Procoagulant Activity

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There is evidence that impaired fibrinolysis and a hypercoaguable state are associated with insulin resistance/hyperinsulinemia.

1. Plasminogen Activator Inhibitor-1 (PAI-1)

PAI concentrations are higher in patients with hypertriglyceridemia, hypertension, and CHD, suggesting that PAI-1 concentrations are related to insulin resistance and/or compensatory hyperinsulinemia. Epidemiological evidence in sup- -o port of this view comes from the European Concerted Action on Thrombosis and | Disabilities Angina Pectoris Study, indicating that PAI-1 concentrations were S significantly associated with hyperinsulinemia, hypertriglyceridemia, and hypertension in 1500 patients with angina pectoris. Furthermore, insulin-resistant/ <j hyperinsulinemic women have a higher PAI-1 concentrations, associated with J| higher TG and lower HDL cholesterol concentrations, than insulin-sensitive women matched for age, body mass index, and abdominal obesity. Thus, high concentrations of PAI-1 are another manifestation of syndrome X. |

2. Fibrinogen

Elevated fibrinogen levels have also been postulated to be part of the syndrome X cluster, but the evidence is not as strong as the case of PAI-1. Although insulin resistance and fibrinogen levels have been shown to be correlated, the relationship, in this case, may not be an independent one, but rather the manifestation of an acute phase reaction in patients with CHD.

F. Reproductive System

Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality in premenopausal women, and insulin resistance and compensatory hyperinsuli-nemia play a fundamental role in the etiology of this syndrome. This is another example of an organ, in this case the ovary, responding normally to hyperinsuli-nemia by increasing testosterone secretion in the face of muscle and adipose tissue insulin resistance. Indeed, in this instance, the ovary may be supersensitive to insulin stimulation. In any event, the primary clinical manifestations of PCOS (hirsutism, abnormal menstruation, and difficulty in conceiving) are secondary to increased insulin-stimulated testosterone secretion by the ovary. Women with PCOS are at increased risk to develop both type 2 diabetes and the dyslipidemia of syndrome X. Both of these changes suggest that insulin-resistant and hyperin-sulinemic women with PCOS will be at increased risk of CHD, and there is now evidence of enhanced atherogenesis in middle-aged women with PCOS.

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