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Methods: This study employed bidirectional Mendelian randomization (MR) using genetic variants as instrumental variables to infer causality in both directions: from T1D to cataracts and cataracts to T1D. Genetic data for T1D, its complications, and cataracts were sourced from independent genome-wide association study (GWAS) datasets. A two-step multivariable MR combined with mediation analysis was conducted to evaluate the indirect effects of serum metabolites in the causal pathway from T1D to cataracts. Results: The MR analysis demonstrated a significant causal association between T1D and an increased risk of cataracts (OR = 1.01\u20131.05; p &lt; 0.05). Further analysis showed that patients with T1D complications such as coma, ketoacidosis, nephropathy, and retinopathy exhibited a significantly higher risk of developing cataracts compared to those without complications. Sensitivity analyses upheld the robustness of these findings, with no evidence of heterogeneity or pleiotropy. Additionally, 102 serum metabolites were found to exhibit statistically significant mediation effects on cataract risk, with four (13-HODE + 9-HODE, 2-naphthol sulfate, docosadienoate (22:2n6), and X-12906) showing significant mediation effects. Specifically, 13-HODE + 9-HODE had a protective effect, while the other three metabolites were linked to an increased cataract risk. Conclusions: This study provides strong evidence of a causal link between T1D and cataracts, highlighting the mediating role of specific serum metabolites. These findings underscore the importance of early detection and management of cataracts in patients with T1D and suggest potential therapeutic targets for mitigating cataract risk. Further research should focus on replicating these findings in diverse populations and exploring the underlying metabolic pathways in greater detail.<\/jats:p>","DOI":"10.3390\/metabo14110644","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T10:37:35Z","timestamp":1732099055000},"page":"644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Type 1 Diabetes and Cataracts: Investigating Mediating Effects of Serum Metabolites Using Bidirectional Mendelian Randomization"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9612-8989","authenticated-orcid":false,"given":"Yumeng","family":"Shi","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Eye Institute, Eye and Ear, Nose, and Throat Hospital of Fudan University, 83 Fenyang Road, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxi","family":"Qin","sequence":"additional","affiliation":[{"name":"Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yankai","family":"Li","sequence":"additional","affiliation":[{"name":"Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Eye Institute, Eye and Ear, Nose, and Throat Hospital of Fudan University, 83 Fenyang Road, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0245-7392","authenticated-orcid":false,"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Eye Institute, Eye and Ear, Nose, and Throat Hospital of Fudan University, 83 Fenyang Road, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1016\/S0140-6736(18)31320-5","article-title":"Type 1 diabetes","volume":"391","author":"DiMeglio","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Keindl, M., Fedotkina, O., du Plessis, E., Jain, R., Bergum, B., Mygind Jensen, T., Laustrup M\u00f8ller, C., Falhammar, H., Nystr\u00f6m, T., and Catrina, S.B. (2020). Increased Plasma Soluble Interleukin-2 Receptor Alpha Levels in Patients With Long-Term Type 1 Diabetes With Vascular Complications Associated With IL2RA and PTPN2 Gene Polymorphisms. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.575469"},{"key":"ref_3","first-page":"6763586","article-title":"Cataract as Early Ocular Complication in Children and Adolescents with Type 1 Diabetes Mellitus","volume":"2018","year":"2018","journal-title":"Int. J. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S0140-6736(17)30544-5","article-title":"Cataracts","volume":"390","author":"Liu","year":"2017","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0140-6736(05)70803-5","article-title":"Age-related cataract","volume":"365","author":"Asbell","year":"2005","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.biopha.2018.09.058","article-title":"Molecular pathways associated with oxidative stress in diabetes mellitus","volume":"108","author":"Ighodaro","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wojnar, W., Zych, M., Borymski, S., and Kaczmarczyk-Sedlak, I. (2020). Chrysin Reduces Oxidative Stress but Does Not Affect Polyol Pathway in the Lenses of Type 1 Diabetic Rats. Antioxidants, 9.","DOI":"10.3390\/antiox9020160"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108230","DOI":"10.1016\/j.exer.2020.108230","article-title":"Status of oxidative stress markers, advanced glycation index, and polyol pathway in age-related cataract subjects with and without diabetes","volume":"200","author":"Chitra","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1080\/02713683.2018.1484146","article-title":"Ameliorative Influence of Dietary Fenugreek (Trigonella foenum-graecum) Seeds and Onion (Allium cepa) on Eye Lens Abnormalities via Modulation of Crystallin Proteins and Polyol Pathway in Experimental Diabetes","volume":"43","author":"Pradeep","year":"2018","journal-title":"Curr. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2020). 11. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes-2020. Diabetes Care, 43, S135\u2013S151.","DOI":"10.2337\/dc20-S011"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2020). 13. Children and Adolescents: Standards of Medical Care in Diabetes-2020. Diabetes Care, 43, S163\u2013S182.","DOI":"10.2337\/dc20-S013"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e227437","DOI":"10.1136\/bcr-2018-227437","article-title":"Diabetes cataract in a 10-year-old girl with new-onset type 1 diabetes mellitus","volume":"12","author":"Quintos","year":"2019","journal-title":"BMJ Case Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1097\/PEC.0b013e318209bf0a","article-title":"Cataracts as the initial manifestation of type 1 diabetes mellitus","volume":"27","author":"Uspal","year":"2011","journal-title":"Pediatr. Emerg. Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e12874","DOI":"10.1097\/MD.0000000000012874","article-title":"Bilateral cataracts as the first manifestation of type 1 diabetes mellitus: A case report","volume":"97","author":"Wu","year":"2018","journal-title":"Medicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s00592-020-01589-3","article-title":"Effects of real-time continuous glucose monitoring in type 1 diabetes: A meta-analysis of randomized controlled trials","volume":"58","author":"Dicembrini","year":"2021","journal-title":"Acta Diabetol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2337\/dc21-0629","article-title":"Continuous Glucose Monitoring in Adults With Type 1 Diabetes With 35 Years Duration From the DCCT\/EDIC Study","volume":"45","author":"Braffett","year":"2022","journal-title":"Diabetes Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"875","DOI":"10.2337\/dc18-2308","article-title":"Risk Factors for Retinopathy in Type 1 Diabetes: The DCCT\/EDIC Study","volume":"42","author":"Hainsworth","year":"2019","journal-title":"Diabetes Care"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1681\/ASN.2016010098","article-title":"Mendelian Randomization as an Approach to Assess Causality Using Observational Data","volume":"27","author":"Sekula","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_19","first-page":"a041302","article-title":"Mendelian Randomization","volume":"12","author":"Birney","year":"2022","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"a040980","DOI":"10.1101\/cshperspect.a040980","article-title":"Using Mendelian Randomization to Improve the Design of Randomized Trials","volume":"11","author":"Ference","year":"2021","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1001\/jama.2021.18236","article-title":"Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization: The STROBE-MR Statement","volume":"326","author":"Skrivankova","year":"2021","journal-title":"JAMA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"n2233","DOI":"10.1136\/bmj.n2233","article-title":"Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): Explanation and elaboration","volume":"375","author":"Skrivankova","year":"2021","journal-title":"BMJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1038\/s41562-022-01412-9","article-title":"Bidirectional two-sample Mendelian randomization analysis identifies causal associations between relative carbohydrate intake and depression","volume":"6","author":"Yao","year":"2022","journal-title":"Nat. Hum. Behav."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1007\/s00125-022-05705-6","article-title":"Mediators of the association between educational attainment and type 2 diabetes mellitus: A two-step multivariable Mendelian randomisation study","volume":"65","author":"Zhang","year":"2022","journal-title":"Diabetologia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"784","DOI":"10.2337\/db19-0831","article-title":"Rare Genetic Variants of Large Effect Influence Risk of Type 1 Diabetes","volume":"69","author":"Forgetta","year":"2020","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/s41586-021-03552-w","article-title":"Interpreting type 1 diabetes risk with genetics and single-cell epigenomics","volume":"594","author":"Chiou","year":"2021","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1038\/s41588-021-00931-x","article-title":"A cross-population atlas of genetic associations for 220 human phenotypes","volume":"53","author":"Sakaue","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/s41586-022-05473-8","article-title":"FinnGen provides genetic insights from a well-phenotyped isolated population","volume":"613","author":"Kurki","year":"2023","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41588-022-01270-1","article-title":"Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases","volume":"55","author":"Chen","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1001\/jama.2017.17219","article-title":"Mendelian Randomization","volume":"318","author":"Emdin","year":"2017","journal-title":"JAMA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"186","DOI":"10.12688\/wellcomeopenres.15555.3","article-title":"Guidelines for performing Mendelian randomization investigations: Update for summer 2023","volume":"4","author":"Burgess","year":"2023","journal-title":"Wellcome Open Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8160256","DOI":"10.1155\/2020\/8160256","article-title":"High Risk of Early Cataracts in Young Type 1 Diabetes Group: A Nationwide Cohort Study","volume":"2020","author":"Lu","year":"2020","journal-title":"Int. J. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1097\/j.jcrs.0000000000001167","article-title":"Comparison of cataract surgery outcomes in patients with type 1 vs type 2 diabetes mellitus and patients without diabetes mellitus","volume":"49","author":"Xia","year":"2023","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Marsiglio, J., McPherson, J.P., Kovacsovics-Bankowski, M., Jeter, J., Vaklavas, C., Swami, U., Grossmann, D., Erickson-Wayman, A., Soares, H.P., and Kerrigan, K. (2023). A single center case series of immune checkpoint inhibitor-induced type 1 diabetes mellitus, patterns of disease onset and long-term clinical outcome. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1229823"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e207","DOI":"10.1016\/j.jemermed.2020.02.005","article-title":"Acute Cataract Development in a Pediatric Patient With Type 1 Diabetes","volume":"58","author":"Cook","year":"2020","journal-title":"J. Emerg. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1007\/s00125-020-05107-6","article-title":"Metabolic alterations in immune cells associate with progression to type 1 diabetes","volume":"63","author":"Sen","year":"2020","journal-title":"Diabetologia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.diabres.2019.04.026","article-title":"Study of the difficult glycemic control in relation to the presence of diabetes-autoantibodies in a sample of Egyptians with type 1 diabetes","volume":"152","author":"Hamed","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejphar.2015.03.096","article-title":"Hydroxyoctadecadienoic acids: Oxidised derivatives of linoleic acid and their role in inflammation associated with metabolic syndrome and cancer","volume":"785","author":"Vangaveti","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mastrogiovanni, M., Trostchansky, A., Naya, H., Dominguez, R., Marco, C., Povedano, M., L\u00f3pez-Vales, R., and Rubbo, H. (2022). HPLC-MS\/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis Patients. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030674"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mrugacz, M., Pony-Uram, M., Bryl, A., and Zorena, K. (2023). Current Approach to the Pathogenesis of Diabetic Cataracts. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076317"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4288004","DOI":"10.1155\/2023\/4288004","article-title":"Action Mechanisms of Metformin Combined with Exenatide and Metformin Only in the Treatment of PCOS in Obese Patients","volume":"2023","author":"Gan","year":"2023","journal-title":"Int. J. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1002\/ijc.29576","article-title":"Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha-tocolpherol, beta-carotene cancer prevention (ATBC) study","volume":"137","author":"Mondul","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.bbrc.2018.04.098","article-title":"Fatty acids modulate the efficacy of lutein in cataract prevention: Assessment of oxidative and inflammatory parameters in rats","volume":"500","author":"Padmanabha","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.bbrc.2020.06.021","article-title":"Fatty acids influence the efficacy of lutein in the modulation of \u03b1-crystallin chaperone function: Evidence from selenite induced cataract rat model","volume":"529","author":"Padmanabha","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Guan, F., Du, W., Zhang, J., Su, C., Zhang, B., Deng, K., Du, S., and Wang, H. (2021). Amino Acids and Lipids Associated with Long-Term and Short-Term Red Meat Consumption in the Chinese Population: An Untargeted Metabolomics Study. Nutrients, 13.","DOI":"10.3390\/nu13124567"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hole\u010dek, M. (2024). Origin and Roles of Alanine and Glutamine in Gluconeogenesis in the Liver, Kidneys, and Small Intestine under Physiological and Pathological Conditions. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137037"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4563","DOI":"10.1172\/JCI131931","article-title":"Hungry for your alanine: When liver depends on muscle proteolysis","volume":"129","author":"Sarabhai","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Hatazawa, Y., Qian, K., Gong, D.W., and Kamei, Y. (2018). PGC-1\u03b1 regulates alanine metabolism in muscle cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0190904"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4671","DOI":"10.1172\/JCI129913","article-title":"Regulation of hepatic mitochondrial oxidation by glucose-alanine cycling during starvation in humans","volume":"129","author":"Petersen","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_50","first-page":"1875870","article-title":"Oxidative Stress, Apoptosis, and Mitochondrial Function in Diabetic Nephropathy","volume":"2018","year":"2018","journal-title":"Int. J. Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Huang, Q., Zhao, D., Lian, F., Li, X., and Qi, W. (2023). The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1112363"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3420187","DOI":"10.1155\/2018\/3420187","article-title":"The Oxidative Stress and Mitochondrial Dysfunction during the Pathogenesis of Diabetic Retinopathy","volume":"2018","author":"Wu","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kang, Q., and Yang, C. (2020). Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications. Redox. Biol., 37.","DOI":"10.1016\/j.redox.2020.101799"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kowluru, R.A., and Mohammad, G. (2022). Mitochondrial Fragmentation in a High Homocysteine Environment in Diabetic Retinopathy. Antioxidants, 11.","DOI":"10.3390\/antiox11020365"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/14\/11\/644\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:36:13Z","timestamp":1760114173000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/14\/11\/644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":54,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["metabo14110644"],"URL":"https:\/\/doi.org\/10.3390\/metabo14110644","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]}}}