Vascular Risk Factors and Markers of Endothelial Function as Determinants of Inflammatory Markers in Type 1 Diabetes

Abstract

OBJECTIVE—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. RESEARCH DESIGN AND METHODS—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-α, 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. RESULTS—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 βs 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 βs with the general score of inflammatory markers 0.28 [P < 0.0001] and 0.19 [P < 0.0001]). CONCLUSIONS—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.