Kahn Steven E, Zinman Bernard, Haffner Steven M, O'Neill M Colleen, Kravitz Barbara G, Yu Dahong, Freed Martin I, Herman William H, Holman Rury R, Jones Nigel P, Lachin John M, Viberti Giancarlo C
Department of Internal Medicine, Division of Metbolism, Endocrinology and Nurtrition, VA Puget Sound Health Care System, 151, 1660 S. Columbian Way, Seattle, WA 98108, USA.
Diabetes. 2006 Aug;55(8):2357-64. doi: 10.2337/db06-0116.
The inflammatory factor C-reactive protein (CRP) and the fibrinolytic variables fibrinogen and plasminogen activator-1 (PAI-1) are associated with long-term cardiovascular morbidity. To determine the contribution of body adiposity (BMI), insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], and glycemia (HbA(1c) [A1C]) to the levels of these inflammatory and fibrinolytic variables in recently diagnosed (<or=3 years), drug-naive, type 2 diabetic subjects (fasting plasma glucose <or=10 mmol/l), we examined a representative subgroup (n = 921) of the U.S. cohort in ADOPT (A Diabetes Outcome Progression Trial). The relationship between levels of CRP, fibrinogen, PAI-1 antigen and PAI-1 activity, and baseline variables including National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome phenotype were explored. All four factors increased significantly with increasing numbers of metabolic syndrome components (P = 0.0136 to P < 0.0001). BMI (P < 0.0001) and HOMA-IR (P < 0.0001) but not A1C (P = 0.65) increased with increasing numbers of metabolic syndrome components. Adjustment of CRP levels for BMI eliminated the association between CRP and the number of metabolic syndrome components, while adjusting for HOMA-IR did not (P = 0.0028). The relationships of PAI-1 antigen and PAI-1 activity with the number of metabolic syndrome components were maintained after adjusting for BMI (P = 0.0002 and P = <0.0001, respectively) or HOMA-IR (P = 0.0008 and P = <0.0001, respectively), whereas that with fibrinogen was eliminated after adjusting for BMI but not after adjusting for HOMA-IR (P = 0.013). Adjustment for A1C had no effect on any of the relationships between the inflammatory and fibrinolytic factors and the metabolic syndrome. We conclude that in recently diagnosed, drug-naive type 2 diabetic subjects, markers of inflammation and fibrinolysis are strongly related to the number of metabolic syndrome components. Further, for CRP and fibrinogen this relationship is determined by body adiposity and not by insulin sensitivity or glucose control.
炎症因子C反应蛋白（CRP）以及纤溶变量纤维蛋白原和纤溶酶原激活物-1（PAI-1）与长期心血管疾病发病率相关。为了确定身体肥胖程度（体重指数[BMI]）、胰岛素敏感性（胰岛素抵抗稳态模型评估[HOMA-IR]）和血糖水平（糖化血红蛋白[HbA(1c)][A1C]）对最近确诊（≤3年）、未接受过药物治疗的2型糖尿病患者（空腹血糖≤10 mmol/l）这些炎症和纤溶变量水平的影响，我们在美国糖尿病转归进展试验（ADOPT）队列研究中选取了一个具有代表性的亚组（n = 921）进行研究。探讨了CRP、纤维蛋白原、PAI-1抗原和PAI-1活性水平与包括美国国家胆固醇教育计划成人治疗组第三次报告代谢综合征表型在内的基线变量之间的关系。随着代谢综合征组分数量的增加，所有这四个因素均显著升高（P = 0.0136至P < 0.0001）。随着代谢综合征组分数量的增加，BMI（P < 0.0001）和HOMA-IR（P < 0.0001）升高，但A1C未升高（P = 0.65）。对BMI进行校正后，CRP水平与代谢综合征组分数量之间的关联消失，而对HOMA-IR进行校正后则未消失（P = 0.0028）。对BMI进行校正后，PAI-1抗原和PAI-1活性与代谢综合征组分数量之间的关系依然存在（分别为P = 0.0002和P < 0.0001），对HOMA-IR进行校正后也是如此（分别为P = 0.0008和P < 0.0001），而对纤维蛋白原而言，对BMI进行校正后其与代谢综合征组分数量之间的关系消失，但对HOMA-IR进行校正后则未消失（P = 0.013）。对A1C进行校正对炎症和纤溶因子与代谢综合征之间的任何关系均无影响。我们得出结论，在最近确诊、未接受过药物治疗的2型糖尿病患者中，炎症和纤溶指标与代谢综合征组分数量密切相关。此外，对于CRP和纤维蛋白原而言，这种关系是由身体肥胖程度决定的，而非由胰岛素敏感性或血糖控制决定。
