title: Fibrinogen is a marker for nephropathy and peripheral vascular disease in type 1 diabetes: studies of plasma fibrinogen and fibrinogen gene polymorphism in the DCCT/EDIC cohort.
abstract: We examined whether plasma fibrinogen levels and the beta-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 beta-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.
authors.affiliation: Division of Endocrinology, Metabolism, and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston 29425, USA. kleinrl@musc.edu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Klein
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hunter
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Jenkins
authors.forename: Deyi
authors.initials: D
authors.lastname: Zheng
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Semler
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clore
authors.forename: W Timothy
authors.initials: WT
authors.lastname: Garvey
mesh_terms: D000225:Adenine; D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000235:genetics; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000097:blood / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000097:blood; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000235:genetics*; D006147:Guanine; D006801:Humans; D008297:Male; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012044:Regression Analysis
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D006147:Guanine; D005340:Fibrinogen; D000225:Adenine