Schram Miranda T, Chaturvedi Nish, Schalkwijk Casper, Giorgino Francesco, Ebeling Pertti, Fuller John H, Stehouwer Coen D
Institute for Cardiovascular Research, and Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
Diabetes Care. 2003 Jul;26(7):2165-73. doi: 10.2337/diacare.26.7.2165.
Inflammatory activity is increased in type 1 diabetes and may predispose to vascular disease. Its origin is not clear. We therefore investigated determinants of inflammation in type 1 diabetes.
We performed a nested case-control study from the EURODIAB Prospective Complications Study of 543 European individuals having type 1 diabetes (278 men), diagnosed at <36 years of age. Case subjects (n = 348) were those with one or more complications of diabetes; control subjects (n = 195) were all those with no evidence of any complication. We determined levels of C-reactive protein, interleukin-6, and tumor necrosis factor-alpha, combined them in a "general score of inflammatory markers," and investigated their associations with vascular risk factors and markers of endothelial dysfunction by use of multiple linear regression analysis.
Measures of inflammation were associated with sex, diabetes duration, glycemic control, the advanced glycation end product pentosidine, BMI, HDL cholesterol, triglycerides, and systolic blood pressure (standardized betas with the general score of inflammatory markers 0.15 [P = 0.002], 0.15 [P = 0.006], 0.18 [P < 0.0001], 0.12 [P = 0.005], 0.10 [P = 0.057], -0.15 [P = 0.001], 0.16 [P < 0.0001], and 0.09 [P = 0.042], respectively). In addition, measures of inflammation were strongly associated with markers of endothelial dysfunction, soluble vascular cell adhesion molecule-1, and soluble E-selectin (standardized betas with the general score of inflammatory markers 0.28 [P < 0.0001] and 0.19 [P < 0.0001]).
We have shown that conventional risk factors for vascular disease and endothelial adhesion molecules are important determinants of inflammation in type 1 diabetic individuals, suggesting that strategies to decrease inflammatory activity in type 1 diabetes should focus not only on control of conventional risk factors, but also on improvement of endothelial function.
1型糖尿病患者的炎症活动增强，可能易患血管疾病。其起源尚不清楚。因此，我们研究了1型糖尿病炎症的决定因素。
我们从欧洲糖尿病前瞻性并发症研究中进行了一项巢式病例对照研究，纳入了543名1型糖尿病患者（278名男性），诊断时年龄小于36岁。病例组（n = 348）为有一项或多项糖尿病并发症的患者；对照组（n = 195）为无任何并发症证据的患者。我们测定了C反应蛋白、白细胞介素-6和肿瘤坏死因子-α的水平，将它们合并为一个“炎症标志物综合评分”，并通过多元线性回归分析研究它们与血管危险因素及内皮功能障碍标志物的关联。
炎症指标与性别、糖尿病病程、血糖控制、晚期糖基化终产物戊糖苷、体重指数、高密度脂蛋白胆固醇、甘油三酯和收缩压相关（炎症标志物综合评分的标准化β值分别为0.15 [P = 0.002]、0.15 [P = 0.006]、0.18 [P < 0.0001]、0.12 [P = 0.005]、0.10 [P = 0.057]、-0.15 [P = 0.001]、0.16 [P < 0.0001]和0.09 [P = 0.042]）。此外，炎症指标与内皮功能障碍标志物、可溶性血管细胞黏附分子-1和可溶性E选择素密切相关（炎症标志物综合评分的标准化β值分别为0.28 [P < 0.0001]和0.19 [P < 0.0001]）。
我们已经表明，血管疾病的传统危险因素和内皮黏附分子是1型糖尿病患者炎症的重要决定因素，这表明降低1型糖尿病炎症活动的策略不仅应关注传统危险因素的控制，还应关注内皮功能的改善。
