Risk factors for COVID-19 case fatality rate in people with type 1 and type 2 diabetes mellitus: A nationwide retrospective cohort study of 235,248 patients in the Russian Federation
M V Shestakova, O K Vikulova, A R Elfimova, A A Deviatkin, I I Dedov, N G Mokrysheva
Frontiers in Endocrinology, doi:10.3389/fendo.2022.909874
The aim: To study the association of demographic, clinical, and laboratory factors and the use of glucose-lowering drugs and anti-coronavirus disease (COVID-19) vaccination with the COVID-19-related case fatality rate (CFR) in diabetes mellitus (DM) patients. Methods: This study is a nationwide observational cohort study based on the data from the National Diabetes Register (NDR) that is the database containing online clinical information about the population with DM. The outcomes (death or recovery) for COVID-19 were registered in 235,248 patients with DM [type 1 diabetes mellitus (T1DM), n = 11,058; type 2 diabetes mellitus (T2DM), n = 224,190] from March 20, 2020, until November 25, 2021. The unadjusted odds ratio (OR) and 95% confidence interval (CI) were used to estimate the risk factors for CFR. Then the ranging of significant factors was performed and the most vulnerable groups of factors for the lethal outcome were chosen.
Results: The CFR due to COVID-19 was 8.1% in T1DM and 15.3% in T2DM. Increased CFR was associated with the male population [OR = 1.25 (95% CI: 1.09-1.44) in T1DM and 1.18 (95% CI: 1.15-1.21) in T2DM], age ≥65 years [OR = 4.44 (95% CI: 3.75-5.24) in T1DM and 3.18 (95% CI: 3.09-3.26) in T2DM], DM duration ≥10 years [OR = 2.46 (95% CI: 2.06-2.95) in T1DM and 2.11 (95% CI: 2.06-2.16) in T2DM], body mass index (BMI) ≥30 kg/m 2 [OR = 1.95 (95% CI: 1.52-2.50)] in T1DM, HbA1c ≥7% [OR = 1.35 (95% CI: 1.29-1.43)] in T2DM. The atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD) were associated with higher CFR in T1DM but not in T2DM. The pre-COVID-19 glucose-lowering therapy in T2DM was differently associated with CFR (OR): 0.61 (95% CI: 0.59-0.62) for metformin, 0.59 (95% CI: 0.57-0.61) for dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), 0.46 (95% CI: 0.44-0.49) for sodium-glucose co-transporter-2 (SGLT2) inhibitors, 0.38 (95% CI: 0.29-0.51) for glucagon-like peptide-1 receptor agonists (arGLP-1), 1.34 (95% CI: 1.31-1.37) for sulfonylurea (SU), and 1.47 (95% CI: 1.43-1.51) for insulin. Anti-Frontiers in Endocrinology frontiersin.org 01
Ethics statement The studies involving human participants (human data of register medical reports) were reviewed and approved by local ethics committee of Endocrinology Research Centre, Moscow, Russia. The patients/participants provided their written informed consent for use of medical data register records for the study.
Author contributions MS, OV, ID and NM conceived and designed the study. AE, AD, and OV analyzed the data. OV, AD, AE, MS wrote the paper. ID and NM have done final revision of article. All authors, reviewed, edited, and approved the manuscript.
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/ fendo.2022.909874/full#supplementary-material
References
Ando, Horii, Uematsu, Hanaki, Atsuda et al., Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the united states, Sci Rep,
doi:10.1038/s41598-021-96720-xBarron, Bakhai, Kar, Weaver, Bradley et al., Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: A whole-population study, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(20)30272-2Bermingham, Morgan, Nafilyan, Deaths involving COVID-19 by vaccination status
Bornstein, Rubino, Khunti, Mingrone, Hopkins et al., Practical recommendations for the management of diabetes in patients with COVID-19, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(20)30152-2Breland, Wong, Steers, Yuan, Haderlein et al., The effect of metformin consumption on mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis, Diabetes Metab Syndr Clin Res Rev,
doi:10.1016/j.dsx.2020.11.006Chen, Yang, Cheng, Chen, Peng et al., Clinical characteristics and outcomes of patients with diabetes and COVID-19 in association with glucose-lowering medication, Diabetes Care,
doi:10.2337/dc20-0660Corona, Pizzocaro, Vena, Rastrelli, Semeraro et al., Diabetes is most important cause for mortality in COVID-19 hospitalized patients: Systematic review and meta-analysis, Rev Endocr Metab Disord,
doi:10.1007/s11154-021-09630-8Daniels, Ren, Kumar, Bui, Zhang et al., Relation of prior statin and anti-hypertensive use to severity of disease among patients hospitalized with COVID-19: Findings from the American heart association's COVID-19 cardiovascular disease registry, PloS One,
doi:10.1371/journal.pone.0254635Dedov, Shestakova, Vikulova, Zheleznyakova, Isakov, Epidemiological characteristics of diabetes mellitus in the Russian federation: Clinical and statistical analysis according to the federal diabetes register data of 01.01, Diabetes Mellit,
doi:10.14341/DM12759Dispinseri, Lampasona, Secchi, Bazzigaluppi, Negri, Robust neutralizing antibodies to SARS-CoV-2 develop and persist in subjects with diabetes and COVID-19 pneumonia, J Clin Endocrinol Metab,
doi:10.1210/clinem/dgab055Douros, Dell'aniello, Yu, Filion, Azoulay et al., Sulfonylureas as second line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycaemic events: Population based cohort study, BMJ,
doi:10.1136/bmj.k2693Gregg, Sophiea, Weldegiorgis, Diabetes and COVID-19: Population impact 18 months into the pandemic, Diabetes Care,
doi:10.2337/dci21-0001Han, Ma, Sun, Zhang, Qu et al., The association between anti-diabetic agents and clinical outcomes of COVID-19 in patients with diabetes: A systematic review and meta-analysis, Arch Med Res,
doi:10.1101/2021.01.26.21250506Hariyanto, Intan, Hananto, Putri, Kurniawan, Pre-admission glucagon-like peptide-1 receptor agonist (GLP-1RA) and mortality from coronavirus disease 2019 (Covid-19): A systematic review, meta-analysis, and meta-regression, Diabetes Res Clin Pract,
doi:10.1016/j.diabres.2021.109031Holden, Currie, Schramm, Tk, Gislason et al., Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study, Diabetes Obes Metab,
doi:10.1093/eurheartj/ehr077Holman, Knighton, Kar, 'keefe, Curley et al., Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(20)30271-0Hussain, Mahawar, Xia, Yang, El-Hasani, Retraction notice to obesity a nd mortality of COVID-19. Meta-analysis, Obesity Res Clin Pract,
doi:10.1016/j.orcp.2020.12.008Iheanacho, Odili, Eze, Risk of SARS-CoV-2 infection and COVID-19 prognosis with the use of renin-angiotensin-aldosterone system (RAAS) inhibitors: A systematic review, Futur J Pharm Sci,
doi:10.1186/s43094-021-00224-4Kan, Zhang, Han, Xu, Ye et al., Mortality risk of antidiabetic agents for type 2 diabetes with COVID-19: A systematic review and meta-analysis, Front Endocrinol,
doi:10.3389/fendo.2021.708494/fullKhunti, Knighton, Zaccardi, Bakhai, Barron et al., Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: A nationwide observational study in England, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(21)00244-8Kosiborod, Esterline, Furtado, Oscarsson, Gasparyan et al., Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): A randomised, double-blind, placebocontrolled, phase 3 trial, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(21)00180-7Li, Yang, Yan, Sun, Zeng et al., Metformin in patients with COVID-19: A systematic review and meta-analysis, Front Med,
doi:10.3389/fmed.2021.704666Logunov, Dolzhikova, Shcheblyakov, Tukhvatulin, Zubkova et al., Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: An interim analysis of a randomised controlled phase 3 trial in Russia, Lancet,
doi:10.1016/S0140-6736(21)00234-8Mcallister, Risks of and risk factors for COVID-19 disease in people with diabetes: A cohort study of the total population of Scotland, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(20)30405-8Mcgurnaghan, Weir, Bishop, Kennedy, Blackbourn, None
Meijer, Hoekstra, Van Den Oever, Simsek, Van Den Bergh et al., Treatment with a DPP-4 inhibitor at time of hospital admission for COVID-19 is not associated with improved clinical outcomes: Data from the COVID-PREDICT cohort study in the Netherlands, J Diabetes Metab Disord,
doi:10.1007/s40200-021-00833-zPatel, Strong, Fontes, Carvalho, Santos-Ferreira et al., Protective effects of SGLT-2 inhibitors across the cardiorenal continuum: two faces of the same coin, Diabetes Ther Res Treat Educ Diabetes Relat Disord,
doi:10.1093/eurjpc/zwab034Prattichizzo, De Candia, Nicolucci, Ceriello, Elevated HbA1c levels in pre-Covid-19 infection increases the risk of mortality: A sistematic review and meta-analysis, Diabetes Metab Res Rev,
doi:10.1002/DMRR.3476/v2/response1Rakhmat, Kusmala, Handayani, Juliastuti, Nawangsih et al., Dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in coronavirus disease 2019 (COVID-19) -a systematic review, meta-analysis, and meta-regression, Diabetes Metab Syndr,
doi:10.1016/j.dsx.2021.03.027Rawshani, Kjölhede, Rawshani, Sattar, Eeg-Olofsson et al., Severe COVID-19 in people with type 1 and type 2 diabetes in Sweden: A nationwide retrospective cohort study, Lancet Reg Heal -Eur,
doi:10.1016/j.lanepe.2021.100105Santoro, Nuñez-Gil, Vitale, Viana-Llamas, Martinez et al., Antiplatelet therapy and outcome in COVID-19: The health outcome predictive evaluation registry, Heart,
doi:10.1136/heartjnl-2021-319552Sharma, Ray, Sadasivam, Krejner, Bienias et al., DPP4 inhibitors and COVID-19-Holy grail or another dead end?, Arch Immunol Ther Exp (Warsz),
doi:10.1007/s00005-020-00602-5Shestakova, Vikulova, Isakov, Dedov, Diabetes and COVID-19: Analysis of the clinical outcomes according to the data of the Russian diabetes registry, Probl Endokrinol (Mosk),
doi:10.14341/probl12458Williamson, Walker, Bhaskaran, Bacon, Bates et al., Factors associated with COVID-19-related death using OpenSAFELY, Nature,
doi:10.1038/s41586-020-2521-4Yang, Cai, Zhang, Insulin treatment may increase adverse outcomes in patients with COVID-19 and diabetes: A systematic review and meta-analysis, Front Endocrinol,
doi:10.3389/fendo.2021.696087/full
