Glycemic dysregulation and insulin resistance across acute and post-acute COVID-19: a systematic review and meta-analysis of etiologic and prognostic evidence
6 affiliations
- 1Laboratorio de Inmunología, Centro Universitario de los Lagos, Universidad de Guadalajara, Jalisco
- 2Centro de Investigación e Innovación, Global University, Aguascalientes
- 3Facultad de Medicina, Unidad de Ciencias de la Salud, Universidad Veracruzana, Veracruz
- 4Ingenieria Bioquímica, Centro Universitario de los Lagos, Universidad de Guadalajara, Jalisco
- 5Departamento de Ciencias de la Tierra y de la Vida, Centro Universitario de Los Lagos, Universidad de Guadalajara, Jalisco
- 6Programa de Estancias Posdoctorales por Mexico, Secretaría de Ciencia, Humanidades, Tecnología e Innovación, Centro Universitario de Los Lagos, Universidad de Guadalajara, Jalisco
Abstract
Background: Coronavirus disease 2019 (COVID-19) can disrupt glucose regulation through inflammation, adipose-tissue dysfunction, impaired insulin signaling, and variable β-cell compensation. These evidence domains remain incompletely integrated.
Objective: To synthesize evidence on glycemic dysregulation and insulin resistance or insulin sensitivity across acute and post-acute COVID-19, including metabolic trajectories and associations with adverse clinical outcomes.
Methods: PubMed, Embase, Scopus, Web of Science, and ScienceDirect were searched. Eligible studies evaluated glucose regulation and at least one insulin-resistance or insulin-sensitivity measure during or after COVID-19. Etiological and prognostic evidence was analyzed as related but distinct domains. Prognostic meta-analysis evaluated study-defined acute hyperglycemic phenotypes; insulin-resistance or insulin-sensitivity assessment was a study-level eligibility criterion rather than part of a participant-level composite exposure. Unadjusted risk ratios (RRs) from event counts were pooled using restricted maximum-likelihood random-effects models with Hartung–Knapp adjustment. Non-combinable evidence was synthesized according to Synthesis Without Meta-analysis principles. Risk of bias was assessed using design-appropriate tools, and certainty was evaluated with GRADE. The protocol and analytical plan were retrospectively registered in OSF on August 21, 2026 ( https://doi.org/10.17605/OSF.IO/K5FWU ).
Results: Twenty independent studies represented by 23 reports. Acute hyperglycemic phenotypes were associated with increased short-term all-cause mortality (four studies; 1,079 participants; RR 2.09, 95% confidence interval [CI] 1.21–3.64; I ² =31.3%; 95% prediction interval 0.96–4.56) and invasive mechanical ventilation (three studies; 679 participants; RR 3.64, 95% CI 1.74–7.61; I ² =0%). Mortality estimates remained directionally stable in sensitivity analysis. Adding a large study using peak in-hospital glucose preserved the mortality association but produced substantial heterogeneity for ventilation. Etiological evidence showed no uniform post-COVID trajectory: insulin resistance or glycemic abnormalities resolved in some populations, persisted in others, and progressed toward newly diagnosed diabetes in a subset. Mechanistic evidence implicated inflammatory stress, adipose-tissue dysfunction, impaired insulin signaling, and variable β-cell responses.
Conclusions: Study-defined acute hyperglycemic phenotypes were associated with adverse COVID-19 outcomes in studies that also assessed insulin resistance or insulin sensitivity. These unadjusted estimates should not be interpreted as effects of a combined phenotype or as causal associations. Persistent metabolic abnormalities occurred heterogeneously, supporting standardized participant-level definitions and controlled longitudinal studies.
Systematic review registration: https://doi.org/10.17605/OSF.IO/K5FWU , identifier 10.17605/OSF.IO/K5FWU.
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BibTeX
@article{munozcarrillo2026glycemic,
title = {{Glycemic dysregulation and insulin resistance across acute and post-acute COVID-19: a systematic review and meta-analysis of etiologic and prognostic evidence}},
author = {José Luis Muñoz-Carrillo and Oscar Gutiérrez-Coronado and Edrei Lopez-Hernandez and Sandra Estefanía Rodríguez López and Miriam Alejandra Olivares Mendoza and Diego Octavio Ramírez Águila and Paola Trinidad Villalobos-Gutiérrez and Cesar Soria-Fregozo and Gilberto Uriel Rosas-Sánchez and Alejandro David Soriano-Hernández},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1975728},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1975728/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Glycemic dysregulation and insulin resistance across acute and post-acute COVID-19: a systematic review and meta-analysis of etiologic and prognostic evidence
AU - José Luis Muñoz-Carrillo
AU - Oscar Gutiérrez-Coronado
AU - Edrei Lopez-Hernandez
AU - Sandra Estefanía Rodríguez López
AU - Miriam Alejandra Olivares Mendoza
AU - Diego Octavio Ramírez Águila
AU - Paola Trinidad Villalobos-Gutiérrez
AU - Cesar Soria-Fregozo
AU - Gilberto Uriel Rosas-Sánchez
AU - Alejandro David Soriano-Hernández
PY - 2026
DA - 2026/10/14
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1975728
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1975728/full
AB - Background: Coronavirus disease 2019 (COVID-19) can disrupt glucose regulation through inflammation, adipose-tissue dysfunction, impaired insulin signaling, and variable β-cell compensation. These evidence domains remain incompletely integrated. Objective: To synthesize evidence on glycemic dysregulation and insulin resistance or insulin sensitivity across acute and post-acute COVID-19, including metabolic trajectories and associations with adverse clinical outcomes. Methods: PubMed, Embase, Scopus, Web of Science, and ScienceDirect were searched. Eligible studies evaluated glucose regulation and at least one insulin-resistance or insulin-sensitivity measure during or after COVID-19. Etiological and prognostic evidence was analyzed as related but distinct domains. Prognostic meta-analysis evaluated study-defined acute hyperglycemic phenotypes; insulin-resistance or insulin-sensitivity assessment was a study-level eligibility criterion rather than part of a participant-level composite exposure. Unadjusted risk ratios (RRs) from event counts were pooled using restricted maximum-likelihood random-effects models with Hartung–Knapp adjustment. Non-combinable evidence was synthesized according to Synthesis Without Meta-analysis principles. Risk of bias was assessed using design-appropriate tools, and certainty was evaluated with GRADE. The protocol and analytical plan were retrospectively registered in OSF on August 21, 2026 ( https://doi.org/10.17605/OSF.IO/K5FWU ). Results: Twenty independent studies represented by 23 reports. Acute hyperglycemic phenotypes were associated with increased short-term all-cause mortality (four studies; 1,079 participants; RR 2.09, 95% confidence interval [CI] 1.21–3.64; I ² =31.3%; 95% prediction interval 0.96–4.56) and invasive mechanical ventilation (three studies; 679 participants; RR 3.64, 95% CI 1.74–7.61; I ² =0%). Mortality estimates remained directionally stable in sensitivity analysis. Adding a large study using peak in-hospital glucose preserved the mortality association but produced substantial heterogeneity for ventilation. Etiological evidence showed no uniform post-COVID trajectory: insulin resistance or glycemic abnormalities resolved in some populations, persisted in others, and progressed toward newly diagnosed diabetes in a subset. Mechanistic evidence implicated inflammatory stress, adipose-tissue dysfunction, impaired insulin signaling, and variable β-cell responses. Conclusions: Study-defined acute hyperglycemic phenotypes were associated with adverse COVID-19 outcomes in studies that also assessed insulin resistance or insulin sensitivity. These unadjusted estimates should not be interpreted as effects of a combined phenotype or as causal associations. Persistent metabolic abnormalities occurred heterogeneously, supporting standardized participant-level definitions and controlled longitudinal studies. Systematic review registration: https://doi.org/10.17605/OSF.IO/K5FWU , identifier 10.17605/OSF.IO/K5FWU.
SN - 1664-2392
ER -