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

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; I2=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; I2=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.