Maternal lipids, BMI and IL-17/IL-35 imbalance in concurrent gestational diabetes mellitus and preeclampsia

Abstract

The objective of the present study was to investigate the role of blood glucose, lipid metabolism, body mass index (BMI), C-reactive protein (CRP) as well as an interleukin (IL)-17/IL-35 imbalance in the pathogenesis of concurrent gestational diabetes mellitus (GDM) and preeclampsia (PE) (DPE). The mRNA expression of forkhead box protein 3 (FoxP3), IL-35 [including Epstein-Barr virus-induced gene 3 (EBI3) and P35 subunits] and IL-17 in the peripheral blood mononuclear cells of patients with DPE (n=30), GDM (n=33), PE (n=33) and normal pregnancy (n=33) were determined by reverse transcription-quantitative polymerase chain reaction. The serum levels of IL-35, IL-17 and CRP were analyzed using ELISA. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and fasting blood glucose (FBG) were also detected. The levels of low-density lipoprotein (LDL) were calculated using the Friedewald formula. Body weight and height were determined in order to calculate the BMI. It was observed that the levels of FBG were markedly elevated in patients with GDM, PE and DPE. In addition, significantly higher serum TG, TC, LDL and very LDL were detected in patients with GDM, PE and DPE compared with those in subjects with normal pregnancies. By contrast, the concentration of HDL was lower in the patient groups. In addition, higher BMI values were identified in patients with GDM, PE and DPE. A decreased expression of FoxP3, P35 and EBI3 mRNA, and an elevated expression of IL-17 in PBMCs was detected in patients with GDM, PE and DPE. In addition, higher serum levels of IL-17 and CRP, as well as lower levels of IL-35, were observed. Furthermore, in patients with DPE, positive correlations of diastolic blood pressure with IL-17 levels, BMI and TG, as well as IL-17 levels with BMI and proteinuria were identified. In conclusion, the present study indicated that abnormal maternal lipids, hyperglycemia, high BMI, high CRP and IL-17/IL-35 imbalance may have a role in the pathophysiology of DPE. Therefore, pregnant women and clinicians should be made aware that maternal hyperlipidaemia, hyperglycemia, high BMI, high CRP levels and IL-17/IL-35 imbalance may lead to DPE.

Keywords: body mass index; gestational diabetes complicated by preeclampsia; interleukin-35/interleukin-17; maternal lipids; pregnancy.

Figure 1.

Blood pressure in patients with GDM, PE and DPE. (A) The SBP, (B) DBP and (C) MAP of the patients in each group. GDM, gestational diabetes mellitus; PE, preeclampsia; DPE, GDM with PE; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; NP, normal pregnant subjects.

Figure 2.

Levels of FBG in patients with GDM, PE and DPE. FBG, fasting blood glucose; GDM, gestational diabetes mellitus; PE, preeclampsia; DPE, GDM with PE; NP, normal pregnant subjects.

Figure 3.

Lipid profile and BMI of patients with GDM, PE and DPE. Levels of (A) TG, (B) TC, (C) LDL, (D) VLDL and (E) Serum HDL of patients in each group. (F) The BMI of patients in the GDM, PE and DPE group upon enrollment. BMI body mass index; DPE, GDM with PE; GDM, gestational diabetes mellitus; PE, preeclampsia; TG, triglyceride; TC, total cholesterol; LDL, low-density lipoprotein; VLDL, very LDL; HDL, high-density lipoprotein; NP, normal pregnant subjects.

Figure 4.

mRNA expression of FoxP3, P35, EBI3 and IL-17 in patients with GDM, PE and DPE. mRNA Levels of (A) IL-17, (B) P35, (C) EB13 and (D) FoxP3 in each group. FoxP3, forkhead box protein 3; EBI3, Epstein-Barr virus-induced gene 3; IL, interleukin; GDM, gestational diabetes mellitus; PE, preeclampsia; DPE, GDM with PE; NP, normal pregnant subjects.

Figure 5.

Serum levels of CRP and cytokines IL-17 and IL-35 in patients with GDM, PE and DPE. Serum levels of (A) IL-17, (B) IL-35 and. (C) CRP of patients in each group. CRP, C-reactive protein; IL, interleukin; GDM, gestational diabetes mellitus; PE, preeclampsia; DPE, GDM with PE; NP, normal pregnant subjects.

Figure 6.

Correlations between various parameters in patients with DPE. (A) A significant positive correlation was detected between elevated IL-17 and DBP. (B) Positive correlation between increased BMI and DBP. (C) Positive correlation between elevated TG levels and DBP. (D) There was a significant positive correlation between serum IL-17 and proteinuria in patients with DPE. (E) A positive correlation was detected between serum IL-17 and the BMI. IL, interleukin; BMI, body mass index; TG, triglyceride; DBP, diastolic blood pressure; DPE, gestational diabetes mellitus with preeclampsia.