Uric Acid and Diabetic Retinopathy: A Systematic Review and Meta-Analysis

Background: The relationship between uric acid (UA) and diabetic retinopathy (DR) remains ambiguous, and the results of current studies on the UA levels in patients with DR are conflicting. A meta-analysis was performed to provide a better understanding of the relationship between UA levels and DR. Methods: PubMed, Web of Science, Embase, and the Cochrane Library databases were searched until December 11, 2021 to identify eligible studies, that compared the UA levels of the case group (patients with DR) and control group (controls with diabetes and healthy participants). The weighted mean difference (WMD) with a 95% confidence interval (CI) was used to evaluate the difference in UA levels between the case and control groups. Results: Twenty-one studies involving 4,340 patients with DR and 8,595 controls (8,029 controls with diabetes and 566 healthy participants) were included in this meta-analysis. We found that patients with DR had significantly higher UA levels than those in the controls with diabetes (WMD = 36.28; 95% CI: 15.68, 56.89; P < 0.001) and healthy participants (WMD = 70.80; 95% CI: 19.85, 121.75; P = 0.006). There was an obvious heterogeneity among the 21 studies (I-2 = 97%, P < 0.001). Subgroup analyses of different phases of DR showed that UA levels were significantly increased in participants with proliferative diabetic retinopathy (PDR) (WMD = 46.57; 95% CI: 28.51, 64.63; P < 0.001) than in controls with diabetes; however, the difference is not statistically significant when comparing UA levels in patients with non-proliferative diabetic retinopathy (NPDR) and controls with diabetes (WMD = 22.50; 95% CI: -6.07, 51.08; P = 0.120). In addition, UA levels were higher in participants with a body mass index (BMI) >= 25.0 kg/m(2) and over 15 years of diabetes. Univariate meta-regression analysis revealed that BMI (P = 0.007, Adj R-2 = 40.12%) and fasting blood glucose (FBG) (P = 0.040, Adj R-2 = 29.72%) contributed to between-study heterogeneity. Conclusions: In conclusion, our study provides evidence that UA levels are higher in patients with DR than those in the controls, but this difference is not statistically significant in the early phases. UA might be a potential biomarker for identifying disease severity in patients with DR, rather than predicting the onset of DR among patients with diabetes. However, more prospective and high-quality clinical evidence is required to confirm these present findings.