{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T04:44:05Z","timestamp":1771562645235,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900910"],"award-info":[{"award-number":["81900910"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Results showed that genetically predicted lower fasting glucose were significantly associated with a higher risk of keratoconus [IVW: odds ratio (OR)\u2009=\u20090.382; 95% confidence interval (CI)\u2009=\u20090.261\u20130.560; <jats:italic>p<\/jats:italic>\u2009=\u20098.162\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>]. Genetically predicted lower proinsulin levels were potentially linked to a higher risk of keratoconus (IVW: OR\u2009=\u20090.739; 95% CI\u2009=\u20090.568\u20130.963; <jats:italic>p<\/jats:italic>\u2009=\u20090.025). In addition, genetically predicted type 2 diabetes negatively correlated with keratoconus (IVW: BMI-unadjusted: OR\u2009=\u20090.869; 95% CI\u2009=\u20090.775\u20130.974, <jats:italic>p<\/jats:italic>\u2009=\u20090.016; BMI-adjusted: OR\u2009=\u20090.880, 95% CI\u2009=\u20090.789\u20130.982, <jats:italic>p<\/jats:italic>\u2009=\u20090.022). These associations were further corroborated by the evidence from all sensitivity analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2023.1264061","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T16:11:22Z","timestamp":1699287082000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Causal relationships between type 2 diabetes, glycemic traits and 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