Diabetologia

, Volume 61, Issue 5, pp 1071–1080 | Cite as

Impact of type 1 diabetes on maternal long-term risk of hospitalisation and mortality: a nationwide combined clinical and register-based cohort study (The EPICOM study)

  • Sine Knorr
  • Svend Juul
  • Birgitte Bytoft
  • Zuzana Lohse
  • Tine D. Clausen
  • Rikke B. Jensen
  • Peter Damm
  • Henning Beck-Nielsen
  • Elisabeth R. Mathiesen
  • Dorte M. Jensen
  • Claus H. Gravholt
Article

Abstract

Aims/hypothesis

The aims of this study were to examine long-term mortality and morbidity rates in mothers with type 1 diabetes, both overall and according to the level of albuminuria prior to pregnancy, the presence of hypertension, pre-eclampsia and periconceptional HbA1c.

Methods

This study was a part of the EPICOM (Environmental Versus Genetic and Epigenetic Influences on Growth, Metabolism and Cognitive Function in Offspring of Mothers with Type 1 Diabetes) study, which is a prospective follow-up study focusing on pregnancies complicated by maternal type 1 diabetes. We carried out a nationwide combined clinical and register-based cohort study of mortality rates and hospital admissions in mothers with diabetes (n = 986) who gave birth between 1992 and 2000. Control mothers (n = 91,441) were women from the background population, matched according to age and year of childbirth. Age at follow-up was 32–66 years.

Results

Mortality rate was increased threefold in mothers with diabetes compared with control mothers (HR 3.41 [95% CI 2.42, 4.81]; p < 0.0001), and was also increased with pre-gestational kidney dysfunction (normoalbuminuria, HR 2.17 [95% CI 1.28, 3.68]; microalbuminuria, HR 3.36 [95% CI 0.82, 13.8]; macroalbuminuria, HR 12.9 [95% CI 5.45, 30.7]). Moreover, the presence of hypertension prior to or at any time during pregnancy and of pre-eclampsia also increased mortality rate (hypertension, HR 4.34 [95% CI 2.13, 8.84]; pre-eclampsia, HR 5.55 [95% CI 2.71, 11.4]). Mortality rate also increased with higher levels of HbA1c in early pregnancy (HbA1c ≤75 mmol/mol [≤9%], HR 2.15 [95% CI 1.31, 3.53]; HbA1c >75 mmol/mol [>9%], HR 6.10 [95% CI 2.67, 14.0]). However, in mothers with diabetes and HbA1c <64 mmol/mol (<8%) in the first trimester and normal pre-gestational urinary albumin excretion rate (n = 517), mortality rate was comparable with that of control mothers. Among mothers with diabetes, mortality rate was associated with HbA1c level: per 11 mmol/mol (1 percentage point) increase in HbA1c, HR was 1.52 (95% CI 1.19, 1.94; p = 0.001). In mothers with diabetes, the overall incidence of hospital admissions was more than double (incidence rate ratio [IRR] 2.69 [95% CI 2.59, 2.80]; p < 0.0001) that of control mothers, as were admissions with various diagnoses from 14 out of 19 ICD-10 chapters. Among mothers with diabetes, the IRR for hospital admissions increased with the level of HbA1c: per 11 mmol/mol (1 percentage point) increase in HbA1c, HR was 1.07 (95% CI 1.04, 1.10; p < 0.0001).

Conclusions/interpretation

Overall, mothers with type 1 diabetes have a two- to threefold increase in mortality and morbidity rates. HbA1c levels, level of albuminuria around the time of conception, and the presence of hypertension and pre-eclampsia are important risk factors for mortality/morbidity in this cohort. However, it is reassuring that mothers with type 1 diabetes without kidney complications and with HbA1c <64 mmol/mol (<8%) in early pregnancy have a similar survival potential during the period where they are raising their children to that of control mothers from the background population.

Keywords

Albuminuria HbA1c Hypertension Maternal Morbidity Mortality Pre-eclampsia Type 1 diabetes 

Abbreviations

IRR

Incidence rate ratio

UAER

Urinary albumin excretion rate

Notes

Acknowledgements

The Danish Diabetes Association is acknowledged for originally assisting in the creation of a registry of pregnant women with type 1 diabetes. In addition, data collection in the original registry was performed by P. Ovesen, L. Mølsted-Pedersen, J. Klebe, N. Hahnemann, M. Møller, J. G. Westergaard, H. Gjessing, J. Kragh Mostrup, K. H. Frandsen, E. Stage, A. Thomsen, T. Lousen, K. Rubeck Petersen, B. Øvlisen, J. Kvetny and H. Poulsen (Working Group for Type 1 Diabetes Pregnancy). Apart from H. Beck-Nielsen and P. Damm, the original registry working group included A. Frøland, L. Mølsted-Pedersen, J. Klebe and C. E. Mogensen.

Contribution statement

HB-N and PD contributed to the establishment of the original registry, and PD and DMJ contributed to data collection. SK, ZL, BB, TDC, RBJ, PD, ERM, HB-N, DMJ and CHG all contributed substantially to the conception and design of the study. SK, SJ and CHG analysed and interpreted the data, and SK drafted the manuscript and designed the tables. All authors critically revised the article and approved the final version for publication. SK had full access to the data and takes full responsibility for the contents of the paper.

Data availability

The dataset generated and analysed during this study is not publicly available due both to considerations of the privacy and anonymity of the participants and also due to restrictions from Statistics Denmark. Other researchers may apply for access to the data if they have obtained official approval.

Duality of interest

SK, ZL, BB, TDC, RBJ and SJ declare that there is no duality of interest associated with their contribution to this manuscript. HB-N, PD and CHG have received lecture fees from Novo Nordisk. DMJ has received lecture fees from Eli Lilly. ERM and HB-N receive grant support from Novo Nordisk.

Supplementary material

125_2018_4575_MOESM1_ESM.pdf (199 kb)
ESM Tables (PDF 199 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Sine Knorr
    • 1
    • 2
  • Svend Juul
    • 3
  • Birgitte Bytoft
    • 4
    • 5
  • Zuzana Lohse
    • 6
  • Tine D. Clausen
    • 7
  • Rikke B. Jensen
    • 5
    • 8
  • Peter Damm
    • 4
    • 5
  • Henning Beck-Nielsen
    • 6
  • Elisabeth R. Mathiesen
    • 5
    • 9
  • Dorte M. Jensen
    • 6
  • Claus H. Gravholt
    • 1
    • 2
  1. 1.Department of Endocrinology and Internal MedicineAarhus University HospitalAarhus CDenmark
  2. 2.Department of Molecular MedicineAarhus University HospitalAarhusDenmark
  3. 3.Section for Epidemiology, Department of Public HealthAarhus UniversityAarhusDenmark
  4. 4.Center for Pregnant Women with Diabetes, Department of ObstetricsRigshospitaletCopenhagenDenmark
  5. 5.Institute of Clinical Medicine, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  6. 6.Department of EndocrinologyOdense University HospitalOdenseDenmark
  7. 7.Department of Gynaecology and ObstetricsNordsjællands HospitalHillerødDenmark
  8. 8.Department of Growth and ReproductionRigshospitaletCopenhagenDenmark
  9. 9.Center for Pregnant Women with Diabetes, Department of EndocrinologyRigshospitaletCopenhagenDenmark

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