Ignite Creation Date:
2024-05-06 @ 4:14 PM
Last Modification Date:
2024-10-26 @ 2:06 PM
Study NCT ID:
NCT04924504
Status:
RECRUITING
Last Update Posted:
2022-11-23
First Post:
2021-06-07
Brief Title:
Mechanisms Behind Severe Insulin Resistance During Pregnancy in Women With Glucose Metabolic Disorders SIR-MET
Sponsor:
University of Aarhus
Organization:
University of Aarhus
Study Overview
Official Title:
Mechanisms Behind Severe Insulin Resistance During Pregnancy in Women With Glucose Metabolic Disorders SIR-MET
Status:
RECRUITING
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
This is a prospective observational study including app 24 pregnant women from the outpatient clinics at Department of Obstetrics and Gynecology at Aalborg and Aarhus University Hospital
The study includes 8 healthy women without pregestational or gestational diabetes 8 women with gestational diabetes or type 2 diabetes with a total daily insulin dose 75 unitsday and 8 women with gestational diabetes or type 2 diabetes with a total daily insulin dose 100 unitsday
There are three study days One in gestational week 28-36 day 1 one during labour day 2 and one 6 months postpartum day 3
Hormonal profiles and inflammatory markers will be measured at all three study days During labour both maternal and umbilical blood will be collected The blood sample analysis will include HbA1c glukose insulin C-peptid human anti-insulin antibody lipid profile liver enzymes creatinine FGF-21 TSH Cortisol human chorionic gonadotropin estradiol progesterone SHBG prolactin human placental lactogen placental growth hormone PAPP-A sFlt-1 PP13 IGF-1 IGF-BPs Leptin Adiponectin 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 Furthermore whole genome analysis will be applied to find genetic variants associated with overweight and diabetes genetic analysis will not be performed on umbilical cord blood Insulin sensitivity will be estimated using the homeostasis model assessment IS-HOMA based on fasting C-peptid and glucose concentrations
In addition to the blood samples the following examinations will be performed at day 1
Height weight and bioelectrical impedance analysis
Urine sample Albumin-to-creatinine ratio
Blood pressure and 24-hour ambulatory blood pressure monitoring
Central arterial pressure waveform analysis SphygmoCor
Echocardiography
Fetal ultrasound
MRI scan of the placenta and heart
In addition to the blood samples the following examinations will be performed at day 2
Placenta will be collected for a postpartum histopathological examination
Breast milk analyzed for lipid profile leptin adiponectin prolactin prolactin-binding protein oxytocin ghrelin insulin hs-CRP IL-6 IL-10 IL-1α IFN-ɣ TNF-α ICAM1 VCAM CD163 and untargeted metabolomics
Skinfold measurement of the newborn with a caliper
In addition to the blood samples the following examinations will be performed at day 3
Height weight and bioelectrical impedance analysis
Urine sample Albumin-to-creatinine ratio
Blood pressure and 24-hour ambulatory blood pressure monitoring
Central arterial pressure waveform analysis SphygmoCor
Echocardiography
Breast milk analyzed for lipid profile leptin adiponectin prolactin prolactin-binding protein oxytocin ghrelin insulin hs-CRP IL-6 IL-10 IL-1α IFN-ɣ TNF-α ICAM1 VCAM CD163 and untargeted metabolomics
The study includes 8 healthy women without pregestational or gestational diabetes 8 women with gestational diabetes or type 2 diabetes with a total daily insulin dose 75 unitsday and 8 women with gestational diabetes or type 2 diabetes with a total daily insulin dose 100 unitsday
There are three study days One in gestational week 28-36 day 1 one during labour day 2 and one 6 months postpartum day 3
Hormonal profiles and inflammatory markers will be measured at all three study days During labour both maternal and umbilical blood will be collected The blood sample analysis will include HbA1c glukose insulin C-peptid human anti-insulin antibody lipid profile liver enzymes creatinine FGF-21 TSH Cortisol human chorionic gonadotropin estradiol progesterone SHBG prolactin human placental lactogen placental growth hormone PAPP-A sFlt-1 PP13 IGF-1 IGF-BPs Leptin Adiponectin 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 Furthermore whole genome analysis will be applied to find genetic variants associated with overweight and diabetes genetic analysis will not be performed on umbilical cord blood Insulin sensitivity will be estimated using the homeostasis model assessment IS-HOMA based on fasting C-peptid and glucose concentrations
In addition to the blood samples the following examinations will be performed at day 1
Height weight and bioelectrical impedance analysis
Urine sample Albumin-to-creatinine ratio
Blood pressure and 24-hour ambulatory blood pressure monitoring
Central arterial pressure waveform analysis SphygmoCor
Echocardiography
Fetal ultrasound
MRI scan of the placenta and heart
In addition to the blood samples the following examinations will be performed at day 2
Placenta will be collected for a postpartum histopathological examination
Breast milk analyzed for lipid profile leptin adiponectin prolactin prolactin-binding protein oxytocin ghrelin insulin hs-CRP IL-6 IL-10 IL-1α IFN-ɣ TNF-α ICAM1 VCAM CD163 and untargeted metabolomics
Skinfold measurement of the newborn with a caliper
In addition to the blood samples the following examinations will be performed at day 3
Height weight and bioelectrical impedance analysis
Urine sample Albumin-to-creatinine ratio
Blood pressure and 24-hour ambulatory blood pressure monitoring
Central arterial pressure waveform analysis SphygmoCor
Echocardiography
Breast milk analyzed for lipid profile leptin adiponectin prolactin prolactin-binding protein oxytocin ghrelin insulin hs-CRP IL-6 IL-10 IL-1α IFN-ɣ TNF-α ICAM1 VCAM CD163 and untargeted metabolomics
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None