Abstract
Purpose :
To investigate the relation between interleukin 6 (IL-6), Tumor necrosis factor-alpha (TNF-α) and high sensitivity C-reactive protein (CRP) levels with the presence and severity of diabetic retinopathy (DR) in persons with type 2 diabetes.
Methods :
Post-hoc analysis of participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study, a randomized controlled trial of intensive versus standard medical therapies, with biomarkers tested and DR status determined at baseline and at 12 months. Biomarker levels were log-transformed and analyzed via regression models for associations of IL-6, TNF-α and CRP with DR presence adjusted for demographics, treatment assignment and DR grade.
Results :
397 participants (mean age 62.8±5.8 years, 59.4% females) were analyzed. Median baseline TNF-α, IL-6, and CRP levels were 4.93 pg/mL, 9.06 pg/mL, and 0.33 mg/dL. At baseline, TNF-α was greater in participants with presence of DR (n=221) as compared to those without (n=176) (least squares geometric means (LSGM), presence of DR: 5.89 (95% CI: 4.82-7.20), absence of DR: 4.60 (3.84-5.50) (p=.02)). IL-6 and CRP did not differ by DR status. At 1-year, median TNF-α, IL-6 and CRP levels were 5.09 pg/mL, 8.05 pg/mL and 0.15 mg/dL. The intensive glycemic treatment arm demonstrated significantly lower CRP levels than the standard treatment arm (LSGM 0.13 and 0.16, respectively) (p=.007), yet TNF-α and IL-6 were not different between treatment groups. There were no differences in biomarkers LSGM between DR status. A regression with a 4-level DR variable predicting TNF-α, IL-6 and CRP levels from the presence of mild, moderate, severe DR and absence of DR did not demonstrate significant associations at 12 months. At baseline, TNF-α was significantly higher for participants with mild DR vs. absence of DR, but no associations were observed for IL-6 or CRP.
Conclusions :
In this well-characterized cohort, IL-6 and CRP were not correlated with DR status of diabetic type 2 participants. TNF-α was significantly increased in participants with presence of DR and particularly mild DR, but not in those without at baseline; however, no difference was observed at 12 months. This suggests TNF-α may serve as a systemic biomarker for DR prediction, especially earlier in DR pathogenesis, but this association warrants further longitudinal studies in the future.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.