Assessment of Changes in the Expression of Genes Involved in Insulin Signaling and Glucose Transport in Leukocytes of Women with Gestational Diabetes During Pregnancy and in the Postpartum Period

Abstract

Not much is currently known about disturbances in insulin signaling and glucose transport in leukocytes of women with gestational diabetes mellitus (GDM) during and after pregnancy. In this study, the expression of insulin signaling (INSR, IRS1, IRS2 and PIK3R1)- and glucose transporter (SLC2A1, SLC2A3 and SLC2A4)-related genes in the leukocytes of 92 pregnant women was assayed using quantitative RT-PCR. The cohort consisted of 44 women without GDM (NGT group) and 48 with GDM (GDM group) at 24-28 weeks of gestation. GDM women were then tested again one year after childbirth (pGDM group: 14 women (29.2%) with abnormal glucose tolerance (AGT) and 34 women (70.8%) with normoglycemia). The GDM and NGT groups were closely matched for gestational age and parameters of obesity, such as pre-pregnancy body mass index (BMI), pregnancy weight, and gestational weight gain (GWG) (p > 0.05). Compared to the NGT group, the GDM and pGDM groups were hyperglycemic, but the GDM group featured a more highly insulin-resistant condition than the pGDM group, as reflected by higher fasting insulin (FI) levels and the values of the homeostasis model assessment for insulin resistance (HOMA-IR) (p < 0.05). In leukocytes from the GDM and pGDM groups, PIK3R1, SLC2A1, and SLC2A3 were upregulated and IRS1 was downregulated, with a larger magnitude in fold change (FC) values for PIK3R1 and IRS1 in the GDM group and for SLC2A1 and SLC2A3 in the pGDM group. The expression of SLC2A4 was unchanged in the GDM group but upregulated in the pGDM group, where it was inversely correlated with HOMA-IR (rho = -0.48; p = 0.007). Although the INSR and IRS2 levels did not significantly differ between the groups, the IRS2 transcript positively correlated with pregnancy weight, fasting plasma glucose, FI, and HOMA-IR in the GDM group. Our findings indicate that pronounced quantitative changes exist between the GDM and pGDM groups with respect to the expression of certain genes engaged in insulin signaling and glucose transport in leukocytes, with insulin resistance of a variable degree. These data also highlight the relationship of leukocyte SLC2A4 expression with insulin resistance in the postpartum period.

Keywords: gestational diabetes mellitus (GDM); glucose transporters; insulin signaling; leukocytes.

Figure 1

Predictive accuracy of logistic regression model based on pregnancy INSR expression and body weight for postpartum AGT. The presented ROC curves reflect performance of the model on learning and validation datasets.

Figure 2

Allocation of patients to appropriate study groups at GDM diagnosis and 1 year after childbirth based on OGTT measurements.