The Association Between Anion Gap and Diabetic Retinopathy: Based on Hospital Registry Data in Liaoning Diabetic Microvascular Complications Study

Background: Current evidences supported a highly relevant between acid-load and diabetes. The rise of serum anion gap (AG) has performed the significances in metabolic acidosis. Some factors correlated to diabetes might affect its complications such as diabetic retinopathy (DR). Methods: A total of 3,411 Chinese adults with type 2 diabetes were selected form the hospital registry data on DR Sub-study of Liaoning Diabetic Microvascular Complications Study (LD-MCS), included 1,137 DR as the cases and 2,274 non-DR as the matching controls. Fasting venous blood test was applied to ascertain the ion levels, and serum AG (mmol/L) was computed by: AG = (sodium + potassium) – (chlorine + bicarbonate). According to Early Treatment for Diabetic Retinopathy Study standards, DR was diagnosed by two-field fundus photographs and classified as mild non-proliferative DR (NPDR), moderate NPDR, and vision-threatening DR (VTDR). Logistic regression models and linear regression models were used to analyze the relationships. Results: In setting of the non-acidosis, higher AG was significantly associated with DR (P = 0.001), increased with aggravating retinopathy but decreased in VTDR level (P < 0.001). Multivariable-adjusted models showed that AG quartiles were independently linked with higher odds to occurrence (P for trend < 0.001) and severity (P for trend < 0.05) of DR, but with attention to the fluctuation of 75th AG quartiles. Linear logistic regression by stepwise method suggested the growth of age (P = 0.014), glycated hemoglobin (P = 0.018), and the homeostasis model assessment of insulin resistance index (P < 0.001) played an intimate role in the association between AG and DR. Conclusions: Higher AG was independently related to the occurrence and progression of DR. Our findings suggested that serum AG might alter the risk of DR by affecting glucose metabolism and insulin sensitivity in patients with type 2 diabetes.