In early phases of the COVID-19 pandemic, persons who recovered from infection had increased risks for new-onset cardiometabolic diseases, including diabetes, hypertension, and hyperlipidemia.1-3 In the current pandemic phase, which is dominated by less virulent Omicron variants,4 it remains unclear whether risks of cardiometabolic disease after COVID-19 infection persist or have become attenuated and whether vaccination status is associated with these risks.
This large cohort study of adult patients with 1 or more COVID-19 infections treated within the Cedars-Sinai Health System in Los Angeles, California from March 2020 to June 2022 used International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes (eTable in Supplement 1) to identify cardiometabolic diagnoses (hypertension, hyperlipidemia, and diabetes) newly reported before or after a patient’s first COVID-19 infection.5 A self-controlled exposure-crossover design6 was used to estimate odds of a new cardiometabolic diagnosis occurring 90 days after vs 90 days before COVID-19 infection. To account for temporal confounders arising from disruptions in health care use during the pandemic, we compared the odds of a new cardiometabolic diagnosis with those of a new benchmark diagnosis (ie, urinary tract infection and gastroesophageal reflux), representing a marker of health care engagement unrelated to COVID-19. In multivariable logistic regression models, we estimated the odds ratio (OR) for a new cardiometabolic vs new benchmark diagnosis occurring 90 days after vs before infection while adjusting for age, sex, timing of infection (before vs after emergence of Omicron variant), and COVID-19 vaccination status (eMethods in Supplement 1). The study was approved by the Cedars Sinai Medical Center Institutional Review Board, which waived the informed consent requirement given the study’s retrospective nature. We followed the STROBE reporting guideline.
Data were analyzed using R, version 4.2.1 (R Foundation for Statistical Computing). The threshold for statistical significance was a 2-tailed P <.05.
The cohort of 23 709 patients (mean [SD] age, 47.4 [19.3] years) included 12 706 females (54%) and 10 981 males (46%) (22 patients of unknown sex) with 1 or more COVID infection. Rates of new-onset diabetes, hypertension, hyperlipidemia, and benchmark diagnoses occurring in the 90 days after COVID-19 infection were higher than those before infection (Figure). The highest odds postinfection were for diabetes (2.35; 95% CI, 1.94-2.89; P < .001), followed by hypertension (1.54; 95% CI, 1.35-1.76; P < .001), benchmark diagnoses (1.42; 95% CI, 1.25-1.61; P < .001), and hyperlipidemia (1.22; 95% CI, 1.03-1.47; P = .03). In adjusted multivariable models, risk of new-onset diabetes (vs benchmark) diagnosis occurring after vs before COVID-19 infection was significantly elevated (OR, 1.58; 95% CI, 1.24-2.02; P < .001); however, risks of hypertension and hyperlipidemia vs benchmark diagnoses were not (Table). Although the diabetes risk after infection was higher among unvaccinated (OR, 1.78; 95% CI, 1.35-2.37; P < .001) than vaccinated (OR, 1.07; 95% CI, 0.64-1.77; P = .80) patients, the interaction term between vaccination status and diabetes diagnosis was not statistically significant (OR, 0.59; 95% CI, 0.34-1.06; P = .08). There was no evidence of interaction by age, sex, or preexisting cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any model (Table).
In this cohort study, COVID-19 infection was associated with increased risk of diabetes, consistent findings of a meta-analysis.1 Our results suggest that this risk persisted as the Omicron variant became predominant, and the association remained even after accounting for temporal confounders. Diabetes risk after COVID-19 infection was higher in unvaccinated than vaccinated patients, suggesting a benefit of vaccination. Mechanisms contributing to postinfection diabetes risk remain unclear, although persistent inflammation contributing to insulin resistance is a proposed pathway. Study limitations include reliance on diagnostic coding, unaccounted confounders (infection severity indices), and insufficient sample size and statistical power for testing multiple interactions. Additional studies are needed to understand cardiometabolic sequelae of COVID-19 and whether COVID-19 vaccination attenuates risk of cardiometabolic disease.
Accepted for Publication: December 26, 2022.
Published: February 14, 2023. doi:10.1001/jamanetworkopen.2022.55965
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2023 Kwan AC et al. JAMA Network Open.
Corresponding Author: Alan C. Kwan, MD, MSc, 127 S San Vicente Blvd, AHSP A3600, Los Angeles, CA 90048 (alan.kwan@cshs.org).
Author Contributions: Alan Kwan and Susan Cheng had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Kwan, Cheng.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Kwan, Cheng.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Kwan, Claggett.
Obtained funding: Cheng.
Administrative, technical, or material support: Kwan, Ebinger, Botting, Cheng.
Supervision: Cheng.
Conflict of Interest Disclosures: Dr Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study. Dr Claggett reported receiving personal fees from consulting for Cardurion, Corvia, Cytokinetics, Intellia, and Novartis outside the submitted work. Dr Cheng reported receiving grants from the National Institutes of Health (NIH) and personal fees from Zogenix outside the submitted work. No other disclosures were reported.
Funding/Support: This work was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation (grant 2020059; Dr Kwan), and NIH grants R01-HL151828 (Dr Cheng), R01-HL131532 (Dr Cheng), and K23-HL153888 (Dr Ebinger).
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 2.