Elsevier

Ophthalmology

Volume 119, Issue 5, May 2012, Pages 1041-1046
Ophthalmology

Original article
Systemic Soluble Tumor Necrosis Factor Receptors 1 and 2 Are Associated with Severity of Diabetic Retinopathy in Hispanics

This study was presented at: the 2011 Annual Meeting of the Association for Research in Vision and Ophthalmology, May 1–5, 2011, Fort Lauderdale, Florida.
https://doi.org/10.1016/j.ophtha.2011.10.040Get rights and content

Purpose

To investigate the associations of serum amyloid A (SAA) protein and soluble tumor necrosis factor receptors 1 and 2 (sTNF-R1 and sTNF-R2) with diabetic retinopathy (DR) in Hispanics.

Design

Prospective, nonrandomized, cross-sectional, family-based observational cohort study.

Participants

A total of 473 Hispanic type II diabetic subjects in families ascertained via proband with DR.

Methods

Levels of SAA, sTNF-R1, and sTNF-R2 were measured with enzyme-linked immunosorbent assay. Diabetic retinopathy was assessed by fundus photography and graded using modified Airlie House classification.

Main Outcome Measures

Levels of SAA, sTNF-R1, and sTNF-R2 to severity of DR with and without covariates.

Results

A direct association of sTNF-R1 (2.37±0.13, 2.15±0.09, 3.09±0.24, 3.25±0.46, 5.02±0.61 ng/ml; P < 0.0001) and sTNF-R2 (6.04±0.20, 6.25±0.52, 7.96±0.70, 8.14±1.13, 14.83±1.68 ng/ml; P < 0.0001) was found for no DR, mild nonproliferative DR (NPDR), moderate NPDR, severe NPDR, and proliferative DR, respectively. These associations remained significant after adjusting for age, gender, body mass index, glycosylated hemoglobin, diabetes duration, systolic blood pressure, and serum creatinine (P < 0.0001 for sTNF-R1 and P=0.0004 for sTNF-R2). A similar pattern was observed when we adjusted for urinary albumin:creatinine ratio in place of serum creatinine (P=0.005 for sTNF-R1 and P=0.02 for sTNF-R2).

Conclusions

Levels of sTNF-R1 and sTNF-R2 are highly correlated with the severity of DR, suggesting that inflammation and insulin resistance may play a critical role in the development of DR. These may be useful biomarkers for DR, aiding in etiologic studies and possibly identifying at-risk patients for active intervention.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Materials and Methods

From October 2007 to December 2010, we performed a cross-sectional study of 473 Hispanic type II diabetic subjects who were recruited in a joint study of Cedars-Sinai Medical Center and the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (HUMC) after informed consent and approval by the institutional review board/ethics committee. This study assessed siblings of a proband (with type II diabetes and either known DR or a diabetes duration of ≥10 years) and, when possible,

Results

A total of 473 type II diabetic subjects with DR (cases, n = 266) and without DR (controls, n = 207) were included in the analysis (demographics of the cohort are summarized in Table 1). The mean ± standard error of the mean (SEM) age was 53.7±0.8 years in the controls and 53.6±0.7 years in the cases. There were 66 (31.9%) and 114 (42.9%) male subjects in the controls and cases, respectively. The mean body mass index (BMI) ± SEM was 33.4±0.5 and 32.1±0.4 in the controls and cases, respectively,

Discussion

After controlling for confounding risk factors, including age, gender, BMI, HbA1c, diabetes duration, systolic blood pressure, and serum creatinine or urinary albumin:creatinine ratio, both sTNF-R1 and sTNF-R2 were cross-sectionally associated with increasing severity of DR in Hispanic type II diabetic subjects. These findings reveal novel systemic biomarkers, namely, soluble TNF receptors, which may serve as a biochemical link between 2 important pathophysiologic processes involved:

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    Manuscript no. 2011-1038.

    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    Supported in part by National Institutes of Health grant R01 EY014684 GOLDR, BioEye grant from the Eye Birth Defects Foundation, Clinical and Translational Sciences Institute grant UL1RR033176, and Diabetes Endocrinology Research Center grant P30 DK063491. The sponsor or funding organization had no role in the design or conduct of this research.

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