Nitric oxide and TNF-α are correlates of diabetic retinopathy independent of hs-CRP and HbA1c



Regarding the role of inflammation in progression of diabetes this study was conducted to investigate the association between inflammatory biomarkers such as nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) with the chance of existence of diabetic retinopathy and its progression in patients with diabetes.


A total of 83 patients with T2DM (Type 2 diabetes mellitus) were divided into three groups of patients with proliferative diabetic retinopathy (PDR), patients with non-proliferative diabetic retinopathy (NPDR) and patients without diabetic retinopathy (NDR) based on ophthalmologic funduscopic examination. Twenty six healthy controls were also enrolled. Blood samples were taken after 12 h of overnight fasting, NO, TNF-α, and hs-CRP were measured. Association of the level of these biomarkers with retinopathy was analyzed.


The levels of TNF-α, NO and hs-CRP were higher among patients with diabetic retinopathy. Multinomial Logistic Regression model showed that TNF-α and NO could predict the presence of retinopathy among patients with diabetes when adjusted for hs-CRP, HbA1c, FBS, gender, total cholesterol, triglyceride, HDL, LDL, BMI, and age (respectively OR = 1.76, CI 95% = 1.01–3.02, p = 0.046 and OR = 1.12, CI 95% = 1.05–1.18, p < 0.001); however they could not predict the severity of retinopathy. In ROC analysis AUC for TNFα was 0.849 (p < 0.001) and for NO was 0.907 (p < 0.001). Serum TNF-α level of 7.10 pmol/L could be suggestive of the presence of retinopathy (sensitivity = 92.2% and specificity = 66.0%), also serum NO level of 45.96 μmol/L could be suggestive of the presence of retinopathy (sensitivity = 96.1% and specificity = 86%).


Our results suggest elevated levels of NO and TNF-α can be suggestive of diabetic retinopathy.

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Research is reported in this publication was supported by Elite Researcher Grant Committee under award number 963276 from the National Institutes for Medical Research Development (NIMAD), Tehran, Iran.

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Correspondence to Manouchehr Nakhjavani.

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Khaloo, P., Qahremani, R., Rabizadeh, S. et al. Nitric oxide and TNF-α are correlates of diabetic retinopathy independent of hs-CRP and HbA1c. Endocrine (2020).

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  • Diabetic retinopathy
  • Type 2 diabetes
  • Inflammation
  • Nitric oxide
  • Tumor necrosis factor alpha
  • High-sensitivity C-reactive protein