Association of Elevated Plasma FGF21 and Activated FGF21 Signaling in Visceral White Adipose Tissue and Improved Insulin Sensitivity in Gestational Diabetes Mellitus Subtype: A Case-Control Study.

Ning Wang,Bo Sun,Huan Chen,Wei Cui,Yang Mi,Mengjun Wang,Haonan Guo,Lin Song,Yingyu Jing,Qi Ruan

doi:10.3389/fendo.2021.795520

Abstract

ObjectiveTo study the discrepancy of the insulin sensitivity alteration pattern, circulating fibroblast growth factor (FGF21) levels and FGF21 signaling in visceral white adipose tissue (vWAT) of gestational diabetes mellitus (GDM) subtypes.Methods26 GDM women with either a predominant of insulin-secretion defect (GDM-dysfunction, n = 9) or insulin-sensitivity defect (GDM-resistance, n = 17) and 13 normal glucose tolerance (NGT) women scheduled for caesarean-section at term were studied. Blood and vWAT samples were collected at delivery.ResultsThe insulin sensitivity was improved from the 2nd trimester to delivery in the GDM-resistance group. Elevated circulating FGF21 concentration at delivery, increased FGF receptor 1c and decreased klotho beta gene expression, enhanced ERK1/2 phosphorylation, and increased GLUT1, IR-B, PPAR-γ gene expression in vWAT were found in the GDM-resistance group as compared with the NGT group. The circulating FGF21 concentration was negatively correlated with fasting blood glucose (r = -0.574, P < 0.001), and associated with the GDM-resistance group (r = 0.574, P < 0.001) in pregnant women at delivery. However, we observed no insulin sensitivity alteration in GDM-dysfunction and NGT groups during pregnancy. No differences of plasma FGF21 level and FGF21 signaling in vWAT at delivery were found between women in the GDM-dysfunction and the NGT group.ConclusionsWomen with GDM heterogeneity exhibited different insulin sensitivity alteration patterns. The improvement of insulin sensitivity may relate to the elevated circulating FGF21 concentration and activated FGF21 signaling in vWAT at delivery in the GDM-resistance group.

Highlights

Gestational diabetes mellitus (GDM) is a common obstetric diseases during pregnancy with spontaneous hyperglycemia during the second and third trimesters without pre-gestational diabetes mellitus [1]
We found that women of the GDM-resistance group showed improved insulin sensitivity before delivery compared with that
At the same time, increased plasma FGF21 concentrations and activated FGF21 signaling in the visceral WAT (vWAT) were found in the GDM-resistance group at delivery

Summary

Introduction

Gestational diabetes mellitus (GDM) is a common obstetric diseases during pregnancy with spontaneous hyperglycemia during the second and third trimesters without pre-gestational diabetes mellitus [1]. GDM increases the risk for a variety of maternal metabolic diseases and adverse perinatal outcomes for the infant, such as postpartum type 2 diabetes mellitus [2], macrosomia and shoulder dystocia [3]. Women with GDM can be divided into subtypes based on insulin secretion and sensitivity heterogeneity [4]. We found differences in the risk factors of GDM subtypes [5], and having large-for-gestational-age infants is associated with specific GDM subtypes [6]. Fibroblast growth factor 21(FGF21) is a pleiotropic hormonelike protein regulates glucose and lipid metabolism [7], such as increasing tissue glucose uptake, improving insulin sensitivity, and inhibiting lipolysis [8]. FGF21 is mainly produced by liver, and acts on target organs such as liver, adipose tissue and skeletal muscle [7, 9]. The main peripheral site of FGF21 that promotes glucose uptake is the white adipose tissue (WAT) [10]

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Conclusion