{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T15:10:24Z","timestamp":1777648224401,"version":"3.51.4"},"reference-count":36,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"unspecified","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["R21AR071681"],"award-info":[{"award-number":["R21AR071681"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Diab Res Care"],"accepted":{"date-parts":[[2021,8,25]]},"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>People with type 2 diabetes (T2D) have an increased rate of hospitalization and mortality related to COVID-19. To identify ahead of time those who are at risk of developing severe diseases and potentially in need of intensive care, we investigated the independent associations between longitudinal glycated hemoglobin (HbA1c), the impact of common medications (metformin, insulin, ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and corticosteroids) and COVID-19 severity in people with T2D.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Research design and methods<\/jats:title>\n                  <jats:p>Retrospective cohort study was conducted using deidentified claims and electronic health record data from the OptumLabs Data Warehouse across the USA between January 2017 and November 2020, including 16\u2009504 individuals with T2D and COVID-19. A univariate model and a multivariate model were applied to evaluate the association between 2 and 3-year HbA1c average, medication use between COVID-19 diagnosis and intensive care unit admission (if applicable), and risk of intensive care related to COVID-19.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>With covariates adjusted, the HR of longitudinal HbA1c for risk of intensive care was 1.12 (per 1% increase, p&lt;0.001) and 1.48 (comparing group with poor (HbA1c \u22659%) and adequate glycemic control (HbA1c 6%\u20139%), p&lt;0.001). The use of corticosteroids and the combined use of insulin and metformin were associated with significant reduction of intensive care risk, while ACEIs and ARBs were not associated with reduced risk of intensive care.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Two to three-year longitudinal glycemic level is independently associated with COVID-19-related severity in people with T2D. Here, we present a potential method to use HbA1c history, which presented a stronger association with COVID-19 severity than single-point HbA1c, to identify in advance those more at risk of intensive care due to COVID-19 in the T2D population. The combined use of metformin and insulin and the use of corticosteroids might be significant to prevent patients with T2D from becoming critically ill from COVID-19.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjdrc-2021-002299","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T12:35:13Z","timestamp":1631018113000},"page":"e002299","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Evaluation and management of COVID-19-related severity in people with type 2 diabetes"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0049-1623","authenticated-orcid":false,"given":"Bowen","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Biotechnology and Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA"},{"name":"OptumLabs Visiting Fellow, Optum Health, Eden Prairie, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin S","family":"Glicksberg","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA"},{"name":"Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girish N","family":"Nadkarni","sequence":"additional","affiliation":[{"name":"Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, New York, USA"},{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York City, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak","family":"Vashishth","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA"},{"name":"OptumLabs Visiting Fellow, Optum Health, Eden Prairie, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"2025073112551896000_9.1.e002299.1","unstructured":"WHO . WHO coronavirus (COVID-19) dashboard, 2021. Available: https:\/\/covid19.who.int"},{"key":"2025073112551896000_9.1.e002299.2","unstructured":"Ritchie H , Ortiz-Ospina E , Beltekian D . Coronavirus pandemic (COVID-19). Our World Data, 2020. Available: https:\/\/ourworldindata.org\/covid-vaccinations"},{"key":"2025073112551896000_9.1.e002299.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2108891"},{"key":"2025073112551896000_9.1.e002299.4","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/S2213-8587(20)30238-2","article-title":"COVID-19 in people with diabetes: understanding the reasons for worse outcomes","volume":"8","author":"Apicella","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2025073112551896000_9.1.e002299.5","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S2213-2600(20)30079-5","article-title":"Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study","volume":"8","author":"Yang","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2025073112551896000_9.1.e002299.6","doi-asserted-by":"publisher","DOI":"10.1111\/all.14238"},{"key":"2025073112551896000_9.1.e002299.7","doi-asserted-by":"crossref","DOI":"10.1007\/s42000-020-00259-x","article-title":"The association of diabetes with COVID-19 disease severity: evidence from adjusted effect estimates","volume":"20","author":"Liang","year":"2021","journal-title":"Hormones"},{"key":"2025073112551896000_9.1.e002299.8","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30271-0"},{"key":"2025073112551896000_9.1.e002299.9","unstructured":"Conlen M , Keefe J , Leatherby L , et al . How full are hospital I.C.U.s near you? The New York Times, 2020. Available: https:\/\/www.nytimes.com\/interactive\/2020\/us\/covid-hospitals-near-you.html"},{"key":"2025073112551896000_9.1.e002299.10","doi-asserted-by":"crossref","DOI":"10.3390\/jcm8122219","article-title":"Type 2 Diabetes Mellitus and Altered Immune System Leading to Susceptibility to Pathogens, Especially Mycobacterium tuberculosis","volume":"8","author":"Ferlita","year":"2019","journal-title":"J Clin Med"},{"key":"2025073112551896000_9.1.e002299.11","doi-asserted-by":"publisher","DOI":"10.2174\/1568010042634488"},{"key":"2025073112551896000_9.1.e002299.12","first-page":"S64","article-title":"Diagnosis and classification of diabetes mellitus","volume":"35 Suppl 1","year":"2012","journal-title":"Diabetes Care"},{"key":"2025073112551896000_9.1.e002299.13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41413-020-00105-1","article-title":"Fracture risk in type 2 diabetes: longitudinal glycemic control based prediction and the efficacy of medications","volume":"35","author":"Wang","year":"2020","journal-title":"Journal of Bone and Mineral Research"},{"key":"2025073112551896000_9.1.e002299.14","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.pcd.2020.06.010","article-title":"COVID-19 and diabetes: what does the clinician need to know?","volume":"14","author":"Papadokostaki","year":"2020","journal-title":"Prim Care Diabetes"},{"key":"2025073112551896000_9.1.e002299.15","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.therap.2020.05.006","article-title":"And COVID-19","volume":"75","author":"Bouhanick","year":"2020","journal-title":"Therapies"},{"key":"2025073112551896000_9.1.e002299.16","doi-asserted-by":"crossref","first-page":"423-426","DOI":"10.1016\/j.diabet.2020.07.006","article-title":"Metformin and COVID-19: from cellular mechanisms to reduced mortality","volume":"46","author":"Scheen","year":"2020","journal-title":"Diabetes Metab"},{"key":"2025073112551896000_9.1.e002299.17","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.chest.2020.10.054","article-title":"Impact of corticosteroids in coronavirus disease 2019 outcomes: systematic review and meta-analysis","volume":"159","author":"Cano","year":"2021","journal-title":"Chest"},{"key":"2025073112551896000_9.1.e002299.18","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-020-04641-3","article-title":"Corticosteroid therapy for critically ill patients with COVID-19: a structured summary of a study protocol for a prospective meta-analysis of randomized trials","volume":"21","author":"Sterne","year":"2020","journal-title":"Trials"},{"key":"2025073112551896000_9.1.e002299.19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2174\/1874306401408010101","article-title":"Effect of inhaled corticosteroids on glycemic status","volume":"8","author":"Egbuonu","year":"2014","journal-title":"Open Respir Med J"},{"key":"2025073112551896000_9.1.e002299.20","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1186\/s13054-020-03195-9","article-title":"ACEI\/ARB therapy in COVID-19: the double-edged sword of ACE2 and SARS-CoV-2 viral docking","volume":"24","author":"Onweni","year":"2020","journal-title":"Crit Care"},{"key":"2025073112551896000_9.1.e002299.21","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-0660"},{"key":"2025073112551896000_9.1.e002299.22","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1161\/CIRCRESAHA.120.317134","article-title":"Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19","volume":"126","author":"Zhang","year":"2020","journal-title":"Circ Res"},{"key":"2025073112551896000_9.1.e002299.23","unstructured":"OptumLabs . OptumLabs and OptumLabs data warehouse (OLDW) descriptions and citation. PDF. Reproduced with permission from OptumLabs. Eden prairie, MN: OptumLabs, 2020."},{"key":"2025073112551896000_9.1.e002299.24","unstructured":"Hang L . Panther user guide: data overview and use in applied research. n.p.. PDF. Reproduced with permission from OptumLabs. Cambridge, MA: OptumLabs, 2021."},{"key":"2025073112551896000_9.1.e002299.25","doi-asserted-by":"publisher","DOI":"10.5888\/pcd9.120065"},{"key":"2025073112551896000_9.1.e002299.26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0108145","article-title":"Defining the role of medication adherence in poor glycemic control among a general adult population with diabetes","volume":"9","author":"Feldman","year":"2014","journal-title":"PLoS One"},{"key":"2025073112551896000_9.1.e002299.27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121698"},{"key":"2025073112551896000_9.1.e002299.28","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.diabres.2017.08.013","article-title":"Longitudinal trends in HbA1c and associations with comorbidity and all-cause mortality in Asian patients with type 2 diabetes: a cohort study","volume":"133","author":"Luo","year":"2017","journal-title":"Diabetes Res Clin Pract"},{"key":"2025073112551896000_9.1.e002299.29","doi-asserted-by":"crossref","DOI":"10.1186\/s13293-020-00330-7","article-title":"Sex differences in severity and mortality from COVID-19: are males more vulnerable?","volume":"11","author":"Pradhan","year":"2020","journal-title":"Biol Sex Differ"},{"key":"2025073112551896000_9.1.e002299.30","doi-asserted-by":"crossref","unstructured":"Jin J-M , Bai P , He W , et al . Gender differences in patients with COVID-19: focus on severity and mortality. Front Public Health 2020;8.doi:10.3389\/fpubh.2020.00152","DOI":"10.3389\/fpubh.2020.00152"},{"key":"2025073112551896000_9.1.e002299.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.04.021"},{"key":"2025073112551896000_9.1.e002299.32","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-020-05180-x"},{"key":"2025073112551896000_9.1.e002299.33","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1111\/dom.14393","article-title":"Preinfection glycaemic control and disease severity among patients with type 2 diabetes and COVID-19: a retrospective, cohort study","volume":"23","author":"Hayek","year":"2021","journal-title":"Diabetes Obes Metab"},{"key":"2025073112551896000_9.1.e002299.34","article-title":"Metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes","author":"Crouse","year":"2020","journal-title":"medRxiv"},{"key":"2025073112551896000_9.1.e002299.35","doi-asserted-by":"crossref","first-page":"100454","DOI":"10.1016\/j.waojou.2020.100454","article-title":"Does hereditary angioedema make COVID-19 worse?","volume":"13","author":"Xu","year":"2020","journal-title":"World Allergy Organ J"},{"key":"2025073112551896000_9.1.e002299.36","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.17023"}],"container-title":["BMJ Open Diabetes Research &amp; Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjdrc-2021-002299","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T19:55:31Z","timestamp":1753991731000},"score":1,"resource":{"primary":{"URL":"https:\/\/drc.bmj.com\/lookup\/doi\/10.1136\/bmjdrc-2021-002299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,9,7]]},"published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1136\/bmjdrc-2021-002299"],"URL":"https:\/\/doi.org\/10.1136\/bmjdrc-2021-002299","relation":{},"ISSN":["2052-4897"],"issn-type":[{"value":"2052-4897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9]]}}}