Improved Pregnancy Outcome in Type 1 Diabetic Women With Microalbuminuria or Diabetic Nephropathy: Effect of intensified antihypertensive therapy?

OBJECTIVE—To describe pregnancy outcome in type 1 diabetic women with normoalbuminuria, microalbuminuria, or diabetic nephropathy after implementation of an intensified antihypertensive therapeutic strategy

Design and rationale of a large, international, prospective cohort study to evaluate the occurrence of malformations and perinatal/neonatal death using insulin detemir in pregnant women with diabetes in comparison with other long-acting insulins

BACKGROUND: There are a lack of data regarding the effect of basal insulin analogues on rates of events like congenital malformation and perinatal mortality in diabetic pregnancy. METHODS: The present study is a prospective, non-interventional, multicentre cohort study conducted in seven countries, designed to assess the safety of insulin detemir during pregnancy, and to monitor the health status of resulting infants (exposed in utero) up to 1 year of age. The study population includes women with type 1 or type 2 diabetes, who are pregnant and being treated with insulin. Data will be collected in the context of routine practice. The primary endpoint is the proportion of pregnancies in women treated with insulin detemir, compared with other basal insulin regimens, which do not result in any of the following events: major congenital malformations, perinatal death or neonatal death. A sample size of 3075 pregnancies was calculated to provide an 80% power to detect a difference of 3.5% between groups in the primary endpoint at a 5% level. DISCUSSION: The study will also examine other important maternal endpoints (e.g., incidences of severe hypoglycaemia and pre-eclampsia) and perinatal outcomes such as overweight neonates, as well as infant outcomes at 1 year of age. It has a fixed recruitment period from 2013 to 2018, enrolling all eligible patients, and is expected to inform future prescribing with basal insulins in diabetic pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01892319 (date registered: 27.06.2013). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12884-016-1177-4) contains supplementary material, which is available to authorized users

Poor pregnancy outcome in women with type 1 diabetes is predicted by elevated HbA1c and spikes of high glucose values in the third trimester

OBJECTIVE: To analyse data from a randomised, controlled study of prandial insulin aspart versus human insulin, both with NPH insulin, in pregnant women with type 1 diabetes for potential factors predicting poor pregnancy outcomes. RESEARCH DESIGN/METHOD: Post hoc analysis including 91 subjects randomised prior to pregnancy with known outcome in early pregnancy and 259 subjects randomised prior to pregnancy/during pregnancy of <10 weeks’ gestation with known late-pregnancy outcomes. Poor early-pregnancy outcomes included fetal loss <22 gestational weeks and/or congenital malformation (n = 18). Poor late-pregnancy outcomes included: composite endpoint including pre-eclampsia, preterm delivery and perinatal death (n = 78); preterm delivery (n = 63); and excessive fetal growth (n = 88). RESULTS: 18 patients experienced a malformed/lost fetus in early pregnancy – none preceded by severe hypoglycaemia. Albuminuria in early pregnancy was a significant predictor of poor late-pregnancy outcome (composite endpoint; p = 0.012). In the third trimester, elevated HbA(1c), ≥ 1 plasma glucose (PG) measurement >11 mmol/L (198 mg/dL) and %PG values outside 3.9–7.0 mmol/L (70–126 mg/dL) were significant predictors of poor late-pregnancy outcomes (all p < 0.05). CONCLUSIONS: Elevated HbA(1c), high glucose spikes and out-of-range %PG in the third trimester, and albuminuria in early pregnancy, are associated with poor late-pregnancy outcomes

A randomized trial comparing perinatal outcomes using insulin detemir or neutral protamine Hagedorn in type 1 diabetes

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

Differential adipokine DNA methylation and gene expression in subcutaneous adipose tissue from adult offspring of women with diabetes in pregnancy

Abstract Background Offspring of women with diabetes in pregnancy are at increased risk of type 2 diabetes mellitus (T2DM), potentially mediated by epigenetic mechanisms. The adipokines leptin, adiponectin, and resistin (genes: LEP, ADIPOQ, RETN) play key roles in the pathophysiology of T2DM. We hypothesized that offspring exposed to maternal diabetes exhibit alterations in epigenetic regulation of subcutaneous adipose tissue (SAT) adipokine transcription. We studied adipokine plasma levels, SAT gene expression, and DNA methylation of LEP, ADIPOQ, and RETN in adult offspring of women with gestational diabetes (O-GDM, N = 82) or type 1 diabetes (O-T1DM, N = 67) in pregnancy, compared to offspring of women from the background population (O-BP, N = 57). Results Compared to O-BP, we found elevated plasma leptin and resistin levels in O-T1DM, decreased gene expression of all adipokines in O-GDM, decreased RETN expression in O-T1DM, and increased LEP and ADIPOQ methylation in O-GDM. In multivariate regression analysis, O-GDM remained associated with increased ADIPOQ methylation and decreased ADIPOQ and RETN gene expression and O-T1DM remained associated with decreased RETN expression after adjustment for potential confounders and mediators. Conclusions In conclusion, offspring of women with diabetes in pregnancy exhibit increased ADIPOQ DNA methylation and decreased ADIPOQ and RETN gene expression in SAT. However, altered methylation and expression levels were not reflected in plasma protein levels, and the functional implications of these findings remain uncertain

Assessment of Attention Deficits in Adolescent Offspring Exposed to Maternal Type 1 Diabetes

The aim of this study was to examine the potential association between intrauterine exposure to maternal diabetes and attention deficits in the offspring.Adolescent offspring of a prospectively followed cohort of women with type 1 diabetes (n = 269) and a control group from the background population (n = 293) participated in a follow-up assessment in 2012-2013. We used scores from Conners Continuous Performance Test II to assess attention and based on a principal component analysis we evaluated scores on five different attention factors: focused attention, vigilance, hyperactivity/impulsivity, sustained attention and response style.A higher frequency of the exposed offspring had a parent/self-reported use of Attention Deficit Hyperactivity Disorder (ADHD) medication compared to the control group (2.2% vs. 0.0%, p = 0.01). Clinical significant differences between adolescents exposed to maternal diabetes and unexposed controls were not found in either single scores on Conners Continuous Performance Test or on any of the five attention factors identified.Exposure to maternal type 1 diabetes did not seem to increase the risk of attention deficits in the adolescent offspring. However, a higher self-reported use of ADHD medication in the exposed group could suggest a difference in attention not revealed by the applied test

Beliefs, barriers and preferences of European overweight women to adopt a healthier lifestyle in pregnancy to minimize risk of developing gestational diabetes mellitus: an explorative study

Introduction: Overweight and obese women are at high risk of developing gestational diabetes mellitus (GDM). Lifestyle programs might help curb the GDM risk. We explored beliefs, perceived barriers and preferences regarding lifestyle changes among overweight European pregnant women to help inform the development of future high quality lifestyle interventions. Methods: An explorative mixed methods, two-staged study was conducted to gather information from pregnant European women (BMI≥25kg/m2). In three European countries (Belgium, Netherlands, United Kingdom) interviews were conducted, followed by questionnaires in six other European countries (Austria, Denmark, Ireland, Italy, Poland, Spain). Content analysis, descriptive and chi square statistics were applied (p&#60;0.05). Results: Women preferred to obtain detailed information about their personal risk. The health of their baby was major motivating factor. Perceived barriers for physical activity included pregnancy-specific issues such as tiredness and experiencing physical complaints. Insufficient time was a barrier more frequently reported by women with children. Abstaining from snacking was identified as a challenge for the majority of women, especially for those without children. Women preferred to obtain support from their partner, as well as health professionals and valued flexible lifestyle programs. Conclusions: Healthcare professionals need to inform overweight pregnant women about their personal risk, discuss lifestyle modification and assist in weight management. Lifestyle programs should be tailored to the individual, taking into account barriers experienced by overweight first-time mothers and multipara women