Simple Blood Ratio May Flag Eye Damage Risk in Type 2 Diabetes

A routine blood test already performed in almost every diabetes clinic may carry a hidden warning about the eyes. New research from China suggests that the ratio between serum uric acid and serum creatinine—two inexpensive markers measured on standard metabolic panels—is significantly associated with diabetic retinopathy, the leading cause of vision loss among people with type 2 diabetes. The study, published in Frontiers in Endocrinology, analyzed 427 patients treated at Hefei First People’s Hospital between 2022 and 2024 and found that those with retinopathy had a markedly higher uric acid-to-creatinine ratio than those without.

Diabetic retinopathy is one of the most feared complications of type 2 diabetes mellitus. It damages the delicate microvessels of the retina, and macular thickening and macular edema are among the leading causes of blindness in affected patients. The condition is particularly insidious because early stages often produce no obvious symptoms, which contributes to frequent underdiagnosis. Data from a national screening program in Singapore cited by the researchers indicate that initial retinopathy signs tend to appear roughly eight years after diabetes onset, with progression across disease stages occurring within just one to two years. That narrow window makes reliable early screening markers a pressing clinical need.

The research team, led by Lei Wang and colleagues at the Department of Endocrinology and Metabolism of The First People’s Hospital of Hefei, in collaboration with Bengbu Medical University, focused on an understudied angle: the role of serum uric acid. Uric acid is the end product of purine metabolism, with roughly three-quarters of circulating levels derived from hepatic metabolism of endogenous purines and one-quarter from dietary intake. About two-thirds is eliminated through the kidneys, which means raw uric acid concentrations are strongly correlated with renal function—a confounder the authors argue has been overlooked in most prior investigations of uric acid and retinopathy.

To correct for this, the team normalized uric acid against serum creatinine, producing the serum uric acid-to-creatinine ratio, or SUA/SCr. Because creatinine reflects kidney clearance capacity, dividing by it compensates for renal dysfunction and better reflects the net endogenous urate burden and the associated oxidative stress status. The approach matters clinically: elevated uric acid can promote monosodium urate crystal formation, and accumulating evidence indicates these crystals activate the NLRP3 inflammasome, releasing interleukin-1β and interleukin-18 while driving broader inflammatory responses involving TNF-α, interleukin-6, and C-reactive protein. Inflammation is a central driver of retinal microvascular injury, so a marker capturing net urate production could plausibly track disease activity.

Methodologically, the study began with 1,091 patients with type 2 diabetes who visited the hospital’s Department of Internal Medicine between 2022 and 2024. After applying predefined inclusion and exclusion criteria, 427 eligible subjects remained, stratified into 183 with diabetic retinopathy and 244 without. Type 2 diabetes was verified using Chinese guideline criteria, fasting and postprandial glucose, HbA1c, and autoantibody testing to rule out autoimmune diabetes. Retinopathy was diagnosed and graded by dilated fundus examination and fundus photography according to the Early Treatment Diabetic Retinopathy Study Severity Scale, with two masked ophthalmologists independently reviewing images and discrepancies resolved by consensus. Patients with severe renal dysfunction, other ocular diseases, malignancies, active infection, or use of drugs affecting uric acid—such as allopurinol, febuxostat, glucocorticoids, and immunosuppressants—were excluded.

The statistical architecture was layered. Spearman rank-order correlation analysis evaluated associations between retinopathy status and clinical variables; univariable binary logistic regression screened potential risk factors; and variables reaching P<0.05 entered a multivariable logistic regression model. A post-hoc power calculation confirmed that with an assumed odds ratio of 1.22, an alpha of 0.05, and a case-to-noncase ratio of 1:1.3, the sample of 427 provided adequate statistical power. Receiver operating characteristic (ROC) analysis then quantified discrimination, and C-statistics were compared via DeLong’s test, supplemented by net reclassification improvement (NRI) and integrated discrimination improvement (IDI) metrics to measure incremental predictive value.

The results painted a consistent picture. Baseline comparisons showed significant between-group differences in age, disease duration, HbA1c, albumin, liver enzymes, total bilirubin, triglycerides, serum uric acid, and SUA/SCr, while sex, C-peptide, fasting plasma glucose, cholesterol fractions, glomerular filtration rate, and creatinine showed no differences. Spearman analysis revealed that retinopathy status correlated positively with age, disease duration, HbA1c, uric acid, and SUA/SCr, and negatively with C-peptide, albumin, and bilirubin. In the multivariable model, elevated SUA/SCr remained independently associated with retinopathy, with an odds ratio of 1.220 (95% CI: 1.015–1.465)—a 1.22-fold higher odds per unit increase after adjustment for total bilirubin, triglycerides, total cholesterol, and LDL-C.

The predictive performance numbers are where the story becomes nuanced. SUA/SCr alone discriminated retinopathy with an AUC of 0.774 (95% CI: 0.720–0.827), a moderate value. The optimal cut-off was 3.68, corresponding to a sensitivity of 79.8% and specificity of 67.2%—meaning the ratio catches most cases but flags a meaningful share of false positives. When SUA/SCr was added to a baseline model containing sex, age, diabetes duration, and HbA1c, the C-statistic rose from 0.655 to 0.676. The IDI reached statistical significance at 0.021 (P=0.006), but the NRI of 0.140 did not (P=0.187). Interestingly, adding raw uric acid to the same baseline model produced a significant NRI of 0.253 (P=0.017) and an IDI of 0.017 (P=0.008), suggesting the creatinine-corrected ratio provides limited supplementary information beyond uric acid itself in this cohort.

The authors interpret these findings cautiously. SUA exhibits dual redox properties and may exert context-dependent antioxidant or pro-oxidant effects, so elevated uric acid does not directly trigger oxidative stress. Clinical evidence remains inconsistent: one Turkish study found no significant differences in ischemia-modified albumin or total oxidant and antioxidant capacity between uncomplicated type 2 diabetes patients with elevated versus normal uric acid. Yet in patients with retinopathy, elevated uric acid may shift toward pro-oxidant activity, promoting retinal inflammatory injury. Mechanistically, hyperglycemia triggers oxidative stress, accumulation of advanced glycation end products, and upregulation of vascular endothelial growth factor—core drivers of retinopathy—while elevated uric acid suppresses endothelial nitric oxide synthesis, activates the renin-angiotensin system, and under hyperglycemic conditions may exacerbate retinal inflammation and activate the Notch signaling pathway.

The study’s limitations are explicitly acknowledged. As a single-center cross-sectional investigation, it can demonstrate association but not causality, and reverse causality is possible: renal and vascular alterations accompanying retinopathy could affect renal urate excretion and handling, in turn influencing the SUA/SCr ratio. Limited sample size, single-region enrollment, and uncollected information on hypoglycemic agents, diet, and physical activity may introduce selection bias and residual confounding. The NRI and IDI analyses are also sensitive to sample size, which may limit the reliability of the incremental performance estimates. Still, the authors conclude that SUA/SCr was significantly associated with diabetic retinopathy and may serve as a supportive auxiliary indicator for identifying high-risk patients with type 2 diabetes—potentially helping clinicians target interventions for diabetic microvascular complications when integrated with comprehensive ophthalmic evaluations including visual acuity testing, dilated fundus examination, fundus photography, and OCT assessment. Further large-scale, prospective, externally validated studies will be needed to confirm its clinical utility.

Subject of Research: Health & Medicine

Article Title: Correlation between serum uric acid-to-creatinine ratio and diabetic retinopathy in type 2 diabetes mellitus patients

Article References: Wang, L., Zhu, Z., Gong, Y., & Wang, G. (2026). Correlation between serum uric acid-to-creatinine ratio and diabetic retinopathy in type 2 diabetes mellitus patients. Frontiers in Endocrinology, 17, Article 1977560. https://doi.org/10.3389/fendo.2026.1977560

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1977560

Keywords: diabetic retinopathy, type 2 diabetes, serum uric acid, biomarkers, ophthalmology, endocrinology, Correlation, between, serum, uric, acid-to-creatinine, ratio