Insulin-controlled Gestational Diabetes Mellitus Research Articles

Antenatal Glycemic Management and Postpartum Cardiovascular Disease Risk Screening

ObjectivesThis study aims to evaluate the cardiovascular disease (CVD) risk profiles of patients referred to the Maternal Health Clinic (MHC) with a history of gestational diabetes mellitus (GDM). MethodsEligible patients had their MHC appointment at 6 months postpartum between November 2011 and May 2022 and experienced GDM in their most recent pregnancy. Included participants were then divided into subgroups comparing methods of glycemic control: diet-controlled GDM and insulin-controlled GDM. Additionally, the MHC recruited 47 patients who have not experienced a complication in pregnancy to act as a comparator group in research studies. Demographics, medical and pregnancy history, and CVD risk scores were compared between the 3 groups. ResultsIn total, 344 patients with GDM were included in the analysis; 165 were insulin-controlled and 179 diet-controlled. When measuring the median 30-year Framingham risk score based on both BMI and lipids, there was a significant stepwise increase seen from the unexposed group, the diet-controlled GDM, and the insulin-controlled groups, respectively (all P < 0.05). The presence of metabolic syndrome showed a stepwise increase in prevalence when comparing the unexposed group, diet-exposure group, and the insulin-exposure group, respectively (16.7%; 21.5%–44.8%, P < 0.05). ConclusionsOur findings reinforce the prevalence of maternal CVD risk among GDM-diagnosed patients in the postpartum period and the necessity for screening. More specifically, our findings show how CVD risk may differ based on required interventions for glycemic control throughout pregnancy. Future research should aim to compare a more diverse patient population to optimise the generalizability of glycemic control-specific CVD outcomes.

Pre-labour Rupture of Membranes at Term in Women With Gestational Diabetes and the Risk of Neonatal Hypoglycemia

ObjectivesThe management for improving maternal and neonatal outcomes of women with gestational diabetes mellitus (GDM) arriving at the delivery ward with pre-labour rupture of membranes (PROM) has not been elucidated. We tested the hypothesis that prolonged PROM in women with GDM would result in higher rates of neonatal hypoglycemia. MethodsWe retrospectively enrolled women with diet or insulin-controlled GDM who presented with spontaneous clear PROM. Each woman was allocated into one of two groups based on the PROM-delivery time: <18 hours (group 1) and ≥18 hours (group 2). The primary outcome was the incidence of neonatal hypoglycemia, defined as glucose <40 mg/dL (2.2 mmol/L) within 24 hours of birth. ResultsWe ultimately analyzed 631 cases of GDM (6.7%), 371 with PROM-delivery <18 hours, and 260 with PROM-delivery ≥18 hours. The incidence of neonatal hypoglycemia did not differ between the two groups, reaching 7.3%. Women in group 2 were at increased risk of both cesarean delivery (20% vs. 12.4%, P < 0.01) and maternal chorioamnionitis morbidity (6.5% vs. 1.3%, P < 0.001). ConclusionsIn a sub-group of women with GDM, a PROM-delivery time ≥18 hours is not associated with higher rates of neonatal hypoglycemia, but higher rates of chorioamnionitis and cesarean delivery were noted. Therefore, we suggest consideration for early delivery when managing women with GDM and PROM.

Oxidative stress markers in saliva and plasma differ between diet-controlled and insulin-controlled gestational diabetes mellitus

ObjectivesThe aims of the study were as follows: to investigate possible differences between plasma oxidative status (OS) in late-onset GDM and well-characterized healthy pregnant women (oral health, diet); to verify the existence of possible differences between GDMG1 (diet-treated) and GDMG2 (insulin-treated GDM); to determine whether oxidative stress markers could be detected in saliva. Material and methodsA total of 89 pregnant women (n = 89; 59 with GDM and 30 controls) were evaluated. Malondialdehyde (MDA), total antioxidant capacity (ORAC), inactivation of aldehyde dehydrogenase (IALDH), activity of glutathione peroxidase (GPx) and glutathione transferase (GST)) in plasma and/or saliva were analyzed. ResultsThe activity of GPx and GST in plasma was higher in GDMG2 as compared to GDMG1 and controls. Also, in GDMG2, elevated concentrations of salivary MDA and higher IALDH were observed. In contrast, GDMG1 had higher plasma ORAC and lower GPx activity as compared to controls, probably due to low-energy diet, high in antioxidants and fibers. Salivary and plasma OS were correlated and most significant for ORAC. ConclusionOxidative stress were not observed in GDMG1 but were confirmed to be moderate in GDMG2. However, large variability of the analyzed markers in GDM groups encourages screening of all patients, regardless of the treatment option. Saliva may be considered useful for the estimation of oxidative stress levels in GDM populations

123. Peripheral maternal haemodynamic gestation across pregnancy in gestational diabetes mellitus

Introduction Haemodynamic maladaptation has been associated with gestational diabetes mellitus (GDM), a risk factor for hypertensive disorders of pregnancy. Recent RCT’s suggested that metformin treatment may reduce the risk for preeclampsia in very obese women. Objectives To evaluate maternal haemodynamics across gestation in uncomplicated pregnancies and those complicated by GDM. Study design Prospective cohort study from 2015 to 2018 of healthy, nulliparous, singleton-bearing women. Maternal haemodynamics assessed at 11 and 32 weeks’ gestation in pregnancies complicated by GDM, grouped by treatment: diet, metformin or insulin, compared to uncomplicated pregnancies using mixed-effects linear modelling. Main outcome measures Maternal haemodynamics assessed by Uscom BP+ [peripheral and central blood pressure (BP), and augmentation index (AIx)] in uncomplicated pregnancies and those complicated by GDM. Results Eighty-five women developed GDM (insulin: 19, metformin: 12, diet: 53) and 294 women had uncomplicated pregnancies. All 379 women showed a mean increase in peripheral systolic BP (SBP; 2.89 mmHg, 1.75–4.02), peripheral diastolic BP (DBP; 2.06 mmHg, 1.20–2.92), peripheral mean arterial pressure (MAP; 1.85, 0.90–2.80), central DBP (2.36 mmHg, 1.49–3.22), central MAP (1.39 mmHg, 0.55–2.24) but not peripheral pulse pressure (PP) nor central SBP across gestation. Central PP decreased across gestation (2.88 mmHg, 2.14–3.63), as did AIx (18.22%, 16.57–19.96). AIx decreased less in women with diet-controlled GDM (9.27%, 4.78–13.77) and metformin-controlled GDM (8.76%, 0.33–17.18), but not in those with insulin-controlled GDM, compared to uncomplicated pregnancies. Changes across gestation for peripheral SBP, DBP, MAP, PP and central SBP, DBP, MAP and PP were not different in women with GDM compared to those with uncomplicated pregnancies. Conclusion Across gestation, AIx decreased less in women with diet-controlled and metformin-controlled GDM, compared to those with uncomplicated pregnancies. Those with insulin-controlled GDM showed comparable haemodynamic adaptation to those with uncomplicated pregnancies. This suggests that women with diet-controlled or metformin-controlled GDM have cardiovascular maladaptation to pregnancy which disappears with insulin treatment.

Analysis of correlations between the placental expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus

Purpose: The aim of the study was to analyze the correlations between the expression of glucose transporters GLUT-1, GLUT-4, and GLUT-9 in human term placenta and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus (DM). Materials and methods: Placental samples were obtained from healthy control (n = 25) and diabetic pregnancies, including diet-controlled gestational diabetes mellitus (GDMG1) (n = 16), insulin-controlled gestational diabetes mellitus (GDMG2) (n = 6), and pregestational DM (PGDM) (n = 6). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected glucose transporter proteins. For the purposes of correlation analysis, the following parameters were selected: type of diabetes, gestational age, maternal prepregnancy body mass index (BMI), gestational weight gain, third trimester glycated hemoglobin concentration, placental weight, fetal birth weight (FBW) as well as ultrasonographic indicators of fetal adiposity, including subscapular (SSFM), abdominal (AFM), and midthigh (MTFM) fat mass measurements. Results: In the PGDM group, the analysis demonstrated positive correlations between the placental expression of GLUT-1, GLUT-4, and GLUT-9 and FBW, AFM, and SSFM measurements (p < .05). Similarly in the GDMG2 patients positive correlations between GLUT-4 expression, FBW and SSFM were observed (p < .05). In the multivariate regression analysis, only the type of diabetes and FBW were significantly associated with GLUTs expression (p < .001). In addition, maternal prepregnancy BMI significantly contributed to GLUT-1 expression (p < .001). Conclusions: The study results revealed that placental expression of GLUT-1, GLUT-4, and GLUT-9 may be involved in the intensification of the fetal growth in pregnancies complicated by GDM/PGDM.

Cerebroplacental ratio in pregnancies complicated by gestational diabetes mellitus.

To assess the relationship between the cerebroplacental ratio (CPR) and intrapartum and perinatal outcomes in pregnancies complicated by gestational diabetes mellitus (GDM). This was a retrospective cohort study of women with a non-anomalous singleton pregnancy diagnosed with GDM who delivered at Mater Mothers' Hospital between 2007 and 2015. CPR was measured in 1089 cases between 34 + 0 and 36 + 6 weeks' gestation. CPR values were compared between groups categorized according to GDM treatment (by diet, oral hypoglycemic agent (OHA) or insulin). The association between CPR and intrapartum and perinatal outcomes was evaluated. No difference in CPR was observed between treatment groups. Fetuses with CPR < 10th centile were significantly more likely to have adverse composite perinatal outcome (odds ratio (OR) = 2.93 (95% CI, 1.95-4.40)), preterm delivery and low birth weight than fetuses with CPR ≥ 10th centile (all P < 0.001). These associations were present regardless of the type of GDM treatment. Fetuses of women with insulin-controlled GDM had poorer neonatal outcomes than did fetuses of women treated with OHA or dietary control alone. The risk of adverse outcome was significantly increased in the insulin-treated group (OR = 1.75 (95% CI, 1.34-2.28); P < 0.001), which also had higher rates of preterm delivery and higher birth weight. Regardless of the type of treatment, a low CPR is associated with poorer neonatal outcome in women with GDM. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Impact of pre-gestational and gestational diabetes mellitus on the expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 in human term placenta

PurposeVarious studies in placental tissue suggest that diabetes mellitus alters the expression of glucose transporter (GLUT) proteins, with insulin therapy being a possible modulatory factor. The aim of the present study was quantitative evaluation of the expression of glucose transporters (GLUT-1, GLUT-4, GLUT-9) in the placenta of women in both, uncomplicated and diabetic pregnancy. Additionally, the effect of insulin therapy on the expression of selected glucose transporter isoforms was analyzed.MethodsTerm placental samples were obtained from healthy control (n = 25) and diabetic pregnancies, including diet-controlled gestational diabetes mellitus (GDMG1) (n = 16), insulin-controlled gestational diabetes mellitus (GDMG2) (n = 6), and pre-gestational diabetes mellitus (PGDM) (n = 6). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected glucose transporter proteins.ResultsMorphometric analysis revealed a significant increase in the expression of GLUT-4 and GLUT-9 in insulin-dependent diabetic women (GDMG2 + PGDM) as compared to both, control and GDMG1 groups (p < .05). Significantly increased GLUT-1 expression was observed only in placental specimens from patients with PGDM (p < .05). No statistically significant differences in GLUT expression were found between GDMG1 patients and healthy controls.ConclusionsThe results of the study confirmed the presence of GLUT-1, GLUT-4 and GLUT-9 proteins in the trophoblast from both, uncomplicated and diabetic pregnancies. In addition, insulin therapy may increase placental expression of GLUT-4 and GLUT-9, and partially GLUT-1, in women with GDMG2/PGDM.

Fatty acid profile in cord blood of neonates born to optimally controlled gestational diabetes mellitus

ObjectiveTo evaluate the fatty acid profile of cord blood phospholipids (PL), cholesteryl esters (CE), triglycerides (TG) and non-esterified fatty acids (NEFA) in neonates born to mothers with gestational diabetes mellitus (GDM) compared to non-diabetic mothers. MethodsThe offspring of 30 pregnant women (15 non-diabetic controls, 15 with diet- or insulin-controlled GDM) were recruited before delivery. Cord blood was collected. After lipid extraction, PL, CE, TG and NEFA were separated by thin layer chromatography and analysed by gas chromatography. ResultsIn GDM vs. control mothers, maternal glycated haemoglobin (A1C, mean±SD) was not different between groups: 5.3±0.5% vs. 5.3±0.3% (p=0.757), respectively. Cord plasma fatty acids were not different in TG, CE and NEFA between GDM and non-diabetic mothers. However, in PL, levels of palmitate, palmitoleate, oleate, vaccinate and di-homo-gamma-linolenate were significantly lower, with a trend for lower arachidonate (p=0.078), in neonates born to GDM mothers compared to controls. ConclusionIn contrast to other studies on cord blood docosahexaenoic acid (DHA) levels in GDM mothers, we did not found lower levels of DHA in cord PL, CE, TG or NEFA in neonates born to GDM compared to non-diabetic mothers.

Diabetes and obesity during pregnancy alter insulin signalling and glucose transporter expression in maternal skeletal muscle and subcutaneous adipose tissue

Severe insulin resistance is a defining attribute of gestational diabetes mellitus (GDM). It is postulated that alterations in the insulin-signalling pathway and subsequent glucose disposal are the underlying cause of insulin resistance in patients with GDM. The purpose of this study was to profile the insulin-signalling pathway and intermediates in insulin-sensitive tissues. Subcutaneous adipose tissue and skeletal muscle were collected from normal glucose-tolerant (NGT) and insulin-controlled GDM in both non-obese and obese cohorts (n=6-8 per subgroup). Expression studies of the insulin-signalling pathway were performed using western blotting and quantitative reverse transcription-PCR. This study demonstrated altered mRNA expression of insulin receptor substrate (IRS)-1, IRS-2, glucose transporter (GLUT)-1, GLUT-4 and glycogen synthase kinase (GSK)-3 isoforms genes in adipose tissue in GDM women in comparison to NGT pregnant controls. In skeletal muscle, insulin-controlled GDM was associated with decreased IRS-1, phosphatidylinositol-3-kinase (PI3-K) p85alpha, GLUT-1 and -4, GSK-3 isoforms and phosphoinositide-dependent kinase-1. Both adipose tissue and skeletal muscle from women with GDM displayed decreased IRS-1 and GLUT-4 and increased PI3-K p85alpha protein expression. Both skeletal muscle and adipose tissue from obese women demonstrated lower GLUT-1 and -4 mRNA expression and diminished GLUT-4 protein expression in skeletal muscle only. Collectively, our results suggest that diabetes and obesity during pregnancy cause defects in insulin-signalling transduction in adipose tissue and skeletal muscle and may be the underlying cause of GDM.

Defective insulin signaling in placenta from pregnancies complicated by gestational diabetes mellitus

Studies in adipose tissue and skeletal muscle suggest that impaired insulin action is due to defects in the insulin signaling pathway and may play a role in the pathophysiology of insulin resistance associated with gestational diabetes mellitus (GDM) and obesity. The present study tested the hypothesis that endogenous expression levels in the human term placenta of insulin signaling components are altered in placental tissue from GDM women in comparison with normal controls and maternal obesity. Placental tissue was collected from normal, diet-controlled GDM, and insulin-controlled GDM in both non-obese and obese women (n=6-7 per group). Western blotting and quantitative RT-PCR was performed to determine the level of expression in the insulin signaling pathway. There was a significant increase in insulin receptor (IR) substrate (IRS)-1 protein expression with a concurrent decrease in IRS-2 protein expression in non-obese women with insulin-controlled GDM compared with diet-controlled GDM and normal controls. Furthermore, a decrease in both protein and mRNA expression of phosphatidyl-inositol-3-kinase (PI3-K) p85alpha and glucose transporter (GLUT)-4 was observed in non-obese and obese women with insulin controlled GDM compared with normal controls. When comparing non-obese to obese patients, significant decreases in mRNA expression of IR-beta, PI3K p85alpha and GLUT-4 was found in obese patients. Our results suggest that post receptor defects are present in the insulin signaling pathway in placenta of women with pregnancies complicated by diabetes and obesity. In addition, expression studies demonstrate post receptor alterations in insulin signaling possibly under selective maternal regulation and not fetal regulation.

Evaluation of Metabolic Control in Women with Gestational Diabetes Mellitus by the Continuous Glucose Monitoring System: A Pilot Study

To evaluate the blood glucose concentrations in a group of women with gestational diabetes mellitus (GDM), by the use of a continuous glucose monitoring system (CGMS). Seven women with diet-controlled GDM (group G1), 5 with diet- and insulin-controlled GDM (group G2), and 7 healthy, pregnant women (group N) were included in the study. The treatment was adjusted on the basis of self-monitoring of blood glucose (SMBG). The self-monitoring was performed 4 times a day, with the goals of fasting blood glucose values of <90 mg/dL and postprandial (2 hours after each meal) values of <120 mg/dL. Then patients were submitted to a 72-hour period of use of the CGMS. In the 3 study groups--N, G1, and G2, respectively--no significant differences were noted in individual study parameters, measured with the CGMS in regard to the following: mean 24-hour glycemia (85, 87, and 91 mg/dL), fasting blood glucose (79, 88, and 82 mg/dL), postprandial glucose (96, 97, and 105 mg/dL), mean glucose level during the night (77, 71, and 75 mg/dL), and area under the glycemia curve (281, 315, and 310). Moreover, no significant difference was found in the total duration of glycemia below 60 mg/dL (317, 300, and 370 minutes) or the duration of glycemia of more than 120 mg/dL (259, 225, and 394 minutes) in group N, G1, and G2, respectively. With use of the CGMS, however, in comparison with SMBG, a wider range of glycemic levels was observed in all 3 study groups: for the healthy, pregnant women, 41 to 194 mg/dL versus 61 to 151 mg/dL; for G1, 40 to 244 mg/dL versus 40 to 180 mg/dL; and for G2, 40 to 173 mg/dL versus 50 to 157 mg/dL. The therapy, based on SMBG levels, when applied to the group of women with GDM, brought the glucose levels under effective control, with mean outcome values similar to those observed in the group of normal pregnant women. Nevertheless, using the CGMS, we detected long, asymptomatic periods of high and low blood glucose levels, both in the patients with GDM and in the unaffected pregnant women. The use of the CGMS for monitoring blood glucose profiles might be beneficial in this group of pregnant women.

Release and regulation of leptin, resistin and adiponectin from human placenta, fetal membranes, and maternal adipose tissue and skeletal muscle from normal and gestational diabetes mellitus-complicated pregnancies

The aim of this study was to determine the release and regulation of leptin, resistin and adiponectin from human placenta and fetal membranes, and maternal subcutaneous adipose tissue and skeletal muscle obtained from normal and gestational diabetes mellitus (GDM)-complicated pregnancies at the time of Cesarean section. Tissue explants were incubated in the absence (basal control) or presence of 10 mug/ml lipopolysaccharide (LPS), 10, 20 or 40 ng/ml tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-8, 1 microM phorbol myristate acetate, 10, 20 and 40 mM glucose, 0.1, 1 and 10 microM insulin and 0.1 1 and 10 microM dexamethasone, progesterone and estrogen. After an 18-h incubation, the medium was collected and the release of leptin, resistin and adiponectin was quantified by ELISA. Human gestational tissues and maternal tissues released immunoreactive leptin, resistin and adiponectin; however, there was no difference in the release of either resistin or adiponectin between normal pregnant women and women with gestational diabetes. The release of leptin was significantly higher in placenta, amnion and choriodecidua obtained from normal pregnant women compared with women with GDM. However, in maternal tissues, the situation was reversed, with adipose tissue and skeletal muscle obtained from women with GDM releasing significantly greater amounts of leptin. In adipose tissue and skeletal muscle the release of leptin was significantly greater in insulin-controlled GDM compared with diet-controlled GDM, and leptin release from adipose tissue was significantly correlated with maternal body mass index. In all tissues tested, there was no effect of incubation with LPS, IL-6, IL-8 or TNF-alpha on leptin, resistin or adiponectin release. PMA significantly increased the release of resistin from placenta and adipose tissue. Insulin increased placental resistin release, whereas the hormones dexamethasone, progesterone and estrogen significantly decreased placental resistin release. The data presented in this study demonstrate that dysregulation of leptin metabolism and/or function in the placenta may be implicated in the pathogenesis of GDM. Furthermore, resistin release is greatly affected by a variety of inflammatory mediators and hormones.