, Volume 62, Issue 11, pp 2118–2128 | Cite as

Characteristics and pregnancy outcomes across gestational diabetes mellitus subtypes based on insulin resistance

  • Katrien BenhalimaEmail author
  • Paul Van Crombrugge
  • Carolien Moyson
  • Johan Verhaeghe
  • Sofie Vandeginste
  • Hilde Verlaenen
  • Chris Vercammen
  • Toon Maes
  • Els Dufraimont
  • Christophe De Block
  • Yves Jacquemyn
  • Farah Mekahli
  • Katrien De Clippel
  • Annick Van Den Bruel
  • Anne Loccufier
  • Annouschka Laenen
  • Caro Minschart
  • Roland Devlieger
  • Chantal Mathieu



This study aimed to determine the characteristics and pregnancy outcomes across different subtypes of gestational diabetes mellitus (GDM) based on insulin resistance.


GDM subtypes were defined in 1813 pregnant women from a multicentre prospective cohort study, stratified according to insulin resistance, based on Matsuda index below the 50th percentile of women with normal glucose tolerance (NGT), during a 75 g OGTT at 24–28 weeks’ gestation. GDM was diagnosed in 12.4% (n = 228) of all participants based on the 2013 WHO criteria.


Compared with women with NGT (1113 [61.4%] of the total cohort) and insulin-sensitive women with GDM (39 [17.1%] women with GDM), women with GDM and high insulin resistance (189 [82.9%] women with GDM) had a significantly higher BMI, systolic BP, fasting plasma glucose (FPG), fasting total cholesterol, LDL-cholesterol and triacylglycerol levels in early pregnancy. Compared with women with NGT, insulin-sensitive women with GDM had a significantly lower BMI but similar BP, FPG and fasting lipid levels in early pregnancy. Compared with women with NGT, women with GDM and high insulin resistance had higher rates of preterm delivery (8.5% vs 4.7%, p = 0.030), labour induction (42.7% vs 28.1%, p < 0.001), Caesarean section (total Caesarean sections: 28.7% vs 19.4%, p = 0.004; emergency Caesarean sections: 16.0% vs 9.7%, p = 0.010), neonatal hypoglycaemia (15.4% vs 3.5%, p < 0.001) and neonatal intensive care unit admissions (16.0% vs 8.9%, p = 0.003). In multivariable logistic regression analyses using different models to adjust for demographics, BMI, FPG, HbA1c, lipid levels and gestational weight gain in early pregnancy, preterm delivery (OR 2.41 [95% CI 1.08, 5.38]) and neonatal hypoglycaemia (OR 4.86 [95% CI 2.04, 11.53]) remained significantly higher in women with GDM and high insulin resistance compared with women with NGT. Insulin-sensitive women with GDM had similar pregnancy outcomes as women with NGT. The need for insulin treatment during pregnancy and the rate of glucose intolerance in the early postpartum period were not significantly different among the GDM subtypes.


GDM with high insulin resistance represents a more adverse metabolic profile with a greater risk of adverse pregnancy outcomes.


Gestational diabetes mellitus Pregnancy outcomes Subtypes, insulin resistance, 2013 WHO criteria 



Belgian Diabetes in Pregnancy Study


Fasting plasma glucose


50 g Glucose challenge test


Gestational diabetes mellitus


Insulin secretion-sensitivity index-2


Large for gestational age


Normal glucose tolerance


Neonatal intensive care unit



KB and RD are the recipients of a ‘Fundamenteel Klinisch Navorserschap FWO Vlaanderen’. We thank I. Beckstedde (Department of Obstetrics, University Hospital of Antwerp, Belgium) and S. Van Imschoot (Department of Endocrinology, AZ St Jan Brugge, Belgium) for their help with participant recruitment and study assessments. We thank the research assistants, paramedics and physicians at all participating centres for their support, and we thank all of the women who participated in the study.

Contribution statement

KB, PVC and CMath conceived the project. CMoyso prepared the data and ALaen performed the statistical analysis. KB conducted the literature review. KB and CMath wrote the first draft of the manuscript. All authors contributed to the study design, including data collection, data interpretation and manuscript revision, and all authors have approved the final version. KB had full access to all of the data in the study and has final responsibility for the contents of the article and the decision to submit for publication.


This investigator-initiated study was funded by the Belgian National Lottery, the Fund of Academic studies of UZ Leuven and the Fund Yvonne and Jacques François – de Meurs of the King Boudewijn Foundation. The sponsors of the study had no role in the design of the study or in the collection, handling, analysis or interpretation of the data, or in the decision to write and submit the manuscript for publication.

Duality of interest

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

Supplementary material

125_2019_4961_MOESM1_ESM.pdf (249 kb)
ESM Tables (PDF 248 kb)


  1. 1.
    Crowther CA, Hiller JE, Moss JR et al (2005) Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 352(24):2477–2486. CrossRefGoogle Scholar
  2. 2.
    Landon MB, Spong CY, Thom E et al (2009) A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 361(14):1339–1348. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bellamy L, Casas JP, Hingorani AD, Williams D (2009) Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 373(9677):1773–1779. CrossRefPubMedGoogle Scholar
  4. 4.
    Catalano PM (2014) Trying to understand gestational diabetes. Diabet Med 31(3):273–281. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Powe CE, Allard C, Battista MC et al (2016) Heterogeneous contribution of insulin sensitivity and secretion defects to gestational diabetes mellitus. Diabetes Care 39(6):1052–1055. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Benhalima K, Van Crombrugge P, Verhaeghe J et al (2014) The Belgian Diabetes in Pregnancy Study (BEDIP-N), a multi-centric prospective cohort study on screening for diabetes in pregnancy and gestational diabetes: methodology and design. BMC Pregnancy Childbirth 14(1):226. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Benhalima K, Van Crombrugge P, Moyson C et al (2018) The sensitivity and specificity of the glucose challenge test in a universal two-step screening strategy for gestational diabetes mellitus using the 2013 World Health Organization criteria. Diabetes Care 41(7):e111–e112. CrossRefPubMedGoogle Scholar
  8. 8.
    Benhalima K, Van Crombrugge P, Moyson C et al (2018) A modified two-step screening strategy for gestational diabetes mellitus based on the 2013 WHO criteria by combining the glucose challenge test and clinical risk factors. J Clin Med 7(10):351. CrossRefPubMedCentralGoogle Scholar
  9. 9.
    American Diabetes Association (2013) Standards of medical care in diabetes – 2013. Diabetes Care 36(Suppl 1):S11–S66. CrossRefGoogle Scholar
  10. 10.
    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. CrossRefGoogle Scholar
  11. 11.
    Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22(9):1462–1470. CrossRefPubMedGoogle Scholar
  12. 12.
    Kahn SE, Prigeon RL, McCulloch DK et al (1993) Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42(11):1663–1672. CrossRefPubMedGoogle Scholar
  13. 13.
    Retnakaran R, Qi Y, Goran MI, Hamilton JK (2009) Evaluation of proposed oral disposition index measures in relation to the actual disposition index. Diabet Med 26(12):1198–1203. CrossRefPubMedGoogle Scholar
  14. 14.
    Stumvoll M, Van Haeften T, Fritsche A, Gerich J (2001) Oral glucose tolerance test indexes for insulin sensitivity and secretion based on various availabilities of sampling times. Diabetes Care 24(4):796–797. CrossRefPubMedGoogle Scholar
  15. 15.
    Devlieger HMG, Bekaert A, Eeckels R (2000) Standaarden van geboortegewicht-voor-zwangerschapsduur voor de Vlaamse boreling. Tijdschr voor Geneeskunde 56(1):1–14 [article in Dutch]. CrossRefGoogle Scholar
  16. 16.
    Rasmussen KM, Yaktine AL (eds) (2009) Weight gain during pregnancy: reexamining the guidelines. National Academies Press, Washington, DCGoogle Scholar
  17. 17.
    Cheney C, Shragg P, Hollingsworth D (1985) Demonstration of heterogeneity in gestational diabetes by a 400-kcal breakfast meal tolerance test. Obstet Gynecol 65(1):17–23PubMedGoogle Scholar
  18. 18.
    Chen Q, Francis E, Hu G, Chen L (2018) Metabolomic profiling of women with gestational diabetes mellitus and their offspring: review of metabolomics studies. J Diabetes Complicat 32(5):512–523. CrossRefPubMedGoogle Scholar
  19. 19.
    Barbour LA, Hernandez TL (2018) Maternal non-glycemic contributors to fetal growth in obesity and gestational diabetes: spotlight on lipids. Curr Diab Rep 18(6):37. CrossRefPubMedGoogle Scholar
  20. 20.
    Barbour LA, Farabi SS, Friedman JE et al (2018) Postprandial triglycerides predict newborn fat more strongly than glucose in women with obesity in early pregnancy. Obesity 26(8):1347–1356. CrossRefPubMedGoogle Scholar
  21. 21.
    Elbein SC, Wegner K, Kahn SE (2000) Reduced beta-cell compensation to the insulin resistance associated with obesity in members of Caucasian familial type 2 diabetic kindreds. Diabetes Care 23(2):221–227. CrossRefPubMedGoogle Scholar
  22. 22.
    Retnakaran R, Hanley AJ, Raif N et al (2005) Adiponectin and beta cell dysfunction in gestational diabetes: pathophysiological implications. Diabetologia 48(5):993–1001. CrossRefPubMedGoogle Scholar
  23. 23.
    Retnakaran R, Shen S, Hanley AJ, Vuksan V, Hamilton JK, Zinman B (2008) Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test. Obesity 16(8):1901–1907. CrossRefPubMedGoogle Scholar
  24. 24.
    Benhalima K, Jegers K, Devlieger R, Verhaeghe J, Mathieu C (2016) Glucose intolerance after a recent history of gestational diabetes based on the 2013 WHO Criteria. PLoS One 11(6):e0157272. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Katrien Benhalima
    • 1
    Email author
  • Paul Van Crombrugge
    • 2
  • Carolien Moyson
    • 1
  • Johan Verhaeghe
    • 3
  • Sofie Vandeginste
    • 4
  • Hilde Verlaenen
    • 4
  • Chris Vercammen
    • 5
  • Toon Maes
    • 5
  • Els Dufraimont
    • 6
  • Christophe De Block
    • 7
  • Yves Jacquemyn
    • 8
  • Farah Mekahli
    • 9
  • Katrien De Clippel
    • 10
  • Annick Van Den Bruel
    • 11
  • Anne Loccufier
    • 12
  • Annouschka Laenen
    • 13
  • Caro Minschart
    • 1
  • Roland Devlieger
    • 3
  • Chantal Mathieu
    • 1
  1. 1.Department of Endocrinology, UZ GasthuisbergKU LeuvenLeuvenBelgium
  2. 2.Department of EndocrinologyOLV Ziekenhuis Aalst-Asse-NinoveAalstBelgium
  3. 3.Department of Obstetrics & Gynecology, University Hospital GasthuisbergKU LeuvenLeuvenBelgium
  4. 4.Department of Obstetrics & GynecologyOLV Ziekenhuis Aalst-Asse-NinoveAalstBelgium
  5. 5.Department of EndocrinologyImelda ZiekenhuisBonheidenBelgium
  6. 6.Department of Obstetrics & GynecologyImelda ZiekenhuisBonheidenBelgium
  7. 7.Department of Endocrinology-Diabetology-MetabolismAntwerp University HospitalEdegemBelgium
  8. 8.Department of Obstetrics & GynecologyAntwerp University HospitalEdegemBelgium
  9. 9.Department of EndocrinologyKliniek St-Jan BrusselBrusselsBelgium
  10. 10.Department of Obstetrics & GynecologyKliniek St-Jan BrusselBrusselsBelgium
  11. 11.Department of EndocrinologyAZ St-Jan BruggeBruggeBelgium
  12. 12.Department of Obstetrics & GynecologyAZ St-Jan BruggeBruggeBelgium
  13. 13.Center of Biostatics and Statistical BioinformaticsKU LeuvenLeuvenBelgium

Personalised recommendations