Defective Visceral Adipose Tissue Adaptation in Gestational Diabetes Mellitus

Context: Gestational diabetes mellitus (GDM) is a complex obstetric condition affecting localized glucose metabolism, resulting in systemic metabolic dysfunction. Objective: This cross-sectional study aimed to explore visceral adipose tissue (VAT) as an integral contributor to GDM, focusing on elucidating the specific contribution of obesity and GDM pathology to maternal outcomes. Methods: Fifty-six nulliparous pregnant women were recruited, including normal glucose tolerant (NGT) (n = 30) and GDM (n = 26) participants. Participants were subgrouped as nonobese (BMI <30 kg/m²) or obese (BMI ≥30 kg/m²). Metabolic markers in circulation, VAT, and placenta were determined. Morphological analysis of VAT and immunoblotting of the insulin signaling cascade were performed. Results: GDM participants demonstrated hyperinsulinemia and elevated homeostatic model assessment for insulin resistance (HOMA-IR) scores relative to NGT participants. The GDM-obese subgroup had significant VAT adipocyte hypoplasia relative to NGT-nonobese tissue. GDM-obese VAT had significantly lower insulin receptor substrate (IRS)-2 expression, with elevated ser312 phosphorylation of IRS-1, relative to NGT-nonobese. GDM-obese participants had significantly elevated circulating leptin levels and placental adipsin secretion, while GDM-nonobese participants had elevated circulating adipsin levels with reduced placental adiponectin secretion. Conclusion: These findings suggest that GDM-obese pregnancy is specifically characterized by inadequate VAT remodeling and dysfunctional molecular signaling, which contribute to insulin resistance and hinder metabolic health.