Imprinting in Metabolic Diseases - Identifying Epigenetic Mechanisms in Human Gestational Diabetes Through Cell-free DNA (Epi_GDM)

This clinical trials aims to investigate the impact of parental metabolism during pregnancy on fetal epigenetic signatures.

The metabolic profiles of both parents will be evaluated through a blood sample collected from the father and an oral glucose tolerance test administered to the pregnant mother. Additionally, epigenetic signatures will be assessed using parental blood samples. Fetal epigenetic signatures can be identified by analyzing fetal cell-free DNA that circulates in the mother's bloodstream.

Study Overview

• Status: Recruiting
• Conditions: Gestational Diabetes Mellitus (GDM)
• Intervention / Treatment: Other: Metabolic and epigenetic characterization of parents ans fetuses

Detailed Description

Epigenetic patterns inherited from both parents significantly influence gene expression and disease susceptibility in their offspring, with particularly negative effects in gestational diabetes, as indicated in animal and observational studies. However, human studies are limited due to the complexity and ethical concerns of collecting samples from fetuses and newborns. Invasive fetal sampling methods carry a risk of pregnancy loss, but the discovery of fetal cell-free DNA in maternal blood has revolutionized prenatal diagnostics by providing a non-invasive alternative. Recent advancements have made it possible to use cell-free DNA analyses also for epigenetic characterizations. The primary objective of this project is to elucidate the bidirectional epigenetic interactions between maternal gestational metabolism and the fetal epigenome, with a focus on identifying and understanding the biological impacts of epigenetic modifications in both the mother and fetus. Additionally, the research seeks to uncover epigenetic biomarkers that are linked to gestational diabetes and to assess the influence of parental epigenetic marks on the fetus. It will examine how parental epigenetics and parental glucose metabolism affects these modifications, facilitating a detailed analysis of the origins and mechanisms of epigenetic transmission.

We will recruit couples between gestational weeks 24 and 28, with and without gestational diabetes, and perform metabolic characterizations. Maternal cell-free DNA (including fetal DNA), maternal nuclear DNA, and paternal nuclear and cell-free DNA will be collected for methylation analyses.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Martin Heni, Prof, MD; Phone Number: +49 731 500 44505; Email: martin.heni@uniklinik-ulm.de
• Study Contact Backup: Name: Sabrina Wangler; Phone Number: +49 731 500 44782; Email: sabrina.wangler@uniklinik-ulm.de

Study Locations

• Germany
  • Baden-Wurttemberg
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Recruiting
      • Ulm University Hospital
      • Contact: Martin Heni, Prof.; Phone Number: +49 731 500 44505; Email: martin.heni@uniklinik-ulm.de
      • Contact: Sabrina Wangler; Phone Number: +49 731 500 44782; Email: sabrina.wangler@uniklinik-ulm.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the outpatient clinic of the department of obstetrics and gynaecology at Ulm University Hospital as well as from as well as through public advertisements posted at Ulm University.

Description

Inclusion Criteria:

• Pregnant women between 20 and 28 weeks of gestation
• The father of the child is known and willing to participate in the study
• No known underlying medical conditions in either parent
• No fetal abnormalities detected in first-trimester screening, detailed fetal anatomy ultrasound, non-invasive prenatal testing (NIPT), or any additional prenatal examinations performed, if applicable
• No known underlying diseases
• Understanding and voluntary signing of a consent form before study- related examinations

Exclusion Criteria:

• Age < 18 years
• Type 1 or type 2 diabetes mellitus
• Pharmacological treatment affecting blood glucose levels (e.g., steroids, insulin)
• Endocrine disorders (e.g., hyperthyroidism, polycystic ovary syndrome [PCOS])
• Current depression or other psychiatric disorders
• Eating disorders
• Regular use of medication during pregnancy
• Pre-existing cardiovascular disease
• Drug and/or alcohol abuse
• Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m²
• C-reactive protein > 10 mg/l
• Transaminase elevation of 2 times the upper norm
• No consent to be informed about incidentally discovered pathological findings
• Any other (clinical) condition that would endanger participants safety or question scientific success according to the physicians opinion.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Pregnant women + fathers of the unborn child; Metabolic and epigenetic characterization

Other: Metabolic and epigenetic characterization of parents ans fetuses; Pregnant women will undergo an oral glucose tolerance test to characterize metabolism and assess the presence of gestational diabetes. Moreover, they will undergo blood sampling to assess the mothers' epigenetic signatures and the fetal epigenetic signatures based on circulating fetal cell-free DNA. Fathers will undergo (if possible fasting) blood sample to characterize metabolism and epigenetic signatures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epigenetic profiles of parents and fetuses	Methylation pattern of CpG sites in fathers, mothers and fetuses assessed from blood samples from the father and the mother. Genome-wide DNA methylation will be quantified as 5-methylcytosine (5mC) levels at CpG sites in maternal and paternal nuclear DNA from peripheral blood. Long-read sequencing will be used to detect genomic sequences and base modifications. Fetal DNA methylation will be assessed from fetal cell-free DNA isolated from maternal plasma using long-read sequencing. Allelic phasing will be applied to assign epigenetic modifications to parental origin. Deconvolution analysis will be used to subtract blood cell-derived epigenetic patterns and infer tissue-of-origin signals.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epigenetic signatures of gestational diabetes	Differentially methylated regions will be computed across parental genomic DNA and fetal cell-free DNA between women with and without gestational diabetes. Differentially methylated regions will be bioinformatically annotated to candidate genes and pathogenic pathways.	Baseline
Correlation of epigenetic signatures and glycemia	Glucose level assessed from glucose measurements from fasting blood sample or oral glucose tolerance test.	Baseline
Correlation of epigenetic signatures and insulin sensitivity	Insulin sensitivity assessed by Homeostasis Model Assessment of insulin resistance based on glucose and insulin measurements from fasting blood sample or oral glucose tolerance test.	Baseline
Correlation of epigenetic signatures and insulin secretion	Insulin secretion assessed by Homeostasis Model Assessment of beta-cell function based on glucose and insulin measurements from fasting blood sample and oral glucose tolerance test.	Baseline
Correlation of epigenetic signatures and lipids	Lipid profiles assessed from lipid measurements from fasting blood sample.	Baseline

Collaborators and Investigators

• Sponsor: University of Ulm

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: February 13, 2026
• First Submitted That Met QC Criteria: February 20, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: pregnancy; gestational diabetes; Cell-free DNA; epigenetics; parental metabolism
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes, Gestational; Metabolism; Metabolic Networks and Pathways
• Other Study ID Numbers: 28/25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No