Mechanisms Behind Severe Insulin Resistance During Pregnancy in Women With Glucose Metabolic Disorders (SIR-MET)

NCT04924504 | Unknown

• 1 other identifier: PADME
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of this study is to describe the metabolic changes during pregnancy in women with type 2 diabetes or gestational diabetes in order to detect the pathophysiological mechanisms behind severe insulin resistance during pregnancy as well as the short- and long term consequences for mother and child. Included pathophysiological mechanisms potentially associated with severe insulin resistance are: Maternal hormonal, inflammatory and metabolic markers in the blood, as well as the level, content and bioactivity of exosomes and genetic variants associated with overweight and diabetes. In addition to the analysis on maternal blood, the same analysis will be performed on umbilical cord blood in order to determine the correlation between markers associated with insulin sensitivity in maternal and umbilical blood. Furthermore, fetal metabolic changes influence on fetal growth and development will be evaluated. Postpartum, the breast milk will also be examined for metabolic active substances that could influence the newborns growth and metabolism. Investigating one potential short-term consequence of diabetes during pregnancy, the association between insulin resistance and structural and functional changes in the placenta will be examined as well as the consequences of such changes on fetal growth and development. Investigating one potential long-term consequence of diabetes during pregnancy, the association between treatment with high doses of insulin during pregnancy and the future risk of developing cardiovascular diseases and heart failure will be examined.

Conditions

Diabetes Mellitus, Type 2; Gestational Diabetes; Overweight and Obesity; Pregnancy in Diabetic; Insulin Resistance; Insulin Sensitivity; Pregnancy, High Risk

Outcome Measures

Primary Outcomes (1)

• Association between insulin sensitivity Versus structural and functional changes in the placenta

  Structural and functional changes in the placenta will be evaluated using a functional T2-weighted MRI scan. Specifically the function of placenta will be evaluated using a T2-value. Furthermore, structural and functional changes in the placenta will be evaluated through a postpartum histopathological examination of the placenta. Insulin sensitivity will be estimated using the homeostasis model assessment (HOMA-IR) based on fasting C-peptid and glucose concentrations.

  Gestational week 28-36

Secondary Outcomes (12)

• Association between structural and functional changes in the placenta Versus fetal growth and development

  Gestational week 28-36

• Changes from baseline in serum or plasma concentration of metabolic, hormonal and inflammatory markers

  Gestational week 28-36, at labour and 6 months postpartum

• Assocation between the serum or plasma concentration of metabolic, hormonal and inflammatory markers Versus Insulin sensitivity

  Gestational week 28-36, at labour and 6 months postpartum

• Assocation between the serum or plasma concentration of metabolic, hormonal and inflammatory markers in maternal blood Versus the serum or plasma concentrations of the same markers in umbilical cord blood

  At labour

• Changes from baseline in the level, content and bioactivity of exosomes in serum and plasma.

  Gestational week 28-36, at labour and 6 months postpartum

Study Arms (3)

Type A

Healthy pregnant women without pregestational or gestational diabetes

Other: No interventions

Type B

Pregnant women with type 2 diabetes or gestational diabetes with a total daily insulin dose \<= 75 units/day

Other: No interventions

Type C

Pregnant women with type 2 diabetes or gestational diabetes with a total daily insulin dose \>= 100 units/day

Other: No interventions

Interventions

No interventions OTHER

No interventions

Type A; Type B; Type C

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Only pregnant women are eligible for participation.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study population consist of pregnant women followed at The Department of Gynaecology and Obstetrics at Aarhus University Hospital or Aalborg University Hospital. Cases are diagnosed with gestational diabetes or pregestational type 2 diabetes and are treated with a total daily insulin dose \>= 100 units/day. Controls are either healthy without pregestational or gestational diabetes or diagnosed with gestational diabetes or pregestational type 2 diabetes and are treated with a total daily insulin dose \<= 75 units/day

You may qualify if:

• Pregnant women at The Department of Gynaecology and Obstetrics at Aarhus University Hospital or Aalborg University Hospital.
• Women have to be in 1 of 3 categories: Healthy without pregestational or gestational diabetes, type 2 diabetes treated with insulin or gestational diabetes treated with insulin.

You may not qualify if:

• Age \< 18 years
• Not able to read and understand danish
• Previous bariatric surgery
• Treatment with systemic corticosteroids
• Other severe chronic diseases such as inflammatory bowel disease, cystic fibrosis and type 1 diabetes

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator
• Aalborg University Hospital: collaborator
• The University of Queensland: collaborator

Study Sites (2)

Aarhus University Hospital

Aarhus, Aarhus N, 8200, Denmark

RECRUITING

Aalborg University Hospital

Aalborg, 9100, Denmark

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples (maternal and umbilical) Placenta

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes, Gestational; Overweight; Obesity; Pregnancy in Diabetics; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism

Study Officials

• Anna S Koefoed, MD

  Aarhus University, Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna S Koefoed, MD

CONTACT

+45 93 50 80 69; annask@clin.au.dk

Per G Ovesen, Prof., MD

CONTACT

perovese@rm.dk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2021
• First Posted: June 14, 2021
• Study Start: May 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: November 23, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)