Gestational Diabetes Mellitus: The Genetic Susceptibility Behind the Disease

Gestational diabetes mellitus (GDM), a type of pregnancy-specific glucose intolerance or hyperglycemia, is one of the most common metabolic disorders in pregnant women with 16.9% of the global prevalence of gestational hyperglycemia. Not only are women with GDM likely to develop T2DM, but their children are also at risk for birth complications or metabolic disease in adulthood. Therefore, identifying the potential risk factors for GDM is very important in the prevention and treatment of GDM. Previous studies have shown that genetic predisposition is an essential component in the occurrence of GDM. In this narrative review, we describe the role of polymorphisms in different functional genes associated with increased risk for GDM, and available evidence on genetic factors in the risk of GDM is summarized and discussed.

Breastfeeding may benefit cardiometabolic health of children exposed to gestational hyperglycemia in utero - Supplementary materials

Supplementary tables, figures, as well as materials and methods, for the study titled "Breastfeeding may benefit cardiometabolic health of children exposed to gestational hyperglycemia in utero"

Epigenome-wide association study of maternal hemoglobin A1c in pregnancy and cord blood DNA methylation

Background: Gestational hyperglycemia is associated with adverse perinatal outcomes and long-term offspring metabolic programming, likely through dysregulation of DNA methylation (DNAm). Materials & methods: We tested associations between maternal HbA1c and cord blood DNAm among 412 mother–child pairs in the genetics of glucose regulation in gestation and growth (Gen3G) and implemented Mendelian randomization to infer causality. We sought replication in an independent sample from Healthy Start. Results: Higher second trimester HbA1c levels were associated with lower DNAm at cg21645848 (p = 3.9 × 10-11) near URGCP. Mendelian randomization and replication analyses showed same direction of effect between HbA1c and DNAm at cg21645848, but did not reach statistical significance. Conclusion: We found that higher maternal glycemia reflected by HbA1c is associated with cord blood DNAm at URGCP, a gene related with inflammatory pathways.

Symphysis-Fundal Height Curve in Pregnancies Complicated by Maternal Hyperglycemia: Comparison with Curves of Nondiabetic Pregnant Women

Background. Reference symphysis-fundal height (SFH) curves for pregnancies complicated by maternal hyperglycemia are not available. Objective. To build an SFH curve according to gestational age for pregnant women with hyperglycemia-type 2 diabetes (T2DM), gestational diabetes mellitus (GDM), or mild gestational hyperglycemia (MGH) and compare it with three other curves in use in Brazil. Methods. Prospective cohort study of 422 pregnant women with hyperglycemia attending the Perinatal Diabetes Research Center (PDRC) of Botucatu Medical School, São Paulo State University/UNESP. Between 13 and 41 weeks of pregnancy, 2470 SFH measurements were obtained (mean 5.85 per woman). For the assessment of glycemic control, 2074 glucose level measurements were taken and the glycemic mean (GM) at each gestational week was estimated. Results. GM was adequate (<120 mg/dL) in 94.9% and inadequate (≥120 mg/dL) in 5.1% of the cases. The equation applied for SFH prediction was expressed as SFH=1.082+0.966∗week (r2=84.6%). At visual analysis, P10 and P90 SFH measurements were higher in the study curve than in the three other curves. Statistical analysis confirmed that SFH median values in this study were higher than those in the reference curve of habitual risk pregnancies, especially after 19 weeks of pregnancy. Conclusion. Taking into account that the maternal hyperglycemia was at strict control, our unedited results suggest that the current SFH curve can be a useful tool in prenatal care of T2DM, GDM, and MGH pregnant women.

Gestational hyperglycemia on diet and medication: impact on placental pathology and pregnancy outcomes

Background: To evaluate the placental morphology and perinatal outcome in patients with gestational hyperglycemia on diet and medication.Methods: Placental examinations performed at the Department of Pathology between August 2016 to August 2018 were retrospectively reviewed. Of the received 140 placentas, 35 of gestational diabetes (GDM) and pre gestational diabetes were identified and segregated into hyperglycemia on diet and on medication. The clinical details, placental findings and perinatal outcome of patients in both the groups (gestational hyperglycemia on diet and medication) were collected and analyzed.Results: Among the 35 cases, there were 24 cases of mild gestational hyperglycemia controlled with diet and 11 cases of hyperglycemia on medication (oral hypoglycemic drugs ± insulin).Most of the placentae in both the groups weighed less than tenth centile. The cord abnormalities such as hyper coiling, velamentous /marginal insertion and furcate cord were observed more in women with GDM on diet. There was no significant gross placental lesion in those on medication. Placental histological features most consistently associated with both the groups include, disturbances of villous maturation (DVM), Derangements in uteroplacental / foetoplacental circulation and villous capillary lesions. Small for gestational age and intrauterine foetal death were found in both the groups, but more commonly in patients with hyperglycemia on medication.Conclusions: Villous maturation defects, uteroplacental / foetoplacental malperfusion are the essential placental changes which can result in adverse perinatal outcomes in women with hyperglycemia irrespective of the diabetic control.

High glucose alters fetal rat islet transcriptome and induces progeny islet dysfunction

Offspring of diabetic mothers are susceptible to developing type 2 diabetes due to pancreatic islet dysfunction. However, the initiating molecular pathways leading to offspring pancreatic islet dysfunction are unknown. We hypothesized that maternal hyperglycemia alters offspring pancreatic islet transcriptome and negatively impacts offspring islet function. We employed an infusion model capable of inducing localized hyperglycemia in fetal rats residing in the left uterine horn, thus avoiding other factors involved in programming offspring pancreatic islet health. While maintaining euglycemia in maternal dams and right uterine horn control fetuses, hyperglycemic fetuses in the left uterine horn had higher serum insulin and pancreatic beta cell area. Upon completing infusion from GD20 to 22, RNA sequencing was performed on GD22 islets to identify the hyperglycemia-induced altered gene expression. Ingenuity pathway analysis of the altered transcriptome found that diabetes mellitus and inflammation/cell death pathways were enriched. Interestingly, the downregulated genes modulate more diverse biological processes, which includes responses to stimuli and developmental processes. Next, we performed ex and in vivo studies to evaluate islet cell viability and insulin secretory function in weanling and adult offspring. Pancreatic islets of weanlings exposed to late gestation hyperglycemia had decreased cell viability in basal state and glucose-induced insulin secretion. Lastly, adult offspring exposed to in utero hyperglycemia also exhibited glucose intolerance and insulin secretory dysfunction. Together, our results demonstrate that late gestational hyperglycemia alters the fetal pancreatic islet transcriptome and increases offspring susceptibility to developing pancreatic islet dysfunction.

Obstetric and Neonatal Outcomes of Pregnancies with Mild Gestational Hyperglycemia Diagnosed at Gestational Diabetes Mellitus Screening

<p><strong>Objective:</strong> The aim of this study was to evaluate obstetric and neonatal outcomes of pregnancies with mild gestational hyperglycemia diagnosed at gestational diabetes mellitus screening.</p><p><strong>Study design:</strong> Between September 2016 and August 2017, the pregnant women diagnosed as normal glycaemia or mild gestational hyperglycemia according to the results of gestational diabetes mellitus screening with 50 g oral glucose challenge test, and 100 g oral glucose tolerance test were compared [Normal glycaemia: Blood glucose value &lt;140 mg/dL 1 hour after 50 g oral glucose challenge test].</p><p><strong>Results:</strong> The following results were obtained in the normal glycaemia and mild gestational hyperglycemia groups respectively: Mean gestational age at birth, 38.9±1.6 and 39±1.9 weeks; preterm, term, post-term birth rates, 6%, 86.2% 7.8% and 6.8%, 86.4% and 6.8%; cesarean delivery rate, 30.9% and 34.9%; birth weight 3227.9±394.9 and 3241.05±418.5 g; small for gestational age, 4.4% and 2.3%; large for gestational age 4.6% and 7%; without any significant difference between the groups. Five minute APGAR scores were significantly lower in the mild gestational hyperglycemia group compared to the normal glycaemia group.</p><p><strong>Conclusion:</strong> There was no significant increase in adverse pregnancy outcomes such as preterm birth, post-term birth, increased caesarean delivery rate, small for gestational age and large for gestational age, except for a significant decrease in 5 minute APGAR scores in the mild gestational hyperglycemia group compared to the normal glycaemia group in our study.</p>