Quantitative Proteomics by SWATH-MS Suggest an Association Between Circulating Exosomes and Maternal Metabolic Changes in Gestational Diabetes Mellitus.

Several factors including placental hormones (PH) released from the human placenta have been associated with the development of insulin resistance and gestational diabetes mellitus (GDM). However, circulating levels of PH do not correlate well with maternal insulin sensitivity across gestation, suggesting that other, previously unrecognized, mechanisms may be involved. The levels of circulating exosomes are higher in GDM compared to normal. GDM derived exosomes produce greater release of pro-inflammatory cytokines from endothelial cells compared to exosomes from normal, suggesting that their contents may differ compared to normal pregnancies. Using a quantitative, information-independent acquisition (Sequential Windowed Acquisition of All Theoretical Mass Spectra [SWATH]) approach, we identify differentially abundance circulating exosome proteins in women with normal glucose tolerance (NGT) and GDM at the time of GDM diagnosis. A total of 78 statistically significant proteins in the relative expression of exosomal proteins in GDM compared with NGT. Bioinformatic analysis showed the exosomal proteins in GDM target pathways were mainly associated with energy production, inflammation, and metabolism. Finally, we used an independent cohort of patients to validate some of the proteins identified by SWATH. The data obtained may be of utility in elucidating the underlying physiological mechanisms associated with insulin resistant in GDM. This article is protected by copyright. All rights reserved.