Insulin-treated Gestational Diabetes Research Articles

Characterization of human placental fetal vessels in gestational diabetes mellitus.

Gestational diabetes mellitus is one of the most common complications during pregnancy. Its prevalence is rapidly increasing worldwide. Gestational diabetes mellitus is leading to an elevated risk for the development of endothelial dysfunction and cardiovascular diseases both in the mother and the child in later life. The underlying pathophysiological mechanisms are not well-understood. Therefore, we aimed to characterize the endothelial function in fetal placental vessels from mothers with gestational diabetes mellitus. In this study, we distinguished between insulin-treated and diet-controlled gestational diabetes mothers and compared them to a normoglycemic control group. The clinical data confirmed pre-conceptional overweight as a risk factor in women with insulin-treated gestational diabetes mellitus. The insulin-treated gestational diabetes group was also characterized by a recent family history of diabetes compared to mothers of the control or diet-controlled gestational diabetes group. Analyses of blood serum from umbilical cords suggested a reduced fetal insulin metabolism in the insulin-treated gestational diabetes group. Vascular function analysis in fetal placental vessels revealed an altered substance P-induced vasorelaxation in vessels from patients with insulin-dependent gestational diabetes. Inhibition of nitric oxide synthase affected only fetal vessel segments from the control group or diet-controlled gestational diabetes group, but not from insulin-dependent gestational diabetes. Finally, we found a significantly decreased substance P receptor (TACR1) mRNA expression in fetal vessel segments from patients with insulin-treated gestational diabetes. In conclusion, we provide evidence that different pathophysiological mechanisms might be responsible for the development of insulin-treated versus diet-controlled gestational diabetes. Only in fetal vessels from patients with insulin-treated gestational diabetes were we able to detect an endothelial dysfunction and a reduced fetal insulin conversion. This provides novel insights into the pathophysiology of the subtypes of gestational diabetes.

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.

The effect of couple supportive counseling on self-efficacy in women with insulin-treated gestational diabetes: A randomized clinical trial.

Gestational diabetes is the most common medical complication and a common metabolic disorder during pregnancy. Increasing people's self-efficacy is one of the best ways to control this disease. As there is a lag of intervention in this regard, the purpose of this study was to determine the effect of couple supportive counseling on self-efficacy in women with insulin-treated gestational diabetes. In this randomized clinical trial, 64 women with gestational diabetes who referred to diabetes clinic of Mashhad Ommolbanin Hospital were divided into intervention and control groups through block randomization during 2019. Their gestational age was in 26-30 weeks. For the couples in the intervention group, three couple supportive counseling session was held. Each session lasted 1 h and was held one time per week. The instruments were diabetes self-efficacy questionnaire, fasting and 2-h postprandial checklist and Cassidy social support, which were assessed before and 4 weeks after intervention in both groups. Data was analyzed by SPSS software version 25 through Mann-Whitney and Wilcoxon test. P values of < 0.05 were reported to be significant. In the preintervention, the diabetes self-efficacy score had no significant difference in the intervention (30/6 ± 38/50) and control groups (09/8 ± 56/51) (P = 515/0). However, in the postintervention, the diabetes self-efficacy score was significantly higher in the intervention group (58/6 ± 41/71) compared to the control group (15/7 ± 31/51) (P < 001/0). Also, before the intervention, there was no significant difference between the intervention (30/2 ± 72/10) and control group (87/1 ± 63/11) (P = 137/0) regarding social support. However, after the intervention, there was a significant difference between the intervention and control groups (879/0 ± 53/13, 03/2 ± 41/11, P < 0/001 respectively). Also, data analysis showed a significant correlation between self-efficacy and social support (r = 0.451, P < 0.001), self-efficacy and fasting blood sugar (P < 0.001, r = -0.577), and 2 h post prandial (r = -0.778, P < 0.001). Couple supportive counseling leads to increased self-efficacy and social support in pregnant women with gestational diabetes. Therefore, it is recommended to use this counseling as an effective method in the management of diabetic pregnant women during their prenatal care to have a healthier pregnancy.

Polypharmacy in diabetes: A nation-wide, pharmacy-based, observational study

AimThe aim of the present study was to build a classification of diabetes according to the time-sequence of treatment. A second aim was to describe the diversity of drugs prescribed for diabetes and associated conditions in a nation-wide cohort of patients with diabetes. Patients and methodLRx is an outpatient care nation-wide medication dispense database. It consists of a panel of 10,000 retail pharmacies in France. We developed an algorithm to find out the number of patients treated for diabetes from July 2018 to June 2019 and to classify diabetes types and the sequence of drugs dispense over the years, including treatments for the control of diabetes itself and drugs for associated conditions. ResultsA raw number of 2.3 million patients was studied, corresponding to an extrapolated 3.9 million patients in mainland France. Seven percent were classified as having Type 1 Diabetes, 86% Type 2 Diabetes (T2D), 0.5% insulin-treated gestational diabetes, and 6% remained unclassified. In subjects with T2D, metformin was the most frequently prescribed glucose lowering drug, followed by DPP4 inhibitors and sulfonylureas. Main coprescribed medication classes were lipid-modifying agents and antihypertensive agents. Of note, about a third of the patients received neuropsychiatric drugs and 40% a proton-pump inhibitor. We also had an unbiased view of compliance to treatment, that was below 50%. ConclusionThe algorithm we built could be used to monitor changes of strategies to control blood glucose and comorbidities. Our findings highlight the burden of polypharmacy in patients with diabetes.

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).

F21. Electroclinical manifestations in term newborns with neonatal hypoglycemia

Neonatal hypoglycemia is a relatively common event with a variable clinical presentation, ranging from asymptomatic forms to refractory status epilepticus. It may present as a primary problem or appear in the context of other conditions, such as prematurity or severe systemic disorders (sepsis, hypoxic ischemic encephalopathy, ...), making it difficult to separate its effects on the CNS from those due to the underlying disorder. Aim: To describe the EEG features in term-newborns with primary hypoglycemia admitted to our neonatal unit between 10/2016 and 10/2017. Retrospective review of clinical records of patients fulfilling the following: Inclusion criteria – Term newborns (Gestational age ⩾37 weeks). – Hypoglycemia (plasma glucose ⩽40 mg/dL or ⩽47 mg/dL if symptomatic: CNS dysfunction; dysautonomia). Exclusion criteria – Any antecedent disorder that may explain CNS dysfunction (Primary: e.g. genetic epileptic encephalopathy; Secondary: e.g. cardiorespiratory arrest). We identified 3 patients: 1. Female, presenting with irritability and tremor 48 h. after birth, with plasma glucose of 18 mg/dL, treated with oral glucose with good response. She presented recurrent asymptomatic hypoglycemia, with disproportionately high levels of insulin and C-peptide, and was treated with Cortisone and Diazoxide. Genetic tests confirmed congenital hyperinsulinism (ABCC8-mutation). MR and EEG were normal. At follow-up, 7 months old, she had a normal psychomotor development. 2. Male, presenting with hypoactivity, diaphoresis, and apnea 12 h. after birth, with plasma glucose of 15 mg/dL, metabolic acidosis and high lactate, improving rapidly on i.v. Glucose. His mother had insulin-treated gestational diabetes. He developed focal seizures evolving into status epilepticus, requiring treatment with PB, LEV, MDZ and Lidocaine to achieve control (48 h. after onset). MR showed extensive bilateral cortico-subcortical lesions, predominantly parieto-occipital. Initial EEG showed a discontinuous pattern and 8 focal temporal seizures. Control EEG showed persistent discontinuous pattern (silent periods up to 2 min) and absent cortical reactivity. He died aged 4 days. 3. Male, presenting with hypoactivity with plasma glucose of 16 mg/dL, rapidly improving with i.v. Glucose. He developed focal motor seizures evolving into status epilepticus, requiring PB, LEV and MDZ to achieve control (clinically after 24 h, but seizures persisted on CFM 12 h longer). MR showed bilateral cortico-subcortical lesions, predominantly parieto-occipital. Initial EEG showed normal background with left centro-temporal interictal epileptiform activity. Control EEG showed focal slowing over the same regions. He was discharged on LEV 23 days after onset, with axial hypertonia and brisk reflexes. Neonatal hypoglycemia may present with refractory seizures, which can aggravate CNS damage and impair outcome. EEG monitoring is necessary to identify subclinical seizures and correlates with prognosis.

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.

Oxidative-Nitrative Stress and Poly (ADP-Ribose) Polymerase Activation 3 Years after Pregnancy.

Background Oxidative-nitrative stress and poly (ADP-ribose) polymerase activation have been previously observed in healthy and gestational diabetic pregnancies, and they were also linked to the development of metabolic diseases. The aim of the present study was to examine these parameters and their correlation to known metabolic risk factors following healthy and gestational diabetic pregnancies. Methods Fasting and 2 h postload plasma total peroxide level, protein tyrosine nitration, and poly (ADP-ribose) polymerase activation were measured in circulating leukocytes three years after delivery in women following healthy, “mild” (diet-treated) or “severe” (insulin-treated) gestational diabetic pregnancy during a standard 75 g OGTT. Nulliparous women and men served as control groups. Results Fasting plasma total peroxide level was significantly elevated in women with previous pregnancy (B = 0.52 ± 0.13; p < 0.001), with further increase in women with insulin-treated gestational diabetes (B = 0.36 ± 0.17; p < 0.05) (R2 = 0.419). Its level was independently related to previous pregnancy (B = 0.47 ± 0.14; p < 0.01) and current CRP levels (B = 0.06 ± 0.02; p < 0.05) (R2 = 0.306). Conclusions Elevated oxidative stress but not nitrative stress or poly (ADP-ribose) polymerase activation can be measured three years after pregnancy. The increased oxidative stress may reflect the cost of reproduction and possibly play a role in the increased metabolic risk observed in women with a history of severe gestational diabetes mellitus.

Randomized controlled trial of induction at 38 weeks versus 40 weeks gestation on maternal and infant outcomes in women with insulin-controlled gestational diabetes

To compare the impact of induction of labor at 38weeks of gestation with the induction of labor at 40weeks of gestation in women with insulin-treated gestational diabetes on maternal and fetal outcome. In this study 100pregnant women with insulin-treated gestational diabetes were randomized to either induction of labor at 38(groupI) or 40weeks (groupII) to evaluate the rate of large for gestational age newborns, neonatal hypoglycemia, success rate of deliveries within 48h and cesarean section rate after induction in both groups. The difference of large for gestational age newborns was not significant between the two groups (6.8% vs. 12.8%, p= 0.49), 16(36.4%) newborns in groupI and 8(17.0%) newborns in groupII developed hypoglycemia <35 mg/dl (p= 0.04). The success rate for deliveries within 48h after induction of labor for groupsI andII was 77.3% and 92.3%, respectively (p= 0.25). The cesarean section rate after induction of labor was not significantly different between the two groups (24.1% vs. 18.7%, p= 0.49). In acohort of women with insulin-treated gestational diabetes, induction of labor at 38weeks did not significantly reduce the rate of large for gestational age newborns compared to induction at 40weeks but seems to increase the rate of neonatal hypoglycemia.

Risk of Diabetes Treated in Early Adulthood After Growth Hormone Treatment of Short Stature in Childhood.

Growth hormone (GH) is known to be diabetogenic, but the risk of diabetes in individuals treated with GH in childhood has been little evaluated, and conflicting results have been obtained. To investigate the prevalence of diabetes and gestational diabetes in a population-based cohort of patients treated with GH for short stature in childhood in France. Participants were a population-based cohort of 5100 children with idiopathic isolated GH deficiency, idiopathic short stature, or short stature in children born short for gestational age who started GH treatment between 1985 and 1996. Data on the delivery of diabetes drugs in 2009 and 2010 were obtained from the French national health insurance database. Cases in patients and controls were identified from diabetes drugs deliveries. The prevalence of diabetes was calculated and compared with that in the general population, determined on the basis of data from the same source, with the same definition. At a mean age of 30 years, no difference in the prevalence of treated diabetes (oral drugs or insulin) was found between subjects treated with GH and the general population in France, regardless of sex. Similarly, the risk of insulin-treated gestational diabetes was similar in patients and in the reference population. No difference in the risk of diabetes was found between GH-treated patients and the reference population. These results are reassuring, but further studies with a longer follow-up are required to evaluate the risk of diabetes with age in these patients.

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).

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.

Modulation of Cholesterol Transport by Insulin-Treated Gestational Diabetes Mellitus in Human Full-Term Placenta1

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that is characterized by glucose intolerance, leads to dyslipidemia, and is aggravated by obesity. Cholesterol is taken up by the placenta as part of lipoproteins through the scavenger receptor class B type I receptor (SRBI), low-density lipoprotein receptor (LDLR), and very low density lipoprotein receptor (VLDLR), and its efflux is then mediated by ABCA1 and ABCG1. PCSK9 is involved in the degradation of LDLR and VLDLR. The goal of this study was to evaluate the impact of GDM and prepregnancy body mass index (BMI) on cholesterol transport through the modulation of the expression of several key players. Human full-term placenta, maternal, and venous cord blood samples were obtained at delivery from normal-weight women without GDM (n = 10), normal-weight women with GDM (n = 6), and overweight/obese women with GDM (n = 6). Lipids (total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, free fatty acids, apolipoprotein A1, apolipoprotein B100) levels were evaluated in blood samples. Messenger RNA and protein expression levels (LDLR, VLDLR, SRBI, ABCA1, ABCG1, proprotein convertase subtilisin/kexin type 9, liver x receptors, peroxisome proliferator-activated receptors) were assessed in human full-term placenta, respectively, by real-time RT-PCR and Western blots. Lipoprotein lipase activity was evaluated using a commercial kit on tissue homogenates. Overall, our study demonstrates that GDM affects the maternal and neonatal lipid profiles as well as different key players of placental cholesterol transfer from the maternal to the fetal circulation, depending on the maternal BMI. These changes could affect the fetal metabolism and predispose the fetus to future metabolic diseases.

Amniotic Fluid Oxidative and Nitrosative Stress Biomarkers Correlate with Fetal Chronic Hypoxia in Diabetic Pregnancies

Background: In spite of improvement in obstetrical care, pregnancy in women with type 1 diabetes mellitus is associated with increased perinatal morbidity and mortality. Hyperglycemia during pregnancy causes excessive fetal growth and chronic fetal hypoxia as reflected in increased erythropoietin (EPO) levels in amniotic fluid (AF). Objectives: We hypothesized that the degree of fetal hypoxia would correlate with fetal oxidative and nitrosative stress as evidenced by the concentration of specific biomarkers in AF. Material and Methods: 19 pregnant women with type 1 or insulin-treated gestational diabetes mellitus were studied. AF samples were collected and processed for EPO, meta-tyrosine, nitro-tyrosine and 8-hydroxy-2-deoxiguanosine by chemiluminescent immunoassay and high-performance liquid chromatography coupled to tandem mass spectrometry methods, respectively. Results: The mean (SD) of the last HbA_1c concentration before delivery was 7.7% (1.1). Median gestational age was 258 days (range 231–268). Birth weight was 3,868 ± 695 g with a z-score >2 SD in 47% of the cases. A significant correlation was found between the concentrations of AF EPO and meta-tyrosine/phenylalanine ratio (p < 0.001), nitro-tyrosine (p < 0.01) and 8-oxo-dG/2dG ratio (p < 0.001). Conclusions: We confirmed that fetuses of type 1 diabetes or insulin-treated gestational diabetes pregnancies experience chronic hypoxia as reflected by increased EPO concentrations in AF near term. Moreover, EPO levels significantly correlated with the concentration of oxidative and nitrosative stress biomarkers in AF. This pro-oxidant status may predispose newborn infants to poor postnatal adaptation and early neonatal complications.

273: Hypoglycemia in insulin-treated gestational diabetes: is it dose dependent?

273: Hypoglycemia in insulin-treated gestational diabetes: is it dose dependent?

Pregnancy Outcome Among Obese Women: A Prospective Study

We investigated pregnancy outcome among obese women using a prospective cohort study comparing consecutive deliveries of obese and nonobese patients. Stratified analysis, using the Mantel-Haenszel technique, was done to assess the association between obesity and the risk for cesarean delivery (CD) while controlling for confounding variables. Complete data were abstracted for 376 women, of whom 21% ( N = 79) were obese. CD rate was significantly higher among obese women (32.9% versus 18.9%; P = 0.006). Maternal obesity was associated with multiparity (odds ratio [OR] 2.97, 95% confidence interval [CI] 1.27 to 6.97; P = 0.012), fertility treatments (OR 11.3, 95% CI 2.84 to 44.89; P = 0.001), insulin-treated gestational diabetes (OR 24.55, 95% CI 2.28 to 264.08; P = 0.008), and hydramnios (OR 20.46, 95% CI 2.17 to 192.89; P = 0.008). When controlling for possible confounders, the association between maternal obesity and CD remained significant (weighted OR 2.2, 95% CI 1.2 to 4.1; P = 0.018). No significant differences were noted between the groups regarding neonatal complications. Both first and second stages of labor were longer in obese women. Obesity is a risk factor for developing gestational hypertension, insulin-treated gestational diabetes, and hydramnios. Moreover, maternal obesity is an independent risk factor for CD. Additional independent risk factors for CD were fertility treatments, insulin-treated gestational diabetes, and hydramnios. However, neonatal outcome of obese women is comparable to women with normal prepregnancy body mass index.

Large-for-gestational-age newborns in women with insulin-treated gestational diabetes under strict metabolic control

To assess the influence of strict metabolic control in women with insulin-treated gestational diabetes on the risk of large-for-gestational-age (LGA) newborns, the frequency of obstetrical complications and fetal outcome. In this prospective cohort study, 875 women were screened for gestational diabetes mellitus with a 75 g oral glucose tolerance test (OGTT) between weeks 24 and 28 of gestation. The study group (n = 162) consisted of women with insulin-treated gestational diabetes mellitus (GDM) and the control group (n = 713) of women with normal glucose tolerance (NGT). In the women with diabetes, strict adjustments of fasting glucose levels to 90 mg/dl and 130 mg/dl postprandially were achieved with insulin administration. No increased risk for LGA newborns was observed in women with GDM and good metabolic control (16.7% vs. 12.3%; p = 0.1). In women with NGT, maternal prepregnancy BMI was significantly higher in those who delivered LGA newborns than in those who gave birth to newborns below the 90th percentile [27.2 kg/m(2) (5.0) vs. 24.4 kg/m(2) (5.6); p = 0.006], whereas there was no influence of maternal BMI on birth weight of newborns in women with GDM. There was no difference between the two groups with respect to maternal birth traumata and fetal outcome, except for plexus palsy which occurred in three GDM women with macrosomic newborns. Strict metabolic control and surveillance in women with insulin-treated GDM seems to attenuate the risk for LGA newborns, diabetic fetopathia, and the influence of maternal BMI on fetal growth.

Effect of maternal diabetes on phosphorylation of insulin‐like growth factor binding protein‐1 in cord serum

The insulin-like growth factor (IGF) system is considered important in the regulation of fetal growth. Binding of IGFs to specific binding proteins (IGFBPs) modifies their actions. In fetal blood, IGFBP-1 is the primary IGF binding protein whose phosphorylation generates proteins with different affinities for IGF-I. We studied cord serum IGFBP-1 phosphoisoform profiles in normal pregnancies and in diabetic pregnancies, which are frequently complicated by macrosomia. Cord serum IGFBP-1 phosphoisoform concentrations were measured at birth by two immunoenzymometric assays in 67 pregnancies complicated by Type 1 diabetes, in 28 pregnancies complicated by insulin-treated gestational diabetes, and in 62 normal pregnancies. Cord serum highly phosphorylated IGFBP-1 (hpIGFBP-1) concentrations were lower in pregnancies complicated by Type 1 diabetes (204 +/- 36 microg/l, P = 0.032) and in pregnancies complicated by gestational diabetes (170 +/- 28 microg/l, P = 0.031) than in controls (316 +/- 34 microg/l). Cord serum lesser phosphorylated IGFBP-1 (lpIGFBP-1) concentrations were similar in diabetic and normal pregnancies (P = 0.692 between groups by analysis of variance). Relative birth weight correlated negatively with cord serum hpIGFBP-1 and lpIGFBP-1 in diabetic pregnancies, and with cord serum lpIGFBP-1 in normal pregnancies. Maternal diabetes is associated with suppressed hpIGFBP-1 but unaltered lpIGFBP-1 concentrations in cord serum, suggesting that IGFBP-1 phosphoisoforms are differentially regulated in the fetus. Because hpIGFBP-1 has a higher affinity for IGF-I than does lpIGFBP-1, diabetes-related changes in fetal IGFBP-1 phosphorylation may increase IGF-I bioavailability and, consequently, stimulate fetal growth. This may partly explain the increased occurrence of macrosomia in diabetic pregnancies.

Concentration of cord serum placenta growth factor in normal and diabetic pregnancies

To investigate whether maternal diabetes or diabetes-related complications, such as macrosomia and chronic fetal hypoxia, are associated with altered placenta growth factor (PlGF) levels in cord serum. Case-control study. Helsinki University Central Hospital, Helsinki, Finland. Sixty-two normal pregnancies, 67 pregnancies complicated by type 1 diabetes and 28 pregnancies complicated by insulin-treated gestational diabetes. Cord serum PlGF concentration was measured by an enzyme-linked immunosorbent assay. Amniotic fluid erythropoietin concentration was measured by a chemiluminescent immunologic method. Umbilical artery gas variables were analysed with standard blood gas and pH electrodes. PlGF concentration in cord serum at birth. Cord serum PlGF concentration was similar in normal pregnancies [13.4 (1.0) ng/L], in pregnancies complicated by type 1 diabetes [15.1 (1.8) ng/L, P= 0.583 vs controls] and in pregnancies complicated by insulin-treated gestational diabetes [13.6 (0.9) ng/L, P= 0.991 vs controls]. Cord serum PlGF did not correlate with relative birthweight. In diabetic pregnancies, cord serum PlGF correlated negatively with amniotic fluid erythropoietin (r=-0.449, P < 0.0001) and positively with umbilical artery Po(2) (r= 0.333, P= 0.001). There was a trend toward lower cord serum PlGF levels in diabetic pregnancies with pre-eclampsia compared with those without any hypertensive disorders. Maternal diabetes per se is not associated with altered PlGF levels in cord serum. The correlation between PlGF and indices of fetal hypoxia in diabetic pregnancies may be related to the role of PlGF in potentiating the angiogenic response to vascular endothelial growth factor in ischaemia.