Metabolomic Biomarkers in Gestational Diabetes Mellitus: A Review of the Evidence

Abstract

Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes, affecting between 2 to 38% of pregnancies worldwide, varying considerably depending on diagnostic criteria used and sample population studied. Adverse obstetric outcomes include an increased risk of macrosomia, and higher rates of stillbirth, instrumental delivery, and birth trauma. Metabolomics, which is a platform used to analyse and characterise a large number of metabolites, is increasingly used to explore the pathophysiology of cardiometabolic conditions such as GDM. This review aims to summarise metabolomics studies in GDM (from inception to January 2021) in order to highlight prospective biomarkers for diagnosis, and to better understand the dysfunctional metabolic pathways underlying the condition. We found that the most commonly deranged pathways in GDM include amino acids (glutathione, alanine, valine, and serine), carbohydrates (2-hydroxybutyrate and 1,5-anhydroglucitol), and lipids (phosphatidylcholines and lysophosphatidylcholines). We also highlight the possibility of using certain metabolites as predictive markers for developing GDM, with the use of highly stratified modelling techniques. Limitations for metabolomic research are evaluated, and future directions for the field are suggested to aid in the integration of these findings into clinical practice.

Keywords: biomarkers; gestational diabetes mellitus; lipidomics; mass spectrometry; metabolites; metabolomics.

Figure 1

Proposed pathophysiology of gestational diabetes at different stages of pregnancy. During normal pregnancy, β-cells undergo compensatory hypertrophy/hyperplasia in order to meet the metabolic demands of pregnancy. A reduction in insulin sensitivity leads to a rise in glucose concentration. Following pregnancy, insulin sensitivity and blood glucose concentration return to normal. In gestational diabetes, β-cells inadequately compensate for the metabolic demands of pregnancy. The reduced insulin sensitivity results in hyperglycaemia. This is exacerbated by a precipitous reduction in insulin-receptor-substrate (IRS)-1, phosphoinositide 3-kinase (PI3K), and glucose transporter type 4 (GLUT4) expression. Following pregnancy, β-cells, blood glucose concentration, and insulin sensitivity may return to normal or remain impaired, resulting in an increased risk of developing obesity, a sustained impairment to insulin resistance, and dislipideamia.