Elisabeth Qvigstad

• Ueland, Thor; Michelsen, Annika Elisabet; Qvigstad, Elisabeth; Roland, Marie Cecilie; Westerberg, Ane Cecilie & Michelsen, Trond Melbye [Show all 9 contributors for this article] (2026). Secreted frizzled-related protein 3 is associated with metabolic disturbances in gestational diabetes. Frontiers in Endocrinology. 17. doi: 10.3389/fendo.2026.1905877. Full text in Research Archive
• Bonnichsen, Maja Lecic; Qvigstad, Elisabeth; Nyfløt, Lill Trine; Haugen, Guttorm Nils; Denault, William Robert Paul & Roland, Marie Cecilie (2026). Effects of gestational weight gain and HbA1C on fetal growth and birthweight in women with obesity. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. doi: 10.1111/aogs.70298. Full text in Research Archive
• Stalheim, Astrid; Qvigstad, Elisabeth; Anurathan, Jesini Selvarasa; Steintorsdottir, Sandra Dis; Lukasse, Mirjam & Wisting, Line [Show all 9 contributors for this article] (2026). Postnatal experiences and perspectives on future pregnancies among women with type 1 diabetes - a qualitative study. Sexual & Reproductive HealthCare. ISSN 1877-5756. 49, p. 1–7. doi: 10.1016/j.srhc.2026.101264. Full text in Research Archive Show summary

  Objective: Women with type 1 diabetes (T1D) tend to have fewer children and the postnatal period can be particularly challenging, as the rapid decline in pregnancy-induced insulin resistance often complicates diabetes management. The aim of this study was to explore postnatal experiences of women with T1D and their perspectives regarding future pregnancies. Methods: This qualitative study is part of the “Reproductive health in diabetes and prediabetes-study”. Individual interviews using a semi-structured interview guide were conducted with 17 women with T1D, with or without pregnancy experience, aged 18–45 years. For the present analysis, we included a sub-sample of eight women who had previously given birth. Data were analysed employing thematic analysis. Results: Three themes were identified, each with two corresponding sub-themes. 1) The women faced challenges in early postnatal diabetes management, dealing with unpredictable blood glucose and hypoglycaemia. 2) They expressed a sudden shift in the level of diabetes support after birth and that the health care providers at the maternity ward lacked diabetes competence. 3) Although they did not want diabetes to affect family planning, they acknowledged that T1D complicated their lives and influenced their pregnancy timing. Conclusion: Women with T1D experienced considerable challenges in postnatal diabetes management, primarily due to unpredictable blood glucose levels and insufficient postnatal follow-up. These findings highlight the importance of more systematic and individualized postnatal support. Moreover, the impact of diabetes on family planning underscores the need for comprehensive information and tailored guidance in reproductive health decision making.

• Anurathan, Jesini Selvarasa; Varsi, Cecilie; Stalheim, Astrid Melteig; Steintorsdottir, Sandra Dis; Wisting, Line & Berntorp, Kerstin [Show all 9 contributors for this article] (2026). Expectations and experiences regarding family planning, pregnancy, and motherhood in women with type 1 diabetes – A qualitative study. Women's Health. ISSN 1745-5057. 22, p. 1–11. doi: 10.1177/17455057261425791. Full text in Research Archive Show summary

  Background: Optimal treatment and support in family planning for women with type 1 diabetes (T1D) and follow-up during pregnancy are important, however, there is limited knowledge from the women’s perspective on their considerations of family planning, pregnancy, and motherhood. Objectives: To explore expectations and experiences of family planning, pregnancy, and motherhood among women with T1D. Design: We employed a qualitative study design with semi-structured interviews. Methods: We conducted semi-structured individual interviews (June to November 2022) with 17 women with T1D aged 18–45 at a diabetes outpatient clinic in Norway. We analyzed the data using thematic analysis. Results: Four main themes, each with sub-themes, linked to a timeline from planning the pregnancy to becoming a mother were identified: (1) Existential considerations in family planning; (2) Ambiguous information sources and the need for individualized guidance about pregnancy and T1D; (3) Preparations for pregnancy and balancing uncertainties during pregnancy; and (4) Motherhood intertwined with diabetes. Overall, the women expressed a need for support in handling and managing their glucose control in the phase of family planning, during pregnancy, and when preparing for the role of mother. Conclusion: Women with T1D reported many worries and concerns related to family planning, pregnancy, and motherhood, and thus, individualized information and support related to diabetes and reproductive health should be an integrated part of follow-up care. Women with T1D seem to have high expectations and strong commitment to their diabetes self-management during pregnancy, conditional on support and guidance from health care providers (HCPs). A sensitive approach from HCPs in clinical consultations is vital to meet the individual woman’s need for support. More research about reproductive health in women with T1D is needed, especially regarding how motherhood and diabetes intersect in everyday life.

• Hindenes, Lars Bakke; Ruiz, Paz Lopez-Doriga; Tapia, German; Bakken, Inger Johanne Landsjøåsen; Qvigstad, Elisabeth & Gulseth, Hanne Løvdal [Show all 7 contributors for this article] (2026). Type 2 diabetes in Norway 2009–2021: Have declining incidence rates continued? Diabetic Medicine. ISSN 0742-3071. 43(8). doi: 10.1111/dme.70225. Full text in Research Archive Show summary

  Aims To describe updated trends in the incidence and prevalence of diagnosed type 2 diabetes in Norway by age, sex, country of birth and education. Methods A nationwide cohort study using registries on primary and specialist healthcare, dispensed drugs and demographic factors in Norway. We analysed incidence trends 2009–2021 using Poisson regression and JoinPoint. Results During 2009–2021, 195,935 incident type 2 diabetes cases were identified. After a decline in incidence 2009–2014, the incidence was largely stable over time, with a suggestive upward trend 2019–2021. The overall incidence rates were 651 per 100,000 person-years in 2009 and 530 per 100,000 in 2021. There were 165,432 prevalent cases of type 2 diabetes in 2009 (5.5% of the population), consistently increasing throughout the study period to a peak at 259017 (7.6%) in 2021. The time trends were largely consistent across age, sex, country of birth and education. Inhabitants with lower education and born in Asia or Africa had substantially higher incidence and prevalence than those with higher education and born in Norway or other continents, respectively. Conclusions The previously described decline in incidence of diagnosed type 2 diabetes during 2009–2014 was not sustained, and prevalence continued to increase throughout 2009–2021.

• Suntharalingam, Anita; Sharma, Archana; Qvigstad, Elisabeth; Sattar, Naveed; Gill, Jason M. R. & Bjørnvall, Christina Dybdrodt [Show all 12 contributors for this article] (2025). Differences in tissue-specific insulin resistance between South Asian and Nordic women with prediabetes after gestational diabetes. Diabetologia. ISSN 0012-186X. 68(12), p. 2696–2708. doi: 10.1007/s00125-025-06546-9. Full text in Research Archive Show summary

  Aims/hypothesis The aim of this work was to investigate tissue-specific insulin resistance in South Asian and Nordic women with previous gestational diabetes mellitus (pGDM) and to evaluate potential ethnic differences contributing to type 2 diabetes risk. Methods A cross-sectional study using a two-step hyperinsulinaemic–euglycaemic clamp with a glucose tracer was conducted to assess insulin sensitivity in muscle, liver and adipose tissue in 19 South Asian and 16 Nordic women with pGDM and prediabetes (impaired glucose tolerance and/or impaired fasting glucose), along with 16 ethnicity-specific control women. We assessed inflammation and mitochondrial genes by mRNA sequencing of adipose tissue. Results Both South Asian and Nordic women with pGDM showed reduced total glucose disposal (mainly due to muscle insulin resistance) and hyperinsulinaemia compared with the control group. Endogenous glucose production (mainly due to hepatic insulin resistance) was elevated in Nordics with pGDM, while South Asians with pGDM showed pronounced adipose tissue insulin resistance (reduced suppression of glycerol during clamp). mRNA sequencing of adipose tissue indicated increased tissue inflammation in South Asian women compared with Nordic women with pGDM. Furthermore, we observed a differential response to hyperinsulinaemia in South Asians vs Nordics related to mitochondrial mRNA, such as thymidine kinase 2 (TK2). Correlations between adiposity markers and insulin sensitivity also differed by ethnicity, suggesting that the pathways leading to type 2 diabetes may vary across populations. Conclusions/interpretation South Asian and Nordic women with pGDM exhibited differences in insulin resistance profiles, with South Asians showing greater adipose tissue insulin resistance and inflammation.

• Bargas, Nicolas Fragoso; Mcbride, Nancy S.; Lee-Ødegård, Sindre; Lawlor, Deborah A.; Yousefi, Paul D. & Moen, Gunn-Helen [Show all 14 contributors for this article] (2025). Epigenome-wide association study of objectively measured physical activity in peripheral blood leukocytes. BMC Genomics. 26. doi: 10.1186/s12864-025-11262-0. Full text in Research Archive Show summary

  Background: Few studies have explored the association between DNA methylation and physical activity. The aim of this study was to evaluate the association of objectively measured hours of sedentary behavior (SB) and moderate physical activity (MPA) with DNA methylation. We further aimed to explore the association between SB or MPA related CpG sites and cardiometabolic traits, gene expression, and genetic variation. Results: For discovery, we performed cross sectional analyses in pregnant women from the Epigenetics in pregnancy (EPIPREG) sample with both DNA methylation (Illumina MethylationEPIC BeadChip) and objectively measured physical activity data (SenseWear™ Pro 3 armband) (European = 244, South Asian = 109). For EWAS of SB and MPA, two main models were designed: model (1) a linear mixed model adjusted for age, smoking, blood cell composition, including ancestry as random intercept, and model (2) which was additionally adjusted for the total number of steps per day. In model 1, we did not identify any CpG sites associated with neither SB nor MPA. In model 2, SB was positively associated (false discovery rate, FDR < 0.05) with two CpG sites within the VSX1 gene. Both CpG sites were positively associated with BMI and were associated with several genetic variants in cis. MPA was associated with 122 significant CpG sites at FDR < 0.05 (model 2). We further analyzed the ten most statistically significant MPA related CpG sites and found that they presented opposite associations with sedentary behavior and BMI. We were not able to replicate the SB and MPA-related CpG sites in the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC had available objectively measured physical activity data from Actigraph (without steps/day available) and leucocyte DNA methylation data collected during adolescence (n = 408, European). Conclusion: This study suggests associations of objectively measured SB and MPA with maternal DNA methylation in peripheral blood leukocytes, that needs to be confirmed in larger samples of similar study design.

• Lekva, Tove; Roland, Marie Cecilie; Qvigstad, Elisabeth; Khan, Yusuf; Godang, Kristin & Michelsen, Annika Elisabet [Show all 7 contributors for this article] (2025). Oxidative stress, senescence and mRNA decay in peripheral blood mononuclear cells of women with gestational diabetes mellitus-link to increased cardiovascular disease risk. Diabetes, obesity and metabolism. ISSN 1462-8902. 27(9), p. 4802–4811. doi: 10.1111/dom.16521. Full text in Research Archive Show summary

  Aims Women who develop gestational diabetes mellitus (GDM) have a pancreatic β-cell defect that cannot compensate for the insulin resistance of pregnancy. The glucose intolerance may, in addition to direct effects, negatively impact lipid metabolism, promote vascular dysfunction and contribute to cardiovascular disease (CVD). We assessed associations between oxidative stress and senescence markers with indices of glucose and lipid metabolism in women developing GDM and with CVD risk after 5 years. Materials and Methods The oxidative stress and senescence markers NRF2, GPX4, TERC, XRN1 and DCP2 were assessed in peripheral blood mononuclear cells (PBMCs), advanced oxidation protein products (AOPP) and β-galactosidase in plasma, from healthy (n = 253) and women with GDM (n = 31) during pregnancy and at 5-year follow-up, from the STORK study. We investigated their associations with established markers of disease activity and later CVD. Results Plasma AOPP and β-galactosidase were increased early in pregnancy in women developing GDM later and associated with indices of glucose metabolism and TG/HDL-Cholesterol. RNA levels of transcripts involved in telomer maintenance and antioxidant responses were decreased in women with GDM during pregnancy and at follow-up. DCP2 and XRN1 expression were positively associated with β-cell function at all timepoints and with pulse wave velocity at 5-year follow-up in women with previous GDM. Conclusions Markers of vascular oxidative stress and senescence are increased and correlate with indices of glucose and lipid metabolism early in pregnancy in women developing GDM. Cellular markers reflecting attenuated defence against oxidative stress and senescence decrease throughout pregnancy and at 5-year follow-up and correlate with aortic stiffness in women with previous GDM.

• Drabløs, Mari; Risstad, Hilde; Alnæs-Katjavivi, Patji & Qvigstad, Elisabeth (2024). Pregnancy outcomes in type 2 versus type 1 diabetes: systematic review with meta-analyses. Endocrine Connections. 13(12). doi: 10.1530/EC-24-0066. Full text in Research Archive
• Opsahl, Julia Onsrud; Bargas, Nicolas Fragoso; Lee, Y.; Carlsen, E. Ø.; Kiryushchenko, Nadezhda & Qvigstad, E. [Show all 13 contributors for this article] (2024). Epigenome-wide association study of DNA methylation in maternal blood leukocytes with BMI in pregnancy and gestational weight gain. International Journal of Obesity. ISSN 0307-0565. 48(4), p. 584–593. doi: 10.1038/s41366-024-01458-x. Full text in Research Archive Show summary

  Objectives We aimed to discover CpG sites with differential DNA methylation in peripheral blood leukocytes associated with body mass index (BMI) in pregnancy and gestational weight gain (GWG) in women of European and South Asian ancestry. Furthermore, we aimed to investigate how the identified sites were associated with methylation quantitative trait loci, gene ontology, and cardiometabolic parameters. Methods In the Epigenetics in pregnancy (EPIPREG) sample we quantified maternal DNA methylation in peripheral blood leukocytes in gestational week 28 with Illumina’s MethylationEPIC BeadChip. In women with European (n = 303) and South Asian (n = 164) ancestry, we performed an epigenome-wide association study of BMI in gestational week 28 and GWG between gestational weeks 15 and 28 using a meta-analysis approach. Replication was performed in the Norwegian Mother, Father, and Child Cohort Study, the Study of Assisted Reproductive Technologies (MoBa-START) (n = 877, mainly European/Norwegian). Results We identified one CpG site significantly associated with GWG (p 5.8 × 10−8) and five CpG sites associated with BMI at gestational week 28 (p from 4.0 × 10–8 to 2.1 × 10–10). Of these, we were able to replicate three in MoBa-START; cg02786370, cg19758958 and cg10472537. Two sites are located in genes previously associated with blood pressure and BMI. DNA methylation at the three replicated CpG sites were associated with levels of blood pressure, lipids and glucose in EPIPREG (p from 1.2 × 10−8 to 0.04). Conclusions We identified five CpG sites associated with BMI at gestational week 28, and one with GWG. Three of the sites were replicated in an independent cohort. Several genetic variants were associated with DNA methylation at cg02786379 and cg16733643 suggesting a genetic component influencing differential methylation. The identified CpG sites were associated with cardiometabolic traits.

• Ruiz, Paz Lopez-Doriga; Karlstad, Øystein; Nøkleby, Kjersti; Slåtsve, Kristina Barbara; Gulseth, Hanne Løvdal & Meyer, Haakon E. [Show all 9 contributors for this article] (2024). Pharmacological treatment of obesity in adults in Norway 2004–2022. Diabetes, obesity and metabolism. ISSN 1462-8902. 26(6), p. 2102–2110. doi: 10.1111/dom.15515. Full text in Research Archive Show summary

  Aims To describe trends in the use of anti-obesity drugs in Norway during the period 2004–2022. Materials and Methods We assessed the annual utilization of any available drug indicated for obesity recorded in the nationwide Norwegian Prescribed Drug Register for adults (age 18–79 years) from 1 January 2004 to 31 December 2022. Prevalence was stratified by sex and age group (18–29 years and 10-year age groups thereafter). Additional analyses were performed in individuals initiating treatment with an anti-obesity drug and on the cost of the anti-obesity drugs since 2017. Results The prevalence of anti-obesity drug use decreased from 2009, when sibutramine and rimonabant were withdrawn from the market, and increased again after the approval of bupropion-naltrexone in 2017 and liraglutide in 2018. The use of the peripheral-acting anti-obesity drug orlistat decreased from 2004. In 2022, 1.04% of the adult Norwegian population (72.8% women) filled at least one prescription of bupropion-naltrexone, 0.91% used liraglutide (Saxenda; 74.2% women), and semaglutide without reimbursement was used by 0.68% (76.7% women). The prevalence increased with age, peaking in the age group 50 to 59 years, and decreased in older age groups. From 2017 to 2022, 2.8% of the adult residents initiated treatment with an anti-obesity drug. The total sale of those drugs increased from 1.1 million euros in 2017 to 91.8 million euros in 2022. Conclusions The use of anti-obesity drugs in Norway has increased substantially in recent years, especially among women aged 40 to 59 years. Changes in availability and reimbursement have influenced the use of these drugs in recent years.

• Nunes, Caroline Brito; Borges, Maria Carolina; Freathy, Rachel M.; Lawlor, Deborah A.; Qvigstad, Elisabeth & Evans, David M. [Show all 7 contributors for this article] (2024). Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy. Metabolites. 14(9). doi: 10.3390/metabo14090508. Full text in Research Archive Show summary

  Background/Objectives: During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion to maintain glucose homeostasis. For some women, this change is insufficient to maintain normoglycemia, leading to gestational diabetes mellitus (GDM), a condition characterized by maternal glucose intolerance and hyperglycaemia first diagnosed during the second or third trimester of pregnancy. GDM is diagnosed in approximately 14.0% of pregnancies globally, and it is often associated with short- and long-term adverse health outcomes in both mothers and offspring. Although recent studies have highlighted the role of genetic determinants in the development of GDM, research in this area is still lacking, hindering the development of prevention and treatment strategies. Methods: In this paper, we review recent advances in the understanding of genetic determinants of GDM and glycaemic traits during pregnancy. Results/Conclusions: Our review highlights the need for further collaborative efforts as well as larger and more diverse genotyped pregnancy cohorts to deepen our understanding of the genetic aetiology of GDM, address research gaps, and further improve diagnostic and treatment strategies.

• Sharma, Archana; Birkeland, Kåre Inge; Nermoen, Ingrid; Sommer, Christine; Qvigstad, Elisabeth & Lee-Ødegård, Sindre [Show all 11 contributors for this article] (2024). N-terminal pro-B-type natriuretic peptide levels vary by ethnicity and are associated with insulin sensitivity after gestational diabetes mellitus. Cardiovascular Diabetology. 23(1). doi: 10.1186/s12933-024-02349-1. Full text in Research Archive Show summary

  Background Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers? Methods We examined 162 South Asian and 107 Nordic women in Norway 1–3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP. Results The mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m2, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26  (15–38)  vs. 42 (22–66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1–4.4) vs. 1.2 (0.3–4.2) mg/L), IL-6 (2.3 (1.5–3.2) vs. 1.5 (1.5–2.5) pg/mL), leptin (1647 (1176–2480) vs. 1223 (876–2313) pmol/L), and lower adiponectin levels (7.2 (5.3–9.3) vs. 10.0 (7.2–13.5) mg/L) and Matsuda ISI (2.4 (1.7–3.7) vs. 4.2 (2.9–6.1), pall<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP. Conclusions NT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.

• Linares-Pineda, Teresa M.; Bargas, Nicolas Fragoso; Picón, María José; Molina-Vega, Maria; Jenum, Anne Karen & Sletner, Line [Show all 14 contributors for this article] (2024). DNA methylation risk score for type 2 diabetes is associated with gestational diabetes. Cardiovascular Diabetology. 23(1). doi: 10.1186/s12933-024-02151-z. Full text in Research Archive Show summary

  Background Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) share many pathophysiological factors including genetics, but whether epigenetic marks are shared is unknown. We aimed to test whether a DNA methylation risk score (MRS) for T2DM was associated with GDM across ancestry and GDM criteria. Methods In two independent pregnancy cohorts, EPIPREG (n = 480) and EPIDG (n = 32), DNA methylation in peripheral blood leukocytes was measured at a gestational age of 28 ± 2. We constructed an MRS in EPIPREG and EPIDG based on CpG hits from a published epigenome-wide association study (EWAS) of T2DM. Results With mixed models logistic regression of EPIPREG and EPIDG, MRS for T2DM was associated with GDM: odd ratio (OR)[95% CI]: 1.3 [1.1–1.8], P = 0.002 for the unadjusted model, and 1.4 [1.1–1.7], P = 0.00014 for a model adjusted by age, pre-pregnant BMI, family history of diabetes and smoking status. Also, we found 6 CpGs through a meta-analysis (cg14020176, cg22650271, cg14870271, cg27243685, cg06378491, cg25130381) associated with GDM, and some of their methylation quantitative loci (mQTLs) were related to T2DM and GDM. Conclusion For the first time, we show that DNA methylation marks for T2DM are also associated with GDM, suggesting shared epigenetic mechanisms between GDM and T2DM.

• Kvist, Ahalya Anita Suntharalingam; Sharma, Archana; Sommer, Christine; Qvigstad, Elisabeth; Gulseth, Hanne Løvdal & Sollid, Stina Therese [Show all 12 contributors for this article] (2024). Adipose Tissue Insulin Resistance in South Asian and Nordic Women after Gestational Diabetes Mellitus. Metabolites. 14(5). doi: 10.3390/metabo14050288. Full text in Research Archive Show summary

  South Asians (SAs) have a higher risk of developing type 2 diabetes (T2D) than white Europeans, especially following gestational diabetes mellitus (GDM). Despite similar blood glucose levels post-GDM, SAs exhibit more insulin resistance (IR) than Nordics, though the underlying mechanisms are unclear. This study aimed to assess markers of adipose tissue (AT) IR and liver fat in SA and Nordic women post-GDM. A total of 179 SA and 108 Nordic women in Norway underwent oral glucose tolerance tests 1–3 years post-GDM. We measured metabolic markers and calculated the AT IR index and non-alcoholic fatty liver disease liver fat (NAFLD-LFS) scores. Results showed that normoglycaemic SAs had less non-esterified fatty acid (NEFA) suppression during the test, resembling prediabetes/T2D responses, and higher levels of plasma fetuin-A, CRP, and IL-6 but lower adiponectin, indicating AT inflammation. Furthermore, normoglycaemic SAs had higher NAFLD-LFS scores, lower insulin clearance, and higher peripheral insulin than Nordics, indicating increased AT IR, inflammation, and liver fat in SAs. Higher liver fat markers significantly contributed to the ethnic disparities in glucose metabolism, suggesting a key area for intervention to reduce T2D risk post-GDM in SAs.

• Rai, Anam Shakil; Sletner, Line; Jenum, Anne Karen; Øverby, Nina Cecilie; Stafne, Signe Nilssen & Qvigstad, Elisabeth [Show all 8 contributors for this article] (2023). Employing fasting plasma glucose to safely limit the use of oral glucose tolerance tests in pregnancy: a pooled analysis of four Norwegian studies. Frontiers in Endocrinology. 14. doi: 10.3389/fendo.2023.1278523. Full text in Research Archive Show summary

  Background/objective: There is no international consensus about the optimal approach to screening and diagnosis of gestational diabetes mellitus (GDM). Fasting plasma glucose (FPG) has been proposed as an alternative universal screening test to simplify the diagnosis of GDM. We investigate the ability of the FPG to predict a 2-hour glucose value below the cut-off for GDM, thereby “ruling out” the necessity of a full OGTT and assess the proportion of GDM-related complications associated with the identified FPG level. Materials and methods: This study included secondary data from four Norwegian pregnancy cohorts (2002-2013), encompassing 2960 women universally screened with late mid-pregnancy 75g OGTT measuring FPG and 2-hour glucose. For a range of FPG thresholds, we calculated sensitivity to predict elevated 2-hour glucose, number of OGTTs needed and percentage of GDM cases missed, applying modified World Health Organization (WHO) 2013 criteria (2013WHO) and 2017 Norwegian criteria (2017Norwegian). We analyzed pregnancy outcomes for women above and below our selected threshold. Results: The prevalence of GDM was 16.6% (2013WHO) and 10.1% (2017Norwegian). A FPG threshold of 4.7 mmol/L had a sensitivity of 76% (2013WHO) and 80% (2017Norwegian) for detecting elevated 2-hour glucose, with few missed GDM cases (2.0% of those ruled out and 7.5% of all GDM cases for 2013WHO, and 1.1% of those ruled out and 7% of all GDM cases for 2017Norwegian). When excluding women with FPG <4.7mmol/l and those with GDM based on FPG, only 24% (2013WHO) and 29% (2017Norwegian) would require OGTT. Women with FPG <4.7mmol/l, including missed GDM cases, had low risk of large-for-gestational-age newborns, cesarean section and operative vaginal delivery. Conclusion: A FPG threshold of 4.7mmol/l as a first step when screening for GDM could potentially eliminate the need for OGTT in 70-77% of pregnancies. Women with FPG below this threshold appear to carry low risk of GDM-associated adverse pregnancy outcomes.

• Fragoso-Bargas, Nicolas; Page, Christian Magnus; Joubert, Bonnie R.; London, Stephanie J.; Lee-Ødegård, Sindre & Opsahl, Julia Onsrud [Show all 13 contributors for this article] (2023). Epigenome-wide association study of serum folate in maternal peripheral blood leukocytes. Epigenomics. ISSN 1750-1911. 15(1), p. 39–52. doi: 10.2217/epi-2022-0427. Full text in Research Archive Show summary

  Aim: To perform an epigenome-wide association study (EWAS) of serum folate in maternal blood. Methods: Cross-ancestry (Europeans = 302, South Asians = 161) and ancestry-specific EWAS in the EPIPREG cohort were performed, followed by methyl quantitative trait loci analysis and association with cardiometabolic phenotypes. Replication was attempted using maternal folate intake and blood methylation data from the MoBa study and verified if the findings were significant in a previous EWAS of maternal serum folate in cord blood. Results & conclusion: cg19888088 (cross-ancestry) in EBF3, cg01952260 (Europeans) and cg07077240 (South Asians) in HERC3 were associated with serum folate. cg19888088 and cg01952260 were associated with diastolic blood pressure. cg07077240 was associated with variants in CASC15. The findings were not replicated and were not significant in cord blood.

• Stalheim, Astrid Melteig; Iversen, Marjolein M.; Jenum, Anne Karen; Sletner, Line; Stafne, Signe Nilssen & Qvigstad, Elisabeth [Show all 10 contributors for this article] (2023). Seasonal variation in gestational diabetes mellitus among women in Norway: a national population-based study. BMJ Open. 13(3), p. 1–8. doi: 10.1136/bmjopen-2022-063725. Full text in Research Archive Show summary

  Objectives Previous research on seasonal variation in the incidence of gestational diabetes mellitus (GDM) has shown inconclusive results. Furthermore, little is known about whether a seasonal variation in GDM might be associated with the maternal country of birth. We examined whether there was seasonal variation in GDM incidence by the maternal country background. Design National population-based registry study. Setting and participants We used national population-based data from the Medical Birth Registry of Norway (MBRN), n=1 443 857 (1990–2016) and data from four merged community-based studies (4GDM) with universal screening for GDM, n=2 978 (2002–2013). Outcome measures The association between season of pregnancy onset with incidence of GDM was examined separately in both datasets using logistic regression analyses, stratified by the mother’s country background using two broad geographical categories (MBRN: Norwegian and immigrant; 4GDM: European and African/Asian ethnicity). Winter season was used as reference category. Results The incidence of GDM in MBRN was highest when the pregnancy started during the winter (Norwegian-born: 1.21%; immigrants: 3.32%) and lowest when pregnancy started during the summer for both Norwegian and immigrant women (Norwegian-born: 1.03% (OR 0.85, 95% CI 0.81 to 0.98); immigrants: 2.99% (OR 0.90, 95% CI 0.84 to 0.96)). The 4GDM data showed that women with European ancestry had the highest incidence of GDM when pregnancy started during autumn (10.7%, OR 1.01, 95% CI 0.69 to 1.46) and winter (10.6%), while ethnic African and Asian women had the highest incidence when pregnancy onset was during the summer (15.3%, OR 1.17, 95% CI 0.54 to 2.53). Conclusions Based on national population-based data, this study suggests that GDM incidence varies by season in both Norwegian-born and immigrant women. The 4GDM dataset did not show a clear seasonal variation in GDM incidence, possibly due to the relatively small sample. Causes for the seasonal variation in GDM should be explored further.

• Rai, Anam Shakil; Sletner, Line; Jenum, Anne Karen; Øverby, Nina Cecilie; Stafne, Signe Nilssen & Qvigstad, Elisabeth [Show all 8 contributors for this article] (2023). Adverse pregnancy outcomes among women in Norway with gestational diabetes using three diagnostic criteria. PLOS ONE. 18(7). doi: 10.1371/journal.pone.0280750. Full text in Research Archive Show summary

  Introduction The aim of this study was to examine the risk of adverse perinatal outcomes in women diagnosed with GDM by the World Health Organization (WHO) 1999 criteria, and in those retrospectively identified by the Norwegian-2017 and WHO-2013 criteria but not by WHO-1999 criteria. We also examine the effect of maternal overweight/obesity and ethnicity. Material and methods We used pooled data from four Norwegian cohorts (2002–2013), encompassing 2970 mother-child pairs. Results from universally offered 75-g oral glucose tolerance tests measuring fasting plasma glucose (FPG) and 2-hour glucose (2HG) were used to assign women into three diagnostic groups: Diagnosed and treated by WHO-1999 (FPG≥7.0 or (2HG ≥7.8 mmol/L), identified by WHO-2013 (FPG ≥5.1 or 2HG ≥8.5 mmol/L), and identified by Norwegian-2017 criteria (FPG ≥5.3 or 2HG ≥9.0 mmol/L). Perinatal outcomes included large-for-gestational-age (LGA) infants, cesarean section, operative vaginal delivery, preterm birth and preeclampsia. Results Compared to the non-GDM group, women diagnosed with GDM by either of the three criteria had an increased risk of large-for-gestational-age infants (adjusted odds ratios (OR) 1.7–2.2). Those identified by the WHO-2013 and Norwegian-2017 criteria but not diagnosed and treated by WHO-1999 criteria had an additional increased risk of cesarean section (OR 1.36, 95% CI 1.02,1.83 and 1.44, 95% CI 1.03,2.02, respectively) and operative vaginal delivery (OR 1.35, 95% CI 1.1,1.7 and 1.5, 95% CI 1.1,2.0, respectively). The proportions of LGA neonates and cesarean section were higher for women with GDM in both normal-weight and overweight/obese women. Asians had a lower risk of delivering large-for-gestational-age infants than Europeans applying national birthweight references, but maternal glucose values were similarly positively associated with birthweight in all ethnic groups. Conclusions Women who met the WHO-2013 and Norwegian-2017 criteria, but were not diagnosed by the WHO-1999 criteria and therefore not treated, had an increased risk of LGA, cesarean section and operative vaginal delivery compared to women without GDM.

• Solé-Navais, Pol; Flatley, Christopher; Steinthorsdottir, Valgerdur; Vaudel, Marc; Juodakis, Julius & Chen, Jing [Show all 85 contributors for this article] (2023). Genetic effects on the timing of parturition and links to fetal birth weight. Nature Genetics. ISSN 1061-4036. 55, p. 559–567. doi: 10.1038/s41588-023-01343-9. Full text in Research Archive Show summary

  The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed seven associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal–fetal relationship between gestational duration and birth weight.

• Tronstad, Christian; Amini, Maryam; Olesen, Eline; Qvigstad, Elisabeth; Pabst, Oliver & Martinsen, Tormod [Show all 11 contributors for this article] (2022). Diabetic foot assessment using skin impedance in a custom made sensor-sock. Journal of Electrical Bioimpedance. 13(1), p. 136–142. doi: 10.2478/joeb-2022-0019. Full text in Research Archive Show summary

  Abstract Diabetic peripheral neuropathy (DPN) may lead to several changes in the skin, and some of these may influence the skin impedance spectrum. In the present study we have developed a prototype solution for skin impedance spectroscopy at selected skin sites (big toe pulp, heel and toe ball) that was tested in a pilot study on five patients with DPN and five healthy controls. At the big toe, most of the controls had markedly lower impedance than the DPN group, especially in the range of 1-100 kHz. The separation between the groups seems to be weaker at the heel and weakest at the toeball. The results may indicate that monitoring of the skin impedance spectrum may be a method for detection of skin changes associated with DPN, encouraging further studies with the big toe sensor in particular.

• Sharma, Archana; Lee-Ødegård, Sindre; Qvigstad, Elisabeth; Sommer, Christine; Sattar, Naveed & Gill, Jason M.R. [Show all 10 contributors for this article] (2022). β-Cell Function, Hepatic Insulin Clearance, and Insulin Sensitivity in South Asian and Nordic Women After Gestational Diabetes Mellitus. Diabetes. ISSN 0012-1797. 71(12), p. 2530–2538. doi: 10.2337/db22-0622. Full text in Research Archive Show summary

  South Asian women have a higher risk of type 2 diabetes after gestational diabetes mellitus (GDM) than Nordic women; however, the mechanisms behind this difference remain unclear. We investigated insulin sensitivity, β-cell function, and hepatic insulin clearance in 179 South Asian and 108 Nordic women ∼17 months after GDM (mean age 35.3 years, BMI 29.1 kg/m2) by oral glucose tolerance test using deconvolution of C-peptide kinetics. Thirty-one percent of South Asian and 53% of Nordic participants were normoglycemic at the time of measurement. South Asian women had higher areas under the curve (AUCs) for glucose, prehepatic insulin, and peripheral insulin and lower insulin sensitivity, disposition index, and fasting hepatic insulin clearance than Nordic women. In the group with prediabetes or diabetes, South Asian women had similar AUCs for glucose and prehepatic insulin but a higher AUC for peripheral insulin, lower disposition index, and lower fasting hepatic insulin clearance than Nordic women. The waist-to-height ratio mediated ∼25–40% of the ethnic differences in insulin sensitivity in participants with normoglycemia. Overall, our novel data revealed that South Asian women with normoglycemia after GDM showed lower insulin secretion for a given insulin resistance and lower hepatic insulin clearance than Nordic women. South Asian women are at high risk of developing type 2 diabetes after GDM, and preventive efforts should be prioritized.

• Tronstad, Christian; Pabst, Oliver; Amini, Maryam; Kleggetveit, Inge Petter; Elvebakk, Ole & Martinsen, Ørjan Grøttem [Show all 10 contributors for this article] (2022). Development of a prototype toe sensor for detection of diabetic peripheral small fiber neuropathy. Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). doi: 10.1109/EMBC48229.2022.9871101. Full text in Research Archive
• Pervjakova, Natalia; Moen, Gunn-Helen Øiseth; Borges, Maria-Carolina; Ferreira, Teresa; Cook, James P. & Allard, Catherine [Show all 73 contributors for this article] (2022). Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes. Human Molecular Genetics. ISSN 0964-6906. 31(19), p. 3377–3391. doi: 10.1093/hmg/ddac050. Full text in Research Archive Show summary

  Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (P < 5 × 10−8) with GDM, mapping to/near MTNR1B (P = 4.3 × 10−54), TCF7L2 (P = 4.0 × 10−16), CDKAL1 (P = 1.6 × 10−14), CDKN2A-CDKN2B (P = 4.1 × 10−9) and HKDC1 (P = 2.9 × 10−8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomization analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.

• Fragoso-Bargas, Nicolas; Elliott, Hannah R.; Lee-Ødegård, Sindre; Opsahl, Julia Onsrud; Sletner, Line & Jenum, Anne Karen [Show all 12 contributors for this article] (2022). Cross-Ancestry DNA Methylation Marks of Insulin Resistance in Pregnancy: An Integrative Epigenome-Wide Association Study. Diabetes. ISSN 0012-1797. 72(3), p. 415–426. doi: 10.2337/db22-0504. Full text in Research Archive
• Sharma, Archana; Nermoen, Ingrid; Qvigstad, Elisabeth; Tran, Anh Thi; Sommer, Christine & Sattar, Naveed [Show all 10 contributors for this article] (2022). High prevalence and significant ethnic differences in actionable HbA1C after gestational diabetes mellitus in women living in Norway. BMC Medicine. 20(1), p. 1–10. doi: 10.1186/s12916-022-02515-w. Full text in Research Archive Show summary

  Background The type 2 diabetes risk after gestational diabetes mellitus (GDM) is twice as high in South Asian compared to European women. Current guidelines differ regarding which test to use as a screening-tool post-GDM. We aimed to identify ethnic differences in the prevalence rates and early predictors for actionable HbA1c (defined as prediabetes and diabetes) short time after GDM. Methods This cross-sectional study, enrolling South Asian and Nordic women 1–3 years after a diagnosis of GDM, was undertaken at three hospitals in Norway. We performed a clinical and laboratory evaluation including an oral glucose tolerance test (OGTT). Medical records were used to retrieve data during pregnancy. Prediabetes was classified with HbA1c alone or combined with OGTT glucose measurements according to the WHO, WHO-IEC, and ADA criteria (fasting plasma glucose (FPG) 6.1–6.9 mmol/L, FPG 6.1–6.9 mmol/L and/or HbA1c 42-47 mmol/mol (6.0-6.4%), and FPG 5.6–6.9 mmol/L and/or HbA1c 39-47 mmol/mol (5.7-6.4%)). Ethnic differences in prevalence and predictors of glucose deterioration were assed by χ2 (Pearson) tests and logistic regression models. Results We included 163 South Asian and 108 Nordic women. Actionable HbA1c levels were highly prevalent and more so among South Asian than Nordic women (WHO-IEC-HbA1c: 25.8% vs. 6.5% (p ≤ 0.001), ADA-HbA1c: 58.3% vs. 22.2% (p ≤ 0.001)). Although adding OGTT-data gave higher combined prevalence rates of prediabetes and diabetes (WHO: 65.6% vs. 47.2% (p ≤ 0.05), WHO-IEC: 70.6% vs. 47.2% (p ≤ 0.001), ADA: 87.8% vs. 65.7% (p ≤ 0.001)), the excess risk in the South Asian women was best captured by the HbA1c. Important predictors for glucose deterioration after GDM were: South Asian ethnicity, GDM before the index pregnancy, use of glucose-lowering drugs in pregnancy, higher age, and higher in-pregnancy fasting glucose levels. Conclusions In women with GDM 1–3 year previously, we found high prevalence and significant ethnic differences in actionable ADA-HbA1c levels, with South Asian ethnicity, GDM before the index pregnancy, and the use of glucose-lowering drugs in pregnancy as the most important risk factors. This study reinforces the importance of annual screening—preferably with HbA1c measurements—to facilitate early intervention after GDM.

• Sharma, Archana; Birkeland, Kåre I.; Nermoen, Ingrid; Qvigstad, Elisabeth; Tran, Anh T. & Gulseth, Hanne L. [Show all 9 contributors for this article] (2021). Understanding mechanisms behind unwanted health behaviours in Nordic and South Asian women and how they affect their gestational diabetes follow-ups: A qualitative study. Diabetic Medicine. ISSN 0742-3071. 38(10), p. 1–12. doi: 10.1111/dme.14651. Full text in Research Archive Show summary

  Aims: The type 2 diabetes risk following gestational diabetes mellitus (GDM) is high, particularly among South Asian women in Western countries. Our study aimed to advance the knowledge regarding the mechanisms behind suboptimal follow-up in the Nordic and South Asian women with previous GDM by comparing (1) their experiences, (2) health and disease perceptions and (3) barriers to and facilitators of health-promoting behaviours. Methods: This qualitative study was conducted in three hospital outpatient clinics in Norway, comprising six focus group interviews with 28 women 1–3 years after a pregnancy with GDM. The participants were purposively sampled and grouped according to their ethnicity. The data were analysed using thematic analysis, and a theoretical approach was applied to support the analysis and discuss the study's findings. Results: Five main themes were identified: lack of resilience, emotional distress, ‘caught between a rock and a hard place’, postpartum abandonment and insufficient guidance. The key determinants of the maintenance of unwanted health behaviours after GDM were consistent across the ethnic groups. Although the importance of a culturally sensitive approach was emphasised, it appeared secondary to the need for a more organised public healthcare during and after GDM. Conclusions: Women's real-life constraints, combined with the inadequate healthcare-service implementation, could explain the non-adherence to the lifestyle-changes guidelines essential for preventing diabetes post-GDM. We suggest promoting specific coping strategies and changing the healthcare service approach rather than relying on women's capacity to initiate the necessary changes.

• Fragoso-Bargas, Nicolas; Opsahl, Julia Onsrud; Kiryushchenko, Nadezhda; Böttcher, Yvonne; Lee-Ødegård, Sindre & Qvigstad, Elisabeth [Show all 15 contributors for this article] (2021). Cohort profile: Epigenetics in Pregnancy (EPIPREG) – Population-based sample of European and South Asian pregnant women with epigenome-wide DNA methylation (850k) in peripheral blood leukocytes. PLOS ONE. 16(8), p. 1–15. doi: 10.1371/journal.pone.0256158. Full text in Research Archive Show summary

  Pregnancy is a valuable model to study the association between DNA methylation and several cardiometabolic traits, due to its direct potential to influence mother’s and child’s health. Epigenetics in Pregnancy (EPIPREG) is a population-based sample with the aim to study associations between DNA-methylation in pregnancy and cardiometabolic traits in South Asian and European pregnant women and their offspring. This cohort profile paper aims to present our sample with genetic and epigenetic data and invite researchers with similar cohorts to collaborative projects, such as replication of ours or their results and meta-analysis. In EPIPREG we have quantified epigenome-wide DNA methylation in maternal peripheral blood leukocytes in gestational week 28±1 in Europeans (n = 312) and South Asians (n = 168) that participated in the population-based cohort STORK Groruddalen, in Norway. DNA methylation was measured with Infinium MethylationEPIC BeadChip (850k sites), with technical validation of four CpG sites using bisulphite pyrosequencing in a subset (n = 30). The sample is well characterized with few missing data on e.g. genotype, universal screening for gestational diabetes, objectively measured physical activity, bioelectrical impedance, anthropometrics, biochemical measurements, and a biobank with maternal serum and plasma, urine, placenta tissue. In the offspring, we have repeated ultrasounds during pregnancy, cord blood, and anthropometrics up to 4 years of age. We have quantified DNA methylation in peripheral blood leukocytes in nearly all eligible women from the STORK Groruddalen study, to minimize the risk of selection bias. Genetic principal components distinctly separated Europeans and South Asian women, which fully corresponded with the self-reported ethnicity. Technical validation of 4 CpG sites from the methylation bead chip showed good agreement with bisulfite pyrosequencing. We plan to study associations between DNA methylation and cardiometabolic traits and outcomes.

• Lund, Agnethe; Ebbing, Cathrine; Rasmussen, Svein; Qvigstad, Elisabeth; Kiserud, Torvid & Kessler, Jørg (2021). Pre-gestational diabetes: Maternal body mass index and gestational weight gain are associated with augmented umbilical venous flow, fetal liver perfusion, and thus birthweight. PLOS ONE. 16(8), p. 1–17. doi: 10.1371/journal.pone.0256171. Full text in Research Archive Show summary

  Objectives To assess how maternal body mass index and gestational weight gain are related to on fetal venous liver flow and birthweight in pregnancies with pre-gestational diabetes mellitus. Methods In a longitudinal observational study, 49 women with pre-gestational diabetes mellitus were included for monthly assessments (gestational weeks 24–36). According to the Institute Of Medicine criteria, body mass index was categorized to underweight, normal, overweight, and obese, while gestational weight gain was classified as insufficient, appropriate or excessive. Fetal size, portal flow, umbilical venous flow and distribution to the fetal liver or ductus venosus were determined using ultrasound techniques. The impact of fetal venous liver perfusion on birthweight and how body mass index and gestational weight gain modified this effect, was compared with a reference population (n = 160). Results The positive association between umbilical flow to liver and birthweight was more pronounced in pregnancies with pre-gestational diabetes mellitus than in the reference population. Overweight and excessive gestational weight gain were associated with higher birthweights in women with pre-gestational diabetes mellitus, but not in the reference population. Fetuses of overweight women with pre-gestational diabetes mellitus had higher umbilical (p = 0.02) and total venous liver flows (p = 0.02), and a lower portal flow fraction (p = 0.04) than in the reference population. In pre-gestational diabetes mellitus pregnancies with excessive gestational weight gain, the umbilical flow to liver was higher than in those with appropriate weight gain (p = 0.02). Conclusions The results support the hypothesis that umbilical flow to the fetal liver is a key determinant for fetal growth and birthweight modifiable by maternal factors. Maternal pre-gestational diabetes mellitus seems to augment this influence as shown with body mass index and gestational weight gain.

• Sletner, Line; Jenum, Anne Karen; Qvigstad, Elisabeth & Hammerstad, Sara Salehi (2021). Thyroid Function during Pregnancy in A Multiethnic Population in Norway. Journal of the Endocrine Society (JES). 5(7), p. 1–12. doi: 10.1210/jendso/bvab078. Full text in Research Archive Show summary

  Abstract Context Ethnic differences in thyroid function during pregnancy have been reported. However, it is unclear if this is equally valid across ethnic groups within multiethnic populations. Objective We aimed to assess ethnic differences in thyrotropin (TSH) and free thyroxine (FT4), and the prevalence of thyroid dysfunction and thyroid autoimmunity during pregnancy. Methods In a population-based cohort of 785 pregnant women in Oslo, Norway, TSH, FT4, and thyroid peroxidase antibodies (TPO Abs) were measured twice: at gestational week (GW) 15 and 28, and urine iodine concentration at GW 15. Associations were assessed using multivariate linear regression. Results We found ethnic differences in TSH levels at both time points, but not for fT4. South Asians had 0.42 mU/L (95% CI, 0.20-0.64) higher TSH than Europeans in GW 15. This difference persisted after adjusting for covariates (including TPO Ab positivity and iodine status), and increased further as pregnancy progressed. In contrast, East Asians had the lowest TSH. No new cases of overt hypothyroidism were detected in early pregnancy, but subclinical hypothyroidism was found in 6.6% among all, highest in South Asians (14.2%). Hyperthyroidism early in pregnancy was observed in 3.7% (almost all subclinical), highest in East Asians (11.9%). The prevalence of TPO Ab positivity was 4%, highest in South Asians (8%). Conclusion In a multiethnic population of presumably healthy women, we found ethnic variations in TSH but not FT4 levels throughout pregnancy. South Asians had higher TSH and more subclinical hypothyroidism, not explained by their higher prevalence of TPO Ab positivity. Larger studies are needed to define ethnic- and trimester-specific reference ranges in pregnancy.

• Opsahl, Julia; Moen, Gunn-Helen Øiseth; Qvigstad, Elisabeth; Böttcher, Yvonne; Birkeland, Kåre Inge & Sommer, Christine (2020). Epigenetic signatures associated with maternal body mass index or gestational weight gain: a systematic review. Journal of Developmental Origins of Health and Disease. ISSN 2040-1744. doi: 10.1017/S2040174420000811. Full text in Research Archive
• Opsahl, Julia Onsrud; Moen, Gunn-Helen; Qvigstad, Elisabeth; Böttcher, Yvonne; Birkeland, Kåre I. & Sommer, Christine (2020). Epigenetic signatures associated with maternal body mass index or gestational weight gain: A systematic review. Journal of Developmental Origins of Health and Disease. ISSN 2040-1744. p. 1–11. doi: 10.1017/S2040174420000811. Full text in Research Archive Show summary

  Abstract Maternal body mass index (BMI) and gestational weight gain (GWG) impacts both the mother’s and the child’s health, and epigenetic modifications have been suggested to mediate some of these effects in offspring. This systematic review aimed to summarize the current literature on associations between maternal BMI and GWG and epigenetic marks. We performed systematic searches in PubMed and EMBASE and manual searches of reference lists. We included 49 studies exploring the association between maternal BMI and/or GWG and DNA methylation or miRNA; 7 performed in maternal tissues, 13 in placental tissue and 38 in different offspring tissues. The most consistent findings were reported for the relationship between maternal BMI, in particular pre-pregnant BMI, and expression of miRNA Let-7d in both maternal blood and placental tissue, methylation of the gene HIF3A in umbilical cord blood and umbilical tissue, and with expression in the miR-210 target gene, BDNF in placental tissue and cord blood. Correspondingly, methylation of BDNF was also found in placental tissue and cord blood. The current evidence suggests that maternal BMI is associated with some epigenetic signatures in the mother, the placenta and her offspring, which could indicate that some of the effects proposed by the Developmental Origins of Health and Disease-hypothesis may be mediated by epigenetic marks. In conclusion, there is a need for large, well-designed studies and meta-analyses that can clarify the relationship between BMI, GWG and epigenetic changes.

• Arora, G. P.; Åkerlund, M.; Bruns, C; Moen, Gunn-Helen; Wasenius, N. S. & Sommer, Christine [Show all 17 contributors for this article] (2019). Phenotypic and genotypic differences between Indian and Scandinavian women with gestational diabetes mellitus. Journal of Internal Medicine. ISSN 0954-6820. doi: 10.1111/joim.12903. Full text in Research Archive
• Moen, Gunn-Helen Øiseth; LeBlanc, Marissa; Sommer, Christine; Prasad, Rashmi B.; Lekva, Tove & Normann, Kjersti Ringvoll [Show all 11 contributors for this article] (2018). Genetic determinants of glucose levels in pregnancy: Genetic risk scores analysis and GWAS in the Norwegian STORK cohort. European Journal of Endocrinology (EJE). ISSN 0804-4643. 179(6), p. 363–372. doi: 10.1530/EJE-18-0478. Full text in Research Archive
• Lekva, Tove; Godang, Kristin; Michelsen, Annika; Qvigstad, Elisabeth; Normann, Kjersti Ringvoll & Norwitz, Errol R. [Show all 11 contributors for this article] (2018). Prediction of gestational diabetes mellitus and pre-diabetes 5 years postpartum using 75 g oral glucose tolerance test at 14-16 Weeks' gestation. Scientific Reports. 8:13392, p. 1–9. doi: 10.1038/s41598-018-31614-z. Full text in Research Archive Show summary

  Early detection and treatment of women at risk for gestational diabetes mellitus (GDM) could improve perinatal and long-term outcomes in GDM women and their offspring. We explored if a 75 g oral glucose tolerance test (OGTT) at 14-16 weeks of gestation could identify women who will (1) develop GDM or give birth to large-for-gestational-age (LGA) babies in 1031 pregnant women from the STORK study using different diagnostic criteria (WHO1999, IADPSG2010, WHO2013, NORWAY2017) and (2) develop pre-diabetes 5 years postpartum focusing on first trimester β-cell function in a separate study of 300 women from the STORK cohort. The sensitivity of the 14-16 week OGTT to identify women who would develop GDM or have LGA babies was low, and we could not identify alternative cut-offs to exclude women not at risk or identify women that could benefit from early intervention. First trimester β-cell function was a stronger determinant than third trimester β-cell function of predicting maternal pre-diabetes. In conclusion, in our normal low-risk population, the 75 g OGTT at 14-16 weeks is insufficient to identify candidates for early treatment of GDM or identify women not likely to develop GDM or have LGA babies. First trimester β-cell function may predict pre-diabetes 5 years postpartum.

• Moen, Gunn-Helen Øiseth; Qvigstad, Elisabeth; Birkeland, Kåre I.; Evans, David & Sommer, Christine (2018). Are serum concentrations of vitamin B-12 causally related to cardiometabolic risk factors and disease? A Mendelian randomization study. American Journal of Clinical Nutrition. ISSN 0002-9165. 108(2), p. 398–404. doi: 10.1093/ajcn/nqy101. Full text in Research Archive
• Moen, Gunn-Helen Øiseth; Sommer, Christine; Prasad, Rashmi B.; Sletner, Line; Groop, Leif & Qvigstad, Elisabeth [Show all 7 contributors for this article] (2017). Epigenetic modifications and gestational diabetes: A Systematic review of published literature. European Journal of Endocrinology (EJE). ISSN 0804-4643. 176(5), p. R247–R267. doi: 10.1530/EJE-16-1017. Full text in Research Archive
• Qvigstad, Elisabeth; Gulseth, Hanne Løvdal; Risstad, Hilde; Roux, Carel W. le; Berg, Tore Julsrud & Mala, Tom [Show all 7 contributors for this article] (2016). A novel technique of Roux-en-Y gastric bypass reversal for postprandial hyperinsulinemic hypoglycaemia: A case report. International Journal of Surgery Case Reports (IJSCR). 21, p. 91–94. doi: 10.1016/j.ijscr.2016.02.033. Full text in Research Archive
• Christensen, Jacob J.; Retterstøl, Kjetil; Godang, Kristin; Paasche, Marie Cecilie Roland; Qvigstad, Elisabeth & Bollerslev, Jens [Show all 9 contributors for this article] (2016). LDL cholesterol in early pregnancy and offspring cardiovascular disease risk factors. Journal of Clinical Lipidology. ISSN 1933-2874. 10(6), p. 1369–1378. doi: 10.1016/j.jacl.2016.08.016. Full text in Research Archive Show summary

  Background Vast amounts of data show associations between maternal obesity, dysglycemia, diabetes, and undernutrition during pregnancy and increased cardiovascular disease risk in offspring. However, elevated maternal LDL cholesterol (LDL-C) in pregnancy and offspring cardiovascular disease (CVD) risk has scarcely been studied. Objective Our objective was to investigate the associations between elevated maternal LDL-C in pregnancy and CVD risk factors in 6-to-13-year-old offspring. Methods We recruited 6-to-13-year-old children whose mothers attended a pregnancy cohort and who had high or low cholesterol in pregnancy, defined as LDL-C over the 90th percentile or below the 10th percentile within the pregnancy cohort, respectively. We measured CVD risk factors in the children in the 2 groups. Results Maternal plasma LDL-C at gestational week 14 to 16 was 4.0 and 1.4 mmol/L in the hypercholesterolemic (n = 27) and hypocholesterolemic (n = 34) groups, respectively (P < .001). Interestingly, offspring plasma LDL-C was 0.4 mmol/L higher in children whose mothers had hypercholesterolemia during pregnancy (P < .01). We found no difference in birthweight or any other clinical or biochemical CVD risk factors or dietary intake between the children at 6–13 years. Conclusions Women with elevated LDL-C during early pregnancy have offspring with higher LDL-C already at the age of 6–13 years. Unless cholesterol-reducing measures are successfully implemented, the affected children may be at increased cardiovascular risk.

• Frøslie, Kathrine Frey; Røislien, Jo; Qvigstad, Elisabeth; Godang, Kristin; Bollerslev, Jens & Henriksen, Tore [Show all 7 contributors for this article] (2014). Shape information in repeated glucose curves during pregnancy provided significant physiological information for neonatal outcomes. PLOS ONE. 9(3). doi: 10.1371/journal.pone.0090798. Full text in Research Archive
• Godang, Kristin; Frøslie, Kathrine Frey; Henriksen, Tore; Qvigstad, Elisabeth & Bollerslev, Jens (2014). Seasonal variation in maternal and umbilical cord 25(OH) vitamin D and their associations with neonatal adiposity. European Journal of Endocrinology (EJE). ISSN 0804-4643. 170(4), p. 609–617. doi: 10.1530/EJE-13-0842. Full text in Research Archive
• Frøslie, Kathrine Frey; Røislien, Jo; Qvigstad, Elisabeth; Godang, Kristin; Bollerslev, Jens & Voldner, Nanna [Show all 8 contributors for this article] (2013). Shape information from glucose curves: Functional data analysis compared with traditional summary measures. BMC Medical Research Methodology. 13. doi: 10.1186/1471-2288-13-6. Full text in Research Archive Show summary

  Background Plasma glucose levels are important measures in medical care and research, and are often obtained from oral glucose tolerance tests (OGTT) with repeated measurements over 2–3 hours. It is common practice to use simple summary measures of OGTT curves. However, different OGTT curves can yield similar summary measures, and information of physiological or clinical interest may be lost. Our mean aim was to extract information inherent in the shape of OGTT glucose curves, compare it with the information from simple summary measures, and explore the clinical usefulness of such information. Methods OGTTs with five glucose measurements over two hours were recorded for 974 healthy pregnant women in their first trimester. For each woman, the five measurements were transformed into smooth OGTT glucose curves by functional data analysis (FDA), a collection of statistical methods developed specifically to analyse curve data. The essential modes of temporal variation between OGTT glucose curves were extracted by functional principal component analysis. The resultant functional principal component (FPC) scores were compared with commonly used simple summary measures: fasting and two-hour (2-h) values, area under the curve (AUC) and simple shape index (2-h minus 90-min values, or 90-min minus 60-min values). Clinical usefulness of FDA was explored by regression analyses of glucose tolerance later in pregnancy. Results Over 99% of the variation between individually fitted curves was expressed in the first three FPCs, interpreted physiologically as “general level” (FPC1), “time to peak” (FPC2) and “oscillations” (FPC3). FPC1 scores correlated strongly with AUC (r=0.999), but less with the other simple summary measures (−0.42≤r≤0.79). FPC2 scores gave shape information not captured by simple summary measures (−0.12≤r≤0.40). FPC2 scores, but not FPC1 nor the simple summary measures, discriminated between women who did and did not develop gestational diabetes later in pregnancy. Conclusions FDA of OGTT glucose curves in early pregnancy extracted shape information that was not identified by commonly used simple summary measures. This information discriminated between women with and without gestational diabetes later in pregnancy.

• Friis, Camilla Margrethe; Qvigstad, Elisabeth; Paasche, Marie Cecilie; Godang, Kristin; Voldner, Nanna & Bollerslev, Jens [Show all 7 contributors for this article] (2013). Newborn Body Fat: Associations with Maternal Metabolic State and Placental Size. PLOS ONE. 8(2). doi: 10.1371/journal.pone.0057467. Full text in Research Archive
• Frøslie, Kathrine Frey; Godang, Kristin; Bollerslev, Jens; Henriksen, Tore; Røislien, Jo & Veierød, Marit Bragelien [Show all 7 contributors for this article] (2011). Time-dependent trends in glucose values during long-term use of a glucose measurement system. Clinical Biochemistry. ISSN 0009-9120. 44(17-18), p. 1483–1486. doi: 10.1016/j.clinbiochem.2011.08.1150. Full text in Research Archive
• Voldner, Nanna; Qvigstad, Elisabeth; Frøslie, Kathrine Frey; Godang, Kristin; Henriksen, Tore & Bollerslev, Jens (2010). Increased risk of macrosomia among overweight women with high gestational rise in fasting glucose. Journal of Maternal-Fetal & Neonatal Medicine. ISSN 1476-7058. 23(1), p. 74–81. doi: 10.3109/14767050903121472. Full text in Research Archive
• Godang, Kristin; Qvigstad, Elisabeth; Voldner, Nanna; Isaksen, Gunhild Aker; Frøslie, Kathrine Frey & Nøtthellen, Jacob A [Show all 8 contributors for this article] (2010). Assessing Body Composition in Healthy Newborn Infants: Reliability of Dual-Energy X-Ray Absorptiometry. Journal of clinical densitometry. ISSN 1094-6950. 13(2), p. 151–160. doi: 10.1016/j.jocd.2010.01.121. Full text in Research Archive
• Frøslie, Kathrine Frey; Røislien, Jo; Laake, Petter; Henriksen, Tore; Qvigstad, Elisabeth & Veierød, Marit Bragelien (2010). Categorisation of continuous exposure variables revisited. A response to the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Study. BMC Medical Research Methodology. 10. doi: 10.1186/1471-2288-10-103. Full text in Research Archive Show summary

  Background Although the general statistical advice is to keep continuous exposure variables as continuous in statistical analyses, categorisation is still a common approach in medical research. In a recent paper from the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Study, categorisation of body mass index (BMI) was used when analysing the effect of BMI on adverse pregnancy outcomes. The lowest category, labelled "underweight", was used as the reference category. Methods The present paper gives a summary of reasons for categorisation and methodological drawbacks of this approach. We also discuss the choice of reference category and alternative analyses. We exemplify our arguments by a reanalysis of results from the HAPO paper. Results Categorisation of continuous exposure data results in loss of power and other methodological challenges. An unfortunate choice of reference category can give additional lack of precision and obscure the interpretation of risk estimates. A highlighted odds ratio (OR) in the HAPO study is the OR for birth weight >90th percentile for women in the highest compared to the lowest BMI category ("obese class III" versus "underweight"). This estimate was OR = 4.55 and OR = 3.52, with two different multiple logistic regression models. When using the "normal weight" category as the reference, our corresponding estimates were OR = 2.03 and OR = 1.62, respectively. Moreover, our choice of reference category also gave narrower confidence intervals. Summary Due to several methodological drawbacks, categorisation should be avoided. Modern statistical analyses should be used to analyse continuous exposure data, and to explore non-linear relations. If continuous data are categorised, special attention must be given to the choice of reference category.

• Grill, Valdemar; Radtke, Maria; Qvigstad, Elisabeth; Kollind, Magnus & Bjorklund, A (2009). Beneficial effects of K-ATP channel openers in diabetes: an update on mechanisms and clinical experiences. Diabetes, obesity and metabolism. ISSN 1462-8902. 11, p. 143–148. doi: 10.1111/j.1463-1326.2009.01119.x. Full text in Research Archive
• Radtke, Maria; Kollind, Magnus; Qvigstad, Elisabeth & Grill, Valdemar (2007). Twelve weeks' treatment with diazoxide without insulin supplementation in Type 2 diabetes is feasible but does not improve insulin secretion. Diabetic Medicine. ISSN 0742-3071. 24(2), p. 172–177. doi: 10.1111/j.1464-5491.2006.02056.x. Full text in Research Archive
• Qvigstad, Elisabeth; Kollind, M & Grill, Valdemar (2004). Nine weeks of bedtime diazoxide is well tolerated and improves beta-cell function in subjects with Type 2 diabetes. Diabetic Medicine. ISSN 0742-3071. 21(1), p. 73–76. Full text in Research Archive
• Mostad, Ingrid Løvold; Qvigstad, Elisabeth; Bjerve, Kristian S & Grill, Valdemar (2004). Effects of a 3-day low-fat diet on metabolic control, insulin sensitivity, lipids and adipocyte hormones in Norwegian subjects with hypertriacylglycerolaemia and type 2 diabetes. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 64(6), p. 565–74. Full text in Research Archive
• Qvigstad, Elisabeth; Kollind, Magnus & Grill, Valdemar (2004). Nine weeks of bedtime diazoxide is well tolerated and improves beta-cell function in subjects with Type 2 diabetes. Diabetic Medicine. ISSN 0742-3071. 21, p. 73–76. Full text in Research Archive
• Qvigstad, Elisabeth; Grill, Valdemar; Bjerve, Kristian S & Mostad, Ingrid Løvold (2003). Acute lowering of fatty acids improves insulin secretion in a subset of type II diabetes subjects. American Journal of Physiology. Endocrinology and Metabolism. ISSN 0193-1849. 284, p. E129–E137. Full text in Research Archive Show summary

  We tested the effects of acute perturbations of elevated fatty acids (FA) on insulin secretion in type II diabetes. Twenty-one type II diabetes subjects with hypertriglyceridemia (triacylglycerol > 2.2mmol/l) and ten age-matched non-diabetic subjects participated. Glucose-stimulated insulin secretion was monitored during hyperglycemic clamps for 120 min. An infusion of Intralipid and heparin was added during min 60-120. In one of two tests, the subjects ingested 250mg of Acipimox 60 min before the hyperglycemic clamp. A third test (also with Acipimox) was performed in seventeen of the diabetic subjects after three days of a low-fat diet. Acipimox lowered FA levels and enhanced insulin sensitivity in non-diabetic diabetic and diabetic subjects alike. Acipimox administration failed to affect insulin secretion rates in non-diabetic subjects and in the group of diabetic subjects as a whole. However, in the diabetic subjects Acipimox increased integrated insulin secretion rates during min 60-120 min in the 50% having the lowest levels of hemoglobin A1c (379 ± 34 with vs. 326 ± 30 pmol·kg-1·min-1 without Acipimox, P<0.05). A three day dietary intervention diminished energy from fat from 39 to 23% without affecting FA levels and without improving the insulin response during clamps. Elevated FA levels may tonically inhibit stimulated insulin secretion in a subset of type II diabetic subjects.

• Qvigstad, Elisabeth; Mostad, Ingrid Løvold; Bjerve, Kristian S & Grill, Valdemar (2002). Acute lowering of circulating fatty acids improves insulin secretion in a subset of type 2 diabetes subjects. American Journal of Physiology. Endocrinology and Metabolism. ISSN 0193-1849. 284, p. 129–137. Full text in Research Archive
• Qvigstad, Elisabeth; Grill, Valdemar & Bjerve, Kristian S (2002). Effects of long-term fasting on insulin responses to fatty acids in man. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 62, p. 271–278. Full text in Research Archive Show summary

  Objective: To investigate whether the prolonged physiological elevation of non-esterified fatty acids (NEFA) seen in man during fasting associates with an altered acute insulin response to NEFA. Subjects and methods: Fourteen non-diabetic subjects, age18-25 years, BMI 23,2 ± 0,8 kg/m2 underwent hyperglycemic clamps (blood glucose 11 mM) for 120 min. during which either saline or Intralipid was administered during the last 60 min. Subjects were tested after an overnight as well as after a 58h fast. Results: After the overnight fast insulin levels increased during Intralipid infusion, reaching at min 120 an increment of 33,0 ± 8,5 mU/ml vs. 9,5 ± 4,4 mU/ml during saline, p<0,05 for difference. Conversely, after the 58 h fast, Intralipid failed to promote a successive increase of insulin levels (increment during Intralipid at min 120: 0,5 ± 5,8 mU/ml versus -4,3 ± 2,5 mU/ml during saline, NS). Insulin sensitivity as assessed by the amount of infused glucose and its ratio to insulin was enhanced by Intralipid after an overnight fast but was decreased after a 58 h fast. Conclusion: Long term elevated NEFA during fasting associates with diminished beta cell responsiveness to an acute elevation of fatty acids in conjunction with negative effects on insulin sensitivity.

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• Bargas, Nicolas Fragoso; Mcbride, Nancy S.; Lee-Ødegård, Sindre; Lawlor, Deborah A.; Yousefi, Paul D. & Moen, Gunn-Helen [Show all 14 contributors for this article] (2025). Correction to: Epigenome-wide association study of objectively measured physical activity in peripheral blood leukocytes (BMC Genomics, (2025), 26, 1, (62), 10.1186/s12864-025-11262-0). BMC Genomics. 26(1). doi: 10.1186/s12864-025-11311-8. Full text in Research Archive
• Hewitt, Stephen I; Hofsø, Dag; Qvigstad, Elisabeth; Berg, Tore Julsrud; Chahal-Kummen, Monica & Kristinsson, Jon Adalsteinn [Show all 7 contributors for this article] (2025). Hypoglykemi etter fedmekirurgi. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 145(6). doi: 10.4045/tidsskr.24.0396. Full text in Research Archive Show summary

  Omfanget av fedmekirurgi har økt vår erkjennelse av hypoglykemi som en komplikasjon, og forekomsten synes høyere enn tidligere anslått. Pasientene har oftest milde til moderate symptomer, og de fleste har god effekt av kostholdstilpasninger. Et fåtall får kramper, synkoperer eller klarer ikke ta vare på seg selv. Hypoglykemien knyttes til både vektavhengige og vektuavhengige mekanismer, med både bedret insulinsensitivitet og økt frigjøring av inkretinhormoner, som glukagonlignende peptid 1. Hovedprinsippet i behandlingen er å begrense svingninger i nivåene av blodglukose og insulin etter måltider. Enkelte medikamenter kan avhjelpe tilstanden, men brukes lite. I denne kliniske oversikten oppsummeres noen viktige hensyn for leger som møter disse pasientene.

• Solé-Navais, Pol; Flatley, Christopher; Steinthorsdottir, Valgerdur; Vaudel, Marc; Juodakis, Julius & Chen, Jing [Show all 85 contributors for this article] (2023). Author Correction: Genetic effects on the timing of parturition and links to fetal birth weight (Nature Genetics, (2023), 55, 4, (559-567), 10.1038/s41588-023-01343-9). Nature Genetics. ISSN 1061-4036. doi: 10.1038/s41588-023-01412-z. Full text in Research Archive
• Ruiz, Paz Lopez-Doriga; Cohen, Jacqueline Mallory; Kjerpeseth, Lars Jøran; Furu, Kari & Qvigstad, Elisabeth (2023). Paternal use of Metformin and Risk of Major Congenital Malformations. Full text in Research Archive
• Bargas, Nicolas Fragoso; Linares-Pineda, Teresa; Molina-Vega, María; Picón, María José; Jenum, Anne Karen & Sletner, Line [Show all 14 contributors for this article] (2023). Methylation risk score for gestational diabetes on DNA methylation patterns associated with type 2 diabetes. Full text in Research Archive
• Stalheim, Astrid M.; Iversen, Marjolein M.; Jenum, Anne Karen; Sletner, Line; Stafne, Signe Nilssen & Qvigstad, Elisabeth [Show all 10 contributors for this article] (2022). Seasonal variation in gestational diabetes mellitus. Full text in Research Archive
• Fragoso-Bargas, Nicolas; Lee-Ødegård, Sindre; Moen, Gunn-Helen Øiseth; oppsahl, JO; Sletner, Line & Jenum, Anne Karen [Show all 13 contributors for this article] (2022). Epigenome-Wide Association Study of objectively measured moderate physical activity in pregnan. Full text in Research Archive Show summary

  Epigenome-Wide Association Study of objectively measured moderate physical activity in pregnancy Nicolas Fragoso-Bargas1,2, Sindre Lee-Ødegård2, Gunn-Helen Moen2,3,4,5, Julia O. Opsahl2, Line Sletner2,6, Anne Karen Jenum2, Paul Franks7, Rashmi B. Prasad8, Leif C. Groop8, Elisabeth Qvigstad1,2, Kåre I. Birkeland2, Kåre R. Richardsen9, Christine Sommer1 1Oslo University Hospital, Oslo, Norway, 2University of Oslo, Oslo, Norway, 3The University of Queensland Diamantina Institute, Brisbane, Australia, 4Norwegian University of Science and Technology, Trondheim, Norway, 5University of Bristol, UK, 6Akershus University Hospital, Oslo, Norway, 7Lund University Genetic and Molecular Epidemiology, Malmö, Sweden, 8Lund University Diabetes Centre, Malmö, Sweden,9Oslo Metropolitan University, Oslo, Norway. Physical activity (PA) is recommended during pregnancy to reduce the risk of excessive weight gain and gestational diabetes mellitus, and to improve general health. DNA methylation (DNAm) has been proposed as a potential molecular mechanism through which physical activity (PA) mediates the effects on the transcriptome. Here we performed an epigenome-wide association study (EWAS) of objectively measured moderate physical activity in pregnancy, which has not been performed previously. In EPIPREG (a sub-sample of the population-based STORK Groruddalen study) we quantified DNAm at gestational week 28 (±2 SD) with Illumina’s Infinium Methylation EPIC BeadChip. With SenseWear™ Pro3 Armband, we measured hours per day of moderate PA (3.0 to 6.0 metabolic equivalent for task (MET)) and steps/day. DNAm outliers that were 4 times the interquartile range below or above the 25TH and 75TH percentiles respectively were removed, before the beta values were transformed to M-values. Of the 472 that passed the EWAS quality control, 239 European (EUR) and 109 South Asian women (SA) had two valid days of recorded PA (19.2h per day), and were non-outliers (±4 SD) in their respective ethnic group. We used two approaches to test the association between M-values and moderate PA (hours/day): 1) A trans-ethnic approach using mixed linear models adjusted for blood cell proportions, age, smoking, number of steps, number of valid days (between 2 to 8), and ethnicity as a random intercept, and 2) through separate analyses in EUR and SA using linear modelling adjusted with the before mentioned covariates. We accepted a false discovery rate of 10%. In the trans-ethnic analysis, only cg08148261 located in the promoter area of LDHB was significantly associated with moderate PA. In Europeans, eight sites were significant: cg19031974 (BSN-AS2), cg19053287 (MCF2L) cg14930390 (MUTED), cg18517050 (CIAPIN1) and cg26191378 (TMUB1), located near promoter areas, cg27160968 (ESRRA) and cg15879426 (c17orf101) located in exon boundaries, and cg10421808 which is unannotated. In South Asians, only cg05999993 in the promoter area of AOAH was associated with moderate PA. Most of the sites showed decreased DNAm at increased moderate PA (hours/day), while in cg10421808, cg14930390 and cg15879426 the opposite was observed. In conclusion, we found several significant associations between DNAm and moderate PA. Several CpGs were located near gene promoter areas, which could imply altered transcription of the respective genes. These findings suggest that PA may exert changes in DNAm with important transcriptional implications during pregnancy.

• Fragoso-Bargas, Nicolas; Lee-Ødegård, Sindre; Moen, Gunn-Helen Øiseth; Oppsahl, JO; Sletner, Line & Jenum, Anne Karen [Show all 12 contributors for this article] (2022). Epigenome-Wide Association Study of objectively measured physical activity in pregnancy. Full text in Research Archive
• Qvigstad, Elisabeth (2018). The diversity of gestational diabetes: A therapeutic challenge. European Journal of Endocrinology (EJE). ISSN 0804-4643. 178(3), p. C1–C5. doi: 10.1530/EJE-18-0012. Full text in Research Archive
• Christensen, Jacob J.; Retterstøl, Kjetil; Godang, Kristin; Roland, Marie Cecilie; Qvigstad, Elisabeth & Bollerslev, Jens [Show all 9 contributors for this article] (2017). LDL cholesterol in early pregnancy and offspring cardiovascular disease risk factors. Full text in Research Archive
• Christensen, Jacob J.; Retterstøl, Kjetil; Godang, Kristin; Roland, Marie Cecilie Paasche; Qvigstad, Elisabeth & Bollerslev, Jens [Show all 9 contributors for this article] (2016). Women with elevated LDL-C in early pregnancy have offspring with elevated LDL-C at 6-13 years of age. Full text in Research Archive
• Christensen, Jacob J.; Retterstøl, Kjetil; Godang, Kristin; Roland, Marie Cecilie Paasche; Qvigstad, Elisabeth & Bollerslev, Jens [Show all 9 contributors for this article] (2016). LDL cholesterol in early pregnancy and offspring cardiovascular disease risk factors. Full text in Research Archive
• Christensen, Jacob J.; Retterstøl, Kjetil; Godang, Kristin; Roland, Marie Cecilie Paasche; Qvigstad, Elisabeth & Bollerslev, Jens [Show all 9 contributors for this article] (2016). Women with elevated LDL-C in early pregnancy have offspring with elevated LDL-C at 6-13 years of age. Full text in Research Archive
• Christensen, Jacob J.; Retterstøl, Kjetil; Godang, Kristin; Roland, Marie Cecilie Paasche; Qvigstad, Elisabeth & Bollerslev, Jens [Show all 9 contributors for this article] (2016). Women with elevated LDL-C in early pregnancy have offspring with elevated LDL-C at 6-13 years of age. Full text in Research Archive
• Christensen, Jacob J.; Retterstøl, Kjetil; Godang, Kristin; Roland, Marie Cecilie Paasche; Qvigstad, Elisabeth & Bollerslev, Jens [Show all 9 contributors for this article] (2016). Women with elevated LDL-C in early pregnancy have offspring with elevated LDL-C at 6-13 years of age. Full text in Research Archive
• Christensen, Jacob J.; Retterstøl, Kjetil; Godang, Kristin; Roland, Marie Cecilie Paasche; Qvigstad, Elisabeth & Bollerslev, Jens [Show all 9 contributors for this article] (2016). LDL cholesterol in early pregnancy and offspring cardiovascular disease risk factors. Full text in Research Archive
• Qvigstad, Elisabeth; Voldner, Nanna; Bollerslev, Jens & Henriksen, Tore (2009). Diabetes i svangerskapet - forebygging over generasjoner. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 129(23), p. 2494–2496. Full text in Research Archive
• Qvigstad, Elisabeth; Grill, Valdemar & Kollind, Magnus (2002). Nine weeks of bedtime diazoxide is well tolerated and beta cell beneficial in subjects with type 2 diabetes. Full text in Research Archive Show summary

  Twenty-seven type 2 diabetic subjects (17M, 10F) using BTI and metformin participated. Half of the subjects received added treatment with Diazoxide, 100mg at bedtime, and half with placebo for 9 weeks. We registered no side effects of Diazoxide. Treatment with Diazoxide did not incur any increase in BTI. Plasma C-peptide responses to glucagon increased (0,15 ± 0,06nmol/l vs. -0,01 ± 0,04nmol/l for placebo, p<0,06 for difference). Plasma insulin levels were 66,2 ± 41,7pmol/l for Diazoxide vs. -84,2 ± 51,5, for placebo p<0,03. Bedtime Diazoxide decreased fasting glucagon levels by 41% vs. placebo, p<0,03. HbA1c levels did not change, whereas levels of blood glucose post breakfast were higher during Diazoxide (1,34 ± 0,43mmol/l, p<0,01 vs. placebo), but not at other time points. A breakfast test in the presence of repaglinide elicited a robust insulin response in Diazoxide treated subjects. Diazoxide taken at bedtime with BTI was well tolerated and produced beneficial effects on insulin and glucagon secretion, but failed to improve metabolic control.

• Grill, Valdemar; Qvigstad, Elisabeth & Kollind, Magnus (2002). Nine weeks of bedtime diazoxide is well tolerated and beta cell beneficial in subjects with type 2 diabetes. Full text in Research Archive Show summary

  Twenty-seven type 2 diabetic subjects (17M, 10F) using BTI and metformin participated. Half of the subjects received added treatment with Diazoxide, 100mg at bedtime, and half with placebo for 9 weeks. We registered no side effects of Diazoxide. Treatment with Diazoxide did not incur any increase in BTI. Plasma C-peptide responses to glucagon increased (0,15 ± 0,06nmol/l vs. -0,01 ± 0,04nmol/l for placebo, p<0,06 for difference). Plasma insulin levels were 66,2 ± 41,7pmol/l for Diazoxide vs. -84,2 ± 51,5, for placebo p<0,03. Bedtime Diazoxide decreased fasting glucagon levels by 41% vs. placebo, p<0,03. HbA1c levels did not change, whereas levels of blood glucose post breakfast were higher during Diazoxide (1,34 ± 0,43mmol/l, p<0,01 vs. placebo), but not at other time points. A breakfast test in the presence of repaglinide elicited a robust insulin response in Diazoxide treated subjects. Diazoxide taken at bedtime with BTI was well tolerated and produced beneficial effects on insulin and glucagon secretion, but failed to improve metabolic control.

• Grill, Valdemar; Kollind, Magnus & Qvigstad, Elisabeth (2002). Nine weeks of bedtime diazoxide is well tolerated and beta cell beneficial in subjects with type 2 diabetes. Full text in Research Archive
• Qvigstad, Elisabeth (2001). Effekter av frie fettsyrer på insulinfrigjøringen. Full text in Research Archive Show summary

  En omdiskutert faktor for beta-cellesvikten ved type-2 diabetes er effekten av høye nivåer av sirkulerende frie fettsyrer, som er forhøyet under faste og ved type-2 diabetes. En langvarig forhøyelse av fettsyrer hemmer insulinfrigjøring o g insulinbio s yntese. Med denne bakgrunn, startet vi en studie med 21 type-2 diabetes pasienter med hypertriglyceridemi (>2.2 mmol/l) for å se om en akutt reduksjon av fettsyrer med acipimox vil bedre insulinfrigjøringen. Den akutte reduksjonen av fr ie fettsy rer på grunn av acipimox var assosiert med en noe bedret insulinfrigjøring og glukoseforbruk. Effekten var tydeligst hos de individene som hadde relativt god blodsukkerkontroll. 17 av forsøkspersonene deltok deretter i en kostholdsintervensj o n. Kos t ble registrert i 3 dager, deretter var det et intervall på 2-4 uker, deltakerne fikk så kostråd for å oppnå en redusert fettmengde, som de gjennomførte i 3 dager. Den kortvarige intervensjonen med fettredusert kost gav ingen økning i insul infrig jøri ng, men hadde en overraskende negativ effekt på insulinfølsomheten. Fettsyrene øker også betydelig ved faste. Vi undersøkte derfor om et økt fettsyrenivå forårsaket av langvarig faste ville virke negativt på insulinfrigjøringen. 14 fr iske personer gjennomførte både en 10t og en 58t faste, med etterfølgende tester. Langvarig faste hos ikke-diabetiske individer i hovedsak er assosiert med en negativ påvirkning av fettsyrer på glukose-stimulert insulinfrigjøring og også en parallell negativ virkning på insulinfølsomheten. Begge effektene kan være tilpasninger til redusert tilgang av føde og behov for å unngå hypoglykemi. Man kan tenke seg at disse effektene er utviklet som en fysiologisk respons og at de samme fettsyre-ef fekte ne trer i funksjon også ved type-2 diabetes - men da med et uhensiktsmessig resultat. Forandringer i fettsyrenivåene har betydning for insulinfrigjøringen hos mennesker. Dog er det foreløpig for tidlig å trekke linjen til klinisk anvendelse ved ty pe-2 diabetes.

• Qvigstad, Elisabeth & Grill, Valdemar (2000). Modulation by fatty acids of glucose-induced insulin secretion: diminished stimulatory effects after prolonged fasting. Full text in Research Archive
• Qvigstad, Elisabeth & Grill, Valdemar (2000). Modulation by fatty acids of glucose-induced insulin secretion: diminished stimulatory effects after prolonged fasting. Full text in Research Archive
• Mostad, Ingrid Løvold; Qvigstad, Elisabeth; Bjerve, Kristian S & Grill, Valdemar (2000). A low-fat diet for three days decreases insulin sensitivity in type-2 diabetes patients with hypertriglyceridemia. Full text in Research Archive
• Qvigstad, Elisabeth; Mostad, Ingrid Løvold; Bjerve, Kristian & Grill, Valdemar (1999). Akutt senking av fettsyrer øker insulinfrigjøringen ved type 2-diabetes. Full text in Research Archive
• Qvigstad, Elisabeth; Mostad, Ingrid Løvold; Bjerve, Kristian S & Grill, Valdemar (1999). Acute reduction of fatty acids increases insulin secretion in type-2 diabetes. Full text in Research Archive
• Qvigstad, Elisabeth; Mostad, Ingrid Løvold; Bjerve, Kristian S & Grill, Valdemar (1999). Lowering of fatty acids by acipimox improves insulin secretion in type-2 diabetes. Full text in Research Archive

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