Background: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy.
View Article and Find Full Text PDFThe fetal insulin hypothesis proposes that low birthweight and type 2 diabetes (T2D) in adulthood may be two phenotypes of the same genotype. In this study we aimed to explore this theory further by testing the effects of GWAS-identified genetic variants related to insulin release and sensitivity on fetal growth and blood flow from week 20 of gestation to birth and on placental weight at birth. We calculated genetic risk scores (GRS) of first phase insulin release (FPIR), fasting insulin (FI), combined insulin resistance and dyslipidaemia (IR + DLD) and insulin sensitivity (IS) in a study population of 665 genotyped newborns.
View Article and Find Full Text PDFAim: The aim of this study was to explore the perceptions of women with gestational diabetes mellitus (GDM) in Denmark, with a particular focus on GDM-specific stigma.
Method: We conducted semi-structured interviews with 20 women with GDM from January to May 2022. All interviews were transcribed and analysed abductively using Braun and Clarke's framework for applied reflexive analysis.
Biomedicines
May 2022
Maternal gestational diabetes and obesity are associated with adverse outcomes in offspring, including increased risk of diabetes and cardiovascular diseases. Previously, we identified a lower DNA methylation degree at genomic sites near the genes , , and in the blood cells of adolescent offspring exposed to gestational diabetes and/or maternal obesity in utero. In the present study, we aimed to investigate if altered methylation and expression of these genes were detectable in blood, as well in the metabolically relevant subcutaneous adipose tissue, in a separate cohort of adult offspring exposed to gestational diabetes and obesity (O-GDM) or type 1 diabetes (O-T1D) in utero, compared with the offspring of women from the background population (O-BP).
View Article and Find Full Text PDFBackground: In order to explore the pathophysiology underlying type 2 diabetes we examined the impact of gene variants associated with type 2 diabetes on circulating levels of glucagon during an oral glucose tolerance test (OGTT). Furthermore, we performed a genome-wide association study (GWAS) aiming to identify novel genomic loci affecting plasma glucagon levels.
Methods: Plasma levels of glucagon were examined in samples obtained at three time points during an OGTT; 0, 30 and 120 min, in two separate cohorts with a total of up to 1899 individuals.
This review summarises the knowledge of recurrent diploid biparental hydatidiform mole, which is a rare genetic condition. Pathogenic variants in both alleles of NLRP7 or KHDC3L are associated with maternal imprinting defects and can cause the condition. Women with biallelic inactivation of NLRP7 can achieve a normal pregnancy by oocyte donation, and it is highly likely, that this applies to women with biallelic inactivation of KHDCL3 as well.
View Article and Find Full Text PDFHarlequin ichthyosis (HI) is a rare and severe form of the autosomal recessive congenital ichthyosis. This is a case report of a 30-year-old healthy woman with a pregnancy resulting in preterm birth of a child with severe HI, who did not survive. At the autopsy, the child was found with HI and a diaphragmatic hernia of the Bochdalek type.
View Article and Find Full Text PDFOffspring of women with diabetes in pregnancy exhibit skeletal muscle insulin resistance and are at increased risk of developing type 2 diabetes, potentially mediated by epigenetic mechanisms or changes in the expression of small non-coding microRNAs. Members of the miR-15 family can alter the expression or function of important proteins in the insulin signalling pathway, affecting insulin sensitivity and secretion. We hypothesized that exposure to maternal diabetes may cause altered expression of these microRNAs in offspring skeletal muscle, representing a potential underlying mechanism by which exposure to maternal diabetes leads to increased risk of cardiometabolic disease in offspring.
View Article and Find Full Text PDFBackground: Fetal exposure to maternal diabetes increases the risk of type 2 diabetes (T2DM), possibly mediated by epigenetic mechanisms. Low blood TXNIP DNA methylation has been associated with elevated glucose levels and risk of T2DM, and increased skeletal muscle TXNIP gene expression was reported in subjects with impaired glucose metabolism or T2DM. Subcutaneous adipose tissue (SAT) and skeletal muscle play a key role in the control of whole body glucose metabolism and insulin action.
View Article and Find Full Text PDFBackground: Offspring of women with diabetes in pregnancy are at increased risk of type 2 diabetes mellitus (T2DM), potentially mediated by epigenetic mechanisms. The adipokines leptin, adiponectin, and resistin (genes: , , ) play key roles in the pathophysiology of T2DM. We hypothesized that offspring exposed to maternal diabetes exhibit alterations in epigenetic regulation of subcutaneous adipose tissue (SAT) adipokine transcription.
View Article and Find Full Text PDFContext: Offspring of women with gestational diabetes (O-GDM) or type 1 diabetes mellitus (O-T1DM) have been exposed to hyperglycemia in utero and have an increased risk of developing metabolic disease in adulthood.
Design: In total, we recruited 206 adult offspring comprising the two fetal hyperglycemic groups, O-GDM and O-T1DM, and, as a control group, offspring from the background population (O-BP). Subcutaneous fat biopsies were obtained and preadipocyte cell cultures were established from adult male O-GDM (n = 18, age 30.
Prenatal exposure to maternal hyperglycemia is associated with an increased risk of later adverse metabolic health. Changes in the regulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) in skeletal muscle and subcutaneous adipose tissue (SAT) is suggested to play a role in the developmental programming of dysmetabolism based on studies of human subjects exposed to an abnormal intrauterine environment (e.g.
View Article and Find Full Text PDFGestational diabetes mellitus (GDM) is defined as glucose intolerance of varying severity and is present in about 2-6% of all pregnancies in Europe, making it one of the most common pregnancy disorders. Aside from the short-term maternal, fetal and neonatal consequences associated with GDM, there are long-term consequences for both mother and child. Although maternal glucose tolerance often normalises shortly after pregnancy, women with GDM have a substantially increased risk of developing type 2 diabetes later in life.
View Article and Find Full Text PDFPlasma levels of the inflammatory marker YKL-40 were investigated in 597 adult offspring born to women with and without diabetes during pregnancy. No association between fetal exposure to maternal hyperglycemia and levels of YKL-40 was found. However, female sex and increasing BMI in the offspring were associated to YKL-40.
View Article and Find Full Text PDFContext: Fetal exposure to maternal diabetes is associated with increased risk of type 2 diabetes mellitus (T2DM) later in life. The pathogenesis of T2DM involves dysfunction of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), as well as hyperglucagonemia.
Objective: Our aim was to investigate circulating plasma levels of GLP-1, GIP, and glucagon during the oral glucose tolerance test (OGTT) in adult offspring of women with diabetes in pregnancy.
Context: Offspring of women with diabetes during pregnancy have an increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown.
Objective: We aimed to investigate the effects of intrauterine hyperglycemia on insulin secretion and action in adult offspring of mothers with diabetes.
Design, Setting, And Participants: A cohort of 587 Caucasian offspring, without known diabetes, was followed up at the age of 18-27 years.
Objective: Since January 2008, obese women with type 2 diabetes were advised to gain 0-5 kg during pregnancy. The aim with this study was to evaluate fetal growth and perinatal morbidity in relation to gestational weight gain in these women.
Research Design And Methods: A retrospective cohort comprised the records of 58 singleton pregnancies in obese women (BMI ≥30 kg/m(2)) with type 2 diabetes giving birth between 2008 and 2011.
Nat Rev Endocrinol
November 2012
Type 1 diabetes mellitus in pregnant women increases the risk of adverse outcomes for mother and offspring. Careful preconception counselling and screening is important, with particular focus on glycaemic control, indications for antihypertensive therapy, screening for diabetic nephropathy, diabetic retinopathy and thyroid dysfunction, as well as review of other medications. Supplementation with folic acid should be initiated before conception in order to minimize the risk of fetal malformations.
View Article and Find Full Text PDFDiabetes Res Clin Pract
August 2012
Aim: To investigate associations between fetal exposure to intrauterine hyperglycemia and plasma concentrations of interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) in adult offspring.
Method: We studied 597 offspring, aged 18-27 years, from four different groups concerning exposure to intrauterine hyperglycemia and genetic predisposition to type 2 diabetes (offspring of women with: gestational diabetes mellitus (GDM), risk factors for GDM but normal glucose tolerance, type 1 diabetes and women from the background population, respectively). The participants were characterized by fasting plasma levels of IL-6 and hs-CRP, a 75 g oral glucose tolerance test and anthropometric measurements.