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D.A. Schaumberg, T.J. Lyons, R.J. Glynn, D.M. Nathan, J.E. Manson; A Prospective Study of Inflammatory Biomarkers and Diabetic Retinopathy in Type 1 Diabetes Mellitus . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2055.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose. Recent research supports the hypothesis that chronic subclinical inflammation may contribute to the vascular pathology of diabetic retinopathy (DR). If related to DR, biomarkers of inflammation could be useful as markers of increased risk and as surrogate endpoints in studies of therapies designed to reduce inflammation. This investigation was designed to test the hypothesis that plasma levels of inflammatory biomarkers predict future risk of DR. Methods. We conducted a prospective cohort study in which we analyzed stored baseline plasma specimens from the 1441 participants in the Diabetes Control and Complications Trial for levels of C-reactive protein (CRP), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and tumor necrosis factor alpha receptor 1 (TNFR1). We used proportional hazards regression models to estimate the relationship of these inflammatory biomarkers with progression of DR, proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), and retinal hard exudate (HE). Results. In models controlling for baseline DR level and treatment group (intensive versus conventional control), higher ICAM levels were associated with increased risk of progression of DR (RR for top versus bottom quintile=1.51, P[trend]=0.007), and PDR (RR=2.24, P[trend]=0.02). In addition, both ICAM (RR=1.67, P[trend]=0.03) and CRP (RR=1.80, P[trend]=0.04) were associated with CSME. However, each of these relationships was attenuated with further adjustment for hemoglobin A1c (HbA1c). ICAM and CRP were also associated with the development of HE, and the association with CRP remained significant after adjustment for HbA1c (RR=1.41, P[trend]=0.05). Finally, among subjects with CRP at or above versus below the 95th percentile we observed significant relationships that persisted after adjustment for HbA1c with PDR (RR=2.79, CI=1.43 - 5.41) and HE (RR=2.09, CI=1.21 - 3.61). Conclusions. Our finding of some significant associations between systemic markers of inflammation and DR endpoints is consistent with the possibility that subclinical inflammation is one mechanism through which hyperglycemia causes DR. Further study is necessary to determine whether these or other inflammatory biomarkers can be useful as markers of increased risk of DR or as surrogate endpoints in studies of interventions to decrease inflammation among subjects with type 1 diabetes mellitus.
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