Elisabeth R Mathiesen

IT University of Copenhagen, København, Capital Region, Denmark

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Publications (185)900.51 Total impact

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    ABSTRACT: Ways to prevent gestational diabetes mellitus (GDM) remain unproven. We compared the impact of three lifestyle interventions (healthy eating [HE], physical activity [PA], and both HE and PA [HE+PA]) on GDM risk in a pilot multicenter randomized trial. Pregnant women at risk for GDM (BMI ≥29 kg/m(2)) from nine European countries were invited to undertake a 75-g oral glucose tolerance test before 20 weeks gestation. Those without GDM were randomized to HE, PA, or HE+PA. Women received five face-to-face and four optional telephone coaching sessions, based on the principles of motivational interviewing. A gestational weight gain (GWG) <5 kg was targeted. Coaches received standardized training and an intervention toolkit. Primary outcome measures were GWG, fasting glucose, and insulin sensitivity (HOMA) at 35-37 weeks. Among the 150 trial participants, 32% developed GDM by 35-37 weeks and 20% achieved GWG <5 kg. HE women had less GWG (-2.6 kg [95% CI -4.9, -0.2]; P = 0.03) and lower fasting glucose (-0.3 mmol/L [-0.4, -0.1]; P = 0.01) than those in the PA group at 24-28 weeks. HOMA was comparable. No significant differences between HE+PA and the other groups were observed. An antenatal HE intervention is associated with less GWG and lower fasting glucose compared with PA alone. These findings require a larger trial for confirmation but support the use of early HE interventions in obese pregnant women. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes care 06/2015; DOI:10.2337/dc15-0360 · 8.57 Impact Factor
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    ABSTRACT: We aimed to investigate metabolic risk factors, insulin sensitivity and insulin secretion in adolescent offspring of mothers with type 1 diabetes compared with offspring of non-diabetic mothers. During 1993-1999, pregnancies of women with type 1 diabetes in Denmark were prospectively reported to a central registry in the Danish Diabetes Association. Data included information on maternal demography, diabetes status and pregnancy outcome. We invited 746 eligible children from this cohort (index offspring) to a follow-up examination. Control offspring were identified through The Danish Central Office of Civil Registration and matched with respect to date of birth, sex and postal code. Anthropometric measurements and blood sampling for metabolic characterisation, including an oral glucose tolerance test, were performed. We examined 278 index offspring (mean age 16.7 years; range 13.0-19.8 years) and 303 control offspring (mean age 16.8 years; range 13.5-20.4 years). Index offspring had higher BMI SD score (0.44: 95% CI 0.21, 0.66) compared with controls, after adjustments for pubertal development and maternal pre-pregnancy BMI. Furthermore, index offspring had a higher prevalence of components included in metabolic syndrome and prediabetes (impaired fasting glucose and/or impaired glucose tolerance), with reduced insulin sensitivity and relative insulin secretion deficiency, compared with controls. Maternal HbA1c levels in pregnancy were not directly associated with offspring metabolic outcomes. Adolescent offspring of mothers with type 1 diabetes had a less favourable metabolic profile and higher frequency of prediabetes than the background population. Significant associations between these outcomes and maternal HbA1c levels in pregnancy could not be demonstrated. ClinicalTrials.gov NCT01559181.
    Diabetologia 04/2015; DOI:10.1007/s00125-015-3589-5 · 6.88 Impact Factor
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    ABSTRACT: Continuous glucose monitoring (CGM) is increasingly used to assess glucose control in diabetes. The objective was to examine how analysis of glucose data might improve our understanding of the role temporal glucose variation has on large-for-gestational-age (LGA) infants born to women with diabetes. Functional data analysis (FDA) was applied to 1.68 million glucose measurements from 759 measurement episodes, obtained from two previously published randomized controlled trials of CGM in pregnant women with diabetes. A total of 117 women with type 1 diabetes (n = 89) and type 2 diabetes (n = 28) who used repeated CGM during pregnancy were recruited from secondary care multidisciplinary obstetric clinics for diabetes in the U.K. and Denmark. LGA was defined as birth weight ≥90th percentile adjusted for sex and gestational age. A total of 54 of 117 (46%) women developed LGA. LGA was associated with lower mean glucose (7.0 vs. 7.1 mmol/L; P < 0.01) in trimester 1, with higher mean glucose in trimester 2 (7.0 vs. 6.7 mmol/L; P < 0.001) and trimester 3 (6.5 vs. 6.4 mmol/L; P < 0.01). FDA showed that glucose was significantly lower midmorning (0900-1100 h) and early evening (1900-2130 h) in trimester 1, significantly higher early morning (0330-0630 h) and throughout the afternoon (1130-1700 h) in trimester 2, and significantly higher during the evening (2030-2330 h) in trimester 3 in women whose infants were LGA. FDA of CGM data identified specific times of day that maternal glucose excursions were associated with LGA. It highlights trimester-specific differences, allowing treatment to be targeted to gestational glucose patterns. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes care 04/2015; DOI:10.2337/dc15-0070 · 8.57 Impact Factor
  • Peter Damm, Elisabeth R Mathiesen
    Nature Reviews Endocrinology 04/2015; 11(6). DOI:10.1038/nrendo.2015.54 · 12.96 Impact Factor
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    ABSTRACT: AimTo explore the role of early pregnancy health-related quality of life, anxiety, depression and locus of control for pregnancy outcome in women with pregestational diabetes.Methods This was a cohort study of 148 pregnant women with pregestational diabetes (118 with Type 1 diabetes and 30 with Type 2 diabetes), who completed three internationally validated questionnaires: the 36-item Short-Form Health Survey, the Hospital Anxiety and Depression Scale and the Multidimensional Health Locus of Control survey at 8 weeks. Selected pregnancy outcomes were preterm delivery (<37 weeks) and large for gestational age infants (birth weight >90th percentile). Differences between groups in the questionnaires were analysed using an unpaired t-test.ResultsWomen with preterm deliveries (n=28) had lower (i.e. worse) mean (sd) quality-of-life scores for the two 36-item Short-Form Health Survey scales, Role-Emotional domain [58.3 (38.1) vs. 82.9 (31.3); P=0.0005] and Mental Health domain [67.7 (20.4) vs. 75.2 (15.8), P=0.04], and lower scores for the 36-item Short-Form Health Survey Mental Component Summary (42.8 (13.1) vs. 48.8 (9.7), P=0.03) in early pregnancy, compared with women with term deliveries. Depression symptoms (Hospital Anxiety and Depression Scale depression score ≥8) were more frequent in women with preterm vs. term deliveries (seven (25%) vs. six women (5%); P=0.003), while levels of anxiety and locus of control were similar in these two groups. No difference in early pregnancy scores for health-related quality of life, anxiety, depression and locus of control were seen in women delivering large or appropriate for gestational age infants.Conclusions Poor mental quality of life and the presence of depressive symptoms in early pregnancy were associated with preterm delivery in women with pregestational diabetes.This study was accepted in abstract form as a poster at the 50th European Association for the Study of Diabetes Annual Meeting, Vienna, Austria, 15–19 September 2014 and for the 46th Annual Meeting of the Diabetic Pregnancy Study Group, Budapest, Hungary, 2–5 October 2014.This article is protected by copyright. All rights reserved.
    Diabetic Medicine 04/2015; DOI:10.1111/dme.12777 · 3.06 Impact Factor
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    ABSTRACT: Fetal exposure to maternal diabetes is associated with increased risk of type 2 diabetes (T2DM) later in life. The pathogenesis of T2DM involves dysfunction of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), as well as hyperglucagonemia. Our aim was to investigate circulating plasma levels of GLP-1, GIP and glucagon during OGTT in adult offspring of women with diabetes in pregnancy. Follow-up study of 567 offspring, aged 18-27 years. We included two groups exposed to maternal diabetes in utero: Offspring of women with diet-treated gestational diabetes mellitus (O-GDM, N=163) or type 1 diabetes (O-T1DM, N=146). Two reference groups were included: offspring of women with risk factors for GDM, but normoglycemia during pregnancy (O-NoGDM, N=133) and offspring from the background population (O-BP, N=125). The subjects underwent a 75-g oral glucose tolerance test (OGTT) with venous samples at 0, 30, 120 min. Fasting plasma levels of GLP-1 were lower in the two diabetes-exposed groups compared to O-BP (O-GDM: p=0.040; O-T1DM: p=0.008). Increasing maternal blood glucose during OGTT in pregnancy was associated with reduced postprandial suppression of glucagon in the offspring. Lower levels of GLP-1 and higher levels of glucagon during the OGTT were present in offspring characterized by overweight or pre-diabetes/T2DM at follow-up, irrespective of exposure status. Lower levels of fasting GLP-1 and impaired glucagon suppression in adult offspring exposed to maternal diabetes during pregnancy are diabetogenic traits that may contribute to glucose intolerance in these persons but further investigations are needed.
    Journal of Clinical Endocrinology &amp Metabolism 03/2015; 100(5):jc20143978. DOI:10.1210/jc.2014-3978 · 6.31 Impact Factor
  • Elisabeth R Mathiesen
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    ABSTRACT: In this issue of Diabetologia, Klemetti and colleagues [1] present the results of the largest evaluation of clinical care in pregnant women with type 1 diabetes and diabetic nephropathy ever. This paper adds knowledge about the outcome, in present time, of these diabetic patients. The study is population based and covers more than 100 pregnant women with type 1 diabetes and nephropathy. A careful and proper evaluation of patient records was conducted, and the paper comes from a well-known centre with a long tradition for research and development within the field of diabetes and pregnancy.The good news is that the perinatal mortality rate is reported to be 3% for these patients. This rate is comparable with that for diabetic patients without kidney involvement [2]. Advancements in ultrasound fetal flow measurements may have contributed to the prevention of stillbirths, and the intensification of the care of preterm infants may have contributed to the prevention of early neonatal deaths. ...
    Diabetologia 02/2015; 58(4). DOI:10.1007/s00125-015-3530-y · 6.88 Impact Factor
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    ABSTRACT: Abstract Aim: To evaluate whether initiation of anti-hypertensive treatment with methyldopa affects fetal hemodynamics in women with pregestational diabetes. Methods: Prospective study of unselected singleton pregnant women with diabetes (seven type 1 and two type 2 diabetes), normal blood pressure and kidney function at pregnancy booking. Methyldopa treatment was initiated at blood pressure >135/85 mmHg and/or urinary albumin excretion (UAE) >300 mg/g creatinine. Pulsatility indices (PI) of the uterine, umbilical, middle cerebral arteries before and 1 week after initiation of methyldopa treatment (250 mg three times daily) was performed and the cerebro-placental ratio (CPR) was calculated. Results: Methyldopa treatment was initiated at median 249 (range 192-260) gestational days, mainly due to gestational hypertension (n = 7). Blood pressure declined from 142 (112-156)/92 (76-103) mmHg before to 129 (108-144)/82 (75-90) mmHg after initiation of methyldopa treatment (p = 0.11 and 0.04 for systolic and diastolic blood pressure, respectively). There were no significant changes in the umbilical artery PI (0.82 (0.72-1.40) versus 0.87 (0.64-0.95), p = 0.62) or CPR (1.94 (0.96-2.33) versus 1.78 (1.44-2.76), (p = 0.73). Gestational age was 265 (240-270) d. Apgar scores were normal. Conclusions: Stable Doppler flow velocity waveforms were documented after initiation of methyldopa treatment for pregnancy-induced hypertensive disorders in this cohort of pregnant women with pregestational diabetes.
    Journal of Maternal-Fetal and Neonatal Medicine 02/2015; DOI:10.3109/14767058.2015.1010198 · 1.21 Impact Factor
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    ABSTRACT: Late familial hyperinsulinemic hypoglycemia is characterized by recurrent episodes of hypoglycemia and an inappropriate insulinemic response. Treatment with octreotide (somatostatin analogue) reduces the prevalence of clinical significant hypoglycemia and might be beneficial during pregnancy. To our knowledge this is the first report of a woman with late familial hyperinsulinemic hypoglycemia experiencing pregnancies with and without octreotide treatment. A 35-year-old Caucasian woman known to suffer from late familial hyperinsulinemic hypoglycemia due to a well-known mutation in the insulin receptor gene has been pregnant 6 times. The patient was treated with injections of Sandostatin LAR® (octreotide) during the first four pregnancies. Her first pregnancy in 1999 was unknown until approximately 25th gestational weeks with fatal intrauterine growth retardation. The following two pregnancies were terminated on parental request after a chorion villus biopsy revealed the mutation causing late familial hyperinsulinemic hypoglycemia. During the fourth pregnancy, in which the fetus also had the mutation, serial ultrasound examinations showed a small fetus with appropriate growth. At birth the girl was small for gestational age. She was admitted to the neonatal special care unit due to low blood glucose and intravenous glucose and early feeding was initiated. One day old, her condition deteriorated with signs of an abdominal catastrophe indicating necrotizing enterocolitis. After two laparotomies - both confirming necrotizing enterocolitis - the child died 8 days after birth.In the following two pregnancies Sandostatin LAR® was stopped before pregnancy and the patient was treated only with diet restriction and intensive glucose monitoring. Both pregnancies ended successfully. One child carried the mutation and was small for gestational age at birth while the other child did not carry the mutation and had normal birth weight. In a woman with late familial hyperinsulinemic hypoglycemia octreotide was given during the first four pregnancies resulting in 2 cases of early termination of pregnancy on parental request and 2 cases of inappropriate fetal growth and unviable outcome. The following two pregnancies treated with diet only had a successful outcome.
    BMC Research Notes 11/2014; 7(1):804. DOI:10.1186/1756-0500-7-804
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    ABSTRACT: Background Uraemia is associated with a highly increased risk of cardiovascular disease. Mannose-binding lectin (MBL) has been shown to be involved in cardiovascular pathophysiology and a protective effect of MBL is suggested. The purpose of the present study was to evaluate a potential impact of MBL on vascular parameters in uraemic patients. Methods A cohort of 98 patients with end stage renal disease (ESRD) awaiting kidney transplantation had pulse wave velocity (PWV) and augmentation index (AIX) examined by tonometry and endothelial dependent flow-mediated (FMD) and endothelial independent nitroglycerin-induced (NID) dilatory capacities of the brachial artery measured by ultrasound. An oral glucose tolerance test (OGTT) was performed and serum levels of MBL were measured using Luminex xMAP bead array technology. Results The cohort was divided in two groups according to MBL-concentration below or above the median concentration. These groups were comparable regarding age, BMI, and duration of ESRD. PWV was significantly lower in the group with high MBL levels compared to the group with low MBL levels and trends toward better AIX and higher insulin sensitivity (ISI) was also seen in the group with high MBL levels. No difference was seen in FMD and NID. Conclusions High levels of MBL are associated with lower PWV and the use of antihypertensive drugs in a cohort of patients with ESRD awaiting kidney transplantation suggesting a beneficial role of high levels of MBL on arterial stiffness in uraemia.
    BMC Nephrology 10/2014; 15(1):162. DOI:10.1186/1471-2369-15-162 · 1.52 Impact Factor
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    ABSTRACT: OBJECTIVE We evaluate the association between gestational weight gain and offspring birth weight in singleton term pregnancies of women with type 1 diabetes. RESEARCH DESIGN AND METHODS One hundred fifteen consecutive women referred at <14 weeks were retrospectively classified as underweight (prepregnancy BMI <18.5 kg/m(2); n = 1), normal weight (18.5-24.9; n = 65), overweight (25.0-29.9; n = 39), or obese (>= 30.0; n = 10). Gestational weight gain was categorized as excessive, appropriate, or insufficient according to the Institute of Medicine recommendations for each BMI class. Women with nephropathy, preeclampsia, and/or preterm delivery were excluded because of restrictive impact on fetal growth and limited time for total weight gain. RESULTS HbA(1c) was comparable at similar to 6.6% (49 mmol/mol) at 8 weeks and similar to 6.0% (42 mmol/mol) at 36 weeks between women with excessive (n = 62), appropriate (n = 37), and insufficient (n = 16) gestational weight gain. Diabetes duration was comparable, and median prepregnancy BMI was 25.3 (range 18-41) vs. 23.5 (18-31) vs. 22.7 (20-30) kg/m(2) (P = 0.05) in the three weight gain groups. Offspring birth weight and birth weight SD score decreased across the groups (3,681 [2,374-4,500] vs. 3,395 [2,910-4,322] vs. 3,295 [2,766-4,340] g [P = 0.02] and 1.08 [-1.90 to 3.25] vs. 0.45 [-0.83 to 3.18] vs. -0.02 [-1.51 to 2.96] [P = 0.009], respectively). In a multiple linear regression analysis, gestational weight gain (kg) was positively associated with offspring birth weight (g) (beta = 19; P = 0.02) and birth weight SD score (beta = 0.06; P = 0.008) when adjusted for prepregnancy BMI, HbA1c at 36 weeks, smoking, parity, and ethnicity. CONCLUSIONS Higher gestational weight gain in women with type 1 diabetes was associated with increasing offspring birth weight independent of glycemic control and prepregnancy BMI.
    Diabetes Care 10/2014; 37(10):2677-84. DOI:10.2337/dc14-0896 · 8.57 Impact Factor
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    ABSTRACT: Objective Several studies have shown an increase in beta cell mass during pregnancy. Somatolactogenic hormones are known to stimulate proliferation of existing beta cells in rodents whereas the mechanism in humans is still unclear. We hypothesize that in addition to somatolactogenic hormones there are other circulating factors involved in beta cell adaptation to pregnancy. This study aimed at screening for potential pregnancy associated circulating beta cell growth factors.SamplesSerum samples from non-pregnant and pregnant women.Methods The effect of serum from pregnant women on the proliferation of rat beta cells was studied using [3H]thymidine incorporation and EdU proliferation assays. In addition, serum from pregnant and non-pregnant women was fractionated by gel filtration and high performance liquid chromatography. The fractionated serum was screened for mitogenic activity in INS-1E cells. Proteins and peptides in mitogenic active serum fractions were identified by amino acid sequencing and mass spectrometry.Main outcome measuresPresence of circulating beta cell proliferating factors.ResultsLate gestational pregnancy serum significantly increased proliferation of rat beta cells compared to early pregnancy and non-pregnancy. The mitogenic active serum fractions contained proteins and peptides derived from kininogen-1, fibrinogen-alpha, alpha1-antitrypsin, apolipoprotein-A1, placental lactogen, angiotensinogen and serum albumin.Conclusion Pregnancy serum is able to stimulate proliferation of rat beta cells. We have identified several circulating factors that may contribute to beta cell adaptation to pregnancy. Further studies are needed in order to elucidate their possible role in glucose homeostasis in the mother and her offspring.This article is protected by copyright. All rights reserved.
    Acta Obstetricia Et Gynecologica Scandinavica 09/2014; 93(11). DOI:10.1111/aogs.12505 · 1.99 Impact Factor
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    ABSTRACT: AimsTo evaluate fetal growth in relation to gestational weight gain in women with Type 2 diabetes.MethodsA retrospective cohort study of 142 consecutive pregnancies in 28 women of normal weight, 39 overweight women and 75 obese women with Type 2 diabetes (pre-pregnancy BMI <25, 25–29.9, ≥30 kg/m2, respectively). Gestational weight gain was categorized as excessive (exceeding the US Institute of Medicine recommendations) or as non-excessive (within or below the Institute of Medicine recommendations).ResultsExcessive and non-excessive gestational weight gain were seen in 61 (43%) and 81 women (57%) with a median (range) gestational weight gain of 14.3 (9–32) vs 7.0 (-5–16) kg (P<0.001), respectively. Infants of women with excessive gestational weight gain were characterized by higher birth weight (3712 vs 3258 g; P=0.001), birth weight z-score (1.14 vs -0.01, P=0.001) and prevalence of large-for-gestational-age infants (48 vs 20%; P<0.001). In normal weight, overweight and obese women with non-excessive gestational weight gain, the median weight gain in the first half of pregnancy was 371, 114 and 81 g/week, and in the second half of pregnancy 483, 427 and 439 g/week, respectively. In multiple linear regression analysis, gestational weight gain was associated with a higher infant birth weight z-score independent of pre-pregnancy BMI, smoking, HbA1c and insulin dose at last visit, ethnicity and parity [β=0.1 (95% CI 0.06– 0.14), P<0.001].Conclusions Infant birth weight was almost 0.5 kg higher in women with Type 2 diabetes and excessive gestational weight gain than in women with Type 2 diabetes and non-excessive weight gain.This article is protected by copyright. All rights reserved.
    Diabetic Medicine 08/2014; 31(12). DOI:10.1111/dme.12558 · 3.06 Impact Factor
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    ABSTRACT: Abstract The impact of the quality and quantity of carbohydrate intake on glycaemic control and pregnancy outcome was evaluated with focus on pregnant women with type 1 diabetes. For women with type 1 diabetes a gestational weight gain within the lower range of the guidelines of the Institute of Medicine, is generally recommended. A low-glycaemic index diet is considered safe, and has shown, positive effects on the glycaemic control and pregnancy outcomes for both healthy women, those with type 2 diabetic and gestational diabetes (GDM). In general carbohydrate counting does improve glycaemic control in type 1 diabetes. A moderate low carbohydrate diet with a carbohydrate content of 40 % of the calories results in better glycaemic control and comparable obstetric outcomes in Type 2 diabetes and GDM when compared to a diet with a higher carbohydrate content, and is regarded safe in diabetic pregnancy. In type 1 diabetes pregnancy a moderate low carbohydrate diet with 40% carbohydrates has been suggested, however a minimum intake of 175 g carbohydrate daily is recommended. Conclusion: Despite limited evidence the combination of a low-glycaemic index diet with a moderately low carbohydrate intake, using carbohydrate counting can be recommended for pregnant women with type 1 diabetes.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 03/2014; 28(2). DOI:10.3109/14767058.2014.906577 · 1.21 Impact Factor
  • 03/2014; 2(3):194-5. DOI:10.1016/S2213-8587(13)70179-7
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    ABSTRACT: Among women who have had severe hypoglycaemia the year before pregnancy, 70% with Type 1 diabetes also experience this complication in pregnancy, and particularly in the first half of pregnancy. We evaluated whether the routine use of real-time continuous glucose monitoring from early pregnancy onwards could prevent severe hypoglycaemia in these women. All 136 consecutive pregnant women with Type 1 diabetes referred to our centre were asked about severe hypoglycaemic events in the year before pregnancy and early in pregnancy at their first antenatal visit. Women with a relevant recent history were informed about their additional high risk of severe hypoglycaemia, their treatment was focused on restricted insulin doses during the first 16 gestational weeks, and they were offered real-time continuous glucose monitoring on top of self-monitored plasma glucose measurements. Among 28 women with a recent history of severe hypoglycaemia, 12 (43%) used real-time continuous glucose monitoring from a median (range) of 10 (7-13) gestational weeks for a median (range) of 10 (1-32) weeks. Among these 12 women, eight had experienced a total of 34 (range 1-11) severe hypoglycaemic events in the year before pregnancy and nine had experienced 23 (range: 1-10) events early in pregnancy. After initiation of real-time continuous glucose monitoring, two (17%) women experienced one event each. The incidence rates of severe hypoglycaemia were 2.8,17.5 and 0.3 events/patient-year. Among the 16 women in the high risk group not using real-time continuous glucose monitoring, the corresponding figures were 1.6, 5.0 and 0.1 events/patient-year. Further evaluation is required to determine whether continuous real-time continuous glucose monitoring from early pregnancy onwards in highly selected women may reduce the risk of severe hypoglycaemia. Other elements of focused intervention probably also contribute to the risk reduction. This article is protected by copyright. All rights reserved.
    Diabetic Medicine 12/2013; 31(3). DOI:10.1111/dme.12383 · 3.06 Impact Factor
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    ABSTRACT: Pregnancy is associated with decreased insulin sensitivity, which is usually overcome by a compensatory increase in insulin secretion. Some pregnant women are not able to increase their insulin secretion sufficiently, and consequently develop gestational diabetes mellitus (GDM). The disease normally disappears after delivery. Nevertheless, women with previous GDM have a high risk of developing type 2 diabetes (T2D) later in life. We aim to investigate the early development of T2D in women with previous GDM and to evaluate whether treatment with the glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, may modify their risk of developing T2D. 100 women with previous GDM will be randomised to either liraglutide or placebo treatment for 1 year (blinded) with an open-label extension for another 4 years. Additionally, 15 women without previous GDM will constitute a baseline control group. Women will be tested with an oral glucose tolerance test (primary endpoint: area under the curve for plasma glucose) and an isoglycaemic intravenous glucose infusion at baseline, after 1 year and after 5 years. Additional evaluations include a glucagon test, dual-energy X-ray absorptiometry, imaging of the liver (ultrasound elastography and fibroscanning), an ad libitum meal for food intake evaluation and questionnaires related to appetite, quality of life and alcohol consumption habits. The protocol has been approved by the Danish Medicines Agency, the Scientific-Ethical Committee of the Capital Region of Denmark, and the Danish Data Protection Agency and will be carried out under the surveillance and guidance of the GCP unit at Copenhagen University Hospital Bispebjerg in compliance with the ICH-GCP guidelines and in accordance with the Helsinki Declaration. Positive, negative and inconclusive results will be published at scientific conferences and as one or more scientific manuscripts in peer-reviewed journals. The trial is registered at https://eudract.ema.europa.eu (2012-001371-37) and http://www.clinicaltrials.gov (NCT01795248).
    BMJ Open 10/2013; 3(10):e003834. DOI:10.1136/bmjopen-2013-003834 · 2.06 Impact Factor
  • Diabetes research and clinical practice 09/2013; 102(2). DOI:10.1016/j.diabres.2013.09.011 · 2.54 Impact Factor
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    ABSTRACT: OBJECTIVE To evaluate the prevalence of diabetic nephropathy and microalbuminuria in pregnant women with type 2 diabetes in comparison with type 1 diabetes and to describe pregnancy outcomes in these women following the same antihypertensive protocol.RESEARCH DESIGN AND METHODS Among 220 women with type 2 diabetes and 445 women with type 1 diabetes giving birth from 2007-2012, 41 women had diabetic nephropathy (albumin-creatinine ratio ≥300 mg/g) or microalbuminuria (albumin-creatinine ratio 30-299 mg/g) in early pregnancy. Antihypertensive therapy was initiated if blood pressure ≥135/85 mmHg or albumin-creatinine ratio ≥300 mg/g.RESULTSThe prevalence of diabetic nephropathy was 2.3% (5 of 220) in women with type 2 diabetes and 2.5% (11 of 445) in women with type 1 diabetes (P = 1.00). The figures for microalbuminuria were 4.5 (10 of 220) vs. 3.4% (15 of 445) (P = 0.39). Baseline glycemic control was comparable between women with type 2 diabetes (n = 15) and type 1 diabetes (n = 26). Blood pressure at baseline was median 128 (range 100-164)/81 (68-91) vs. 132 (100-176)/80 (63-100) mmHg (not significant) and antihypertensive therapy in type 2 versus type 1 diabetes was used in 0 and 62%, respectively, at baseline, increasing to 33 and 96%, respectively, in late pregnancy. Pregnancy outcome was comparable regardless type of diabetes; gestational age at delivery: 259 days (221-276) vs. 257 (184-271) (P = 0.19); birth weight 3,304 g (1,278-3,914) vs. 2,850 (370-4,180) (P = 0.67).CONCLUSIONS The prevalence of diabetic nephropathy and microalbuminuria in early pregnancy was similar in type 2 and type 1 diabetes. Antihypertensive therapy was used more frequently in type 1 diabetes. Pregnancy outcome was comparable regardless type of diabetes.
    Diabetes care 09/2013; 36(11). DOI:10.2337/dc13-1031 · 8.57 Impact Factor
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    ABSTRACT: Abstract Objective: To explore insulin pump settings in a cohort of pregnant women with type 1 diabetes on insulin pump therapy with a bolus calculator. Methods: Twenty-seven women with type 1 diabetes on insulin pump therapy were included in this study. At 8, 12, 21, 27 and 33 weeks, insulin pump settings and HbA1c were recorded. Results were compared to 96 women with type 1 diabetes on multiple daily injection therapy. Results: Throughout pregnancy, the carbohydrate-to-insulin ratio decreased at all three main meals. The most pronounced decrease was observed at breakfast, where the carbohydrate-to-insulin ratio was reduced, from median 12 (range 4-20) in early pregnancy to 3 (2-10) grams carbohydrate per unit insulin in late pregnancy. Basal insulin delivery increased by approximately 50%, i.e. from 0.8 (0.5-2.2) to 1.2 (0.6-2.5) international units (IU)/hour at 5 a.m., and from 1.0 (0.6-1.5) to 1.3 (0.2-2.3) /hour at 5 p.m. during pregnancy. HbA1c levels during pregnancy, the occurrence of severe hypoglycemia, and pregnancy outcomes were similar in the two groups. Conclusions: In women with type 1 diabetes on insulin pump therapy with a bolus calculator the carbohydrate-to-insulin ratio declined four-fold from early to late pregnancy, while changes in basal insulin delivery were smaller.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 08/2013; 27(7). DOI:10.3109/14767058.2013.837444 · 1.21 Impact Factor

Publication Stats

6k Citations
900.51 Total Impact Points

Institutions

  • 2008–2015
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2006–2014
    • Copenhagen University Hospital
      København, Capital Region, Denmark
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 2013
    • Tel Aviv University
      • Sackler Faculty of Medicine
      Tell Afif, Tel Aviv, Israel
  • 2010
    • University of Southern California
      • Department of Obstetrics and Gynecology
      Los Ángeles, California, United States
  • 2009
    • Sheffield Teaching Hospitals NHS Foundation Trust
      Sheffield, England, United Kingdom
  • 1989–2008
    • Hillerød Hospital
      Hillerød, Capital Region, Denmark
  • 2007
    • Novo Nordisk
      København, Capital Region, Denmark
    • Frederiksberg Hospital
      Фредериксберг, Capital Region, Denmark
  • 1992–2005
    • Steno Diabetes Center
      Gjentofte, Capital Region, Denmark
  • 2003–2004
    • Odense University Hospital
      Odense, South Denmark, Denmark
  • 2002
    • Rigshospitalet
      København, Capital Region, Denmark
  • 1991
    • Herlev Hospital
      Herlev, Capital Region, Denmark
  • 1986
    • Glostrup Hospital
      Glostrup, Capital Region, Denmark
  • 1985
    • Bispebjerg Hospital, Copenhagen University
      København, Capital Region, Denmark