Glucose Homeostasis, Metabolomics and Pregnancy Outcomes After Bariatric Surgery

Study Overview
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Brief Summary
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The aim of the GLORIA study is to determine whether an altered glucose metabolism (with more hypoglycaemia and glycaemic variability) and altered metabolomics during pregnancy after bariatric surgery contribute to the increased risk for adverse pregnancy outcomes such as small-for-gestational age infants. In addition, the investigators also aim to evaluate whether continuous glucose monitoring (CGM) can be used to diagnose gestational diabetes (GDM).

Detailed Description
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The GLORIA study is a Belgian multicenter prospective cohort study. The investigators aim to recruit 95 pregnant women after bariatric surgery (gastric bypass or sleeve gastrectomy) and as a control group, an age and BMI-matched cohort of 95 pregnant women without bariatric surgery. Participants will be recruited before 12 weeks of pregnancy. To evaluate glucose homeostasis, a masked CGM will be used for 10 days during each trimester in pregnancy and at the time of screening for GDM (at 24-28 weeks). The primary outcome is the mean glycaemia levels and glycaemic variability (SD) measured by CGM in pregnancy. At the different time points, anthropometric measurements (including body composition), food diary, questionnaires and micronutrients will be evaluated. In addition, in collaboration with the lab of Cristina Legido Quigle from the Steno Diabetes Center in Copenhagen, metabolomics will be analyzed. Women with a history of bariatric surgery will receive screening for GDM between 24-28 weeks of pregnancy by performing self- monitoring of blood glucose (SMBG) with a glucometer during one week. In addition to SMBG, women will receive a masked CGM during one week.

Official Title
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Glucose Homeostasis, Metabolomics and Pregnancy Outcomes After Bariatric Surgery

Conditions
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Bariatric Surgery Status Complicating Pregnancy

Intervention / Treatment
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* Diagnostic Test: CGM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-45 years and with a singleton pregnancy with ultrasound-confirmed gestational age up to 11 weeks and 6 days for the group with bariatric surgery: history of gastric bypass (RYBG) or sleeve gastrectomy (SG) Participants need to speak and understand Flemish, French or English and have e-mail access. Exclusion Criteria: multiple pregnancy pregnancy ≥12 weeks other types of bariatric surgery than RYBG or SG known pregestational diabetes a physical or psychological disease likely to interfere with the conduct of the study medications known to interfere with glucose metabolism.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| pregnant group with bariatric surgery<br>pregnant women with a history of gastric bypass or sleeve gastrectomy | Diagnostic Test: CGM<br>* blinded CGM used at 4 different time points in pregnancy<br>|
| matched pregnant group without history of bariatric surgery<br>age-and BMI matched pregnant women without history of bariatric surgery | Diagnostic Test: CGM<br>* blinded CGM used at 4 different time points in pregnancy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean glycaemia | mean glycaemia measured by CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| Standard deviation of glycaemia | SD measured by CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time <54mg/dl | time <54mg/dl measured by CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| glycaemic variability measured by coefficient of variation (CV) | CV measured by CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| glycaemic variability measured by mean amplitude of glucose excursions (MAGE) | MAGE measured by CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| time <70mg/dl | time <70mg/dl measured by CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| time <63mg/dl | time <63mg/dl measured by CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| time <50mg/dl | time <50mg/dl measured by CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| low blood glucose index (LBGI) | low blood glucose index (LBGI) based on CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| time > 120mg/dl | time >120mg/dl measured by CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| time > 140mg/dl | time >140mg/dl measured by CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| time > 180mg/dl | time >180mg/dl measured by CGM | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| prevalence of gestational diabetes | gestational diabetes based on capillairy monitoring or oral glucose tolerance test | 24-28 weeks of pregnancy | 
| gestational weight gain | total gestational weight gain in pregnancy | at end of pregnancy | 
| preterm delivery | delivery <37 weeks of pregnancy | delivery | 
| cesarean sections | planned and emergency cesarean sections combined | delivery | 
| large-for-gestational age infant | gestational age adjusted birth weight >90th percentile according to the standardized Flemish birth charts adjusted for parity and sex | delivery | 
| small-for-gestational infant | gestational age adjusted birth weight <10th percentile according to the standardized Flemish birth charts adjusted for parity and sex | delivery | 
| neonatal hypoglycaemia | neonatal hypoglycaemia requiring intravenous dextrose | delivery | 
| Neonatal intensive care admission (NICU) | NICU admission defined as requiring a duration of at least 24 h | delivery | 
| gestational hypertension | gestational hypertension ≥20 weeks of gestation: blood pressure ≥140/90mmHg | delivery | 
| pre-eclampsia | pre-eclampsia [≥20 weeks of gestation: new onset of hypertension and proteinuria or the new onset of hypertension and significant end-organ dysfunction with or without proteinuria (dipstick ≥ 2+, ≥0.3 g protein/24 hours or ≥30 mg/dL protein in spot urine or spot urine protein / creatinine ratio ≥30 mg protein/mmol creatinine) | delivery | 
| micronutrient deficiencies | vitamin A, vitamin D, B12, folate, prothrombin time and iron | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy and 30-34 weeks of pregnancy | 
| body fat percentage women | body fat measured by bioelectrical impedance analysis | between 6-12 weeks of pregnancy | 
| body fat percentage newborns | body fat calculated by measurements of skinfolds at triceps, flank and subscapular | within 3 days after birth | 
| fetal abdominal circumference (AC) | fetal abdominal circumference (AC) to evaluate fetal body composition | at 12, 20, 30 and 34 weeks of gestation | 
| fetal abdominal subcutaneous fat thickness (ASCF) | fetal abdominal subcutaneous fat thickness (ASCF) to evaluate fetal body composition | at 12, 20, 30 and 34 weeks of gestation | 
| placental function | the pulsatility index (PI) of the Doppler wave in the arteriae uterinae at 12 weeks and in the arteria umbilicalis at 20, 30 and 34 weeks of gestation. | at 12, 20, 30 and 34 weeks of gestation | 
| macronutrient intake baseline | food diary taken in early pregnancy | between 6-12 weeks of pregnancy | 
| macronutrient intake in pregnancy | frequency food questionnaire | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| physical activity | the Kaiser physical activity survey | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| symptoms of depression | the 20-item Center for Epidemiologic Studies-Depression (CES-D) questionnaire | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| symptoms of anxiety | six-item short-form the State-Trait Anxiety Inventory (STAI) questionnaire on anxiety | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy | 
| index of quality of life | 36-Item Short Form Health Survey (SF-36) questionnaire | between 6-12 weeks of pregnancy, 18-22 weeks of pregnancy, 24-28 weeks of pregnancy and 30-34 weeks of pregnancy |