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

Abstract

Aims/hypothesis

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.

Methods

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.

Results

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.

Conclusions/interpretation

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.

Graphical abstract

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Fig. 1
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Data availability

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

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Funding

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.

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Authors

Contributions

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). https://doi.org/10.1007/s00125-020-05154-z

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Keywords

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