Increased Insulin Resistance and Hyperglycemia in Long COVID disease: A Systematic Review and Meta-Analysis

Background accumulating evidence suggests that Long COVID (LC) is mediated by chronic immune activation, oxidative stress, and metabolic dysregulation. These processes may impair glucose homeostasis and promote insulin resistance (IR). However, no prior meta-analysis has systematically and quantitatively evaluated IR indices and related biomarkers in LC compared with normal controls. Objectives To systematically review and meta-analyze composite and solitary indices of IR, β-cell function, and adipokine levels in individuals with LC compared with normal controls. Methods PubMed, SCOPUS, and Google Scholar databases were searched for relevant studies from inception to August 2025. Sixty-three eligible studies were included, comprising 12,409 participants—5,891 LC patients and 6,518 normal controls. Results LC disease is characterized by elevated global IR (standardized mean difference, SMD = 0.395; 95% confidence intervals, CI: 0.226;0.563), Fasting insulin + C-peptide + FBG composite score (SMD = 0.605; 95% CI: 0.306;0.904) and acute + chronic glycemia composite scores (SMD = 0.424; 95% CI: 0.258;0.590). Furthermore, significant increases in HOMA-IR (SMD = 0.621; 95% CI: 0.379;0.863), Insulin (SMD = 0.488; 95% CI: 0.202;0.774), HbA1c (SMD = 0.308; 95% CI: 0.053;0.563), and fasting and random blood glucose (SMD = 0.831; 95% CI: 0.271;1.391, SMD = 0.396; 95% CI: 0.188;0.605) alongside reduced HOMA-%B and HOMA-%S were observed in LC patients versus normal controls. No publication bias observed in the results. Conclusion The current study suggests that LC disease is characterized by persistent insulin resistance, hyperglycemia, and β-cell dysfunction, suggesting sustained metabolic disturbances beyond the acute phase