Inflammatory and Other Biomarkers: Role in Pathophysiology and Prediction of Gestational Diabetes Mellitus

Abstract

Understanding pathophysiology and identifying mothers at risk of major pregnancy complications is vital to effective prevention and optimal management. However, in current antenatal care, understanding of pathophysiology of complications is limited. In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Hence, universal screening is widely recommended. Here, we will explore the literature on GDM and biomarkers including inflammatory markers, adipokines, endothelial function and lipids to advance understanding of pathophysiology and explore risk prediction, with a goal to guide prevention and treatment of GDM.

Keywords: biomarkers; gestational diabetes mellitus; inflammatory markers; pregnancy; risk prediction.

Figure 1

The vicious cycle of obesity and reproductive complications. Women with adverse lifestyle factors and excess weight are more likely to develop polycystic ovarian syndrome (PCOS) and subfertility. They are likely to enter pregnancy overweight and are at increased risk for excess gestational weight gain (GWG). Obesity and excess GWG results in a three-fold increased risk of adverse pregnancy outcomes including gestational diabetes mellitus (GDM), and may have epigenetic impacts including long term metabolic syndrome and cardiovascular disease for mother and baby. Post-partum weight retention contributes to prevalent obesity and type 2 diabetes mellitus (T2DM) long-term and to risks in subsequent pregnancies [10].

Figure 2

A proposed model of inflammation and insulin resistance in obesity, pregnancy and GDM. Women who are obese have features of chronic low-grade inflammation, manifest by increased tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-12 (IL-12), and high sensitivity C-reactive protein (hsCRP). Obesity is characterised by insulin resistance, and down-regulation of adiponectin and up-regulation of leptin, resistin and retinol-binding protein-4 (RBP4) contribute to this. Pregnancies occurring in obese women are characterised by further inflammation and a Th-2 predominant immune response, which may contribute to pregnancy complications. Foetal and placental hormones, production of abnormal growth factors and tissue remodelling may contribute to inflammation and increasing insulin resistance. GDM develops when beta cell dysfunction coexists, and may be characterised by further abnormalities in adipokine and cytokine profiles, increased free fatty acids (FFA), triglycerides (TG), low vitamin D and endothelial dysfunction.