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Longitudinal clinical and proteomic diabetes signatures in women with a history of gestational diabetes
Heaseung Sophia Chung, Lawrence Middleton, Manik Garg, Ventzislava A. Hristova, Rick B. Vega, David Baker, Benjamin G. Challis, Dimitrios Vitsios, Sonja Hess, Kristina Wallenius, Agneta Holmäng, Ulrika Andersson-Hall
Heaseung Sophia Chung, Lawrence Middleton, Manik Garg, Ventzislava A. Hristova, Rick B. Vega, David Baker, Benjamin G. Challis, Dimitrios Vitsios, Sonja Hess, Kristina Wallenius, Agneta Holmäng, Ulrika Andersson-Hall
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Research Article Metabolism

Longitudinal clinical and proteomic diabetes signatures in women with a history of gestational diabetes

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Abstract

We characterized the longitudinal serum protein signatures of women 6 and 10 years after having gestational diabetes mellitus (GDM) to identify factors associated with the development of type 2 diabetes mellitus (T2D) and prediabetes in this at-risk post-GDM population, aiming to discover potential biomarkers for early diagnosis and prevention of T2D. Our study identified 75 T2D-associated serum proteins and 23 prediabetes-associated proteins, some of which were validated in an independent T2D cohort. Machine learning (ML) performed on the longitudinal proteomics highlighted protein signatures associated with progression to post-GDM diabetes. We also proposed prognostic biomarker candidates that were differentially regulated in healthy participants at 6 years postpartum who later progressed to having T2D. Our longitudinal study revealed T2D risk factors for post-GDM populations who are relatively young and healthy, providing insights for clinical decisions and early lifestyle interventions.

Authors

Heaseung Sophia Chung, Lawrence Middleton, Manik Garg, Ventzislava A. Hristova, Rick B. Vega, David Baker, Benjamin G. Challis, Dimitrios Vitsios, Sonja Hess, Kristina Wallenius, Agneta Holmäng, Ulrika Andersson-Hall

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Figure 2

Proteins associated with diabetes severity or clinical traits.

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Proteins associated with diabetes severity or clinical traits.
(A) Inten...
(A) Intensities of the selected proteins (1-way ANOVA, Padj. <0.01) across subpopulations. Log2 intensity of participants in each subpopulation were displayed as a box-and-whiskers plot showing median and interquartile range (IQR). Adjusted P value by Brown-Forsythe and Welch 1-way ANOVA tests and Dunnett’s T3 multiple comparisons test were labeled if P < 0.05. (B) Associations of post-GDM T2D markers from Figure 1, B and C, with clinical characteristics. Selected proteins with absolute Spearman correlation ρ > 0.4 with at least 1 of the clinical characteristics were displayed. Heatmaps show correlation coefficients between protein levels in serum and clinical characteristics of all participants at 10 years follow-up visits. Row clustering was based on log2 intensity of the protein. (C) Examples of the correlations from B; abundance of PON3 protein with HDL and insulin resistance of all participants at 10-year time point.

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