Liver Enzyme Biomarkers Before or in Early Pregnancy as Predictors for Gestational Diabetes Mellitus

Background: Liver enzymes may reflect early metabolic disturbances and insulin resistance preceding gestational diabetes mellitus (GDM). This systematic review and meta-analysis evaluated whether liver enzyme biomarkers measured before or in early pregnancy are associated with subsequent development of GDM. Methodology: PubMed, Cochrane, EBSCOHost, and SCOPUS databases were searched through May 2025 for observational studies or trials assessing pre- or early pregnancy liver enzymes in relation to GDM development. Pooled mean differences (MD) and odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. Risk of bias was assessed using RoB 2.0 and ROBINS-E; certainty of evidence was evaluated using GRADE. Results: Twenty-seven studies were included in the analyses. GDM was associated with higher AST (MD 0.97 U/L; OR 1.42), ALT (MD 2.38 U/L; OR 1.69), GGT (MD 3.77 U/L; OR 2.57), and hepatic steatosis index (HSI) (MD 2.82; OR 2.19). ALP showed no significant mean difference but an elevated GDM risk (OR 1.47). Substantial heterogeneity was observed with very low certainty of evidence across outcomes. Conclusion: Elevated liver enzymes, especially GGT and HSI, are associated with increased GDM risk at a population level. However, high heterogeneity and very low certainty of evidence limit current clinical applicability, warranting further prospective validation.