Fibrinogen Is a Marker for Nephropathy and Peripheral Vascular Disease in Type 1 Diabetes

Abstract

ABSTRACT— We examined whether plasma fibrinogen levels and the β-fibrinogen gene G⁻⁴⁵⁵→A polymorphism were related to microvascular or macrovascular disease in patients (n = 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 = 0.15; P < 0.0001), HbA_1c (r = 0.11; P = 0.0014), total cholesterol (r = 0.17; P < 0.0001), and LDL cholesterol (r = 0.16; P < 0.0001) in all patients. In men, but not women, waist-to-hip ratio (r = 0.20; P < 0.0001) and triglycerides (r = 0.13; P = 0.0047) also became powerful predictors of fibrinogen level; in women, but not men, fibrinogen was correlated with both diastolic (r = 0.16; P = 0.0011) and systolic (r = 0.11; P = 0.0241) blood pressure. Fibrinogen was correlated with urinary albumin excretion rates in men (r = 0.13; P = 0.0033), but not in women. In both sexes, however, the development of proteinuria (albumin excretion >300 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 = −0.13; P = 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⁻⁴⁵⁵→A polymorphism in the 5′ promoter region of the β-fibrinogen gene did not influence circulating fibrinogen levels. However, the presence of the more common G⁻⁴⁵⁵ allele was associated with greater intima-medial thickness in the internal carotid artery (ANCOVA P = 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.