Liraglutide treatment for the prevention of glucose tolerance deterioration in women with prior gestational diabetes mellitus: A 52-week randomized controlled clinical trial.

AIM: We investigated the effect of 52-week treatment with liraglutide, a glucagon-like peptide 1 receptor agonist, on glucose tolerance and incretin effect in women with previous gestational diabetes mellitus (pGDM). MATERIALS AND METHODS: Women with overweight/obesity and pGDM were randomized to once daily subcutaneous liraglutide 1.8 mg or placebo for 52 weeks. Participants underwent oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion at baseline and at 52 weeks, and an additional OGTT after the drug wash-out. RESULTS: In total, 104 women [age: mean ± SD, 38 ± 5 years; fasting plasma glucose (FPG): 5.5 ± 0.4 mmol/L; glycated haemoglobin (HbA1c): 33 ± 4 mmol/mol, bodyweight: 88.2 ± 14.8 kg, body mass index: 31.1 ± 4.3 kg/m2 ] were assigned to liraglutide (n = 49) or placebo (n = 55). Estimated treatment difference (ETD) for area under curve during OGTT was -173 (95% confidence interval -250 to -97) mmol/L × min, p < .0001, but after wash-out the difference disappeared [ETD 58 (-30 to 146) mmol/L × min, p = .536]. Liraglutide reduced FPG [ETD -0.2 (-0.4 to -0.1) mmol/L, p = .018], HbA1c [-2.2 (-3.5 to -0.8) mmol/mol, p = .018] and bodyweight [-3.9 (-6.2 to -1.6) kg, p = .012]. No change in the incretin effect was observed. The number of women with prediabetes was reduced from 64% to 10% with liraglutide vs. 50% with placebo [adjusted odds ratio 0.10 (0.03-0.32), p = .002]. CONCLUSIONS: Treatment with liraglutide for 52 weeks improved glucose tolerance, FPG, HbA1c and bodyweight in women with overweight/obesity and pGDM. Progression to prediabetes while on drug was markedly reduced, but after a 1-week drug wash-out, the effect was lost.

Effects of Physical Activity on Blood Lipids and Hemoglobin A1c in Healthy Pregnant Women: The FitMum Randomized Controlled Trial.

OBJECTIVE: Maternal blood lipid and glucose concentrations during pregnancy affect fetal growth and the risk of pregnancy and delivery complications. We aimed to investigate the effects of physical activity (PA) during pregnancy on maternal blood lipid and hemoglobin A1c (HbA1c) concentrations. We hypothesized that higher PA was associated with improved lipid profile and glycemic control. METHODS: In a secondary analysis of a randomized controlled trial, we included 216 pregnant women before week 15 + 0 and tested the effects of two different PA interventions throughout pregnancy compared to standard care on maternal blood lipid and HbA1c concentrations. Additionally, we investigated the effect of PA per se measured by an activity tracker. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, and HbA1c concentrations were measured at week ≤15 + 0, 28+0-6, 34+0-6, and at delivery (week 32 + 1 to 42 + 0). Effects of the interventions and PA per se were tested using linear mixed effects models and linear regression analyses, respectively. RESULTS: No effects of the PA interventions were detected on maternal lipids or HbA1c during pregnancy. In PA per se analyses, more minutes per week of moderate-to-vigorous intensity PA were associated with less increase in TC (-1.3E-04, P = .020) and LDL-C (-8.5E-05, P = .035) as pregnancy progresses. More active kilocalories were associated with less increase in TC (-5.5E-05, P < .001), HDL-C (-9.5E-06, P = .024), and LDL-C (-3.2E-05, P = .005). CONCLUSION: Whilst there were no effects of offering PA interventions, higher PA was associated with reduced increases in TC, HDL-C, and LDL-C as pregnancy progressed.

The effect of exercise training and motivational counselling on physical activity behaviour and psychosocial factors in pregnant women: secondary analyses of the FitMum randomised controlled trial investigating prenatal physical activity.

BACKGROUND: A physically active lifestyle is beneficial during pregnancy. However, little is known about physical activity (PA) behaviour and psychosocial factors in women during and after pregnancy. This study examined exercise behavioural regulation, exercise self-efficacy, health-related quality of life, sickness absence and musculoskeletal pain in pregnant women offered either structured supervised exercise training, motivational counselling on PA, or standard prenatal care in the FitMum randomised controlled trial. METHODS: Two hundred and eighteen healthy inactive pregnant women were randomised to structured supervised exercise training (n = 87), motivational counselling on PA (n = 86) or standard prenatal care (n = 45). The women answered the Behavioural Regulation in Exercise Questionnaire-2 (BREQ-2), the Pregnancy Exercise Self-Efficacy Scale (P-ESES-DK) and the Short Form 36 Health Survey Questionnaire (SF-36) at baseline (gestational age (GA) of max 15 weeks), GA 28 and 34 weeks, and one year after delivery. Sickness absence and low back and/or pelvic girdle pain were likewise reported in questionnaires at baseline and GA 28 weeks. RESULTS: Participants offered structured supervised exercise training or motivational counselling on PA had higher autonomous motivation for exercise during pregnancy compared with participants receiving standard prenatal care (e.g., difference in intrinsic regulation at GA 28 weeks, structured supervised exercise training vs. standard prenatal care: mean difference in score 0.39 [0.16; 0.64], p < 0.001). Participants offered structured supervised exercise training also had higher exercise self-efficacy during pregnancy (e.g., GA 28 weeks, structured supervised exercise training vs. standard prenatal care: mean difference in score 6.97 [2.05; 12.02], p = 0.005). All participants reported high exercise self-efficacy at baseline and medium exercise self-efficacy during pregnancy and one year after delivery. No differences were found between groups in health-related quality of life, sickness absence or low back and/or pelvic girdle pain during pregnancy. No group differences were found one year after delivery. CONCLUSION: Structured supervised exercise training and motivational counselling on PA had important effects on autonomous exercise motivation during pregnancy. Exercise self-efficacy was also increased with structured supervised exercise training compared to standard prenatal care. No group differences in health-related quality of life, sickness absence, or pain were found during and after pregnancy. No effects were found one year post-delivery after intervention cessation. TRIAL REGISTRATION: The study was approved by the Danish National Committee on Health Research Ethics (#H-18011067) and the Danish Data Protection Agency (#P-2019-512). The study adheres to the principles of the Helsinki declaration. Written informed consent was obtained at inclusion.

Mean Glucose and Gestational Weight Gain as Predictors of Large-for-Gestational-Age Infants in Pregnant Women with Type 1 Diabetes Using Continuous Glucose Monitoring.

Aims/hypothesis: To compare glycemic metrics during pregnancy between women with type 1 diabetes (T1D) delivering large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) infants, and to identify predictors of LGA infants. Materials and Methods: A cohort study including 111 women with T1D using intermittently scanned continuous glucose monitoring from conception until delivery. Average sensor-derived metrics: mean glucose, time in range in pregnancy (TIRp), time above range in pregnancy, time below range in pregnancy, and coefficient of variation throughout pregnancy and in pregnancy intervals of 0-10, 11-21, 22-33, and 34-37 weeks were compared between women delivering LGA and AGA infants. Predictors of LGA infants were sought for. Infant growth was followed until 3 months postdelivery. Results: In total, 53% (n = 59) delivered LGA infants. Mean glucose decreased during pregnancy in both groups, with women delivering LGA infants having a 0.4 mmol/L higher mean glucose from 11-33 weeks (P = 0.01) compared with women delivering AGA infants. Mean TIRp >70% was obtained from 34 weeks in women delivering LGA infants and from 22-33 weeks in women delivering AGA infants. Independent predictors for delivering LGA infants were mean glucose throughout pregnancy and gestational weight gain. At 3 months postdelivery, infant weight was higher in infants born LGA compared with infants born AGA (6360 g ± 784 and 5988 ± 894, P = 0.04). Conclusions/interpretations: Women with T1D delivering LGA infants achieved glycemic targets later than women delivering AGA infants. Mean glucose and gestational weight gain were independent predictors for delivering LGA infants. Infants born LGA remained larger postdelivery compared with infants born AGA.

Effects of prenatal exercise interventions on maternal body composition: A secondary analysis of the FitMum randomized controlled trial.

The main objective of the study was to investigate the effects of prenatal exercise interventions on maternal body composition at 28 weeks gestation and 7-14 days after delivery. We also explored associations between physical activity (PA) per se and body composition. This study presents secondary outcomes of the FitMum randomized controlled trial, which included healthy inactive pregnant women at gestational age ≤ 15+0 weeks. They were randomized to structured supervised exercise training, motivational counselling on PA, or standard care. Maternal body composition was measured by doubly labeled water at 28 weeks gestation (n = 134) and by dual-energy X-ray absorptiometry scan 7-14 days after delivery (n = 117). PA, including moderate-to-vigorous-intensity PA (MVPA), active kilocalories, and steps, were measured continuously from inclusion to delivery by a wrist-worn activity tracker. One hundred fifty pregnant women were included with a median pre-pregnancy body mass index (BMI) of 24.1 (21.6-27.9) kg/m2. We found no differences between groups in fat mass, fat percentage or fat-free mass at 28 weeks gestation or 7-14 days after delivery. Visceral adipose tissue mass and bone mineral density measured 7-14 days after delivery did not differ between groups either. Linear regression analyses adjusted for pre-pregnancy BMI showed that a higher number of daily steps was associated with lower fat mass, fat percentage, and visceral adipose tissue mass at 28 weeks gestation and 7-14 days after delivery. Active kilocalories during pregnancy was positively associated with fat-free mass 7-14 days after delivery. Neither structured supervised exercise training nor motivational counselling on PA during pregnancy affected maternal body composition at 28 weeks gestation or 7-14 days after delivery compared to standard care. Interestingly, when adjusted for pre-pregnancy BMI, higher number of daily steps was associated with lower fat content during pregnancy and after delivery, whereas MVPA and active kilocalories were not. Trial registration: ClinicalTrials.gov; NCT03679130; 20/09/2018.

Danish Diabetes Birth Registry 2: a study protocol of a national prospective cohort study to monitor outcomes of pregnancies of women with pre-existing diabetes.

INTRODUCTION: Despite technological developments and intensified care, pregnancies in women with pre-existing diabetes are still considered high-risk pregnancies. The rate of adverse outcomes in pregnancies affected by diabetes in Denmark is currently unknown, and there is a limited understanding of mechanisms contributing to this elevated risk. To address these gaps, the Danish Diabetes Birth Registry 2 (DDBR2) was established. The aims of this registry are to evaluate maternal and fetal-neonatal outcomes based on 5 years cohort data, and to identify pathophysiology and risk factors associated with short-term and long-term outcomes of pregnancies in women with pre-existing diabetes. METHODS AND ANALYSIS: The DDBR2 registry is a nationwide 5-year prospective cohort with an inclusion period from February 2023 to February 2028 of pregnancies in women with all types of pre-existing diabetes and includes registry, clinical and questionnaire data and biological samples of mother-partner-child trios. Eligible families (parents age ≥18 years and sufficient proficiency in Danish or English) can participate by either (1) basic level data obtained from medical records (mother and child) and questionnaires (partner) or (2) basic level data and additional data which includes questionnaires (mother and partner) and blood samples (all). The primary maternal outcome is Hemoglobin A1c (HbA1c) levels at the end of pregnancy and the primary offspring endpoint is the birth weight SD score. The DDBR2 registry will be complemented by genetic, epigenetic and metabolomic data as well as a biobank for future research, and the cohort will be followed through data from national databases to illuminate possible mechanisms that link maternal diabetes and other parental factors to a possible increased risk of adverse long-term child outcomes. ETHICS AND DISSEMINATION: Approval from the Ethical Committee is obtained (S-20220039). Findings will be sought published in international scientific journals and shared among the participating hospitals and policymakers. TRIAL REGISTRATION NUMBER: NCT05678543.