Klein Richard L, Hunter Steven J, Jenkins Alicia J, Zheng Deyi, Semler Andrea J, Clore Jennifer, Garvey W Timothy
Division of Endocrinology, Metabolism, and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston 29425, USA.
Diabetes Care. 2003 May;26(5):1439-48. doi: 10.2337/diacare.26.5.1439.
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.
我们在参与糖尿病控制与并发症试验/糖尿病干预与并发症流行病学研究（DCCT/EDIC）的909例1型糖尿病患者中，研究血浆纤维蛋白原水平及β - 纤维蛋白原基因G(-455)→A多态性与微血管或大血管疾病是否相关。单因素回归分析显示，在所有患者中，纤维蛋白原水平与体重指数（r = 0.15；P < 0.0001）、糖化血红蛋白（r = 0.11；P = 0.0014）、总胆固醇（r = 0.17；P < 0.0001）及低密度脂蛋白胆固醇（r = 0.16；P < 0.0001）相关。在男性而非女性中，腰臀比（r = 0.20；P < 0.0001）和甘油三酯（r = 0.13；P = 0.0047）也成为纤维蛋白原水平的有力预测指标；在女性而非男性中，纤维蛋白原与舒张压（r = 0.16；P = 0.0011）和收缩压（r = 0.11；P = 0.0241）均相关。纤维蛋白原在男性中与尿白蛋白排泄率相关（r = 0.13；P = 0.0033），但在女性中无此关联。然而，在两性中，与排泄正常或微量白蛋白尿的患者相比，蛋白尿（白蛋白排泄>300 mg/24 h）的发生伴随着血浆纤维蛋白原增加1.5倍。此外，高纤维蛋白原水平与女性较低的平均踝臂指数相关（r = -0.13；P = 0.0075），但与男性无关。多因素回归分析表明，血浆纤维蛋白原在男性中与高白蛋白排泄率独立相关，在女性中与低平均踝臂指数独立相关。纤维蛋白原与视网膜病变的严重程度无关。颈动脉内膜中层厚度与纤维蛋白原无关，β - 纤维蛋白原基因5'启动子区域的G(-455)→A多态性不影响循环纤维蛋白原水平。然而，较常见的G(-455)等位基因的存在与颈内动脉内膜中层厚度增加相关（协方差分析P = 0.045）。最后，1型糖尿病中的高纤维蛋白原血症与胰岛素抵抗综合征特征簇的组分相关，且这种关联受性别影响。
