Proteomics Studies in Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

Abstract

Gestational Diabetes Mellitus (GDM) is the most common metabolic complication during pregnancy and is associated with serious maternal and fetal complications such as pre-eclampsia and stillbirth. Further, women with GDM have approximately 10 times higher risk of diabetes later in life. Children born to mothers with GDM also face a higher risk of childhood obesity and diabetes later in life. Early prediction/diagnosis of GDM leads to early interventions such as diet and lifestyle, which could mitigate the maternal and fetal complications associated with GDM. However, no biomarkers identified to date have been proven to be effective in the prediction/diagnosis of GDM. Proteomic approaches based on mass spectrometry have been applied in various fields of biomedical research to identify novel biomarkers. Although a number of proteomic studies in GDM now exist, a lack of a comprehensive and up-to-date meta-analysis makes it difficult for researchers to interpret the data in the existing literature. Thus, we undertook a systematic review and meta-analysis on proteomic studies and GDM. We searched MEDLINE, EMBASE, Web of Science and Scopus from inception to January 2022. We searched Medline, Embase, CINHAL and the Cochrane Library, which were searched from inception to February 2021. We included cohort, case-control and observational studies reporting original data investigating the development of GDM compared to a control group. Two independent reviewers selected eligible studies for meta-analysis. Data collection and analyses were performed by two independent reviewers. The PROSPERO registration number is CRD42020185951. Of 120 articles retrieved, 24 studies met the eligibility criteria, comparing a total of 1779 pregnant women (904 GDM and 875 controls). A total of 262 GDM candidate biomarkers (CBs) were identified, with 49 CBs reported in at least two studies. We found 22 highly replicable CBs that were significantly different (nine CBs were upregulated and 12 CBs downregulated) between women with GDM and controls across various proteomic platforms, sample types, blood fractions and time of blood collection and continents. We performed further analyses on blood (plasma/serum) CBs in early pregnancy (first and/or early second trimester) and included studies with more than nine samples (nine studies in total). We found that 11 CBs were significantly upregulated, and 13 CBs significantly downregulated in women with GDM compared to controls. Subsequent pathway analysis using Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatics resources found that these CBs were most strongly linked to pathways related to complement and coagulation cascades. Our findings provide important insights and form a strong foundation for future validation studies to establish reliable biomarkers for GDM.

Exosome Proteomics Reveals the Deregulation of Coagulation, Complement and Lipid Metabolism Proteins in Gestational Diabetes Mellitus

“…C6, C7, C8B, C8G and C9 are the final complement components, essential in creating the membrane attack complex, which is the main effector of complement-mediated tissue damage [ 23 ]. Our data reveal that F12 is upregulated and confirms previous results [ 31 ]. Women with GDM have higher serum exosomal levels of F12 when compared to women with healthy pregnancies.…”

“…In 2022, a systematic review and meta-analysis of biomarkers that are differentially expressed in women with and without GDM revealed that in GDM, C6, C7, C8B, C8G, C9 and C4BPA are downregulated [ 31 ]. It is important to note that this recent report mentioned that there are not case-control studies performed with sample collection from serum exosomes.…”

Atualizações sobre a influência da obesidade no surgimento do diabetes gestacional e suas complicações para mãe e para concepto

“…Já para a prole dessas mulheres os riscos incluem macrossomia (20-30%), serem pequenos para a idade gestacional (7-10%), distocia de ombro, hipoglicemia neonatal, hiperbilirrubinemia neonatal, síndrome do desconforto respiratório até mesmo serem natimortos, e quando sobrevivem, possuem um risco maior de obesidade infantil e diabetes na vida adulta. Além disso, as mulheres com DMG têm dez vezes mais riscos de desenvolver diabetes mellitus tipo 2 ao longo da vida em até 10 anos após o parto (Sriboonvorakul et al, 2022).…”

“…A revisão sistemática e meta-análise produzida por Sriboonvorakul et al, (2022) é uma das mais abrangentes e atualizadas sobre biomarcadores (CB) para DMG. Este estudo identificou 22 CB altamente replicáveis que eram significativamente diferentes (9 CBs foram regulados positivamente e 12 CBs regulados negativamente) entre mulheres com DMG e as que eram controles em várias plataformas proteômicas, tipos de amostras, frações de sangue e tempo de coleta de sangue e continentes.…”

“…Análise de caminhos subsequentes usando banco de dados para anotação, visualização e integração e os recursos de bioinformática Discovery (DAVID) descobriram que esses CBs eram mais fortemente ligados a vias relacionadas com as cascatas do complemento e da coagulação. Essas descobertas fornecem caminhos importantes e formam uma base sólida para futuros estudos de validação para estabelecer biomarcadores confiáveis para DMG (Sriboonvorakul et al, 2022)…”