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Thursday, 17. May 2012

Diabetes mellitus and metabolic syndrome: special categories of high risk


Pathophysiology of the metabolic syndrome

Insulin resistance plays a central role in the metabolic syndrome and is associated with atherogenic dyslipidemia and with hyperglycemia leading to diabetes and hypertension1. With introduction of the NCEP ATP III clinical criteria of the metabolic syndrome, a cluster of abnormalities that were initially defined on the basis of pathophysiology (insulin resistance) was developed into an operational definition to facilitate clinical diagnosis. Thus, while the NCEP ATP III or the IDF criteria are helpful in identifying a group of individuals likely to be insulin resistant, not every patient with a clinical diagnosis of the metabolic syndrome is insulin resistant.2

There is substantial evidence that the pathophysiology of insulin resistance is linked to an impairment in the metabolism of free fatty acids.3-5 Obesity, especially abdominal obesity associated with an excess of visceral adipose tissue and with ectopic fat deposition in the liver, heart, skeletal muscle and pancreas, is not only associated with insulin resistance and impaired free fatty acid metabolism, but also with inflammation and an altered production of adiponectin.6 On that basis, it has been proposed that the most prevalent form of the metabolic syndrome is associated with a dysfunctional and insulinresistant adipose tissue and with an altered production of inflammatory cytokines and adipokines. Visceral obesity and ectopic fat deposition are therefore frequent partners of insulin resistance and of the metabolic syndrome, although the respective roles of these two factors are not yet clear.

Prevalence of metabolic syndrome according to age

Irrespective of the clinical criteria used, the prevalence of the metabolic syndrome increases with age. This phenomenon might be explained by the sedentary lifestyle habits of older individuals and their consumption of an energy-dense diet that contributes to a positive energy balance, weight gain and abdominal obesity.

Influence of metabolic syndrome on risk of MI

Meta-analyses and several reviews have concluded that a clinical diagnosis of metabolic syndrome approximately doubles the risk of CHD. Essentially, the risk of developing all manifestations of CVD is increased by the metabolic syndrome.7,8 Metabolic syndrome is highly prevalent among individuals who suffer an MI, in whom it is associated with lower survival rates9. To reduce cardiovascular mortality, it is therefore of primary importance to prevent the development of the metabolic syndrome. If present in a patient who has experienced an acute coronary event, vigorous treatment of existing cardiovascular risk factors and weight loss are recommended on the basis of indirect evidence, although no trial has yet shown that reducing weight and intra-abdominal fat improve short- and long-term survival of patients who have had an acute coronary event.

Reducing coronary risk in patients with diabetes mellitus and impaired glucose tolerance or impaired fasting glucose

Because of the increased CVD risk of patients with diabetes and the metabolic syndrome, all risk factors in such patients should be treated vigorously.10-12 Studies have shown the benefits of statin therapy13-16 and of lowering blood pressure.17,18 In addition, because the most prevalent form of the metabolic syndrome is abdominal obesity, weight loss (which leads to a selective loss of visceral fat19) should be promoted by a lifestyle modification program that incorporates healthy eating and more physical activity. Such a program has been shown to reduce substantially the risk of developing type 2 diabetes among high-risk prediabetic subjects who were abdominally obese.20,21

 

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