HI-MET: Hormonal and Inflammatory Changes During Pregnancy in Women With Glucose Metabolic Disorders.

Sponsor

University of Aarhus (Other)

Overall Status

Recruiting

CT.gov ID

NCT04617405

Collaborator

Aarhus University Hospital (Other), Aalborg University Hospital (Other), Odense University Hospital (Other), The University of Queensland (Other)

300

Enrollment

Locations

21.7

Anticipated Duration (Months)

100

Patients Per Site

4.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The first aim of this study is to describe maternal hormonal and inflammatory changes during pregnancy in women that differ metabolically (limited to women with type 2 diabetes, gestational diabetes and/or overweight). The second aim of this study is to examine maternal hormonal, inflammatory and metabolic factors associated with insulin sensitivity in human pregnancy.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2 Gestational Diabetes Overweight and Obesity Pregnancy in Diabetic Insulin Resistance Insulin Sensitivity Pregnancy, High Risk	Other: No interventions

Detailed Description

This is a prospective observational study including app. 300 pregnant women from the outpatient clinics at Department of Obstetrics and Gynecology at Aalborg, Odense and Aarhus University Hospital.

The study includes 50 healthy normal-weight women, 150 healthy overweight women, 50 women with gestational diabetes and 50 women with type 2 diabetes.

Hormonal profiles and inflammatory markers will be measured at gestational week 8-10, 10-14, 18-22, 24-28 and 34-38. The blood samples will include HbA1c, glukose, insulin, C-peptid, lipid profile, liver enzymes, creatinine, FGF-21, TSH, Cortisol, human chorionic gonadotropin, estradiol, progesterone, prolactin, human placental lactogen, placental growth hormone, IGF-1, IGF-BP's, Leptin, Adiponectin, GLP-1, GIP, hs-CRP, IL-6, IL-10, IL-1α, IFN-ɣ, TNF-α, ICAM1, VCAM and CD163. In addition to this, exosomes will be isolated precisely and profiling of the content of exosomes will be performed using in vitro assays. Proteomics and miRNAs sequencing will be employed.

Height, weight, and blood pressure will be measured at every visit and a urine sample will be collected.

Insulin sensitivity will be estimated using the homeostasis model assessment, IS-HOMA, based on fasting insulin and glucose concentrations.

Study Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Hormonal and Inflammatory Changes During Pregnancy in Women With Glucose Metabolic Disorders.

Actual Study Start Date :

Jan 11, 2021

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Type A Healthy normal-weight pregnant women	Other: No interventions No interventions
Type B Pregnant women with gestational diabetes diagnosed at early screening (before gestational week 20)	Other: No interventions No interventions
Type C Pregnant women with type 2 diabetes	Other: No interventions No interventions
Type D Healthy overweight pregnant women	Other: No interventions No interventions

Outcome Measures

Primary Outcome Measures

Changes from baseline in serum or plasma concentration of metabolic, hormonal and inflammatory markers at four other times during pregnancy. [Gestational week 8-10 (baseline), gestational week 10-14, gestational week 18-22, gestational week 24-28 and gestational week 34-38]
Serum concentration of IGF-1, IGFBP-3, IGFBP-1, FGF-21, Leptin, Adiponectin, CD163, Human Chorionic Gonadotropin, Progesterone, C-peptide, Cortisol, Prolactin, Sex Hormone Binding Globulin, Estradiol, Free fatty acids, Human Placental Lactogen and Human Placental Growth Hormone. Plasma concentrations of IL-6, IL-10, IL-1alpha, IFN-gamma, TNF-alpha, ICAM1, VCAM, LDL, HDL, Triglyceride, Gamma-Glutamyl Transferase, Thyrotropin, glucose and HbA1c.
Assocation between the serum or plasma concentration of metabolic, hormonal and inflammatory markers Versus Insulin sensitivity at five times during pregnancy. [Gestational week 8-10, gestational week 10-14, gestational week 18-22, gestational week 24-28 and gestational week 34-38]
Association between the metabolic, hormonal and inflammatory markers listed as Primary Outcome 1 and the Insulin sensitivity. Insulin sensitivity will be estimated using the homeostasis model assessment (HOMA-IR) based on fasting insulin and glucose concentrations.
Changes from baseline in the level, content and bioactivity of exosomes in serum and plasma at four other times during pregnancy. [Gestational week 8-10 (baseline), gestational week 10-14, gestational week 18-22, gestational week 24-28 and gestational week 34-38]
Exosomes will be isolated and profiling of the content will be performed using SWATH mass spectrometry and miRNA sequencing.
Association between the level, content and bioactivity of exosomes in serum and plasma Versus Insulin sensitivity at five times during pregnancy. [Gestational week 8-10, gestational week 10-14, gestational week 18-22, gestational week 24-28 and gestational week 34-38]
Exosomes will be isolated and profiling of the content will be performed using SWATH mass spectrometry and miRNA sequencing. Insulin sensitivity will be estimated using the homeostasis model assessment (HOMA-IR) based on fasting insulin and glucose concentrations.

Secondary Outcome Measures

Changes from baseline in blood pressure (systolic and diastolic) at four other times during pregnancy. [Gestational week 8-10 (baseline), gestational week 10-14, gestational week 18-22, gestational week 24-28 and gestational week 34-38]
Blood pressure includes the measurement of both systolic and diastolic blood pressure (mmHg).
Changes from baseline in body weight at four other times during pregnancy. [Gestational week 8-10 (baseline), gestational week 10-14, gestational week 18-22, gestational week 24-28 and gestational week 34-38]
Body weight measured in kilograms.
Association between the blood pressure (systolic and diastolic) Versus Insulin sensitivity at five times during pregnancy. [Gestational week 8-10, gestational week 10-14, gestational week 18-22, gestational week 24-28 and gestational week 34-38]
Blood pressure includes the measurement of both systolic and diastolic blood pressure (mmHg). Insulin sensitivity will be estimated using the homeostasis model assessment (HOMA-IR) based on fasting insulin and glucose concentrations.
Association between the body weight Versus Insulin sensitivity at five times during pregnancy. [Gestational week 8-10, gestational week 10-14, gestational week 18-22, gestational week 24-28 and gestational week 34-38]
Body weight measured in kilograms. Insulin sensitivity will be estimated using the homeostasis model assessment (HOMA-IR) based on fasting insulin and glucose concentrations.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Inclusion Criteria:

Pregnant women at The Department of Gynaecology and Obstetrics at Aarhus University Hospital, Aalborg University Hospital or Odense University Hospital.
Women have to be in 1 of 4 categories: Healthy with a BMI < 25, healthy with a BMI >= 25, diagnosed with gestational diabetes before gestational week 20 or diagnosed with pregestational type 2 diabetes