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Plasma protein profiling of women after a GDM pregnancy

ABSTRACT: Gestational diabetes (GDM) is a distinctive form of diabetes that first presents in pregnancy. While most women return to normoglycemia after delivery, they are predisposed to an accelerated development of type 2 diabetes. Current prevention strategies remain limited due to our incomplete understanding of the early underpinnings of progression. We therefore examined the protein profiles of women shortly after a GDM pregnancy (using a nested case-control study design within the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy) for a comprehensive mechanistic inquiry. At 6-9 weeks postpartum (baseline), differences between women who later developed diabetes (case group) and those who did not (control group) were detected. Notably, protein profiles comprised protease inhibitors, extracellular matrix components, and lipoprotein molecules involved in inflammation. We also identified co-expression networks of differentially altered triglycerides and protein involved in wound healing, highlighting the interplay between dyslipidemia and inflammation. Overall, our findings warrant earlier intervention than previously thought, as defects in postpartum wound healing after a GDM pregnancy, in association with dysmetabolism and insulin resistance, may accelerate type 2 diabetes progression.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Julie Anh Dung Van

LAB HEAD: Michael Wheeler

PROVIDER: PXD041243 | Pride | 2024-09-04

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20210901_timsTOF_Evo_22min_CDS_VanJ_100_S4-C8_1_604.d.zip	Other
	20210901_timsTOF_Evo_22min_CDS_VanJ_101_S4-C10_1_606.d.zip	Other
	20210901_timsTOF_Evo_22min_CDS_VanJ_102_S4-C11_1_607.d.zip	Other
	20210901_timsTOF_Evo_22min_CDS_VanJ_103_S4-C12_1_608.d.zip	Other
	20210901_timsTOF_Evo_22min_CDS_VanJ_104_S4-D1_1_610.d.zip	Other

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Project description:Genomic expression profiles of blood and placenta reveal significant immune-related pathways and categories in Chinese women with Gestational Diabetes Gestational diabetes mellitus (GDM) is a complex metabolic disease which occurs in pregnancy with high prevalence, and its pathogenesis remains elusive. Thus far, there has been no comprehensive gene expression profiling in Chinese women with GDM. In this study, we attempt to define the genes and/or pathways that are involved in GDM with Chinese ethnicity, by the Illumina microarray technique. We found 5,197 and 243 genes with significantly altered expression due to GDM in blood and placenta tissues, respectively. Previously known genes (such as TNF, IL1B, LEP, IFNG, and HLA-G) with altered gene expression in GDM were also validated here. In addition, we identified undescribed genes VAV3, PTPN6, CD48 and IL15, in which expression was related to GDM by microarray and Q-RT-PCR assays. To identify GDM-associated pathways, we used analyses with integrated functional annotation (i.e. KEGG) and extracted two significant pathways, which were Natural killer cell mediated cytotoxicity (hsa04650; FDR = 7.10E-09) in blood and Cytokine-cytokine receptor interaction (hsa04060; FDR = 1.07E-03) in placenta tissues. Immune system process (GO: 0002376) was identified by GO analysis with FDR P-value = 7.01E-60 in blood and FDR P-value = 3.57E-08 in placenta tissues, indicating the importance of immunological and inflammatory categories in GDM. Furthermore, despite differences in the quantity of gene expression, we observed a similar functional distribution between expression of blood and placenta tissues in GDM under the categories of immunity. These newly identified key genes and pathways may provide valuable information for the pathogenesis of GDM and advance disease diagnosis, prevention, medication design, and clinical treatment of the disease. One individual GDM blood tissue sample and one pooled GDM blood tissue sample were compared to one pooled healthy blood tissue sample. One pooled GDM placenta tissue sample was compared to one pooled healthy placenta tissue sample.

Project description:Objectives To perceive the temporal features of breast milk proteome between women with gestational diabetes mellitus (GDM) and healthy controls across various lactation periods, as well as to explore the potential impacts of these differences on the growth of offspring. Methods The study cohort included twenty mothers with GDM and twenty healthy mothers. Human milk samples were obtained at four distinct time points: colostrum (4-6 days postpartum), transitional milk (12-14 days postpartum), early mature milk (42 days postpartum) and mature milk (4 months postpartum). Shotgun proteomics with label free quantification was applied to analyze the milk proteome. Gene Ontology (GO) enrichment analysis, alongside other bioinfomatic tools were conducted to elucidate the function of differentially expressed proteins. Subsequently, a random forest model was utilized to discern proteins that could reliably differentiate milk samples from mothers with gestational diabetes mellitus (GDM) from those of healthy counterparts. Furthermore, correlative analysis was employed to investigate the association between these proteins and the anthropometric indices of infants. Results Principal coordinate analysis (PCoA) revealed distinct separations in the milk proteome of GDM and healthy mothers during the initial lactation stages, with these differences diminishing over time. The up-regulated proteins in GDM were predominantly associated with the innate immune system, complement and coagulation cascades, cellular secretion, enzymatic and binding activity, and platelet activation. Six proteins were identified as effective markers for distinguishing milk samples from the two groups, with an average area under the curve (AUC) value of 0.91. Twenty-eight proteins exhibited consistent changes between GDM and healthy groups across at least two lactation stages, many of which were significantly correlated to the anthropometric indices of the offsprings. Conclusions GDM significantly influences the milk proteome, with the extent of alteration diminishing as lactation progresses into the mature milk phase.

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Plasma protein profiling of women after a GDM pregnancy

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