Elisabeth R Mathiesen

Copenhagen University Hospital, København, Capital Region, Denmark

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Publications (228)

  • [Show abstract] [Hide abstract] ABSTRACT: Prenatal exposure to maternal hyperglycemia is associated with increased risk of later adverse metabolic health. Changes in regulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) in skeletal muscle and subcutaneous adipose tissue (SAT) is suggested to play a role in developmental programming of dysmetabolism based on studies in human subjects exposed to abnormal intrauterine environment e.g. low birth weight individuals.We studied 206 adult offspring of women with gestational diabetes (O-GDM), type 1 diabetes (O-T1DM) and from the background population (O-BP) including clinical examination, oral glucose tolerance test, gene expression and DNA methylation of PPARGC1A in skeletal muscle and SAT.Plasma glucose was significantly higher for both O-GDM and O-T1DM compared to O-BP (p<0.05). PPARGC1A gene expression in muscle was lower in O-GDM compared to O-BP (p=0.0003) while no differences were found between O-T1DM and O-BP in either tissue. Muscle and SAT PPARGC1A DNA methylation percentage were similar in all groups.Decreased PPARGC1A gene expression in muscle has previously been associated with abnormal insulin function and may thus contribute to the increased risk of metabolic disease in O-GDM. The unaltered muscle PPARGC1A gene expression in O-T1DM suggests factors other than intrauterine hyperglycemia may contribute to the decreased PPARGC1A expression in O-GDM.
    Article · Jul 2016 · Diabetes
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    [Show abstract] [Hide abstract] ABSTRACT: Objective: Exposure to maternal diabetes in utero may have a negative impact on the developing brain. The objective was to examine long-term cognitive consequences of intrauterine hyperglycemia in adolescent offspring of women with type 1 diabetes and to ascertain a possible association with maternal HbA1c. Research design and methods: Offspring of a prospectively followed cohort of women with type 1 diabetes (n = 277) participated in a follow-up examination at the age of 13-19 years. A control group from the background population was identified (n = 301). Cognitive function was evaluated using Reynolds Intellectual Assessment Scales and classified into indices of composite intelligence, verbal and nonverbal intelligence, and composite memory. Frequencies of reading and writing problems and attendance to classes for children with learning difficulties were assessed. Results: Offspring of women with type 1 diabetes scored lower in all normalized and standardized intelligence indices compared with controls: composite intelligence (95.7 vs. 100, P = 0.001), verbal intelligence (96.2 vs. 100, P = 0.004), nonverbal intelligence (96.4 vs. 100, P = 0.008), and composite memory (95.7 vs. 100, P = 0.001). A higher frequency of diabetes-exposed offspring had parent-reported learning difficulties in primary school. Differences between groups remained after adjustment for confounders and potential mediators. We found no direct association between maternal HbA1c and offspring cognitive function in the exposed group. Conclusions: Adolescent offspring of women with type 1 diabetes had lower cognitive function compared with a control group, also after adjustment for confounders and potential mediators. These differences may reflect direct harmful effects of maternal diabetes on neurodevelopment in the offspring.
    Full-text Article · Jun 2016 · Diabetes Care
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    Full-text Article · Jun 2016 · Diabetes
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    [Show abstract] [Hide abstract] ABSTRACT: Gestational diabetes mellitus (GDM) is defined as glucose intolerance of varying severity and is present in about 2–6% of all pregnancies in Europe, making it one of the most common pregnancy disorders. Aside from the short-term maternal, fetal and neonatal consequences associated with GDM, there are long-term consequences for both mother and child. Although maternal glucose tolerance often normalises shortly after pregnancy, women with GDM have a substantially increased risk of developing type 2 diabetes later in life. Studies have reported that women are more than seven times as likely to develop diabetes after GDM, and that approximately 50% of mothers with GDM will develop diabetes within 10 years, making GDM one of the strongest predictors of type 2 diabetes. In women with previous GDM, development of type 2 diabetes can be prevented or delayed by lifestyle intervention and/or medical treatment. Systematic follow-up programmes would be ideal to prevent progression of GDM to diabetes, but such programmes are unfortunately lacking in the routine clinical set-up in most countries. Studies have found that the risks of obesity, the metabolic syndrome, type 2 diabetes and impaired insulin sensitivity and secretion in offspring of mothers with GDM are two- to eightfold those in offspring of mothers without GDM. The underlying pathogenic mechanisms behind the abnormal metabolic risk profile in offspring are unknown, but epigenetic changes induced by exposure to maternal hyperglycaemia during fetal life are implicated. Animal studies indicate that treatment can prevent long-term metabolic complications in offspring, but this remains to be confirmed in humans. Thus, diabetes begets diabetes and it is likely that GDM plays a significant role in the global diabetes epidemic. This review summarises a presentation given at the ‘Gestational diabetes: what’s up?’ symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Marja Vääräsmäki, DOI: 10. 1007/ s00125-016-3976-6, and by Cuilin Zhang and colleagues, DOI: 10. 1007/ s00125-016-3979-3) and an overview by the Session Chair, Kerstin Berntorp (DOI: 10. 1007/ s00125-016-3975-7).
    Full-text Article · May 2016 · Diabetologia
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    [Show abstract] [Hide abstract] ABSTRACT: Background: -Maternal diabetes is associated with an increased risk of offspring congenital heart disease (CHD); however, the causal mechanism is poorly understood. We further investigated this association in a Danish nationwide cohort. Methods and results: -In a national cohort study, we identified 2,025,727 persons born in 1978-2011, among them 7,296 (0.36%) persons exposed to maternal pre-gestational diabetes. Pre-gestational diabetes was identified using the National Patient Register and individual-level information on all prescriptions filled in Danish pharmacies. Persons with CHD (n=16,325) were assigned to embryologically-related cardiac phenotypes. The CHD prevalence in the offspring of mothers with pre-gestational diabetes was 318 per 10,000 live births (n=232), compared with a baseline risk of 80 per 10,000; the adjusted relative risk (RR) for CHD was 4.00 (95% confidence interval (CI) 3.51-4.53). The association was not modified by year of birth, maternal age at diabetes onset, or diabetes duration, and CHD risks associated with type 1 (insulin-dependent) and type 2 (insulin-independent) diabetes did not differ significantly. Persons born to women with previous acute diabetes complications had a higher CHD risk than those exposed to maternal diabetes without complications (RR 7.62, 95% CI 5.23-10.6, and RR 3.49, 95% CI 2.91-4.13, respectively, p=0.0004). All specific CHD phenotypes were associated with maternal pre-gestational diabetes (RR range: 2.74-13.8). Conclusions: -The profoundly increased CHD risk conferred by maternal pre-gestational diabetes neither changed over time nor differed by diabetes subtype. The association with acute pre-gestational diabetes complications was particularly strong, suggesting a role for glucose in the causal pathway.
    Full-text Article · May 2016 · Circulation
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    Full-text Article · May 2016 · Diabetes Care
  • Michael Concillado · Henrik Lund-Andersen · Elisabeth R Mathiesen · Michael Larsen
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: To describe the management of diabetic macular edema during pregnancy with the use of a dexamethasone slow-release intravitreal implant. Design: Retrospective, observational, consecutive case series. Methods: The study included 5 pregnant women who presented with diabetic macular edema during pregnancy in the period from 2011 to 2014. Review of charts and photographs comprised best-corrected visual acuity (BCVA), foveal center field thickness assessed by optical coherence tomography, blood pressure, glycated hemoglobin, medications and changes in such parameters after implant injection. Results: Diabetic macular edema involving the foveal center was observed between gestational weeks 9 and 23 in 10 eyes in 5 patients. Dexamethasone intravitreal implant injection was given 10 times in 9 eyes with a mean pre-injection center field retinal thickness of 535 μm (range 239-727 μm) and a mean pre-injection best-corrected visual acuity (BCVA) of 63 approxETDRS (approximated Early Treatment Diabetic Retinopathy Study) letters (range 50-77 letters). One eye was unavailable for follow-up. In 7 of 8 eyes injection was followed, within 3 weeks, by a greater than 145 μm reduction in foveal center field thickness and in 6 of 8 eyes by an increase in BCVA of 5 or more approxETDRS letters. A mild transient rise in intraocular pressure occurred in 3 out of 8 eyes. Conclusion: Diabetic macular edema involving the foveal center that presented during pregnancy responded promptly to intravitreal dexamethasone therapy by foveal thickness reduction and visual acuity improvement without clinically significant intraocular pressure increases.
    Article · Feb 2016 · American Journal of Ophthalmology
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    Lene Ringholm · Julie Agner Damm · Marianne Vestgaard · [...] · Elisabeth R. Mathiesen
    [Show abstract] [Hide abstract] ABSTRACT: In women with preexisting diabetes and nephropathy or microalbuminuria, it is important to deliver careful preconception counselling to assess the risk for the mother and the foetus, for optimizing glycaemic status and to adjust medical treatment. If serum creatinine is normal in early pregnancy, kidney function is often preserved during pregnancy, but complications such as severe preeclampsia and preterm delivery are still common. Perinatal mortality is now comparable with that in women with diabetes and normal kidney function. Besides strict glycaemic control before and during pregnancy, early and intensive antihypertensive treatment is important to optimize pregnancy outcomes. Methyldopa, labetalol, nifedipine and diltiazem are considered safe, whereas angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers should be stopped before or at confirmation of pregnancy. Supplementation with folic acid in early pregnancy and low-dose aspirin from 10 to 12 weeks reduces the risk of adverse pregnancy outcomes. During breastfeeding, several ACE inhibitors are considered safe.
    Full-text Article · Feb 2016 · Current Diabetes Reports
  • [Show abstract] [Hide abstract] ABSTRACT: Objective To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes. Design and setting Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design, conducted at 8 hospitals in Denmark. Participants and interventions Participants with type 2 diabetes (glycated haemoglobin (HbA1c)≥7.5% (≥58 mmol/mol), body mass index >25 kg/m2) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1–3 times daily (n=137) versus insulin aspart 3 times daily in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA1c≤7.0% (≤53 mmol/mol). Outcomes Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight, and hypoglycaemic and serious adverse events were other prespecified outcomes. Results Carotid IMT change did not differ between groups (biphasic −0.009 mm (95% CI −0.022 to 0.004), aspart+detemir 0.000 mm (95% CI −0.013 to 0.013), detemir −0.012 mm (95% CI −0.025 to 0.000)). HbA1c was more reduced with biphasic (−1.0% (95% CI −1.2 to −0.8)) compared with the aspart+detemir (−0.4% (95% CI −0.6 to −0.3)) and detemir (−0.3% (95% CI −0.4 to −0.1)) groups (p<0.001). Weight gain was higher in the biphasic (3.3 kg (95% CI 2.7 to 4.0) and aspart+detemir (3.2 kg (95% CI 2.6 to 3.9)) compared with the detemir group (1.9 kg (95% CI 1.3 to 2.6)). Insulin dose was higher with detemir (1.6 IU/kg/day (95% CI 1.4 to 1.8)) compared with biphasic (1.0 IU/kg/day (95% CI 0.9 to 1.1)) and aspart+detemir (1.1 IU/kg/day (95% CI 1.0 to 1.3)) (p<0.001). Number of participants with severe hypoglycaemia and serious adverse events did not differ. Conclusions Carotid IMT change did not differ between 3 insulin regimens despite differences in HbA1c, weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results. Trial registration number NCT00657943.
    Article · Feb 2016 · BMJ Open
  • [Show abstract] [Hide abstract] ABSTRACT: Objective To assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 diabetes. Design and setting Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design conducted at eight hospitals in Denmark. Participants and interventions 412 participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥7.5% (≥58 mmol/mol); body mass index >25 kg/m2) were in addition to open-labelled insulin treatment randomly assigned 1:1 to 18 months blinded metformin (1 g twice daily) versus placebo, aiming at an HbA1c ≤7.0% (≤53 mmol/mol). Outcomes The primary outcome was change in the mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight and hypoglycaemic and serious adverse events were other prespecified outcomes. Results Change in the mean carotid IMT did not differ significantly between the groups (between-group difference 0.012 mm (95% CI −0.003 to 0.026), p=0.11). HbA1c was more reduced in the metformin group (between-group difference −0.42% (95% CI −0.62% to −0.23%), p<0.001)), despite the significantly lower insulin dose at end of trial in the metformin group (1.04 IU/kg (95% CI 0.94 to 1.15)) compared with placebo (1.36 IU/kg (95% CI 1.23 to 1.51), p<0.001). The metformin group gained less weight (between-group difference −2.6 kg (95% CI −3.3 to −1.8), p<0.001). The groups did not differ with regard to number of patients with severe or non-severe hypoglycaemic or other serious adverse events, but the metformin group had more non-severe hypoglycaemic episodes (4347 vs 3161, p<0.001). Conclusions Metformin in combination with insulin did not reduce carotid IMT despite larger reduction in HbA1c, less weight gain, and smaller insulin dose compared with placebo plus insulin. However, the trial only reached 46% of the planned sample size and lack of power may therefore have affected our results. Trial registration number NCT00657943; Results.
    Article · Feb 2016 · BMJ Open
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    [Show abstract] [Hide abstract] ABSTRACT: Introduction. We explored beliefs, perceived barriers, and preferences regarding lifestyle changes among overweight European pregnant women to help inform the development of future lifestyle interventions in the prevention of gestational diabetes mellitus. Methods. An explorative mixed methods, two-staged study was conducted to gather information from pregnant European women (BMI ≥ 25 kg/m2). In three European countries 21 interviews were conducted, followed by 71 questionnaires in six other European countries. Content analysis and descriptive and chi-square statistics were applied ( p < 0.05 ). Results. Women preferred to obtain detailed information about their personal risk. The health of their baby was a major motivating factor. Perceived barriers for physical activity included pregnancy-specific issues such as tiredness and experiencing physical complaints. Insufficient time was a barrier more frequently reported by women with children. Abstaining from snacking was identified as a challenge for the majority of women, especially for those without children. Women preferred to obtain support from their partner, as well as health professionals and valued flexible lifestyle programs. Conclusions. Healthcare professionals need to inform overweight pregnant women about their personal risk, discuss lifestyle modification, and assist in weight management. Lifestyle programs should be tailored to the individual, taking into account barriers experienced by overweight first-time mothers and multipara women.
    Full-text Article · Jan 2016 · Journal of pregnancy
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    [Show abstract] [Hide abstract] ABSTRACT: Plasma levels of the inflammatory marker YKL-40 was investigated in 597 adult offspring born to women with and without diabetes during pregnancy. No association between fetal exposure to maternal hyperglycemia and levels of YKL-40 was found. However, female sex and increasing BMI in the offspring were associated to YKL-40.
    Full-text Article · Jan 2016
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    [Show abstract] [Hide abstract] ABSTRACT: Glucagon is believed to be a pancreas-specific hormone and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from alpha cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy controls to a 75g-oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich enzyme-linked immunosorbent assay and mass-spectrometry-based proteomics) and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy.
    Full-text Article · Dec 2015 · Diabetes
  • [Show abstract] [Hide abstract] ABSTRACT: Polycystic ovary syndrome (PCOS) is associated with insulin resistance, infertility, obesity and gestational complications. Metformin is widely used in fertility treatment of women with PCOS, due to a suggested positive effect of continued metformin treatment beyond the first trimester on pregnancy complications. Larger randomized trials have failed to confirm this. Metformin treatment has not been found to be superior to insulin treatment in women with gestational diabetes and may be associated with long-term consequences in the children in the form of overweight and disturbed glucose metabolism.
    Article · Dec 2015 · Ugeskrift for laeger
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    Lene Ringholm · Anders Juul · Ulrik Pedersen-Bjergaard · [...] · Elisabeth R. Mathiesen
    [Show abstract] [Hide abstract] ABSTRACT: Objective: To evaluate whether levels of placental growth hormone (GH) and Insulin-like Growth Factor-I (IGF-I) are associated with development of LGA infants in pregnant women with type 1 diabetes. Design: Observational study of 103 consecutive pregnant women with long-term type 1 diabetes and median HbA1c 6.6% (range 4.9-10.5) (49mmol/mol (30-91)) in early pregnancy. At 8, 14, 21, 27 and 33weeks weight was recorded and blood was sampled for measurements of placental GH, IGF-I and HbA1c. LGA was defined as birth weight >90th percentile after adjustment for gender and gestational age. Results: Throughout pregnancy placental GH levels were similar in 51 (50%) women delivering LGA infants compared with the remaining women except at 8. weeks where placental GH levels were lower in women with LGA infants (1.1. ng/ml (0.1-4.3) vs. 1.7 (0.3-11.7), p = 0.04). IGF-I levels were similar in women with and without LGA infants (p = 0.97). Gestational age at first blood sampling was similar in women with and without LGA infants (60. days (37-89) vs. 61.5 (42-94), p = 0.42). Placental GH levels at 14. weeks correlated negatively with weight gain in early pregnancy (r = -0.32, p = 0.002). As predictors of LGA infants, multivariate logistic regression analysis identified placental GH levels at 8. weeks (OR 0.4 (95% CI: 0.2-0.9), p = 0.02), HbA1c at 33. weeks (3.6 (1.3-9.9), p = 0.01) and parity ≥. 1 (3.1 (1.3-7.5), p = 0.01) after adjustment for pre-pregnancy BMI. Conclusions: Women delivering LGA infants had lower placental GH levels in early pregnancy. Growth factors and maternal weight gain in early pregnancy may be important for healthy fetal growth.
    Full-text Article · Nov 2015
  • Article · Nov 2015 · Wiener klinische Wochenschrift
  • Camilla W. Herskin · Edna Stage · Charlotte Barfred · [...] · Elisabeth R. Mathiesen
    [Show abstract] [Hide abstract] ABSTRACT: Objective: To investigate the prevalence of long-term breastfeeding among women with type 2 diabetes compared to women with type 1 diabetes and to identify predictors of long-term breastfeeding for women with pre-gestational diabetes. Methods: In total, 149 women with diabetes were interviewed about long-term breastfeeding, defined as any breastfeeding 4 months postpartum. Results: Ninety-eight percent of the women aimed to breastfeed. At time of discharge, any breastfeeding was frequent for both groups of women (86% versus 93%, p = 0.17). However, 4 months postpartum, the 44 women with type 2 diabetes showed significantly lower prevalence of breastfeeding than the 105 women with type 1 diabetes (34% versus 61%, p < 0.01). Number of feedings in the first 24 h was an independent positive predictor, whereas pre-pregnancy body mass index (BMI) and smoking were independent negative predictors of long-term breastfeeding. Conclusion: The prevalence of long-term breastfeeding among women with type 2 diabetes was considerably lower than in women with type 1 diabetes. Number of feedings in the first 24 h was positive and BMI and smoking were negative predictors of long-term breastfeeding in women with pre-gestational diabetes.
    Article · Oct 2015 · Journal of Maternal-Fetal and Neonatal Medicine
  • Anna L. Secher · Elisabeth R. Mathiesen · Henrik U. Andersen · [...] · Lene Ringholm
    Article · Sep 2015 · Diabetes Research and Clinical Practice
  • Article · Sep 2015 · Wiener klinische Wochenschrift
  • Conference Paper · Sep 2015

Publication Stats

7k Citations


  • 2004-2015
    • Copenhagen University Hospital
      København, Capital Region, Denmark
    • Odense University Hospital
      Odense, South Denmark, Denmark
  • 2013
    • Tel Aviv University
      • Sackler Faculty of Medicine
      Tell Afif, Tel Aviv, Israel
  • 2011
    • University of Copenhagen
      København, Capital Region, Denmark
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2010
    • University of Southern California
      • Department of Obstetrics and Gynecology
      Los Ángeles, California, United States
  • 2007
    • Frederiksberg Hospital
      Фредериксберг, Capital Region, Denmark
    • Novo Nordisk
      København, Capital Region, Denmark
  • 2006
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 1992-1999
    • Steno Diabetes Center
      • Epidemiology
      Gjentofte, Capital Region, Denmark
  • 1985
    • Bispebjerg Hospital, Copenhagen University
      København, Capital Region, Denmark