Diet-controlled Gestational Diabetes Mellitus Research Articles

Correlation of sonographically measured fetal abdominal wall thickness with birth weight in diabetes

ObjectiveTo determine the association between sonographically measured abdominal wall thickness (AWT) and birth weight of fetuses of pregnant women with diabetes. MethodsThis retrospective study included 185 pregnant women who presented to a level I perinatal centre between January 2021 and December 2022. All mothers had diabetes, and were divided into the following subgroups: diet-controlled gestational diabetes mellitus; insulin-dependent gestational diabetes mellitus; type 1 diabetes mellitus; and type 2 diabetes mellitus. At the time of admission, gestational age varied between 29 + 2 and 41 + 2 weeks (+days) of gestation. Weight estimation was performed routinely using the Hadlock I formula. Fetal AWT was determined retrospectively at the same axial level as used for the measurement of abdominal circumference. Only women with a sonographic fetal weight estimation within 5 days before delivery were included. ResultsFor the whole cohort, a moderate positive correlation was found between fetal AWT and estimated fetal weight (r = 0.411, p < 0.001), a moderate correlation was found between fetal AWT and birth weight (r = 0.493, p < 0.001), a weak correlation was found between fetal AWT and body length (r = 0.365, p < 0.001), and a weak correlation was found between fetal AWT and body length percentile (r = 0.276, p < 0.001). No strong differences in parameters were found between the diabetes subgroups. Receiver operating characteristic (ROC) curve analysis was performed to identify newborns with birth weight > 4000 g (macrosomia) and birth weight > 90th percentile according to Voigt in the group with gestational age > 37 weeks. ROC curve analysis was performed to identify newborns with birth weight > 90th percentile in the whole cohort. AWT and sonographically estimated fetal weight were included in the calculation. The combination of AWT and estimated fetal weight only led to a marginal improvement compared with estimated fetal weight alone for predicting newborns with birth weight > 4000 g in the group with gestational age > 37 weeks [area under the curve (AUC) 0.857 vs 0.871], and for predicting newborns with birth weight > 90th percentile in the group with gestational age > 37 weeks (AUC 0.840 vs 0.846) and in the whole cohort (AUC 0.816 vs 0.826). ConclusionA sonographically measured AWT of 7.1 mm in fetuses of diabetic mothers is predictive of birth weight > 90th percentile with sensitivity of 61 %, specificity of 85 %, and AUC of 0.748. ROC curve analysis showed that estimated fetal weight determined by ultrasound (using Hadlock formula I) seems to be slightly superior for the identification of macrosomic fetuses with birth weight > 90th percentile. A threshold value for estimated fetal weight of 3774 g had sensitivity of 70 %, specificity of 86 %, and AUC of 0.816. The combination of AWT and estimated fetal weight in a single formula only yielded a marginal improvement in accuracy compared with the use of estimated fetal weight alone.

Impact of previous gestational diabetes management on perinatal outcomes in subsequent pregnancies affected by gestational diabetes mellitus.

To determine the impact of prior gestational diabetes mellitus (GDM) on perinatal outcomes in a subsequent GDM pregnancy. This retrospective cohort study included 544 multiparous patients with two consecutive pregnancies between 2012-2019, where the second (index) pregnancy was affected by GDM. The primary exposure was prior GDM diagnosis, categorized into medical and dietary management. The primary outcome was a composite including need for pharmacotherapy, large-for-gestational age, or neonatal hypoglycemia. Adjusted odds ratios (aOR) were calculated using multivariable logistic regressioncontrolling for maternal age, pre-pregnancy body mass index, and gestational age at GDM diagnosis in the index pregnancy. Of the 544 patients, 164 (30.1%) had prior GDM. Prior GDM significantly increased the likelihood ofcomposite outcome compared to no prior GDM (74.4% vs. 57.4%; P < 0.001). After adjusting for confounders, prior GDM remained significantly associated with the composite outcome (aOR 2.03, 95% confidence interval [CI] 1.31-3.15). Stratifying by prior GDM treatment modality, a significant association was found for prior pharmacotherapy-controlledGDM (aOR 3.29, 95% CI 1.64-6.59), but not for prior diet-controlled GDM (aOR = 1.54, 95% CI 0.92-2.60). A history of pharmacotherapy-controlled GDM in a previous pregnancy increases odds of adverse perinatal outcomes in a subsequent GDM pregnancy.

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.

Comparisons of the Rates of Large-for-Gestational-Age Newborns between Women with Diet-Controlled Gestational Diabetes Mellitus and Those with Non-Gestational Diabetes Mellitus.

(1) Objectives: The primary objective is to compare the rate of large-for-gestational-age (LGA) between women with diet-controlled gestational diabetes mellitus (GDM) and those with non-GDM, and to assess whether or not diet-controlled GDM is an independent factor of LGA fetuses. The secondary objectives are to compare the rates of other common adverse pregnancy outcomes, such as preeclampsia, cesarean section rate, preterm birth, and low Apgar score, between pregnancies with diet-controlled GDM and non-GDM pregnancies. (2) Methods: A retrospective cohort study was conducted on singleton pregnancies, diagnosed with GDM and non-GDM between 24 and 28 weeks of gestation, based on a two-step screening test. The prospective database of the obstetric department was accessed to retrieve the records meeting the inclusion criteria, and full medical records were comprehensively reviewed. The patients were categorized into two groups, GDM (study group) and non-GDM (control group). The main outcome was the rate of LGA newborns, and the secondary outcomes included pregnancy-induced hypertension, preterm birth, cesarean rate, low Apgar scores, etc. (3) Results: Of 1364 recruited women, 1342 met the inclusion criteria, including 1177 cases in the non-GDM group and 165 (12.3%) in the GDM group. Maternal age and pre-pregnancy BMI were significantly higher in the GDM group. The rates of LGA newborns, PIH, and cesarean section were significantly higher in the GDM group (15.1% vs. 7.1%, p-value < 0.001; 7.8% vs. 2.6%, p-value = 0.004; and 54.5% vs. 41.5%, p-value = 0.002; respectively). On logistic regression analysis, GDM was not significantly associated with LGA (odds ratio 1.64, 95% CI: 0.97-2.77), while BMI and gender were still significantly associated with LGA. Likewise, GDM was not significantly associated with the rate of PIH (odds ratio: 1.7, 95% CI: 0.825-3.504), while BMI and maternal age were significantly associated with PIH, after controlling confounding factors. (4) Conclusions: The rates of LGA newborns, PIH, and cesarean section are significantly higher in women with diet-controlled GDM than those with non-GDM. Nevertheless, the rates of LGA newborns and PIH are not directly caused by GDM but mainly caused high pre-pregnancy BMI and advanced maternal age, which are more commonly encountered among women with GDM.

Correlation between Serum Fructosamine and Self- Monitoring Blood Glucose in Patients with Diet-Controlled Gestational Diabetes Mellitus

Objective: To determine the correlation between serum fructosamine and self-monitoring blood glucose (SMBG) levels in gestational diabetes mellitus (GDM) patients treated by dietary control and to identify the cutoff level of serum fructosamine for determining poorly controlled GDM. Materials and Methods: A cross-sectional study conducted between October 2021 and August 2022 at Queen Savang Vadhana Memorial Hospital that included 78 singleton pregnancies diagnosed with GDM assigned to diet therapy with lifestyle modification. The daily home SMBG was performed following the standard protocol and the serum fructosamine was measured one month after starting dietary control. The correlation between serum fructosamine and means of SMBG were analyzed. The receiver operating characteristics (ROC) curve was plotted to identify the cutoff level of serum fructosamine for predicting poorly controlled GDM based on SMBG levels. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the cutoff level were calculated. Results: The correlation between serum fructosamine and SMBG were 0.436 (p&lt;0.001) and 0.618 (p&lt;0.001) in pre-prandial and post-prandial glucose levels, respectively. The poorly controlled SMBG group had serum fructosamine greater than the well-controlled group with a mean of 165.7±35 and 132.8±23 μmol/L (p&lt;0.001). The ROC curve showed that using 160 μmol/L as the optimal cutoff level to determine poorly controlled GDM had 72.7% sensitivity, 88% specificity, 50% PPV, 95.2% NPV, and 85.9% accuracy. Conclusion: The serum fructosamine was very useful for monitoring dietary control of GDM in terms of drawing blood less frequently, convenient, and more economical. An optimal cutoff point for screening a poorly controlled GDM was 160 mol/L. Keywords: Gestational diabetes mellitus; Serum fructosamine; Self-monitoring blood glucose

Gestational diabetes mellitus in pregnancies conceived after infertility treatment: a population-based study in the United States, 2015–2020

To evaluate the risk of gestational diabetes mellitus (GDM) in singleton pregnancies conceived using infertility treatment and examine the influence of race and ethnicity as well as prepregnancy body mass index (BMI). Cross-sectional study using the US vital records data of women that delivered singleton births. United States, 2015-2020. Any infertility treatment was divided into two groups: those that used fertility-enhancing drugs, artificial insemination, or intrauterine insemination, and those that used assisted reproductive technology (ART). Gestational diabetes mellitus, defined as a diagnosis of diabetes mellitus during pregnancy, includes both diet-controlled GDM and medication-controlled GDM in singleton pregnancies conceived with infertility treatment or spontaneously and delivered between 20- and 44-weeks' gestation. We also examined whether the infertility treatment-GDM association was modified by maternal race and ethnicity as well as prepregnancy BMI. Associations were expressed as a rate ratio (RR) and 95% confidence interval (CI), derived from log-linear models after adjustment for potential confounders. A total of 21,943,384 singleton births were included, with 1.5% (n = 318,086) undergoing infertility treatment. Rates of GDM among women undergoing infertility treatment and those who conceived spontaneously were 11.0% (n = 34,946) and 6.5% (n = 1,398,613), respectively (adjusted RR 1.24, 95% CI 1.23, 1.26). The RRs were adjusted for maternal age, parity, education, race and ethnicity, smoking, BMI, chronic hypertension, and year of delivery. The risk of GDM was modestly increased for those using fertility-enhancing drugs (adjusted RR 1.28, 95% CI 1.27, 1.30) compared with ART (adjusted RR 1.18, 95% CI 1.17, 1.20), and this risk was especially apparent for non-Hispanic White women (adjusted RR 1.29, 95% CI 1.26, 1.31) and Hispanic women (adjusted RR 1.35, 95% CI 1.29, 1.41). The number of women who needed to be exposed to infertility treatment to diagnose one case of GDM was 46. Prepregnancy BMI did not modify the infertility treatment-GDM association overall and within strata of race and ethnicity. These general patterns were stronger after potential corrections for misclassification of infertility treatment and unmeasured confounding. Infertility treatment, among those who received fertility-enhancing drugs, is associated with an increased GDM risk. The persistently higher risk of GDM among women who seek infertility treatment, irrespective of prepregnancy weight classification, deserves attention. Infertility specialists must be vigilant with preconception counseling and ensure that all patients, regardless ofrace and ethnicity or BMI, are adequately tested for GDM early in pregnancy using a fasting blood glucose level or a traditional 50-g oral glucose tolerance test. Testing may be completed by the infertility specialist or deferred to the primary prenatal care provider at the first prenatal visit.

1181-P: Substituting Protein for Fat Lowers Postprandial Glycemic Response in Gestational Diabetes

Background: Dietary guidelines in gestational diabetes mellitus (GDM) focus on carbohydrate without regard to other macronutrients. We tested the impact of fat and protein on postprandial glycemia in GDM and analyzed whether the physiology underlying GDM influenced this response. Methods: In a pilot crossover trial, participants ate two isocaloric breakfast meals with the same carbohydrate content and different protein and fat content (High protein meal: 390 kCal, 35 g protein, 9 g fat, 45 g carb, High fat meal: 411 kCal, 15 g protein, 19 g fat, 46 g carb) on subsequent days in a random order. We measured peak postprandial glucose (primary outcome) using continuous glucose monitors. We used homeostatic model assessment to determine if participants had insulin resistant (IR) or insulin deficient (ID) GDM. We used paired t-tests to test if glycemic response to the meals differed and linear regression to test if differential response to meals was influenced by having IR vs ID GDM. Results: We studied 16 women with diet-controlled GDM (median [IQR] 31 [30-33] weeks’ gestation). Mean [SD] peak glucose after the high fat meal (146 [20] mg/dl) was higher than after the high protein meal (137 [21] mg/dl) (P=0.03), but individuals varied in their differential response to the meals (range: 25 mg/dl higher after high protein meal to 35 mg/dl higher after high fat meal). Median time to peak glucose (IQR) was 72 (63-74) minutes after the high protein meal and 65 (60-73) minutes after the high fat meal (P=0.11). There was no difference in differential glycemic response to the meals in IR (n=8) vs ID (n=4) GDM (P=0.98); age (median [IQR] 36 [33-38] yrs) and BMI (median [IQR] 27 [24-30]) adjustment did not change results (P=0.82). Conclusion: On average, women with GDM have lower post prandial glucose levels after a high protein meal compared to a high fat meal with equivalent carbohydrate content. This may inform GDM dietary recommendations and motivate research on determinants of individual-level response to macronutrients. Disclosure E.A.Rosenberg: None. T.Thaweethai: None. K.James: None. E.Kelty: None. R.L.Azevedo: None. S.Nelson: None. J.L.Garry: None. E.W.Seely: None. C.E.Powe: Consultant; Mediflix, Inc., Other Relationship; Wolters Kluwer Health. Funding Robert Wood Johnson Foundation; National Institutes of Health (5F32DK12634302); Endocrine Fellows Foundation

Physical Activity, but Not Glycaemic Load, Is Associated with Lower Real-Time Glycaemic Control in Free-Living Women with Gestational Diabetes Mellitus.

Maintaining blood glucose within the target range is the primary treatment goal for women with gestational diabetes mellitus (GDM). Foods with low glycaemic loads are recommended in clinical practice; however, the relative importance of other key lifestyle variables is unexplored. This pilot study explored the associations of glycaemic load, carbohydrates and physical activity parameters on blood glucose concentrations in free-living women with GDM. Twenty-nine women (28-30 weeks gestation, 34 ± 4 years) with GDM were enrolled. Continuous glucose monitoring, physical activity (ActivPAL inclinometer) and dietary intake and dietary quality were measured concurrently for 3 days. Pearson correlation analyses determined the association between glucose levels and lifestyle variables. Despite all receiving the same nutrition education, only 55% of women were following a low glycaemic load diet with a large range of carbohydrate intakes (97-267 g/day). However, the glycaemic load did not correlate with 3-hr postprandial glucose (r2 = 0.021, p = 0.56) or 24-h glucose iAUC (r2 = 0.021, p = 0.58). A significant relationship between total stepping time and lower 24-h glucose iAUC (r2 = 0.308, p = 0.02) and nocturnal glucose (r2 = 0.224, p = 0.05) was found. In free-living women with diet-controlled GDM, more physical activity, i.e., steps accumulated across the day, may be a simple and effective strategy for improving maternal blood glucose concentrations.

High Free T3 Levels in the Second Trimester are Correlated with the Control of Gestational Diabetes Mellitus

Gestational Diabetes Mellitus (GDM) and abnormal thyroid function are two common endocrine disorders occurring during pregnancy. In this study, we evaluated the correlation between the levels of different thyroid hormones and blood glucose control in pregnant women with diet-controlled GDM. Mid-pregnancy serum samples were obtained from 439 participants with GDM controlled by diet for analyses of thyroid function. A 2-h 75-g oral glucose tolerance test was used to evaluate the effect of blood glucose controlled by diet. According to blood glucose levels before and 2h after a meal, mothers were grouped into GDM-A1 (≤5.3mmol/L, ≤6.7mmol/L, respectively) and GDM-A2 (&gt;5.3 mmol, &gt;6.7mmol/L, respectively) and these groups were compared to the associated thyroid levels using multivariate logistic regression analysis. Our results show that fT3 was positively associated with GDM-A2. The adjusted odds ratio (95% confidence interval) comparing the highest and lowest fT3 quartile was 3.12 (1.66, 15.87) at the second trimester. Neither TSH nor fT4 was significantly associated with GDM-A2. Higher FT3 levels during the second trimester of pregnancy are a risk for GDM-A2 incidence. This provides new ideas for the control of GDM.

Abstract 11687: Diagnosis and Management of High-Risk Pulmonary Embolism in a Term Neonate

Case Presentation: A 5 day old, term infant born to a 39-year-old G1P0 with a history of diet-controlled gestational diabetes mellitus presented with hypernatremic dehydration in the setting of poor feeding. On hospital day 2, the infant suffered a bradycardic cardiac arrest requiring 2 minutes of CPR prior to return of spontaneous circulation. An echocardiogram (Figure 1A) revealed moderately depressed right ventricular (RV) function, elevated RV pressure and a large mobile mass extending from the main pulmonary artery (PA) into the left PA with obstruction of flow. D-dimer was markedly elevated at 2740 ng/mL. A subsequent CT angiogram revealed acute pulmonary emboli in the distal left and right branch PAs (Figure 1B). Additional imaging was obtained and showed dural venous sinus, left portal vein and right cephalic vein thromboses. The infant was managed with a heparin infusion and supportive therapy for the RV dysfunction and pulmonary hypertension including mechanical ventilation, inhaled nitric oxide as well as epinephrine and milrinone infusions. Over the course of two weeks, the infant improved clinically with normalization of RV function. Discussion: Neonatal pulmonary arterial thrombosis is an exceedingly rare phenomenon. The majority of cases described in the literature are associated with either an inherited thrombophilia or with underlying congenital heart disease, which were not found to be present in this case. However, this patient presented with severe dehydration and a history of maternal diabetes, both of which are risk factors for neonatal thrombosis. Fortunately, this patient responded to treatment with anticoagulation alone and did not require more invasive therapies, such as surgical thrombectomy or systemic and catheter-directed thrombolysis. Although rare, neonatal pulmonary arterial thrombosis can occur and delays in recognition and treatment may lead to significant RV dysfunction, morbidity, and even death.

Establishing the Optimal Time for Induction of Labor in Women with Diet-Controlled Gestational Diabetes Mellitus: A Single-Center Observational Study.

To determine the optimal week for labor induction in women with diet-controlled gestational diabetes mellitus by comparing differences in perinatal and neonatal outcomes of labor induction to expectant management at different gestational weeks. Methods: This was a retrospective analysis of a prospectively recruited cohort of 797 singleton pregnancies complicated by diet-controlled gestational diabetes mellitus that were diagnosed, treated, and delivered after 37 weeks in a tertiary, university-affiliated perinatal center between January 2016 and December 2021. Results: The incidence of neonatal complications was highest when delivery occurred at 37 weeks, whereas fetal macrosomia occurred mostly at 41 weeks (20.7%); the frequency of large for gestational age infants did not differ between the groups. Conversely, the best neonatal outcomes were observed at 40 weeks due to the lowest number of neonates requiring phototherapy for neonatal jaundice (1.7%) and the smallest proportion of neonates experiencing composite adverse neonatal outcomes defined as neonatal hypoglycemia, phototherapy, clavicle fracture, or umbilical artery pH &lt; 7.15 (10.4%). Compared with expectant management, the risk for neonatal hypoglycemia was increased for induction at 39 weeks (adjusted odds ratio 12.29, 95% confidence interval 1.35-111.75, p = 0.026) and that for fetal macrosomia was decreased for induction at 40 weeks (adjusted odds ratio 0.11, 95% confidence interval 0.01-0.92, p = 0.041), after adjusting for maternal pre-pregnancy body mass index, nulliparity, and mean pregnancy A1c. Conclusions: The lowest rate of neonatal complications was observed at 40 weeks. Labor induction at 40 weeks prevented fetal macrosomia.

Establishing the Optimal Time for Induction of Labor in Women with Diet-Controlled Gestational Diabetes Mellitus: A Single-Center Observational Study

Establishing the Optimal Time for Induction of Labor in Women with Diet-Controlled Gestational Diabetes Mellitus: A Single-Center Observational Study

Optimal delivery time for patients with diet-controlled gestational diabetes mellitus: a single-center real-world study

BackgroundTo determine the optimal delivery time for women with diet-controlled gestational diabetes mellitus by comparing differences in adverse maternal–fetal outcome and cesarean section rates.MethodsThis real-world retrospective study included 1,050 patients with diet-controlled gestational diabetes mellitus who delivered at 35–42 weeks’ gestation. Data on patient characteristics, maternal–fetal outcomes, and cesarean section rate based on fetal gestational age were collected and analyzed. Differences between deliveries with and without iatrogenic intervention were also analyzed.ResultsThe cesarean section rate at ≥ 41 weeks’ gestation was significantly higher than that at 39–39 + 6 weeks (56% vs. 39%, p = 0.031). There were no significant differences in multiple adverse maternal or neonatal outcomes at delivery before and after 39 weeks. Vaginal delivery rates were increased significantly at 39–39 + 6 weeks due to iatrogenic intervention (p = 0.005) and 40–40 + 6 weeks (p = 0.003) in patients without and with spontaneous uterine contractions, respectively.ConclusionsIt’s recommended that optimal delivery time for patients with diet-controlled gestational diabetes mellitus should be between 39- and 40 + 6 weeks’ gestation. Patients who have Bishop scores higher than 4 can undergo iatrogenic intervention at 39–39 + 6 weeks. However iatrogenic interventions are not recommended for patients with low Bishop scores.

Metabolomic profile associated with obstructive sleep apnoea severity in obese pregnant women with gestational diabetes mellitus: A pilot study.

Obstructive sleep apnoea (OSA) is prevalent in obese women with gestational diabetes mellitus (GDM). The present pilot study explored associations between OSA severity and metabolites in women with GDM. A total of 81 obese women with diet-controlled GDM had OSA assessment (median gestational age [GA] 29weeks). The metabolic profile was assayed from fasting serum samples via liquid chromatography-mass spectrometry (LC-MS) using an untargeted approach. Metabolites were extracted and subjected to an Agilent 1,290 UPLC coupled to an Agilent 6,545 quadrupole time-of-flight (Q-TOF) MS. Data were acquired using electrospray ionisation in positive and negative ion modes. The raw LC-MS data were processed using the OpenMS toolkit to detect and quantify features, and these features were annotated using the Human Metabolite Database. The feature data were compared with OSA status, apnea-hypopnea index (AHI), body mass index (BMI) and GA using "limma" in R. Correlation analyses of the continuous covariates were performed using Kendall's Tau test. The p values were adjusted for multiple testing using the Benjamini-Hochberg false discovery rate correction. A total of 42 women (51.8%) had OSA, with a median AHI of 9.1events/hr. There were no significant differences in metabolomics profiles between those with and without OSA. However, differential analyses modelling in GA and BMI found 12 features that significantly associated with the AHI. These features could be annotated to oestradiols, lysophospholipids, and fatty acids, with higher levels related to higher AHI. Metabolites including oestradiols and phospholipids may be involved in pathogenesis of OSA in pregnant women with GDM. A targeted approach may help elucidate our understanding of their role in OSA in this population.

Evaluation of serum Angiopoietin-like protein 2 (ANGPTL-2), Angiopoietin-like protein 8 (ANGPTL-8), and high-sensitivity C-reactive protein (hs-CRP) levels in patients with gestational diabetes mellitus and normoglycemic pregnant women

Objective In the present study, we aimed to investigate the role of the fasting serum levels of Anjiopoetın 2 - like protein (ANGPTL2), Anjiopoetın 8-like protein (ANGPTL8), and high-sensitivity C-reactive protein (hs-CRP) in the etiopathogenesis of gestational diabetes mellitus (GDM), and analyze the relationships between insulin resistance parameters. Material and method The 90 individuals admitted to İzmir Katip Celebi University Hospital Internal Medicine, Endocrinology and Obstetrics, and gynecology outpatient clinic were included in the study of similar ages and similar demographic characteristics. Forty-five women with diet-controlled GDM and 45 women with normoglycemic pregnancy were enrolled. ANGPTL-2, ANGPTL-8, hs-CRP, creatinine, ALT, GGT, lipid profile, HBA1c(%), and serum insülin, c-peptide levels were studied in the fasting serum samples of research groups. All individuals had 75-g OGTT testing. GDM screening was performed at 24–28 weeks’ gestation. Exclusion criteria were as follows: Age <18 years or >40 years, pregestational diabetes (type 1 or 2), drug or alcohol abuse, thyroid dysfunction, Hepatitis B, and other infectious diseases (Herpes virus, Streptococcus B carriers, Chlamydia and Candida), Thalassemia carriers or other significant medical conditions, the use of any medication that interferes with lipid or glucose metabolism that would affect glucose regulation. Result Forty-five women with GDM and for the control group, 45 women with normoglycemic pregnant women were identified. The mean gestational age was 30.7 (18–38) for GDM and 29.6 (24–39) for the control group. Serum ANGPTL-8 (GDM =19.5 ± 93 Control = 0.73 ± 3.78 p = <.001). There was a statistically significant difference between the case and control groups for serum ANGPTL-8 levels. Serum ANGPTL-2 (GDM =19.9 ± 23.1 Control = 26.0 ± 23.4 p = .105) and serum hs-CRP(GDM =106 ± 65.1 Control =98.2 ± 87.3 p = .768). There was no statistically significant difference between the case and control groups for serum ANGPTL-2 and hsCRP levels. Serum ANGPTL8 levels were positively correlated with FPG (r = 0.391, p = <.001), FPI (r = 0.212, p = .045), 1-h PPG (r = 0.514, p = <.001), 2-h PPG (r = 0.502, p = <.001), HOMA-IR) score (r = 0.310, p = .003), TG (r = 0.245, p = .020); they were not except for BMI, hs-CRP levels and ANGPTL2 levels. Conclusions ANGPTL8 levels were significantly higher in GDM than in healthy control group. ANGPTL2 levels and hs-CRP levels were similar to the healthy control group. Elevated serum ANGPTL8 levels were correlated significantly with insulin resistance parameters, the main component of GDM pathophysiology. Our data showed that ANGPTL8 could be a new biomarker for diagnosing GDM.

Fetal and Placental Weight in Pre-Gestational Maternal Obesity (PGMO) vs. Excessive Gestational Weight Gain (EGWG)-A Preliminary Approach to the Perinatal Outcomes in Diet-Controlled Gestational Diabetes Mellitus.

Both pre-gestational maternal obesity (PGMO) and excessive gestational weight gain (EGWG) increase the risk of gestational diabetes mellitus (GDM). Here, we conducted a retrospective study to comparatively examine the relation between fetal birth weight (FW) and placental weight (PW) in PGMO (n = 100) compared to EGWG (n = 100) with respect to perinatal outcomes in diet-controlled GDM. The control group was made up of 100 healthy pregnancies. The mean FW and the mean PW in EGWG were correlated with lowered fetal weight/placental weight ratio (FW/PW ratio). The percentage of births completed by cesarean section accounted for 47%, 32%, and 18% of all deliveries (EGWG, PGMO, and controls, respectively), with the predominance of FW-related indications for cesarean section. Extended postpartum hospital stays due to neonate were more frequent in EGWG, especially due to neonatal jaundice (p < 0.05). The results indicate the higher perinatal risk in mothers with EGWG compared to PGMO during GDM-complicated pregnancy. Further in-depth comparative studies involving larger patient pools are needed to validate these findings, the intent of which is to formulate guidelines for GDM patients in respect to management of PGMO and EGWG.

Compromised barrier integrity of human feto-placental vessels from gestational diabetic pregnancies is related to downregulation of occludin expression

Aims/hypothesisReduced occupancy of junctional occludin is a feature of human placental vessels in the diabetic milieu. However, the functional consequence of this and whether this loss is due to differential expression of occludin splice variants is not known. Our study aimed to investigate the effects of gestational diabetes mellitus (GDM), and its treatment, on endothelial junctional integrity, gene and protein expression of occludin splice variants, and potential regulation of expression by microRNAs (miRNAs).MethodsTerm placentas were obtained from normal pregnancies (n = 21), and pregnancies complicated by GDM where glucose levels were controlled by diet (n = 11) or metformin (n = 6). Gene and microRNA (miRNA) expression were determined by quantitative real-time PCR; protein expression by immunoblotting; endothelial junctional occupancy by fluorescence microscopy and systematic sampling; and paracellular leakage by perfusion of placental microvascular beds with 76 Mr dextran. Transfection studies of miRNAs that target OCLN were performed in HUVECs, and the trans-endothelial electrical resistance and tracer permeability of the HUVECs were measured.ResultsAll three predicted OCLN gene splice variants and two occludin protein isoforms were found in human placental samples. In placental samples from diet-controlled GDM (d-GDM) pregnancies we found a lower percentage of conduit vessels showing occludin immunoreactivity (12%, p < 0.01), decreased levels of the fully functional occludin isoform-A protein (29%), and differential gene expression of OCLN variant 2 (33% decrease), variant 3 (3.3-fold increase). These changes were not seen in samples from the group with metformin-controlled GDM. In d-GDM placentas, increased numbers of conduit microvessels demonstrated extravasation of 76 Mr dextran (2.0-fold). In d-GDM expression of one of the five potential miRNAs targeting OCLN, miR-181a-5p, expression was 2.1-fold that in normal pregnancies. Experimental overexpression of miR-181a-5p in HUVECs from normal pregnancies resulted in a highly significant downregulation of OCLN variant 1 (69%) and variant 2 (46%) gene expression, with decreased trans-endothelial resistance (78%) and increase in tracer permeability (1.3-fold).Conclusions/interpretationDownregulation of expression of OCLN variant 2 and the fully functional occludin isoform-A protein are a feature of placentas in d-GDM pregnancies. These may be behind the loss of junctional occludin and the increased extravasation of exogenous dextran observed. miR-181a-5p was in part responsible for the downregulation of occludin in placentas from d-GDM pregnancies. Induced overexpression of miR-181a-5p compromised the integrity of the endothelial barrier. Our data suggest that, despite good glucose control, the adoption of lifestyle changes alone during a GDM pregnancy may not be enough to prevent an alteration in the expression of occludin and the subsequent functional consequences in placentas and impaired vascular barrier function in offspring.Graphical abstract

Management of Gestational Diabetes Mellitus.

Once a woman is diagnosed with gestational diabetes mellitus (GDM), two strategies are considered for management; life-style modifications and pharmacological therapy. The management of GDM aims to maintain a normoglycemic state and to prevent excessive weight gain in order to reduce maternal and fetal complications. Lifestyle modifications include nutritional therapy and exercise. Calorie restriction with a low glycemic index diet is recommended to avoid postprandial hyperglycemia and to reduce insulin resistance. Blood glucose levels, HbA1c levels, and ketonuria are monitored to analyze the efficacy of conservative management. Pharmacological treatment is initiated if conservative strategies fail to provide expected glucose levels during follow-ups.Insulin has been the first choice for the treatment of diabetes during pregnancy. Recently, metformin has been used more commonly in diabetic pregnant women in cases when insulin cannot be prescribed, after its safety has been proven. However, a high percentage of women, which may be up to 46% may require additional insulin to maintain expected blood glucose levels. The evidence on the long-term safety of other oral anti-diabetics has been lacking yet.Women with diet-controlled GDM can wait for spontaneous labor expectantly in case there are no obstetric indications for birth. However, in women with GDM under insulin therapy or with poor glycemic control, elective induction at term is recommended by authorities.The women who have GDM during pregnancy should be counseled about their increased risks of impaired glucose tolerance, type 2 diabetes mellitus, hypertensive disorders, cardiovascular diseases, and metabolic syndrome.

Implications of the introduction of new criteria for the diagnosis of gestational diabetes: a health outcome and cost of care analysis

ObjectiveTo identify effects on health outcomes from implementing new criteria diagnosing gestational diabetes mellitus(GDM) and to analyse costs-of-care associated with this change.DesignQuasi-experimental study comparing data from the calendar year before...

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.