{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:57:56Z","timestamp":1787165876086,"version":"build-2736575974"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2506000, 2023YFC2506001"],"award-info":[{"award-number":["2023YFC2506000, 2023YFC2506001"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"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>Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder associated with a substantial metabolic burden. However, large-scale, real-world studies assessing sex-specific multimorbidity patterns in T1DM remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize the clinical profiles and multimorbidity patterns in patients with T1DM, using age- and sex-matched individuals with type 2 diabetes mellitus (T2DM) as comparators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the Shanghai Hospital Link Database, we identified patients aged 10\u201379 years with a first T1DM-coded diagnosis between 2014 and 2023 and selected 1:1 sex- and index-age\u2013matched T2DM comparators. Clinical characteristics were compared between groups overall and stratified by sex. Sex-stratified multimorbidity networks were constructed and analyzed using standard network metrics. Subgroup-unique comorbid disease pairs were identified using the Salton Cosine Index.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 18,971 patients with T1DM and 18,971 matched T2DM comparators. Compared with T2DM, T1DM showed shorter observed follow-up, higher glycated hemoglobin, higher high-density lipoprotein cholesterol, and lower triglyceride, with more pronounced differences among females. Hypertension and dyslipidemia were the most central comorbidities across all networks, closely linked to cardiovascular and cerebrovascular conditions. The female T1DM network exhibited greater complexity and connectivity than the male T1DM network. Subgroup-unique pairs were more frequent in T1DM, including peripheral vascular disease\u2013nonalcoholic fatty liver disease and diabetic eye complications\u2013stroke in males, and neuropathy\u2013osteoporosis, nephropathy\u2013chronic gastritis, and chronic gastritis\u2013asthma in females.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We identified shared cardiometabolic comorbidities (hypertension and dyslipidemia) across diabetes types and sexes, and sex-specific multimorbidity co-occurrence signatures in T1DM. These findings support integrating blood pressure and lipid optimization with glycemic management, and underscore the need for sex-sensitive surveillance of subgroup-specific clusters, highlighting broader multisystem clustering in females and vascular-risk co-occurrence signals in males that may warrant intensified multifactorial atherosclerotic cardiovascular disease prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1712484","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:55:27Z","timestamp":1771397727000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mapping sex-based multimorbidity networks in type 1 diabetes: a real-world study from Shanghai"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuxuan","family":"Sheng","sequence":"first","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"He","sequence":"additional","affiliation":[{"name":"Link Healthcare Engineering and Information Department, Shanghai Hospital Development Center","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlei","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haolei","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayan","family":"Yao","sequence":"additional","affiliation":[{"name":"Computer Net Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbin","family":"Xue","sequence":"additional","affiliation":[{"name":"Computer Net Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Wonders Information Co. Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zizheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqiong","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"B1","volume-title":"IDF Diabetes Atlas","year":"2025"},{"key":"B2","doi-asserted-by":"publisher","first-page":"9357","DOI":"10.3390\/ijms24119357","article-title":"Effects of hypoglycemia on cardiovascular function in patients with diabetes","volume":"24","author":"Christou","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-0830","article-title":"Incidences\u00a0of severe hypoglycemia and diabetic ketoacidosis and prevalence of microvascular complications stratified by age and glycemic control in U.S. Adult patients with type 1 diabetes: A real-world study","volume":"42","author":"Pettus","year":"2019","journal-title":"Diabetes Care"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-024-06273-7","article-title":"Metabolic health in people living with type 1 diabetes in Belgium: a repeated cross-sectional study","volume":"67","author":"Lavens","year":"2024","journal-title":"Diabetologia"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3967\/bes2024.162","article-title":"Report on cardiovascular health and diseases in China 2023: an updated summary","volume":"37","year":"2024","journal-title":"BioMed Environ Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e000503","DOI":"10.1136\/bmjdrc-2017-000503","article-title":"Real-world crude incidence of hypoglycemia in adults with diabetes: Results of the InHypo-DM Study, Canada","volume":"6","author":"Ratzki-Leewing","year":"2018","journal-title":"BMJ Open Diabetes Res Care"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1177\/1932296820965261","article-title":"Multimorbidity among adult outpatients with type 1 diabetes in Germany","volume":"16","author":"van den Boom","year":"2022","journal-title":"J Diabetes Sci Technol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsb1609216","article-title":"Real-world evidence - what is it and what can it tell us","volume":"375","author":"Sherman","year":"2016","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e213","DOI":"10.3346\/jkms.2018.33.e21","article-title":"Real-world evidence versus randomized controlled trial: clinical research based on electronic medical records","volume":"33","author":"Kim","year":"2018","journal-title":"J Korean Med Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-023-01458-6","article-title":"The role of real-world evidence in treatment decision-making, regulatory assessment, and understanding the perspectives of people with type 2 diabetes: examples with gliclazide MR","volume":"14","author":"Khunti","year":"2023","journal-title":"Diabetes Ther"},{"key":"B11","doi-asserted-by":"publisher","first-page":"107979","DOI":"10.1016\/j.isci.2023.107979","article-title":"A network-based study reveals multimorbidity patterns in people with type 2 diabetes","volume":"26","author":"Zhang","year":"2023","journal-title":"iScience"},{"key":"B12","doi-asserted-by":"publisher","first-page":"101584","DOI":"10.1016\/j.eclinm.2022.101584","article-title":"Variations in comorbidity burden in people with type 2 diabetes over disease duration: A population-based analysis of real world evidence","volume":"52","author":"Pearson-Stuttard","year":"2022","journal-title":"EClinicalMedicine"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2416","DOI":"10.1038\/s41598-020-59336-1","article-title":"MorbiNet: multimorbidity networks in adult general population. Analysis of type 2 diabetes mellitus comorbidity","volume":"10","author":"Aguado","year":"2020","journal-title":"Sci Rep"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-7552(98)00110-X","article-title":"The anatomy of a large-scale hypertextual web search engine","volume":"30","author":"Brin","year":"1998","journal-title":"Comput Netw"},{"key":"B15","doi-asserted-by":"publisher","first-page":"102229","DOI":"10.1016\/j.ijinfomgt.2020.102229","article-title":"Which similarity measure to use in network analysis: Impact of sample size on phi correlation coefficient and Ochiai index","volume":"55","author":"Kalgotra","year":"2020","journal-title":"Int J Inf Manag"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/asi.21009","article-title":"The relation between Pearson\u2019s correlation coefficient r and Salton\u2019s cosine measure","volume":"60","author":"Egghe","year":"2009","journal-title":"J Am Soc Inf Sci Technol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nrg2918","article-title":"Network medicine: a network-based approach to human disease","volume":"12","author":"Barab\u00e1si","year":"2011","journal-title":"Nat Rev Genet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e1000353","DOI":"10.1371\/journal.pcbi.1000353","article-title":"A dynamic network approach for the study of human phenotypes","volume":"5","author":"Hidalgo","year":"2009","journal-title":"PloS Comput Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S2589-7500(22)00187-X","article-title":"Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a population-based study","volume":"5","author":"Kuan","year":"2023","journal-title":"Lancet Digit Health"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmedinf.2017.09.014","article-title":"Examining health disparities by gender: A multimorbidity network analysis of electronic medical record","volume":"108","author":"Kalgotra","year":"2017","journal-title":"Int J Med Inform"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01225-8","article-title":"Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis","volume":"387","author":"Ettehad","year":"2016","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61350-5","article-title":"Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials","volume":"376","author":"Baigent","year":"2010","journal-title":"Lancet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1706292","article-title":"Mortality and cardiovascular disease in type 1 and type 2 diabetes","volume":"377","author":"Rawshani","year":"2017","journal-title":"N Engl J Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00172-8","article-title":"Long-term population-based trends in the incidence of cardiovascular disease in individuals with type 1 diabetes from Finland: a retrospective, nationwide, cohort study","volume":"9","author":"Harjutsalo","year":"2021","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.04.030","article-title":"Prevalence of non-alcoholic fatty liver disease and its association with cardiovascular disease in patients with type 1 diabetes","volume":"53","author":"Targher","year":"2010","journal-title":"J Hepatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1161\/ATV.0000000000000153","article-title":"Nonalcoholic fatty liver disease and cardiovascular risk: A scientific statement from the american heart association","volume":"42","author":"Duell","year":"2022","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0912063","article-title":"Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease","volume":"363","author":"Targher","year":"2010","journal-title":"N Engl J Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0669","article-title":"Incidence of stroke according to presence of diabetic nephropathy and severe diabetic retinopathy in patients with type 1 diabetes","volume":"36","author":"H\u00e4gg","year":"2013","journal-title":"Diabetes Care"},{"key":"B29","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1186\/s12933-024-02235-w","article-title":"Stroke incidence increases with diabetic retinopathy severity and macular edema in type 1 diabetes","volume":"23","author":"Eriksson","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1161\/01.STR.0000254547.91276.50","article-title":"Is diabetic retinopathy an independent risk factor for ischemic stroke","volume":"38","author":"Cheung","year":"2007","journal-title":"Stroke"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2007.12.001","article-title":"Diabetic retinopathy and systemic vascular complications","volume":"27","author":"Cheung","year":"2008","journal-title":"Prog Retin Eye Res"},{"key":"B32","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/S2213-8587(14)70248-7","article-title":"Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis","volume":"3","author":"Huxley","year":"2015","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e2230710","DOI":"10.1001\/jamanetworkopen.2022.30710","article-title":"Cardiometabolic risk factors and incident cardiovascular disease events in women vs men with type 1 diabetes","volume":"5","author":"Braffett","year":"2022","journal-title":"JAMA Netw Open"},{"key":"B34","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1186\/s12933-025-02791-9","article-title":"Cardiovascular disease in women\u00a0with type 1 diabetes: a narrative review and insights from a population-based cohort analysis","volume":"24","author":"Mesa","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1186\/s12933-024-02419-4","article-title":"Sex\u00a0inequalities in cardiovascular risk factors and their management in primary prevention in adults living with type 1 diabetes in Germany and France: findings from DPV and SFDT1","volume":"23","author":"Cosson","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1089\/jwh.2019.7935","article-title":"Sex differences in autoimmune multimorbidity in type 1 diabetes mellitus and the risk of cardiovascular and renal disease: A longitudinal study in the United States, 2001-2017","volume":"29","author":"Rogers","year":"2020","journal-title":"J Womens Health (Larchmt)"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1712484\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:55:29Z","timestamp":1771397729000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1712484\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":36,"alternative-id":["10.3389\/fendo.2026.1712484"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1712484","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"article-number":"1712484"}}