The relationship between diabetes mellitus and keratoconus remains controversial. This study aimed to assess the potential causal relationships among type 2 diabetes, glycemic traits, and the risk of keratoconus.
We used a two-sample Mendelian randomization (MR) design based on genome-wide association summary statistics. Fasting glucose, proinsulin levels, adiponectin, hemoglobin A1c (HbA1c) and type 2 diabetes with and without body mass index (BMI) adjustment were used as exposures and keratoconus was used as the outcome. MR analysis was performed using the inverse-variance weighted method, MR-Egger regression method, weighted-mode method, weighted median method and the MR-pleiotropy residual sum and outlier test (PRESSO).
Results showed that genetically predicted lower fasting glucose were significantly associated with a higher risk of keratoconus [IVW: odds ratio (OR) = 0.382; 95% confidence interval (CI) = 0.261–0.560;
These findings provide genetic evidence that higher fasting glucose levels are associated with a lower risk of keratoconus. However, further studies are required to confirmed this hypothesis and to understand the mechanisms underlying this putative causative relationship.