Research Article: Association of the glucose metabolism continuum (fasting plasma glucose/HbA1c) with tear-film stability and secretion: ocular surface evidence across non-diabetes, prediabetes, and diabetes
Abstract:
Whether gradations in glycemia across non-diabetes, prediabetes, and diabetes relate to tear?film homeostasis and dry eye disease (DED) remains uncertain, and explicitgraded association evidence is limited.
In a single?center cross?sectional study (April 2024–March 2025), we enrolled 300 adults by quota ( n = 100 per stratum). Same?day hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) classified strata and were also modeled continuously. Co?primary outcomes were non-invasive tear break?up time (NIBUT) and Schirmer I (no anesthesia). Secondary outcomes included fluorescein tear break-up time (TBUT), ocular surface disease index (OSDI), National Eye Institute (NEI) staining, meiboscore, tear meniscus height, bulbar redness, tear osmolarity, and matrix metalloproteinase-9 (MMP?9). DED was defined as OSDI ?13 plus ?1 sign [NIBUT <10 s, osmolarity ?308 mOsm/L or intereye difference ?8 mOsm/L, or NEI staining score ?2 (beyond trace)]. Multivariable analysis of covariance (ANCOVA) and logistic regression adjusted for prespecified demographic, clinical, and environmental covariates. Restricted cubic splines tested non-linearity, and Benjamini–Hochberg false discovery rate (FDR) controlled multiplicity for secondary endpoints.
Mean NIBUT was 11.8, 10.5, and 9.2 s, and Schirmer I was 13.8, 12.1, and 10.4 mm across non-diabetes, prediabetes, and diabetes (both p ?trend < 0.001). Adjusted differences versus non-diabetes were ?1.20 and ?2.50 s for NIBUT and ?1.60 and ?3.10 mm for Schirmer (all p ? 0.006). Per 1% higher HbA1c, NIBUT decreased by 0.72 s and Schirmer by 1.15 mm, and DED odds increased (aOR 1.31; all p < 0.001) with no significant non-linearity. DED proportion within strata was 24.0%, 34.0%, and 51.0% (prediabetes aOR 1.60, p = 0.049; diabetes aOR 2.90, p = 0.001). Osmolarity abnormality and MMP?9 positivity rose across strata and with HbA1c, remaining significant after FDR control. Using FPG instead of HbA1c yielded concordant effects.
Higher glycemic status, including prediabetes, was associated with shorter NIBUT, lower Schirmer, and higher odds of DED and inflammatory signs, although the absolute between-stratum differences were modest in magnitude. Longitudinal studies are needed to assess the temporality and the practical relevance of these cross-sectional associations.
Introduction:
Whether gradations in glycemia across non-diabetes, prediabetes, and diabetes relate to tear?film homeostasis and dry eye disease (DED) remains uncertain, and explicitgraded association evidence is limited.
Read more