Pregnancy Outcomes and Maternal Insulin Sensitivity

Diabetes Mellitus, Type 2 Clinical Trial

— PROMIS  

Official title:

Pregnancy Outcomes and Maternal Insulin Sensitivity

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04315545
• Other study ID #: 68845
• Status: Recruiting
• Start date: February 6, 2020
• Est. completion date: December 2023

Study information

• Verified date: April 2023
• Source: University Medical Center Groningen
• Contact: Anoush Kdekian, MSc
• Phone: +31641743476
• Email: a.kdekian[@]umcg.nl
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The PROMIS study will focus on maternal insulin sensitivity thourghout pregnancy and postpartum in a moderate to high risk population (BMI ≥25 kg/m2) in developing adverse pregnancy outcomes. Next to the OGTT, the meal tolerance test (MTT) will be used as a tool for metabolic testing. The investigators hypothesize that (early) pregnancy assessment of maternal glucose-insulin metabolism with a MTT in a moderate to high risk group identify more mothers at risk for adverse pregnancy outcomes compared with standard OGTT testing at 24-28 weeks.

Description:

The worldwide prevalence of overweight and obesity is rapidly increasing, also affecting women of reproductive age. The prevalence of overweight women between 30-40 years in the Netherlands in 2017 was 39%. Women with a BMI ≥25 kg/m2 have excess adipose tissue which reduces insulin sensitivity and explains the correlated adverse outcomes for both mother and child. Insulin sensitivity changes over the course of pregnancy due to the effect of placental hormones and is therefore normally decreased by the end of the second trimester to ensure a continuous supply of nutrients towards the growing fetus. Insulin resistance leads to beta-cell proliferation and larger volume of individual beta-cells, returning to non-pregnant levels after parturition. When beta-cell proliferation is not or inadequately increased, this may lead to hyperglycemia. It is shown that small increases in maternal glucose levels have a linear relationship with adverse outcomes. Maternal adverse outcomes are pre-eclampsia, caesarian section and gestational diabetes mellitus (GDM) on the short term and increased risk of weight retention and non-communicable diseases like cardiovascular diseases and diabetes mellitus type 2 (DM2) on the longer term. Adverse outcomes in infants are macrosomia, large for gestational age (LGA), small for gestational age (SGA) on the short term and a higher risk on childhood obesity and non-communicable diseases on the longer term. Adequate maternal insulin sensitivity throughout pregnancy is therefore critical. Small maternal glucose increases could already be detected in an early stage of pregnancy. In the Netherlands hyperglycemia is standardly examined at the end of the second trimester in an at risk population by an oral glucose tolerance test (OGTT). This test is less suitable to detect mild hyperglycemia in early stages of pregnancy, with merely blood glucose levels as a result, and shows a lot of within subject variability. However markers of insulin sensitivity and related metabolic adaptations, for instance in lipid metabolism, may be a more straightforward measure that could potentially be detected earlier and allow for early intervention. An integration of postprandial responses of glucose/insulin following a meal challenge combined with lipid markers could provide clearer insights in maternal metabolic function. A test that could be used to examine this in more detail is a liquid meal tolerance test (MTT) which contains a balanced macro- and micronutrient composition. Assessing glucose homeostasis is not possible by only measuring glucose concentrations as there are numerous perturbations where glucose production and its utilization increases or decreases to the same extent without any changes in concentrations. For the understanding of the physiology and pathophysiology of glucose uptake and metabolism during pregnancy, glucose tracers should be followed. The PROMIS study will specifically focus on the associations between insulin sensitivity in the mother in early pregnancy and fetal and neonatal outcomes with emphasis on growth and body composition. The investigators therefore hypothesize that when overweight pregnant women are challenged in early pregnancy with a MTT, the group of women with disturbed insulin sensitivity could be identified much earlier, and can therefore have a predictive role in adverse outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2023
• Est. primary completion date: July 2023
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Healthy singleton pregnant women (10-12 weeks of gestation)
• BMI =25 kg/m2
• FPG =7.0 mmol/l
• Dutch or English speaking
• Written informed consent

Exclusion Criteria:

• Serious health complications (Hypertension, Hyperlipidemia, Asthma, Haemochromatosis) or medication use that influence the glucose metabolism or fetal growth (e.g. corticosteroids).
• Multiple pregnancy
• pre-existing Diabetes type 1 and 2 defined as FPG =7.0 mmol/l or use of diabetes medication
• Participation in any other studies involving the investigation of medication or nutritional products or severe illness or antibiotic use in the two weeks prior to entry into the study
• HIV/Hepatitis
• Expectation of non-compliance to the study protocol, among others, a fear of needles
• Known allergies or intolerances for one or more nutritional ingredients in the MTT
• Psychological dysfunctions

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetes, Gestational
• Gestational Diabetes
• Hypersensitivity
• Insulin Resistance
• Other Heavy-For-Dates Infants
• Small for Gestational Age Infant

Intervention

Diagnostic Test:
• meal tolerance test
In addition to the standard oral glucose tolerance (which is normally performed between 24-28 weeks of pregnancy), is used to test the metabolic resilience capacity of glucose, we will provide our participants with a different diagnostic tool named 'meal tolerance test' in an earlier stage of pregnancy (12-16 weeks), mid pregnancy (24-28 weeks) and 3 months postpartum.

Locations

Country	Name	City	State
Netherlands	University Medical Centre Groningen	Groningen
Netherlands	Medical Center Leeuwarden	Leeuwarden

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

References & Publications (26)

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	FFQ	Food frequency questionnaire	between week 12-16 of gestation
Other	FFQ	Food frequency questionnaire	between 24-28 of gestation
Other	FFQ	Food frequency questionnaire	1 month postpartum
Other	FFQ	Food frequency questionnaire	3 months postpartum
Other	AEBQ	Adult eating behaviour questionnaire	between week 12-16 of gestation
Other	AEBQ	Adult eating behaviour questionnaire	between 24-28 of gestation
Other	AEBQ	Adult eating behaviour questionnaire	1 month postpartum
Other	AEBQ	Adult eating behaviour questionnaire	3 months postpartum
Other	BEBQ	Baby eating behaviour questionnaire	1 month postpartum in child
Other	BEBQ	Baby eating behaviour questionnaire	3 months postpartum in child
Other	EQ	EQ-5D questionnaire	Between week 12-16 of gestation
Other	EQ	EQ-5D questionnaire	between week 24-28 of gestation
Other	EQ	EQ-5D questionnaire	1 month postpartum
Other	EQ	EQ-5D questionnaire	3 months postpartum
Other	PA	Pregnancy physical activity questionnaire	between week 12-16 of gestation
Other	PA	Pregnancy physical activity questionnaire	between week 24-28 of gestation
Other	PA	International physical activity questionnaire	1 month postpartum
Other	PA	International physical activity questionnaire	3 months postpartum
Other	MP	Meal test preference questionnaire	In week 24 of gestation
Other	MP	Meal test preference questionnaire	In week 25 of gestation
Primary	fasting glucose	Bloood will be collected fasted and after intake of the MTT and OGTT	T=0 min, before intake of test drink
Primary	postprandial glucose	Bloood will be collected fasted and after intake of the MTT and OGTT	T=10 min postprandial
Primary	postprandial glucose	Bloood will be collected fasted and after intake of the MTT and OGTT	T=20 min postprandial
Primary	postprandial glucose	Bloood will be collected fasted and after intake of the MTT and OGTT	T=30 min postprandial
Primary	postprandial glucose	Bloood will be collected fasted and after intake of the MTT and OGTT	T=45 min postprandial
Primary	postprandial glucose	Bloood will be collected fasted and after intake of the MTT and OGTT	T=60 min postprandial
Primary	postprandial glucose	Bloood will be collected fasted and after intake of the MTT and OGTT	T=90 min postprandial
Primary	postprandial glucose	Bloood will be collected fasted and after intake of the MTT and OGTT	T=120 min postprandial
Primary	fasting and postprandial glucose	Bloood will be collected fasted and after intake of the MTT and OGTT	AUC and postprandial curve
Primary	fasting insulin	Blood will be collected fasted and after intake of the MTT and OGTT	T=0 min, before intake of test drink
Primary	postprandial insulin	Blood will be collected fasted and after intake of the MTT and OGTT	T=10 min postprandial
Primary	postprandial insulin	Blood will be collected fasted and after intake of the MTT and OGTT	T=20 min postprandial
Primary	postprandial insulin	Blood will be collected fasted and after intake of the MTT and OGTT	T=30 min postprandial
Primary	postprandial insulin	Blood will be collected fasted and after intake of the MTT and OGTT	T=45 min postprandial
Primary	postprandial insulin	Blood will be collected fasted and after intake of the MTT and OGTT	T=60 min postprandial
Primary	postprandial insulin	Blood will be collected fasted and after intake of the MTT and OGTT	T=90 min postprandial
Primary	postprandial insulin	Blood will be collected fasted and after intake of the MTT and OGTT	T=120 min postprandial
Primary	fasting and postprandial insulin	Blood will be collected fasted and after intake of the MTT and OGTT	AUC and postprandial curve
Secondary	Triglycerides	Blood will be collected fasted	T=0 min, before intake of test drink
Secondary	Total cholesterol	Blood will be collected fasted	T=0 min, before intake of test drink
Secondary	HDL-cholesterol	Blood will be collected fasted	T=0 min, before intake of test drink
Secondary	Free fatty acids	Blood will be collected fasted	T=0 min, before intake of test drink
Secondary	Hba1c	Blood will be collected fasted	T=0 min, before intake of test drink
Secondary	Fasting stable glucose isotopes	Blood will be collected fasted and after intake of the MTT and OGTT	T=0, before intake of test drink
Secondary	postprandial stable glucose isotopes	Blood will be collected fasted and after intake of the MTT and OGTT	T=10 min postprandial
Secondary	postprandial stable glucose isotopes	Blood will be collected fasted and after intake of the MTT and OGTT	T=20 min postprandial
Secondary	postprandial stable glucose isotopes	Blood will be collected fasted and after intake of the MTT and OGTT	T=30 min postprandial
Secondary	postprandial stable glucose isotopes	Blood will be collected fasted and after intake of the MTT and OGTT	T=45 min postprandial
Secondary	postprandial stable glucose isotopes	Blood will be collected fasted and after intake of the MTT and OGTT	T=60 min postprandial
Secondary	postprandial stable glucose isotopes	Blood will be collected fasted and after intake of the MTT and OGTT	T=90 min postprandial
Secondary	postprandial stable glucose isotopes	Blood will be collected fasted and after intake of the MTT and OGTT	T=120 min postprandial
Secondary	fasting and postprandial stable glucose isotopes	Blood will be collected fasted and after intake of the MTT and OGTT	AUC and postprandial curve