Advertisement

Diabetologia

, 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
Article

Abstract

Aims/hypothesis

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).

Methods

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.

Results

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.

Conclusions/interpretation

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

Keywords

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

Abbreviations

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

FLI

Fatty liver index

GCT

Glucose challenge screening test

GDM

Gestational diabetes mellitus

GGT

γ-Glutamyl transferase

HSI

Hepatic steatosis index

ICD

International Classification of Diseases

NAFLD

Non-alcoholic fatty liver disease

Notes

Acknowledgements

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.

Funding

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)

References

  1. 1.
    Cho HC (2016) Prevalence and factors associated with nonalcoholic fatty liver disease in a nonobese Korean population. Gut Liver 10(1):117–125.  https://doi.org/10.5009/gnl14444 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Choi SY, Kim D, Kim HJ et al (2009) The relation between non-alcoholic fatty liver disease and the risk of coronary heart disease in Koreans. Am J Gastroenterol 104(8):1953–1960.  https://doi.org/10.1038/ajg.2009.238 CrossRefPubMedGoogle Scholar
  3. 3.
    Vernon G, Baranova A, Younossi ZM (2011) Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34(3):274–285.  https://doi.org/10.1111/j.1365-2036.2011.04724.x CrossRefPubMedGoogle Scholar
  4. 4.
    Loomba R, Sanyal AJ (2013) The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 10(11):686–690.  https://doi.org/10.1038/nrgastro.2013.171 CrossRefPubMedGoogle Scholar
  5. 5.
    Ramesh S, Sanyal AJ (2005) Evaluation and management of non-alcoholic steatohepatitis. J Hepatol 42 Suppl(1):S2–12.  https://doi.org/10.1016/j.jhep.2004.11.022
  6. 6.
    Targher G, Bertolini L, Padovani R et al (2007) Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 30(5):1212–1218.  https://doi.org/10.2337/dc06-2247 CrossRefPubMedGoogle Scholar
  7. 7.
    Marchesini G, Brizi M, Bianchi G et al (2001) Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 50(8):1844–1850.  https://doi.org/10.2337/diabetes.50.8.1844 CrossRefPubMedGoogle Scholar
  8. 8.
    Das K, Das K, Mukherjee PS et al (2010) Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology 51(5):1593–1602.  https://doi.org/10.1002/hep.23567 CrossRefPubMedGoogle Scholar
  9. 9.
    Amarapurkar D, Kamani P, Patel N et al (2007) Prevalence of non-alcoholic fatty liver disease: population based study. Ann Hepatol 6(3):161–163PubMedGoogle Scholar
  10. 10.
    Singh SP, Nayak S, Swain M et al (2004) Prevalence of nonalcoholic fatty liver disease in coastal eastern India: a preliminary ultrasonographic survey. Tropical gastroenterology : official journal of the Digestive Diseases Foundation 25(2):76–79Google Scholar
  11. 11.
    Koo BK, Joo SK, Kim D et al (2018) Additive effects of PNPLA3 and TM6SF2 on the histological severity of non-alcoholic fatty liver disease. J Gastroenterol Hepatol 33(6):1277–1285.  https://doi.org/10.1111/jgh.14056 CrossRefPubMedGoogle Scholar
  12. 12.
    Tiikkainen M, Tamminen M, Hakkinen AM et al (2002) Liver-fat accumulation and insulin resistance in obese women with previous gestational diabetes. Obes Res 10(9):859–867.  https://doi.org/10.1038/oby.2002.118 CrossRefPubMedGoogle Scholar
  13. 13.
    Forbes S, Taylor-Robinson SD, Patel N, Allan P, Walker BR, Johnston DG (2011) Increased prevalence of non-alcoholic fatty liver disease in European women with a history of gestational diabetes. Diabetologia 54(3):641–647.  https://doi.org/10.1007/s00125-010-2009-0 CrossRefPubMedGoogle Scholar
  14. 14.
    Foghsgaard S, Andreasen C, Vedtofte L et al (2017) Nonalcoholic fatty liver disease is prevalent in women with prior gestational diabetes mellitus and independently associated with insulin resistance and waist circumference. Diabetes Care 40(1):109–116.  https://doi.org/10.2337/dc16-1017 CrossRefPubMedGoogle Scholar
  15. 15.
    Ajmera VH, Gunderson EP, Vanwagner LB, Lewis CE, Carr JJ, Terrault NA (2016) Gestational diabetes mellitus is strongly associated with non-alcoholic fatty liver disease. Am J Gastroenterol 111(5):658–664.  https://doi.org/10.1038/ajg.2016.57 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Page LM, Girling JC (2011) A novel cause for abnormal liver function tests in pregnancy and the puerperium: non-alcoholic fatty liver disease. BJOG 118(12):1532–1535.  https://doi.org/10.1111/j.1471-0528.2011.03070.x CrossRefPubMedGoogle Scholar
  17. 17.
    Sharma DL, Lakhani HV, Klug RL et al (2017) Investigating molecular connections of non-alcoholic fatty liver disease with associated pathological conditions in West Virginia for biomarker analysis. J Clin Cell Immunol 8(5).  https://doi.org/10.4172/2155-9899.1000523
  18. 18.
    Misu H, Takamura T, Takayama H et al (2010) A liver-derived secretory protein, selenoprotein P, causes insulin resistance. Cell Metab 12(5):483–495.  https://doi.org/10.1016/j.cmet.2010.09.015 CrossRefPubMedGoogle Scholar
  19. 19.
    Ewing JA (1984) Detecting alcoholism. The CAGE questionnaire. JAMA 252(14):1905–1907.  https://doi.org/10.1001/jama.1984.03350140051025 CrossRefPubMedGoogle Scholar
  20. 20.
    Saadeh S, Younossi ZM, Remer EM et al (2002) The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 123(3):745–750.  https://doi.org/10.1053/gast.2002.35354 CrossRefPubMedGoogle Scholar
  21. 21.
    Taylor KJ, Riely CA, Hammers L et al (1986) Quantitative US attenuation in normal liver and in patients with diffuse liver disease: importance of fat. Radiology 160(1):65–71.  https://doi.org/10.1148/radiology.160.1.3520657 CrossRefPubMedGoogle Scholar
  22. 22.
    Bedogni G, Bellentani S, Miglioli L et al (2006) The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 6(1):33.  https://doi.org/10.1186/1471-230X-6-33 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gastaldelli A, Kozakova M, Hojlund K et al (2009) Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population. Hepatology 49(5):1537–1544.  https://doi.org/10.1002/hep.22845 CrossRefPubMedGoogle Scholar
  24. 24.
    Bozkurt L, Gobl CS, Tura A et al (2012) Fatty liver index predicts further metabolic deteriorations in women with previous gestational diabetes. PLoS One 7(2):e32710.  https://doi.org/10.1371/journal.pone.0032710 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Lee JH, Kim D, Kim HJ et al (2010) Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis 42(7):503–508.  https://doi.org/10.1016/j.dld.2009.08.002 CrossRefPubMedGoogle Scholar
  26. 26.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419.  https://doi.org/10.1007/BF00280883 CrossRefPubMedGoogle Scholar
  27. 27.
    Committee on Practice B-O (2013) Practice Bulletin No. 137: gestational diabetes mellitus. Obstet Gynecol 122:406–416CrossRefGoogle Scholar
  28. 28.
    Carpenter MW, Coustan DR (1982) Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 144(7):768–773.  https://doi.org/10.1016/0002-9378(82)90349-0 CrossRefPubMedGoogle Scholar
  29. 29.
    Firth D (1993) Bias reduction of maximum likelihood estimates. Biometrika 80(1):27–38.  https://doi.org/10.1093/biomet/80.1.27 CrossRefGoogle Scholar
  30. 30.
    Ryu S, Suh BS, Chang Y et al (2015) Menopausal stages and non-alcoholic fatty liver disease in middle-aged women. Eur J Obstet Gynecol Reprod Biol 190:65–70.  https://doi.org/10.1016/j.ejogrb.2015.04.017 CrossRefPubMedGoogle Scholar
  31. 31.
    Lee JY, Shin DW, Oh JW et al (2017) Non-alcoholic fatty liver disease as a risk factor for female sexual dysfunction in premenopausal women. PLoS One 12(8):e0182708.  https://doi.org/10.1371/journal.pone.0182708 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    De Souza LR, Berger H, Retnakaran R et al (2016) Non-alcoholic fatty liver disease in early pregnancy predicts dysglycemia in mid-pregnancy: prospective study. Am J Gastroenterol 111(5):665–670.  https://doi.org/10.1038/ajg.2016.43 CrossRefPubMedGoogle Scholar
  33. 33.
    Hagstrom H, Hoijer J, Ludvigsson JF et al (2016) Adverse outcomes of pregnancy in women with non-alcoholic fatty liver disease. Liver Int 36(2):268–274.  https://doi.org/10.1111/liv.12902 CrossRefPubMedGoogle Scholar
  34. 34.
    Mousa N, Abdel-Razik A, Shams M et al (2018) Impact of non-alcoholic fatty liver disease on pregnancy. Br J Biomed Sci 75:197–199Google Scholar
  35. 35.
    Mccullough AJ (2004) The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis 8:521–533 viiiCrossRefGoogle Scholar
  36. 36.
    Porepa L, Ray JG, Sanchez-Romeu P, Booth GL (2010) Newly diagnosed diabetes mellitus as a risk factor for serious liver disease. CMAJ 182(11):E526–E531.  https://doi.org/10.1503/cmaj.092144 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Despres JP (1993) Abdominal obesity as important component of insulin-resistance syndrome. Nutrition 9(5):452–459PubMedGoogle Scholar
  38. 38.
    Meng K, Lee CH, Saremi F (2010) Metabolic syndrome and ectopic fat deposition: what can CT and MR provide? Acad Radiol 17(10):1302–1312.  https://doi.org/10.1016/j.acra.2010.03.019 CrossRefPubMedGoogle Scholar
  39. 39.
    Larter CZ, Chitturi S, Heydet D, Farrell GC (2010) A fresh look at NASH pathogenesis. Part 1: the metabolic movers. J Gastroenterol Hepatol 25(4):672–690.  https://doi.org/10.1111/j.1440-1746.2010.06253.x CrossRefPubMedGoogle Scholar
  40. 40.
    Lebensztejn DM, Flisiak-Jackiewicz M, Bialokoz-Kalinowska I, Bobrus-Chociej A, Kowalska I (2016) Hepatokines and non-alcoholic fatty liver disease. Acta Biochim Pol 63(3):459–467.  https://doi.org/10.18388/abp.2016_1252 CrossRefPubMedGoogle Scholar
  41. 41.
    Kim JY, Park KJ, Hwang JY et al (2017) Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis. J Hepatol 67(2):349–359.  https://doi.org/10.1016/j.jhep.2017.03.023 CrossRefPubMedGoogle Scholar
  42. 42.
    Misu H, Ishikura K, Kurita S et al (2012) Inverse correlation between serum levels of selenoprotein P and adiponectin in patients with type 2 diabetes. PLoS One 7(4):e34952.  https://doi.org/10.1371/journal.pone.0034952 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Metzger BE, Buchanan TA, Coustan DR et al (2007) Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care 30 (Suppl 2):S251–S260.  https://doi.org/10.2337/dc07-s225
  44. 44.
    Committee on Practice B-O (2018) ACOG Practice Bulletin No. 190: gestational diabetes mellitus. Obstet Gynecol 131:e49–e64CrossRefGoogle Scholar
  45. 45.
    Bril F, Ortiz-Lopez C, Lomonaco R et al (2015) Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver disease in overweight and obese patients. Liver Int 35(9):2139–2146.  https://doi.org/10.1111/liv.12840 CrossRefPubMedGoogle Scholar

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

Personalised recommendations