Pigment Epithelium-Derived Factor, a Novel Adipokine, Contributes to Gestational Diabetes Mellitus.

Abstract

Excessive insulin resistance, inadequate insulin compensation, or both could result in gestational diabetes mellitus (GDM). Levels of pigment epithelium-derived factor (PEDF), a novel adipokine that could induce insulin resistance, are high in patients with obesity and diabetes. However, the impact of PEDF in pregnancy remains unknown. This study aimed to elucidate the role of PEDF on insulin resistance and compensatory elevation of insulin levels during normal pregnancy and in patients with GDM. In this population-based and cohort study, logistic regression analysis was performed to determine the association of PEDF/adiponectin/leptin levels with the risk of developing GDM and to predict postpartum prediabetes. PEDF protein, PEDF transgenic mice, PEDF knockout mice, and PEDF-neutralized antibodies were used to observe changes in insulin resistance and insulin levels with pregnancy. Plasma PEDF levels were increased in normal pregnancy and higher in GDM women. Higher PEDF levels were associated with the increased risk of developing GDM and emerged as a significant independent determinant of postpartum prediabetes in GDM women. Mechanistically, in vivo and in vitro experiments revealed that PEDF induced insulin resistance by inhibiting the insulin signaling pathway. In addition to insulin resistance and upregulated insulin levels in normal pregnancy and GDM, aberrant PEDF levels can serve as a "fingerprint" of metabolic abnormalities during pregnancy. Thus, PEDF is a valuable biomarker but could interfere with the time course for early diagnosis and prognosis of GDM.