Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later Life

Background. Women with previous gestational diabetes mellitus (GDM) have evidence of postpartum β-cell dysfunction, which increases their risk of developing type 2 diabetes (T2DM) later in life. Elevated levels of circulating cell-free preproinsulin (INS) DNA correlate with dying β-cells in both mic...

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Main Authors: Martha Lappas, Harry M. Georgiou, Jane C. Willcox, Michael Permezel, Alexis Shub, Cody-Lee Maynard, Mugdha V. Joglekar, Anandwardhan A. Hardikar
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2019/3264184
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author Martha Lappas
Harry M. Georgiou
Jane C. Willcox
Michael Permezel
Alexis Shub
Cody-Lee Maynard
Mugdha V. Joglekar
Anandwardhan A. Hardikar
author_facet Martha Lappas
Harry M. Georgiou
Jane C. Willcox
Michael Permezel
Alexis Shub
Cody-Lee Maynard
Mugdha V. Joglekar
Anandwardhan A. Hardikar
author_sort Martha Lappas
collection DOAJ
description Background. Women with previous gestational diabetes mellitus (GDM) have evidence of postpartum β-cell dysfunction, which increases their risk of developing type 2 diabetes (T2DM) later in life. Elevated levels of circulating cell-free preproinsulin (INS) DNA correlate with dying β-cells in both mice and humans. The aim of this study was to determine if cell-free circulating INS DNA levels are higher in women with previous GDM who develop T2DM. Methods. We used droplet digital (dd) PCR to measure the levels of cell-free circulating methylated and unmethylated INS DNA in plasma from 97 women with normal glucose tolerance (NGT), 12 weeks following an index GDM pregnancy. Women were assessed for up to 10 years for the development of T2DM. Results. In the follow-up period, 22% of women developed T2DM. Compared with NGT women, total cell-free INS DNA levels were significantly higher in women who developed T2DM (P=0.02). There was no difference in cell-free circulating unmethylated and methylated INS DNA levels between NGT women and women who developed T2DM (P=0.09 and P=0.07, respectively). Conclusions. In women with a previous index GDM pregnancy, postpartum levels of cell-free circulating INS DNA are significantly higher in those women who later developed T2DM.
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spelling doaj-art-84788d45b3d5402fb2e7eb6f7aae70c62025-08-20T02:08:42ZengWileyJournal of Diabetes Research2314-67452314-67532019-01-01201910.1155/2019/32641843264184Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later LifeMartha Lappas0Harry M. Georgiou1Jane C. Willcox2Michael Permezel3Alexis Shub4Cody-Lee Maynard5Mugdha V. Joglekar6Anandwardhan A. Hardikar7Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, AustraliaDepartment of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, AustraliaSchool of Allied Health, College of Science, Health and Engineering, La Trobe University, Bundoora, Victoria, AustraliaDepartment of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, AustraliaDepartment of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, AustraliaIslet Biology and Diabetes Group, NHMRC Clinical Trials Centre, The University of Sydney, Camperdown, NSW, AustraliaIslet Biology and Diabetes Group, NHMRC Clinical Trials Centre, The University of Sydney, Camperdown, NSW, AustraliaIslet Biology and Diabetes Group, NHMRC Clinical Trials Centre, The University of Sydney, Camperdown, NSW, AustraliaBackground. Women with previous gestational diabetes mellitus (GDM) have evidence of postpartum β-cell dysfunction, which increases their risk of developing type 2 diabetes (T2DM) later in life. Elevated levels of circulating cell-free preproinsulin (INS) DNA correlate with dying β-cells in both mice and humans. The aim of this study was to determine if cell-free circulating INS DNA levels are higher in women with previous GDM who develop T2DM. Methods. We used droplet digital (dd) PCR to measure the levels of cell-free circulating methylated and unmethylated INS DNA in plasma from 97 women with normal glucose tolerance (NGT), 12 weeks following an index GDM pregnancy. Women were assessed for up to 10 years for the development of T2DM. Results. In the follow-up period, 22% of women developed T2DM. Compared with NGT women, total cell-free INS DNA levels were significantly higher in women who developed T2DM (P=0.02). There was no difference in cell-free circulating unmethylated and methylated INS DNA levels between NGT women and women who developed T2DM (P=0.09 and P=0.07, respectively). Conclusions. In women with a previous index GDM pregnancy, postpartum levels of cell-free circulating INS DNA are significantly higher in those women who later developed T2DM.http://dx.doi.org/10.1155/2019/3264184
spellingShingle Martha Lappas
Harry M. Georgiou
Jane C. Willcox
Michael Permezel
Alexis Shub
Cody-Lee Maynard
Mugdha V. Joglekar
Anandwardhan A. Hardikar
Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later Life
Journal of Diabetes Research
title Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later Life
title_full Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later Life
title_fullStr Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later Life
title_full_unstemmed Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later Life
title_short Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later Life
title_sort postpartum circulating cell free insulin dna levels are higher in women with previous gestational diabetes mellitus who develop type 2 diabetes in later life
url http://dx.doi.org/10.1155/2019/3264184
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