Work

Glycemic dysregulation and insulin resistance across acute and post-acute COVID-19: a systematic review and meta-analysis of etiologic and prognostic evidence

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

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: =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.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2026.1975728