Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy.

BACKGROUND: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. METHODS: To identify DMRs, we employed the bump hunter method in samples from young (9-16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28-33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. RESULTS: One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring's own adiposity. CONCLUSIONS: Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.

Pre-analytical diagnostic differences despite high adherence to guidelines for gestational diabetes mellitus.

Regional variations in the prevalence of gestational diabetes mellitus (GDM) have been found across Denmark. The objectives of this exploratory survey were to evaluate adherence to the national guideline for screening and diagnosing GDM and to identify variations in pre-analytical or analytical factors, which could potentially contribute to variations in GDM prevalence across regions. In a national interview-based survey, obstetric departments and laboratories throughout Denmark handling GDM screening or diagnostic testing were invited to participate. Survey questionnaires were completed through personal interviews. In total, 21 of 22 identified obstetric departments and 44 of 45 identified laboratories participated. Adherence to guideline among obstetric departments ranged 67-100% and uniformity in laboratory procedures was high. However, the gestational age at the time of late diagnostic testing with oral glucose tolerance test (OGTT) varied considerably, with 48% (10/21) of departments testing outside the recommended 24-28 weeks' gestation. Procedural heterogeneity was most pronounced for the parts not described in current guidelines, with choice of laboratory equipment being the most diverse factor ranging 3-39% nationally. In conclusion, the overall adherence to the national guidelines was high across regions, and obstetric departments and laboratories had high uniformity in the procedures for screening and diagnosing GDM. Uniformity was generally high for procedures included in the guideline and low if not included. However, a high proportion of GDM testing was performed outside the recommended gestational window in late pregnancy, which may be a pre-analytical contributor to regional differences in GDM prevalence.

Health promotion intervention among women with recent gestational diabetes mellitus: penetration, participation, and baseline findings from the Face-it randomized controlled trial.

INTRODUCTION: Face-it is a randomized controlled trial for women with recent gestational diabetes mellitus (GDM) and their families designed to evaluate the effect of a health promotion intervention on type 2 diabetes mellitus (T2DM) risk and quality of life. This study examined (1) the penetration and participation rates for the Face-it trial, (2) the characteristics of the participating women and the potential differences in characteristics according to partner participation status, and (3) representativity of the women at baseline. RESEARCH DESIGN AND METHODS: We identified women with GDM during pregnancy and invited them and their partners to a baseline examination 10-14 weeks after delivery. Representativity was assessed by comparing the baseline participants with non-participating women, the general population of women with GDM delivering in Denmark, and populations from other intervention trials. RESULTS: The penetration rate was 38.0% (867/2279) and the participation rate was 32.9% (285/867). The 285 women who attended baseline had a mean age of 32.7 (±4.8) years and body mass index (BMI) of 28.1 (±5.4) kg/m2, and 69.8% had a partner who participated. The women participating with a partner were more often primiparous, born in Denmark (82.8% vs 68.2%), were younger, and more often had a BMI ≤24.9 kg/m2 (35.7% vs 21.2%) compared with women without a partner. Compared with the general population of women with GDM in Denmark, these women broadly had similar degree of heterogeneity, but had higher rates of primiparity and singleton deliveries, and lower rates of preterm delivery and prepregnancy obesity. CONCLUSIONS: The penetration and participation rates were acceptable. We found a high rate of partner participation. Overall, women participating with a partner were comparable with those participating without a partner. Participating women were broadly similar to the general national GDM population, however with prepregnancy obesity, multiparity, preterm delivery, and multiple pregnancy being less represented. TRIAL REGISTRATION NUMBER: NCT03997773.

Applying WHO2013 diagnostic criteria for gestational diabetes mellitus reveals currently untreated women at increased risk.

AIMS: To estimate the prevalence of gestational diabetes mellitus (GDM) in a Danish cohort comparing the current Danish versus the WHO2013 diagnostic criteria, and to evaluate adverse pregnancy outcomes among currently untreated women in the gap between the diagnostic thresholds. METHODS: Diagnostic testing was performed by a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks' gestation in a cohort of pregnant women. GDM diagnosis was based on the current Danish criterion (2-h glucose ≥ 9.0 mmol/L, GDMDK) and on the WHO2013 criteria (fasting ≥ 5.1, 1 h ≥ 10.0 or 2 h glucose ≥ 8.5 mmol/L, GDMWHO2013). Currently untreated women fulfilling the WHO2013 but not the Danish diagnostic criteria were defined as New-GDM-women (GDMWHO2013-positive and GDMDK-negative). Adverse outcomes risks were calculated using logistic regression. RESULTS: OGTT was completed by 465 women at a median of 25.7 weeks' gestation. GDMDK prevalence was 2.2% (N = 10) and GDMWHO2013 21.5% (N = 100). New-GDM was present in 19.4% (N = 90), of whom 90.0% had elevated fasting glucose. Pregnancies complicated by New-GDM had higher frequencies of pregnancy-induced hypertension (13.3% vs 4.1%, p = 0.002), large-for-gestational-age infants (22.2% vs 9.9%, p = 0.004), neonatal hypoglycaemia (8.9% vs 1.9%, p = 0.004) and neonatal intensive care unit admission (16.7% vs 5.8%, p = 0.002) compared to pregnancies without GDM. CONCLUSIONS: GDM prevalence increased tenfold when applying WHO2013 criteria in a Danish population, mainly driven by higher fasting glucose levels. Untreated GDM in the gap between the current Danish and the WHO2013 diagnostic criteria resulted in higher risks of adverse pregnancy outcomes.

Maturity-onset diabetes of the young and pregnancy.

Maturity-onset diabetes of the young (MODY) is a group of hereditary monogenetic forms of diabetes. MODY accounts for 1-3% of all persons with diabetes but is often undiagnosed or misdiagnosed as type 1 diabetes, type 2 diabetes, or gestational diabetes. Diagnosing MODY is essential, as the most optimal treatment both during and outside of pregnancy depends on the MODY type. This review focuses on the outcome and treatment of the three most common types of MODY during pregnancy.

Major congenital malformations in offspring of women with chronic diseases-impact of the disease or the treatment?

In a narrative review, we summarized previous findings on the risk of major congenital malformations in offspring of women with chronic hypertension, hypothyroidism, or depression compared with the background population, and evaluated whether exposure to medical treatment in the first trimester affected this risk. In a literature search in the PubMed database, cohort studies were included if they were published from 2010 to 2022 and contained data on major congenital malformations from ≥500 offspring of women with chronic hypertension, hypothyroidism, or depression during the first trimester of pregnancy, and data on both untreated and treated women. Data were compared with the background population of women without these diseases. In total, 7 cohort studies were identified. In comparison with the background population, 2 studies including 54,996 offspring of women with chronic hypertension showed an adjusted odds ratio of 1.20 to 1.30 for major congenital malformations in the offspring, regardless of antihypertensive treatment. One study including 16,364 offspring of women with hypothyroidism showed an adjusted odds ratio of 1.14 (1.06-1.22) for major congenital malformations in the offspring, regardless of thyroid substitution. Four studies including 48,913 offspring of women with depression showed adjusted odds ratios of 1.07 to 1.27 (0.91-1.78) for major congenital malformations in the offspring of untreated women. Three of these 4 studies showed similar prevalence of malformations in women treated for depression. The findings of this narrative review suggest that chronic hypertension and hypothyroidism, rather than exposure to their medical treatments in the first trimester, were associated with increased risk of major congenital malformations, whereas depression was generally not associated with major congenital malformations.

Dietary Advice to Support Glycaemic Control and Weight Management in Women with Type 1 Diabetes during Pregnancy and Breastfeeding.

In women with type 1 diabetes, the risk of adverse pregnancy outcomes, including congenital anomalies, preeclampsia, preterm delivery, foetal overgrowth and perinatal death is 2-4-fold increased compared to the background population. This review provides the present evidence supporting recommendations for the diet during pregnancy and breastfeeding in women with type 1 diabetes. The amount of carbohydrate consumed in a meal is the main dietary factor affecting the postprandial glucose response. Excessive gestational weight gain is emerging as another important risk factor for foetal overgrowth. Dietary advice to promote optimized glycaemic control and appropriate gestational weight gain is therefore important for normal foetal growth and pregnancy outcome. Dietary management should include advice to secure sufficient intake of micro- and macronutrients with a focus on limiting postprandial glucose excursions, preventing hypoglycaemia and promoting appropriate gestational weight gain and weight loss after delivery. Irrespective of pre-pregnancy BMI, a total daily intake of a minimum of 175 g of carbohydrate, mainly from low-glycaemic-index sources such as bread, whole grain, fruits, rice, potatoes, dairy products and pasta, is recommended during pregnancy. These food items are often available at a lower cost than ultra-processed foods, so this dietary advice is likely to be feasible also in women with low socioeconomic status. Individual counselling aiming at consistent timing of three main meals and 2-4 snacks daily, with focus on carbohydrate amount with pragmatic carbohydrate counting, is probably of value to prevent both hypoglycaemia and hyperglycaemia. The recommended gestational weight gain is dependent on maternal pre-pregnancy BMI and is lower when BMI is above 25 kg/m2. Daily folic acid supplementation should be initiated before conception and taken during the first 12 gestational weeks to minimize the risk of foetal malformations. Women with type 1 diabetes are encouraged to breastfeed. A total daily intake of a minimum of 210 g of carbohydrate is recommended in the breastfeeding period for all women irrespective of pre-pregnancy BMI to maintain acceptable glycaemic control while avoiding ketoacidosis and hypoglycaemia. During breastfeeding insulin requirements are reported approximately 20% lower than before pregnancy. Women should be encouraged to avoid weight retention after pregnancy in order to reduce the risk of overweight and obesity later in life. In conclusion, pregnant women with type 1 diabetes are recommended to follow the general dietary recommendations for pregnant and breastfeeding women with special emphasis on using carbohydrate counting to secure sufficient intake of carbohydrates and to avoid excessive gestational weight gain and weight retention after pregnancy.

Home Blood Pressure for the Prediction of Preeclampsia in Women With Preexisting Diabetes.

CONTEXT: Outside of pregnancy, home blood pressure (BP) has been shown to be superior to office BP for predicting cardiovascular outcomes. OBJECTIVE: This work aimed to evaluate home BP as a predictor of preeclampsia in comparison with office BP in pregnant women with preexisting diabetes. METHODS: A prospective cohort study was conducted of 404 pregnant women with preexisting diabetes; home BP and office BP were measured in early (9 weeks) and late pregnancy (35 weeks). Discriminative performance of home BP and office BP for prediction of preeclampsia was assessed by area under the receiver operating characteristic curves (AUC). RESULTS: In total 12% (n = 49/404) developed preeclampsia. Both home BP and office BP in early pregnancy were positively associated with the development of preeclampsia (adjusted odds ratio (95% CI) per 5 mm Hg, systolic/diastolic): home BP 1.43 (1.21-1.70)/1.74 (1.34-2.25) and office BP 1.22 (1.06-1.40)/1.52 (1.23-1.87). The discriminative performance for prediction of preeclampsia was similar for early-pregnancy home BP and office BP (systolic, AUC 69.3 [61.3-77.2] vs 64.1 [55.5-72.8]; P = .21 and diastolic, AUC 68.6 [60.2-77.0] vs 66.6 [58.2-75.1]; P = .64). Similar results were seen when comparing AUCs in late pregnancy (n = 304). In early and late pregnancy home BP was lower than office BP (early pregnancy P < .0001 and late pregnancy P < .01 for both systolic and diastolic BP), and the difference was greater with increasing office BP. CONCLUSION: In women with preexisting diabetes, home BP and office BP were positively associated with the development of preeclampsia, and for the prediction of preeclampsia home BP and office BP were comparable.

Prevalence and severity of diabetic retinopathy in pregnant women with diabetes-time to individualize photo screening frequency.

AIMS: To evaluate the prevalence and severity of diabetic retinopathy including macular oedema in pregnant women with diabetes and to identify women in whom the frequency of retinal screening can be reduced to minimize the burden of health care visits. METHODS: A cohort study of 348 women with pre-existing diabetes were routinely screened with retinal photo in early (12 weeks) and late pregnancy (27 weeks). Diabetic retinopathy was classified in five stages in accordance with National Danish Guidelines based on the eye with the highest retinopathy level. Sight-threatening retinopathy was defined as the presence of proliferative retinopathy and/or clinically significant macular oedema (CSMO). RESULTS: Retinopathy was present in 52% (116/223) vs. 14% (17/125), with sight-threatening retinopathy in 16% (35/223) vs. 6% (7/125) of women with type 1 and type 2, respectively. Women without retinopathy in early and late pregnancy were characterized by shorter diabetes duration (p < 0.0001 and p = 0.008) and predominance of type 2 diabetes. Amongst the 50% (175/348) of the cohort having no retinopathy in early pregnancy and HbA1c<53 mmol/mol (7.0%), none developed sight-threatening retinopathy and 94% (165/175) remained without any retinopathy during pregnancy. Development of sight-threatening retinopathy was mainly observed in women with retinopathy in early pregnancy. Treatment for sight-threatening retinopathy was given to a minority (2.7 and 2.4%, respectively). CONCLUSION: Good glycaemic control and no retinopathy was seen in a large proportion of women in early pregnancy and none of these women developed sight-threatening retinopathy. The frequency of retinal screening can probably be safely reduced during pregnancy in these women.

Pregnancy outcomes in women with type 1 diabetes using insulin degludec.

AIMS: To evaluate pregnancy outcomes in a real-world setting of pregnant women with type 1 diabetes using the ultra-long-acting insulin analog degludec compared to other long-acting insulin analogs throughout pregnancy. METHODS: This was a secondary analysis of a prospective cohort study. The prospective cohort included consecutive, singleton pregnant women with type 1 diabetes receiving long-acting insulin analogs both before and during pregnancy: 67 women using degludec compared to 95 women using other long-acting insulin analogs in a routine care setting. RESULTS: Women using degludec had similar clinical characteristics as women using other long-acting insulin analogs including HbA1c at 9 gestational weeks [6.5 (6.2-6.9) % (48 (44-52) mmol/mol) versus 6.5 (6.0-7.0) % (47 (42-53) mmol/mol), p = 0.52] and at 35 gestational weeks [6.0 (5.6-6.5) % (42 (38-47) mmol/mol) versus 6.1 (5.6-6.5) % (43 (38-48) mmol/mol), p = 0.68]. Pregnancy outcomes were similar regarding preeclampsia [10% (7/67) versus 8% (8/95), p = 0.66] and preterm delivery before 37 gestational weeks [16% (11/67) versus 23% (22/95), p = 0.29]. There were no perinatal deaths, and neonatal outcomes as large for gestational age infants [37% (25/67) versus 39% (37/95), p = 0.83], small for gestational age infants [4% (3/67) versus 5% (5/95), p = 1.0] and neonatal hypoglycemia [32% (21/65) versus 41% (34/83), p = 0.28] were similar between women using degludec and other long-acting insulin analogs. CONCLUSIONS: The use of degludec during pregnancy resulted in similar pregnancy outcomes as use of other long-acting insulin analogs in women with type 1 diabetes in a real-world setting. This suggests that degludec initiated before pregnancy can be continued throughout gestation.

Systematically developing a family-based health promotion intervention for women with prior gestational diabetes based on evidence, theory and co-production: the Face-it study.

BACKGROUND: Women with prior gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes; however, this risk can be reduced by engaging in positive health behaviours e.g. healthy diet and regular physical activity. As such behaviours are difficult to obtain and maintain there is a need to develop sustainable behavioural interventions following GDM. We aimed to report the process of systematically developing a health promotion intervention to increase quality of life and reduce diabetes risk among women with prior GDM and their families. We distil general lessons about developing complex interventions through co-production and discuss our extensions to intervention development frameworks. METHODS: The development process draws on the Medical Research Council UK Development of complex interventions in primary care framework and an adaptation of a three-stage framework proposed by Hawkins et al. From May 2017 to May 2019, we iteratively developed the Face-it intervention in four stages: 1) Evidence review, qualitative research and stakeholder consultations; 2) Co-production of the intervention content; 3) Prototyping, feasibility- and pilot-testing and 4) Core outcome development. In all stages, we involved stakeholders from three study sites. RESULTS: During stage 1, we identified the target areas for health promotion in families where the mother had prior GDM, including applying a broad understanding of health and a multilevel and multi-determinant approach. We pinpointed municipal health visitors as deliverers and the potential of using digital technology. In stage 2, we tested intervention content and delivery methods. A health pedagogic dialogue tool and a digital health app were co-adapted as the main intervention components. In stage 3, the intervention content and delivery were further adapted in the local context of the three study sites. Suggestions for intervention manuals were refined to optimise flexibility, delivery, sequencing of activities and from this, specific training manuals were developed. Finally, at stage 4, all stakeholders were involved in developing realistic and relevant evaluation outcomes. CONCLUSIONS: This comprehensive description of the development of the Face-it intervention provides an example of how to co-produce and prototype a complex intervention balancing evidence and local conditions. The thorough, four-stage development is expected to create ownership and feasibility among intervention participants, deliverers and local stakeholders. TRIAL REGISTRATION: ClinicalTrials.gov NCT03997773 , registered retrospectively on 25 June 2019.

Comparison of Glycemic Metrics Measured Simultaneously by Intermittently Scanned Continuous Glucose Monitoring and Real-Time Continuous Glucose Monitoring in Pregnant Women with Type 1 Diabetes.

Background: We aimed to compare clinically important glycemic metrics with focus on mean sensor glucose and time-below-target range (TBR) during nighttime obtained with intermittently scanned continuous glucose monitoring (isCGM) and real-time CGM (rtCGM) in early pregnancy in women with type 1 diabetes. Materials and Methods: A prospective, observational study including 20 women with type 1 diabetes simultaneously monitored with isCGM (Freestyle Libre; Abbott) and rtCGM (Envision™ Pro; Medtronic) for 7 days in early pregnancy. Time-in-target range (TIR) was defined as 3.5-7.8 mmol/L. Results: Gestational age was median 66 (interquartile range 63-74) days and HbA1c was 48 mmol/mol (43-54). Median difference between isCGM and rtCGM was 0.1 mmol/L (-0.1 to 0.5) (P = 0.50) and -0.1 mmol/L (-0.4 to 0.2) (P = 0.35) for 24 h and during nighttime, respectively. For 24 h, TBR was 3.9% (1.6-7.0) versus 2.0% (0.6-3.7) (P = 0.06) and TIR was 57.2% (50.8-76.5) versus 69.6% (55.4-81.5) (P = 0.001) for isCGM and rtCGM, respectively. During nighttime TBR was 6.5% (0.4-16.7) versus 0% (0.0-0.8) (P = 0.003), TIR was 55.4 (41.1-81.0) versus 68.8 (52.4-80.3) (P = 0.005) and 75% versus 40% of the women had ≥1 glucose reading <3.5 mmol/L. Conclusions: In pregnant women with type 1 diabetes, mean sensor glucose was reported similar when measured by isCGM and rtCGM. However, during nighttime isCGM measured a clinically relevant higher percentage of TBR compared with rtCGM. Thus, the type of CGM device used may influence adjustments of insulin dose based on the concern for nocturnal hypoglycemia. ClinicalTrials.gov (NCT03770767).

CopenFast trial: Faster-acting insulin Fiasp versus insulin NovoRapid in the treatment of women with type 1 or type 2 diabetes during pregnancy and lactation - a randomised controlled trial.

INTRODUCTION: Faster-acting insulin aspart (Fiasp) is approved for use in pregnancy and lactation, but no clinical study has evaluated its effects during this life stage in women with pre-existing diabetes. The aim of the CopenFast trial is to evaluate the effect of Fiasp compared with insulin aspart (NovoRapid) on maternal glycaemic control during pregnancy, delivery and lactation and on fetal growth and infant health. METHODS AND ANALYSIS: An open-label randomised controlled trial of pregnant women with type 1 or type 2 diabetes including women on multiple daily injection (MDI) therapy or insulin pump therapy. During a 2-year inclusion period, approximately 220 women will be randomised 1:1 to Fiasp or NovoRapid in early pregnancy and followed until 3 months after delivery. At 9, 21 and 33 gestational weeks and during planned induction of labour or caesarean section, women are offered blinded continuous glucose monitoring (CGM) for 7 days. Randomisation will stratify for type of diabetes and insulin treatment modality (MDI or insulin pump therapy, respectively). Health status of the infants will be followed until 3 months of age. The primary outcome is birth weight SD score adjusted for gestational age and gender. Secondary outcomes include maternal glycaemic control including glycated haemoglobin, preprandial and postprandial self-monitored plasma glucose levels, episodes of mild and severe hypoglycaemia, maternal gestational weight gain and weight retention, CGM time spent in, above and below target ranges as well as pregnancy outcomes including pre-eclampsia, preterm delivery, perinatal mortality and neonatal morbidity. Data analysis will be performed according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The trial has been approved by the Regional Ethics Committee (H-19029966) on 7 August 2019. Results will be sought disseminated in peer-reviewed journals and at scientific meetings. TRIAL REGISTRATION NUMBER: NCT03770767.

Less sedentary time is associated with a more favourable glucose-insulin axis in obese pregnant women-a secondary analysis of the DALI study.

BACKGROUND/OBJECTIVES: Obese pregnant women are at high risk of developing gestational diabetes mellitus (GDM), which might be reduced by sufficient physical activity (PA) and reduced sedentary time (ST). We assessed whether PA and ST are longitudinally associated with the glucose-insulin axis in obese pregnant women. SUBJECTS/METHODS: In this secondary analysis of the DALI (vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention) study, pregnant women, <20 weeks gestation, with a pre-pregnancy body mass index (BMI) ≥ 29 kg/m2, without GDM on entry were included. Time spent in moderate-to-vigorous PA (MVPA) and ST were measured objectively with accelerometers at <20 weeks, 24-28 weeks and 35-37 weeks of gestation. Fasting glucose (mmol/l) and insulin (mU/l), insulin resistance (HOMA-IR) and first-phase and second-phase insulin release (Stumvoll first and second phase) were assessed at the same time. Linear mixed regression models were used to calculate between-participant differences and within-participant changes over time. Analyses were adjusted for gestational age, randomisation, pre-pregnancy BMI, education and age. MVPA, Insulin, HOMA-IR and Stumvoll first and second phase were log-transformed for analyses due to skewness. RESULTS: 232 women were included in the analysis. Concerning differences between participants, more ST was associated with higher fasting glucose (Estimate: 0.008; 95% CI: 0.002, 0.014), fasting insulin (0.011; 0.002, 0.019), HOMA-IR (0.012; 0.004, 0.021) and Stumvoll first and second phase (0.008; 0.001, 0.014 and 0.007; 0.001, 0.014). Participants with more MVPA had lower Stumvoll first and second phase (-0.137; -0.210, -0.064 and -0.133; -0.202, -0.063). Concerning changes over time, an increase in ST during gestation was associated with elevated Stumvoll first and second phase (0.006; 0.000, 0.011). CONCLUSIONS: As the glucose-insulin axis is more strongly associated with ST than MVPA in our obese population, pregnant women could be advised to reduce ST in addition to increasing MVPA. Moreover, our findings suggest that behaviour change interventions aiming at GDM risk reduction should start in early or pre-pregnancy.

Possible mechanisms involved in improved beta cell function in pregnant women with type 1 diabetes.

Pregnancy is known to be associated with an increased demand for insulin that is normally compensated by an increased beta cell mass and insulin secretion. Recent studies have suggested enhanced beta cell function during pregnancy in women with type 1 diabetes (T1D). To explore the possible mechanisms behind enhanced beta cell function during pregnancy in women with T1D we investigated the impact of circulating factors in serum from nine women from each group of pregnant women with and without T1D, after pregnancy and non-diabetic non-pregnant women on rat islet cell proliferation and apoptosis, and on T-lymphocyte activation. In addition, circulating levels of pancreatic hormones and selected cytokines and adipokines were measured. Rat islet cell proliferation was higher in serum from pregnant women with T1D (p < 0.05) compared to T1D women after pregnancy. Apoptosis in INS-1E cell was lower (p < 0.05) in serum from pregnant women with T1D compared to T1D women after pregnancy. T-lymphocyte cell (Jurkat) proliferation was reduced by serum from pregnant women without T1D only (p < 0.05). Higher C-peptide levels and lower levels of ghrelin, IL-6, MCP-1, IL-8 and adipsin were observed in pregnant women with T1D compared to T1D women after pregnancy. In conclusion, the improved beta cell function in women with T1D during pregnancy may be due to lower levels of proinflammatory cytokines and/or higher levels of pregnancy-associated growth factors.

Protocol for a randomised controlled trial of a co-produced, complex, health promotion intervention for women with prior gestational diabetes and their families: the Face-it study.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with an increased risk of future diabetes in both mother, father and offspring. More knowledge is needed about how to effectively reduce the risk of diabetes through sustained behavioural interventions in these families. The Face-it intervention is a complex health promotion intervention embedded in multi-level supportive environments. The aim of the intervention is to reduce type 2 diabetes risk and increase quality of life among families in the first year following a GDM-affected pregnancy by promoting physical activity, healthy dietary behaviours and breastfeeding through a focus on social support, motivation, self-efficacy, risk perception and health literacy. METHODS: This national multicentre study is a two-arm randomised controlled trial including 460 women with GDM in a ratio of 2 (intervention):1 (usual care). The Face-it intervention consists of three main components: 1) additional visits from municipal health visitors, 2) digital health coaching tailored to family needs and 3) a structured cross-sectoral communication system in the health care system. The intervention runs from 3 to 12 months after delivery. The primary outcome is maternal body mass index at 12 months after delivery as a proxy for diabetes risk. The women will be examined at baseline and at follow-up, and this examination will include blood tests, oral glucose tolerance test (OGTT), anthropometrics, blood pressure, self-reported diet and physical activity, breastfeeding, quality of life, health literacy, physical and mental health status, risk perception and social support. Aside from those data collected for OGTT and breastfeeding and offspring parameters, the same data will be collected for partners. Data on offspring anthropometry will also be collected. Information on pregnancy- and birth-related outcomes will be derived from the medical records of the woman and child. DISCUSSION: This randomised controlled trial seeks to demonstrate whether the Face-it intervention, addressing the individual, family and health care system levels, is superior to usual care in reducing diabetes risk for mothers and their families. Coupled with a process evaluation and an economic analysis, the study will provide evidence for policymakers and health services about health promotion among families affected by GDM and the potential for reducing risk of type 2 diabetes and associated conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03997773. Registered June 25, 2019 - Retrospectively registered.

Physical activity, sedentary behavior and development of preeclampsia in women with preexisting diabetes.

AIMS: To explore the association between physical activity in early pregnancy and development of preeclampsia in women with preexisting diabetes. METHODS: In a prospective cohort study of 189 women with preexisting diabetes (110 type 1 and 79 type 2 diabetes), physical activity during pregnancy including sedentary behavior was evaluated with the Pregnancy Physical Activity Questionnaire. Primary outcome was preeclampsia. Secondary outcomes were preterm delivery, large and small for gestational age infants. RESULTS: Women developing preeclampsia (n = 23) had higher diastolic blood pressure in early pregnancy (mean 82 ± 9 SD vs. 77 ± 8, p = 0.004) and were more often nulliparous (91 vs. 52%, p < 0.001) compared with the remaining women (n = 166). Total physical activity in early pregnancy was similar between the groups (median 148 metabolic equivalent of task hours per week (MET-h/week) (interquartile range 118-227) versus 153 (121-205), p = 0.97). In early pregnancy, women developing preeclampsia reported a higher level of sedentary behavior (15 MET-h/week (7-18) versus 7 (4-15); p = 0.04); however, when adjusting for parity, diastolic blood pressure and smoking, the association attenuated (p = 0.13). Total physical activity and sedentary behavior in early pregnancy were not associated with preterm delivery, large or small for gestational age infants. CONCLUSIONS: Among women with diabetes, sedentary behavior was reported higher in early pregnancy in women developing preeclampsia compared with the remaining women, while total physical activity was similar. Sedentary behavior was a predictor of preeclampsia in the univariate analysis, but not in the multiple regression analysis, and larger studies are needed to evaluate this possible modifiable risk factor. Trial registration The study was registered at ClinicalTrials.gov (ID: NCT02890836).

Treatment with the long-acting insulin analog degludec during pregnancy in women with type 1 diabetes: An observational study of 22 cases.

AIM: To report glycemic control and pregnancy outcome in pregnant women with type 1 diabetes on insulin degludec. METHODS: Twenty-two women with type 1 diabetes on degludec from conception to delivery between 2014 and 2018 were compared with 51 pregnant women with type 1 diabetes on glargine. RESULTS: Baseline characteristics were comparable, however HbA1c was higher at median 9 (range 5-19) weeks in women on degludec compared to women on glargine (6.9% (5.7-8.7); (52 (39-72) mmol/mol) versus 6.4% (5.1-10.1); (46 (32-87) mmol/mol), p = 0.04). HbA1c was similar in late pregnancy (6.3% (5.6-7.1); (45 (38-54) mmol/mol) versus 6.1% (5.2-9.0); (43 (33-75) mmol/mol), p = 0.28). The prevalence of severe hypoglycemia was 3 (14%) versus 6 (12%), p = 1.00 during pregnancy and 0 versus 1, p = 1.00 during hospital admittance after delivery. Most women on degludec used one daily injection in early (20 (91%) versus 25 (49%), p = 0.001) and late pregnancy (21 (96%) versus 19 (37%), p < 0.001). No significant differences in obstetrical and neonatal outcomes were found between the groups. Maternal hospital admittance after delivery was 2 (1-5) versus 3 (2-11) days (p = 0.004). CONCLUSIONS: Glycemic control in late pregnancy, severe hypoglycemia during and immediately after pregnancy as well as pregnancy outcome were comparable in women on degludec or glargine. Degludec initiated preconceptionally may be continued in pregnancy.

The impact of restricted gestational weight gain by dietary intervention on fetal growth in women with gestational diabetes mellitus.

AIMS/HYPOTHESIS: We aimed to investigate the impact of maternal gestational weight gain (GWG) during dietary treatment on fetal growth in pregnancies complicated by gestational diabetes (GDM). METHODS: This was a retrospective cohort study of 382 women consecutively diagnosed with GDM before 34 weeks' gestation with live singleton births in our centre (Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark) between 2011 and 2017. The women were stratified into three groups according to restricted (53%), appropriate (16%) and excessive (31%) weekly GWG during dietary treatment (using the Institute of Medicine guidelines) to estimate compliance with an energy-restricted 'diabetes diet' (6000 kJ/day [1434 kcal/day], with approximately 50% of energy intake coming from carbohydrates with a low glycaemic index, and a carbohydrate intake of 175 g/day). Insulin therapy was initiated if necessary, according to local clinical guidelines. RESULTS: Glucose tolerance, HbA1c, weekly GWG before dietary treatment (difference between weight at GDM diagnosis and pre-pregnancy weight, divided by the number of weeks) and SD score for fetal abdominal circumference were comparable across the three groups at diagnosis of GDM at 276 ± 51 weeks (gestation time is given as weeksdays). The women were followed for 100 ± 51 weeks, during which 54% received supplementary insulin therapy and the average (mean) GWG during dietary treatment was 0 kg, 3 kg and 5 kg in the three groups, respectively. Excessive weekly GWG during dietary treatment, reflecting poor dietary adherence was associated with increasing HbA1c (p = 0.014) from diagnosis of GDM to late pregnancy and infants with a birthweight-SD score of 0.59 ± 1.6. In contrast, restricted weekly GWG during dietary treatment, reflecting strict dietary adherence, was associated with decreasing HbA1c (p = 0.001) from diagnosis of GDM to late pregnancy and infants with a birthweight-SD score of 0.15 ± 1.1, without increased prevalence of infants born small for gestational age. Excessive GWG during dietary treatment and late-pregnancy HbA1c were identified as potentially modifiable clinical predictors of infant birthweight-SD score (p = 0.02 for both variables) after correction for confounders. CONCLUSIONS/INTERPRETATION: Restricted GWG during dietary treatment was associated with healthier fetal growth in women with GDM. GWG during dietary treatment and late-pregnancy HbA1c were identified as potentially modifiable clinical predictors of infant birthweight-SD score.