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Early second-trimester plasma protein profiling using multiplexed isobaric tandem mass tag (TMT) labeling predicts gestational diabetes mellitus

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Abstract

Aims

Gestational diabetes mellitus (GDM) is associated with an increased risk of serious complications for mother and child during pregnancy. The main option for diagnosis of GDM is 75 g oral glucose tolerance test (OGTT) at 24–28 gestation weeks, when harms to both mother and child have already potentially occurred. The aim of this study was to investigate new biomarkers for earlier detection and assessment of GDM at early second trimester (16–18 gestation weeks).

Methods

We systematically used multiplexed isobaric tandem mass tag labeling combined with liquid chromatography mass spectrometry (LC-MS/MS) to screen differentially expressed proteins in plasma collected at 16–18 gestational weeks between pregnant women with and without GDM outcome.

Results

A total of 828 proteins were identified, of which 36 proteins implicated in immune response, inflammation, transport, platelet aggregation, catalyze and defense response were identified as differentially regulated proteins in GDM. To assess the validity of the results, four selected proteins including C-reactive protein, sex hormone-binding globulin, Ficolin 3 and pregnancy-specific beta-1-glycoprotein 4 were selected for subsequent Western blot analysis.

Conclusions

This is the first comprehensive study that integrates multiple state-of-the-art proteomic technologies to discover the earlier potential plasma biomarkers for GDM.

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Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (81000258, 81100436), the Natural Science Foundation of Jiangsu Province (BK2010586), the Bureau of Nanjing City Science and Technology Development Fund (201104014), the Open topic of State Key Laboratory of Reproductive Medicine (SKLRM-KF-201109, SKLRM-B12) and the Nanjing Medical Technology Development Project [Grant Numbers YKK14126, QRX11210, QRX11211].

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    Authors and Affiliations

    1. State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China

      Chun Zhao, Fuqiang Wang, Hongjuan Ding & Zhonghua Shi

    2. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 210029, China

      Xiaoyan Huang

    3. Liver Transplantation Center of the First Affiliated Hospital to Nanjing Medical University, Nanjing, 210029, China

      Ping Wang

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    1. Chun Zhao
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    2. Fuqiang Wang
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    3. Ping Wang
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    4. Hongjuan Ding
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    5. Xiaoyan Huang
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    Correspondence to Xiaoyan Huang or Zhonghua Shi.

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    All authors have no conflicts of interest to declare.

    Ethical standard

    This study was performed in accordance with the Ethics Committee of Nanjing Medical University with an Institutional Review Board Number of 2012-NFLZ-32, the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

    Human and animal rights

    The study was approved by the Ethics Committee of Nanjing Medical University with an Institutional Review Board (IRB) Number of 2012-NFLZ-32. The blood sample-collection was performed in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the revised Helsinki Declaration in 2008.

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    Informed consent was obtained from all patients for being included in the study.

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    Zhao, C., Wang, F., Wang, P. et al. Early second-trimester plasma protein profiling using multiplexed isobaric tandem mass tag (TMT) labeling predicts gestational diabetes mellitus. Acta Diabetol 52, 1103–1112 (2015). https://doi.org/10.1007/s00592-015-0796-y

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    • DOI: https://doi.org/10.1007/s00592-015-0796-y

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