Serum cortisol is a biomolecular biomarker for severity of diabetic retinopathy

Cortisol and prolactin are multifunctional hormones essential for various metabolic processes in the human body. This study evaluated for the first time the association between serum cortisol and prolactin levels and severity of diabetic retinopathy (DR) and their role as biomolecular biomarkers for disease progression.

A tertiary care center-based cross-sectional study was conducted. Forty-six consecutive cases of type 2 diabetes mellitus (DM) were included. Retinopathy was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) classification: diabetes with no retinopathy (NoDR, n = 15), nonproliferative DR (NPDR, n = 16), and proliferative DR (PDR, n = 15). Healthy controls (n = 15) were also included. All study participants underwent complete ophthalmological evaluations. Serum levels of cortisol and prolactin were analyzed using the chemiluminescence microparticle assay method. Statistical analysis was performed using ANOVA, univariate and multivariate ordinal logistic regression, and receiver operating characteristics (ROC) area under the curve (AUC).

The mean serum cortisol levels (µg/dl) were 10.25±1.380 for the NoDR group, 12.00±2.540 for the NPDR group, 13.19±2.170 for the PDR group, and 8.22±2.97 for the control group. The mean serum prolactin levels (ng/ml) were13.13±1.97 for the NoDR group, 11.04±2.59 for the NPDR group, 7.84±1.17 for the PDR group, and 7.38±3.34 for the control group. ANOVA showed a statistically significant increase in serum cortisol levels (F = 12.87, p<0.001) and a decrease in serum prolactin levels (F = 19.31, p<0.001) with severity of DR. However, the multivariate ordinal logistic regression analysis showed serum cortisol is a statistically significant independent predictor for severity of DR (odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.36-0.68, p<0.001). The AUC analysis of the serum cortisol levels to discriminate between severity of DR showed statistically significant diagnostic accuracy (NoDR group: AUC = 0.787, p<0.001; NPDR group: AUC = 0.852, p<0.001; PDR group: AUC = 0.887, p<0.001). Serum cortisol levels of >9.5 µg/dl and >10.2 µg/dl were found to be statistically significantly associated with occurrence of NPDR and PDR, respectively.

Statistically significantly elevated serum cortisol levels are observed before development of signs of DR. Serum cortisol levels are statistically significantly associated with severity of DR and serve as a sensitive and specific biomolecular biomarker for disease progression.