Emerging Protein Biomarkers for the Diagnosis or Prediction of Gestational Diabetes—A Scoping Review

Abstract

Introduction: Gestational diabetes (GDM), defined as hyperglycemia with onset or initial recognition during pregnancy, has a rising prevalence paralleling the rise in type 2 diabetes (T2DM) and obesity. GDM is associated with short-term and long-term consequences for both mother and child. Therefore, it is crucial we efficiently identify all cases and initiate early treatment, reducing fetal exposure to hyperglycemia and reducing GDM-related adverse pregnancy outcomes. For this reason, GDM screening is recommended as part of routine pregnancy care. The current screening method, the oral glucose tolerance test (OGTT), is a lengthy, cumbersome and inconvenient test with poor reproducibility. Newer biomarkers that do not necessitate a fasting sample are needed for the prompt diagnosis of GDM. The aim of this scoping review is to highlight and describe emerging protein biomarkers that fulfill these requirements for the diagnosis of GDM. Materials and Methods: This scoping review was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for scoping reviews using Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing & Allied Health Literature (CINAHL), PubMed, Embase and Web of Science with a double screening and extraction process. The search included all articles published in the literature to July 2020. Results: Of the 3519 original database citations identified, 385 were eligible for full-text review. Of these, 332 (86.2%) were included in the scoping review providing a total of 589 biomarkers studied in relation to GDM diagnosis. Given the high number of biomarkers identified, three post hoc criteria were introduced to reduce the items set for discussion: we chose only protein biomarkers with at least five citations in the articles identified by our search and published in the years 2017–2020. When applied, these criteria identified a total of 15 biomarkers, which went forward for review and discussion. Conclusions: This review details protein biomarkers that have been studied to find a suitable test for GDM diagnosis with the potential to replace the OGTT used in current GDM screening protocols. Ongoing research efforts will continue to identify more accurate and practical biomarkers to take GDM screening and diagnosis into the 21st century.

Early Identification of the Maternal, Placental and Fetal Dialog in Gestational Diabetes and Its Prevention

“…Due to the increased prevalence of GDM and the poor reproducibility of the OGTT, extensive research in recent years attempted to identify biomarkers that could aid in GDM prediction. In fact, a recent review found 589 different biomarkers evaluated for association with GDM [36]. Tested biomarkers include glycemic-related markers, adipokines, growth factors, pregnancy-related proteins, inflammatory markers, different hormones, coagulation factors, nucleic acids, glycoproteins, complement components, and many others (Figure 1).…”

Putrescine as a Novel Biomarker of Maternal Serum in First Trimester for the Prediction of Gestational Diabetes Mellitus: A Nested Case-Control Study

“…Therefore, their clinical benefit when applied to the most recent GDM definition has not yet been well investigated. Recently, a number of new markers have been evaluated for use in predicting GDM with variable success, such as protein biomarkers (23), adiponectin (24) and leptin (25), pentraxin 3 (26), trace elements (27), RNA (28), singlenucleotide polymorphisms (29), and other combined metabolite models (30)(31)(32)(33). The AUC values of some of these models can reach above 0.8.…”

Theranostic Advances of Bionanomaterials against Gestational Diabetes Mellitus: A Preliminary Review

“…The essential biomarkers for GDM detection are adipokines (leptin, tumor necrosis factor (TNF), interleukin 6 (IL-6), etc. ), glycoproteins (afamin, CD59, sex-hormone binding protein (SHBG)), pregnancy-associated plasma protein-A (PAPP-A), C-reactive protein (CRP), and retinol-binding protein 4 (RBP4) (Figure 1) [44,45]. To bring the screening and diagnosis of GDM disease into the 21st century, several ongoing research efforts will continue to develop more effective and accurate biomarkers.…”