Pregnancy loss is associated with type 2 diabetes: a nationwide case–control study



Type 2 diabetes is killing more people than ever, and early-life predictors remain critical for the development of effective preventive strategies. Pregnancy loss is a common event associated with later atherosclerotic disease and ischaemic heart failure and might constitute a predictor for type 2 diabetes. The objective of this study was to investigate whether pregnancy loss is associated with later development of type 2 diabetes.


Using a Danish nationwide cohort, we identified all women born from 1957 through to 1997 and who had a diagnosis of type 2 diabetes during the period 1977 to 2017. The women were matched 1:10 on year of birth and educational level to women without diabetes in the general Danish population. Conditional logistic regression models provided odds ratios for type 2 diabetes with different numbers of pregnancy losses.


We identified 24,774 women with type 2 diabetes and selected 247,740 controls without diabetes. Women who had ever been pregnant (ever-pregnant women) with 1, 2 and ≥ 3 pregnancy losses had ORs of type 2 diabetes of 1.18 (95% CI 1.13, 1.23), 1.38 (95% CI 1.27, 1.49) and 1.71 (95% CI 1.53, 1.92) compared with ever-pregnant women with no pregnancy losses, respectively. Women who never achieved a pregnancy had an OR of type 2 diabetes of 1.56 (95% CI 1.51, 1.61) compared with ever-pregnant women with any number of losses. Similar results were found after adjustment for obesity and gestational diabetes.


We found a significant and consistent association between pregnancy loss and later type 2 diabetes that increased with increasing number of losses. Thus, pregnancy loss and recurrent pregnancy loss are significant risk factors for later type 2 diabetes. Future studies should explore whether this association is due to common background factors or whether prediabetic metabolic conditions are responsible for this association.

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Data availability

The datasets from this study are not publicly available due to pseudo-anonymised data.


  1. 1.

    World Health Organization (2018) Diabetes fact sheet. Available from Assesed 15 Jan 2019

  2. 2.

    Abbasi A, Peelen LM, Corpeleijn E et al (2012) Prediction models for risk of developing type 2 diabetes: systematic literature search and independent external validation study. BMJ 345:e5900.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Foghsgaard S, Vedtofte L, Andreasen C et al (2017) Women with prior gestational diabetes mellitus and prediabetes are characterised by a decreased incretin effect. Diabetologia 60(7):1344–1353.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Macklon NS, Geraedts JP, Fauser BC (2002) Conception to ongoing pregnancy: the 'black box' of early pregnancy loss. Hum Reprod Update 8(4):333–343.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Martin JA, Hamilton BE, Osterman MJ, Driscoll AK, Mathews TJ (2017) Births: final data for 2015. Natl Vital Stat Rep 66(1):1 Available from Assesed 15 Jan 2019

    PubMed  Google Scholar 

  6. 6.

    Kolte AM, Bernardi LA, Christiansen OB et al (2015) Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group. Hum Reprod 30(3):495–498.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Hardy K, Hardy PJ, Jacobs PA, Lewallen K, Hassold TJ (2016) Temporal changes in chromosome abnormalities in human spontaneous abortions: results of 40 years of analysis. Am J Med Genet A 170(10):2671–2680.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Ogasawara M, Aoki K, Okada S, Suzumori K (2000) Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril 73(2):300–304.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Lund M, Kamper-Jorgensen M, Nielsen HS, Lidegaard O, Andersen AM, Christiansen OB (2012) Prognosis for live birth in women with recurrent miscarriage: what is the best measure of success? Obstet Gynecol 119(1):37–43.

    Article  PubMed  Google Scholar 

  10. 10.

    Royal College of Obstetricians and Gynaecologists (2011) The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. Green-top Guideline No 17. Available from Accessed 15 Jan 2019

  11. 11.

    Danish Society of Obstetrics and Gynecology (2019) National recurrent pregnancy loss guideline. DSOG, Copenhagen

    Google Scholar 

  12. 12.

    Christiansen OB, Nielsen HS, Kolte AM (2006) Inflammation and miscarriage. Semin Fetal Neonatal Med 11(5):302–308.

    Article  PubMed  Google Scholar 

  13. 13.

    Christiansen OB, Nielsen HS, Lund M, Steffensen R, Varming K (2009) Mannose-binding lectin-2 genotypes and recurrent late pregnancy losses. Hum Reprod 24(2):291–299.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Kolte AM, Steffensen R, Christiansen OB, Nielsen HS (2016) Maternal HY-restricting HLA class II alleles are associated with poor long-term outcome in recurrent pregnancy loss after a boy. Am J Reprod Immunol 76(5):400–405.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Kolte AM, Steffensen R, Nielsen HS, Hviid TV, Christiansen OB (2010) Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage. Hum Immunol 71(5):482–488.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Lund M, Nielsen HS, Hviid TV, Steffensen R, Nyboe Andersen A, Christiansen OB (2010) Hereditary thrombophilia and recurrent pregnancy loss: a retrospective cohort study of pregnancy outcome and obstetric complications. Hum Reprod 25(12):2978–2984.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Nielsen HS (2011) Secondary recurrent miscarriage and H-Y immunity. Hum Reprod Update 17(4):558–574.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Nielsen HS, Christiansen OB (2005) Prognostic impact of anticardiolipin antibodies in women with recurrent miscarriage negative for the lupus anticoagulant. Hum Reprod 20(6):1720–1728.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Nielsen HS, Steffensen R, Varming K et al (2009) Association of HY-restricting HLA class II alleles with pregnancy outcome in patients with recurrent miscarriage subsequent to a firstborn boy. Hum Mol Genet 18(9):1684–1691.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Nielsen HS, Witvliet MD, Steffensen R et al (2010) The presence of HLA-antibodies in recurrent miscarriage patients is associated with a reduced chance of a live birth. J Reprod Immunol 87(1–2):67–73.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Nielsen HS, Steffensen R, Lund M et al (2010) Frequency and impact of obstetric complications prior and subsequent to unexplained secondary recurrent miscarriage. Hum Reprod 25(6):1543–1552.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Kruse C, Steffensen R, Varming K, Christiansen OB (2004) A study of HLA-DR and -DQ alleles in 588 patients and 562 controls confirms that HLA-DRB1*03 is associated with recurrent miscarriage. Hum Reprod 19(5):1215–1221.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Christiansen OB, Kolte AM, Nielsen HS (2006) Secondary recurrent miscarriage - a unique entity with respect to etiology and treatment. Current Women’s Health Reviews 2(2):119–124.

    Article  Google Scholar 

  24. 24.

    Smith GC, Pell JP, Walsh D (2003) Spontaneous loss of early pregnancy and risk of ischaemic heart disease in later life: retrospective cohort study. BMJ 326(7386):423–424.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Ranthe MF, Andersen EA, Wohlfahrt J, Bundgaard H, Melbye M, Boyd HA (2013) Pregnancy loss and later risk of atherosclerotic disease. Circulation 127(17):1775–1782.

    Article  PubMed  Google Scholar 

  26. 26.

    Ranthe MF, Boyd HA (2015) Miscarriage and cardiovascular disease. Heart 101(24):1933–1934.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Horn J, Tanz LJ, Stuart JJ et al (2018) Early or late pregnancy loss and development of clinical cardiovascular disease risk factors: a prospective cohort study. BJOG 126(1):33–42.

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Kharazmi E, Lukanova A, Teucher B, Gross ML, Kaaks R (2012) Does pregnancy or pregnancy loss increase later maternal risk of diabetes? Eur J Epidemiol 27(5):357–366.

    Article  PubMed  Google Scholar 

  29. 29.

    Pedersen CB (2011) The Danish civil registration system. Scand J Public Health 39(Suppl 7):22–25.

    Article  PubMed  Google Scholar 

  30. 30.

    Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sorensen HT (2015) The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol 7:449–490.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Bliddal M, Broe A, Pottegard A, Olsen J, Langhoff-Roos J (2018) The Danish Medical Birth Register. Eur J Epidemiol 33(1):27–36.

    Article  PubMed  Google Scholar 

  32. 32.

    Kildemoes HW, Sorensen HT, Hallas J (2011) The Danish National Prescription Registry. Scand J Public Health 39(7 Suppl):38–41.

    Article  PubMed  Google Scholar 

  33. 33.

    The Danish Health Data Authority. Algorithm for selected chronic diseases and severe psychiatric diagnoses. 2018. Available from Assesed 15 Oct 2018

  34. 34.

    Zhang C, Olsen SF, Hinkle SN et al (2019) Diabetes & Women’s Health (DWH) Study: an observational study of long-term health consequences of gestational diabetes, their determinants and underlying mechanisms in the USA and Denmark. BMJ Open 9(4):e025517.

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    American Diabetes Association (2019) Management of diabetes in pregnancy: standards of medical care in diabetes—2019. Diabetes Care 42(Suppl 1):S165–S172.

    Article  Google Scholar 

  36. 36.

    Maryam K, Bouzari Z, Basirat Z, Kashifard M, Zadeh MZ (2012) The comparison of insulin resistance frequency in patients with recurrent early pregnancy loss to normal individuals. BMC Res Notes 5(1):133.

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Craig LB, Ke RW, Kutteh WH (2002) Increased prevalence of insulin resistance in women with a history of recurrent pregnancy loss. Fertil Steril 78(3):487–490.

    Article  PubMed  Google Scholar 

  38. 38.

    Zolghadri J, Tavana Z, Kazerooni T, Soveid M, Taghieh M (2008) Relationship between abnormal glucose tolerance test and history of previous recurrent miscarriages, and beneficial effect of metformin in these patients: a prospective clinical study. Fertil Steril 90(3):727–730.

    Article  PubMed  Google Scholar 

  39. 39.

    Wang Y, Zhao H, Li Y, Zhang J, Tan J, Liu Y (2011) Relationship between recurrent miscarriage and insulin resistance. Gynecol Obstet Investig 72(4):245–251.

    CAS  Article  Google Scholar 

  40. 40.

    Dayan N, Filion KB, Okano M et al (2017) Cardiovascular risk following fertility therapy: systematic review and meta-analysis. J Am Coll Cardiol 70(10):1203–1213.

    Article  PubMed  Google Scholar 

  41. 41.

    Lohse SR, Farkas DK, Lohse N et al (2010) Validation of spontaneous abortion diagnoses in the Danish National Registry of Patients. Clin Epidemiol 2:247–250.

    Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Nielsen GL, Sorensen HT, Pedersen AB, Sabroe S (1996) Analyses of data quality in registries concerning diabetes mellitus--a comparison between a population based hospital discharge and an insulin prescription registry. J Med Syst 20(1):1–10.

    CAS  Article  PubMed  Google Scholar 

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The study was supported by the Ole Kirks Foundation and the Novo Nordisk Foundation (NNF18SA0034956 and NNF14CC0001). The funders had no influence in study design, data analysis, data interpretation or the publication process.

Author information




The study was conceptualised by ØL and HSN. All authors made contributions to study design, data interpretation and preparation of the manuscript. PE and APM performed the data programming and statistical analysis and vouch for the accuracy and completeness of the data and analyses. The corresponding author (PE) had full access to all the data in the study, takes responsibility for the accuracy of the analysis, had authority over manuscript preparation and the decision to submit for publication and is the guarantor of this work. All authors approved the final version to be published.

Corresponding author

Correspondence to Pia Egerup.

Ethics declarations

AMK has received speaker’s fees from Merck Denmark A/S. HSN has served on the scientific advisory board for Ferring Pharmaceuticals and received speaker’s fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic. FKK has served on scientific advisory panels and/or been part of speakers bureaus for, served as a consultant to and/or received research support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, MedImmune, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Sanofi and Zealand Pharma. PE, APM, SR, DW and ØL declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

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Egerup, P., Mikkelsen, A.P., Kolte, A.M. et al. Pregnancy loss is associated with type 2 diabetes: a nationwide case–control study. Diabetologia 63, 1521–1529 (2020).

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  • Miscarriage
  • Pregnancy loss
  • Recurrent pregnancy loss
  • Reproduction
  • Type 2 diabetes