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.

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.

Automated Insulin Delivery for Pregnant Women With Type 1 Diabetes: Where do we stand?

Automated insulin delivery (AID) systems mimic an artificial pancreas via a predictive algorithm integrated with continuous glucose monitoring (CGM) and an insulin pump, thereby providing AID. Outside of pregnancy, AID has led to a paradigm shift in the management of people with type 1 diabetes (T1D), leading to improvements in glycemic control with lower risk for hypoglycemia and improved quality of life. As the use of AID in clinical practice is increasing, the number of women of reproductive age becoming pregnant while using AID is also expected to increase. The requirement for lower glucose targets than outside of pregnancy and for frequent adjustments of insulin doses during pregnancy may impact the effectiveness and safety of AID when using algorithms for non-pregnant populations with T1D. Currently, the CamAPS® FX is the only AID approved for use in pregnancy. A recent randomized controlled trial (RCT) with CamAPS® FX demonstrated a 10% increase in time in range in a pregnant population with T1D and a baseline glycated hemoglobin (HbA1c) ≥ 48 mmol/mol (6.5%). Off-label use of AID not approved for pregnancy are currently also being evaluated in ongoing RCTs. More evidence is needed on the impact of AID on maternal and neonatal outcomes. We review the current evidence on the use of AID in pregnancy and provide an overview of the completed and ongoing RCTs evaluating AID in pregnancy. In addition, we discuss the advantages and challenges of the use of current AID in pregnancy and future directions for research.

Appendiceal Neuroendocrine Neoplasms: an Update for 2023.

PURPOSE OF REVIEW: To summarize the literature from the last 5 years on treatment of appendiceal neuroendocrine neoplasms (aNEN). Furthermore, to evaluate the prognostic significance of lymph node metastases, indications for adjuvant treatment, and challenges of the current follow-up regimen. RECENT FINDINGS: Simple appendectomy is sufficient in tumors < 1 cm while extended surgery is indicated in tumors > 2 cm. In a multicenter study of aNENs measuring 1-2 cm, extended surgery offered no significant prognostic advantage and is now limited to incomplete tumor resection or high-grade G2 or G3 aNEN. Follow-up remains debatable, as the use of imaging and biomarkers lacks validation. While surgical procedure is well established in aNEN tumors < 1 cm and > 2 cm, the need for extended surgery in aNEN tumors 1-2 cm is questionable. Future studies should address the prognostic impact of lymph node metastases and the optimal design and duration of follow-up.

Faster-acting insulin aspart versus insulin aspart in the treatment of type 1 or type 2 diabetes during pregnancy and post-delivery (CopenFast): an open-label, single-centre, randomised controlled trial.

BACKGROUND: Faster-acting insulin aspart (faster aspart) is considered safe for use during pregnancy and breastfeeding but has not been evaluated in this population. We aimed to evaluate the effect of faster aspart versus insulin aspart on fetal growth, in women with type 1 or type 2 diabetes during pregnancy and post-delivery. METHODS: This open-label, single-centre, superiority trial was conducted at Rigshospitalet, Copenhagen, Denmark. Participants aged 18 years or older with type 1 or type 2 diabetes were stratified by diabetes type and insulin treatment modality (multiple daily injections or insulin pump), randomly assigned 1:1 to faster aspart or insulin aspart, from 8 weeks and 0 days (8+0) of gestation to 13+6 weeks of gestation, and followed up until 3 months post-delivery. Primary outcome was infant birthweight SD score. Secondary outcomes included HbA1c as well as maternal and fetal outcomes in all participants during the trial. This trial is registered with ClinicalTrials.gov, NCT03770767. FINDINGS: Between Nov 11, 2019 and May 10, 2022, 109 participants were included in the faster aspart group and 107 in the insulin aspart group. Primary outcome data were available in 203 (94%) of 216 participants, and no participants discontinued treatment during the trial. Mean birthweight SD score was 1·0 (SD 1·4) in the faster aspart group versus 1·2 (1·3) in the insulin aspart group; estimated treatment difference -0·22 [-0·58 to 0·14]; p=0·23. At 33 weeks of gestation, mean HbA1c was 42 mmol/mol (SD 6 mmol/mol; 6·0% [SD 0·9%]) versus 43 mmol/mol (SD 7 mmol/mol; 6·1% [SD 1·2%]); estimated treatment difference -1·01 (-2·86 to 0·83), p=0·28. No additional safety issues were observed with faster aspart compared with insulin aspart. INTERPRETATION: Treatment with faster aspart resulted in similar fetal growth and HbA1c, relative to insulin aspart, in women with type 1 or type 2 diabetes. Faster aspart can be used in women with type 1 or type 2 diabetes during pregnancy and post-delivery with no additional safety issues. FUNDING: Novo Nordisk. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Prediction and prevention of preeclampsia in women with preexisting diabetes: the role of home blood pressure, physical activity, and aspirin.

Women with type 1 or type 2 (preexisting) diabetes are four times more likely to develop preeclampsia compared with women without diabetes. Preeclampsia affects 9%-20% of pregnant women with type 1 diabetes and 7%-14% of pregnant women with type 2 diabetes. The aim of this narrative review is to investigate the role of blood pressure (BP) monitoring, physical activity, and prophylactic aspirin to reduce the prevalence of preeclampsia and to improve pregnancy outcome in women with preexisting diabetes. Home BP and office BP in early pregnancy are positively associated with development of preeclampsia, and home BP and office BP are comparable for the prediction of preeclampsia in women with preexisting diabetes. However, home BP is lower than office BP, and the difference is greater with increasing office BP. Daily physical activity is recommended during pregnancy, and limiting sedentary behavior may be beneficial to prevent preeclampsia. White coat hypertension in early pregnancy is not a clinically benign condition but is associated with an elevated risk of developing preeclampsia. This renders the current strategy of leaving white coat hypertension untreated debatable. A beneficial preventive effect of initiating low-dose aspirin (150 mg/day) for all in early pregnancy has not been demonstrated in women with preexisting diabetes.

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.

Management of type 1 diabetes in pregnancy: update on lifestyle, pharmacological treatment, and novel technologies for achieving glycaemic targets.

Glucose concentrations within target, appropriate gestational weight gain, adequate lifestyle, and, if necessary, antihypertensive treatment and low-dose aspirin reduces the risk of pre-eclampsia, preterm delivery, and other adverse pregnancy and neonatal outcomes in pregnancies complicated by type 1 diabetes. Despite the increasing use of diabetes technology (ie, continuous glucose monitoring and insulin pumps), the target of more than 70% time in range in pregnancy (TIRp 3·5-7·8 mmol/L) is often reached only in the final weeks of pregnancy, which is too late for beneficial effects on pregnancy outcomes. Hybrid closed-loop (HCL) insulin delivery systems are emerging as promising treatment options in pregnancy. In this Review, we discuss the latest evidence on pre-pregnancy care, management of diabetes-related complications, lifestyle recommendations, gestational weight gain, antihypertensive treatment, aspirin prophylaxis, and the use of novel technologies for achieving and maintaining glycaemic targets during pregnancy in women with type 1 diabetes. In addition, the importance of effective clinical and psychosocial support for pregnant women with type 1 diabetes is also highlighted. We also discuss the contemporary studies examining HCL systems in type 1 diabetes during pregnancies.

Is the Biphasic Effect of Diabetes and Obesity on Fetal Growth a Risk Factor for Childhood Obesity?

In pregnancies of women with obesity or diabetes, neonates are often overgrown. Thus, the pregnancy period in these women offers a window of opportunity to reduce childhood obesity by preventing neonatal overgrowth. However, the focus has been almost exclusively on growth in late pregnancy. This perspective article addresses possible growth deviations earlier in pregnancy and their potential contribution to neonatal overgrowth. This narrative review focuses on six large-scale, longitudinal studies that included ∼14,400 pregnant women with at least three measurements of fetal growth. A biphasic pattern in growth deviation, including growth reduction in early pregnancy followed by overgrowth in late pregnancy, was found in fetuses of women with obesity, gestational diabetes mellitus (GDM), or type 1 diabetes compared with lean women and those with normal glucose tolerance. Fetuses of women with these conditions have reduced abdominal circumference (AC) and head circumference (HC) in early pregnancy (observed between 14 and 16 gestational weeks), while later in pregnancy they present the overgrown phenotype with larger AC and HC (from approximately 30 gestational weeks onwards). Fetuses with early-pregnancy growth reduction who end up overgrown presumably have undergone in utero catch-up growth. Similar to postnatal catch-up growth, this may confer a higher risk of obesity in later life. Potential long-term health consequences of early fetal growth reduction followed by in utero catch-up growth need to be explored.

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.

Secular trend for increasing birthweight in offspring of pregnant women with type 1 diabetes: is improved placentation the reason?

Despite enormous progress in managing blood glucose levels, pregnancy in women with type 1 diabetes still carries risks for the growing fetus. While, previously, fetal undergrowth was not uncommon in these women, with improved maternal glycaemic control we now see an increased prevalence of fetal overgrowth. Besides short-term implications, offspring of women with type 1 diabetes are more likely to become obese and to develop diabetes and features of the metabolic syndrome. Here, we argue that the increase in birthweight is paradoxically related to improved glycaemic control in the pre- and periconceptional periods. Good glycaemic control reduces the prevalence of microangiopathy and improves placentation in early pregnancy, which may lead to unimpeded fetal nutrition. Even mild maternal hyperglycaemia may then later result in fetal overnutrition. This notion is supported by circumstantial evidence that lower HbA1c levels as well as increases in markers of placental size and function in early pregnancy are associated with large-for-gestational age neonates. We also emphasise that neonates with normal birthweight can have excessive fat deposition. This may occur when poor placentation leads to initial fetal undergrowth, followed by fetal overnutrition due to maternal hyperglycaemia. Thus, the complex interaction of glucose levels during different periods of pregnancy ultimately determines the risk of adiposity, which can occur in fetuses with both normal and elevated birthweight. Prevention of fetal adiposity calls for revised goal setting to enable pregnant women to maintain blood glucose levels that are closer to normal. This could be supported by continuous glucose monitoring throughout pregnancy and appropriate maternal gestational weight gain. Future research should consider the measurement of adiposity in neonates.

Regional divergence and time trends in the prevalence of gestational diabetes mellitus: a national Danish cohort study.

AIMS: To evaluate the prevalence and time trends of gestational diabetes mellitus (GDM) across the five regions of Denmark with uniform national guidelines for screening and diagnosing GDM. METHODS: This register-based national cohort study included 287,684 births from 2013 to 2017. Trends in GDM prevalence over time and differences between the five regions were evaluated. Crude and adjusted odd ratios (ORs) for GDM were calculated including potential confounding clinical risk factors as age, BMI, educational level, marital status, parity, country of origin and assisted reproduction. RESULTS: From 2013 to 2017, GDM prevalence in Denmark increased by 7% per year (OR 1.07, 95% CI 1.06-1.09, P < 0.001). GDM prevalence varied considerably between regions and ranged from 3.0 to 5.9% in 2017, corresponding to a maximal regional difference of 97%. In crude analyses, the risk of GDM in 2017 was significantly different in four of five regions compared to the remaining regions (OR ranging from 0.60 to 1.55), and these differences persisted after adjusting for confounding clinical risk factors (adjusted OR: 0.59-1.45). CONCLUSION: The prevalence of GDM increased over time in all Danish regions with substantial regional divergence. Up to a 97%, difference in GDM prevalence was observed between Danish regions, which was not explained by available clinical risk factors. This occurred despite national guidelines and raises the question of whether regional variations in screening efficacy, diagnostic procedures or inequality in clinical health care access may explain the observed differences.

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.

Surgery in Patients with Gastro-Entero-Pancreatic Neuroendocrine Carcinomas, Neuroendocrine Tumors G3 and High Grade Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms.

OPINION STATEMENT: In the 2019 WHO guidelines, the classification of gastro-entero-pancreatic neuroendocrine neoplasms (GEP NEN) has changed from one being based on Ki-67 proliferation index alone to one that also includes tumor differentiation. Consequently, GEP NENs are now classified as well-differentiated neuroendocrine tumor (NET), NET G1 (Ki-67 <3%), NET G2 (Ki-67 3-20%) and NET G3 (Ki-67 >20%), and poorly differentiated neuroendocrine carcinoma (NEC) (Ki-67 >20%). It has been suggested that NET G3 should be treated as NET G2 with respect to surgery, while surgical management of NEC should be expanded from local disease to also include patients with advanced disease where curative surgery is possible. High grade mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) have a neuroendocrine and a non-neuroendocrine component mostly with a poor prognosis. All studies evaluating the effect of surgery in NEC and MiNEN are observational and hold a risk of selection bias, which may overestimate the beneficial effect of surgery. Further, only a few studies on the effect of surgery in MiNEN exist. This review aims to summarize the data on the outcome of surgery in patients with GEP NET G3, GEP NEC and high grade MiNEN. The current evidence suggests that patients with NEN G3 and localized disease and NEN G3 patients with metastatic disease where curative surgery can be achieved may benefit from surgery. In patients with MiNEN, it is currently not possible to evaluate on the potential beneficial effect of surgery due to the low number of studies.

Falling Insulin Requirement in Pregnant Women With Diabetes Delivering Preterm: Prevalence, Predictors, and Consequences.

CONTEXT: Falling insulin requirements often lead to considerations of whether a pregnancy can continue safely or if delivery is indicated. OBJECTIVE: To evaluate prevalence and predictors of falling insulin requirements in pregnant women with preexisting diabetes delivering preterm and to explore the relationship to fetal asphyxia and neonatal morbidity. METHODS: A prospective cohort study of 101 consecutive singleton pregnant women with preexisting diabetes delivering preterm < 37 weeks (68 type 1 and 33 type 2 diabetes) where the prevalence of falling insulin requirements (≥20%) before delivery was recorded. RESULTS: In total, 27% (27/101) experienced falling insulin requirements of median 30% (interquartile range 24-40) before delivery. In all women with type 1 diabetes, the prevalence was 37% (25/68), whereas it was 43% (24/56) in those with indicated preterm delivery and 6% (2/33) among women with type 2 diabetes. In women with type 1 diabetes and indicated preterm delivery, falling insulin requirements were first identified at 34 + 5 (33 + 6-35 + 4) weeks + days and delivery occurred 3 (1-9) days later. Gestational age at delivery, prevalence of suspected fetal asphyxia, and neonatal morbidity were similar in women with and without falling insulin requirements. Neither glycemic control, nausea, or preeclampsia was associated with falling insulin requirement. CONCLUSION: Falling insulin requirements often preceded preterm delivery in women with type 1 diabetes, foremost when preterm delivery was indicated, but was not related to fetal asphyxia or neonatal morbidity. Whether falling insulin requirements in late pregnancy are a warning sign of placental insufficiency or mainly reflects variations in normal physiology needs further investigation.

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.

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.