Synergistic Impact of Fasting Plasma Glucose and Serum Uric Acid on Peripheral Diabetic Retinopathy Severity in T2DM Patients.

Seven independent predictors of severe non-proliferative diabetic retinopathy (S-NPDR) were identified via multivariable logistic regression.

• Predictors included higher FPG (OR = 1.701), SUA (OR = 1.062 per 10 µmol/L), UACR (OR = 1.046 per 10 mg/g), hs-CRP (OR = 1.191), lower SFCT (OR = 1.330 per 10-µm decrease), lower serum albumin (OR = 1.153 per 1-g/L decrease), and the FPG×SUA interaction term (OR = 2.710, P < 0.001).
• The study was a retrospective, single-center study including 900 T2DM patients admitted between January 2018 and December 2023.
• Patients were categorized into No-DR (n = 300), mild to moderate NPDR (n = 350), and S-NPDR (n = 250) groups.
• S-NPDR was compared against the combined No-DR and mild-to-moderate NPDR groups (n = 650).

A strong synergistic interaction between FPG and SUA on S-NPDR severity was confirmed through additive interaction analysis.

• The adjusted OR for the high FPG/high SUA combination was 17.56.
• The relative excess risk due to interaction (RERI) was 12.58, indicating a synergistic additive effect beyond the sum of individual risks.
• The interaction term between FPG and SUA had OR = 2.710 with P < 0.001 in the multivariable logistic regression model.
• Patients with both markers elevated were identified as a high-risk group requiring intensive monitoring.

A predictive nomogram for S-NPDR demonstrated excellent discrimination and good calibration upon internal validation.

• The nomogram achieved an area under the receiver operating characteristic curve (AUC) of 0.925.
• Calibration was good as indicated by a Hosmer-Lemeshow P value of 0.418.
• Internal validation was performed using 1000 bootstrap resamples.
• The nomogram incorporated all seven identified independent predictors including the FPG×SUA interaction.

Higher serum uric acid (SUA) was independently associated with increased odds of S-NPDR.

• SUA was associated with S-NPDR with an OR of 1.062 per 10 µmol/L increase.
• SUA was included as both an independent predictor and as part of an interaction term with FPG.
• The synergistic effect of FPG and SUA was assessed using additive interaction analysis.

Lower subfoveal choroidal thickness (SFCT) was independently associated with increased odds of S-NPDR.

• SFCT was associated with S-NPDR with an OR of 1.330 per 10-µm decrease.
• SFCT was one of seven independent predictors identified in the final multivariable logistic regression model.
• This finding suggests that choroidal thinning is associated with more severe peripheral diabetic retinopathy.

Higher urinary albumin-to-creatinine ratio (UACR) and hs-CRP were independently associated with S-NPDR.

• UACR was associated with S-NPDR with an OR of 1.046 per 10 mg/g increase.
• hs-CRP was associated with S-NPDR with an OR of 1.191.
• Both markers suggest that systemic inflammation and renal involvement are linked to more severe retinopathy.

Lower serum albumin was independently associated with increased odds of S-NPDR.

• Serum albumin was associated with S-NPDR with an OR of 1.153 per 1-g/L decrease.
• Serum albumin was one of seven independent predictors in the final multivariable logistic regression model.
• This finding indicates that nutritional or inflammatory status, as reflected by albumin levels, relates to DR severity.