Diabetes and pregnancy
The nutritional and environmental conditions under which an individual develops from the one cell stage at conception to birth is now known to have major impact on the future health of the newborn child. Inadequate nutrition in the fetal period of life increases the risk of cardiovascular diseases, diabetes, overweight and certain cancers.
The association between the developmental condition of the fetus and future health of the newborn is conceptualized in the term DOHaD (Developmental Origins of Health and Disease or “The Barker hypothesis”). As pointed out in recent international surveys the most effective way of preventing major cardiovascular diseases, diabetes and some forms of cancer is to optimize the developmental environment of the fetus and of early childhood. A variety of factors may influence the condition under which a fetus develops, including maternal obesity and other malnutritional states, infections, preeclampsia with placental dysfunction and exposure to toxic compounds. Worldwide maternal obesity has now become a main risk factor for pregnancy complications and fetal development. In Norway around 20% of young women (mothers to be) are now obese (BMI >30 kg/m2), and obesity has surpassed smoking as a risk factor in pregnancy.
Some of our projects:
1. Healthy and unhealthy overweight in pregnancy
A longitudinal study of metabolic status and body mass index (BMI) in relation to pregnancy complications. The STORK cohort enables us to analyze subgroups of obese pregnant women with respect to the relation between metabolic profiles and pregnancy outcome. This project is highly relevant in terms of selecting obese women for special pregnancy follow up.
2. Genetic studies
The last few years we have also worked with genetic methods, recently genetic risk scores (GRS) were made, after genotyping 529 Norwegian pregnant women and constructing GRS from known genome-wide significant variants and associated with FG, 2hG, BMI and T2D. Shape information from glucose curves during an oral glucose tolerance test was also used. The genetic risk score for fasting glucose explained similar variance during pregnancy as in the non-pregnant population, whereas GRS for BMI and T2D variants explained up to 1.3% of the variation in the glucose traits. The results suggest overlap in the genetic aetiology of FG in pregnant and non-pregnant individuals, but this is less apparent with 2h glucose levels. This work has been done in close collaboration with the Stork Groruddalen study, with Professor K. Birkeland and postdoc C. Sommer and Lund University Diabetes Centre, Malmø with senior postdoc R. Prasad and Professor L. Groop. We hope to replicate these findings in the Norwegian Mother and Child study. Furthermore the genotyping has led to collaborations with an international GDM and birth weight consortium in Sweden.
3. “Gestational diabetes: Correct identification is necessary to improve future health of pregnant women and offspring” (Collaboration).
After the WHO decision to recommend new screening criteria for GDM, there is an acute need for more knowledge from studies with universal OGTT about GDM prevalence by different criteria in the Nordic countries, addressing the challenge of balancing adequate detection with the potential problem of over-diagnosis. This project is a response to needs identified during the revision of the clinical guideline, also to evaluate the performance of the new strategy to correctly diagnose GDM, with substantially lower thresholds for age and BMI than the traditional risk factor strategies, should be. There is also a need to study if easily available biological markers in early pregnancy can be used to predict later GDM, and eventually rule out women not in need for OGTT. This project is based on a new consortium based on four Norwegian pregnancy cohorts (STORK, STORK Groruddalen, Fit for delivery, The TRIP study (NTNU), enabling us to use individual participant data in this PhD project.
4. Post Stork – the 5 year follow up.
Maternal health post pregnancy has been the focus of Tove Lekvas postdoctoral work, among the topics are studies of adipokine levels relative to metabolic dysfunction and later cardiovascular disease. Leptin/adiponectin ratios were higher in GDM women both during pregnancy and follow-up compared to non-GDM women, and during pregnancy associated with cardiovascular risk. Furthermore circulating adipokines and monocyte/macrophage markers were dysregulated in GDM and at 5-year follow-up in GDM women, and these levels were independent of BMI and other GDM risk factors. Thus, activation of monocytes/macrophages may be an important event in the early development of GDM. Furthermore we have also identified that poor β-cell function in the second and/or third trimester is a predictor of pre-diabetes during long-term follow-up. Declining β-cell function already in the first trimester was associated with increased risk for pre-diabetes at 5-years postpartum.
5. Lipids in cardiovascular function in StorK offspring:
The atherosclerotic process is driven by increased cholesterol levels in combination with an enhanced inflammatory response. Hypercholesterolemia is primarily lifestyle induced or it may be caused by a genetic disposition such as familial hypercholesterolemia. Women with FH have been shown to experience very high levels of plasma lipids, in particular LDL cholesterol and they develop a prothrombotic and proinflammatory phenotype during pregnancy compared to non-hypercholesterolemic women. The significance of elevated cholesterol levels and prothrombotic “in utero” environment in relation to markers of risk in offspring has not been thoroughly investigated. Six to 13-year-old children were recruited, their mothers attended StorK, and had high or low cholesterol in pregnancy. CVD risk factors in the children were investigated, and demonstrated that women with elevated LDL-C during early pregnancy have offspring with higher LDL-C already at the age of 6-13 years. There was no difference in birthweight or any other clinical or biochemical CVD risk factors or dietary intake between the children at 6-13 years. This indicates that the affected children may be at increased cardiovascular risk.
6. Fertility in prediabetes
Most publications on assisted reproductive therapy (ART) focus on preconceptional metabolic health, or on the outcome (ie live births). The data collected in the STORK study makes comparisons of anthropometric and metabolic parameters possible in the participants, where approximately 70 women ART. We aim to investigate the influence of ART on metabolic features during pregnancy and on pregnancy outcomes, in comparison to women with GDM and healthy pregnant women in the STORK cohort, and furthermore investigate the influence of ART on maternal risk factors for cardiovascular disease between these three groups, using the 5 year follow up data from the STORK cohort.
The fetal liver is central in the energy use and metabolism of nutrients during fetal development. This project studies how blood flow in the umbilical vein (coming from placenta) is (re-)distributed between the liver and heart (ducus venosus) at different stages in the fetal development, and is led by Professor G. Haugen. Two group members collaborate with the “Dia Doppler” project at Haukeland University hospital, where shifts in fetal liver flow patterns are associated with maternal BMI and hyperglycemia in pregestational diabetes.
Tore Henriksen, Professor, MD, PhD
Guttorm Haugen, Professor, MD, PhD
Jens Bollerslev, Professor, MD, PhD
Svein Olav Kolset, Professor
Kirsten Holven, Professor, MD, PhD
Thor Ueland, Professor, MD, PhD
Elisabeth Qvigstad, MD, PhD
Kristin Godang, MSc
Tove Lekva, postdoc, MSc, Phd
Marie Cecilie Paasche Roland, postdoc, MD, PhD
Camilla M Friis, MD, Phd
Anne Helbig, MD, PhD
Anne Kaasen, PhD, midwife
Jacob Juel Christensen postdoc, Dept. Of Nutrition, UiO