(A) Nutrition: its relevance in the development and treatment of the metabolic syndrome.

The metabolic syndrome is strongly associated with obesity, particularly if the adipose tissue has a central distribution. The prevalence of obesity has increased massively in the last few decades. Over this time, most people have been exposed to an energy dense food supply and decreasing levels of energy expenditure.

Nutritional factors leading to central obesity are complex and the total amount of energy consumed is more important than particular food types. Dietary patterns are associated with socioeconomic group, smoking, alcohol intake and physical activity. However, allowing for these factors, there is evidence that fat intake is positively associated with both BMI and a central distribution of fat, while carbohydrate intake is negatively associated with these factors and alcohol intake is weakly associated with central fat distribution.(1) Dietary factors are also related to features of the metabolic syndrome. A diet high in fruit, vegetables, fish, rice and pasta but low in fried foods, processed meats, potatoes and snack foods is associated with good glucose tolerance and a healthy lipid profile.(2) Diets high in cholesterol and saturated fats are associated with unfavourable lipid profiles and increased risk of coronary heart disease, while diets high in polyunsaturated fats are associated with a more favourable lipid profile and a reduced risk of coronary heart disease.(3) Impaired glucose tolerance and diabetes are more common in individuals who consume more alcohol.(2)

Weight loss is one of the cornerstones of management of the metabolic syndrome and type 2 diabetes. In this respect decreasing calorie intake while increasing energy expenditure is the general aim. This weight loss may be brought about by omitting snacks, having smaller portions and avoiding foods with high energy density in favour of more filling but lower calorie foods. Relatively modest reductions in weight (4-6 kg) can reduce the risk of developing diabetes in those at risk.(4), (5)

There is some evidence that specific dietary changes can have benefits in addition to weight loss alone. In the Finnish Diabetes Prevention Study, a higher consumption of dietary fibre and lower consumption of dietary fat had independent protective effects on the conversion from impaired glucose tolerance to diabetes.(4)

Diets with a high proportion of fat, particularly saturated fat, are associated with worse insulin sensitivity when total calorie intake is the same between groups.(6) Replacing dietary saturated fats with equal amounts of unsaturated fats lowers both LDL cholesterol and triglycerides in insulin resistant individuals. (7)

Diets high in carbohydrate can aggravate the dyslipidaemia associated with the metabolic syndrome.(8) However, the glycaemic index of carbohydrate is an important determinant of the insulin response and the metabolic consequences. Foods with a low glycaemic index as a result of slow digestion and absorption have much less of a dyslipidaemic effect.(8)

A recent study in Italy showed that for people with the metabolic syndrome, the adoption of a “Mediterranean diet” that contained whole grains, fruits, vegetables, nuts and olive oil over 2 years, reduced the prevalence of the metabolic syndrome as well as reducing hsCRP, IL-6, insulin resistance and improving endothelial function.(9)

(B) Exercise and energy expenditure in the metabolic syndrome

Like weight loss, the encouragement to increase levels of physical activity is paramount for patients with the metabolic syndrome.

Habitual physical activity is associated with lower systolic and diastolic blood pressure, proportional to the amount of exercise performed. (10) Hypertensive patients who performed moderate exercise 3 times a week decreased systolic and diastolic blood pressures by 6 and 9 mmHg after 3 months but this increased to 20 and 11 mmHg respectively after 9 months of exercise.(11)

Plasma concentration of HDL varies with the level of habitual physical activity such that very active people have high HDL while very inactive people have very low levels.(12) Cycling or jogging 3 times a week over 20 to 26 weeks has been found to reduce cholesterol by 14% and triglycerides by 34% while doubling HDL.(13)

Regular voluntary exercise improves insulin sensitivity and glucose tolerance. (14) For individuals with impaired glucose tolerance, regular exercise over 12 months can normalize glucose tolerance.(15) In people with diabetes, regular exercise, including walking, is associated with improved glucose tolerance, decreased insulin resistance and decreased HbA1c.(15), (16)

In addition to reducing cardiovascular risk factors, regular exercise has protective effects on the cardiovascular consequences of the metabolic syndrome. Men in the Honolulu heart study who walked less than 400 metres per day had twice the incidence of coronary heart disease as those who walked more than 2400 metres.(17) Walking more than 20 km per week decreased the risk of stroke by 29% compared to walking less than 5 km each week, independent of risk factors such as obesity, hypertension, diabetes mellitus, smoking and pre-existing ischaemic heart disease or stroke.(18) For women who already have type 2 diabetes, the risk of coronary heart disease was 51% lower and the risk of stroke 25% lower in those who spent 7 or more h each week in moderate to vigorous activities compared to those spending less than 1 h per week on these.(19)

(C) Medical treatments Although there is data on excess morbidity and mortality associated with the metabolic syndrome, at present there are no outcome studies for treating the metabolic syndrome. However, there is plenty of evidence for treating the individual components of the syndrome. Because insulin resistance and central obesity are the central components of the syndrome, lifestyle interventions lie at the heart of treatment. 20 weeks of supervised exercise training has been shown to decrease in the prevalence of the metabolic syndrome by 1/3.(20)

For subjects with abnormal glucose metabolism, there are several studies showing that lifestyle modification can decrease the rate of progression to diabetes. In the Finnish Diabetes Prevention Trial, lifestyle changes including weight loss of 4 kg over 3 years, 150 min of exercise per week, a low fat, high fibre diet and smoking cessation decreased the risk of diabetes by 58% compared to the control group.(4) The American Diabetes Prevention Program compared similar lifestyle modifications with a mean weight loss of 7% in the intervention group and found a similar reduction in the development of diabetes. (21) The Da Quing Diabetes prevention study, diet alone reduced the incidence of diabetes by 31%, exercise alone reduced the incidence of diabetes by 46% and the combination of both reduced the incidence by 42% suggesting exercise is the major component of benefit in lifestyle modification.(5)

Studies of drug intervention to prevent diabetes show less impressive reductions in diabetes incidence with orlistat reducing the incidence of diabetes by 37%, (22) acabose reduced the incidence by 36%, (23) metformin by 22% (21) and troglitazone by 50%.(24)

The dyslipidaemia associated with the metabolic syndrome of elevated triglycerides and low HDL-cholesterol is directly associated with BMI (25), (26) and thus weight loss is also important in the management of this. Furthermore, regular physical activity has been shown to decrease triglycerides and improve HDL-cholesterol. (20) However, the improvements in lipid profiles with lifestyle changes are less than that achieved with pharmacological methods. The most effective drugs to treat the dyslipidaemia of the metabolic syndrome are the fibrates and nicotinic acid derivatives in contrast to the use of statins as a first line treatment for elevated LDL cholesterol.

The fibrates work through activation of PPARnuclear receptors and can reduce triglyceride concentrations by up to 50% and increase HDL cholesterol by 15%.(27) Fibrates also have effects on low grade inflammation. Gemfibrozil use in patients with diabetes and low HDL has been shown to reduce the incidence of myocardial infarction and cardiac death from 10.5% to 3.4% over 5 years although this failed to reach statistical significance because of small numbers of patients with diabetes in the study.(28) Fenofibrate use in patients with diabetes has been shown to reduce the progression of coronary atherosclerosis. (29)

Nicotinic acid increases HDL-cholesterol by up to 30% and decreases triglycerides by up to 50%.(30) Although there have been 6 studies looking at cardiovascular endpoints for patients treated with nicotinic acid, only one used it as monotherapy although all showed reduction in risk for patients in the nicotinic acid groups.(31)

Lifestyle modifications, including decreasing salt intake, are recommended for the hypertension of the metabolic syndrome although antihypertensive drugs are usually required to control blood pressure. Angiotensin converting enzyme inhibitors and angiotensin II receptor blocking drugs are often the drugs of choice as in addition to their blood pressure lowering effect they can improve insulin sensitivity and decrease the rate of progression to diabetes by 14-34%.(32) Beta blockers and thiazide diuretics worsen insulin sensitivity, decrease HDL cholesterol and increase triglyceride concentrations.(33), (34)

Table 1:    Treatments, and associated references, to prevent complications of metabolic syndrome.

Prevention of NASH
Rosiglitazone (35)
Prevention of CVD
Statins (36-38)
Fibrates (39)
Exercise (17), (19)
Pioglitazone (40)
Fenofibrate (29)
Nicotinic acid (31)
Prevention of diabetes
Exercise (15)
Weight loss (4), (5)
Acabose (23)
Orlistat (23)
Metformin (21)
Troglitazone (24)

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