Relationship between continuous glucose monitoring and corneal neuropathy in type 2 diabetes

Abstract Context The relationship between corneal neuropathy measured by in vivo confocal microscopy (IVCM) and continuous glucose monitoring (CGM) remains unclear. Objective We describe the associations between corneal neuropathy and CGM metrics. Methods A single-center cross-sectional study recruited people with type 2 diabetes. All participants wore a 14-day blinded Freestyle Libre Pro CGM and underwent corneal IVCM. Multiple generalized estimating equation models were created to study the association of independent variables (HbA1c and CGM metrics) on dependent variables (corneal nerve fiber and cellular metrics) adjusted for age, sex, ethnicity, hypertension, hyperlipidemia, body mass index (BMI), and diabetes duration. Benjamini–Hochberg procedure controlled for multiplicity. Results Of 307 recruited people, 277 were included in the analysis (median age 58 years, 49.5% female, 60.6% Chinese, BMI 26.6 kg/m², diabetes duration 12 years, HbA1c 8.1%). HbA1c associated negatively (β −0.609, pseudoR² = 0.068, P = .013) with corneal nerve fiber density and positively (β .003, pseudoR² = 0.066, P = .027) with corneal nerve fiber width (CNFW). Time-in-range (TIR) and time-in-tight-range (TITR) negatively (both β −.006; pseudoR² = 0.075 and 0.066, respectively; both P < .03), and time-above-range (TAR) (β .006, pseudoR² = 0.073, P = .021) positively, associated with CNFW. Among corneal cellular metrics, TAR (β .088, pseudoR² = 0.055, P = .004), mean glucose (β .049, pseudoR² = 0.055, P = .004), and glucose variability (SD, mean amplitude of glycemic excursions, and mean of daily differences: β .13, 0.046, and .164; pseudoR²= 0.053, 0.044, and 0.060, respectively, all P < .03) associated positively with average epithelial size, while TIR and TITR had a negative association (β −.084 and −.104; pseudoR² = 0.052 and 0.057, respectively, both P < .01). Conclusion CGM measures, including mean glycemia, TIR, TITR, and glucose variability, were significantly associated with corneal neuropathy, supporting the role of CGM metrics in optimizing glycemia.