Skip to main content
Log in

The long-term effects of stillbirth on women with and without gestational diabetes: a population-based cohort study

  • Article
  • Published:
Diabetologia Aims and scope Submit manuscript

Abstract

Aims/hypothesis

The aim of this study was to estimate the incidence of type 2 diabetes (primary objective) and hospitalisation for cardiovascular events (secondary objective) in women with previous gestational diabetes mellitus (GDM) and in those with normal glucose tolerance (NGT) in pregnancy, and to evaluate the role of stillbirth in differentiating the risks.

Methods

This was a population-based cohort study using administrative data and involving 12 local health authorities. Women with GDM (n = 3,851) during the index period from 2002 to 2010 were propensity matched with women with NGT (n = 11,553). Information was collected on type 2 diabetes development and hospitalisation for cardiovascular events.

Results

During a median follow-up of 5.4 years, the incidence rate per 1,000 person-years of type 2 diabetes was 2.1 (95% CI 1.8, 2.5) in women without GDM and 54.0 (95% CI 50.2, 58.0) among women with GDM and pregnancy at term (incidence rate ratio [IRR] 26.9; 95% CI 22.1, 32.7 compared with NGT and pregnancy at term). A history of stillbirth increased the risk of type 2 diabetes development by about twofold, irrespective of GDM status. No significant interaction between stillbirth and GDM on type 2 diabetes risk was found. GDM was associated with a significantly higher risk of cardiovascular events compared with NGT (IRR 2.4; 95% CI 1.5, 3.8).

Conclusions/interpretation

Pregnancy complicated by GDM and ending in stillbirth represents an important contributory factor in determining type 2 diabetes development. Women with GDM are at a high risk of future cardiovascular events. Women with pregnancy complicated by GDM and stillbirth deserve careful follow-up.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ATC:

Anatomical Therapeutic Chemical

CVD:

Cardiovascular disease

GDM:

Gestational diabetes mellitus

IR:

Incidence rates

IRR:

Incidence rate ratio

NGT:

Normal glucose tolerance

References

  1. Whiting DR, Guariguata L, Weil C, Shaw J (2011) IDF Diabetes Atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 94:311–321

    Article  PubMed  Google Scholar 

  2. ADA (2013) Economic costs of diabetes in the U.S. in 2012. Diabetes Care 36:1033–1046

    Article  Google Scholar 

  3. ADA (2014) Standards of medical care in diabetes 2014. Diabetes Care 37:S14–S80

    Article  Google Scholar 

  4. Canadian Diabetes Association (2013) Clinical Practice Guidelines Expert Committee. Reducing the risk of developing diabetes. Can J Diabetes 37:S16–S19

    Google Scholar 

  5. Mosca L, Benjamin EJ, Berra K et al (2011) Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the American Heart Association. Circulation 123:1243–1262

    Article  PubMed Central  PubMed  Google Scholar 

  6. Metzger BE, Coustan DR (1998) Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care 21(Suppl 2):B161–B167

    PubMed  Google Scholar 

  7. Casey BM, Lucas MJ, Mcintire DD, Leveno KJ (1997) Pregnancy outcomes in women with gestational diabetes compared with the general obstetric population. Obstet Gynecol 90:869–873

    Article  CAS  PubMed  Google Scholar 

  8. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS (2005) Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 352:2477–2486

    Article  CAS  PubMed  Google Scholar 

  9. Landon MB, Spong CY, Thom E et al (2009) A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 361:1339–1348

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Kim C, Tabaei BP, Burke R et al (2006) Missed opportunities for type 2 diabetes mellitus screening among women with a history of gestational diabetes mellitus. Am J Public Health 96:1643–1648

    Article  PubMed Central  PubMed  Google Scholar 

  11. Carr DB, Utzschneider KM, Hull RL et al (2006) Gestational diabetes mellitus increases the risk of cardiovascular disease in women with a family history of type 2 diabetes. Diabetes Care 29:2078–2083

    Article  PubMed  Google Scholar 

  12. Shah BR, Retnakaran R, Booth GL (2008) Increased risk of cardiovascular disease in young women following gestational diabetes mellitus. Diabetes Care 31:1668–1669

    Article  PubMed Central  PubMed  Google Scholar 

  13. Dawson SI (2009) Glucose tolerance in pregnancy and the long-term risk of cardiovascular disease. Diabetes Res Clin Pract 85:14–19

    Article  CAS  PubMed  Google Scholar 

  14. Fraser A, Nelson SM, Macdonald-Wallis C, Cherry L, Butler E (2012) Associations of pregnancy complications with calculated cardiovascular disease risk and cardiovascular risk factors in middle age: the Avon longitudinal study of parents and children. Circulation 125:1367–1380

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Kessous R, Shoham-Vardi I, Pariente G, Sherf M, Sheiner E (2013) An association between gestational diabetes mellitus and long-term maternal cardiovascular morbidity. Heart 99:1118–1121

    Article  PubMed  Google Scholar 

  16. Rosenstein MG, Cheng YW, Snowden JM, Nicholson JM, Doss AE, Caughey AB (2012) The risk of stillbirth and infant death stratified by gestational age in women with gestational diabetes. Am J Obstet Gynecol 4:309.e1–7

    Google Scholar 

  17. 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 27:357–366

    Article  PubMed  Google Scholar 

  18. Oliver-Williams CT, Heydon EE, Smith GC, Wood AM (2013) Miscarriage and future maternal cardiovascular disease: a systematic review and meta-analysis. Heart 99(22):1636–1644

    Article  PubMed Central  PubMed  Google Scholar 

  19. World Health Organisation ATC Index with DDDs. Norway, Oslo: WHO Collaborating Centre for Drug Statistics Methodology. Available: http://www.whocc.no/atcddd. Accessed 29 Oct 2013

  20. Macchia A, Romero M, D’Ettorre A, Mariani J, Tognoni G (2012) Temporal trends of the gaps in post-myocardial infarction secondary prevention strategies of co-morbid and elderly populations vs younger counterparts: an analysis of three successive cohorts between 2003 and 2008. Eur Heart J 33:515–522

    Article  PubMed  Google Scholar 

  21. De Berardis G, D’Ettorre A, Graziano G et al (2012) The burden of hospitalization related to diabetes mellitus: a population-based study. Nutr Metab Cardiovasc Dis 22:605–612

    Article  PubMed  Google Scholar 

  22. Winkler WE Comparative analysis of record linkage decision rules. Proceedings of Survey Research Methods Section. Am Stat Assoc 1992;829–834. Available: http://www.amstat.org/sections/srms/proceedings. Accessed 29 Oct 2013

  23. De Berardis G, Lucisano G, D’Ettorre A et al (2012) Association of aspirin use with major bleeding in patients with and without diabetes. JAMA 307:2286–2294

    Article  PubMed  Google Scholar 

  24. Italian Republic. Determination of the Italian Medicines Agency of March 20, 2008 [in Italian]. Official Gazette of the Italian Republic. General Series No. 76; 31 March 31 2008

  25. Carpenter MW, Coustan DR (1982) Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 144:768–773

    CAS  PubMed  Google Scholar 

  26. ADA (2004) Position statement gestational diabetes mellitus. Diabetes Care 27(Suppl 1):S88–S90

    Google Scholar 

  27. McAlister FA, Campbell NR, Duong-Hua M, Chen Z, Tu K (2006) Antihypertensive medication prescribing in 27,822 elderly Canadians with diabetes over the past decade. Diabetes Care 29:836–841

    Article  PubMed  Google Scholar 

  28. Yanovitzky I, Zanutto E, Hornik R (2005) Estimating causal effects of public health education campaigns using propensity score methodology. Eval Program Plann 28:209–220

    Article  Google Scholar 

  29. Parsons LS. Reducing bias in a propensity score matched-pair sample using greedy matching techniques. In: Proceedings of the Twenty-Sixth Annual SAS Users Group International Conference. Cary, NC: SAS Institute. Available: http://www2.sas.com/proceedings/sugi26/p214-26.pdf. Accessed 29 Oct 2013

  30. Austin PC, Grootendorst P, Anderson GM (2007) A comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study. Stat Med 26:734–753

    Article  PubMed  Google Scholar 

  31. Bellamy L, Casas JP, Hingorani AD, Williams D (2009) Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 373:1773–1779

    Article  CAS  PubMed  Google Scholar 

  32. Volpe L, Cuccuru I, Lencioni C et al (2008) Early subclinical atherosclerosis in women with previous gestational diabetes mellitus. Diabetes Care 31:e32

    Article  PubMed  Google Scholar 

  33. Anastasiou E, Lekakis JP, Alevizaki M et al (1998) Impaired endothelium-dependent vasodilatation in women with previous gestational diabetes. Diabetes Care 21:2111–2115

    Article  CAS  PubMed  Google Scholar 

  34. Heitritter SM, Solomon CG, Mitchell GF, Skali-Ounis N, Seely EW (2005) Subclinical inflammation and vascular dysfunction in women with previous gestational diabetes mellitus. J Clin Endocrinol Metab 90:3983–3988

    Article  CAS  PubMed  Google Scholar 

  35. Vrachnis N, Augoulea A, Iliodromiti Z, Lambrinoudaki I, Sifakis S, Creatsas G (2012) Previous gestational diabetes mellitus and markers of cardiovascular risk. Int J Endocrinol 458610

  36. Farmer SA, Black B, Bonow RO (2013) Tension between quality measurement, public quality reporting, and pay for performance. JAMA 309:349–350

    Article  CAS  PubMed  Google Scholar 

  37. Albareda M, Caballero A, Badell G et al (2003) Diabetes and abnormal glucose tolerance in women with previous gestational diabetes. Diabetes Care 26:1199–1205

    Article  PubMed  Google Scholar 

  38. Moreno-Castilla C, Hernandez M, Bergua M et al (2013) Low-carbohydrate diet for the treatment of gestational diabetes mellitus: a randomized controlled trial. Diabetes Care 36:2233–2238

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Likis FE, Sathe NA, Carnahan R, McPheeters ML (2013) A systematic review of validated methods to capture stillbirth and spontaneous abortion using administrative or claims data. Vaccine 31:K74–K82

    Article  PubMed  Google Scholar 

  40. Kim C (2014) Maternal outcomes and follow-up after gestational diabetes mellitus. Diabet Med 3:292–301

    Article  Google Scholar 

Download references

Acknowledgements

We thank the Regional Health Agency and the Department of Health of the Puglia Region for their cooperation, general interest and provision of data.

Funding

The study had no external funding source.

Duality of interest

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

Contribution statement

AN had full access to all study data and takes responsibility for the integrity of the data and the accuracy of data analysis. BP, AN and GDV made substantial contributions to the conception and design of the study. ADE and VL acquired data, and GL, FP, AN, BP, GT, MSc, MSa, GDB and MCR analysed and interpreted the data. BP, GDV and AN drafted the article. FP, GL, GDB, GT, MSa, MCR, VL, ADE and MSc revised the article critically for intellectual content. All authors approved the final version.

AN is the manuscript’s guarantor and affirms that the manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted; and that everyone who contributed significantly to the work is listed in this author contribution section.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio Nicolucci.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM Table 1

(PDF 64 kb)

ESM Table 2

(PDF 67 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pintaudi, B., Lucisano, G., Pellegrini, F. et al. The long-term effects of stillbirth on women with and without gestational diabetes: a population-based cohort study. Diabetologia 58, 67–74 (2015). https://doi.org/10.1007/s00125-014-3403-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00125-014-3403-9

Keywords

Navigation