{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:44:48Z","timestamp":1773326688505,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2016YFC0901200"],"award-info":[{"award-number":["2016YFC0901200"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2022YFS0612"],"award-info":[{"award-number":["2022YFS0612"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>In recent years, proteomics research has surged, with numerous observational studies identifying associations between plasma proteins and type 2 diabetes. However, research specifically focusing on the ratios of plasma proteins in type 2 diabetes remains relatively scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study primarily employed a two\u2010sample, two\u2010step Mendelian randomization (MR) approach, leveraging genetic data from several large, publicly accessible genome\u2010wide association studies, wherein single nucleotide polymorphisms served as proxies for exposures and diseases. Within this framework, we applied two\u2010sample MR to assess the associations between the 2821 plasma protein\u2010to\u2010protein ratios and type 2 diabetes along with its complications and utilized reverse MR to confirm the unidirectionality of these causal relationships. In addition, we employed two\u2010step MR to investigate the potential mediating role of body mass index in these associations. To augment the robustness of our findings, we systematically implemented a series of sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results gleaned from the inverse\u2010variance weighted method elucidated that a cumulative sum of 23 protein\u2010to\u2010protein ratios bore a causal nexus with type 2 diabetes across both sample cohorts. With each incremental elevation of 1 standard deviation in the genetically anticipated protein\u2010to\u2010protein ratio, the susceptibility to type 2 diabetes oscillated from 0.93 (95% confidence interval: 0.87, 1.00) for the CNTN3\/NCSS1 protein level ratio to 1.13 (1.06, 1.22) for the DBNL\/NCK2 protein level ratio. Moreover, a tally of eight protein\u2010to\u2010protein ratios correlated with a minimum of one complication linked to type 2 diabetes. Diverse sensitivity analyses corroborated the robustness of these observations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The outcomes of our investigation unveiled correlations between 23 plasma protein\u2010to\u2010protein ratios and type 2 diabetes, with eight of these ratios entwined with complications of type 2 diabetes. These discoveries offer novel perspectives on the diagnosis and management of type 2 diabetes and its associated complications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15792","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T03:25:17Z","timestamp":1721273117000},"page":"4410-4417","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The causal relationship between plasma protein\u2010to\u2010protein ratios and type 2 diabetes and its complications: Proteomics mendelian randomization study"],"prefix":"10.1111","volume":"26","author":[{"given":"Yue\u2010Yang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Affiliated Hospital of Southwest Medical University  Luzhou China"},{"name":"Metabolic Vascular Disease Key Laboratory of Sichuan Province  Luzhou China"},{"name":"Sichuan Clinical Research Center for 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