{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:58:05Z","timestamp":1789466285137,"version":"build-2803163510"},"reference-count":200,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2023,8]]},"abstract":"Abstract<\/jats:title>\n Aims\/hypothesis<\/jats:title>\n To provide a systematic overview of the current body of evidence on high-risk phenotypes of diabetes associated with COVID-19 severity and death.<\/jats:p>\n <\/jats:sec>\n Methods<\/jats:title>\n This is the first update of our recently published living systematic review and meta-analysis. Observational studies investigating phenotypes in individuals with diabetes and confirmed SARS-CoV-2 infection with regard to COVID-19-related death and severity were included. The literature search was conducted from inception up to 14 February 2022 in PubMed, Epistemonikos, Web of Science and the COVID-19 Research Database and updated using PubMed alert to 1 December 2022. A random-effects meta-analysis was used to calculate summary relative risks (SRRs) with 95% CIs. The risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) tool and the certainty of evidence using the GRADE approach.<\/jats:p>\n <\/jats:sec>\n Results<\/jats:title>\n A total of 169 articles (147 new studies) based on approximately 900,000 individuals were included. We conducted 177 meta-analyses (83 on COVID-19-related death and 94 on COVID-19 severity). Certainty of evidence was strengthened for associations between male sex, older age, blood glucose level at admission, chronic insulin use, chronic metformin use (inversely) and pre-existing comorbidities (CVD, chronic kidney disease, chronic obstructive pulmonary disease) and COVID-19-related death. New evidence with moderate to high certainty emerged for the association between obesity (SRR [95% CI] 1.18 [1.04, 1.34], n<\/jats:italic>=21 studies), HbA1c<\/jats:sub> (53\u201375 mmol\/mol [7\u20139%]: 1.18 [1.06, 1.32], n<\/jats:italic>=8), chronic glucagon-like peptide-1 receptor agonist use (0.83 [0.71, 0.97], n<\/jats:italic>=9), pre-existing heart failure (1.33 [1.21, 1.47], n<\/jats:italic>=14), pre-existing liver disease (1.40 [1.17, 1.67], n<\/jats:italic>=6), the Charlson index (per 1 unit increase: 1.33 [1.13, 1.57], n<\/jats:italic>=2), high levels of C-reactive protein (per 5 mg\/l increase: 1.07 [1.02, 1.12], n<\/jats:italic>=10), aspartate aminotransferase level (per 5 U\/l increase: 1.28 [1.06, 1.54], n<\/jats:italic>=5), eGFR (per 10 ml\/min per 1.73 m2<\/jats:sup> increase: 0.80 [0.71, 0.90], n<\/jats:italic>=6), lactate dehydrogenase level (per 10 U\/l increase: 1.03 [1.01, 1.04], n<\/jats:italic>=7) and lymphocyte count (per 1\u00d7109<\/jats:sup>\/l increase: 0.59 [0.40, 0.86], n<\/jats:italic>=6) and COVID-19-related death. Similar associations were observed between risk phenotypes of diabetes and severity of COVID-19, with some new evidence on existing\u00a0COVID-19\u00a0 vaccination status (0.32 [0.26, 0.38], n<\/jats:italic>=3), pre-existing hypertension (1.23 [1.14, 1.33], n<\/jats:italic>=49), neuropathy and cancer, and high IL-6 levels. A limitation of this study is that the included studies are observational in nature and residual or unmeasured confounding cannot be ruled out.<\/jats:p>\n <\/jats:sec>\n Conclusions\/interpretation<\/jats:title>\n Individuals with a more severe course of diabetes and pre-existing comorbidities had a poorer prognosis of COVID-19 than individuals with a milder course of the disease.<\/jats:p>\n <\/jats:sec>\n Registration<\/jats:title>\n PROSPERO registration no. CRD42020193692.<\/jats:p>\n <\/jats:sec>\n Previous version<\/jats:title>\n This is a living systematic review and meta-analysis. The previous version can be found at https:\/\/link.springer.com\/article\/10.1007\/s00125-021-05458-8<\/jats:ext-link><\/jats:p>\n <\/jats:sec>\n Funding<\/jats:title>\n The German Diabetes Center (DDZ) is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State North Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD).<\/jats:p>\n <\/jats:sec>\n Graphical Abstract<\/jats:title>\n \n <\/jats:sec>","DOI":"10.1007\/s00125-023-05928-1","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T14:02:11Z","timestamp":1684504931000},"page":"1395-1412","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Risk phenotypes of diabetes and association with COVID-19 severity and death: an update of a living systematic review and meta-analysis"],"prefix":"10.1007","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4244-0832","authenticated-orcid":false,"given":"Sabrina","family":"Schlesinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0584-3213","authenticated-orcid":false,"given":"Alexander","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikoletta","family":"Christodoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Linnerz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4293-3514","authenticated-orcid":false,"given":"Kalliopi","family":"Pafili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3301-5869","authenticated-orcid":false,"given":"Oliver","family":"Kuss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2050-093X","authenticated-orcid":false,"given":"Christian","family":"Herder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-2225","authenticated-orcid":false,"given":"Manuela","family":"Neuenschwander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0855-2769","authenticated-orcid":false,"given":"Janett","family":"Barbaresko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-6382","authenticated-orcid":false,"given":"Michael","family":"Roden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"issue":"7","key":"5928_CR1","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1007\/s00125-021-05458-8","volume":"64","author":"S Schlesinger","year":"2021","unstructured":"Schlesinger S, Neuenschwander M, Lang A et al (2021) Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis. 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Schiemann from the German Diabetes Center (Institute for Biometric and Epidemiology) for assistance in contacting authors of studies with missing information and for data preparation.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgement"}},{"value":"Data were extracted from published research papers, all of which are available and accessible. All datasets generated during the current study are available from the corresponding author on reasonable request. The study protocol has been published (PROSPERO registration no. CRD42020193692; ) and is available without restrictions.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"The German Diabetes Center (DDZ) is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State of North Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD). The funders had no role in the study design or data collection, analysis and interpretation. \u00a0Open Access funding enabled and organised by Projekt DEAL.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"CH is a member of the editorial board of Diabetologia<\/i>. MR received personal fees from Boehringer Ingelheim Pharma, Eli Lilly, Fishawack Group, Novo Nordisk, Sanofi US, Target NASH and Terra Firma, and investigator-initiated research support from Boehringer Ingelheim, Nutricia\/Danone and Sanofi-Aventis. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"MR and SS designed the study and wrote the first draft of the manuscript. AL, NC, PL, MN, JB and SS performed the literature search and literature screening. CH assisted in the selection of eligible studies. AL, NC, PL and MN extracted data and KP assisted with extraction of data on treatment. AL, NC, PL, MN and SS assessed the risk of bias of the studies and JB, MN and SS assessed the certainty of evidence of the associations. SS performed the statistical analysis and OK assisted with the statistical analysis. All authors contributed to data acquisition, data interpretation and revision of manuscript drafts and read and approved the final manuscript. SS is the guarantor of this work.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}