Reduced fecal intestinal alkaline phosphatase is associated with gestational diabetes mellitus: A hospital-based multicentre cross-sectional study in Bangladesh

Gestational diabetes mellitus (GDM) is a major metabolic complication of pregnancy with significant maternal and fetal adverse consequences. Beyond classical mechanisms, emerging evidence suggests that gut-derived metabolic endotoxemia may contribute to dysglycemia. Intestinal alkaline phosphatase (IAP), a key enzyme involved in maintaining gut barrier integrity and detoxifying lipopolysaccharides, has been linked to type 2 diabetes mellitus; however, its role in GDM remains largely unexplored. This hospital-based cross-sectional analytical study evaluated fecal IAP levels and their association with GDM among 198 pregnant women recruited from three antenatal care clinics representing three tiers of ANC services. Participants were screened for GDM using a 75-g oral glucose tolerance test and classified as having GDM (n=55) or normal glucose tolerance (NGT; n=143) according to WHO 2013 criteria. Stool samples were collected, and fecal IAP levels were measured using an enzymatic colorimetric assay. Fecal IAP level was significantly lower in women with GDM than in those with NGT (median 23.59 vs 46.48 U/g stool; p<0.001). Lower IAP level remained independently associated with GDM after adjustment for body mass index and previous GDM (adjusted OR 0.98 per unit increase; 95% CI 0.97-0.99; p<0.001). A graded relationship was observed between declining IAP level and GDM. Receiver operating characteristic analysis demonstrated modest discrimination (AUC 0.676), while a threshold of approximately 65 U/g stool yielded high sensitivity (89.1%) but lower specificity. Reduced fecal IAP is independently associated with GDM, supporting a potential role of gut-derived metabolic dysregulation in gestational glucose intolerance. While not suitable as a standalone diagnostic tool, fecal IAP may serve as a complementary biomarker for risk stratification during pregnancy. Prospective studies are warranted to determine its predictive value and explore its potential as a therapeutic target.