Insulin-treated Gestational Diabetes Mellitus Research Articles

Kidney Disease in Women With Previous Gestational Diabetes Mellitus: A Nationwide Register-Based Cohort Study.

The association between gestational diabetes mellitus (GDM) and incident kidney disease, the mediating effects of diabetes and hypertension, and the impact of severity of metabolic dysfunction during pregnancy on the risk of incident kidney disease were investigated in this study. This Danish, nationwide, register-based cohort study included all women giving birth between 1997 and 2018. Outcomes included chronic kidney disease (CKD) and acute kidney disease, based on diagnosis codes. Cox regression analyses explored the association between GDM and kidney disease. A proxy for severity of metabolic dysfunction during pregnancy was based on GDM diagnosis and insulin treatment during GDM in pregnancy and was included in the models as an interaction term. The mediating effects of subsequent diabetes and hypertension prior to kidney disease were quantified using mediation analyses. Data from 697,622 women were used. Median follow-up was 11.9 years. GDM was associated with higher risk of CKD (adjusted hazard ratio [aHR] 1.92; 95% CI 1.67-2.21), whereas acute kidney disease was unrelated to GDM. The proportions of indirect effects of diabetes and hypertension on the association between GDM and CKD were 75.7% (95% CI 61.8-89.6) and 30.3% (95% CI 25.2-35.4), respectively, as assessed by mediation analyses. The CKD risk was significantly increased in women with insulin-treated GDM and no subsequent diabetes compared with women without GDM (aHR 2.35; 95% CI 1.39-3.97). The risk of CKD was significantly elevated after GDM irrespective of subsequent development of diabetes and hypertension. Furthermore, women with severe metabolic dysfunction during pregnancy had the highest CKD risk.

Continuous glucose monitoring metrics and pregnancy outcomes in insulin-treated diabetes: A post-hoc analysis of the GlucoMOMS trial.

To investigate the association between continuous glucose monitoring (CGM) metrics and perinatal outcomes in insulin-treated diabetes mellitus in pregnancy. In a post-hoc analysis of the GlucoMOMS randomized controlled trial, we investigated the association between the metrics of an offline, intermittent CGM, glycated haemoglobin (HbA1c) and perinatal outcomes per trimester in different types of diabetes (type 1, 2 or insulin-treated gestational diabetes mellitus [GDM]). Data were analysed using multivariable binary logistic regression. Outcomes of interest were neonatal hypoglycaemia, pre-eclampsia, preterm birth, large for gestational age (LGA) and Neonatal Intensive Care Unit (NICU) admission. The glucose target range was defined as 3.5-7.8 mmol/L (63-140 mg/dL). Of the 147 participants (N = 50 type 1 diabetes, N = 94 type 2 diabetes/insulin-treated GDM) randomized to the CGM group of the GlucoMOMS trial, 115 participants had CGM metrics available and were included in the current study. We found that, in pregnancies with type 1 diabetes, a higher second trimester mean glucose was associated with LGA (odds ratio 2.6 [95% confidence interval 1.1-6.2]). In type 2 and insulin-treated gestational diabetes, an increased area under the curve above limit was associated with LGA (odds ratio 10.0 [95% confidence interval 1.4-72.8]). None of the CGM metrics were associated with neonatal hypoglycaemia, pre-eclampsia, shoulder dystocia, preterm birth and NICU admission rates for pregnancies complicated by any type of diabetes. In this study, in type 2 diabetes or insulin-treated GDM, the glucose increased area under the curve above limit was associated with increased LGA. In type 1 diabetes, the mean glucose was the major determinant of LGA. Our study found no evidence that other CGM metrics determined adverse pregnancy outcomes.

Diet-Treated Gestational Diabetes Mellitus Is an Underestimated Risk Factor for Adverse Pregnancy Outcomes: A Swedish Population-Based Cohort Study.

In Sweden, diet-treated gestational diabetes mellitus (GDM) pregnancies have been managed as low risk. The aim was to evaluate the risk of adverse perinatal outcomes among women with diet-treated GDM compared with the background population and with insulin-treated GDM. This is a population-based cohort study using national register data between 1998 and 2012, before new GDM management guidelines and diagnostic criteria in Sweden were introduced. Singleton pregnancies (n = 1,455,580) without pregestational diabetes were included. Among 14,242 (1.0%) women diagnosed with GDM, 8851 (62.1%) were treated with diet and 5391 (37.9%) with insulin. In logistic regression analysis, the risk was significantly increased in both diet- and insulin-treated groups (vs. background) for large-for-gestational-age newborns, preeclampsia, cesarean section, birth trauma and preterm delivery. The risk was higher in the insulin-treated group (vs. diet) for most outcomes, but perinatal mortality rates neither differed between treatment groups nor compared to the background population. Diet as a treatment for GDM did not normalize pregnancy outcomes. Pregnancies with diet-treated GDM should therefore not be considered as low risk. Whether changes in surveillance and treatment improve outcomes needs to be evaluated.

Differential placental ceramide levels during gestational diabetes mellitus (GDM)

BackgroundGestational diabetes mellitus (GDM) is associated with important factors that influence fetal development. Sphingolipids are known to be associated with the development of diabetes. Our objective was to examine ceramide, a key sphingolipid, hyperosmolarity, and apoptosis in placentas from GDM patients treated with insulin or diet.MethodsCeramide levels were assessed in placental tissues using immunohistochemistry. Immunoblot was performed to quantify serine palmitoyltransferase (SPT), the rate-limiting enzyme in ceramide biosynthesis, NFAT5, SMIT, AR, caspase 3 and the X-linked inhibitor of apoptosis. Trophoblast cells were treated with insulin or ceramide and assessments for mitochondrial respiration, caspase 3 and XIAP were also performed.ResultsImmunohistochemistry showed increased ceramides in the placental villous trophoblasts of the insulin-treated GDM patients. Nuclear SPT was upregulated only in the insulin-treated GDM placenta when compared to controls. Nuclear NFAT5 was also increased in the GDM placenta. Active caspase 3 was elevated in placentas from both insulin- and diet-treated GDM patients. Mitochondrial respiration was decreased in trophoblasts treated with ceramide. Active caspase was not changed while XIAP protein was increased in trophoblasts treated with ceramide.ConclusionsOur findings confirm the presence of ceramide in the human placenta of control and GDM patients. Furthermore, we conclude that ceramide is increased in the placental trophoblast during insulin treatment and that its upregulation correlates with elevated NFAT5, SMIT, increased apoptosis and decreased trophoblast mitochondrial respiration.

Thrombin Generation in Chinese Pregnant Women and the Effect of Insulin Use on Thrombin Generation in Patients with GDM.

Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis. Calibrated automated thrombogram (CAT) is a test to monitor the thrombin generation (TG), a laboratory marker of thrombosis risk, and increases during normal pregnancy, but it is still unclear whether TG is related to the use of insulin in pregnant women with gestational diabetes mellitus (GDM). We performed thrombin generation by CAT on 135 normal pregnant women, including 43 in first trimester, 32 in second trimester, 60 in third trimester, respectively; 68 pregnant women with GDM were also enrolled, 19 patients with GDM using insulin to control blood glucose and 49 patients control their blood glucose through diet and exercise with noninsulin treatment. The overall CAT parameters were calculated using descriptive statistics method with mean ± standard deviation. Mean endogenous thrombin potential, peak thrombin generation, and StartTail time increased significantly with the pregnancy. There was no significant difference in TG test parameters except StartTail time(P = .003) in insulin-treated GDM group when compared to those without insulin in the GDM group. The normal ranges for CAT parameters in pregnant women were determined. Thrombin generation increased significantly in first trimester and remains stable in second and third trimester. The use of insulin in patient with GDM did not affect thrombin generation test. Our study helps to establish the reference range of thrombin generation in Chinese normal pregnant population and provide more basis to predict the risk of thrombus complicating during pregnancy.

Incidence and risk factors for gestational diabetes mellitus in twin versus singleton pregnancies.

To compare the incidence and risk factors for gestational diabetes mellitus (GDM) between women with twin and singleton pregnancies. Retrospective study of all women who had a twin or singleton birth in Ontario (2012-2016). Risk ratios (RR) and 95% CIs for GDM (stratified by type of treatment) were adjusted for relevant confounding variables. Multivariable Poisson regression analysis was used to identify risk factors for GDM in twin and singleton gestations. Of 270,843 women who met inclusion criteria, 266,942 (98.6%) and 3901 (1.4%) had a singleton and a twin pregnancy, respectively. Women with twins had a significantly higher risk for overall GDM (aRR = 1.13, 95% CI 1.01-1.28) and diet-treated GDM (aRR = 1.20, 95% CI 1.01-1.42) while the association with insulin-treated GDM was not significant (aRR = 1.07, 95% CI 0.89-1.28). Maternal age ≥ 35years, non-Caucasian ethnicity and BMI > 30kg/m2 were independent risk factors for GDM among women with twins and singletons, and the magnitude of the association of these factors with GDM was similar. Women with twins are at increased risk of GDM, mainly due to a higher rate of diet-treated GDM. Despite higher baseline risk of GDM in women with twins, the effect of known risk factors for GDM is similar to that observed in singletons.

Using technology to support care in gestational diabetes mellitus: Quantitative outcomes of an exploratory randomised control trial of adjunct telemedicine for gestational diabetes mellitus (TeleGDM)

AimsThe increasing incidence and prevalence of gestational diabetes mellitus (GDM) on a background of limited resources calls for innovative approaches healthcare provision. Our aim was to explore the effects of telemedicine supported GDM care on a range of health service utilisation and maternal and foetal outcomes. MethodsAn exploratory randomised controlled trial of adjunct telemedicine support in the management of insulin-treated GDM compared to usual care control. Outcomes included health service use, maternal and foetal clinical outcomes as well as costs. Groups were compared on outcomes and Poisson and Cox regression analysis were performed for predictors of health service utilisation, glycaemic control and costs. Results95 participants were recruited (intervention n = 61, control n = 34). There were no differences between the groups in number of face-to-face appointments (median (IQR) intervention = 8(7), control = 8(6), p = 0.843), rates of caesareans, macrosomia, large for gestational age, special care nursery admission or newborn birth-weight. The intervention had no impact on total (IRR = 1.04, p = 0.596) or face-to-face (IRR = 1.09, p = 0.257) clinic appointments or service provider costs. Participants receiving the intervention reached optimum glycaemic control quicker: mean (SD) 4.3(4.2) weeks vs. 7.6(4.5) weeks, p = 0.0001). Telemedicine was a significant predictor of better glycaemic control (HR = 1.71(95%CI: 1.11, 2.65, p = 0.015). ConclusionsTelemedicine support for GDM care showed no impact on service utilisation and costs. The intervention produced similar GDM clinical outcomes as usual care and posed no added risk to clinical quality of care. The intervention may be associated with fewer insulin dose titrations and participants achieved optimum glycaemic control sooner.

Continuous glucose monitoring results in lower HbA1c in Malaysian women with insulin-treated gestational diabetes: a randomized controlled trial.

To determine if therapeutic, retrospective continuous glucose monitoring (CGM) improves HbA1c with less hypoglycaemia in women with insulin-treated gestational diabetes mellitus (GDM). This prospective, randomized controlled, open-label trial evaluated 50 women with insulin-treated GDM randomized to either retrospective CGM (6-day sensor) at 28, 32 and 36weeks' gestation (Group 1, CGM, n=25) or usual antenatal care without CGM (Group 2, control, n=25). All women performed seven-point capillary blood glucose (CBG) profiles at least 3days per week and recorded hypoglycaemic events (symptomatic and asymptomatic CBG <3.5mmol/l; non-fasting <4.0mmol/l). HbA1c was measured at 28, 33 and 37weeks. In Group1, both CGM and CBG data were used to manage diabetes, whereas mothers in Group2 were managed based on CBG data alone. Baseline characteristics (age, pre-pregnancy BMI, HbA1c , total insulin dose) were similar between groups. There was a lower increase in HbA1c from 28 to 37weeks' gestation in the CGM group [∆HbA1c : CGM +1mmol/mol (0.09%), control +3mmol/mol (0.30%); P=0.024]. Mean HbA1c remained unchanged throughout the trial in the CGM group, but increased significantly in controls as pregnancy advanced. Mean HbA1c in the CGM group was lower at 37weeks compared with controls [33±4mmol/mol (5.2±0.4%) vs. 38±7mmol/mol (5.6±0.6%), P<0.006]. Some 92% of the CGM group achieved an HbA1c ≤39mmol/mol (≤5.8%) at 37weeks compared with 68% of the control group (P=0.012). Neither group experienced severe hypoglycaemia. CGM use may be beneficial in insulin-treated GDM because it improves HbA1c compared with usual antenatal care without increasing severe hypoglycaemia. (Clinical Trials Registry No.: NCT02204657).

Neonatal Hypoglycemia Following Diet-Controlled and Insulin-Treated Gestational Diabetes Mellitus

To assess the risk of neonatal hypoglycemia following diet-controlled and insulin-treated gestational diabetes mellitus (GDM) and how it relates to birth weight. Prospective cohort study included term neonates born after GDM from January 2013 through December 2015 at the University Medical Center Utrecht (Utrecht, the Netherlands). Routine screening of neonatal blood glucose levels was performed at 1, 3, 6, 12, and 24 h after birth. Main outcome measures were neonatal hypoglycemia defined as blood glucose ≤36 mg/dL (severe) and ≤47 mg/dL (mild). A total of 506 neonates were included, born after pregnancies complicated by GDM treated either with insulin (22.5%) or without insulin (77.5%). The incidence of mild and severe hypoglycemia was similar in the insulin-treated and diet-controlled groups (33 vs. 35%, P = 0.66; and 20 vs. 21%, P = 0.79). A birth weight >90th centile was seen in 17.2% of all infants. Although children with a birth weight >90th centile had the highest risk for hypoglycemia, the vast majority of hypoglycemia (78.6%) was detected in those with a birth weight <90th centile. Over 95% of all hypoglycemia occurred within 12 h after birth. Routine screening for neonatal hypoglycemia following pregnancies complicated by GDM reveals high incidence of both mild and severe hypoglycemia for both diet-controlled and insulin-treated GDM and across the full range of birth weight centiles. We propose routine blood glucose screening for neonatal hypoglycemia within the first 12 h of life in all neonates after GDM, irrespective of maternal insulin use or birth weight.

A Mediterranean diet with additional extra virgin olive oil and pistachios reduces the incidence of gestational diabetes mellitus (GDM): A randomized controlled trial: The St. Carlos GDM prevention study.

BackgroundGestational diabetes mellitus (GDM) prevalence is increasing and becoming a major public health concern. Whether a Mediterranean diet can help prevent GDM in unselected pregnant women has yet to be studied.MethodsWe conducted a prospective, randomized controlled trial to evaluate the incidence of GDM with two different dietary models. All consecutive normoglycemic (<92 mg/dL) pregnant women at 8–12 gestational weeks (GW) were assigned to Intervention Group (IG, n = 500): MedDiet supplemented with extra virgin olive oil (EVOO) and pistachios; or Control Group (CG, n = 500): standard diet with limited fat intake. Primary outcome was to assess the effect of the intervention on GDM incidence at 24–28 GW. Gestational weight gain (GWG), pregnancy-induced hypertension, caesarean section (CS), preterm delivery, perineal trauma, small and large for gestational age (SGA and LGA) and admissions to neonatal intensive care unit were also assessed. Analysis was by intention-to-treat.ResultsA total of 874 women completed the study (440/434, CG/IG). According to nutritional questionnaires and biomarker analysis, women in the IG had a good adherence to the intervention. 177/874 women were diagnosed with GDM, 103/440 (23.4%) in CG and 74/434(17.1%) in IG, p = 0.012. The crude relative risk (RR) for GDM was 0.73 (95% CI: 0.56–0.95; p = 0.020) IG vs CG and persisted after adjusted multivariable analysis, 0.75(95% CI: 0.57–0.98; p = 0.039). IG had also significantly reduced rates of insulin-treated GDM, prematurity, GWG at 24–28 and 36–38 GW, emergency CS, perineal trauma, and SGA and LGA newborns (all p<0.05).ConclusionsAn early nutritional intervention with a supplemented MedDiet reduces the incidence of GDM and improves several maternal and neonatal outcomes.

Gestational diabetes and adverse perinatal outcomes from 716,152 births in France in 2012

Aims/hypothesisThe aim of this study was to assess the risk of adverse perinatal outcomes in gestational diabetes mellitus (GDM) in a large national cohort.MethodsAll deliveries taking place after 22 weeks in France in 2012 were included by extracting data from the hospital discharge database and the national health insurance system. The diabetic status of mothers was determined by the use of glucose-lowering agents and by hospital diagnosis. Outcomes were analysed according to the type of diabetes and, in the GDM group, whether or not diabetes was insulin-treated.ResultsThe cohort of 796,346 deliveries involved 57,629 (7.24%) mothers with GDM. Mother–infant linkage was obtained for 705,198 deliveries. The risks of adverse outcomes were much lower with GDM than with pregestational diabetes. After limiting the analysis to deliveries after 28 weeks to reduce immortal time bias, the risks of preterm birth (OR 1.3 [95% CI 1.3, 1.4]), Caesarean section (OR 1.4 [95% CI 1.4, 1.4]), pre-eclampsia/eclampsia (OR 1.7 [95% CI 1.6, 1.7]), macrosomia (OR 1.8 [95% CI 1.7, 1.8]), respiratory distress (OR 1.1 [95% CI 1.0, 1.3]), birth trauma (OR 1.3 [95% CI 1.1, 1.5]) and cardiac malformations (OR 1.3 [95% CI 1.1, 1.4]) were increased in women with GDM compared with the non-diabetic population. Higher risks were observed in women with insulin-treated GDM than those with diet-treated GDM. After limiting the analysis to term deliveries, an increased risk of perinatal mortality was observed. After excluding women suspected to have undiagnosed pregestational diabetes, the risk remained moderately increased only for those with diet-treated GDM (OR 1.3 [95% CI 1.0, 1.6]).Conclusions/interpretationGDM is associated with a moderately increased risk of adverse perinatal outcomes, which is higher in insulin-treated GDM than in non-insulin-treated GDM for most outcomes.

ATLANTIC DIP: Insulin Therapy for Women With IADPSG-Diagnosed Gestational Diabetes Mellitus. Does It Work?

Approximately 40% of women with gestational diabetes mellitus (GDM) diagnosed using International Association of the Diabetes and Pregnancy Study Group (IADPSG) criteria require insulin therapy. We assessed whether the outcomes for women with GDM treated with insulin are comparable to women with normal glucose tolerance (NGT). This retrospective cohort study included 752 women with insulin-treated GDM and 2496 women with NGT during pregnancy. Maternal and fetal outcomes were examined. Infants of women with insulin-treated GDM had rates of macrosomia [adjusted odds ratio (aOR), 1.19; 95% confidence interval (CI), 0.87 to 1.63; P = 0.26], large for gestational age (LGA) (aOR, 1.07; 95% CI, 0.77 to 1.47; P = 0.67), and small for gestational age (SGA) (aOR, 0.70; 95% CI, 0.38 to 1.38; P = 0.26) similar to women with NGT. They were more likely to be hypoglycemic at birth (aOR, 6.85; 95% CI, 2.31 to 20.28; P < 0.01) and to require neonatal intensive care unit care (NICU) (aOR, 12.09; 95% CI, 8.72 to 16.76; P < 0.01), predominantly for nonmedical reasons. Maternal rates of hypertensive disorders (preeclampsia: aOR, 0.64; 95% CI, 0.34 to 1.12; P = 0.17; pregnancy-induced hypertension: aOR, 1.11; 95% CI, 0.74 to 1.66; P = 0.60) and hemorrhage (ante partum hemorrhage: aOR, 0.56; 95% CI, 0.19 to 1.58; P = 0.27; postpartum hemorrhage: aOR, 1.17; 95% CI, 0.68 to 2.03; P = 0.55) were similar between groups, but the risk of polyhydramnios was increased in the GDM cohort (aOR, 7.75; 95% CI, 3.96 to 15.16; P < 0.01). Insulin treatment of IADPSG-diagnosed GDM results in rates of macrosomia, LGA, SGA, and maternal hypertensive disorders similar to those of women with NGT. Although NICU admissions are greater in the GDM cohort, they are primarily for nonmedical reasons. Neonatal hypoglycemia and polyhydramnios remain greater among women with insulin-treated GDM.

Telemedicine for Gestational Diabetes Mellitus (TeleGDM): A Mixed-Method Study Protocol of Effects of a Web-Based GDM Support System on Health Service Utilization, Maternal and Fetal Outcomes, Costs, and User Experience.

BackgroundWomen with insulin-treated gestational diabetes mellitus (GDM) require close monitoring and support to manage their diabetes. Recent changes to the diagnostic criteria have implications for service provision stemming from increased prevalence, suggesting an increased burden on health services in the future. Telemedicine may augment usual care and mitigate service burdens without compromising clinical outcomes but evidence in GDM is limited.ObjectiveThe Telemedicine for Gestational Diabetes Mellitus (TeleGDM) trial aims to explore the use of telemedicine in supporting care and management of women with GDM treated with insulin.MethodsThe TeleGDM is a mixed-methods study comprising an exploratory randomized controlled trial (RCT) and a qualitative evaluation using semistructured interviews. It involves women with insulin-treated GDM who are up to 35 weeks gestation. Participating patients (n=100) are recruited face-to-face in outpatient GDM clinics at an outer metropolitan tertiary hospital with a culturally diverse catchment and a regional tertiary hospital. The second group of participants (n=8) comprises Credentialed Diabetes Educator Registered Nurses involved in routine care of the women with GDM at the participating clinics. The RCT involves use of a Web-based patient-controlled personal health record for GDM data sharing between patients and clinicians compared to usual care. Outcomes include service utilization, maternal and fetal outcomes (eg, glycemic control, 2nd and 3rd trimester fetal size, type of delivery, baby birth weight), diabetes self-efficacy, satisfaction, and costs. Semistructured interviews will be used to examine user experiences and acceptability of telemedicine.ResultsThe trial recruitment is currently underway. Results are expected by the end of 2016 and will be reported in a follow-up paper.ConclusionsInnovative use of technology in supporting usual care delivery in women with GDM may facilitate timely access to GDM monitoring data and mitigate care burdens without compromising maternal and fetal outcomes. The intervention may potentially reduce health service utilization.Trial RegistrationAustralian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614000934640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366740 (Archived by WebCite® at http://www.webcitation.org/6jRiqzjSv).

Thiol/disulfide homeostasis in predicting adverse perinatal outcomes at 24–28 weeks of pregnancy in gestational diabetes

Objective: The main aim of this study was to investigate thiol/disulfide homeostasis at 24–28 weeks of pregnancy and to evaluate whether it is predictive for adverse perinatal outcomes or not in gestational diabetes mellitus (GDM).Methods: A total of 110 pregnant women at 24–28 weeks of pregnancy (74 GDM patients and 36 age- and BMI-matched healthy pregnant women) were enrolled in this prospective case–control study. Thiol/disulfide homeostasis was evaluated with a novel spectrophotometric method to determine if there is an association with adverse perinatal outcomes in GDM, by using logistic regression analysis.Results: GDM patients, with decreased native thiol levels at 24–28 weeks (OR: 4.890, 95% CI: 1.355–5.764, p = 0.015) and with higher pre-pregnancy BMI (OR: 1.280, 95% CI: 1.072–1.528, p = 0.006), were found to be at increased risk of adverse perinatal outcomes in GDM. There were no statistically significant differences in thiol/disulfide homeostasis between diet- and insulin-treated GDM subgroups. Additionally, 1-h and 2-h glucose levels on 100 g OGTT were found to be predictive for the insulin need in achieving good glycemic control in GDM (OR: 1.022, 95% CI: 1.005–1.038, p = 0.010 and OR: 1.019, 95% CI: 1.004–1.035, p = 0.015).Conclusions: GDM patients, with decreased native thiol levels at 24–28 weeks of pregnancy and with higher pre-pregnancy BMI, have an increased risk of possible adverse perinatal outcomes. Also, increased 1-h and 2-h glucose levels on 100 g OGTT can predict the need for insulin treatment for GDM.

Lipid Fingerprinting in Mild versus Severe Forms of Gestational Diabetes Mellitus.

The blood serum lipid profile of women with Gestational Diabetes Mellitus (GDM) is still under study. There are no data on the serum lipid profile of GDM patients with more severe (insulin treated) compared to milder forms (diet treated) GDM. The aim of our study was to analyze the blood serum lipid profile of patients with milder versus more severe forms of GDM and to compare these findings with those of healthy pregnant women. This cross-sectional analytical study included 30 insulin-treated GDM, 30 diet-only GDM and 30 healthy pregnant women. Serum lipid was extracted from the 90 participants and their lipid profiles were analyzed by lipid fingerprinting using liquid-chromatography-mass spectrometry. A total of 143 parent ions were differentially represented in each of the three groups, belonging to the following classes: Glycerophospholipids, Sterol Lipids, Sphingolipids, Prenol Lipids, Fatty Acyls and Glycerolipids. There were significant differences in the lipid profiles of healthy pregnant women compared to GDM patients and also between milder versus more severe forms of GDM. There are marked differences in lipid fingerprinting between healthy pregnant women compared to those with GDM in the third trimester. Moreover, the lipid profile of women with more severe forms of GDM differs considerably from that of women with milder forms of GDM. These findings may be useful to help clarify the pathogenesis of milder and more severe forms of GDM.

Recurrence of gestational diabetes in primiparous women.

Gestational diabetes mellitus (GDM) increases the risk for diabetes in the next pregnancy and later in life. Thus, estimating the risk of GDM in further pregnancies provides a time frame for possible preventive measures. We aimed to calculate the recurrence rate of GDM in primiparous women and evaluate the factors involved such as age, body mass index, weight gain, time between pregnancy and postpartum OGTT results. We established a prospective cohort during a 5-year period at the Department of Obstetrics at Kolding Hospital. Women with diet-treated GDM in their first pregnancy and a subsequent pregnancy constituted our study population. Multiparity and insulin-treated GDM were exclusion criteria. Among 15 735 deliveries, 535 women were diagnosed with GDM (3.4%). Of these, 209 (39.1%) were nulliparous women, treated with diet only. Seventy-two of these women had a subsequent pregnancy and they all attended the recommended screening procedure, a 75-g oral glucose tolerance test at 14-20 (early) or 27-30 (late) weeks' gestation. The recurrence rate of GDM was 47.2%. The risk of recurrence was less in women who lost weight between the first and the subsequent pregnancy. Recurrence of diet-treated GDM was 47.2% in primiparous women with previous GDM and the recurrence was associated with weight gain between pregnancies.

Prediction of gestational diabetes mellitus by first trimester serum secreted frizzle-related protein-5 levels

Objective: The main aim of this study was to investigate the first trimester maternal serum secreted frizzle-related protein-5 (Sfrp-5) levels and to evaluate the predictive value on the subsequently developed gestational diabetes mellitus (GDM). Methods: A total of 40 pregnant women who subsequently developed GDM and 44 age- and pre-pregnancy BMI-matched healthy pregnant women were enrolled in this prospective case-control study. First trimester serum Sfrp-5 levels were evaluated to determine if there is an association with the onset of GDM, by using logistic regression analysis. Results: Decreased first trimester serum Sfrp-5 levels (OR = 14.332, 95%CI: 4.166–49.301, p < 0.001) were found to be significantly associated with the increased risk of GDM. There were no statistically significant differences in serum Sfrp-5 levels between the diet- and insulin-treated GDM groups and also serum Sfrp-5 levels were not found to be predictive for adverse perinatal outcomes (p > 0.05). Conclusions: Decreased first trimester serum Sfrp-5 levels are significantly associated with the increased risk of GDM.

Immunoregulatory molecules in patients with gestational diabetes mellitus.

Induction of maternal-fetal immune tolerance is essential for the development of normal pregnancy. Impaired expression of costimulatory molecules may lead to intense inflammatory reaction, a mechanism involved in the pathophysiology of gestational diabetes mellitus (GDM). The aim of this study was to investigate whether immunoregulatory molecules are involved in the physiopathology of GDM. This case-control study included 30 healthy pregnant women and 20 GDM patients. Flow cytometry was used to assess peripheral blood T subpopulations (CD4(+) and CD8(+)), the expression of immunoregulatory molecules (CD28, ICOS, CTLA-4, and PD-1) and activation markers (CD69 and HLA-DR). Compared to healthy women, GDM patients had a significantly higher frequency of CD4(+)CD69(+) and CD8(+)CD69(+) T cells; only patients with insulin-treated GDM had increased numbers of CD4(+)HLA-DR(+) T cells. We also observed significantly higher percentages of CD4(+)CD28(+)HLA-DR(+), CD3(+)CD4(+)ICOS(+), CD3(+)CD4(+)PD-1(+), CD8(+)CD28(+)CD69(+), CD8(+)CD28(+)HLA-DR(+), CD8(+)CTLA-4(+)HLA-DR(+), and CD3(+)CD8(+)ICOS(+) T cells and lower frequency of CD3(+)CD4(+)CTLA-4(+), CD3(+)CD8(+)CTLA-4(+), and CD8(+)ICOS(+)HLA-DR(+) T cells in GDM patients compared to healthy pregnant women. This first study assessing costimulatory molecules in GDM patients shows that these patients have exacerbated markers of T cell activation along with CTLA-4 deficiency, findings that indicate that the maternal-fetal tolerance is compromised in these patients.

First trimester concentrations of the TTR-RBP4-retinol complex components as early markers of insulin-treated gestational diabetes mellitus.

The objective of the study was to investigate the relationship between first trimester maternal serum levels of the TTR-RBP4-ROH complex components and the later insurgence of an altered glucose metabolism during pregnancy. Retrospective case control study including 96 patients between the 12th and 14th week of gestation, 32 that developed gestational diabetes mellitus (GDM), respectively, 21 non-insulin-treated (dGDM) and 11 insulin-treated (iGDM), 20 large for gestational age fetuses (LGA) without GDM and 44 patients with normal outcome as control. Serum concentrations of RBP4 and TTR were assessed by ELISA; serum concentration of ROH by reverse-phase high performance liquid chromatography (rpHPLC). The molecular heterogeneity of TTR and RBP4 was analyzed after immunoprecipitation by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). iGDM patients were characterized by reduced TTR, RBP4 and ROH compared to controls (respectively, iGDM vs. controls, mean±SD: TTR 3.96±0.89 μmol/L vs. 4.68±1.21 μmol/L, RBP4 1.13±0.25 μmol/L vs. 1.33±0.38 μmol/L and ROH 1.33±0.17 μmol/L vs. 1.62±0.29 μmol/L, p<0.05). TTR containing Gly10 in place of Cys10 was lower in the iGDM group (p<0.05) compared to controls. In the final logistic regression model ROH significantly predicted the diagnosis of iGDM (OR 0.93, 95% CI 0.87-0.98, p<0.05). First trimester maternal serum ROH, RBP4 and TTR represent potential biomarkers associated with the development of iGDM.

Pregnancy outcomes in women aged 35 years or older with gestational diabetes – a registry-based study in Finland

Objective: To compare pregnancy outcomes of women ≥35 years to women <35 years with and without gestational diabetes.Methods: The data include 230 003 women <35 years and 53 321 women ≥35 years and their newborns from 2004 to 2008. In multivariate modeling, the main outcome measures were preterm delivery (<28, 28–31 and 32–36 weeks' gestation), Apgar scores <7 at 5 min, small for gestational age (SGA), fetal death, asphyxia, preeclampsia, admission to neonatal intensive care unit (NICU), shoulder dystocia and large for gestational age (LGA).Results: In comparison to women <35 with normal glucose tolerance, preeclampsia (OR 1.57, CI 1.30–1.88), admission to the NICU (OR 3.30, CI 2.94–3.69) and shoulder dystocia (OR 2.12, CI 1.05–4.30) were highest in insulin-treated women ≥35 years. In women ≥35, diet- and insulin-treated gestational diabetes mellitus (GDM) increased the rates of preeclampsia, shoulder dystocia and admission to NICU (OR 3.07 CI 2.73–3.45). The effect of advanced maternal age was observed in very preterm delivery (<28 weeks), fetal death, preeclampsia and NICU. The increase in preeclampsia was statistically significant.Conclusions: GDM at advanced age is a high risk state and, more specifically, the risk caused by age and GDM appear to be increasing in preeclampsia.