Expanding the Role of Continuous Glucose Monitoring in Modern Diabetes Care Beyond Type 1 Disease.

Application of continuous glucose monitoring (CGM) has moved diabetes care from a reactive to a proactive process, in which a person with diabetes can prevent episodes of hypoglycemia or hyperglycemia, rather than taking action only once low and high glucose are detected. Consequently, CGM devices are now seen as the standard of care for people with type 1 diabetes mellitus (T1DM). Evidence now supports the use of CGM in people with type 2 diabetes mellitus (T2DM) on any treatment regimen, not just for those on insulin therapy. Expanding the application of CGM to include all people with T1DM or T2DM can support effective intensification of therapies to reduce glucose exposure and lower the risk of complications and hospital admissions, which are associated with high healthcare costs. All of this can be achieved while minimizing the risk of hypoglycemia and improving quality of life for people with diabetes. Wider application of CGM can also bring considerable benefits for women with diabetes during pregnancy and their children, as well as providing support for acute care of hospital inpatients who experience the adverse effects of hyperglycemia following admission and surgical procedures, as a consequence of treatment-related insulin resistance or reduced insulin secretion. By tailoring the application of CGM for daily or intermittent use, depending on the patient profile and their needs, one can ensure the cost-effectiveness of CGM in each setting. In this article we discuss the evidence-based benefits of expanding the use of CGM technology to include all people with diabetes, along with a diverse population of people with non-diabetic glycemic dysregulation.

Flash glucose monitoring in gestational diabetes mellitus (FLAMINGO): a randomised controlled trial.

AIMS: Gestational diabetes mellitus (GDM) is the most common type of hyperglycaemia in pregnancy. GDM is a risk factor of adverse perinatal outcomes, with the incidence rate increasing proportionally to the level of maternal dysglycaemia. Therefore, glycaemic control plays an important role in management of GDM. The aim of this study was to assess the efficacy of flash glucose monitoring (FGM) in GDM. MATERIALS AND METHODS: This was a non-blinded, randomised controlled trial, that recruited 100 pregnant women diagnosed with GDM between 24 and 28 weeks of gestation at the 1st Department of Obstetrics and Gynaecology, Medical University of Warsaw. After meeting the inclusion criteria patients were randomly allocated to the study group (FGM, n = 50) or control group (self-monitoring of blood glucose-SMBG, n = 50). Clinical and laboratory results were assessed at four follow-up visits. The primary outcome was mean fasting and postprandial glycaemia. The secondary outcomes were perinatal outcomes. RESULTS: There was no significant difference in mean glycaemia between the groups (p = 0.437) Compared to the control group, the study group significantly reduced their fasting (p = 0.027) and postprandial glycaemia (p = 0.034) during the first 4 weeks following GDM diagnosis, with no significant difference in progression to insulin therapy (OR 1.09, 95% CI 0.47-2.57). Incidence of fetal macrosomia was significantly higher in SMBG as compared to FGM group (OR 5.63, 95% CI 1.16-27.22). CONCLUSIONS: Study results indicate that FGM has an impact on glycaemic control, dietary habits and incidence of fetal macrosomia in patients with GDM. Trial registration clinicaltrials.gov ID: NCT04422821.

Maturity-onset Diabetes of the Young (MODY) in Pregnancy: A Review.

Hyperglycaemia in pregnancy is one of the most common complications of pregnancy and is generally diagnosed as gestational diabetes mellitus (GDM). Nevertheless, clinical symptoms of hyperglycaemia in pregnancy in some cases do not match the clinical manifestations of GDM. It is suspected that 1-2 % of women diagnosed with GDM are misdiagnosed maturity-onset diabetes of the young (MODY). MODY often has a subclinical course; thus, it is challenging for clinicians to aptly diagnose monogenic diabetes in pregnancy. Proper diagnosis is crucial for the effective treatment of hyperglycaemia in pregnancy. Many studies revealed that misdiagnosis of MODY increases the rate of complications for both mother and fetus. This literature review reports the current knowledge regarding diagnosis, treatment, and complications of the most common types of MODY in pregnancy.

Enlarged Abdominal Lymph Node as a Cause of Polyhydramnios in the Course of Congenital Neonatal Leukaemia: A Case Report and Review of the Literature on Foetal Abdominal Tumours with Coexisting Polyhydramnios.

Polyhydramnios represents a complication found in 0.2-2% of pregnancies, and it is usually diagnosed between 31 and 36 weeks of pregnancy. Although most cases of polyhydramnios are idiopathic, maternal diabetes or foetal malformations constitute frequent causes of the excessive accumulation of the amniotic fluid. Considering the latter, polyhydramnios may rarely be caused by foetal abdominal tumours, with the incidence rate of 2-14 cases per 100,000 live births. Congenital neonatal leukaemia (CNL) is a rare disease with a reported incidence rate of 5-8.6 cases per million live births. In the prenatal period, the ultrasound abnormalities associated with CNL include hepatomegaly and splenomegaly. In this paper, we presented a case of polyhydramnios caused by mechanical pressure on the foetal gastrointestinal tract by an enlarged lymph node in the course of CNL, as well as reviewing the available literature on foetal abdominal tumours with concurrent polyhydramnios.

Is There an Association between the Use of Epidural Analgesia during Labor and the Development of Autism Spectrum Disorder in the Offspring?-A Review of the Literature.

Autism spectrum disorders (ASDs) are multifactorial and complex neurodevelopmental conditions usually diagnosed in the early childhood. The etiology of ASDs is commonly described as a genetic predisposition combined with an environmental impact. As a result of broadening of the diagnostic criteria the prevalence of ASDs has been increasing worldwide and the search for the modifiable factors is still on-going. Epidural analgesia (ELA) provides effective pain relief during labor and is currently the most preferred method of anesthesia during the delivery. The safety of the procedure is well-discussed and documented; nonetheless, in 2020 a single population-based study indicated an association between the use of ELA during labor and newborn risk of ASD development, which led to widespread concern. To explore the possible association between the ELA and ASD occurrence in the offspring several studies in different countries have been conducted to date. In this review we aimed to summarize the current state of knowledge concerning the association between the use of epidural analgesia during labor and risk of ASD. In conclusion, the literature review indicates that there is no significant association.

Efficacy of Continuous Glucose Monitoring on Glycaemic Control in Pregnant Women with Gestational Diabetes Mellitus-A Systematic Review.

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, affecting up to 14% of pregnant women. The population of patients with risk factors of GDM is increasing; thus, it is essential to improve management of this condition. One of the key factors affecting perinatal outcomes in GDM is glycaemic control. Until recently, glucose monitoring was only available with self-monitoring of blood glucose (SMBG). However, nowadays, there is a new method, continuous glucose monitoring (CGM), which has been shown to be safe in pregnancy. Since proper glycaemia assessment has been shown to affect perinatal outcomes, we decided to perform a systematic review to analyse the role of CGM in glycaemic control in GDM. We conducted a web search of the MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science databases according to the PRISMA guidelines. The web search was performed by two independent researchers and resulted in 14 articles included in the systematic review. The study protocol was registered in the PROSPERO database with registration number CRD42021289883. The main outcome of the systematic review was determining that, when compared, CGM played an important role in better glycaemic control than SMBG. Furthermore, glycaemic control with CGM improved qualification for insulin therapy. However, most of the articles did not reveal CGM's role in improving neonatal outcomes. Therefore, more studies are needed to analyse the role of CGM in affecting perinatal outcomes in GDM.

Ambulatory Glucose Profile (AGP) Report in Daily Care of Patients with Diabetes: Practical Tips and Recommendations.

The ambulatory glucose profile (AGP) is now established as the standardised, practical one-page report for graphically presenting a summary of glycaemic control status in patients with diabetes who use continuous glucose monitoring (CGM) systems as part of their daily diabetes care. The AGP report provides both a visual and a statistical summary of the glucose metrics that, as agreed in the 2019 international consensus for assessing glycaemic control, should be analysed in all people with diabetes who are using CGM systems. The AGP report can be analysed in a systematic fashion to understand current glycaemic control and to monitor, in real time, the impact of adjustments to therapy in both type 1 diabetes and type 2 diabetes. Here we provide a practical guide to the glycaemic measures that are summarised in the AGP Report and illustrate the essential components of an AGP review in a series of hypothetical, real-world, patient-centred case studies (see Supplementary Materials).

Hyperglycemia in pregnancy - prevalence and perinatal outcomes. A retrospective multicenter cohort study in Poland.

OBJECTIVES: Hyperglycemia in pregnancy (HIP) is one of the most common complications of pregnancy. Recently adopted new criteria for the diagnosis of HIP as well as the greater prevalence of risk factors could have a significant impact on HIP prevalence. The objective of the study was to assess the rates of HIP and the associated complications. MATERIAL AND METHODS: This was a retrospective analysis of clinical records from pregnant women who delivered in eight tertiary hospitals in Poland in 2016. RESULTS: The number of pregnant women with hyperglycemia totaled 1280 (7.25%), including gestational diabetes mellitus (GDM) in 1169 (6.62%) women and pregestational diabetes mellitus (PGDM) in 111 (0.63%). In addition to dietary modifications, 477 (41% of the GDM group) women received medical treatment (GDMG2). In women with PGDM multiple daily insulin injections (MDI) were used in 53 (47.7%) cases, continuous subcutaneous insulin infusions (CSII) in 57 (51.3%) cases and one woman was treated with metformin. The rate of cesarean sections was 69.4% and 62.9% for PGDM and GDM, respectively. Large-for-gestational-age (LGA) infants accounted for 38% and 21% of births in the PGDM and GDM groups, respectively. Of note are high rates of hyperbilirubinemia in infants born to mothers treated with insulin (13.5% for PGDM and 14.4% for GDMG2) vs infants born to mothers with diet (GDMG1) (3.4%). CONCLUSIONS: In Poland, the prevalence of HIP has nearly doubled in the past twenty years. Even with appropriate management, HIP is a significant risk factor for a cesarean section delivery, bearing an LGA infant and adverse neonatal outcomes.

Twin-to-twin transfusion syndrome complicated with in utero limb ischemia of the donor twin - a case report.

BACKGROUND: In utero limb ischemia is a rare complication of the monochorionic twin pregnancies complicated with twin to twin transfusion syndrome (TTTS). The condition is more often seen in recipient twins. There are few theories of the pathogenesis including in utero venous thromboembolism, but the cause remains unclear. However, limb ischemia is thought to be unrelated with any prenatal intervention. CASE PRESENTATION: We present a case of a monochorionic twin pregnancy complicated with TTTS admitted to the Clinic for selective fetoscopic laser photocoagulation. The invasive procedure failed due to poor visibility. In the following weeks of pregnancy, amnioreduction procedures were performed. At 28 weeks of gestation due to twin anemia-polycythemia sequence diagnosis the patient was qualified for cesarean section. Postnatally, the donor twin was diagnosed with lower right limb ischemic necrosis. The extremity was amputated 2 days later with an uncomplicated recovery. After speculations of the potential pathogeneses it was suggested that the ischemic limb occurred as a complication of the main condition - TTTS. CONCLUSIONS: In literature, there have been no cases reported of TTTS stage I complicated with donor twin limb ischemia. The actual cause of the in utero limb ischemic necrosis in monochorionic twins remains unknown. Nevertheless, increased attention to the potential complication after failed invasive procedures or conservative treatment should be required.

Placental expression of glucose transporters GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in pregnancies complicated by gestational and type 1 diabetes mellitus.

AIMS/INTRODUCTION: The aim of the present study was to evaluate the placental expression of glucose transporters GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in term pregnancies complicated by well-controlled gestational (GDM) and type 1 pregestational diabetes mellitus (PGDM). MATERIALS AND METHODS: A total of 103 placental samples were obtained from patients diagnosed with GDM (n = 60), PGDM (n = 20) and a non-diabetic control group (n = 23). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected GLUT proteins. RESULTS: Immunohistochemical techniques used for the identification of GLUT-1, GLUT-3, GLUT-8 and GLUT-12 revealed the presence of all glucose transporters in the placental tissue. Morphometric evaluation performed for the vascular density-matched placental samples demonstrated a significant increase in the expression of GLUT-1 protein in patients with PGDM as compared to GDM and control groups (P < 0.05). With regard to the expression of the other GLUT isoforms, no statistically significant differences were observed between patients from the diabetic and control populations. Positive correlations between fetal birthweight and the expression of GLUT-1 protein in the PGDM group (rho = 0.463, P < 0.05) and GLUT-12 in the control group (rho = 0.481, P < 0.05) were noted. CONCLUSIONS: In term pregnancies complicated by well-controlled GDM/PGDM, expression of transporters GLUT-3, GLUT-8 and GLUT-12 in the placenta remains unaffected. Increased expression of GLUT-1 among women with type 1 PGDM might contribute to a higher rate of macrosomic fetuses in this population.

Placenta praevia - does it really affect intrauterine fetal growth?

PURPOSE: Placenta praevia affects about 0.5% of pregnancies and due to constant increase in operative deliveries may become an important, clinical challenge throughout the next decades. Location of the placental plate within lower uterine segment is associated with increased risk of adverse perinatal outcomes. There were several reports pointing increased risk of small-for-gestational-age (SGA)/fetal growth restriction (FGR) in patients affected with abnormal location of the placenta. On the other hand, some studies ended up with opposite conclusions. MATERIALS AND METHODS: Due to ambiguous results we have undertaken a case-control study to investigate intrauterine growth among this group. We ran a pilot study to precisely define maternal, obstetrical and neonatal characteristics in order to avoid cofounders. Our study incorporated 56 patients in singleton pregnancies affected with placenta praevia and 124 patients in the control group (between 35 and 37 weeks of gestation). RESULTS: Nonetheless, there were no statistical differences in the birthweight between the study and control group (2882.5 g vs. 2805 g, p = ns). Moreover, rates of the newborns with birthweight corresponding <10th percentile and >90th did not differ significantly. Even further analysis that included parity did not reveal any differences between both groups. CONCLUSION: Placenta praevia does not affect the intrauterine growth and shall not be considered as a risk factor for SGA/FGR. In patients affected with abnormal location of the placenta additional scans for fetal well-being assessment are not indicated.

Differential Expression of Glucose Transporter Proteins GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in the Placenta of Macrosomic, Small-for-Gestational-Age and Growth-Restricted Foetuses.

Placental transfer of glucose constitutes one of the major determinants of the intrauterine foetal growth. The objective of the present study was to evaluate the expression of glucose transporter proteins GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in the placenta of macrosomic, small-for-gestational-age (SGA) and growth-restricted foetuses (FGR). A total of 70 placental tissue samples were collected from women who delivered macrosomic ≥4000 g (n = 26), SGA (n = 11), growth-restricted (n = 13) and healthy control neonates (n = 20). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected GLUT proteins. Immunohistochemical staining identified the presence of all glucose transporters in the placental tissue. Quantitative morphometric analysis performed for the vascular density-matched placental samples revealed a significant decrease in GLUT-1 and increase in GLUT-3 protein expression in pregnancies complicated by FGR as compared to other groups (p < 0.05). In addition, expression of GLUT-8 was significantly decreased among SGA foetuses (p < 0.05). No significant differences in GLUTs expression were observed in women delivering macrosomic neonates. In the SGA group foetal birth weight (FBW) was negatively correlated with GLUT-3 (rho = -0.59, p < 0.05) and positively with GLUT-12 (rho = 0.616, p < 0.05) placental expression. In addition, a positive correlation between FBW and GLUT-12 expression in the control group (rho = 0.536, p < 0.05) was noted. In placentas derived from FGR-complicated pregnancies the expression of two major glucose transporters GLUT-1 and GLUT-3 is altered. On the contrary, idiopathic foetal macrosomia is not associated with changes in the placental expression of GLUT-1, GLUT-3, GLUT-8 and GLUT-12 proteins.

Flash glucose monitoring in gestational diabetes mellitus: study protocol for a randomised controlled trial.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a glucose intolerance occurring in 3%-10% of pregnant women and being a risk factor for multiple maternal and fetal complications. The risk of perinatal complications is proportional to the level of maternal hyperglycaemia. Proper glycaemic control is therefore one of the key elements of GDM therapy. Until recently, determination of blood glucose concentration was performed using glucose meters, which involved multiple fingerpricks. Nowadays, due to the flash glucose monitoring (FGM) availability, it is possible to collect measurements at any time without routine puncturing. The aim of the presented study is to assess the impact of FGM on the efficacy of treatment in population of patients diagnosed with GDM. METHODS AND ANALYSIS: This is a prospective, randomised study, that will recruit 100 women at 24-28 weeks of gestation at the 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Poland. Women diagnosed with GDM, who will meet the inclusion criteria, will be individually randomised to the FGM or self-monitoring of blood glucose groups. Further on, clinical and laboratory results of the mother and their newborns will be collected for analysis during the course of pregnancy. Primary outcome is mean glycaemia result in each group after 1 month analysis and percentage of results in the target glycaemic range. The secondary objectives will be to compare the two groups for maternal and neonatal outcomes in conjunction with long-term glycaemic control using blood glycated haemoglobin and fructosamine serum concentrations. ETHICS AND DISSEMINATION: The study is exempt from regional ethics review due to its nature of quality improvement in patient care. The study has been approved by the Bioethics Committee at the Medical University of Warsaw and the patient privacy protection boards governing over the recruitment sites. Results of the study will be presented in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: NCT04422821.

Ultrasound evaluation of the fetal fat tissue, heart, liver and umbilical cord measurements in pregnancies complicated by gestational and type 1 diabetes mellitus: potential application in the fetal birth-weight estimation and prediction of the fetal macrosomia.

BACKGROUND: The aim of the study was to evaluate the ultrasound-derived measurements of the fetal soft-tissue, heart, liver and umbilical cord in pregnancies complicated by gestational (GDM) and type 1 diabetes mellitus (T1DM), and further to assess their applicability in the estimation of the fetal birth-weight and prediction of fetal macrosomia. METHODS: Measurements were obtained from diet-controlled GDM (GDMG1) (n = 40), insulin-controlled GDM (GDMG2) (n = 40), T1DM (n = 24) and healthy control (n = 40) patients. The following parameters were selected for analysis: fetal sub-scapular fat mass (SSFM), abdominal fat mass (AFM), mid-thigh fat/lean mass (MTFM/MTLM) and inter-ventricular septum (IVS) thicknesses, heart and thorax circumference and area (HeC/HeA; ThC/ThA), liver length (LL), umbilical cord/vein/arteries circumference and area (UmC/UmA; UvC/UvA; UaC/UaA) together with total umbilical vessels (UveA) and Wharton's jelly area (WjA). Regression models were created in order to assess the contribution of selected parameters to fetal birth-weight (FBW) and risk of fetal macrosomia. RESULTS: Measurements of the fetal SSFM, AFM, MTFM, MTFM/MTLM ratio, HeC, HeA, IVS, LL, UmC, UmA, UaC, UaA, UveA and WjA were significantly increased among patients with GDMG2/T1DM as compared to GDMG1 and/or control groups (p < .05). The regression analysis revealed that maternal height as well as fetal biparietal diameter, abdominal circumference (AC), AFM and LL measurements were independent predictors of the FBW (p < .05). In addition, increase in the fetal AFM, AC and femur length (FL) was associated with a significant risk of fetal macrosomia occurrence (p < .05). The equation developed for the FBW estimation [FBW(g) = - 2254,942 + 17,204 * FL (mm) + 105,531 * AC (cm) + 131,347 * AFM (mm)] provided significantly lower mean absolute percent error than standard formula in the sub-group of women with T1DM (5.7% vs 9.4%, p < .05). Moreover, new equation including AC, FL and AFM parameters yielded sensitivity of 93.8%, specificity 77.7%, positive predictive value 54.5% and negative predictive value of 97.8% in the prediction of fetal macrosomia. CONCLUSIONS: Ultrasound measurements of the fetal soft tissue, heart, liver and umbilical cord are significantly increased among women with GDM treated with insulin and T1DM. In addition to standard biometric measurements, parameters, such as AFM, may find application in the management of diabetes-complicated pregnancies.

Expression of placental glucose transporter proteins in pregnancies complicated by fetal growth disorders.

During pregnancy fetal growth disorders, including fetal macrosomia and fetal growth restriction (FGR) are associated with numerous maternal-fetal complications, as well as due to the adverse effect of the intrauterine environment lead to an increased morbidity in adult life. Accumulating evidence suggests that occurrence of fetal macrosomia or FGR, may be associated with alterations in the transfer of nutrients across the placenta, in particular of glucose. The placental expression and activity of specific GLUT transporters are the main regulatory factors in the process of maternal-fetal glucose exchange. This review article summarizes the results of previous studies on the expression of GLUT transporters in the placenta, concentrating on human pregnancies complicated by intrauterine fetal growth disorders. Characteristics of each transporter protein found in the placenta is presented, alterations in the location and expression of GLUT isoforms observed in individual placental compartments are described, and the factors regulating the expression of selected GLUT proteins are examined. Based on the above data, the potential function of each GLUT isoform in the maternal-fetal glucose transfer is determined. Further on, a detailed analysis of changes in the expression of glucose transporters in pregnancies complicated by fetal growth disorders is given, and significance of these modifications for the pathogenesis of fetal macrosomia and FGR is discussed. In the final part novel interventional approaches that might reduce the risk associated with abnormalities of intrauterine fetal growth through modifications of placental GLUT-mediated glucose transfer are explored.