Direct and Indirect Associations Between Diabetes and Intraocular Pressure: The Singapore Epidemiology of Eye Diseases Study

PURPOSE. The association between diabetes and IOP is controversial; diabetes is associated with thicker central corneal thickness (CCT), and thicker CCT is associated with higher IOP. We therefore aimed to clarify the diabetes-IOP association, considering CCT as a potential mediator. METHODS. We included 8636 participants from the Singapore Epidemiology of Eye Diseases (SEED) Study. Associations of diabetes, serum glucose, or HbA1c with IOP were assessed using regressions models, with adjustments for potential confounding factors. Regression-based mediation (path) analyses were further performed to evaluate the indirect effects of diabetes on IOP through the mediator (CCT), in addition to the direct effect of diabetes on IOP. RESULTS. Of the 8636 participants, 2524 (29.23%) had diabetes. Diabetes, higher serum glucose, or HbA1c levels were all associated with higher IOP (all P < 0.01). The effect of diabetes on IOP was partially and minimally mediated through CCT; the proportion of mediating effect of CCT was 11.09% of the total effect of diabetes on IOP. Axial length and spherical equivalent were not mediating variables in the diabetes-IOP association. Findings were consistent across three ethnicity groups. CONCLUSIONS. Diabetes or higher long-term hyperglycemia was associated with higher IOP. CCT contributed a small proportion of mediating effect to the total effect of diabetes on IOP. We conclude that high IOP observed in diabetes is mainly due to the direct association of diabetes and IOP, and this finding may have pathophysiologic significance with respect to the risk of glaucoma among persons with diabetes.