Skip to main content
Top
Published in: Diabetology & Metabolic Syndrome 1/2016

Open Access 01-12-2016 | Research

β-Cell death is decreased in women with gestational diabetes mellitus

Authors: Lauren A. Kenna, John A. Olsen, Michael G. Spelios, Michael S. Radin, Eitan M. Akirav

Published in: Diabetology & Metabolic Syndrome | Issue 1/2016

Login to get access

Abstract

Background

Gestational diabetes mellitus (GDM) affects approximately 7–17 % of all pregnancies and has been recognized as a significant risk factor to neonatal and maternal health. Postpartum, GDM significantly increases the likelihood of developing type 2 diabetes (T2D). While it is well established that insulin resistance and impaired β-cell function contribute to GDM development, the role of active β-cell loss remains unknown. Differentially methylated circulating free DNA (cfDNA) is a minimally invasive biomarker of β-cell loss in type 1 diabetes mellitus. Here we use cfDNA to examine the levels of β-cell death in women with GDM.

Methods

Second to third-trimester pregnant women with GDM were compared with women with normal pregnancy (PRG), women at postpartum (PP), and non-pregnant (NP) women. Fasting glucose levels, insulin, and C-peptide levels were measured. Serum samples were collected and cfDNA purified and bisulfite treated. Methylation-sensitive probes capable of differentiating between β-cell-derived DNA (demethylated) and non-β-cell-derived DNA (methylated) were used to measure the presence of β-cell loss in the blood.

Results

GDM was associated with elevated fasting glucose levels (GDM = 185.9 ± 5.0 mg/dL) and reduced fasting insulin and c-peptide levels when compared with NP group. Interestingly, β-cell derived insulin DNA levels were significantly lower in women with GDM when compared with PRG, NP, and PP groups (demethylation index: PRG = 7.74 × 10−3 ± 3.09 × 10−3, GDM = 1.01 × 10−3 ± 5.86 × 10−4, p < 0.04; NP = 4.53 × 10−3 ± 1.62 × 10−3, PP = 3.24 × 10−3 ± 1.78 × 10−3).

Conclusions

These results demonstrate that β-cell death is reduced in women with GDM. This reduction is associated with impaired insulin production and hyperglycemia, suggesting that β-cell death does not contribute to GDM during the 2nd and 3rd trimester of pregnancy.
Literature
1.
go back to reference Gestational diabetes mellitus. Diabetes Care. 2003; 26 Suppl 1: p. S103–5. Gestational diabetes mellitus. Diabetes Care. 2003; 26 Suppl 1: p. S103–5.
3.
go back to reference Diabetes American. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2006;29(Suppl 1):S43–8. Diabetes American. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2006;29(Suppl 1):S43–8.
4.
go back to reference Group, H.S.C.R., et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358(19):1991–2002.CrossRef Group, H.S.C.R., et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358(19):1991–2002.CrossRef
5.
go back to reference Casey BM, et al. Pregnancy outcomes in women with gestational diabetes compared with the general obstetric population. Obstet Gynecol. 1997;90(6):869–73.CrossRefPubMed Casey BM, et al. Pregnancy outcomes in women with gestational diabetes compared with the general obstetric population. Obstet Gynecol. 1997;90(6):869–73.CrossRefPubMed
6.
go back to reference Bellamy L, et al. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009;373(9677):1773–9.CrossRefPubMed Bellamy L, et al. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009;373(9677):1773–9.CrossRefPubMed
7.
go back to reference Valizadeh M, et al. The risk factors and incidence of type 2 diabetes mellitus and metabolic syndrome in women with previous gestational diabetes. Int J Endocrinol Metab. 2015;13(2):e21696.CrossRefPubMedPubMedCentral Valizadeh M, et al. The risk factors and incidence of type 2 diabetes mellitus and metabolic syndrome in women with previous gestational diabetes. Int J Endocrinol Metab. 2015;13(2):e21696.CrossRefPubMedPubMedCentral
8.
go back to reference Buchanan TA. Pancreatic B-cell defects in gestational diabetes: implications for the pathogenesis and prevention of type 2 diabetes. J Clin Endocrinol Metab. 2001;86(3):989–93.CrossRefPubMed Buchanan TA. Pancreatic B-cell defects in gestational diabetes: implications for the pathogenesis and prevention of type 2 diabetes. J Clin Endocrinol Metab. 2001;86(3):989–93.CrossRefPubMed
9.
go back to reference Saisho Y, et al. Beta cell dysfunction and its clinical significance in gestational diabetes. Endocr J. 2010;57(11):973–80.CrossRefPubMed Saisho Y, et al. Beta cell dysfunction and its clinical significance in gestational diabetes. Endocr J. 2010;57(11):973–80.CrossRefPubMed
10.
go back to reference Catalano PM, et al. Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes. Am J Physiol. 1993;264(1 Pt 1):E60–7.PubMed Catalano PM, et al. Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes. Am J Physiol. 1993;264(1 Pt 1):E60–7.PubMed
11.
go back to reference Homko C, et al. Insulin secretion during and after pregnancy in patients with gestational diabetes mellitus. J Clin Endocrinol Metab. 2001;86(2):568–73.PubMed Homko C, et al. Insulin secretion during and after pregnancy in patients with gestational diabetes mellitus. J Clin Endocrinol Metab. 2001;86(2):568–73.PubMed
12.
go back to reference Kautzky-Willer A, et al. Pronounced insulin resistance and inadequate beta-cell secretion characterize lean gestational diabetes during and after pregnancy. Diabetes Care. 1997;20(11):1717–23.CrossRefPubMed Kautzky-Willer A, et al. Pronounced insulin resistance and inadequate beta-cell secretion characterize lean gestational diabetes during and after pregnancy. Diabetes Care. 1997;20(11):1717–23.CrossRefPubMed
13.
go back to reference Swinn RA, et al. Excessive secretion of insulin precursors characterizes and predicts gestational diabetes. Diabetes. 1995;44(8):911–5.CrossRefPubMed Swinn RA, et al. Excessive secretion of insulin precursors characterizes and predicts gestational diabetes. Diabetes. 1995;44(8):911–5.CrossRefPubMed
14.
go back to reference Akirav EM, et al. Detection of beta cell death in diabetes using differentially methylated circulating DNA. Proc Natl Acad Sci U S A. 2011;108(47):19018–23.CrossRefPubMedPubMedCentral Akirav EM, et al. Detection of beta cell death in diabetes using differentially methylated circulating DNA. Proc Natl Acad Sci U S A. 2011;108(47):19018–23.CrossRefPubMedPubMedCentral
15.
17.
go back to reference Nikolic D, et al. Incretins, pregnancy, and gestational diabetes. Curr Pharm Biotechnol. 2016;17(7):597–602.CrossRefPubMed Nikolic D, et al. Incretins, pregnancy, and gestational diabetes. Curr Pharm Biotechnol. 2016;17(7):597–602.CrossRefPubMed
18.
go back to reference Rizvi AA, et al. Gestational diabetes and the metabolic syndrome: can obesity and small, dense low density lipoproteins be key mediators of this association? Curr Pharm Biotechnol. 2014;15(1):38–46.CrossRefPubMed Rizvi AA, et al. Gestational diabetes and the metabolic syndrome: can obesity and small, dense low density lipoproteins be key mediators of this association? Curr Pharm Biotechnol. 2014;15(1):38–46.CrossRefPubMed
19.
go back to reference Lenzen S, Bailey CJ. Thyroid hormones, gonadal and adrenocortical steroids and the function of the islets of Langerhans. Endocr Rev. 1984;5(3):411–34.CrossRefPubMed Lenzen S, Bailey CJ. Thyroid hormones, gonadal and adrenocortical steroids and the function of the islets of Langerhans. Endocr Rev. 1984;5(3):411–34.CrossRefPubMed
20.
go back to reference Straub SG, et al. Progesterone inhibits insulin secretion by a membrane delimited, non-genomic action. Biosci Rep. 2001;21(5):653–66.CrossRefPubMed Straub SG, et al. Progesterone inhibits insulin secretion by a membrane delimited, non-genomic action. Biosci Rep. 2001;21(5):653–66.CrossRefPubMed
21.
go back to reference Nunes VA, et al. Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism. J Endocrinol. 2014;221(2):273–84.CrossRefPubMed Nunes VA, et al. Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism. J Endocrinol. 2014;221(2):273–84.CrossRefPubMed
22.
go back to reference Rebarber A, et al. Increased incidence of gestational diabetes in women receiving prophylactic 17alpha-hydroxyprogesterone caproate for prevention of recurrent preterm delivery. Diabetes Care. 2007;30(9):2277–80.CrossRefPubMed Rebarber A, et al. Increased incidence of gestational diabetes in women receiving prophylactic 17alpha-hydroxyprogesterone caproate for prevention of recurrent preterm delivery. Diabetes Care. 2007;30(9):2277–80.CrossRefPubMed
23.
go back to reference Xiang AH, et al. Multiple metabolic defects during late pregnancy in women at high risk for type 2 diabetes. Diabetes. 1999;48(4):848–54.CrossRefPubMed Xiang AH, et al. Multiple metabolic defects during late pregnancy in women at high risk for type 2 diabetes. Diabetes. 1999;48(4):848–54.CrossRefPubMed
24.
go back to reference Demirci C, et al. Loss of HGF/c-Met signaling in pancreatic beta-cells leads to incomplete maternal beta-cell adaptation and gestational diabetes mellitus. Diabetes. 2012;61(5):1143–52.CrossRefPubMedPubMedCentral Demirci C, et al. Loss of HGF/c-Met signaling in pancreatic beta-cells leads to incomplete maternal beta-cell adaptation and gestational diabetes mellitus. Diabetes. 2012;61(5):1143–52.CrossRefPubMedPubMedCentral
25.
go back to reference Saisho Y, et al. Beta-cell mass and turnover in humans: effects of obesity and aging. Diabetes Care. 2013;36(1):111–7.CrossRefPubMed Saisho Y, et al. Beta-cell mass and turnover in humans: effects of obesity and aging. Diabetes Care. 2013;36(1):111–7.CrossRefPubMed
26.
go back to reference Scaglia L, Smith FE, Bonner-Weir S. Apoptosis contributes to the involution of beta cell mass in the post partum rat pancreas. Endocrinology. 1995;136(12):5461–8.PubMed Scaglia L, Smith FE, Bonner-Weir S. Apoptosis contributes to the involution of beta cell mass in the post partum rat pancreas. Endocrinology. 1995;136(12):5461–8.PubMed
27.
go back to reference Saisho Y, et al. Marked decline in beta cell function during pregnancy leads to the development of glucose intolerance in Japanese women. Endocr J. 2013;60(4):533–9.PubMed Saisho Y, et al. Marked decline in beta cell function during pregnancy leads to the development of glucose intolerance in Japanese women. Endocr J. 2013;60(4):533–9.PubMed
Metadata
Title
β-Cell death is decreased in women with gestational diabetes mellitus
Authors
Lauren A. Kenna
John A. Olsen
Michael G. Spelios
Michael S. Radin
Eitan M. Akirav
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2016
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-016-0175-z

Other articles of this Issue 1/2016

Diabetology & Metabolic Syndrome 1/2016 Go to the issue