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
View: Text | PDF | Corrigendum
Research Article Metabolism

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

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

×

Figure 1

Comparisons of proteomes in T2D and prediabetes versus healthy participants.

Options: View larger image (or click on image) Download as PowerPoint
Comparisons of proteomes in T2D and prediabetes versus healthy participa...
(A) Overview of clinical cohort and the serum proteomic workflow. Proteomic profiling was performed in serum samples collected at 6-year and 10-year postpregnancy follow-ups from participants diagnosed with GDM. Serum samples were prepared and analyzed by LC-MS/MS using data-independent acquisition (DIA). The total number of participants per subgroup is shown. (B and C) Volcano plots comparing the serum proteomes of T2D versus healthy participants at 6-year (B) and 10-year (C) follow-ups post-GDM. The log2 fold-change in protein abundance is displayed on the x axis, and the –log10 2-tailed t test P value is displayed on the y axis. Color coding is based on P values (P < 0.05: in yellow), with directionality of difference in protein abundance (purple: significantly increased in T2D; blue: significantly decreased in T2D). Highlighted proteins are further discussed in the text. (D) Dysregulated proteins in T2D with the most pronounced magnitude of dysregulation (log2 fold change > 0.5) or observed at both 6- and 10-year visits, as shown in B and C. Proteins significantly dysregulated in T2D compared with healthy controls were marked with a star. (E and F) Volcano plots of prediabetic versus healthy participants proteome at 6-year (E) and 10-year (F) post-GDM visits. Notations are as in B and C. (G) Log2 fold change protein abundance in prediabetes compared with healthy participants at 6 and 10 years after GDM. Proteins found to be T2D associated in B or C are labeled purple and prediabetic-specific proteins are labeled black. Proteins significantly dysregulated in prediabetes compared with healthy controls were marked with a star.