This study aimed to investigate corneal limbus changes in patients with type 2 diabetes mellitus (DM) using in vivo confocal microscopy (IVCM) and explore the correlation between their ocular manifestations and systemic status.Fifty-five patients with type 2 DM and 20 age-matched controls were included. The following IVCM parameters were compared between the 2 groups: palisades of Vogt (POV), corneal epithelial thickness (CET), basal cell density (BCD), subbasal nerve plexus, and dendritic cell density. All subjects underwent blood and urine sampling for laboratory analysis, including fasting blood glucose, glycated hemoglobin, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein, urinary albumin-to-creatinine ratio, urine albumin, and urine creatinine. The correlations between IVCM parameters and blood biomarkers were detected. Receiver operating characteristic curve was used for selecting the cutoff value of risk factors for corneal stem cell injury in patients with DM.Compared with controls, patients with DM displayed a significant reduction of POV (superior region, P = 0.033; inferior region, P = 0.003; nasal region, P < 0.001; temporal region, P < 0.001), central CET (44.8 ± 3.6 μm vs. 51.9 ± 3.6 μm, P < 0.001), central corneal BCD (7415.5 ± 563.2 cells/mm2 vs. 9177.9 ± 977.8 cells/mm2, P < 0.001), and peripheral corneal BCD (6181.3 ± 416.5 cells/mm2 vs. 8576.3 ± 933.2 cells/mm2, P < 0.001). Dendritic cell density (41.0 ± 33.7 cells/mm2 vs. 24.6 ± 7.8 cells/mm2, P = 0.001) was significantly higher in the DM group. The following weak correlations were shown between IVCM parameters and blood biomarkers: central corneal BCD was negatively correlated with DM duration (r = -0.3, P = 0.024), TC (r = -0.36, P = 0.007), and LDL (r = -0.39, P = 0.004). The presence of POV in the superior region was negatively correlated with TC (r = -0.34, P = 0.011) and LDL (r = -0.31, P = 0.022). Cutoff values of 1.215 mmol/L for HDL, 1.59 mmol/L for TG, or 4.75 mmol/L for TC were established to distinguish patients with a high risk from a low risk for stem cell damage.Patients with type 2 DM displayed a lower positive rate of typical POV and a decrease in BCD, CET, and subbasal nerve density. The most relevant indicators for stem cell phenotypes were DM duration, TC, and LDL. Lipid status in diabetic patients could be a predictor of risk for developing corneal limbal stem cell deficiency. Further studies with larger sample sizes or basic research are needed to verify the results.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.