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TerminatedNCT04315545PROMISUpdated Mar 30, 2025

Pregnancy Outcomes and Maternal Insulin Sensitivity

An observational study in Gestational Diabetes, Other "Heavy-For-Dates" Infants and Small for Gestational Age Infant, sponsored by University Medical Center Groningen. Terminated at 2 sites in Netherlands. Open to female participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2025-03-30.

Sponsored by University Medical Center Groningen · Observational

Why this study was terminated
slow recruitment, reached sufficient recruitment numbers for exploratory analysis
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
30
Ages
18 Years to 45 Years
Sex
Female
01

Study 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.

Read the detailed 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.

02

Conditions studied

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

Keywords

  • Insulin sensitivity
  • Insulin insensitivity
  • Pregnancy
  • Metabolism
  • Neonatal outcomes
  • glucose metabolism
  • Oral glucose tolerance test
  • Meal tolerance test
  • neonatal health
  • maternal health
  • maternal insulin sensitivity
  • gestational weight gain
  • diagnostic tool
  • early screening
  • prevention
  • overweight
  • obesitiy
  • metabolic health
  • neonatal adiposity
  • maternal adiposity
03

In context

Diabetes, Gestational

842 studies on the registry are indexed under Diabetes, Gestational; 198 are open to participants now.

This study's enrollment of 30 is below the median of 200 across 269 observational studies indexed under Diabetes, Gestational.

Browse Diabetes, Gestational studies →

Lead sponsor

University Medical Center Groningen is the lead sponsor of 609 studies on the registry; 174 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
No
Sampling method
Probability sample

Study population

The study population will be pregnant women with a BMI ≥25 kg/m2 with a moderate to high 'at risk' of developing gestational diabetes throughout pregnancy

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

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
05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
30 participants (actual)
Target follow-up
10 Months
Patient registry
Yes
Biospecimen retention
Samples without dna

Groups and cohorts

  • Healthy women pregnant of singleton with a BMI ≥25 kg/m2

    Healthy women pregnant of singleton with a BMI ≥25 kg/m2 will be followed from 12 weeks of gestation till 6 months postpartum. Neonates will be followed from birth up to 6 months of age.

    Diagnostic Test: meal tolerance test

Interventions

  • Diagnostic testmeal 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.

06

What researchers measure

Primary outcomes

  1. fasting glucose

    Bloood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=0 min, before intake of test drink

  2. postprandial glucose

    Bloood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=10 min postprandial

  3. postprandial glucose

    Bloood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=20 min postprandial

  4. postprandial glucose

    Bloood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=30 min postprandial

  5. postprandial glucose

    Bloood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=45 min postprandial

  6. postprandial glucose

    Bloood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=60 min postprandial

  7. postprandial glucose

    Bloood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=90 min postprandial

  8. postprandial glucose

    Bloood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=120 min postprandial

  9. fasting and postprandial glucose

    Bloood will be collected fasted and after intake of the MTT and OGTT

    Time frame: AUC and postprandial curve

  10. fasting insulin

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=0 min, before intake of test drink

  11. postprandial insulin

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=10 min postprandial

  12. postprandial insulin

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=20 min postprandial

  13. postprandial insulin

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=30 min postprandial

  14. postprandial insulin

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=45 min postprandial

  15. postprandial insulin

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=60 min postprandial

  16. postprandial insulin

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=90 min postprandial

  17. postprandial insulin

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=120 min postprandial

  18. fasting and postprandial insulin

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: AUC and postprandial curve

Secondary outcomes

  1. Triglycerides

    Blood will be collected fasted

    Time frame: T=0 min, before intake of test drink

  2. Total cholesterol

    Blood will be collected fasted

    Time frame: T=0 min, before intake of test drink

  3. HDL-cholesterol

    Blood will be collected fasted

    Time frame: T=0 min, before intake of test drink

  4. Free fatty acids

    Blood will be collected fasted

    Time frame: T=0 min, before intake of test drink

  5. Hba1c

    Blood will be collected fasted

    Time frame: T=0 min, before intake of test drink

  6. Fasting stable glucose isotopes

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=0, before intake of test drink

  7. postprandial stable glucose isotopes

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=10 min postprandial

  8. postprandial stable glucose isotopes

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=20 min postprandial

  9. postprandial stable glucose isotopes

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=30 min postprandial

  10. postprandial stable glucose isotopes

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=45 min postprandial

  11. postprandial stable glucose isotopes

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=60 min postprandial

  12. postprandial stable glucose isotopes

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=90 min postprandial

  13. postprandial stable glucose isotopes

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: T=120 min postprandial

  14. fasting and postprandial stable glucose isotopes

    Blood will be collected fasted and after intake of the MTT and OGTT

    Time frame: AUC and postprandial curve

Other outcomes

  1. FFQ

    Food frequency questionnaire

    Time frame: between week 12-16 of gestation

  2. FFQ

    Food frequency questionnaire

    Time frame: between 24-28 of gestation

  3. FFQ

    Food frequency questionnaire

    Time frame: 1 month postpartum

  4. FFQ

    Food frequency questionnaire

    Time frame: 3 months postpartum

  5. AEBQ

    Adult eating behaviour questionnaire

    Time frame: between week 12-16 of gestation

  6. AEBQ

    Adult eating behaviour questionnaire

    Time frame: between 24-28 of gestation

  7. AEBQ

    Adult eating behaviour questionnaire

    Time frame: 1 month postpartum

  8. AEBQ

    Adult eating behaviour questionnaire

    Time frame: 3 months postpartum

  9. BEBQ

    Baby eating behaviour questionnaire

    Time frame: 1 month postpartum in child

  10. BEBQ

    Baby eating behaviour questionnaire

    Time frame: 3 months postpartum in child

  11. EQ

    EQ-5D questionnaire

    Time frame: Between week 12-16 of gestation

  12. EQ

    EQ-5D questionnaire

    Time frame: between week 24-28 of gestation

  13. EQ

    EQ-5D questionnaire

    Time frame: 1 month postpartum

  14. EQ

    EQ-5D questionnaire

    Time frame: 3 months postpartum

  15. PA

    Pregnancy physical activity questionnaire

    Time frame: between week 12-16 of gestation

  16. PA

    Pregnancy physical activity questionnaire

    Time frame: between week 24-28 of gestation

  17. PA

    International physical activity questionnaire

    Time frame: 1 month postpartum

  18. PA

    International physical activity questionnaire

    Time frame: 3 months postpartum

  19. MP

    Meal test preference questionnaire

    Time frame: In week 24 of gestation

  20. MP

    Meal test preference questionnaire

    Time frame: In week 25 of gestation

07

Study locations

2 sites
  • University Medical Centre Groningen
    Groningen, 9713 GZ, Netherlands
  • Medical Center Leeuwarden
    Leeuwarden, 8984 AD, Netherlands
08

References and documents

Publications

  • Koning SH, Hoogenberg K, Lutgers HL, van den Berg PP, Wolffenbuttel BH. Gestational Diabetes Mellitus:current knowledge and unmet needs. J Diabetes. 2016 Nov;8(6):770-781. doi: 10.1111/1753-0407.12422. Epub 2016 Jul 28. PubMed 27121958 ↗
  • Venkataraman H, Ram U, Craik S, Arungunasekaran A, Seshadri S, Saravanan P. Increased fetal adiposity prior to diagnosis of gestational diabetes in South Asians: more evidence for the 'thin-fat' baby. Diabetologia. 2017 Mar;60(3):399-405. doi: 10.1007/s00125-016-4166-2. Epub 2016 Dec 2. PubMed 27913848 ↗
  • World Health Organization. World health statistics 2016: Monitoring health for the SDGs sustainable development goals. World Health Organization; 2016.
  • Ko GT, Chan JC, Woo J, Lau E, Yeung VT, Chow CC, Cockram CS. The reproducibility and usefulness of the oral glucose tolerance test in screening for diabetes and other cardiovascular risk factors. Ann Clin Biochem. 1998 Jan;35 ( Pt 1):62-7. doi: 10.1177/000456329803500107. PubMed 9463740 ↗
  • Maegawa Y, Sugiyama T, Kusaka H, Mitao M, Toyoda N. Screening tests for gestational diabetes in Japan in the 1st and 2nd trimester of pregnancy. Diabetes Res Clin Pract. 2003 Oct;62(1):47-53. doi: 10.1016/s0168-8227(03)00146-3. PubMed 14581157 ↗
  • Seshiah V, Cynthia A, Balaji V, Balaji MS, Ashalata S, Sheela R, Thamizharasi M, Arthi T. Detection and care of women with gestational diabetes mellitus from early weeks of pregnancy results in birth weight of newborn babies appropriate for gestational age. Diabetes Res Clin Pract. 2008 May;80(2):199-202. doi: 10.1016/j.diabres.2007.12.008. Epub 2008 Feb 4. PubMed 18249458 ↗
  • HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May 8;358(19):1991-2002. doi: 10.1056/NEJMoa0707943. PubMed 18463375 ↗
  • NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet. 2017 Dec 16;390(10113):2627-2642. doi: 10.1016/S0140-6736(17)32129-3. Epub 2017 Oct 10. PubMed 29029897 ↗
  • Chen C, Xu X, Yan Y. Estimated global overweight and obesity burden in pregnant women based on panel data model. PLoS One. 2018 Aug 9;13(8):e0202183. doi: 10.1371/journal.pone.0202183. eCollection 2018. PubMed 30092099 ↗
  • Catalano PM, Ehrenberg HM. The short- and long-term implications of maternal obesity on the mother and her offspring. BJOG. 2006 Oct;113(10):1126-33. doi: 10.1111/j.1471-0528.2006.00989.x. Epub 2006 Jul 7. PubMed 16827826 ↗
  • Zhu Y, Zhang C. Prevalence of Gestational Diabetes and Risk of Progression to Type 2 Diabetes: a Global Perspective. Curr Diab Rep. 2016 Jan;16(1):7. doi: 10.1007/s11892-015-0699-x. PubMed 26742932 ↗
  • Koning SH, van Zanden JJ, Hoogenberg K, Lutgers HL, Klomp AW, Korteweg FJ, van Loon AJ, Wolffenbuttel BHR, van den Berg PP. New diagnostic criteria for gestational diabetes mellitus and their impact on the number of diagnoses and pregnancy outcomes. Diabetologia. 2018 Apr;61(4):800-809. doi: 10.1007/s00125-017-4506-x. Epub 2017 Nov 22. PubMed 29167927 ↗
  • Koning SH, Hoogenberg K, Scheuneman KA, Baas MG, Korteweg FJ, Sollie KM, Schering BJ, van Loon AJ, Wolffenbuttel BH, van den Berg PP, Lutgers HL. Neonatal and obstetric outcomes in diet- and insulin-treated women with gestational diabetes mellitus: a retrospective study. BMC Endocr Disord. 2016 Sep 29;16(1):52. doi: 10.1186/s12902-016-0136-4. PubMed 27680327 ↗
  • Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care. 2002 Oct;25(10):1862-8. doi: 10.2337/diacare.25.10.1862. PubMed 12351492 ↗
  • Feig DS, Zinman B, Wang X, Hux JE. Risk of development of diabetes mellitus after diagnosis of gestational diabetes. CMAJ. 2008 Jul 29;179(3):229-34. doi: 10.1503/cmaj.080012. Erratum In: CMAJ. 2008 Aug 12;179(4):344. PubMed 18663202 ↗
  • Yang X, Hsu-Hage B, Zhang H, Zhang C, Zhang Y, Zhang C. Women with impaired glucose tolerance during pregnancy have significantly poor pregnancy outcomes. Diabetes Care. 2002 Sep;25(9):1619-24. doi: 10.2337/diacare.25.9.1619. PubMed 12196437 ↗
  • Langer O, Umans JG, Miodovnik M. The proposed GDM diagnostic criteria: a difference, to be a difference, must make a difference. J Matern Fetal Neonatal Med. 2013 Jan;26(2):111-5. doi: 10.3109/14767058.2012.734874. Epub 2012 Oct 30. PubMed 23039192 ↗
  • Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK. Estimation of fetal weight with the use of head, body, and femur measurements--a prospective study. Am J Obstet Gynecol. 1985 Feb 1;151(3):333-7. doi: 10.1016/0002-9378(85)90298-4. PubMed 3881966 ↗
  • Ferrara A, Peng T, Kim C. Trends in postpartum diabetes screening and subsequent diabetes and impaired fasting glucose among women with histories of gestational diabetes mellitus: A report from the Translating Research Into Action for Diabetes (TRIAD) Study. Diabetes Care. 2009 Feb;32(2):269-74. doi: 10.2337/dc08-1184. Epub 2008 Nov 4. PubMed 18984776 ↗
  • Malcolm J, Lawson ML, Gaboury I, Keely E. Risk perception and unrecognized type 2 diabetes in women with previous gestational diabetes mellitus. Obstet Med. 2009 Sep;2(3):107-10. doi: 10.1258/om.2009.080063. Epub 2009 Sep 1. PubMed 27582823 ↗
  • Noctor E, Dunne FP. Type 2 diabetes after gestational diabetes: The influence of changing diagnostic criteria. World J Diabetes. 2015 Mar 15;6(2):234-44. doi: 10.4239/wjd.v6.i2.234. PubMed 25789105 ↗
  • Cobelli C, Man CD, Sparacino G, Magni L, De Nicolao G, Kovatchev BP. Diabetes: Models, Signals, and Control. IEEE Rev Biomed Eng. 2009 Jan 1;2:54-96. doi: 10.1109/RBME.2009.2036073. PubMed 20936056 ↗
  • Sonagra AD, Biradar SM, K D, Murthy D S J. Normal pregnancy- a state of insulin resistance. J Clin Diagn Res. 2014 Nov;8(11):CC01-3. doi: 10.7860/JCDR/2014/10068.5081. Epub 2014 Nov 20. PubMed 25584208 ↗
  • Catalano PM, Huston L, Amini SB, Kalhan SC. Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am J Obstet Gynecol. 1999 Apr;180(4):903-16. doi: 10.1016/s0002-9378(99)70662-9. PubMed 10203659 ↗
  • Lain KY, Catalano PM. Metabolic changes in pregnancy. Clin Obstet Gynecol. 2007 Dec;50(4):938-48. doi: 10.1097/GRF.0b013e31815a5494. PubMed 17982337 ↗
  • Catalano PM, Kirwan JP, Haugel-de Mouzon S, King J. Gestational diabetes and insulin resistance: role in short- and long-term implications for mother and fetus. J Nutr. 2003 May;133(5 Suppl 2):1674S-1683S. doi: 10.1093/jn/133.5.1674S. PubMed 12730484 ↗

Individual participant data

Plan to share: Yes — The study protocol will be submitted for publication in a peer reviewed journal

Supporting information: Study protocol

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 30, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04315545
Lead sponsor
University Medical Center Groningen
Responsible party
eline van der beek (Prof. dr. E.M. van der Beek, University Medical Center Groningen) — Principal investigator
First posted
Mar 19, 2020
Start date
Feb 6, 2020
Primary completion
Jul 8, 2024
Completion
Jul 8, 2024
Last update
Mar 30, 2025

Study contacts

Eline M van der Beek, Prof. Dr.
principal investigator · University Medical Center Groningen

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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