We examined whether plasma fibrinogen levels and the ␤-fibrinogen gene G Ϫ455 3 A polymorphism were related to microvascular or macrovascular disease in patients (n ϭ 909) with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC). Univariate regression showed that fibrinogen levels were correlated with BMI (r ϭ 0.15; P Ͻ 0.0001), HbA 1c (r ϭ 0.11; P ϭ 0.0014), total cholesterol (r ϭ 0.17; P Ͻ 0.0001), and

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... DL cholesterol (r ϭ 0.16; P Ͻ 0.0001) in all patients. In men, but not women, waist-to-hip ratio (r ϭ 0.20; P Ͻ 0.0001) and triglycerides (r ϭ 0.13; P ϭ 0.0047) also became powerful predictors of fibrinogen level; in women, but not men, fibrinogen was correlated with both diastolic (r ϭ 0.16; P ϭ 0.0011) and systolic (r ϭ 0.11; P ϭ 0.0241) blood pressure. Fibrinogen was correlated with urinary albumin excretion rates in men (r ϭ 0.13; P ϭ 0.0033), but not in women. In both sexes, however, the development of proteinuria (albumin excretion Ͼ300 mg/24 h) was accompanied by 1.5-fold increment in plasma fibrinogen compared with patients with normal excretion or microalbuminuria. In addition, high fibrinogen levels were associated with a lower average ankle-brachial index in women (r ϭ Ϫ0.13; P ϭ 0.0075), but not men. Multiple regression analyses demonstrated that plasma fibrinogen was independently correlated with high albumin excretion rate in men, and with low average ankle-brachial index in women. Fibrinogen was not correlated with the severity of retinopathy. Carotid artery intima-medial thickness was not correlated with fibrinogen, and the G Ϫ455 3 A polymorphism in the 5Ј promoter region of the ␤-fibrinogen gene did not influence circulating fibrinogen levels. However, the presence of the more common G Ϫ455 allele was associated with greater intima-medial thickness in the internal carotid artery (ANCOVA P ϭ 0.045). Last, hyperfibrinogenemia in type 1 diabetes is associated with components of the insulin resistance syndrome trait cluster, and the association is influenced by sex.