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Metabolic syndrome

Author: Dr Eugene Tan, Medical Registrar; Dr Amanda Oakley, Dermatologist; Waikato Hospital, Hamilton, New Zealand, 2008.


What is the metabolic syndrome?

Metabolic syndrome is the combination of obesity, hypertension, dyslipidaemia and insulin resistance. Metabolic syndrome results in a proinflammatory state. It at least doubles the chance of suffering from cardiovascular disease compared with the normal population. Those with metabolic syndrome have a 5 to 30 times greater chance of developing type 2 diabetes.

The metabolic syndrome is also known as syndrome X. This is not to be confused with the cardiac syndrome X, which refers to angina-like chest pain with normal coronary arteries.

According to a consensus statement published in 2009, the metabolic syndrome is present if a person has three or more of the five health problems listed in the table below.

1. High blood sugar
  • Glucose > 5.6mmol/L or >100mg/dL
  • Current drug treatment for diabetes
2. Reduced high density lipoprotein (HDL), so-called “good” cholesterol
  • HDL <1.0mmol/L or <40mg/dL (men)
  • HDL <1.3mmol/L or <50mg/dL (women)
  • Current treatment for reduced HDL cholesterol
3. High triglycerides
  • Triglycerides: >1.7mmol/L or 150mg/dL
  • Current treatment for elevated triglycerides
4. High blood pressure
  • Blood pressure >130/85
  • Current drug treatment for hypertension
5. Abdominal obesity
  • Waist circumference >102cm (men)
  • Waist circumference >88 cm (women)
  • Population- and country-specific variations

Metabolic syndrome is associated with:

  • Raised C-reactive protein (CRP), interleukin 6 (IL–6) and tumour necrosis factor-alpha (TNFα), reflecting inflammation
  • Raised fibrinogen or plasminogen activator inhibitor-1, which may result in blood clots
  • Fatty liver, which may progress to non-alcoholic cirrhosis
  • Gallstones
  • Protein in the urine, due to kidney damage
  • Elevated uric acid levels from dietary sugars, which may lead to gout
  • Haemochromatosis (iron overload)
  • Obstructive sleep apnoea
  • Polycystic ovary syndrome
  • Dementia with aging, and cognitive decline in the elderly.

The greater the number of risk factors, the greater the chance of developing heart disease, diabetes, or stroke. The risk for heart disease is also increased by raised high low-density lipoprotein (LDL) cholesterol, so-called “bad” cholesterol, and by smoking, but these factors are not part of metabolic syndrome.

What causes metabolic syndrome?

Important factors contributing to metabolic syndrome include:

  • Genetic predisposition
  • Ageing ie, men over 45 and post-menopausal women
  • Hormonal imbalance
  • Physical inactivity
  • Excessive carbohydrates in the diet
  • Certain medications that contribute to weight increase eg, antidepressants
  • Rarely, congenital lipodystrophy

It is slightly more common in those on an alcohol-free diet.

Metabolic syndrome is present in about 5% of people with normal body weight, 22% of those who are overweight, and 60% of those considered obese. Obesity is a major risk factor for developing metabolic syndrome.

What does it mean to be insulin resistant?

Insulin is a hormone that transfers glucose (sugar) out of the bloodstream into the muscle, fat and liver cells. It is required to store glucose for future energy needs. Low insulin levels result in raised blood glucose. High insulin levels are proinflammatory.

Insulin resistance is defined as a subnormal response to insulin, in which the body cells resist its effects. Blood glucose may be high despite normal or increased amounts of insulin. Insulin resistance may be subclinical (where the patient does not have symptoms or signs) or result in overt type 2 diabetes.

There is debate regarding whether insulin resistance is the cause of the metabolic syndrome or a consequence of it.

In the earliest stage, insulin resistance can only be detected with the euglycaemic insulin clamp technique which is considered as the gold standard. This involves measuring insulin-induced glucose uptake whilst the blood glucose concentration is maintained at a steady concentration (via glucose infusion). However, this technique is impractical in everyday clinical practice. Raised blood sugar levels can be detected as insulin resistance increases.

Type 2 diabetes usually appears in adults over the age of 45 years, but may arise earlier in those with metabolic syndrome.

In contrast, type 1 diabetes usually begins in children and young adults. It often results from progressive destruction of insulin-producing cells in the pancreas by antibodies, and is not caused by insulin resistance. It is also associated with genetic factors but is not related to body fat or activity.

Why is waist circumference important?

Abdominal obesity is associated with metabolic syndrome and cardiovascular problems rather than accumulated fat in the buttocks and thighs. Hence the “apple-shaped” body is more likely to develop cardiovascular disease than the “pear-shaped” body.

In clinical practice, the waist to hip ratio is used to diagnose abdominal obesity, and appears to be more important than the body mass index (BMI).

Asian Indians have more abdominal fat than caucasians and blacks, due to β3-adrenergic receptor polymorphism. Women tend to have fat distributed on buttocks and thighs, due to oestrogen. This is protective.

The lipotoxicity theory

Fat stored in the abdominal region is more likely than fat in other sites to break down into free fatty acids (lipolysis), which get deposited in the liver. These fat cells produce pro-inflammatory cytokines including TNFα, which induce insulin resistance.

Saturated fats, sugars, and fast digesting starches (carbohydrates) in the diet increase the blood levels of triglycerides, which induce fat to be laid down. So the most obvious way to prevent metabolic syndrome is to reduce the intake of saturated fats, sugars and other carbohydrates.

Skin manifestations of the metabolic syndrome

Skin problems are common in patients with metabolic syndrome, associated with obesity, diabetes, hyperlipidaemia, and chronic inflammation.


Obese patients are prone to rashes in body folds (intertrigo) due to sweating, occlusion, the skin surfaces rubbing together, and inverse psoriasis. Adipose tissue increases the production of male hormones (androgens) and obese patients are also at greater risk of polycystic ovarian syndrome.

Skin infections
Altered collagen structure and function
Polycystic ovary syndrome
Mechanical factors

Diabetes / insulin resistance

High blood glucose levels result in infections, nerve damage and poor wound healing. Excess insulin causes the skin cells to grow abnormally.

Nerve damage
Poor wound healing
Circulating growth factors


There is a higher prevalence of psoriasis amongst obese patients than the general population; there is twice the risk of psoriasis in patients with BMI > 35 compared to those of normal weight. This is thought to be due to the chronic inflammation associated with metabolic syndrome and driven by excessive levels of insulin.

  • Cytokines including TNFα promote psoriasis
  • Insulin resistance induces growth factors
  • Persistent intertrigo may lead to flexural psoriasis

Obese patients with psoriasis have greater morbidity compared with those of normal weight.

  • The psoriasis tends to be more severe
  • It is more resistant to treatment
  • Sweating makes the plaques more uncomfortable
  • Treatment expenses are greater
  • Ointments may be difficult to apply
  • Phototherapy is more likely to result in burns as the lamps are closer to the skin surface

Weight loss and medications for diabetes have been shown to improve psoriasis in these patients.

Why is it important to treat the metabolic syndrome?

Early treatment of metabolic syndrome reduces the risk of developing type 2 diabetes and/or cardiovascular disease.

If type 2 diabetes and/or cardiovascular disease have already developed, aggressive lifestyle modifications improve the outlook.

How is metabolic syndrome treated?

The first line treatment is change of lifestyle but drug treatment is frequently required.

Lifestyle changes

Lifestyle changes are required lifelong. They may include:

  • Low calorie diet (800-1200kcal/day) to reduce weight and achieve desirable weight (BMI less than 25 kg/m2)
  • Healthy eating habits: low intake of sugars, high-glycaemic index carbohydrates, saturated fat and trans fat
  • Physical activity: at least 30 minutes of moderate-intensity activity on most days of the week
  • Stopping smoking

A healthy weight loss is 0.5 kg to 1.0 kg a week. Amounts greater than this often involves loss of body water instead of fat. A dietician is important to provide advice on regular meal times, the avoidance of snacking, reducing portion size, and identifying foods that are high in energy. Fad diets are generally avoided as they work in the short term but lack the compliance for the long term.

A detailed discussion of diet therapies, pros and cons of various diets is beyond the scope of this article. However, there is now a trend toward the use of a Mediterranean diet – one that is rich in “good” fats (olive oil) and contains a reasonable amount of carbohydrates and proteins (such as from fish and chicken).

The Mediterranean diet is palatable and easily sustained. In addition, recent studies have shown that when compared to a low fat diet, people on the Mediterranean diet have a greater decrease in body weight, and also had greater improvements in blood pressure, cholesterol levels, and other markers of heart disease.

Exercise has been shown to be of benefit regardless of whether weight loss is achieved or not:

  • Lowers blood pressure
  • Reduces total cholesterol and improved LDL/HDL cholesterol ratio
  • Lowers triglyceride levels
  • Improves insulin sensitivity.

The aim is to increase energy expenditure. This can be by avoiding sitting down (less television) as well as by deliberate visits to a personal trainer at a gym, or by walking, running, or participating in sports.

Drug treatment

Drug treatment may include:

  • Statins to raise HDL and reduce triglyceride and LDL cholesterol levels
  • Diuretics and ACE inhibitors to reduce blood pressure below 130/80
  • Antidiabetic agents to reduce glucose levels
  • Drugs to assist with weight loss.

The aim of prescribing cholesterol lowering agents is primarily to reduce the LDL cholesterol. Lower triglycerides and higher HDL cholesterol are expected benefits as well.

ACE inhibitors have also been shown to reduce the levels of insulin resistance and actually deter the development of type 2 diabetes.

Metformin and thiazolidinediones (eg, pioglitazone) are used to reduce blood sugar in type 2 diabetes. They also decrease insulin resistance and may prevent the onset of diabetes in people with metabolic syndrome although their use for this is controversial. Thiazolidinediones also reduce the thickness of the walls of the carotid arteries (the blood vessels supplying the brain), reducing the risk of stroke.

The role of vitamin D

Vitamin D normally helps maintain adequate insulin levels. It also reduces cell proliferation (particularly in the skin) and has immunosuppressive effects.

Vitamin D deficiency is common in obese individuals and in those with metabolic syndrome. This is because fat retains vitamin D and because obese patients tend to have less sun exposure. In these patients, vitamin D supplements may be helpful.

  • Insulin levels may increase, reducing blood sugar in diabetics
  • HDL cholesterol levels may increase
  • Blood pressure may reduce
  • Heart disease may improve
  • Psoriasis may improve


Surgery such as laporascopic banding of the stomach may be offered to well-motivated morbidly obese patients with a BMI >40 kg/m2. These patient are at high risk of surgical complications. However, weight loss may be dramatic after surgery resulting in marked improvement in diabetes, hypertension, hyperlipidemia, and obstructive sleep apnoea.

Cosmetic surgery including tummy tuck (abdominoplasty) and liposuction may be performed to reduce sagging skin and achieve a smooth, firm contour. Best results are seen in those who are in good health and have reached target weight. Unfortunately, removal of large amounts of abdominal fat does not seem to improve insulin sensitivity, blood pressure, or cholesterol.

Maintaining weight loss

The final step of treatment involves maintenance of weight loss. See your health professional(s) regularly.



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