Practice guideline
The Aim

Primary and secondary prevention of type 2 diabetes, cardiovascular disease (hypertension, coronary heart disease, stroke, intermittent claudication), and possibly also Alzheimer's disease

Definition of Metabolic Syndrome (MBS)

MBS is a clustering of risk factors for type 2 diabetes and cardiovascular diseases. The risk factors are associated with obesity, insulin resistance, endothelial dysfunction, and possibly with cellular membrane disruption (Reaven, 1988; Laakso, 1993).
The clustering of risk factors results in a higher risk of type 2 diabetes and cardiovascular disease than would be estimated if each individual factor were taken into account separately (Tuomilehto et al., 2001; McNeil et al., 2005) Insulin resistance associated with obesity, plays an important role in the accumulation of the components of MBS in any one individual.
In insulin resistance, the biological response to insulin is impaired in the adipose tissues, muscles, the liver, and possibly the brain. The core abnormality of the syndrome includes the clustering of insulin resistance, compensatory hyperinsulinaemia, and dyslipidaemia in an obese hypertensive.
MBS is usually evident from truncal obesity which can be detected in clinical practice by measuring the circumference of the waist. MBS is rare in slim individuals (Vanhala et al., 1998).
The presence of MBS may be detected through medical history, anthropometry, blood pressure readings and by measuring
Lipid values
Blood or plasma glucose (glucose tolerance test or postprandial glucose if fasting glucose is normal).

The Diagnosis of MBS

According to the International Diabetes Federation (IDF) consensus 2005, the diagnostic criteria of MBS are:
Central obesity, defined as waist circumference of >94 cm for Europid men and >80 cm for Europid women PLUS
At least two of the following factors:
Increased serum triglyceride level: fasting value >1.70 mmol/L, or specific treatment for this lipid abnormality
Reduced serum high-density lipoprotein (HDL)-cholesterol: fasting concentration <1.03>130 mmHg or diastolic BP >85 mmHg, or treatment of previously diagnosed hypertension
Increased fasting plasma glucose: >5.6 mmol/L, or previously diagnosed type 2 diabetes. If the value is above 5.6 mmol/L, oral glucose tolerance test is strongly recommended but is not necessary to define the presence of the syndrome.
Other important signs and clinical findings supporting the diagnosis include:
Familial component: first-degree relative with type 2 diabetes
Obesity: body-mass-index (BMI) >30 kg/m2. For calculation see programme 1 included in the original guideline document.
Abnormal glucose tolerance test result: impaired glucose tolerance (IGT) or type 2 diabetes (NIDDM= non-insulin-dependent diabetes mellitus) according to World Health Organization [WHO] criteria)
Hyperuricaemia: fasting serum urate >450 micromoles/L in men, >340 micromoles/L in women
Microalbuminuria: urine albumin >20 milligrams/24 hours
Hyperinsulinaemia: fasting plasma insulin >78 pmol/L (>13.0 mU/L)
Alzheimer's disease, depression, and sleep apnoea may also be associated with MBS.

Prevalence

According to the IDF criteria, the prevalence of MBS in a middle-aged population is 38% for men and 34% for women (Alexander et al., 2003).
About one half of hypertensive patients are hyperinsulinaemic and/or have insulin resistance (Reaven, Lithell, & Landsberg, 1989). In Finnish population, almost half of hypertensive patients fulfill the criteria for MBS (Vanhala et al., 1997).

Treatment

The treatment is principally non-pharmacological and based on lifestyle changes. This approach has been shown to have an excellent effect, for example in the prevention of diabetes (DPS Study) (Tuomilehto et al., 2001; Knowler et al., 2002) [A].
Lifestyle changes are the only treatment form which have an effect on all the components of MBS, and not employing this treatment should be considered ethically wrong.

Non-Pharmacological Treatment
Increasing physical activity
Weight reduction
Dietary changes: increased intake of fibre and decreased intake of fat (particularly saturated fat) and rapidly metabolised carbohydrates (highly refined); salt restriction
Cessation of smoking
Limit alcohol intake to a moderate level
Drug Treatment
Drug treatment encompassing the entire MBS does not exist, and treatment should therefore consist of the management of the individual components of the syndrome.
Unless contraindicated, all patients with MBS should be prescribed low dose aspirin.
The treatment of hypertension in a patient with MBS should not contain drugs that worsen insulin resistance, such as non-selective beta-blockers and high-dose diuretics, unless other reasons (secondary prevention of myocardial infarction) warrant their use. The first-line drugs for the treatment of hypertension are:
Angiotensin-converting enzyme (ACE) inhibitors
Angiotensin-II receptor antagonists (losartan, valsartan, eprosartan, candesartan)
Alpha1 receptor blockers
Calcium-channel blockers
Highly selective beta-blockers

Dyslipidaemia in a patient with MBS should principally be treated with statins bearing in mind that the patient has a high risk of coronary artery disease.

Hypertriglyceridaemia should be treated with fibrates if, in spite of non-pharmacological treatment, the triglyceride values are persistently >5.0 mmol/L. Hypertriglyceridaemia in a patient with MBS should be treated medically (statin or fibrate) if the level of triglycerides is >2.30 mmol/L and total-cholesterol/HDL-cholesterol ratio is higher than 5 or if HDL-cholesterol is lower than 0.9 mmol/L.

Dysglycaemia in a patient with MBS should be treated with metformin or thiazolidine derivatives (pioglitazone or rosiglitazone) since these will not only improve the dysglycaemia but will also have an effect on the other components of the MBS. Insulin may also be used for the treatment of dysglycaemia in a MBS patient to achieve good diabetic control.

Biguanides, acarbose, and guar gum may correct insulin resistance and are thus feasible as a first-line drug for an obese patient with type 2 diabetes.

Orlistat or sibutramine may be indicated in MBS if the BMI is >30 kg/m2. These are anti-obesity drugs that also reduce the amount of visceral fat, in particular. However, the new endocannabinoid-receptor blockers are likely to provide the best benefit among pharmacotherapeutic alternatives. Rimonabant is an example of these drugs, and it has a positive effect on almost all the components of MBS.

Rimonabant should not be prescribed if the patient is concurrently in severe depression. It should be prescribed with caution and the patient should be carefully followed up if he/she has a history of depression.

Follow-up of a Patient with MBS

Motivation and monitoring of lifestyle changes is of the utmost importance.

The monitoring of a patient who requires drug treatment is the responsibility of a doctor. Regular appointments may often act as an important motivator.

The monitoring of a patient who does not require drug treatment may be carried out by a practice nurse. The following should be included in the follow-up: motivation of lifestyle changes, weight and waist circumference measurements, blood pressure readings, and checking of blood lipids and fasting blood glucose. A doctor should be consulted if:
Blood pressure repeatedly >140 mmHg and/or >90 mmHg
Total cholesterol: HDL-cholesterol ratio >5
Triglyceride values repeatedly >2.30 mmol/L
Plasma glucose is >7.8 mmol/L (fasting plasma glucose is >6.7 mmol/L
The patient develops symptoms of another illness (gout, etc.)

reference
Finnish Medical Society Duodecim. Metabolic syndrome. In: EBM Guidelines. Evidence-Based Medicine [Internet]. Helsinki, Finland: Wiley Interscience. John Wiley & Sons; 2007 Dec 13 [Various].