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OBJECTIVE To compare the risk of severe adverse pregnancy complications in women with preexisting diabetes. RESEARCH DESIGN AND METHODS Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations or perinatal or neonatal death (primary end point) following treatment with insulin detemir (detemir) versus other basal insulins. RESULTS Of 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations or perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI −0.01, 0.04]; adjusted risk difference −0.003 [95% CI −0.03, 0.03]). The crude prevalence of one or more congenital malformations (major plus minor) was 9.4% vs. 12.6%, with a similar risk difference before (−0.032 [95% CI −0.064, 0.000]) and after (−0.036 [95% CI –0.081, 0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first trimester (6.5% vs. 6.7% [48 vs. 50 mmol/mol]; estimated mean difference −0.181 [95% CI −0.300, −0.062]) and the second trimester (6.1% vs. 6.3% [43 vs. 45 mmol/mol]; −0.139 [95% CI −0.232, −0.046]) and a lower prevalence of major hypoglycemia (6.0% vs. 9.0%; risk difference −0.030 [95% CI −0.058, −0.002]), preeclampsia (6.4% vs. 10.0%; −0.036 [95% CI −0.064, −0.007]), and stillbirth (0.4% vs. 1.8%; −0.013 [95% CI −0.024, −0.002]) with detemir compared with other basal insulins. However, differences were not significant postadjustment. CONCLUSIONS Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth.

OBJECTIVE Whether hyperglycemia in utero less than overt diabetes is associated with altered childhood glucose metabolism is unknown. We examined associations of gestational diabetes mellitus (GDM) not confounded by treatment with childhood glycemia in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. RESEARCH DESIGN AND METHODS HAPO Follow-up Study (FUS) included 4,160 children ages 10–14 years who completed all or part of an oral glucose tolerance test (OGTT) and whose mothers had a 75-g OGTT at ∼28 weeks of gestation with blinded glucose values. The primary predictor was GDM by World Health Organization criteria. Child outcomes were impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes. Additional measures included insulin sensitivity and secretion and oral disposition index. RESULTS For mothers with GDM, 10.6% of children had IGT compared with 5.0% of children of mothers without GDM; IFG frequencies were 9.2% and 7.4%, respectively. Type 2 diabetes cases were too few for analysis. Odds ratios (95% CI) adjusted for family history of diabetes, maternal BMI, and child BMI z score were 1.09 (0.78–1.52) for IFG and 1.96 (1.41–2.73) for IGT. GDM was positively associated with child’s 30-min, 1-h, and 2-h but not fasting glucose and inversely associated with insulin sensitivity and oral disposition index (adjusted mean difference −76.3 [95% CI −130.3 to −22.4] and −0.12 [−0.17 to −0.064]), respectively, but not insulinogenic index. CONCLUSIONS Offspring exposed to untreated GDM in utero are insulin resistant with limited β-cell compensation compared with offspring of mothers without GDM. GDM is significantly and independently associated with childhood IGT.

Diabetes in pregnancy is associated with adverse pregnancy outcomes including preterm birth. Although the mechanisms leading to these pregnancy complications are still poorly understood, aberrant angiogenesis and endothelial dysfunction play a key role. FKBPL and SIRT-1 are critical regulators of angiogenesis, however, their roles in pregnancies affected by diabetes have not been examined before in detail. Hence, this study aimed to investigate the role of FKBPL and SIRT-1 in pre-gestational (type 1 diabetes mellitus, T1D) and gestational diabetes mellitus (GDM). Placental protein expression of important angiogenesis proteins, FKBPL, SIRT-1, PlGF and VEGF-R1, was determined from pregnant women with GDM or T1D, and in the first trimester trophoblast cells exposed to high glucose (25 mM) and varying oxygen concentrations [21%, 6.5%, 2.5% (ACH-3Ps)]. Endothelial cell function was assessed in high glucose conditions (30 mM) and following FKBPL overexpression. Placental FKBPL protein expression was downregulated in T1D (FKBPL; p

Introduction: Serum progesterone sulfate (P4S) concentrations increase in pregnancy and bind receptors that influence glucose homeostasis. We hypothesized that P4S modulate glucose homeostasis in pregnancy. Methods: Serum P4S were assayed using ultra-performance liquid chromatography- tandem mass spectrometry. Samples were studied in three separate patient groups: women with GDM (n=20) and matched healthy controls (n=38); participants (average 28 weeks’ gestation) from the upper (n=93) and lower (n=94) quartiles of fasting plasma glucose in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study; 11-13 week pregnant women with BMI≤25 or BMI≥35 who subsequently had uncomplicated pregnancies or developed GDM (n=50/group). Glucose-stimulated insulin secretion (GSIS) was quantified in isolated wild-type, Fxr-/- and Tgr5-/- mouse and human islets in the presence of P4S and TRPM3 inhibitor isosakuranetin (ISO). Intracellular calcium concentrations were measured after treatment with P4S in TRPM3 transfected HEK293. Computer modelling using Molecular Operating Environment generated 3D structures of TRPM3 and P4S binding. Results: Epiallopregnanolone sulfate (PM5S) concentrations were reduced in serum samples from the HAPO study participants with higher fasting plasma glucose (p Conclusion: PM5S increases GSIS and concentrations are reduced in the serum of women with GDM. The increased GSIS is mediated by TRPM3. Disclosure H. Fan: None. F. Fraternali: None. K. F. Hunt: None. J. Bowe: None. C. Williamson: Consultant; Self; GlaxoSmithKline plc., Mirum Pharmaceuticals. A. Mitchell: None. M. Giorgi: None. P. M. Jones: None. D. R. Mccance: None. D. A. Andersson: None. S. Bevan: None. H. Marschall: None. I. Eberini: None. Funding Tommy’s; Guy’s and St Thomas’ Biomedical Research Centre; National Health Service

Aims: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). Methods: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. Results: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c 40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. Conclusions: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

Context Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies. Objective To investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44. Design and Intervention FKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling. Settings and Participants Human samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid. Main Outcome Measures Preeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed. Results The CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis. Conclusions The FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.

ContextDiabetes in pregnancy is associated with numerous complications, however the mechanisms are still poorly understood.ObjectiveTo investigate the role of new angiogenesis markers, FKBPL and SIRT-1, in pre-gestational (type 1 diabetes, T1D) and gestational diabetes (GDM).Design and interventionPlacental FKBPL, SIRT-1, PlGF and VEGF-R1 protein expression was determined from pregnant women with GDM or T1D, and in first trimester trophoblast cells exposed to high glucose and varying oxygen concentrations. Endothelial cell function was assessed in high glucose conditions and FKBPL overexpression.Settings and ParticipantsHuman placental samples from pregnant women with GDM (n=6) or T1D (n=8) were collected to assess FKBPL and SIRT-1 protein expression compared to non-diabetic controls.Main outcome measuresTo determine the role of placental FKBPL and/or SIRT-1 in diabetic pregnancies, in first trimester trophoblasts and endothelial cell function in high-glucose environment.ResultsPlacental FKBPL protein expression was downregulated in T1D (FKBPL; pConclusionsFKBPL and/or SIRT-1 downregulation in response to diabetes may have a role in the development of vascular dysfunction in pregnancy, and associated complications such as preeclampsia.

Aim: To evaluate the diagnostic and prognostic performance of alternative diagnostic strategies to oral glucose tolerance tests, including random plasma glucose, fasting plasma glucose and HbA 1c, during the COVID-19 pandemic. Methods: Retrospective service data (Cambridge, UK; 17 736 consecutive singleton pregnancies, 2004–2008; 826 consecutive gestational diabetes pregnancies, 2014–2019) and 361 women with ≥1 gestational diabetes risk factor (OPHELIA prospective observational study, UK) were included. Pregnancy outcomes included gestational diabetes (National Institute of Health and Clinical Excellence or International Association of Diabetes and Pregnancy Study Groups criteria), diabetes in pregnancy (WHO criteria), Caesarean section, large-for-gestational age infant, neonatal hypoglycaemia and neonatal intensive care unit admission. Receiver-operating characteristic curves and unadjusted logistic regression were used to compare random plasma glucose, fasting plasma glucose and HbA 1c performance. Results: Gestational diabetes diagnosis was significantly associated with random plasma glucose at 12 weeks [area under the receiver-operating characteristic curve for both criteria 0.81 (95% CI 0.79–0.83)], fasting plasma glucose [National Institute of Health and Clinical Excellence: area under the receiver-operating characteristic curve 0.75 (95% CI 0.65–0.85); International Association of Diabetes and Pregnancy Study Groups: area under the receiver-operating characteristic curve 0.92 (95% CI 0.85–0.98)] and HbA 1c at 28 weeks' gestation [National Institute of Health and Clinical Excellence: 0.83 (95% CI 0.75–0.90); International Association of Diabetes and Pregnancy Study Groups: 0.84 (95% CI 0.77–0.91)]. Each measure predicts some, but not all, pregnancy outcomes studied. At 12 weeks, ~5% of women would be identified using random plasma glucose ≥8.5 mmol/l (sensitivity 42%; specificity 96%) and at 28 weeks using HbA 1c ≥39 mmol/mol (sensitivity 26%; specificity 96%) or fasting plasma glucose ≥5.2–5.4 mmol/l (sensitivity 18–41%; specificity 97–98%). Conclusions: Random plasma glucose at 12 weeks, and fasting plasma glucose or HbA 1c at 28 weeks identify women with hyperglycaemia at risk of suboptimal pregnancy outcomes. These opportunistic laboratory tests perform adequately for risk stratification when oral glucose tolerance testing is not available.

Gestational diabetes, the most common medical disorder in pregnancy, is defined as glucose intolerance resulting in hyperglycaemia that begins or is first diagnosed in pregnancy. Gestational diabetes is associated with increased pregnancy complications and long-term metabolic risks for the woman and the offspring. However, the current diagnostic and management strategies recommended by national and international guidelines are mainly focused on short-term risks during pregnancy and delivery, except the Carpenter-Coustan criteria, which were based on the risk of future incidence of type 2 diabetes post-gestational diabetes. In this Personal View, first, we summarise the evidence for long-term risk in women with gestational diabetes and their offspring. Second, we suggest that a shift is needed in the thinking about gestational diabetes; moving from the perception of a short-term condition that confers increased risks of large babies to a potentially modifiable long-term condition that contributes to the growing burden of childhood obesity and cardiometabolic disorders in women and the future generation. Third, we propose how the current clinical practice might be improved. Finally, we outline and justify priorities for future research.

Aim: The EVOLVE study examined the risk of major congenital malformations and perinatal or neonatal deaths when using insulin detemir (IDet) versus other basal insulins in pregnant women with pre-existing diabetes. Materials and Methods: A prospective, non-interventional, multinational study in pregnant women with type 1 or type 2 diabetes treated with IDet or other insulin treatment. In the present analysis, 727 women using IDet during pregnancy were compared with 730 women using other basal insulin, mainly insulin glargine. The primary endpoint was the number of women completing ≥22 weeks of gestation without any of the following events: major congenital malformations, perinatal or neonatal deaths. Results: At enrolment 86% of subjects had type 1 diabetes (mean age: 31 years; BMI: 26 kg/m2) and mean A1C was 7.1%. There was no difference between treatment groups in crude or adjusted risk difference for pregnancies without major congenital malformations, perinatal or neonatal deaths (Table). Conclusion: In pregnant women with pre-existing diabetes, IDet was not associated with excess risk of major congenital malformations, perinatal or neonatal deaths vs. other basal insulin. Disclosure E.R. Mathiesen: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Lilly Diabetes, Novo Nordisk A/S, Sanofi-Aventis. A. Alibegovic: Employee; Self; Novo Nordisk A/S. L.N. Husemoen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. P. Kelkar: Employee; Self; Novo Nordisk Service Centre India Private Ltd. D.R. McCance: None. H.W. de Valk: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Funding Novo Nordisk A/S

Vitamin D deficiency is a common occurrence globally, and particularly so in pregnancy. There is conflicting evidence regarding the role of vitamin D during pregnancy in non-skeletal health outcomes for both the mother and the neonate. The aim of this study was to investigate the associations of maternal total 25-hydroxy vitamin D (25OHD) with neonatal anthropometrics and markers of neonatal glycaemia in the Belfast centre of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Serological samples (n 1585) were obtained from pregnant women in the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, between 24 and 32 weeks’ gestation as part of the HAPO study. 25OHD concentrations were measured by liquid chromatography tandem-MS. Cord blood and neonatal anthropometric measurements were obtained within 72 h of birth. Statistical analysis was performed. After adjustment for confounders, birth weight standard deviation scores (SDS) and birth length SDS were significantly associated with maternal total 25OHD. A doubling of maternal 25OHD at 28 weeks’ gestation was associated with mean birth weight SDS and mean birth length SDS higher by 0·05 and 0·07, respectively (both, P=0·03). There were no significant associations with maternal 25OHD and other measures of neonatal anthropometrics or markers of neonatal glycaemia. In conclusion, maternal total 25OHD during pregnancy was independently associated with several neonatal anthropometric measurements; however, this association was relatively weak.

Aims The diagnosis of gestational diabetes mellitus (GDM) during pregnancy can lead to anxiety. This study evaluated the impact of an innovative patient-centred educational DVD on anxiety and glycaemic control in women newly diagnosed with GDM. Methods 150 multi-ethnic women, aged 19-44 years, from three UK hospitals were randomised to either usual care plus DVD (DVD group, n=77) or usual care alone (control group, n=73) at GDM diagnosis. Primary outcomes were anxiety (State-Trait Anxiety Inventory) and mean 1-hour postprandial capillary self-monitored blood glucose for all meals, on day prior to follow-up. Results No significant difference between the DVD and control group were reported, for anxiety (37.7±11.7 vs 36.2±10.9; mean difference after adjustment for covariates (95%CI) 2.5 (-0.8, 5.9) or for mean 1-hour postprandial glucose for all meals (6.9±0.9 vs 7.0±1.2 mmol/L; -0.2 (-0.5, 0.2). However, the DVD group had significantly lower postprandial breakfast glucose compared to the control group (6.8±1.2 vs 7.4±1.9 mmol/L; -0.5 (-1.1, - Conclusions The results in this trial did not highlight any differences between those who received the intervention and those who received usual care. It is possible that women already felt supported by their frequent attendance at specialist clinics for monitoring and advice. Healthcare professional and family support are key elements to empowering women with GDM and require further consideration in future interventions. Nonetheless, educational resources such as this will be beneficial to help support women given the current resource and time implications of the year on year rises in the incidence of gestational diabetes.

Aim To evaluate the effect of regional implementation of a preconception counselling resource into routine diabetes care on pregnancy planning indicators. Methods A preconception counselling DVD was distributed to women by diabetes care teams and general practices. Subsequently, in a prospective population-based study, pregnancy planning indicators were evaluated. The post-DVD cohort (n = 135), including a viewed-DVD subgroup (n = 58), were compared with an historical cohort (pre-DVD, n = 114). Primary outcome was HbA1c at first diabetes-antenatal visit. Secondary outcomes included preconception folic acid consumption, planned pregnancy and HbA1c recorded in the 6 months preconception. Results Mean first visit HbA1c was lower post-DVD vs. pre-DVD: 7.5% vs. 7.8% [58.4 vs. 61.8 mmol/mol]; p = 0.12), although not statistically significant. 53% and 20% of women with type 1 and 2 diabetes, respectively, viewed the DVD. The viewed-DVD subgroup were significantly more likely to have lower first visit HbA1c: 6.9% vs. 7.8% [52.1 vs. 61.8 mmol/mol], P < 0.001; planned pregnancy (88% vs. 59%, P < 0.001); taken folic acid preconception (81% vs. 43%, P = 0.001); and had HbA1c recorded preconception (88% vs. 53%, P < 0.001) than the pre-DVD cohort. Conclusions Implementation of a preconception counselling resource was associated with improved pregnancy planning indicators. Women with type 2 diabetes are difficult to reach. Greater awareness within primary care of the importance of preconception counselling among this population is needed.

Objective: Mild iodine deficiency has re-emerged among school girls in the UK. We wished to study a contemporaneous pregnant population because a relationship between maternal iodine deficiency and offspring cognitive scores has recently been reported. The WHO has set a median population urinary iodine concentration (UIC) of ≥100 and ≥150 µg/L to define adequacy outside of and during pregnancy, respectively. Iodine creatinine ratio (ICR) is also used to correct for dilution effects (sufficiency ≥150 µg/g creatinine in pregnancy). Design and methods: A total of 241 women were followed across trimesters (T) into the postpartum period (PPP) along with 80 offspring with spot urine sampling and food frequency questionnaires. Results: Median UIC was 73 µg/L in the 1st T (ICR 102 µg/g creatinine) despite 55% taking iodine-containing supplements. Median UICs were 94, 117 and 90 µg/L in the 2nd T, 3rd T and PPP, respectively. Corresponding ICRs were 120, 126 and 60 µg/g creatinine. ICR was associated with volume of milk consumed throughout pregnancy. Median UIC among the offspring was 148 µg/L, with no difference between the breast- and formula-fed babies. Conclusions: Pregnant women living in Northern Ireland may be at risk of iodine deficiency across pregnancy and into the PPP while the offspring are iodine sufficient. This is the first study of its kind in the UK with data for pregnant women and their offspring. The UK does not provide an iodine fortification programme nor offer routine iodine dietary advice in pregnancy and this requires consideration by public health agencies.

Congenital malformations and perinatal mortality rates remain severalfold higher in pregnant women with type 1 diabetes than in the background population, and still only a minority of women plan their pregnancy. Optimizing glycemic control is the accepted goal, but remains challenging, and must be constantly balanced against the risks of hypoglycemia. Recent advances including Continuous Glucose Monitoring Systems, Continuous Subcutaneous Insulin Infusion, Closed Loop Devices and very Fast Acting Insulin Aspart analogs offer new possibilities to increase glucose time in target in selected, motivated patients, however their relative roles and indication for use require further elucidation. The importance of education cannot be overstated.

Aim To examine, in a proof-of-concept study, the ability of visceral adipose tissue depth and subcutaneous fat depth measured in early pregnancy to predict subsequent gestational diabetes, and to assess the performance of these measures as screening tests for gestational diabetes compared with use of the current UK criteria. Methods A total of 100 women in early pregnancy were recruited from a maternity hospital in Belfast, UK. Visceral adipose tissue depth and subcutaneous fat depth were measured, and each participant underwent a 75-g oral glucose tolerance test at 28 weeks' gestation for the diagnosis of gestational diabetes using WHO 2013 criteria. Results Eighty women completed the study, of whom 15 (19%) developed gestational diabetes. Increasing visceral adipose tissue depth, but not subcutaneous fat depth, was associated with greater gestational diabetes risk after adjusting for confounding factors (odds ratio for a 1-sd rise 2.09, 95% CI 1.06-4.12; P=0.03). Visceral adipose tissue depth ≥4.27 cm had greater sensitivity compared with current National Institute of Health and Care Excellence criteria (87% vs 40%, respectively; P=0.02) and similar specificity (62% vs 74%, respectively; P=0.15) for identifying gestational diabetes. Conclusions Ultrasonography-measured visceral adipose tissue in early pregnancy is a potential clinical tool for improving sensitivity of selective screening for gestational diabetes, which, compared with universal oral glucose tolerance testing, is likely to reduce by half the numbers requiring this test. Further larger studies are now required for confirmation, including investigation into impact on clinical outcomes.

ObjectiveTo explore the concerns, needs and knowledge of women diagnosed with Gestational Diabetes Mellitus (GDM).DesignA qualitative study of women with GDM or a history of GDM.MethodsNineteen women who were both pregnant and recently diagnosed with GDM or post- natal with a recent history of GDM were recruited from outpatient diabetes care clinics. This qualitative study utilised focus groups. Participants were asked a series of open-ended questions to explore 1) current knowledge of GDM; 2) anxiety when diagnosed with GDM, and whether this changed overtime; 3) understanding and managing GDM and 4) the future impact of GDM. The data were analysed using a conventional content analysis approach.FindingsWomen experience a steep learning curve when initially diagnosed and eventually become skilled at managing their disease effectively. The use of insulin is associated with fear and guilt. Diet advice was sometimes complex and not culturally appropriate. Women appear not to be fully aware of the short or long-term consequences of a diagnosis of GDM.ConclusionsMidwives and other Health Care Professionals need to be cognisant of the impact of a diagnosis of GDM and give individual and culturally appropriate advice (especially with regards to diet). High quality, evidence based information resources need to be made available to this group of women. Future health risks and lifestyle changes need to be discussed at diagnosis to ensure women have the opportunity to improve their health.

Background Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Women with type 1 diabetes are considered a high-risk group for developing pre-eclampsia. Much research has focused on biomarkers as a means of screening for pre-eclampsia in the general maternal population; however, there is a lack of evidence for women with type 1 diabetes. Objectives To undertake a systematic review to identify potential biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes. Search strategy We searched Medline, EMBASE, Maternity and Infant Care, Scopus, Web of Science and CINAHL Selection criteria Studies were included if they measured biomarkers in blood or urine of women who developed pre-eclampsia and had pre-gestational type 1 diabetes mellitus Data collection and analysis A narrative synthesis was adopted as a meta-analysis could not be performed, due to high study heterogeneity. Main results A total of 72 records were screened, with 21 eligible studies being included in the review. A wide range of biomarkers was investigated and study size varied from 34 to 1258 participants. No single biomarker appeared to be effective in predicting pre-eclampsia; however, glycaemic control was associated with an increased risk while a combination of angiogenic and anti-angiogenic factors seemed to be potentially useful. Conclusions Limited evidence suggests that combinations of biomarkers may be more effective in predicting pre-eclampsia than single biomarkers. Further research is needed to verify the predictive potential of biomarkers that have been measured in the general maternal population, as many studies exclude women with diabetes preceding pregnancy.

While overt diabetes during pregnancy is associated with a higher childhood risk of altered glucose metabolism, the contribution of GDM to this disorder is less clear. Using data from HAPO FUS, we examined associations of maternal GDM not confounded by treatment with childhood glucose metabolism. Maternal glycemic status was based on a 75 g oral glucose tolerance test (OGTT) at ∼28 weeks gestation. Offspring disorders of glucose metabolism (impaired glucose tolerance or type 2 diabetes using American Diabetes Association criteria) were assessed at the HAPO FUS visit using an OGTT in 41children at mean age 11.4 (range 7.9-15.5) years. Insulin sensitivity (IS) was calculated using the Matsuda index and insulin secretion using the insulinogenic index. GDM was defined by International Association of Diabetes in Pregnancy Study Groups criteria. Among offspring of mothers with and without GDM, 10.6% and 5.2%, respectively, had a disorder of glucose metabolism. After adjusting for field center, maternal pregnancy variables and child age, Tanner stage and family history of diabetes at HAPO FUS, the odds ratio and 95% confidence interval (CI) for a disorder of glucose metabolism was 1.98 (1.44-2.74), p=3.1 x 10-5. Adjusting for maternal BMI at OGTT, child’s BMI z score, or both did not attenuate risk. Offspring of GDM mothers had lower IS (29.7 ± 12.5, mean ± SD) compared to offspring of non-GDM mothers (33.7 ± 13.8) with a mean difference of -2.1 (95% CI -3.2 - -1.0), p= 1.9 x 10-4 after adjusting for field center, maternal pregnancy variables and child age, Tanner stage and family history of diabetes at HAPO FUS. The association was attenuated but still significant after adjusting for maternal BMI and/or child BMI z score. Maternal GDM was not associated with insulinogenic index. In summary, exposure to untreated GDM in utero is significantly and independently associated with childhood disorders of glucose metabolism, in part through insulin resistance. Disclosure W. Brickman: None. P. Catalano: None. P.E. Clayton: None. C. Deerochanawong: None. J. Hamilton: None. P.M. Lashley: None. J.M. Lawrence: None. Y. Lebenthal: Speaker's Bureau; Self; Novo Nordisk Inc.. Consultant; Self; Kamada. D.R. McCance: None. W.H. Tam: None. A. Kuang: None. L.P. Lowe: None. B.E. Metzger: None. D. Scholtens: None. W. Lowe: None.

Aims To measure total 25-hydroxyvitamin D levels in women in mid-pregnancy who participated in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) observational study, and to investigate the associations between levels of 25-hydroxyvitamin D and markers of gestational diabetes mellitus and lipid biomarkers. Methods A total of 1585 pregnant women had serum samples available for measurement. Participants were recruited from the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, at 24-32 weeks' gestation, as part of the HAPO study. 25-hydroxyvitamin D concentrations were measured using liquid chromatography tandem mass spectrometry. Glucose, C-peptide and lipid levels were previously analysed in a central laboratory. Statistical analysis was performed. Results The median (interquartile range) 25-hydroxyvitamin D concentration during pregnancy was 38.6 (24.1-60.7) nmol/l, with 65.8% of women being vitamin D-deficient (≤50 nmol/l). In regression analysis, the association between maternal 25-hydroxyvitamin D and fasting plasma glucose levels approached significance [regression coefficient -0.017 (95% CI -0.034 to 0.001); P=0.06], and a significant positive association was observed between maternal 25-hydroxyvitamin D and β-cell function [1.013 (95% CI 1.001 to 1.024); P=0.031]. Maternal 25-hydroxyvitamin D level was positively associated with HDL [0.047 (95% CI 0.021 to 0.073) P≤ 0.001] and total cholesterol [0.085 (95% CI 0.002 to 0.167); P=0.044] in regression analysis. Conclusions These results indicate a high prevalence of vitamin D deficiency during pregnancy, which requires identification and treatment; however, only weak associations were observed between 25-hydroxyvitamin D level and markers of glucose and insulin metabolism. This would suggest that these are of doubtful clinical significance.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Adoption of a Mediterranean diet (MD) reduces cardiovascular disease (CVD) risk. However, interventions to achieve dietary behaviour change are typically resource intensive. Peer support offers a potentially low-cost approach to encourage dietary change. The primary objective of this randomised controlled trial is to explore the feasibility of peer support versus a previously tested dietetic-led intervention to encourageMDbehaviour change, and to test recruitment strategies, retention and attrition in order to inform the design of a definitive trial. A total of 75 overweight adults at high CVD risk who do not follow a MD (Mediterranean Diet Score (MDS ≤3)) will be randomly assigned to either: a minimal intervention (written materials), a proven intervention (dietetic support, written materials and key MD foods), or a peer support intervention (group-based community programme delivered by lay peers) for 12 months. The primary end-point is change in MDS from baseline to 6 months (adoption of MD). Secondary end-points include: change in MDS from 6 to 12 months (maintenance of MD), effects on nutritional biomarkers and CVD risk factors, fidelity of implementation, acceptability and feasibility of the peer support intervention. This study will generate important data regarding the feasibility of peer support for ease of adoption of MD in an ‘at risk’ Northern European population. Data will be used to direct a larger scale trial, where the clinical efficacy and cost-effectiveness of peer support will be tested.

Context- Obesity is a global epidemic, and there is a focus on identifying markers of obesity in children with a view to prevention. Objective- We aimed to prospectively examine the association of maternal fasting lipids with adiposity in 5-7-year old offspring in a large observational study.Design- 1612 pregnant women were recruited to the Belfast centre of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study in a large tertiary maternity hospital at an average of 28 weeks gestation. Maternal fasting total cholesterol, LDL-cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) were estimated at 28 weeks gestation. At follow-up (5-7 years later), 1224 offspring were re-examined and adiposity expressed as body mass index (BMI) Z score (1990 British Growth Standard) and sum of skin fold thicknesses (triceps, subscapular and suprailiac). Statistical significance was more rigorously defined as pResults- No linear relation was found between maternal lipids and offspring BMI Z score or sum of skin folds (p≥0.01) using correlation analysis. Using logistic regression, there was no relation between maternal lipids and offspring adiposity controlled for birthweight Z score, offspring age, offspring gender, smoking during pregnancy, maternal BMI during pregnancy and fasting glucose during pregnancy, (p≥0.01), although the association between maternal LDL cholesterol and offspring BMI Z score ≥85th percentile approached significance [OR 1.15 (1.03 to 1.29) p=0.02].Conclusion-Maternal 28 week gestational fasting lipids are not associated with offspring BMI or subcutaneous adiposity at age 5-7 years.

Diabetes in pregnancy is still considered a high-risk condition for both mother and baby. Even in the best centres, malformation and mortality rates are reportedly twofold to fivefold higher than in the background population, and pregnancy planning rates remain obstinately poor. Increasing global rates of type 2 diabetes are now extending into pregnancy, with similarly poor outcomes to type 1 diabetes, and excess maternal weight is adding to the complexity of management. Over the last 5-10 years, several randomised trials have offered new insight into the role of oral hypoglycaemic drugs and insulin analogues in pregnancy, while continuous subcutaneous insulin infusion (CSII) pumps and continuous glucose monitors (CGMs) are under scrutiny. The relevance of minor degrees of hyperglycaemia to adverse pregnancy outcome was clearly demonstrated by the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study, but translation of these data into clinical practice has proved challenging because of the continuum of risk. Long-term metabolic and cardiovascular implications of hyperglycaemia during pregnancy for mother and child are now generally recognised with major implications for public health.

Background: Neuroendocrine tumours (NETs) of the small bowel are difficult to diagnose as symptoms are non-specific and more often found in common gastrointestinal diseases. Chromogranin A (CGA), urinary 5 hydroxy indole acetic acid (U-5HIAA) and Neurokinin A (NKA) are used as laboratory diagnostic tests but results may be misleading or confusing. Aim: To clarify the relevance of NET biomarkers for diagnosis of small bowel NETs. Design: A review of laboratory test results. Methods: We reviewed 500 consecutive raised plasma CGA, U-5HIAA and plasma NKA, results from patients in N Ireland. The diagnosis of NET was confirmed by the Northern Ireland Cancer Registry. Results: In 500 specimens recording raised CGA, 52.2% were from patients with NETs, 13.6% being small bowel tumours, 5.4% of specimens from patients with auto-immune atrophic gastritis and 15.4% from patients taking proton pump inhibitors. In 500 specimens with raised U-5HIAA, 87.8% were from patients with NETs, 68.2% being small bowel tumours. Lung NETs contributed 12.2% and NETs from other sites, 7.4%. Of 500 specimens with raised NKA (reference range (RR) > 20 ng/L), 72.6% were from patients with small bowel NETs and 6% specimens from patients with other NETs. In 20% of specimens NKA concentrations were 21–23 ng/L, within limits of assay precision. Conclusion: CGA remains the best general circulating marker for NETs although only half of raised test results are due to an NET. U-5HIAA is an excellent marker for small bowel and lung NETs with 80% of high test results confirming these diagnoses. NKA is the most specific biomarker for small bowel NETs.

Systematic review of mortality in childhood-/adolescent-diagnosed Type 1 diabetes and examination of factors explaining the mortality variation between studies.Relevant studies were identified from systematic searches of MEDLINE and EMBASE. Observed and expected numbers of deaths were extracted, and standardised mortality ratios (SMRs) and 95 % confidence intervals (CIs) were calculated. Negative binomial regression was used to investigate association between mortality and study/country characteristics.Thirteen relevant publications with mortality data were identified describing 23 independent studies. SMRs varied markedly ranging from 0 to 854 (χ (2) = 70.68, df = 21, P0.0001). Significant associations were observed between SMR and mid-year of follow-up [incidence rate ratio (IRR) 0.95, 95 % CI 0.91-0.99 equivalent to a 5 % decrease per year], between SMR and infant mortality rate (IRR 1.07, 95 % CI 1.02-1.12, a 7 % increase for each death per 1,000 live births) and, after omitting an outlier, between SMR and health expenditure as a percentage of gross domestic product (GDP) (IRR 0.79, 95 % CI 0.68-0.93, a 21 % decrease for each one percent increase in GDP). No relationship was detected between SMR and a country's childhood diabetes incidence rate or GDP.Excess mortality in childhood-/adolescent-diagnosed Type 1 diabetes is apparent across countries worldwide. Excesses were less marked in more recent studies and in countries with lower infant mortality and higher health expenditure.

OBJECTIVE To examine the association between fatty acid binding protein 4 (FABP4) and pre-eclampsia risk in women with type 1 diabetes. RESEARCH DESIGN AND METHODS Serum FABP4 was measured in 710 women from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT) in early pregnancy and in the second trimester (median 14 and 26 weeks’ gestation, respectively). RESULTS FABP4 was significantly elevated in early pregnancy (geometric mean 15.8 ng/mL [interquartile range 11.6–21.4] vs. 12.7 ng/mL [interquartile range 9.6–17]; P < 0.001) and the second trimester (18.8 ng/mL [interquartile range 13.6–25.8] vs. 14.6 ng/mL [interquartile range 10.8–19.7]; P < 0.001) in women in whom pre-eclampsia later developed. Elevated second-trimester FABP4 level was independently associated with pre-eclampsia (odds ratio 2.87 [95% CI 1.24–6.68], P = 0.03). The addition of FABP4 to established risk factors significantly improved net reclassification improvement at both time points and integrated discrimination improvement in the second trimester. CONCLUSIONS Increased second-trimester FABP4 independently predicted pre-eclampsia and significantly improved reclassification and discrimination. FABP4 shows potential as a novel biomarker for pre-eclampsia prediction in women with type 1 diabetes.

OBJECTIVE To examine the impact of maternal obesity on completion of fetal anomaly screening. METHODS A retrospective analysis of 500 anomaly scans (19+0-21+6 weeks) was included. Women were categorised according to the World Health Organisation (WHO) body mass index (BMI) classification: normal weight (18.50-24.99 kg/m2), overweight (25.00-29.99 kg/m2), obese class I (30-34.99 kg/m2), obese class II (35.00-39.99 kg/m2) and obese class III (≥40.00 kg/m2). A fetal anomaly imaging scoring system was developed from the National Health Service (NHS) Fetal Anomaly Screening Programme standard to evaluate scans. RESULTS Image quality deteriorated as BMI increased and was significantly different across the BMI categories (P

Summary Objectives and background Recent guidelines recommend insulin‐like growth factor (IGF‐1), random growth hormone (GH) and nadir GH on an oral glucose tolerance test (OGTT) for assessment of acromegaly. At this Regional Centre, the 24‐hour GH profile has also been used. Design, patients and measurements We evaluated 57 GH profiles from 34 patients from 2008 to 2012. Samples were drawn every 2 hour and matched with 0800 GH, nadir GH after OGTT and IGF‐1. Results Correlations between the mean 13‐point profiles and mean 5‐point profile, OGTT nadir and 0800 GH were as follows: r = .99, .99 and .90, respectively (P 1 μg/L, but 5 required further treatment. Conclusions Growth hormone profiling is not necessary for assessing the majority of patients with acromegaly if there is confidence in the local IGF‐1 assay. When undertaken, a 5‐point profile is adequate. In patients with very high 0800 GH, 24‐hour profiling was useful in demonstrating partial therapeutic success but did not alter management. Further work is needed to explore the possible role of GH profiling in stratifying patients with discordant IGF‐1 and GH results.

A Practical Manual of Diabetes in Pregnancy , A Practical Manual of Diabetes in Pregnancy , کتابخانه دیجیتال جندی شاپور اهواز

OBJECTIVE To examine the monitoring, management, and outcomes of pituitary tumors in pregnancy. METHODS A national, prospective, observational, population-based case series study was conducted in all U.K. consultant-led obstetric units over 3 years using the U.K. Obstetric Surveillance System. To evaluate rates of adverse pregnancy outcomes, women with a macroprolactinoma (10 mm or greater) or nonfunctioning pituitary adenoma, diagnosed before or during pregnancy, were compared with two comparison groups: 1) a U.K. Obstetric Surveillance System cohort with singleton (n=2,205) or twin (n=27) pregnancy; and 2) data from the Office of National Statistics (n=2,703,102). Main outcome measures were the incidence, management, and frequency of adverse maternal and offspring outcomes of pituitary tumors in pregnancy. RESULTS There were 71 confirmed cases of pituitary tumors in pregnancy (49 macrolactinoma, 16 nonfunctioning adenomas, three acromegaly, three Cushing's disease). The women with pituitary tumors were 4 years older than comparison women (P

OBJECTIVE To assess the relationship between second and third trimester glycemic control and adverse outcomes in pregnant women with type 1 diabetes, as uncertainty exists about optimum glycemic targets. RESEARCH DESIGN AND METHODS Pregnancy outcomes were assessed prospectively in 725 women with type 1 diabetes from the Diabetes and Pre-eclampsia Intervention Trial. HbA1c (A1C) values at 26 and 34 weeks’ gestation were categorized into five groups, the lowest, RESULTS An A1C of 6.0–6.4% (42–47 mmol/mol) at 26 weeks’ gestation was associated with a significantly increased risk of large for gestational age (LGA) (odds ratio 1.7 [95% CI 1.0–3.0]) and an A1C of 6.5–6.9% (48–52 mmol/mol) with a significantly increased risk of preterm delivery (odds ratio 2.5 [95% CI 1.3–4.8]), pre-eclampsia (4.3 [1.7–10.8]), need for a neonatal glucose infusion (2.9 [1.5–5.6]), and a composite adverse outcome (3.2 [1.3–8.0]). These risks increased progressively with increasing A1C. Results were similar at 34 weeks’ gestation. Glucose data showed less consistent trends, although the risk of a composite adverse outcome increased with preprandial glucose levels between 6.0 and 6.9 mmol/L at 34 weeks (3.3 [1.3–8.0]). CONCLUSIONS LGA increased significantly with an A1C ≥6.0 (42 mmol/mol) at 26 and 34 weeks' gestation and with other adverse outcomes with an A1C ≥6.5% (48 mmol/mol). The data suggest that there is clinical utility in regular measurement of A1C during pregnancy.

Aim To examine the role of placental protein tyrosine nitration and p38-Mitogen-Activated Protein Kinase α (p38-MAPKα), Extra Cellular-Signal Regulated Kinase (ERK) and c-Jun NH2-Terminal Kinase (JNK) activity, in the pathogenesis of type 1 diabetic pre-eclampsia, and the putative modulation of these indices by maternal vitamin C and E supplementation. Methods Placental samples were obtained from a sub-cohort of the DAPIT trial: a randomised placebo-controlled trial of antioxidant supplementation to reduce pre-eclampsia in type 1 diabetic pregnancy. Placenta from placebo-treated: normotensive (NT) [n = 17], gestational hypertension (GH) [n = 7] and pre-eclampsia (PE) [n = 6] and vitamin-treated: NT (n = 20), GH (n = 4) and PE (n = 3) was analysed. Protein tyrosine nitration was assessed by immunohistochemistry in paraffin-embedded tissue. Catalytic activities of placental p38-MAPKα, ERK and JNK were measured by enzyme-linked immunosorbent assay (ELISA). Results Nitrotyrosine immunostaining was present in placebo-treated NT, GH and PE placentae, with no significant difference observed between the groups. There was a non-significant trend towards decreased p38-MAPKα activity in PE vs NT control placentae. ERK and JNK were similar among the three outcome placebo groups and vitamin supplementation did not significantly alter their activity. Conclusion Nitrotyrosine immunopositivity in normotensive diabetic placentae indicates some degree of tyrosine nitration in uncomplicated diabetic pregnancy, possibly due to inherent oxidative stress and peroxynitrite production. Our results suggest that p38-MAPKα, ERK and JNK are not directly involved in the pathogenesis of type 1 diabetic pre-eclampsia and are not modulated by vitamin-supplementation.

OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of insulin detemir (IDet) with neutral protamine Hagedorn (NPH), both with insulin aspart, in pregnant women with type 1 diabetes. The perinatal and obstetric pregnancy outcomes are presented.METHODS: Subjects were randomized to IDet (n = 152) or NPH (n = 158) ≤12 months before pregnancy or at 8-12 gestational weeks.RESULTS: For IDet and NPH, there were 128 and 136 live births, 11 and 9 early fetal losses, and two and one perinatal deaths, respectively. Gestational age at delivery was greater for children from the IDet arm than the NPH arm (treatment difference: 0.49 weeks [95% CI 0.11;0.88], p = 0.012, linear regression). Sixteen children had a malformation (IDet: n = 8/142, 5.6%; NPH: n = 8/145, 5.5%). The incidence of adverse events was similar between treatments.CONCLUSION: IDet is as well tolerated as NPH as regards perinatal outcomes in pregnant women with type 1 diabetes and no safety issues were identified.

Background This study evaluated the effect of statins in Primary biliary cirrhosis (PBC) on endothelial function, anti-oxidant status and vascular compliance. Methods Primary biliary cirrhosis patients with hypercholesterolaemia were randomized to receive 20 mg simvastatin or placebo in a single blind, randomized controlled trial. Body mass index, blood pressure, glucose, liver function, lipid profile, immunoglobulin levels, serological markers of endothelial function and anti-oxidant status were measured as well as vascular compliance, calculated from pulse wave analysis and velocity, at recruitment and again at 3, 6, 9 and 12 months. Results Twenty-one PBC patients (F = 20, mean age = 55) were randomized to simvastatin 20 mg (n = 11) or matched placebo (n = 10). At completion of the trial, serum cholesterol levels in the simvastatin group were significantly lower compared with the placebo group (4.91 mmol/L vs. 6.15 mmol/L, P = 0.01). Low-density lipoprotein (LDL) levels after 12 months were also significantly lower in the simvastatin group (2.33 mmol/L vs. 3.53 mmol/L, P = 0.01). After 12 months of treatment, lipid hydroperoxides were lower (0.49 μmol/L vs. 0.59 μmol/L, P = 0.10) while vitamin C levels were higher (80.54 μmol/L vs. 77.40 μmol/L, P = 0.95) in the simvastatin group. Pulse wave velocity remained similar between treatment groups at 12 months (8.45 m/s vs. 8.80 m/s, P = 0.66). Only one patient discontinued medication owing to side effects. No deterioration in liver transaminases was noted in the simvastatin group. Conclusions Statin therapy in patients with PBC appears safe and effective towards overall reductions in total cholesterol and LDL levels. Our initial study suggests that simvastatin may also confer advantageous effects on endothelial function and antioxidant status.

A 52-year-old lady presented with a history of occasional, severe abdominal cramps, postprandial diarrhoea and weight loss. After routine gastrointestinal investigations, she was diagnosed with irritable bowel syndrome. Over six months, she developed occasional facial flushing prompting assessment of neuroendocrine tumour markers. Urinary 5HIAA, 5HT, chromogranin A and neurokinin A were significantly elevated. Scans showed extensive hepatic metastases but did not show the location of a primary tumour. Somatostatin analogue therapy was commenced but despite increasing doses, symptoms increased and biomarkers rose dramatically. Interferon alpha was introduced concomitant with somatostatin analogue therapy. Biomarkers were monitored regularly. Within six months, symptoms abated and biomarkers reduced, continuing to fall over the next year, close to reference range. To manage side-effects of interferon alpha, dose was reduced from time to time. During these short periods, neurokinin A showed significant transient increases (75–150 ng/L) and carcinoid symptoms returned. For more than seven years, and with the co-operation of the patient, a balance was achieved between interferon alpha side-effects and disease control. Scans showed tumour load to be stable. The patient survived for 10 years post diagnosis. She chose to discontinue interferon alpha and received peptide receptor radiation therapy in her final year. Throughout, neurokinin A remained the most sensitive monitor of her disease progression.

SummaryObjective Addition of dehydroepiandrosterone sulphate (DHEAS) to standard pituitary replacement may improve quality of life and glucose metabolism. Conflicting results from the previous work probably relate to differences in populations studied and assessment techniques used. We examined the effects of DHEAS on insulin action and the quality of life in female patients with hypopituitary hypoadrenalism. Design Randomized, double-blind, placebo-controlled, crossover design was used. Patients received either DHEAS 50 mg daily or placebo for 12 weeks. Patients Fourteen hypopituitary females on stable standard replacement therapy and with low DHEAS were enrolled. Measurements Insulin action by euglycaemic hyperinsulinaemic clamp and extensive quality of life parameters were assessed after each treatment. Results Serum DHEAS (DHEAS 5·4 ± 0·8 vs placebo

Diabet. Med. 29, 950–956 (2012) Abstract Aims To determine if an educational DVD increases knowledge and changes attitudes of women with diabetes towards preconception care. Methods Ninety-seven women with diabetes (Type 1, n = 89; Type 2, n = 8), aged 18–40 years, completed a pre-DVD and post-DVD intervention study by postal questionnaire. Beliefs and attitudes associated with preventing an unplanned pregnancy and seeking preconception care were assessed using a validated questionnaire; scales included benefits, barriers, personal attitudes and self-efficacy. Knowledge of pregnancy planning and pregnancy-related risks were assessed by a 22-item questionnaire. Results After viewing the DVD there was significant positive change in women’s perceived benefits of, and their personal attitudes to, receiving preconception care and using contraception: change in score post-DVD viewing 0.7 (95% confidence interval 0.3, 1.2), P = 0.003, and 0.8 (0.3, 1.2), P = 0.001, respectively. The DVD significantly improved self-efficacy, that is, self-confidence to use contraception for prevention of an unplanned pregnancy and to access preconception care [3.3 (1.9, 4.7), P

OBJECTIVE To determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. RESEARCH DESIGN AND METHODS Participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were measured. Adverse pregnancy outcomes included birth weight, newborn percent body fat, and cord C-peptide >90th percentiles, primary cesarean delivery, preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT. Multiple logistic regression was used to examine associations of GDM and obesity with outcomes. RESULTS Mean maternal BMI was 27.7, 13.7% were obese (BMI ≥33.0 kg/m2), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women, odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93–2.47), for obesity alone 1.73 (1.50–2.00), and for both GDM and obesity 3.62 (3.04–4.32). Results for primary cesarean delivery and preeclampsia and for cord C-peptide and newborn percent body fat >90th percentiles were similar. Odds for birth weight >90th percentile were progressively greater with both higher OGTT glucose and higher maternal BMI. There was a 339-g difference in birth weight for babies of obese GDM women, compared with babies of normal/underweight women (64.2% of all women) with normal glucose based on a composite OGTT measure of fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women). CONCLUSIONS Both maternal GDM and obesity are independently associated with adverse pregnancy outcomes. Their combination has a greater impact than either one alone.

OBJECTIVE To compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. RESEARCH DESIGN AND METHODS Eligible pregnant women underwent a 75-g OGTT at 24–32 weeks’ gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. RESULTS Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ± SD A1C was 4.79 ± 0.40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skinfolds, and percent body fat >90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight >90th percentile for each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1-, and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide >90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. CONCLUSIONS On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women.

Despite improved obstetric surveillance and better management of maternal hyperglycaemia over the last few decades, perinatal mortality and congenital malformation rates remain several fold higher in pregnancy complicated by diabetes than in the background population. A worldwide increase in the prevalence of type 2 diabetes is now being realized in the pregnancy context with apparently similar or even worse outcomes to type 1 diabetes. While the relevance of periconceptual glycaemic control to maternal fetal outcome is clearly established, only around half of women with type 1 diabetes plan their pregnancy and rates are even lower in type 2 diabetes. In the last 5-10 years, several landmark trials have pointed to the validity of gestational diabetes mellitus as a diagnostic entity, however translation of recently published consensus guidelines for diagnosis and screening into routine clinical practice may prove challenging. An expanding therapeutic armamentarium and increasing awareness of the long-term implications of diabetic pregnancy for both mother and child present new challenges for clinical care, research and public health.

Background and aimsPublic health campaigns recommend increased fruit and vegetable (FV) consumption as an effective means of cardiovascular risk reduction. During an 8 week randomised control trial among hypertensive volunteers, we noted significant improvements in endothelium-dependent vasodilatation with increasing FV consumption. Circulating indices of inflammation, endothelial activation and insulin resistance are often employed as alternative surrogates for systemic arterial health. The responses of several such biomarkers to our previously described FV intervention are reported here.Methods and resultsHypertensive volunteers were recruited from medical outpatient clinics. After a common 4 week run-in period during which FV consumption was limited to 1 portion per day, participants were randomised to 1, 3 or 6 portions daily for 8 weeks. Venous blood samples for biomarker analyses were collected during the pre and post-intervention vascular assessments. A total of 117 volunteers completed the 12 week study. Intervention-related changes in circulating levels of high sensitivity C-reactive protein (hsCRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1) did not differ significantly between FV groups. Similarly, there were no significant between group differences of change in homeostasis model assessment (HOMA) scores.ConclusionsDespite mediating a significant improvement in acetylcholine induced vasodilatation, increased FV consumption did not affect a calculated measure of insulin resistance or concentrations of the circulating biomarkers measured during this study. Functional indices of arterial health such as endothelium-dependent vasomotion are likely to provide more informative cardiovascular end-points during short-term dietary intervention trials.

OBJECTIVE To assess the relationship between glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes. RESEARCH DESIGN AND METHODS Pregnancy outcome (pre-eclampsia or gestational hypertension) was assessed prospectively in 749 women from the randomized controlled Diabetes and Pre-eclampsia Intervention Trial (DAPIT). HbA1c (A1C) values were available up to 6 months before pregnancy (n = 542), at the first antenatal visit (median 9 weeks) (n = 721), at 26 weeks’ gestation (n = 592), and at 34 weeks’ gestation (n = 519) and were categorized as optimal ( RESULTS Pre-eclampsia and gestational hypertension developed in 17 and 11% of pregnancies, respectively. Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia (P < 0.05, respectively). In early pregnancy, A1C ≥8.0% was associated with a significantly increased risk of pre-eclampsia (odds ratio 3.68 [95% CI 1.17–11.6]) compared with optimal control. At 26 weeks’ gestation, A1C values ≥6.1% (good: 2.09 [1.03–4.21]; moderate: 3.20 [1.47–7.00]; and poor: 3.81 [1.30–11.1]) and at 34 weeks’ gestation A1C values ≥7.0% (moderate: 3.27 [1.31–8.20] and poor: 8.01 [2.04–31.5]) significantly increased the risk of pre-eclampsia compared with optimal control. The adjusted odds ratios for pre-eclampsia for each 1% decrement in A1C before pregnancy, at the first antenatal visit, at 26 weeks’ gestation, and at 34 weeks’ gestation were 0.88 (0.75–1.03), 0.75 (0.64–0.88), 0.57 (0.42–0.78), and 0.47 (0.31–0.70), respectively. Glycemic control was not significantly associated with gestational hypertension. CONCLUSIONS Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy. These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes.