, Volume 62, Issue 2, pp 238–248 | Cite as

Non-alcoholic fatty liver disease in the first trimester and subsequent development of gestational diabetes mellitus

  • Seung Mi Lee
  • Soo Heon Kwak
  • Ja Nam Koo
  • Ig Hwan Oh
  • Jeong Eun Kwon
  • Byoung Jae Kim
  • Sun Min Kim
  • Sang Youn Kim
  • Gyoung Min Kim
  • Sae Kyung Joo
  • Bo Kyung Koo
  • Sue Shin
  • Chanthalakeo Vixay
  • Errol R. Norwitz
  • Chan-Wook Park
  • Jong Kwan Jun
  • Won KimEmail author
  • Joong Shin ParkEmail author



Although there is substantial evidence that non-alcoholic fatty liver disease (NAFLD) is associated with impaired glucose homeostasis, the clinical significance of NAFLD in pregnant women has not been well determined. This study investigates the relationship between NAFLD in the first trimester and the subsequent development of gestational diabetes mellitus (GDM).


A multicentre, prospective cohort study was conducted in which singleton pregnant Korean women were assessed for NAFLD at 10–14 weeks using liver ultrasound, fatty liver index (FLI) and hepatic steatosis index (HSI). Maternal plasma adiponectin and selenoprotein P concentrations were measured. Participants were screened for GDM using the two-step approach at 24–28 weeks.


Six hundred and eight women were included in the final analysis. The prevalence of NAFLD was 18.4% (112/608) and 5.9% (36/608) developed GDM. Participants who developed GDM had a higher prevalence of radiological steatosis (55.6% vs 16.1%; p < 0.001) and higher FLI (40.0 vs 10.7; p < 0.001) and HSI (35.5 vs 29.0; p < 0.001). The risk of developing GDM was significantly increased in participants with NAFLD and was positively correlated with the severity of steatosis. This relationship between NAFLD and GDM remained significant after adjustment for metabolic risk factors, including measures of insulin resistance. Maternal plasma adiponectin and selenoprotein P levels were also correlated with both NAFLD severity and the risk of developing GDM.


NAFLD in early pregnancy is an independent risk factor for GDM. Adiponectin may be a useful biomarker for predicting GDM in pregnant women.


Gestational diabetes mellitus Insulin resistance Non-alcoholic fatty liver disease Prediction 



Alanine aminotransferase


Aspartate aminotransferase


Fatty liver index


Glucose challenge screening test


Gestational diabetes mellitus


γ-Glutamyl transferase


Hepatic steatosis index


International Classification of Diseases


Non-alcoholic fatty liver disease



Some of the data were presented as an abstract at The International Liver Congress in 2018. The authors would like to thank S. Oh (the Department of Biostatistics, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Korea) for statistical advice.

Contribution statement

The study was conceived and designed by SML, WK and JSP. WK and JSP supervised the study. All authors acquired, analysed or interpreted data. SML carried out statistical analysis. SML, WK and JSP drafted the manuscript. All authors critically revised the manuscript for important intellectual content and approved the version to be published. SML, WK and JSP are guarantors who had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.


This work was supported by a clinical research grant-in-aid from the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science and ICT of Korea (2016M3A9B6902061) and was also supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (H I17C0912).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2018_4779_MOESM1_ESM.pdf (83 kb)
ESM (PDF 83 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Seung Mi Lee
    • 1
  • Soo Heon Kwak
    • 2
  • Ja Nam Koo
    • 3
  • Ig Hwan Oh
    • 3
  • Jeong Eun Kwon
    • 3
    • 4
  • Byoung Jae Kim
    • 1
    • 5
  • Sun Min Kim
    • 1
    • 5
  • Sang Youn Kim
    • 6
  • Gyoung Min Kim
    • 7
  • Sae Kyung Joo
    • 8
    • 9
  • Bo Kyung Koo
    • 8
    • 9
  • Sue Shin
    • 10
    • 11
  • Chanthalakeo Vixay
    • 12
  • Errol R. Norwitz
    • 13
  • Chan-Wook Park
    • 1
  • Jong Kwan Jun
    • 1
  • Won Kim
    • 8
    • 9
    Email author
  • Joong Shin Park
    • 1
    Email author
  1. 1.Department of Obstetrics and GynecologySeoul National University College of MedicineSeoulSouth Korea
  2. 2.Department of Internal MedicineSeoul National University College of MedicineSeoulSouth Korea
  3. 3.Seoul Women’s HospitalIncheonSouth Korea
  4. 4.Department of Obstetrics and GynecologyHallym University Sacred Heart HospitalGyeonggi-doSouth Korea
  5. 5.Department of Obstetrics and GynecologySeoul Metropolitan Government Seoul National University Boramae Medical CenterSeoulSouth Korea
  6. 6.Department of RadiologySeoul National University College of MedicineSeoulSouth Korea
  7. 7.Department of RadiologyYonsei University College of MedicineSeoulSouth Korea
  8. 8.Department of Internal MedicineSeoul National University College of MedicineSeoulSouth Korea
  9. 9.Division of Gastroenterology and Hepatology, Department of Internal MedicineSeoul Metropolitan Government Seoul National University Boramae Medical CenterSeoulSouth Korea
  10. 10.Department of Laboratory MedicineSeoul National University College of MedicineSeoulSouth Korea
  11. 11.Department of Laboratory MedicineSeoul Metropolitan Government Seoul National University Boramae Medical CenterSeoulSouth Korea
  12. 12.Department of Obstetrics and GynecologyUniversity of Health SciencesVientianeLao PDR
  13. 13.Department of Obstetrics and GynecologyTufts University School of MedicineBostonUSA

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