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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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 HbA 1c. 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 HbA 1c in early pregnancy (HbA 1c ≤75 mmol/mol [≤9%], HR 2.15 [95% CI 1.31, 3.53]; HbA 1c >75 mmol/mol [>9%], HR 6.10 [95% CI 2.67, 14.0]). However, in mothers with diabetes and HbA 1c <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 HbA 1c level: per 11 mmol/mol (1 percentage point) increase in HbA 1c, 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 HbA 1c: per 11 mmol/mol (1 percentage point) increase in HbA 1c, 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. HbA 1c 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 HbA 1c <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.

OriginalsprogEngelsk
TidsskriftDiabetologia
Vol/bind61
Udgave nummer5
Sider (fra-til)1071–1080
ISSN0012-186X
DOI
StatusUdgivet - maj 2018

Fingeraftryk

Cohort Studies
Mothers
Pre-Eclampsia
Albuminuria
Incidence
Kidney
International Classification of Diseases
First Pregnancy Trimester
Epigenomics
Cognition
Population
Albumins

Citer dette

Knorr, Sine ; Juul, Svend ; Bytoft, Birgitte ; Lohse, Zuzana ; Clausen, Tine D ; Jensen, Rikke B ; Damm, Peter ; Beck-Nielsen, Henning ; Mathiesen, Elisabeth R ; Jensen, Dorte M ; Gravholt, Claus H. / 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). I: Diabetologia. 2018 ; Bind 61, Nr. 5. s. 1071–1080.
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title = "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)",
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 HbA 1c. 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 HbA 1c in early pregnancy (HbA 1c ≤75 mmol/mol [≤9{\%}], HR 2.15 [95{\%} CI 1.31, 3.53]; HbA 1c >75 mmol/mol [>9{\%}], HR 6.10 [95{\%} CI 2.67, 14.0]). However, in mothers with diabetes and HbA 1c <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 HbA 1c level: per 11 mmol/mol (1 percentage point) increase in HbA 1c, 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 HbA 1c: per 11 mmol/mol (1 percentage point) increase in HbA 1c, 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. HbA 1c 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 HbA 1c <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.",
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author = "Sine Knorr and Svend Juul and Birgitte Bytoft and Zuzana Lohse and Clausen, {Tine D} and Jensen, {Rikke B} and Peter Damm and Henning Beck-Nielsen and Mathiesen, {Elisabeth R} and Jensen, {Dorte M} and Gravholt, {Claus H}",
year = "2018",
month = "5",
doi = "10.1007/s00125-018-4575-5",
language = "English",
volume = "61",
pages = "1071–1080",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Heinemann",
number = "5",

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

I: Diabetologia, Bind 61, Nr. 5, 05.2018, s. 1071–1080.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Impact of type 1 diabetes on maternal long-term risk of hospitalisation and mortality

T2 - a nationwide combined clinical and register-based cohort study (The EPICOM study)

AU - Knorr, Sine

AU - Juul, Svend

AU - Bytoft, Birgitte

AU - Lohse, Zuzana

AU - Clausen, Tine D

AU - Jensen, Rikke B

AU - Damm, Peter

AU - Beck-Nielsen, Henning

AU - Mathiesen, Elisabeth R

AU - Jensen, Dorte M

AU - Gravholt, Claus H

PY - 2018/5

Y1 - 2018/5

N2 - 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 HbA 1c. 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 HbA 1c in early pregnancy (HbA 1c ≤75 mmol/mol [≤9%], HR 2.15 [95% CI 1.31, 3.53]; HbA 1c >75 mmol/mol [>9%], HR 6.10 [95% CI 2.67, 14.0]). However, in mothers with diabetes and HbA 1c <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 HbA 1c level: per 11 mmol/mol (1 percentage point) increase in HbA 1c, 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 HbA 1c: per 11 mmol/mol (1 percentage point) increase in HbA 1c, 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. HbA 1c 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 HbA 1c <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.

AB - 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 HbA 1c. 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 HbA 1c in early pregnancy (HbA 1c ≤75 mmol/mol [≤9%], HR 2.15 [95% CI 1.31, 3.53]; HbA 1c >75 mmol/mol [>9%], HR 6.10 [95% CI 2.67, 14.0]). However, in mothers with diabetes and HbA 1c <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 HbA 1c level: per 11 mmol/mol (1 percentage point) increase in HbA 1c, 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 HbA 1c: per 11 mmol/mol (1 percentage point) increase in HbA 1c, 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. HbA 1c 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 HbA 1c <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.

KW - Journal Article

KW - Hypertension

KW - Maternal

KW - Type 1 diabetes

KW - HbA

KW - Mortality

KW - Albuminuria

KW - Pre-eclampsia

KW - Morbidity

KW - Albuminuria/complications

KW - Follow-Up Studies

KW - United States

KW - Epigenesis, Genetic

KW - Humans

KW - Middle Aged

KW - Patient Admission

KW - Cognition

KW - Mothers

KW - Case-Control Studies

KW - Pregnancy in Diabetics/mortality

KW - Adult

KW - Female

KW - Registries

KW - Diabetes Mellitus, Type 1/mortality

KW - Kaplan-Meier Estimate

KW - Hospitalization

KW - Pregnancy

KW - Denmark

KW - Aged

KW - Glycated Hemoglobin A/metabolism

KW - Cohort Studies

U2 - 10.1007/s00125-018-4575-5

DO - 10.1007/s00125-018-4575-5

M3 - Journal article

C2 - 29478097

VL - 61

SP - 1071

EP - 1080

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 5

ER -