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Project

The role of GLucose homeostasis and metabOlomics in pregnancy outcomes afteR barIAtric surgery: the GLORIA study.

Glucose homeostasis, metabolomics and pregnancy outcomes after bariatric surgery: the GLORIA study The prevalence of obesity and metabolic syndrome is increasing at an alarming rate worldwide. Obesity in women is associated with infertility and miscarriages. During pregnancy, obesity is associated with increased risk of gestational diabetes mellitus (GDM), preeclampsia, macrosomia and caesarean delivery. For women with a body mass index (BMI) ≥ 40 kg/m² or BMI ≥ 35 kg/m² with comorbidities, bariatric surgery is the most effective treatment for their obesity and comorbidities. Of all patients who undergo bariatric surgery, up to 80% are women of childbearing age. Bariatric surgery causes drastic functional changes in the gastro-intestinal tract. These operations can be divided into two main types: surgeries in which the continuity of the gastro-intestinal tract remains intact, versus bypass procedures. Worldwide, laparoscopic sleeve gastrectomy (SG) and Roux-en-y gastric bypass (RYGB) respectively are the most commonly performed bariatric surgeries. From national cohort studies, it is evident that bariatric surgery decreases the risk of obesity-related adverse pregnancy outcomes. However, there is increasing evidence that previous bariatric surgery can have potential harms for both mother and child during pregnancy. One of the most striking observations is that babies born from mothers with a history of bariatric surgery are at increased risk of being small for gestational age (SGA). The mechanisms behind this growth retardation are not well understood. Our hypothesis is that changing glucose homeostasis and metabolite-flux from mother to child play an important role. A second problem is making an accurate diagnosis of gestational diabetes mellitus (GDM) in this population. Screening for GDM with the standard oral glucose tolerance test (OGTT) is generally not well tolerated by these women and potentially harming because of reactive hypoglycemia with symptoms of dumping syndrome. Reactive hypoglycemia occurs in about half of SG and about four out of five of RYGB patients that undergo an OGTT. In addition, because of wide and rapid glycemic excursions, the interpretation of these OGTT’s is considered unreliable. A safer method is self-monitoring of blood glucose (SMBB). However, this is not a continuous monitoring and does not provide information on glycemic variability and nightly glucose values. Our hypothesis is that continuous glucose monitoring (CGM) will provide a more accurate diagnosis of GDM and give more insight into the glucose homeostasis in this population. The overall aim of this research project is to explore the metabolism of mother and child during a pregnancy after bariatric surgery. The research will therefore focus on the following objectives: To determine whether hypoglycemia and glycemic variability measured by CGM during different time points in pregnancy after bariatric surgery are independent risk factors for SGA and other adverse pregnancy outcomes. To compare the rate of hypoglycemia and glycemic variability between pregnant women after bariatric surgery with age –and BMI matched pregnant women without bariatric surgery. To determine which metabolites (by using metabolomics) mediate fetal growth in pregnant women after bariatric surgery compared to pregnant women without bariatric surgery. To determine whether there are differences in glucose homeostasis and other metabolites (by using metabolomics) between RYBG and SG. To determine the diagnostic accuracy of CGM compared to SMBG for the diagnosis of GDM. To determine the impact of bariatric surgery on body composition of newborns. For this research project, the goal is to include 90 women with a history of SG or RYGB. We will collaborate with six other Belgian hospitals, based on previous collaborations in the BEDIP-N (Belgian Diabetes in Pregnancy Study) and AURORA (bAriatric sUrgery Registration in wOmen of Reproductive Age) studies. We will compare this study group with a control population without history of bariatric surgery. For the metabolomics and data analyzes we will collaborate with the team of the Steno Diabetes Center in Copenhagen, Denmark. 1. Devlieger R, Benhalima K, Damm P, Van Assche A, Mathieu C, Mahmood T, et al. Maternal obesity in Europe: where do we stand and how to move forward?: A scientific paper commissioned by the European Board and College of Obstetrics and Gynaecology (EBCOG). European journal of obstetrics, gynecology, and reproductive biology. 2016 Jun;201:203-8. PubMed PMID: 27160501. 2. Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, et al. 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Effect of new criteria on the diagnosis of gestational diabetes in women submitted to gastric bypass. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2014 Nov-Dec;10(6):1041-6. PubMed PMID: 25066444. 15. Rottenstreich A, Elazary R, Ezra Y, Kleinstern G, Beglaibter N, Elchalal U. Hypoglycemia during oral glucose tolerance test among post-bariatric surgery pregnant patients: incidence and perinatal significance. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2018 Mar;14(3):347-53. PubMed PMID: 29306610. 16. Feichtinger M, Stopp T, Hofmann S, Springer S, Pils S, Kautzky-Willer A, et al. Altered glucose profiles and risk for hypoglycaemia during oral glucose tolerance testing in pregnancies after gastric bypass surgery. Diabetologia. 2017 Jan;60(1):153-7. PubMed PMID: 27757488. 17. Bonis C, Lorenzini F, Bertrand M, Parant O, Gourdy P, Vaurs C, et al. 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Date:8 Jun 2020 →  Today
Keywords:bariatric surgery, sleeve gastrectomy, gastric bypass, gestational diabetes mellitus, glucose homeostasis, metabolomics, small for gestational age, pregnancy outcome, continuous glucose monitoring
Disciplines:Metabolic diseases
Project type:PhD project