{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:10:12Z","timestamp":1793293812371,"version":"4.5.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Whether gradations in glycemia across non-diabetes, prediabetes, and diabetes relate to tear\u2212film homeostasis and dry eye disease (DED) remains uncertain, and explicitgraded association evidence is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a single\u2212center cross\u2212sectional study (April 2024\u2013March 2025), we enrolled 300 adults by quota (\n                      <jats:italic>n<\/jats:italic>\n                      = 100 per stratum). Same\u2212day hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) classified strata and were also modeled continuously. Co\u2212primary outcomes were non-invasive tear break\u2212up 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\u22129). DED was defined as OSDI \u226513 plus \u22651 sign [NIBUT &amp;lt;10 s, osmolarity \u2265308 mOsm\/L or intereye difference \u22658 mOsm\/L, or NEI staining score \u22652 (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\u2013Hochberg false discovery rate (FDR) controlled multiplicity for secondary endpoints.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mean NIBUT was 11.8, 10.5, and 9.2 s, and Schirmer I was 13.8, 12.1, and 10.4\u00a0mm across non-diabetes, prediabetes, and diabetes (both\n                      <jats:italic>p<\/jats:italic>\n                      \u2212trend &amp;lt; 0.001). Adjusted differences versus non-diabetes were \u22121.20 and \u22122.50 s for NIBUT and \u22121.60 and \u22123.10 mm for Schirmer (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2264 0.006). Per 1% higher HbA1c, NIBUT decreased by 0.72 s and Schirmer by 1.15\u00a0mm, and DED odds increased (aOR 1.31; all\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001) with no significant non-linearity. DED proportion within strata was 24.0%, 34.0%, and 51.0% (prediabetes aOR 1.60,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.049; diabetes aOR 2.90,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.001). Osmolarity abnormality and MMP\u22129 positivity rose across strata and with HbA1c, remaining significant after FDR control. Using FPG instead of HbA1c yielded concordant effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1788051","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:48:33Z","timestamp":1776055713000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["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"],"prefix":"10.3389","volume":"17","author":[{"given":"Huan","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, First People\u2019s Hospital of Wuyi County","place":["Jinhua, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengsheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Maternal and Child Health Hospital of Wuyi County","place":["Jinhua, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II definition and classification report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocular Surface"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.003","article-title":"TFOS DEWS II epidemiology report","volume":"15","author":"Stapleton","year":"2017","journal-title":"Ocular Surface"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.118.5.615","article-title":"Reliability and validity of the ocular surface disease index","volume":"118","author":"Schiffman","year":"2000","journal-title":"Arch Ophthalmol (Chicago Ill 1960)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/ICL.0000000000001086","article-title":"Patient-reported dry eye treatment and burden of care","volume":"50","author":"Nau","year":"2024","journal-title":"Eye Contact Lens"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2017.06.033","article-title":"Prevalence of diagnosed dry eye disease in the United States among adults aged 18 years and older","volume":"182","author":"Farrand","year":"2017","journal-title":"Am J Ophthalmol"},{"key":"B6","unstructured":"National Diabetes Statistics Report\n          \n          \n          \n          2024"},{"key":"B7","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocular Surface"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S402556","article-title":"The significance of inter-eye osmolarity difference in dry eye diagnostics","volume":"17","author":"Nilsen","year":"2023","journal-title":"Clin Ophthalmol (Auckland NZ)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2015.10.004","article-title":"The matrix metalloproteinase 9 point-of-care test in dry eye","volume":"14","author":"Lanza","year":"2016","journal-title":"Ocular Surface"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1177\/193229681300700509","article-title":"Corneal confocal microscopy to assess diabetic neuropathy: an eye on the foot","volume":"7","author":"Tavakoli","year":"2013","journal-title":"J Diabetes Sci Technol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6997b","article-title":"The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee","volume":"52","author":"Nelson","year":"2011","journal-title":"Invest Ophthalmol Visual Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.001","article-title":"TFOS DEWS II diagnostic methodology report","volume":"15","author":"Wolffsohn","year":"2017","journal-title":"Ocular Surface"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1036002","article-title":"Tear function in patients with diabetes mellitus: a systematic review and meta-analysis","volume":"13","author":"Kuo","year":"2022","journal-title":"Front Endocrinol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2025.109149","article-title":"Is there a link between dry eye disease and diabetes mellitus? 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