Identification and validation of gestational diabetes subgroups by data-driven cluster analysis.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a heterogeneous condition. Given such variability among patients, the ability to recognise distinct GDM subgroups using routine clinical variables may guide more personalised treatments. Our main aim was to identify distinct GDM subtypes through cluster analysis using routine clinical variables, and analyse treatment needs and pregnancy outcomes across these subgroups. METHODS: In this cohort study, we analysed datasets from a total of 2682 women with GDM treated at two central European hospitals (1865 participants from Charité University Hospital in Berlin and 817 participants from the Medical University of Vienna), collected between 2015 and 2022. We evaluated various clustering models, including k-means, k-medoids and agglomerative hierarchical clustering. Internal validation techniques were used to guide best model selection, while external validation on independent test sets was used to assess model generalisability. Clinical outcomes such as specific treatment needs and maternal and fetal complications were analysed across the identified clusters. RESULTS: Our optimal model identified three clusters from routinely available variables, i.e. maternal age, pre-pregnancy BMI (BMIPG) and glucose levels at fasting and 60 and 120 min after the diagnostic OGTT (OGTT0, OGTT60 and OGTT120, respectively). Cluster 1 was characterised by the highest OGTT values and obesity prevalence. Cluster 2 displayed intermediate BMIPG and elevated OGTT0, while cluster 3 consisted mainly of participants with normal BMIPG and high values for OGTT60 and OGTT120. Treatment modalities and clinical outcomes varied among clusters. In particular, cluster 1 participants showed a much higher need for glucose-lowering medications (39.6% of participants, compared with 12.9% and 10.0% in clusters 2 and 3, respectively, p<0.0001). Cluster 1 participants were also at higher risk of delivering large-for-gestational-age infants. Differences in the type of insulin-based treatment between cluster 2 and cluster 3 were observed in the external validation cohort. CONCLUSIONS/INTERPRETATION: Our findings confirm the heterogeneity of GDM. The identification of subgroups (clusters) has the potential to help clinicians define more tailored treatment approaches for improved maternal and neonatal outcomes.

Maternal overweight and obesity and its association with metabolic changes and fetal overgrowth in the absence of gestational diabetes mellitus: A prospective cohort study.

INTRODUCTION: Previous studies indicated an association between fetal overgrowth and maternal obesity independent of gestational diabetes mellitus (GDM). However, the underlying mechanisms beyond this possible association are not completely understood. This study investigates metabolic changes and their association with fetal and neonatal biometry in overweight and obese mothers who remained normal glucose-tolerant during gestation. MATERIAL AND METHODS: In this prospective cohort study 893 women who did not develop GDM were categorized according to their pregestational body mass index (BMI): 570 were normal weight, 220 overweight and 103 obese. Study participants received a broad metabolic evaluation before 16 weeks and were followed up until delivery to assess glucose levels during the oral glucose tolerance test (OGTT) at mid-gestation as well as fetal biometry in ultrasound and pregnancy outcome data. RESULTS: Increased maternal BMI was associated with an adverse metabolic profile at the beginning of pregnancy, including a lower degree of insulin sensitivity (as assessed by the quantitative insulin sensitivity check index) in overweight (mean difference: -2.4, 95% CI -2.9 to -1.9, p < 0.001) and obese (mean difference: -4.3, 95% CI -5.0 to -3.7, p < 0.001) vs normal weight women. Despite not fulfilling diagnosis criteria for GDM, overweight and obese mothers showed higher glucose levels at fasting and during the OGTT. Finally, we observed increased measures of fetal subcutaneous tissue thickness in ultrasound as well as higher proportions of large-for-gestational-age infants in overweight (18.9%, odds ratio [OR] 1.74, 95% CI 1.08-2.78, p = 0.021) and obese mothers (21.0%, OR 1.99, 95% CI 1.06-3.59, p = 0.027) vs normal weight controls (11.8%). The risk for large for gestational age was further determined by OGTT glucose (60 min: OR 1.11, 95% CI 1.02-1.21, p = 0.013; 120 min: OR 1.13, 95% CI 1.02-1.27, P = 0.025, for the increase of 10 mg/dL) and maternal triglyceride concentrations (OR 1.11, 95% CI 1.01-1.22, p = 0.036, for the increase of 20 mg/dL). CONCLUSIONS: Mothers affected by overweight or obesity but not GDM had a higher risk for fetal overgrowth. An impaired metabolic milieu related to increased maternal BMI as well as higher glucose levels at mid-gestation may impact fetal overgrowth in women still in the range of normal glucose tolerance.

Comment: pregnancy after bariatric surgery - achievements and open questions.

Bariatric surgery confers potential advantages for obese patients, but also risks for pregnancy. Perinatal outcomes may be varying between surgical procedures. This topic was recently addressed by a systematic review in BMC Pregnancy and Childbirth. This commentary will discuss the scientific background and implications for future research.

Characteristics of gestational diabetes subtypes classified by oral glucose tolerance test values.

BACKGROUND: In clinical practice, gestational diabetes mellitus (GDM) is treated as a homogenous disease but emerging evidence suggests that the diagnosis of GDM possibly comprises different metabolic entities. In this study, we aimed to assess early pregnancy characteristics of gestational diabetes mellitus entities classified according to the presence of fasting and/or post-load hyperglycaemia in the diagnostic oral glucose tolerance test performed at mid-gestation. METHODS: In this prospective cohort study, 1087 pregnant women received a broad risk evaluation and laboratory examination at early gestation and were later classified as normal glucose tolerant (NGT), as having isolated fasting hyperglycaemia (GDM-IFH), isolated post-load hyperglycaemia (GDM-IPH) or combined hyperglycaemia (GDM-CH) according to oral glucose tolerance test results. Participants were followed up until delivery to assess data on pharmacotherapy and pregnancy outcomes. RESULTS: Women affected by elevated fasting and post-load glucose concentrations (GDM-CH) showed adverse metabolic profiles already at beginning of pregnancy including a higher degree of insulin resistance as compared to women with normal glucose tolerance and those with isolated defects (especially GDM-IPH). The GDM-IPH subgroup had lower body mass index at early gestation and required glucose-lowering medications less often (28.9%) as compared to GDM-IFH (47.8%, P = .019) and GDM-CH (54.5%, P = .005). No differences were observed in pregnancy outcome data. CONCLUSIONS: Women with fasting hyperglycaemia, especially those with combined hyperglycaemia, showed an unfavourable metabolic phenotype already at early gestation. Therefore, categorization based on abnormal oral glucose tolerance test values provides a practicable basis for clinical risk stratification.

Performance of early risk assessment tools to predict the later development of gestational diabetes.

BACKGROUND: Several prognostic models for gestational diabetes mellitus (GDM) are provided in the literature; however, their clinical significance has not been thoroughly evaluated, especially with regard to application at early gestation and in accordance with the most recent diagnostic criteria. This external validation study aimed to assess the predictive accuracy of published risk estimation models for the later development of GDM at early pregnancy. METHODS: In this cohort study, we prospectively included 1132 pregnant women. Risk evaluation was performed before 16 + 0 weeks of gestation including a routine laboratory examination. Study participants were followed-up until delivery to assess GDM status according to the IADPSG 2010 diagnostic criteria. Fifteen clinical prediction models were calculated according to the published literature. RESULTS: Gestational diabetes mellitus was diagnosed in 239 women, that is 21.1% of the study participants. Discrimination was assessed by the area under the ROC curve and ranged between 60.7% and 76.9%, corresponding to an acceptable accuracy. With some exceptions, calibration performance was poor as most models were developed based on older diagnostic criteria with lower prevalence and therefore tended to underestimate the risk of GDM. The highest variable importance scores were observed for history of GDM and routine laboratory parameters. CONCLUSIONS: Most prediction models showed acceptable accuracy in terms of discrimination but lacked in calibration, which was strongly dependent on study settings. Simple biochemical variables such as fasting glucose, HbA1c and triglycerides can improve risk prediction. One model consisting of clinical and laboratory parameters showed satisfactory accuracy and could be used for further investigations.

Commentary: Implications of SARS-Cov-2 infection for pregnancy with diabetes: achievements and open questions for feto-maternal medicine.

SARS-Cov-2 (Severe Acute Respiratory Coronavirus 2) infection confers a non-negligible risk for younger pregnant women with diabetes, which is still less well investigated. This topic was recently addressed by a systematic scoping review in BMC Pregnancy and Childbirth, aiming to summarize the complex interaction between SARS-Cov-2 infection, pregnancy and diabetes. This commentary will summarize and discuss the main findings of this article and its implications for future research.

Intrauterine Fetal Growth Delay During Late Pregnancy After Maternal Gastric Bypass Surgery.

PURPOSE: To investigate intrauterine fetal growth development and birth anthropometry of fetuses conceived after maternal gastric bypass surgery. MATERIALS AND METHODS: Longitudinal cohort study describing longitudinal growth estimated by ultrasound on 43 singleton pregnancies after gastric bypass compared to 43 BMI-matched controls. RESULTS: In fetuses after maternal gastric bypass surgery, growth percentiles decreased markedly from the beginning of the second trimester until the end of the third trimester (decrease of 3.1 fetal abdomen circumference percentiles (95 %CI 0.9-5.3, p = 0.007) per four gestational weeks). While in the second trimester, fetal anthropometric measures did not differ between the groups, the mean abdomen circumference percentiles appeared significantly smaller during the third trimester in offspring of mothers after gastric bypass (mean difference 25.1 percentiles, p < 0.001). Similar tendencies have been observed in estimated fetal weight resulting in significantly more SGA offspring at delivery in the gastric bypass group. In children born after maternal gastric bypass surgery, weight percentiles (32.12th vs. 55.86th percentile, p < 0.001) as well as placental weight (525.2 g vs. 635.7 g, p < 0.001) were significantly reduced compared to controls. CONCLUSION: In fetuses conceived after maternal gastric bypass, intrauterine fetal growth distinctively declined in the second and third trimester, most prominently observed in fetal abdomen circumferences. Birth weight and placental weight at birth was significantly lower compared to BMI-matched controls, possibly due to altered maternal metabolic factors and comparable to mothers experiencing chronic hunger episodes.

Pregnancy after bariatric surgery: a narrative literature review and discussion of impact on pregnancy management and outcome.

Bariatric surgery (BS) is regarded to be the most effective treatment of obesity with long lasting beneficial effects including weight loss and improvement of metabolic disorders. A considerable number of women undergoing BS are at childbearing age.Although the surgery mediated weight loss has a positive effect on pregnancy outcome, the procedures might be associated with adverse outcomes as well, for example micronutrient deficiencies, iron or B12 deficiency anemia, dumping syndrome, surgical complications such as internal hernias, and small for gestational age (SGA) offspring, possibly due to maternal undernutrition. Also, there is no international consensus concerning the ideal time to conception after BS. Hence, the present narrative review intents to summarize the available literature concerning the most common challenges which arise before and during pregnancy after BS, such as fertility related considerations, vitamin and nutritional deficiencies and their adequate compensation through supplementation, altered glucose metabolism and its implications for gestational diabetes screening, the symptoms and treatment of dumping syndrome, surgical complications and the impact of BS on pregnancy outcome. The impact of different bariatric procedures on pregnancy and fetal outcome will also be discussed, as well as general considerations concerning the monitoring and management of pregnancies after BS.Whereas BS leads to the mitigation of many obesity-related pregnancy complications, such as gestational diabetes mellitus (GDM), pregnancy induced hypertension and fetal macrosomia; those procedures pose new risks which might lead to adverse outcomes for mothers and offspring, for example nutritional deficiencies, anemia, altered maternal glucose metabolism and small for gestational age children.

Assessment of glucose regulation in pregnancy after gastric bypass surgery.

AIMS/HYPOTHESIS: Roux-en-Y gastric bypass (RYGB) surgery is characterised by glycaemic variability. Prospective studies of glucose metabolism in pregnancy after RYGB are not available, therefore this study aimed to evaluate physiological alterations in glucose metabolism in pregnancy following RYGB. METHODS: Sixty-three pregnant women (25 who underwent RYGB, 19 non-operated obese control women and 19 normal weight control women) were included. Frequently sampled 3 h OGTTs and 1 h IVGTTs were performed between 24 and 28 weeks of gestation and, in a subgroup, were repeated at 3-6 months after delivery. RESULTS: We observed major alterations in glucose kinetics during the OGTT, including an early increase in plasma glucose followed by hypoglycaemia in 90% of women who had previously undergone RYGB. The higher degree of glycaemic variability in this group was accompanied by increased insulin, C-peptide and glucagon concentrations after oral glucose load, whereas no differences in insulin response were observed after parenteral glucose administration (RYGB vs normal weight). IVGTT data suggested improved insulin sensitivity (mean difference 0.226 × 10-4 min-1 [pmol/l]-1 [95% CI 0.104, 0.348]; p < 0.001) and disposition index in pregnancies after RYGB when compared with obese control women. However, subtle alterations in insulin action and beta cell function were still observed when comparing women who had undergone RYGB with the normal-weight control group. Moreover, we observed that fetal growth was associated with maternal glucose nadir levels and insulin secretion in offspring of those who had previously undergone RYGB. CONCLUSIONS/INTERPRETATION: Pregnancies after RYGB are affected by altered postprandial glucose, insulin and C-peptide dynamics. Insulin sensitivity is improved by RYGB, although subtle alterations in beta cell function are observed. Longitudinal studies are needed to assess potential consequences for fetal development and pregnancy outcomes.

Altered glucose profiles and risk for hypoglycaemia during oral glucose tolerance testing in pregnancies after gastric bypass surgery.

AIMS/HYPOTHESIS: A history of gastric bypass surgery can influence the results of the OGTT recommended during pregnancy. Therefore, we compared OGTT glucose kinetics and pregnancy outcome between pregnant gastric bypass patients and BMI-matched, lean and obese controls. METHODS: Medical records were used to collect data on glucose measurements during the 2 h 75 g OGTT as well as on pregnancy and fetal outcome for 304 women (n = 76 per group, matched for age and date of delivery). RESULTS: Women after bariatric surgery had lower fasting glucose levels compared with lean, obese and BMI-matched controls, and showed altered postprandial glucose kinetics, including a rise at 60 min followed by hypoglycaemia with serum glucose of <3.34 mmol/l (which occurred in 54.8%). Moreover, their risk of pre-eclampsia or gestational hypertension was reduced, with an increased risk of delivering small for gestational age infants. CONCLUSIONS/INTERPRETATION: Alternative strategies to accurately define impaired glucose metabolism in pregnancies after bariatric surgery should be explored.

To explain the variation of OGTT dynamics by biological mechanisms: a novel approach based on principal components analysis in women with history of GDM.

Early reexamination of carbohydrate metabolism via an oral glucose tolerance test (OGTT) is recommended after pregnancy with gestational diabetes (GDM). In this report, we aimed to assess the dominant patterns of dynamic OGTT measurements and subsequently explain them by meanings of the underlying pathophysiological processes. Principal components analysis (PCA), a statistical procedure that aims to reduce the dimensionality of multiple interrelated measures to a set of linearly uncorrelated variables (the principal components) was performed on OGTT data of glucose, insulin and C-peptide in addition to age and body mass index (BMI) of 151 women (n = 110 females after GDM and n = 41 controls) at 3-6 mo after delivery. These components were explained by frequently sampled intravenous glucose tolerance test (FSIGT) parameters. Moreover, their relation with the later development of overt diabetes was studied. Three principal components (PC) were identified, which explained 71.5% of the variation of the original 17 variables. PC1 (explained 47.1%) was closely related to postprandial OGTT levels and FSIGT-derived insulin sensitivity (r = 0.68), indicating that it mirrors insulin sensitivity in the skeletal muscle. PC2 (explained 17.3%) and PC3 (explained 7.1%) were shown to be associated with ß-cell failure and fasting (i.e., hepatic) insulin resistance, respectively. All three components were related with diabetes progression (occurred in n = 25 females after GDM) and showed significant changes in long-term trajectories. A high amount of the postpartum OGTT data is explained by principal components, representing pathophysiological mechanisms on the pathway of impaired carbohydrate metabolism. Our results improve our understanding of the underlying biological processes to provide an accurate postgestational risk stratification.

Biomarkers of endothelial dysfunction in relation to impaired carbohydrate metabolism following pregnancy with gestational diabetes mellitus.

BACKGROUND: History of gestational diabetes mellitus (GDM) identifies a very young population of females predisposed for type 2 diabetes and cardiovascular disease. Endothelial dysfunction might represent a shared precursor of both disorders. Hence, this study aimed to characterize endothelial biomarkers in relation to impaired insulin sensitivity and progression to overt diabetes early after index pregnancy. METHODS: 108 women with previous GDM and 40 controls were included three to six months after delivery and underwent specific metabolic assessments including a frequently sampled intravenous glucose tolerance test and an oral glucose tolerance test. Diabetes progression was assessed in females with pGDM over 10 years of follow-up. Circulating sICAM-1 (intracellular-adhesion-molecule-1), sVCAM-1 (vascular-cell-adhesion-molecule-1) and sE-selectin, representing biomarkers of endothelial dysfunction were assessed at baseline and annually over five years. RESULTS: Endothelial biomarkers were significantly associated with insulin sensitivity (sICAM-1: r = -0.23, p = 0.009; sVCAM-1: r = -0.22, p = 0.011; sE-selectin: r = -0.21, p = 0.018) as well as with GDM status and parameters of subtle inflammation. Analysis of long-term trajectories revealed constantly elevated sICAM-1 (p = 0.033) and sE-selectin (p = 0.007) in 25 subjects with diabetes progression. Accordingly, sE-selectin levels at the early post partum visit predicted a later development of the disease (HR =1.02 95%CI 1.01 to 1.04, p = 0.013), however, this was attenuated after adjustment for BMI. CONCLUSIONS: Elevated circulating markers of endothelial dysfunction in young females with GDM history might reflect an early stage on the pathway to the manifestation of future cardiometabolic disorders. Timely identification of women at high risk and optimization of follow-up management might provide an opportunity to prevent disease progression.

Glucometabolic Alterations in Pregnant Women with Overweight or Obesity but without Gestational Diabetes Mellitus: An Observational Study.

INTRODUCTION: Maternal overweight is a risk factor for gestational diabetes mellitus (GDM). However, emerging evidence suggests that an increased maternal body mass index (BMI) promotes the development of perinatal complications even in women who do not develop GDM. This study aims to assess physiological glucometabolic changes associated with increased BMI. METHODS: Twenty-one women with overweight and 21 normal weight controls received a metabolic assessment at 13 weeks of gestation, including a 60-min frequently sampled intravenous glucose tolerance test. A further investigation was performed between 24 and 28 weeks in women who remained normal glucose tolerant. RESULTS: At baseline, mothers with overweight showed impaired insulin action, whereby the calculated insulin sensitivity index (CSI) was lower as compared to normal weight controls (3.5 vs. 6.7 10-4 min-1 [microU/mL]-1, p = 0.025). After excluding women who developed GDM, mothers with overweight showed higher average glucose during the oral glucose tolerance test (OGTT) at the third trimester. Moreover, early pregnancy insulin resistance and secretion were associated with increased placental weight in normal glucose-tolerant women. CONCLUSION: Mothers with overweight or obesity show an unfavorable metabolic environment already at the early stage of pregnancy, possibly associated with perinatal complications in women who remain normal glucose tolerant.

Estimating the risk after gestational diabetes mellitus: can we improve the information from the postpartum OGTT?

Risk stratification after pregnancy with gestational diabetes mellitus (GDM) is based on screening with the 2-h oral glucose tolerance test (OGTT). Actually, prediabetes and diabetes are diagnosed by impaired fasting [fasting plasma glucose (FPG)] and 120 min-postload glucose levels (120'-PLG). We hypothesized that the clinical information could be improved by including measurements at different time points from the OGTT in the medical decision-making process. One hundred ten women with previous gestational diabetes (pGDM) and 41 controls were included 3-6 mo after delivery and underwent specific metabolic assessments: 3-h OGTT, frequently sampled intravenous glucose tolerance test (FSIGT) with markers of inflammation and endothelial function. pGDMs were annually invited for reexaminations for a maximum of 10 yr. Multiple linear regression suggested that postload glucose levels at 60 min (60'-PLG) were a better predictor for insulin sensitivity [ß: -0.10, 95% confidence interval (CI) -0.14 to -0.05, P < 0.001] and disposition index (DI) (ß: -0.07, 95% CI -0.12 to -0.02, P = 0.004) estimated from the FSIGT compared with other time points during the OGTT. The association between 60'-PLG and insulin secretion was of particular importance in women after GDM. We further identified associations of 60'-PLG with ultrasensitive C-reactive protein, plasminogen activator inhibitor 1, tissue plasminogen activator, endothelial-leukocyte adhesion molecule 1, and intercellular adhesion molecule (ICAM)-1. There appeared to be no interactions between females with pGDM and controls, suggesting comparable effects. We observed that 60'-PLG levels were closely related to the later onset of diabetes independent from the routinely measured FPG and 120'-PLG levels. Our data suggest that the sole interpretation of FPG and 120'-PLG of the OGTT leads to significant loss of information. Particularly 60'-PLG was shown to distinguish women at low or high metabolic and cardiovascular risk.

Prevalence of gestational diabetes mellitus in women with a family history of type 2 diabetes in first- and second-degree relatives.

AIMS: A family history of type 2 diabetes mellitus (T2DM) markedly increases an individual's lifetime risk of developing the disease. For gestational diabetes (GDM), this risk factor is less well characterized. This study aimed to investigate the relationship between family history of T2DM in first- and second-degree relatives in women with GDM and the differences in metabolic characteristics at early gestation. METHODS: This prospective cohort study included 1129 pregnant women. A broad risk evaluation was performed before 16 + 0 weeks of gestation, including a detailed family history of the different types of diabetes and a laboratory examination of glucometabolic parameters. Participants were followed up until delivery and GDM assessed according to the latest diagnosis criteria. RESULTS: We showed that pregnant women with first- (FHD1, 26.6%, OR 1.91, 95%CI 1.16 to 3.16, p = 0.005), second- (FHD2, 26.3%, OR 1.88, 95%CI 1.16 to 3.05, p = 0.005) or both first- and second-degree relatives with T2DM (FHD1 + D2, 33.3%, OR 2.64, 95%CI 1.41 to 4.94, p < 0.001) had a markedly increased risk of GDM compared to those with negative family history (FHN) (n = 100, 15.9%). The association was strongest if both parents were affected (OR 4.69, 95%CI 1.33 to 16.55, p = 0.009). Women with FHD1 and FHD1 + D2 had adverse glucometabolic profiles already in early pregnancy. CONCLUSIONS: Family history of T2DM is an important risk factor for GDM, also by applying the current diagnostic criteria. Furthermore, we showed that the degree of kinship plays an essential role in quantifying the risk already at early pregnancy.

The impact of regional origin on the incidence of gestational diabetes mellitus in a multiethnic European cohort.

Introduction: Women with migration background present specific challenges related to risk stratification and care of gestational diabetes mellitus (GDM). Therefore, this study aims to investigate the role of ethnic origin on the risk of developing GDM in a multiethnic European cohort. Methods: Pregnant women were included at a median gestational age of 12.9 weeks and assigned to the geographical regions of origin: Caucasian Europe (n = 731), Middle East and North Africa countries (MENA, n = 195), Asia (n = 127) and Sub-Saharan Africa (SSA, n = 48). At the time of recruitment maternal characteristics, glucometabolic parameters and dietary habits were assessed. An oral glucose tolerance test was performed in mid-gestation for GDM diagnosis. Results: Mothers with Caucasian ancestry were older and had higher blood pressure and an adverse lipoprotein profile as compared to non-Caucasian mothers, whereas non-Caucasian women (especially those from MENA countries) had a higher BMI and were more insulin resistant. Moreover, we found distinct dietary habits. Non-Caucasian mothers, especially those from MENA and Asian countries, had increased incidence of GDM as compared to the Caucasian population (OR 1.87, 95%CI 1.40 to 2.52, p < 0.001). Early gestational fasting glucose and insulin sensitivity were consistent risk factors across different ethnic populations, however, pregestational BMI was of particular importance in Asian mothers. Discussion: Prevalence of GDM was higher among women from MENA and Asian countries, who already showed adverse glucometabolic profiles at early gestation. Fasting glucose and early gestational insulin resistance (as well as higher BMI in women from Asia) were identified as important risk factors in Caucasian and non-Caucasian patients.

Sensitivity, specificity, and diagnostic accuracy of WHO 2013 criteria for diagnosis of gestational diabetes mellitus in low risk early pregnancies: international, prospective, multicentre cohort study.

Objective: To evaluate the predictability of gestational diabetes mellitus wth a 75 g oral glucose tolerance test (OGTT) in early pregnancy, based on the 2013 criteria of the World Health Organization, and to test newly proposed cut-off values. Design: International, prospective, multicentre cohort study. Setting: Six university or cantonal departments in Austria, Germany, and Switzerland, from 1 May 2016 to 31 January 2019. Participants: Low risk cohort of 829 participants aged 18-45 years with singleton pregnancies attending first trimester screening and consenting to have an early 75 g OGTT at 12-15 weeks of gestation. Participants and healthcare providers were blinded to the results. Main outcome measures: Fasting, one hour, and two hour plasma glucose concentrations after an early 75 g OGTT (12-15 weeks of gestation) and a late 75 g OGTT (24-28 weeks of gestation). Results: Of 636 participants, 74 (12%) developed gestational diabetes mellitus, according to World Health Organization 2013 criteria, at 24-28 weeks of gestation. Applying WHO 2013 criteria to the early OGTT with at least one abnormal value gave a low sensitivity of 0.35 (95% confidence interval 0.24 to 0.47), high specificity of 0.96 (0.95 to 0.98), positive predictive value of 0.57 (0.41 to 0.71), negative predictive value of 0.92 (0.89 to 0.94), positive likelihood ratio of 10.46 (6.21 to 17.63), negative likelihood ratio of 0.65 (0.55 to 0.78), and diagnostic odds ratio of 15.98 (8.38 to 30.47). Lowering the postload glucose values (75 g OGTT cut-off values of 5.1, 8.9, and 7.8 mmol/L) improved the detection rate (53%, 95% confidence interval 41% to 64%) and negative predictive value (0.94, 0.91 to 0.95), but decreased the specificity (0.91, 0.88 to 0.93) and positive predictive value (0.42, 0.32 to 0.53) at a false positive rate of 9% (positive likelihood ratio 5.59, 4.0 to 7.81; negative likelihood ratio 0.64, 0.52 to 0.77; and diagnostic odds ratio 10.07, 6.26 to 18.31). Conclusions: The results of this prospective low risk cohort study indicated that the 75 g OGTT as a screening tool in early pregnancy is not sensitive enough when applying WHO 2013 criteria. Postload glucose values were higher in early pregnancy complicated by diabetes in pregnancy. Lowering the postload cut-off values identified a high risk group for later development of gestational diabetes mellitus or those who might benefit from earlier treatment. Results from randomised controlled trials showing a beneficial effect of early intervention are unclear. Trial registration: ClinicalTrials.gov NCT02035059.

Impact Of Prepregnancy Overweight And Obesity On Treatment Modality And Pregnancy Outcome In Women With Gestational Diabetes Mellitus.

Background: We aim to evaluate the impact of prepregnancy overweight on treatment modalities of Gestational Diabetes Mellitus (GDM). We assessed the association of increased pregravid Body Mass Index (BMI) with dosing of basal and rapid acting insulin as well as pregnancy outcome. Methods: We included 509 gestational diabetic women (normal weight: 200, overweight: 157, obese: 152), attending the pregnancy outpatient clinic at the Department of Obstetrics and Gynecology, Medical University of Vienna, in this retrospective study. We used a prospectively compiled database to assess patient characteristics, treatment approaches - particularly maximum doses of basal and rapid acting insulin or metformin - and pregnancy outcome. Results: Increased BMI was associated with the need of glucose lowering medication (odds ratio (OR): 1.08 for the increase of 1 kg/m² BMI, 95%CI 1.05-1.11, p<0.001). Mothers with pregestational obesity received the highest amount of insulin. Metformin was more often used in patients with obesity who also required higher daily doses. Maternal BMI was associated with increased risk of cesarean section (OR 1.04, 95%CI 1.01-1.07, p<0.001) and delivering large for gestational age offspring (OR 1.09, 95%CI 1.04-1.13, p<0.001). Birthweight percentiles were highest in patients with obesity who required glucose lowering therapy. Conclusions: Treatment modalities and outcome in GDM pregnancies are closely related to the extent of maternal BMI. Patients with obesity required glucose lowering medication more often and were at higher risk of adverse pregnancy outcomes. It is crucial to further explore the underlying pathophysiologic mechanisms to optimize clinical management and individual treatment approaches.

Fetal Growth and Adipose Fat Tissue Trajectories in Twin Pregnancies after Gastric Bypass Surgery.

INTRODUCTION: Previous studies demonstrated a continuous decline in fetal growth throughout singleton pregnancy after bariatric surgery. However, intrauterine growth in twin pregnancy is subjected to further underlying processes. This study was to investigate the longitudinal assessment of fetal biometry and abdominal fat thickness of twin pregnancies conceived after gastric bypass (GB) surgery and compare them to body mass index-matched (BMIM) and obese (OB) controls. MATERIALS AND METHODS: We retrospectively assessed ultrasound data of 30 women with dichorionic-diamniotic twin pregnancy (11 women after GB surgery, 9 OB mothers with pregestational BMI ≥30 kg/m2, and 10 BMIM and age-matched controls). We assessed fetal growth parameters including fetal subcutaneous adipose tissue thickness (FSCTT) as well as newborn biometry after delivery. Patient characteristics were obtained from the medical records. RESULTS: The rise in FSCTT curves was markedly slower in the twin offspring of women with history of GB as compared to the offspring of OB mothers and offspring of BMIM controls. Hence, FSCTT was significantly decreased in the GB offspring as compared to both control groups at 34 weeks of gestation. Also, growth curves of abdominal circumference were decreased in the offspring of GB patients as compared to OB mothers. Infants of mothers with history of GB showed significantly lower birth weight percentiles compared to newborns of OB mothers (27.2 vs. 48.8 pct, p = 0.025). There was no significant difference in inter-twin birth weight difference between the offspring of GB (median: 9.9%, interquartile ranges [IQR]: 6.5-20.0) versus OB (median: 14.6%, IQR: 8.2-21.6) and BMIM controls (median: 9.0%, IQR: 6.3-12.6, p = 0.714). CONCLUSIONS: In summary, intrauterine growth delay in twin pregnancies after GB is assumed to be a multifactorial event with altered metabolism as the most important factor. However, special attention must be paid to the particularity of twin pregnancies as they seem to be subject to other additional mechanism.

Assessment of glucose levels in pregnant women with history of COVID-19 in a case-control study.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection may negatively affect glucose metabolism. This study aims to assess glucose levels, prevalence of gestational diabetes mellitus (GDM) and perinatal outcome in women with history of COVID-19. To this purpose, a group of 65 patients with history of COVID-19 and 94 control patients were retrospectively recruited among pregnant women who attended the pregnancy outpatient department between 01/2020 and 02/2022. Glucose data from an oral glucose tolerance test (OGTT), GDM status and obstetric complications were assessed. We observed no differences in average (p = 0.37), fasting (p = 0.62) or post-load glucose concentrations (60 min: p = 0.19; 120 min: p = 0.95) during OGTT. A total of 15 (23.1%) women in the COVID-19 group and 18 (19.1%) women in the control group developed GDM (p = 0.55). Moreover, caesarean section rate, weight percentiles and pregnancy outcomes were comparable between the groups (p = 0.49). In conclusion, in this study we did not identify a possible impact of COVID-19 on glucose metabolism in pregnancy, especially with regard to glucose concentrations during the OGTT and prevalence of GDM.