{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:16:52Z","timestamp":1788787012460,"version":"build-2803163510"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","diabetesresearchclinicalpractice.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Research and Clinical Practice"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.diabres.2025.112936","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T09:13:41Z","timestamp":1760001221000},"page":"112936","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Diabetic retinopathy and mortality in adults with diabetes: causal mediation analysis of the role of HbA1c"],"prefix":"10.1016","volume":"229","author":[{"given":"Zhiyi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangshun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7053-2120","authenticated-orcid":false,"given":"Xiaojing","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.diabres.2025.112936_b0005","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ecl.2020.05.012","article-title":"Diabetes insipidus: an update","volume":"49","author":"Refardt","year":"2020","journal-title":"Endocrinol Metab Clin North Am"},{"key":"10.1016\/j.diabres.2025.112936_b0010","article-title":"Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study","volume":"362","author":"Xu","year":"2018","journal-title":"BMJ"},{"key":"10.1016\/j.diabres.2025.112936_b0015","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/ceo.13894","article-title":"Diabetic eye disease: a review of screening and management recommendations","volume":"49","author":"Gale","year":"2021","journal-title":"Clin Exp Ophthalmol"},{"key":"10.1016\/j.diabres.2025.112936_b0020","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1136\/bjophthalmol-2012-302005","article-title":"European consortium for the early treatment of diabetic R. Neurodegeneration is an early event in diabetic retinopathy: therapeutic implications","volume":"96","author":"Simo","year":"2012","journal-title":"Br J Ophthalmol"},{"key":"10.1016\/j.diabres.2025.112936_b0025","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40662-015-0026-2","article-title":"Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss","volume":"2","author":"Lee","year":"2015","journal-title":"Eye Vis (Lond)"},{"key":"10.1016\/j.diabres.2025.112936_b0030","doi-asserted-by":"crossref","DOI":"10.1136\/bmjdrc-2023-003758","article-title":"Ocular microvascular complications in diabetic retinopathy: insights from machine learning","volume":"12","author":"Ahmed","year":"2024","journal-title":"BMJ Open Diabetes Res Care"},{"key":"10.1016\/j.diabres.2025.112936_b0035","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11886-019-1107-y","article-title":"Epidemiology of diabetes mellitus and cardiovascular disease","volume":"21","author":"Glovaci","year":"2019","journal-title":"Curr Cardiol Rep"},{"key":"10.1016\/j.diabres.2025.112936_b0040","doi-asserted-by":"crossref","first-page":"4811","DOI":"10.1038\/s41598-025-86559-x","article-title":"Diabetic retinopathy further increases risk of cardiovascular disease mortality in a high-risk cohort","volume":"15","author":"Kha","year":"2025","journal-title":"Sci Rep"},{"key":"10.1016\/j.diabres.2025.112936_b0045","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12886-024-03492-9","article-title":"Associations of retinal microvascular alterations with diabetes mellitus: an OCTA-based cross-sectional study","volume":"24","author":"Yao","year":"2024","journal-title":"BMC Ophthalmol"},{"key":"10.1016\/j.diabres.2025.112936_b0050","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.583687","article-title":"The role of inflammation in diabetic retinopathy","volume":"11","author":"Forrester","year":"2020","journal-title":"Front Immunol"},{"key":"10.1016\/j.diabres.2025.112936_b0055","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23084226","article-title":"Vitamin D and ocular diseases: a systematic review","volume":"23","author":"Chan","year":"2022","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.diabres.2025.112936_b0060","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1004135","article-title":"Healthy lifestyle behaviors, mediating biomarkers, and risk of microvascular complications among individuals with type 2 diabetes: a cohort study","volume":"20","author":"Geng","year":"2023","journal-title":"PLoS Med"},{"key":"10.1016\/j.diabres.2025.112936_b0065","first-page":"242","article-title":"Clinical predictors of diabetic retinopathy progression; a systematic review","volume":"16","author":"Ghamdi","year":"2020","journal-title":"Curr Diabetes Rev"},{"key":"10.1016\/j.diabres.2025.112936_b0070","article-title":"The role of HbA1c in the follow-up and control of diabetes mellitus","volume":"17","author":"Ghanem","year":"2025","journal-title":"Cureus"},{"key":"10.1016\/j.diabres.2025.112936_b0075","doi-asserted-by":"crossref","first-page":"4731","DOI":"10.1038\/s41598-021-84150-8","article-title":"Long-term HbA1c variability and the development and progression of diabetic retinopathy in subjects with type 2 diabetes","volume":"11","author":"Kim","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.diabres.2025.112936_b0080","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00592-020-01605-6","article-title":"Predictions of diabetes complications and mortality using hba1c variability: a 10-year observational cohort study","volume":"58","author":"Lee","year":"2021","journal-title":"Acta Diabetol"},{"key":"10.1016\/j.diabres.2025.112936_b0085","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.ijcard.2015.09.070","article-title":"HbA1c and all-cause mortality risk among patients with type 2 diabetes","volume":"202","author":"Li","year":"2016","journal-title":"Int J Cardiol"},{"issue":"928\u201342","key":"10.1016\/j.diabres.2025.112936_b0090","first-page":"e7","article-title":"Interleukin-33-activated islet-resident innate lymphoid cells promote insulin secretion through myeloid cell retinoic acid production","volume":"47","author":"Dalmas","year":"2017","journal-title":"Immunity"},{"key":"10.1016\/j.diabres.2025.112936_b0095","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s12944-025-02566-x","article-title":"The association between glycated hemoglobin to high density lipoprotein cholesterol ratio and risk of cardiovascular diseases caused death among adult cancer survivors: evidence from NHANES 1999-2018","volume":"24","author":"Sun","year":"2025","journal-title":"Lipids Health Dis"},{"key":"10.1016\/j.diabres.2025.112936_b0100","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1001\/jama.2018.21554","article-title":"Using the E-value to assess the potential effect of unmeasured confounding in observational studies","volume":"321","author":"Haneuse","year":"2019","journal-title":"J Am Med Assoc"},{"key":"10.1016\/j.diabres.2025.112936_b0105","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.2337\/dc07-0264","article-title":"Diabetic retinopathy and the risk of coronary heart disease: the Atherosclerosis Risk in Communities Study","volume":"30","author":"Cheung","year":"2007","journal-title":"Diabetes Care"},{"key":"10.1016\/j.diabres.2025.112936_b0110","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1186\/s12872-020-01763-z","article-title":"Diabetic retinopathy predicts cardiovascular mortality in diabetes: a meta-analysis","volume":"20","author":"Xu","year":"2020","journal-title":"BMC Cardiovasc Disord"},{"key":"10.1016\/j.diabres.2025.112936_b0115","doi-asserted-by":"crossref","DOI":"10.1016\/j.diabres.2025.112229","article-title":"HbA1c variability and all-cause mortality in type 1 and type 2 diabetes: a population-based cohort study using electronic health records","volume":"225","author":"Bowen","year":"2025","journal-title":"Diabetes Res Clin Pract"},{"key":"10.1016\/j.diabres.2025.112936_b0120","doi-asserted-by":"crossref","DOI":"10.1136\/bmjdrc-2014-000060","article-title":"Relationship of HbA1c variability, absolute changes in HbA1c, and all-cause mortality in type 2 diabetes: a Danish population-based prospective observational study","volume":"3","author":"Skriver","year":"2015","journal-title":"BMJ Open Diabetes Res Care"},{"key":"10.1016\/j.diabres.2025.112936_b0125","doi-asserted-by":"crossref","DOI":"10.3390\/cells14050376","article-title":"Diabetic Retinopathy (DR): mechanisms, current therapies, and emerging strategies","volume":"14","author":"Seo","year":"2025","journal-title":"Cells"},{"key":"10.1016\/j.diabres.2025.112936_b0130","doi-asserted-by":"crossref","unstructured":"Gambini J, Stromsnes K. Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches. Biomedicines. 2022;10.","DOI":"10.3390\/biomedicines10040753"},{"key":"10.1016\/j.diabres.2025.112936_b0135","article-title":"Divergent impacts of glycemic control on mortality and complications in patients with early-versus late-onset type 2 diabetes: a retrospective cohort study","volume":"20","author":"Ma","year":"2025","journal-title":"PLoS One"},{"key":"10.1016\/j.diabres.2025.112936_b0140","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s12933-023-02026-9","article-title":"Glycemic control, HbA1c variability, and major cardiovascular adverse outcomes in type 2 diabetes patients with elevated cardiovascular risk: insights from the ACCORD study","volume":"22","author":"Pei","year":"2023","journal-title":"Cardiovasc Diabetol"},{"key":"10.1016\/j.diabres.2025.112936_b0145","article-title":"Detrimental effect of tight glucose control on CV mortality persists over nine years","volume":"95","author":"Shaughnessy","year":"2017","journal-title":"Am Fam Physician"},{"key":"10.1016\/j.diabres.2025.112936_b0150","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.ophtha.2020.12.019","article-title":"Severity of diabetic retinopathy and the risk of future cerebrovascular disease, cardiovascular disease, and all-cause mortality","volume":"128","author":"Modjtahedi","year":"2021","journal-title":"Ophthalmology"},{"key":"10.1016\/j.diabres.2025.112936_b0155","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0210367","article-title":"Mediation of the association of smoking and microvascular complications by glycemic control in type 1 diabetes","volume":"14","author":"Braffett","year":"2019","journal-title":"PLoS One"},{"key":"10.1016\/j.diabres.2025.112936_b0160","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1902\/jop.2015.150149","article-title":"The influence of glycated hemoglobin on the cross susceptibility between type 1 diabetes mellitus and periodontal disease","volume":"86","author":"Lappin","year":"2015","journal-title":"J Periodontol"},{"key":"10.1016\/j.diabres.2025.112936_b0165","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/9570616","article-title":"Advanced glycation end products: potential mechanism and therapeutic target in cardiovascular complications under diabetes","volume":"2019","author":"Yang","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"10.1016\/j.diabres.2025.112936_b0170","doi-asserted-by":"crossref","unstructured":"The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes. 1995;44:968-83.","DOI":"10.2337\/diabetes.44.8.968"},{"key":"10.1016\/j.diabres.2025.112936_b0175","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1161\/01.CIR.96.1.25","article-title":"High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells","volume":"96","author":"Cosentino","year":"1997","journal-title":"Circulation"},{"key":"10.1016\/j.diabres.2025.112936_b0180","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24119352","article-title":"Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections","volume":"24","author":"Gonzalez","year":"2023","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.diabres.2025.112936_b0185","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1073\/pnas.0511154103","article-title":"Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology","volume":"103","author":"Yu","year":"2006","journal-title":"PNAS"},{"key":"10.1016\/j.diabres.2025.112936_b0190","doi-asserted-by":"crossref","first-page":"456","DOI":"10.4239\/wjd.v6.i3.456","article-title":"Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus","volume":"6","author":"Tangvarasittichai","year":"2015","journal-title":"World J Diabetes"},{"key":"10.1016\/j.diabres.2025.112936_b0195","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1139\/Y10-018","article-title":"Oxidative stress and diabetic cardiovascular disorders: roles of mitochondria and NADPH oxidase","volume":"88","author":"Shen","year":"2010","journal-title":"Can J Physiol Pharmacol"},{"key":"10.1016\/j.diabres.2025.112936_b0200","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/s41433-018-0032-4","article-title":"Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction","volume":"32","author":"Sorrentino","year":"2018","journal-title":"Eye (Lond)"},{"key":"10.1016\/j.diabres.2025.112936_b0205","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1111\/jdi.13020","article-title":"Cutaneous microangiopathy in patients with type 2 diabetes: Impaired vascular endothelial growth factor expression and its correlation with neuropathy, retinopathy and nephropathy","volume":"10","author":"Sugimoto","year":"2019","journal-title":"J Diabetes Invest"},{"key":"10.1016\/j.diabres.2025.112936_b0210","first-page":"e5667","article-title":"Application of negative pressure wound therapy with instillation and dwell time of the open abdomen: initial experience","volume":"11","author":"Fernandez","year":"2019","journal-title":"Cureus"},{"key":"10.1016\/j.diabres.2025.112936_b0215","doi-asserted-by":"crossref","DOI":"10.1016\/j.diabet.2020.03.005","article-title":"Diabetic retinopathy in well-controlled type 2 diabetes: role of glycaemic memory","volume":"47","author":"Ducos","year":"2021","journal-title":"Diabetes Metab"}],"container-title":["Diabetes Research and Clinical Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168822725009507?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168822725009507?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T14:24:18Z","timestamp":1764080658000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168822725009507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":43,"alternative-id":["S0168822725009507"],"URL":"https:\/\/doi.org\/10.1016\/j.diabres.2025.112936","relation":{},"ISSN":["0168-8227"],"issn-type":[{"value":"0168-8227","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Diabetic retinopathy and mortality in adults with diabetes: causal mediation analysis of the role of HbA1c","name":"articletitle","label":"Article Title"},{"value":"Diabetes Research and Clinical Practice","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.diabres.2025.112936","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"112936"}}