Elevated Serum Levels of Soluble TNF Receptors and Adhesion Molecules Are Associated with Diabetic Retinopathy in Patients with Type-1 Diabetes.

Shruti Sharma,Sharad Purohit,Bruce Bode,Leigh Steed,Ruth Caldwell,Jin-Xiong She,Ashok Sharma,Diane Hopkins,Stephen W. Anderson

doi:10.1155/2015/279393

Shruti Sharma, Sharad Purohit + Show 7 more

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https://doi.org/10.1155/2015/279393

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Abstract

Aims. To examine the association of the serum levels of TNF receptors, adhesion molecules, and inflammatory mediators with diabetic retinopathy (DR) in T1D patients. Methods. Using the multiplex immunoassay, we measured serum levels of eight proteins in 678 T1D subjects aged 20–75 years. Comparisons were made between 482 T1D patients with no complications and 196 T1D patients with DR. Results. The levels of sTNFR-I, sTNFR-II, CRP, SAA, sgp130, sIL6R, sVCAM1, and sICAM1 were significantly higher in the T1D patients with DR as compared to T1D patients with no complications. Multivariate logistic regression analysis revealed significant association for five proteins after adjustment for age, sex, and disease duration (sTNFR-I: OR = 1.57, sgp130: OR = 1.43, sVCAM1: OR = 1.27, sICAM1: OR = 1.42, and CRP: OR = 1.15). Conditional logistic regression on matched paired data revealed that subjects in the top quartile for sTNFR-I (OR = 2.13), sTNFR-II (OR = 1.66), sgp130 (OR = 1.82), sIL6R (OR = 1.75), sVCAM1 (OR = 1.98), sICAM1 (OR = 2.23), CRP (OR = 2.40) and SAA (OR = 2.03), had the highest odds of having DR. Conclusions. The circulating markers of inflammation, endothelial injury, and TNF signaling are significantly associated with DR in patients with T1D. TNFR-I and TNFR-II receptors are highly correlated, but DR associated more strongly with TNFR-I in these patients.

Highlights

Diabetic retinopathy (DR) is a sight threatening, microvascular complication of diabetes that affects the retinal vasculature
New markers to define the risk of type-1 diabetes (T1D) associated DR and new therapeutic targets are the critical unmet need
Blood samples from the participants of Phenome and Genome of Diabetes Autoimmunity (PAGODA) study were obtained after the informed consent from the subjects

Summary

Introduction

Diabetic retinopathy (DR) is a sight threatening, microvascular complication of diabetes that affects the retinal vasculature. It is the leading cause of blindness in adults 20–74 years of age in the United States with 28.5% prevalence among 40-year and older patients with diabetes [1]. Clinical trials of anti-VEGF intraocular injections have shown promise in reducing diabetic macular edema [3] These effects are usually transient and the treatment does not promote tissue repair and the need for repeated injections increases the risk of intraocular infection. We examined the levels of soluble TNF receptors (sTNFR-I and sTNFR-II), soluble IL6 receptors (sIL6R, sgp130), adhesion molecules (sICAM-1, sVCAM-1), and inflammatory markers (CRP, SAA) in serum of T1D patients with and without DR. The aim of this study was to examine the association of the serum levels of these inflammatory mediators with DR and to determine if these markers could be used as surrogate endpoints to define the risk of DR in T1D patients

Research Design and Methods

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