Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes - The insulin resistance atherosclerosis study
Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes - The insulin resistance atherosclerosis study
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DOI：
10.2337/diabetes.51.4.1131
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发表时间：
2002-04-01
期刊：
影响因子：
7.7
通讯作者：
Haffner, SM
中科院分区：
文献类型：
--
作者：
Festa, A;D'Agostino, R;Haffner, SM
急性时相蛋白的血清水平升高，表明慢性亚临床炎症，与心血管疾病以及胰岛素抵抗综合征有关。慢性炎症也可能是发展2型糖尿病的危险因素。我们在胰岛素抵抗动脉粥样硬化研究中，研究了1,047名非糖尿病受试者的C反应蛋白（CRP）、纤维蛋白原和纤溶酶原激活物抑制剂-1（派-1）浓度与5年内发生糖尿病的关系。随访时糖尿病受试者（n = 144）的纤维蛋白原基线水平较高（平均SD; 287.8 ± 58.8 vs. 275.1 ± 56.0 mg/dl; P = 0.013）以及CRP（中位数[四分位距]; 2.40 [1.29，5.87] vs. 1.67 mg/l [0.75，3.41];P = 0.0001）和派-1（24 [15，37.5] vs. 16 ng/ml [9，27]; P = 0.0001）。随着炎症标志物基线浓度的增加，转化为糖尿病的比值比（OR）显著增加。与派-1相反，CRP和纤维蛋白原与糖尿病的关联在调整体脂（BMI或腰围）或胰岛素敏感性（SI）后显著减弱，如通过频繁采样的静脉内葡萄糖耐量试验评估的。在包括年龄、性别、种族、临床中心、吸烟、BMI、SI、体力活动和糖尿病家族史的逻辑回归模型中，PAI-1仍然与2型糖尿病发病率显著相关（1 SD增加的OR [95% CI]：1. 61 [1. 20 - 2. 16]; P = 0. 002）。慢性炎症作为2型糖尿病发展的新风险因素出现;派-1预测2型糖尿病，不依赖于胰岛素抵抗和其他已知的糖尿病风险因素。
Elevated serum levels of acute-phase proteins, indicating chronic subclinical inflammation, have been associated with cardiovascular disease as well as the insulin resistance syndrome. Chronic inflammation may also be a risk factor for developing type 2 diabetes. We studied the concentrations of C-reactive protein (CRP), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) in 1,047 nondiabetic subjects in relation to incident diabetes within 5 years in the Insulin Resistance Atherosclerosis Study. Subjects with diabetes at follow-up (n = 144) had higher baseline levels of fibrinogen (mean SD; 287.8 +/- 58.8 vs. 275.1 +/- 56.0 mg/dl; P = 0.013) as well as of CRP (median [interquartile range]; 2.40 [1.29, 5.87] vs. 1.67 mg/l [0.75,3.41];P = 0.0001) and PAI-1 (24 [15, 37.5] vs. 16 ng/ml [9, 27]; P = 0.0001) than nonconverters. The odds ratio (OR) of converting to diabetes was significantly increased with increasing baseline concentrations of the inflammatory markers. In contrast to PAI-1, the association of CRP and fibrinogen with incident diabetes was significantly attenuated after adjustment for body fat (BMI or waist circumference) or insulin sensitivity (SI), as assessed by a frequently sampled intravenous glucose tolerance test. In a logistic regression model that included age, sex, ethnicity, clinical center, smoking, BMI, SI, physical activity, and family history of diabetes, PAI-I still remained significantly related to incident type 2 diabetes (OR [95% CI] for 1 SD increase: 1.61 [1.20-2.16]; P = 0.002). Chronic inflammation emerges as a new risk factor for the development of type 2 diabetes; PAI-1 predicts type 2 diabetes independent of insulin resistance and other known risk factors for diabetes.