

  • Elevated waist circumference- Population and country specifics (see Table 2).
  • Raised triglycerides  ≥1.7mmol/L (≥ 150 mg/dL) (or drug treatment for elevated triglycerides)
  • Fasting triglycerides greater than or equal to 1.69 mmol/L (150 mg/dL)
  • Reduced HDL cholesterol <1.0mmol/L (<40mg/dL) in men, <1.3mmol/L (<50mg/dL) in women.
  • Elevated blood pressure (or drug treatment for hypertension) ≥ 130 systolic or ≥85 diastolic.
  • Elevated Fasting glucose (fasting plasma glucose) ≥5.6 mmol/L (≥100mg/dL) or previously diagnosedd type 2 diabetes.

Table 2
Recommended threshold in waist circumference for abdominal obesity (high risk) 3,4,5     
Population Men Women
European/North American ≥102 cm ≥88 cm
Asian ≥90 cm ≥80 cm
Central and South American ≥90 cm ≥80 cm
Middle Eastern/Mediterranean ≥94 cm ≥80 cm
Sub-Saharan African ≥94 cm ≥80 cm


Also frequently seen with metabolic syndrome are prothrombotic (blood clotting) and proinflammatory tendencies. While these combined criteria and risk factors do not usually cause symptoms that are obvious to the affected person, they 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 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 studied.

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, blood clots 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.
 

New References


1. (AusDiab) study - Baker Institute https://www.baker.edu.au/Assets/Files/Baker%20IDI%20Ausdiab%20Report_interactive_FINAL.pdf
2. Cameron AJ et al. The metabolic syndrome in Australia: prevalence using four definitions. Diabetes Res Clin Pract. 2007 Sep;77(3):471-8.
3. Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. Oct 20 2009;120(16):1640-1645
4. RACGP - The metabolic syndrome https://www.racgp.org.au/afp/2013/august/the-metabolic-syndrome/
5. World Health Organization. Obesity: preventing and managing the global epidemic. Report on an WHO consultation. Geneva: WHO, 2000.


Tests

A doctor may suspect that a patient has metabolic syndrome if he or she has central/abdominal obesity and a sedentary lifestyle, but both laboratory and non-laboratory tests are important in establishing the diagnosis. Recommended tests include:

Laboratory tests

  • Glucose Usually a fasting glucose test is performed but, in some cases, a doctor also may order GTT (glucose tolerance test – several glucose tests that are taken before and at timed intervals after a glucose challenge). The goal of glucose testing is to determine whether a patient has diabetes or an impaired response to glucose.
  • Lipid profile Measures HDL, LDL and triglycerides. If the triglycerides are significantly elevated, a DLDL (direct measurement of the LDL) may need to be done.
  • Haemoglobin A1c (HbA1c). This is a measure of glucose control and can be used for the diagnosis of diabetes.

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

  • C-peptide. This is a reliable indicator of endogenous (a person's own) insulin production.
  • Insulin: The fasting insulin test is considered too variable to be clinically useful in diagnosing metabolic syndrome but, if measured, will usually be elevated in those affected.
  • Albumin/creatinine ratio: An early indicator of kidney disease, this test is used to help monitor diabetics 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 cardiac risk.
  • sdLDL: This is a measurement of the number of smalll dense low-density lipoprotein molecules a person has. LDL varis in size, and the smaller denser molecules, which tend to form when elevated triglyerides and VLDL are present in the blood, are thought to be more aggressive in causing atherosclerosis. This test is performed as "LDL subclasses"assessment by electrophoresis. A Medicare rebate is available if Medicare criteria are met. These are cholestrol ≥6.5 mmol/L and triglyerides >4.0mmol/L or in the diagnosis of types III and IV hyperlipidemia.

Tests for which the clinical utility in diagnosing metabolic syndrome have 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 kilograms) / (height in metres squared).
    For example: (80 kg) / (1.7m X 1.7m) = a BMI of 27.7Kg/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.)

Treatment

The primary "treatment" for metabolic syndrome is "lifestyle modification" to correct obesity. Those affected should lose excess weight and exercise regularly. It is also advisable to stop smoling cigarettes.

 Weight loss and exercise can:

Drug treatment may be necessary to address hypertension and high cholesterol 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 other medical professionals, such as an accredited practising dietitian, to develop an individualised treatment plan and to monitor its effectiveness.


Additional details

Insulin is a hormone that allows 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). 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 create triglyceride-rich very low-density lipoproteins (VLDL). In the bloodstream, an enzyme removes triglycerides from VLDL to first create 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 oxidise 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 molecules are heterogeneous; they are produced in a variety of sizes. Small dense LDL (sdLDL) are thought to be more prone to collect and deposit 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. 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.


Related pages

On this site
Tests: hs-CRP, lipid profile, cholesterol, HDL, LDL, triglycerides, cardiac risk assessment, insulin, glucose and glucose tolerance test (GTT)
Conditions: Insulin resistance, hypertension, diabetes, cardiovascular disease.

Elsewhere on the web
Better Health Channel
Nutrition Australia
Virtual Medical Centre