Box 1 The metabolic syndrome changes associated with insulin resistance

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Cigarette smoking Sedentary behavior


Increased free fatty acids Increased apolipoprotein B Decreased apolipoprotein A-1

Small, dense low-density lipoprotein and high-density lipoprotein Increased apolipoprotein C-III

Prothrombotic Increased fibrinogen

Increased plasminogen activator inhibitor 1 Increased viscosity

Inflammatory markers Increased white blood cell count Increased interleukin 6 Increased tumor necrosis factor Increased resistin Increased C-reactive protein Decreased adiponectin



Increased asymmetric dimethylarginine Increased uric acid Increased homocysteine

Adapted from Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005;365:1420.

Relationship of metabolic syndrome with cardiovascular disease, type 2 diabetes, and depression

The metabolic syndrome is associated with an increased risk of both diabetes and cardiovascular disease. This association is not surprising because the definition of the syndrome comprises established risk factors for diabetes and cardiovascular disease. For cardiovascular disease, the relative hazard ratios range from 2 to 5 [1]. The risk of diabetes is substantial also. The cumulative incidence of diabetes in subjects with impaired glucose tolerance (and obesity) who participated in the diabetes prevention studies was approximately 30% after 3 years of follow-up [4].

A large body of evidence supports an association between type 2 diabetes, cardiovascular disease, and, recently, metabolic syndrome and the occurrence of depression. Individuals who have diabetes are twice as likely to develop depression as individuals who do not have diabetes. Interestingly, one study indicated an increased risk of depression in type 2 diabetes only when comorbid cardiovascular diseases were present [5]. The prevalence of metabolic syndrome among women who have a history of depression is twice as high as that among women who have no history of depression [6]. If one accepts obesity as a surrogate marker of the metabolic syndrome, a potential gender difference may exist. In women in the United States, obesity increases the risk of being diagnosed with major depression by 37%, whereas obese men have a 37% lower risk of depression than men of normal weight [7]. Conversely, depression is associated with an increased incidence of diabetes, which in turn seems to be mediated largely through central adiposity [8]. When depression complicates diabetes, it is significantly associated with nonadherence to medication and self-care recommendations, poor metabolic control, and, thus, increased odds of having diabetic and cardiovascular complications (see the article by Egede in this issue).

Depressed patients who do not have overt diabetes also have an increased relative risk for developing cardiovascular complications that varies between 1.5 and 2.7 depending on the magnitude of depressive symptoms [9]. Notably, also in the absence of predefined psychiatric diagnoses as major depression, psychologic factors (especially when occurring in combination) result in an increased risk for cardiovascular complications are to the risks associated with hypercholesterolemia, hypertension, and other major risk factors [10,11].

Others have postulated that there might exist a subtype of vascular depression in which cerebrovascular disease predisposes, precipitates, or perpetuates a depressive syndrome [12].

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