Search Results (17)

Background/Objectives: During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion to maintain glucose homeostasis. For some women, this change is insufficient to maintain normoglycemia, leading to gestational diabetes mellitus (GDM), a condition characterized by maternal glucose intolerance and hyperglycaemia first diagnosed during the second or third trimester of pregnancy. GDM is diagnosed in approximately 14.0% of pregnancies globally, and it is often associated with short- and long-term adverse health outcomes in both mothers and offspring. Although recent studies have highlighted the role of genetic determinants in the development of GDM, research in this area is still lacking, hindering the development of prevention and treatment strategies. Methods: In this paper, we review recent advances in the understanding of genetic determinants of GDM and glycaemic traits during pregnancy. Results/Conclusions: Our review highlights the need for further collaborative efforts as well as larger and more diverse genotyped pregnancy cohorts to deepen our understanding of the genetic aetiology of GDM, address research gaps, and further improve diagnostic and treatment strategies. Full article

Background: We aimed to explore the still-debated association between smoking and hyperglycaemia in pregnancy (HIP). Methods: A multiethnic prospective study of 15,801 women who delivered at Jean Verdier University Hospital between 2012 and 2018. Of these, 13,943 (88.2%) were non-smokers, 624 (4.5%) former smokers, and 1234 (7.8%) current smokers. Universal HIP screening was proposed to the entire sample (IADPSG/WHO criteria). Results: A total of 13,958 women were screened for HIP. Uptake differed between non-smokers, former smokers, and current smokers (89.5%, 88.3%, and 75.7%, respectively, p < 0.0001). HIP prevalence in these groups was 19.9%, 15.4%, and 12.3%, respectively (p < 0.0001). After adjusting for age, body mass index, family history of diabetes, history of HIP, history of macrosomic baby, and ethnicity, current (odds ratio 0.790 [95% confidence interval 0.636–0.981], p < 0.05) but not former (1.017 [0.792–1.306]) smokers were less likely to have HIP than non-smokers. Furthermore, 1 h and 2 h oral plasma glucose test values were lower in current smokers than in non-smokers (p < 0.01). To exclude potential selection bias, we compared risk factors for HIP and HIP-related adverse pregnancy outcomes in current smokers according to HIP screening status. Compared with screened current smokers (n = 934), their unscreened counterparts (n = 300) were younger, less frequently employed, and more likely to be of non-European origin. Moreover, infant birthweight was lower in this group, and preterm deliveries and perinatal deaths were more likely (all p < 0.01). Conclusions: Smoking during pregnancy was independently associated with lower HIP prevalence. The low HIP screening rate in current smokers did not explain this finding. Full article

The Northern Territory (NT) and Far North Queensland (FNQ) have a high proportion of Aboriginal and Torres Strait Islander women birthing who experience hyperglycaemia in pregnancy. A multi-component health systems intervention to improve antenatal and postpartum care in these regions for women with hyperglycaemia in pregnancy was implemented between 2016 and 2019. We explored health professional perspectives on the impact of the intervention on healthcare. The RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, Maintenance) underpinned this mixed-methods evaluation. Clinicians were surveyed before (n = 183) and following (n = 137) implementation. The constructs explored included usual practice and satisfaction with care pathways and communication between services. Clinicians, policymakers and the implementation team were interviewed (n = 36), exploring the impact of the health systems intervention on practice and systems of care. Survey and interview participants reported improvements in clinical practice and systems of care. Self-reported glucose screening practices improved, including the use of recommended tests (72.0% using recommended first-trimester screening test at baseline, 94.8% post-intervention, p < 0.001) and the timing of postpartum diabetes screening (28.3% screening at appropriate interval after gestational diabetes at baseline, 66.7% post-intervention, p < 0.001). Health professionals reported multiple improvements to care for women with hyperglycaemia in pregnancy following the health systems intervention. Full article

Throughout pregnancy, some degree of insulin resistance is necessary to divert glucose towards the developing foetus. In gestational diabetes mellitus (GDM), insulin resistance is exacerbated in combination with insulin deficiency, causing new-onset maternal hyperglycaemia. The rapid reversal of insulin resistance following delivery strongly implicates the placenta in GDM pathogenesis. In this case–control study, we investigated the proteomic cargo of human syncytiotrophoblast-derived extracellular vesicles (STBEVs), which facilitate maternal–fetal signalling during pregnancy, in a UK-based cohort comprising patients with a gestational age of 38–40 weeks. Medium/large (m/l) and small (s) STBEVs were isolated from GDM (n = 4) and normal (n = 5) placentae using ex vivo dual-lobe perfusion and subjected to mass spectrometry. Bioinformatics were used to identify differentially carried proteins and mechanistic pathways. In m/lSTBEVs, 56 proteins were differently expressed while in sSTBEVs, no proteins reached statistical difference. Differences were also observed in the proteomic cargo between m/lSTBEVs and sSTBEVs, indicating that the two subtypes of STBEVs may have divergent modes of action and downstream effects. In silico functional enrichment analysis of differentially expressed proteins in m/lSTBEVs from GDM and normal pregnancy found positive regulation of cytoskeleton organisation as the most significantly enriched biological process. This work presents the first comparison of two populations of STBEVs’ protein cargos (m/l and sSTBEVs) from GDM and normal pregnancy isolated using placenta perfusion. Further investigation of differentially expressed proteins may contribute to an understanding of GDM pathogenesis and the development of novel diagnostic and therapeutic tools. Full article

Gestational diabetes mellitus (GDM) is defined as hyperglycaemia first detected at any time during pregnancy with values lower than those determined by the WHO for diabetes diagnosis in adults. This pathology, with a worldwide prevalence of 13.4%, causes significant maternal and foetal risks. The first line of treatment consists of maintaining normo-glycaemia through an adequate diet and lifestyle changes. The aim is to synthesize the scientific evidence updating the nutritional recommendations for the effective management of GDM. A systematic review of the scientific literature was conducted following the PRISMA guidelines. Randomized clinical trials published within the last five years and providing information on nutritional recommendations to achieve an effective management of gestational diabetes were selected. The databases searched were PubMed, the WOS Core Collection, SCOPUS, and CINAHL, using the MeSH terms: “Diabetes, Gestational”; “Nutrition Assessment (nutrition*)”; “Diet”; “Eating”; and “Food”; with the Boolean operators “AND” and “OR”. The PEDro scale (Physiotherapy Evidence Database) was used to assess the scientific quality of the studies, with a mean score of 8.9, indicating an average good scientific quality. Results: A total of 809 papers were collected, of which, after applying the inclusion and exclusion criteria, 14 randomized clinical trials were selected. Probiotic supplementation and co-supplementation with vitamin D have been found to be the most beneficial options for both mothers with GDM and neonates, but the most effective regimens are not known. Diets enriched with extra virgin olive oil (EVOO) and oat bran, as well as some recommendations focused on carbohydrates also seem effective, as well as diets designed for this group of women with GDM such as “CHOICE”. Conclusions: Although there are numerous proposals that have been published in recent years focused on the diet of women with GDM in order to improve their results and those of their children, it is the supplementation with probiotics and the co-supplementation with vitamin D that is most agreed upon as beneficial; however, more research is needed into which protocols are most effective. Other proposals that could also be beneficial should be further studied. Full article

Background: Changes in body weight are associated with the regulation of DNA methylation (DNAm). In this study, we investigated the associations between maternal gestational weight gain-related DNAm and foetal and neonatal body composition. Methods: Brazilian pregnant women from the Araraquara Cohort Study were followed up during pregnancy, delivery, and after hospital discharge. Women with normal pre-pregnancy BMI were allocated into two groups: adequate gestational weight gain (AGWG, n = 45) and excessive gestational weight gain (EGWG, n = 30). Foetal and neonatal body composition was evaluated via ultrasound and plethysmography, respectively. DNAm was assessed in maternal blood using Illumina Infinium MethylationEPIC BeadChip arrays. Linear regression models were used to explore the associations between DNAm and foetal and neonatal body composition. Results: Maternal weight, GWG, neonatal weight, and fat mass were higher in the EGWG group. Analysis of DNAm identified 46 differentially methylated positions and 11 differentially methylated regions (DMRs) between the EGWG and AGWG groups. Nine human phenotypes were enriched for these 11 DMRs located in 13 genes (EMILIN1, HOXA5, CPT1B, CLDN9, ZFP57, BRCA1, POU5F1, ANKRD33, HLA-B, RANBP17, ZMYND11, DIP2C, TMEM232), highlighting the terms insulin resistance, and hyperglycaemia. Maternal DNAm was associated with foetal total thigh and arm tissues and subcutaneous thigh and arm fat, as well as with neonatal fat mass percentage and fat mass. Conclusion: The methylation pattern in the EGWG group indicated a risk for developing chronic diseases and involvement of maternal DNAm in foetal lean and fat mass and in neonatal fat mass. Full article

In women with type 1 diabetes, the risk of adverse pregnancy outcomes, including congenital anomalies, preeclampsia, preterm delivery, foetal overgrowth and perinatal death is 2–4-fold increased compared to the background population. This review provides the present evidence supporting recommendations for the diet during pregnancy and breastfeeding in women with type 1 diabetes. The amount of carbohydrate consumed in a meal is the main dietary factor affecting the postprandial glucose response. Excessive gestational weight gain is emerging as another important risk factor for foetal overgrowth. Dietary advice to promote optimized glycaemic control and appropriate gestational weight gain is therefore important for normal foetal growth and pregnancy outcome. Dietary management should include advice to secure sufficient intake of micro- and macronutrients with a focus on limiting postprandial glucose excursions, preventing hypoglycaemia and promoting appropriate gestational weight gain and weight loss after delivery. Irrespective of pre-pregnancy BMI, a total daily intake of a minimum of 175 g of carbohydrate, mainly from low-glycaemic-index sources such as bread, whole grain, fruits, rice, potatoes, dairy products and pasta, is recommended during pregnancy. These food items are often available at a lower cost than ultra-processed foods, so this dietary advice is likely to be feasible also in women with low socioeconomic status. Individual counselling aiming at consistent timing of three main meals and 2–4 snacks daily, with focus on carbohydrate amount with pragmatic carbohydrate counting, is probably of value to prevent both hypoglycaemia and hyperglycaemia. The recommended gestational weight gain is dependent on maternal pre-pregnancy BMI and is lower when BMI is above 25 kg/m². Daily folic acid supplementation should be initiated before conception and taken during the first 12 gestational weeks to minimize the risk of foetal malformations. Women with type 1 diabetes are encouraged to breastfeed. A total daily intake of a minimum of 210 g of carbohydrate is recommended in the breastfeeding period for all women irrespective of pre-pregnancy BMI to maintain acceptable glycaemic control while avoiding ketoacidosis and hypoglycaemia. During breastfeeding insulin requirements are reported approximately 20% lower than before pregnancy. Women should be encouraged to avoid weight retention after pregnancy in order to reduce the risk of overweight and obesity later in life. In conclusion, pregnant women with type 1 diabetes are recommended to follow the general dietary recommendations for pregnant and breastfeeding women with special emphasis on using carbohydrate counting to secure sufficient intake of carbohydrates and to avoid excessive gestational weight gain and weight retention after pregnancy. Full article

Gestational diabetes mellitus (GDM) is one of the most prevalent obstetric conditions, particularly among women with obesity. Pathways to hyperglycaemia remain obscure and a better understanding of the pathophysiology would facilitate early detection and targeted intervention. Among obese women from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), we aimed to compare metabolic profiles early and mid-pregnancy in women identified as high-risk of developing GDM, stratified by GDM diagnosis. Using a GDM prediction model combining maternal age, mid-arm circumference, systolic blood pressure, glucose, triglycerides and HbA1c, 231 women were identified as being at higher-risk, of whom 119 women developed GDM. Analyte data (nuclear magnetic resonance and conventional) were compared between higher-risk women who developed GDM and those who did not at timepoint 1 (15⁺⁰–18⁺⁶ weeks) and at timepoint 2 (23⁺²–30⁺⁰ weeks). The adjusted regression analyses revealed some differences in the early second trimester between those who developed GDM and those who did not, including lower adiponectin and glutamine concentrations, and higher C-peptide concentrations (FDR-adjusted p < 0.005, < 0.05, < 0.05 respectively). More differences were evident at the time of GDM diagnosis (timepoint 2) including greater impairment in β-cell function (as assessed by HOMA2-%B), an increase in the glycolysis-intermediate pyruvate (FDR-adjusted p < 0.001, < 0.05 respectively) and differing lipid profiles. The liver function marker γ-glutamyl transferase was higher at both timepoints (FDR-adjusted p < 0.05). This exploratory study underlines the difficulty in early prediction of GDM development in high-risk women but adds to the evidence that among pregnant women with obesity, insulin secretory dysfunction may be an important discriminator for those who develop GDM. Full article

Diabetic retinopathy (DR) is one of the main causes of vision loss in middle-aged economically active people. Modifiable (i.e., hyperglycaemia, hypertension, hyperlipidaemia, obesity, and cigarette smoke) and non-modifiable factors (i.e., duration of diabetes, puberty, pregnancy and genetic susceptibility) are involved in the development of DR. Epigenetic mechanisms, modulating the oxidative stress, inflammation, apoptosis, and aging, could influence the course of DR. Herein, we conducted a systematic review of observational studies investigating how epigenetics affects type 2 diabetes retinopathy (T2DR). A total of 23 epidemiological studies were included: 14 studies focused on miRNA, 4 studies on lnc-RNA, one study on both miRNA and lnc-RNA, and 4 studies on global or gene-specific DNA methylation. A direct relation between the dysregulation of miR-21, miR-93, and miR-221 and FPG, HbA1c, and HOMA-IR was identified. A panel of three miRNAs (hsa-let-7a-5p, hsa-miR-novel-chr5_15976, and hsa-miR-28-3p) demonstrated a good sensitivity and specificity for predicting T2DR. Little evidence is available regarding the possible role of the long non-coding MALAT1 dysregulation and MTHFR gene promoter hypermethylation. Despite these initial, encouraging findings potentially suggesting a role of epigenetics in T2DR, the use in clinical practice for the diagnosis and staging of this complication encounters several difficulties and further targeted investigations are still necessary. Full article

We aimed to compare pregnancy outcomes in 4665 women according to the following types of hyperglycaemia in pregnancy sub-types: (i) normoglycaemia, (ii) gestational diabetes mellitus (GDM), (iii) diabetes in pregnancy (DIP), (iv) early-diagnosed (i.e., <22 weeks of gestation) GDM (eGDM), and (v) early-diagnosed DIP (eDIP). The prevalence of normoglycaemia, eGDM, eDIP, GDM, and DIP was 76.4%, 10.8%, 0.6%, 11.7%, and 0.6%, respectively. With regard to pregnancy outcomes, gestational weight gain (11.5 ± 5.5, 9.0 ± 5.4, 8.3 ± 4.7, 10.4 ± 5.3, and 10.1 ± 5.0 kg, p < 0.0001) and insulin requirement (none, 46.0%, 88.5%, 25.5%, and 51.7%; p < 0.001) differed according to the glycaemic sub-types. eGDM and eDIP were associated with higher rates of infant malformation. After adjustment for confounders, with normoglycaemia as the reference, only GDM was associated with large-for-gestational-age infant (odds ratio 1.34 (95% interval confidence 1.01–1.78) and only DIP was associated with hypertensive disorders (OR 3.48 (1.26–9.57)). To conclude, early-diagnosed hyperglycaemia was associated with an increased risk of malformation, suggesting that it was sometimes present at conception. Women with GDM, but not those with eGDM, had an increased risk of having a large-for-gestational-age infant, possibly because those with eGDM were treated early and therefore had less gestational weight gain. Women with DIP might benefit from specific surveillance for hypertensive disorders. Full article

MODY2 is caused by heterozygous inactivating mutations in the glucokinase (GCK) gene that result in persistent, stable and mild fasting hyperglycaemia (5.6–8.0 mmol/L, glycosylated haemoglobin range of 5.6–7.3%). Patients with GCK mutations usually do not require any drug treatment, except during pregnancy. The GCK gene is considered to be responsible for about 20% of all MODY cases, transcription factors for 67% and other genes for 13% of the cases. Based on our findings, GCK and HNF1A mutations together are responsible for about 90% of the cases in Hungary, this ratio being higher than the 70% reported in the literature. More than 70% of these patients have a mutation in the GCK gene, this means that GCK-MODY is the most prevalent form of MODY in Hungary. In the 91 index patients and their 72 family members examined, we have identified a total of 65 different pathogenic (18) and likely pathogenic (47) GCK mutations of which 28 were novel. In two families, de novo GCK mutations were detected. About 30% of the GCK-MODY patients examined were receiving unnecessary OAD or insulin therapy at the time of requesting their genetic testing, therefore the importance of having a molecular genetic diagnosis can lead to a major improvement in their quality of life. Full article

Background: To test the feasibility of benchmarking the care of women with pregnancies complicated by hyperglycaemia. Methods: A retrospective audit of volunteer diabetes services in Australia and New Zealand involving singleton pregnancies resulting in live births between 2014 and 2020. Ranges are shown and compared across services. Results: The audit included 10,144 pregnancies (gestational diabetes mellitus (GDM) = 8696; type 1 diabetes (T1D) = 435; type 2 diabetes (T2D) = 1013) from 11 diabetes services. Among women with GDM, diet alone was used in 39.4% (ranging among centres from 28.8–57.3%), metformin alone in 18.8% (0.4–43.7%), and metformin and insulin in 10.1% (1.5–23.4%); when compared between sites, all p < 0.001. Birth was by elective caesarean in 12.1% (3.6–23.7%) or emergency caesarean in 9.5% (3.5–21.2%) (all p < 0.001). Preterm births (<37 weeks) ranged from 3.7% to 9.4% (p < 0.05), large for gestational age 10.3–26.7% (p < 0.001), admission to special care nursery 16.7–25.0% (p < 0.001), and neonatal hypoglycaemia (<2.6 mmol/L) 6.0–27.0% (p < 0.001). Many women with T1D and T2D had limited pregnancy planning including first trimester hyperglycaemia (HbA1c > 6.5% (48 mmol/mol)), 78.4% and 54.6%, respectively (p < 0.001). Conclusion: Management of maternal hyperglycaemia and pregnancy outcomes varied significantly. The maintenance and extension of this benchmarking service provides opportunities to identify policy and clinical approaches to improve pregnancy outcomes among women with hyperglycaemia in pregnancy. Full article

Gestational diabetes mellitus (GDM) is an obstetric complication that affects approximately 5–10% of all pregnancies worldwide. GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy, and is characterized by exaggerated insulin resistance, a condition which is already pronounced in healthy pregnancies. Maternal hyperglycaemia ensues, instigating a ‘glucose stress’ response and concurrent systemic inflammation. Previous findings have proposed that both placental and visceral adipose tissue play a part in instigating and mediating this low-grade inflammatory response which involves altered infiltration, differentiation and activation of maternal innate and adaptive immune cells. The resulting maternal immune dysregulation is responsible for exacerbation of the condition and a further reduction in maternal insulin sensitivity. GDM pathology results in maternal and foetal adverse outcomes such as increased susceptibility to diabetes mellitus development and foetal neurological conditions. A clearer understanding of how these pathways originate and evolve will improve therapeutic targeting. In this review, we will explore the existing findings describing maternal immunological adaption in GDM in an attempt to highlight our current understanding of GDM-mediated immune dysregulation and identify areas where further research is required. Full article

Background: Hyperglycaemia in pregnancy contributes to adverse outcomes for women and their children. The postpartum period is an opportune time to support women to reduce cardiometabolic and diabetes risk in subsequent pregnancies. Aims: To identify strengths and gaps in current care for Aboriginal women after a pregnancy complicated by hyperglycaemia. Methods: A retrospective review of the 12 month postpartum care provided by primary health centres in remote Australia in 2013–2014 identified 195 women who experienced hyperglycaemia in pregnancy (gestational diabetes (GDM) (n = 147), type 2 diabetes (T2D) (n = 39), and unclear diabetes status (n = 9)). Results: Only 80 women (54%) with GDM had postpartum glycaemic checks. Of these, 32 women were diagnosed with prediabetes (n = 24) or diabetes (n = 8). Compared to women with GDM, women with T2D were more likely to have their weight measured (75% vs. 52%, p <0.01), and smoking status documented as “discussed” (65% vs. 34%, p < 0.01). Most women (97%) accessed the health centre at least once in the 12 month postpartum period but, during these visits, only 52% of women had service provision, either structured or opportunistic, related to diabetes. Conclusion: High rates of dysglycaemia among women screened for T2D after GDM in the 12 month postpartum period highlight the need for increased screening and early intervention to prevent the development of T2D and its complications. Whilst a clear strength was high postpartum attendance, many women did not attend health services for diabetes screening or management. Full article