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

Pia Egerup; Anders P Mikkelsen; Astrid Marie Kolte; David Westergaard; Steen Rasmussen; Filip K Knop; Øjvind Lidegaard; Henriette S Nielsen

doi:10.1007/s00125-020-05154-z

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

Pia Egerup, Anders P Mikkelsen, Astrid Marie Kolte, David Westergaard, Steen Rasmussen, Filip K Knop, Øjvind Lidegaard, Henriette S Nielsen

29 Citations (Scopus)

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.

Original language	English
Journal	Diabetologia
Volume	63
Issue number	8
Pages (from-to)	1521-1529
Number of pages	9
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-020-05154-z
Publication status	Published - Aug 2020

Keywords

Miscarriage
Pregnancy loss
Recurrent pregnancy loss
Reproduction
Type 2 diabetes

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title = "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.",

keywords = "Miscarriage, Pregnancy loss, Recurrent pregnancy loss, Reproduction, Type 2 diabetes",

author = "Pia Egerup and Mikkelsen, {Anders P} and Kolte, {Astrid Marie} and David Westergaard and Steen Rasmussen and Knop, {Filip K} and {\O}jvind Lidegaard and Nielsen, {Henriette S}",

year = "2020",

month = aug,

doi = "10.1007/s00125-020-05154-z",

language = "English",

volume = "63",

pages = "1521--1529",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "8",

}

TY - JOUR

T1 - Pregnancy loss is associated with type 2 diabetes

T2 - a nationwide case-control study

AU - Egerup, Pia

AU - Mikkelsen, Anders P

AU - Kolte, Astrid Marie

AU - Westergaard, David

AU - Rasmussen, Steen

AU - Knop, Filip K

AU - Lidegaard, Øjvind

AU - Nielsen, Henriette S

PY - 2020/8

Y1 - 2020/8

N2 - 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.

AB - 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.

KW - Miscarriage

KW - Pregnancy loss

KW - Recurrent pregnancy loss

KW - Reproduction

KW - Type 2 diabetes

U2 - 10.1007/s00125-020-05154-z

DO - 10.1007/s00125-020-05154-z

M3 - Journal article

C2 - 32424542

SN - 0012-186X

VL - 63

SP - 1521

EP - 1529

JO - Diabetologia

JF - Diabetologia

IS - 8

ER -

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

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Keywords

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