Mild Gestational Hyperglycemia Research Articles

Gestational glucose intolerance and pregnancy outcomes: a retrospective study in the primary care setting of Macau.

Although glucose intolerance is prevalent in Macau, it is rarely assessed during pregnancy. This study examined short-term maternal and neonatal outcomes at different maternal glucose levels in Macau. A total of 2388 pregnant women who received antenatal care at Health Centers and delivered at the Centro Hospitalar Conde de São Januário between June 2018 and December 2019 were included in this study. Gestational diabetes mellitus (GDM) was diagnosed using Carpenter and Coustan criteria, involving a 50 g glucose challenge test (GCT) followed by a 100g oral glucose tolerance test (OGTT). Participants were categorized into 4 groups: normal glucose tolerance if GCT was negative; mild gestational hyperglycemia in this study if positive GCT without GDM; GDM patients with normal fasting blood glucose (FBG) or high FBG in OGTT. Logistic regression analysis was employed to compare pregnancy outcomes among these 4 groups. Due to the limited number of cases, we combined several adverse maternal outcomes, including pregnancy-induced hypertension, assisted delivery, primary Caesarean section, moderate to severe perineal trauma, and postpartum hemorrhage, into a composite measure. The results showed higher rates of the aforementioned outcomes for mild gestational hyperglycemia and GDM with high FBG in OGTT groups [adjusted odds ratio (aOR) 1.32, 95% confidence interval (CI) 1.06-1.64; aOR 2.04, 95% CI 1.24-3.37], as well as macrosomia risk (aOR 2.02, 95% CI 1.11-3.66; aOR 5.04, 95% CI 2.03-12.52) and large-for-gestational age infants (aOR 1.48, 95% CI 1.02-2.16; aOR 4.34, 95% CI 2.31-8.15). Pregnancy outcomes were similar for normal glucose tolerance and GDM with normal FBG in OGTT. Mild gestational hyperglycemia raised the likelihood of adverse maternal outcomes and excessive infant birth weights. Even after achieving target glucose levels, GDM patients with elevated fasting glucose readings in OGTT remained at significant risk for these events. Instead, fasting normoglycemic GDM was treated effectively at Macau Health Centers.

Histo-morphometric vicissitudes in diet-controlled diabetic placenta: A quantitative stereological model

BackgroundAn affordable approach accepted worldwide to successfully treat mild maternal hyperglycemia in gestational diabetes (GDM), is diet-controlled therapy. As no elaborate research was available, this study was crafted to investigate morphometric stereological details and to determine the mean placental oxygen diffusion capacity for patients who were kept on diet therapy for mild gestational hyperglycemia. MethodsA clinical trial (NCT04907708) was conducted from January 2018 to February 2019. A total of 70 women completed the study, out of which 35 served as healthy controls as Group A and 35 were diagnosed as mild gestational diabetics according to WHO criteria (Group B). These patients were kept on a restricted calorie diet with light exercise during gestation and were followed regularly during gestation. Soon after delivery, conserved placentas underwent complete gross, microscopic, and stereological investigations with the point and intersection -counting methods. ResultsSignificant differences were observed for placental width and syncytial knots (p＜ ​0.010 and 0.025 respectively) between the groups on gross and light microscopy. Most of the parameters were non-significant, though numerically more in the GDM group. On stereological details, mean placental volume, mean placental components volumes (villi, inter-villous space, fetal capillary, and fetal connective tissue), mean villi and mean fetal capillary diameter, mean villi and capillary surface density and mean morphometric diffusing capacity of placenta showed non-significant results between the groups. ConclusionMinimal changes were observed in gross, microscopy, and morphometric stereological details in the placentae of GDM patients managed with nutritional therapy during gestation compared with the healthy controls.

Study of DNA Damage in Diabetic Mothers and Their Newborn

Background: Previous research declares that gestational diabetes mellitus (GDM) affects both mother and infant during pregnancy and in the long term. Objective: To assess the pattern of DNA damage in mothers with gestational diabetes during pregnancy and their possible impact on their offspring. Patients and Methods: A case-control study was designed and conducted on 120 pregnant women and their infants; divided into two groups: 1-Patients group (60 patients had gestational diabetes mellitus during the third trimester of pregnancy and their infants) 2-Control group (60 apparently healthy pregnant women and their infants). Results: DNA damage of mother and their infants was significantly increased among the cases group than controls (p=0.0001). There was a statistically significant increase among infants who had DNA damage group than who hadn't regarding HBA1C, random blood sugar (RBS) 3 hr and RBS 6 hr (p 0.05). Conclusions: Hyperglycemia affects maternal and fetal DNA integrity and DNA damage response differently, gestational and mild gestational hyperglycemia, were all related to increased oxidative DNA damage and DNA repair may be thus considered an important mechanism to prevent the deleterious effects of hyperglycemia in the genetic material.

Study of DNA Damage in Diabetic Mothers and Their Newborn

Background: Previous research declares that gestational diabetes mellitus (GDM) affects both mother and infant during pregnancy and in the long term. Objective: To assess the pattern of DNA damage in mothers with gestational diabetes during pregnancy and their possible impact on their offspring. Patients and Methods: A case-control study was designed and conducted on 120 pregnant women and their infants; divided into two groups: 1-Patients group (60 patients had gestational diabetes mellitus during the third trimester of pregnancy and their infants) 2-Control group (60 apparently healthy pregnant women and their infants). Results: DNA damage of mother and their infants was significantly increased among the cases group than controls (p=0.0001). There was a statistically significant increase among infants who had DNA damage group than who hadn't regarding HBA1C, random blood sugar (RBS) 3 hr and RBS 6 hr (p 0.05). Conclusions: Hyperglycemia affects maternal and fetal DNA integrity and DNA damage response differently, gestational and mild gestational hyperglycemia, were all related to increased oxidative DNA damage and DNA repair may be thus considered an important mechanism to prevent the deleterious effects of hyperglycemia in the genetic material.

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.

Maternal factors associated with hyperglycemia in pregnancy and perinatal outcomes: a Brazilian reference center cohort study

BackgroundWhile sufficient evidence supporting universal screening is not available, it is justifiable to look for specific risk factors for gestational diabetes mellitus (GDM) or hyperglycemia in pregnancy (HIP). The objective of this study is to identify independent risk factors for HIP and its adverse perinatal outcomes in a Brazilian public referral center.MethodsWe included 569 singleton pregnant women who were split into three groups by glucose status: GDM (n = 207), mild gestational hyperglycemia (MGH; n = 133), and control (n = 229). Women who used corticosteroids or had a history of DM were excluded. HIP comprised both GDM and MGH, diagnosed by a 100 g- or 75 g-oral glucose tolerance test (OGTT) and a glucose profile at 24–28 weeks. Maternal characteristics were tested for their ability to predict HIP and its outcomes. Bivariate analysis (RR; 95% CI) was used to identify potential associations. Logistic regression (RRadj; 95% CI) was used to confirm the independent risk factors for HIP and its perinatal outcomes (p < 0.05).ResultsAge ≥ 25 years [1.83, 1.12–2.99], prepregnancy BMI ≥ 25 kg/m2 [2.88, 1.89–4.39], family history of DM [2.12, 1.42–3.17] and multiparity [2.07, 1.27–3.37] were independent risk factors for HIP. Family history of DM [169, 1.16–2.16] and hypertension [2.00, 1.36–2.98] were independent risk factors for C-section. HbA1c ≥ 6.0% at birth was an independent risk factor for LGA [1.99, 1.05–3.80], macrosomia [2.43, 1.27–4.63], and birthweight Z-score > 2.0 [4.17, 1.57–11.10].ConclusionsMGH presents adverse pregnancy outcomes similar to those observed in the GDM group but distinct from those observed in the control (no diabetes) group. In our cohort, age ≥ 25 years, prepregnancy BMI ≥ 25 kg/m2, family history of DM, and multiparity were independent risk factors for HIP, supporting the use of selective screening for this condition. These results should be validated in populations with similar characteristics in Brazil or other low- and middle-income countries.

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

Objective: The aim of this study was to evaluate obstetric and neonatal outcomes of pregnancies with mild gestational hyperglycemia diagnosed at gestational diabetes mellitus screening.Study design: 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].Results: 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.Conclusion: 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.

Mild maternal hyperglycemia in INSC93S transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring.

ABSTRACTAlongside the obesity epidemic, the prevalence of maternal diabetes is rising worldwide, and adverse effects on fetal development and metabolic disturbances in the offspring's later life have been described. To clarify whether metabolic programming effects are due to mild maternal hyperglycemia without confounding obesity, we investigated wild-type offspring of INSC93S transgenic pigs, which are a novel genetically modified large-animal model expressing mutant insulin (INS) C93S in pancreatic β-cells. This mutation results in impaired glucose tolerance, mild fasting hyperglycemia and insulin resistance during late pregnancy. Compared with offspring from wild-type sows, piglets from hyperglycemic mothers showed impaired glucose tolerance and insulin resistance (homeostatic model assessment of insulin resistance: +3-fold in males; +4.4-fold in females) prior to colostrum uptake. Targeted metabolomics in the fasting and insulin-stimulated state revealed distinct alterations in the plasma metabolic profile of piglets from hyperglycemic mothers. They showed increased levels of acylcarnitines, gluconeogenic precursors such as alanine, phospholipids (in particular lyso-phosphatidylcholines) and α-aminoadipic acid, a potential biomarker for type 2 diabetes. These observations indicate that mild gestational hyperglycemia can cause impaired glucose tolerance, insulin resistance and associated metabolic alterations in neonatal offspring of a large-animal model born at a developmental maturation status comparable to human babies.

Hyperglycemia induces inflammatory mediators in the human chorionic villous

This study was based on the hypothesis that IL-1β and its central regulator, the inflammasome, may play a role in the inflammatory condition exhibited by placental tissues from mothers with different gestational hyperglycemia levels. Pregnant women were classified according to the glycemic reference as non-diabetic (n = 15), mild gestational hyperglycemia (n = 15), gestational diabetes mellitus (n = 15) and type 2 diabetes mellitus (n = 15). We investigated levels of pro-inflammatory factors in maternal plasma and placental tissues (by ELISA or immunohistochemistry) and, NFKB activity (by electrophoretic mobility shift assay) and inflammasome protein expression (by Western blot) in chorionic villous. Maternal plasma and placental levels of inflammatory factors (IL-1β, IL-6, and MCP-1) were increased during all hyperglycemic conditions. Villous stroma cells showed strong immunoreactivity to CD68. In addition, with syncytiotrophoblast, the villous stroma cells were also stained to detect iNOS, MCP-1, TLR2, and TLR4. Although the levels of protein had fluctuated in the groups, NLRP1, NLRP3, ASC, and Caspase 1 were up-regulated in all hyperglycemic groups suggesting the inflammasome may be assembled in these pregnant women. The NFKB activity also exhibited higher levels in hyperglycemic groups, which might imply in pro-inflammatory cytokines production. In summary, increased maternal glucose levels during pregnancy changed systemic and placental inflammatory patterns, which occurred in parallel with the expression of inflammasome factors and processing and secretion of the pro-inflammatory cytokine IL-1β. These results suggest an inflammatory condition in all gestational hyperglycemic conditions, even in hyperglycemia that is less severe than gestational or overt diabetes, likely associated with inflammasome activation and inflammatory cytokine secretion. Inflammasome activation as a possible source of inflammatory factors may be an important target to be considered while managing hyperglycemia and preventing adverse pregnancy outcomes.

The Perinatal Biopsychosocial Consequences of Various Levels of Gestational Hyperglycemia.

This study was to compare biopsychosocial consequences among three groups of women with gestational hyperglycemia. We conducted a repeated-measures study at five time points among 132 women with gestational hyperglycemia. Women's physiological indicators and their psychosocial indicators were measured. There were 22.7% of participants had gestational diabetes mellitus (GDM), 11.4% had gestational impaired glucose tolerance (G-IGT), and 65.9% had mild gestational hyperglycemia (MGH). Women with GDM had higher fasting blood glucose and systolic/diastolic blood pressure than women with MGH. Women with GDM had higher diastolic blood pressure compared to women with G-IGT. Significant differences were found between the five time points regarding women's fasting blood glucose, diastolic blood pressure, depression, and health status. Health care providers should conduct early screening for predictors of metabolic syndrome in women with any degree of gestational hyperglycemia. Nursing interventions could be offered as early as the perinatal period to promote women's health.

The modulatory role of cytokines IL-4 and IL-17 in the functional activity of phagocytes in diabetic pregnant women.

The study investigated the role of cytokines IL-4 and IL-17 in the modulation of the functional activity of mononuclear phagocytes in diabetic pregnant women with hyperglycemia. Sixty pregnant women were assigned to the following groups: nondiabetic (ND), mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM), or type 2 diabetes mellitus (DM2). The functional activity of phagocytes from maternal blood, cord blood, and colostrum was assessed by determining their superoxide release, phagocytosis, microbicidal activity, and intracellular Ca2+ release. Irrespective of glycemic status, colostrum and blood cells treated with IL-4 and IL-17 increased superoxide release in the presence of enteropathogenic Escherichia coli (EPEC). The highest phagocytosis rate was observed in cells from the DM2 group treated with IL-4. In all the groups, phagocytes from colostrum, maternal blood, and cord blood exhibited higher microbicidal activity against EPEC when treated with cytokines. IL-17 increased intracellular Ca2+ release by colostrum phagocytes in diabetic groups. The results indicate that the IL-4 and IL-17 modulate the functional activity of phagocytes in the maternal blood, cord blood, and colostrum of diabetic mother. The natural immunity resulting from the interaction between the cells and cytokines tested may be an alternative procedure to improve the prognosis of maternal and newborn infections.

Diagnostic protocol for gestational diabetes mellitus (GDM) (IADPSG/ADA, 2011): influence on the occurrence of GDM and mild gestational hyperglycemia (MGH) and on the perinatal outcomes

BackgroundIn August 2011, the Specialized Center for Diabetes and Pregnancy of the Botucatu Medical School/Unesp adopted a new diagnostic protocol for gestational diabetes mellitus, recommended by the American Diabetes Association and the International Association of the Diabetes and Pregnancy Study Group. The glycemic profile was evaluated using the 75-g oral glucose tolerance test (OGTT) used to diagnose mild gestational hyperglycemia, recognized and treated in our department as gestational diabetes mellitus. The cost-effectiveness of the new guidelines and the continued need for the evaluation of the glycemic profile, as part of our Service protocol, are controversial and require further investigation. We aimed to assess the impact of the new guidelines on the evaluation of mild gestational hyperglycemia and gestational diabetes mellitus, the incidence of adverse perinatal outcomes, and the association between the 75-g OGTT and the glycemic profile for the diagnosis of mild gestational hyperglycemia.MethodsThis cross-sectional study was performed identifying a convenience sample of pregnant women and their newborns. The women used our Service for diagnostic procedures, prenatal care and delivery, both before (January 2008 to August 14, 2011) and after (August 15, 2011 to December 2014) the protocol modification. The following variables were compared, following stratification according to diagnostic protocol: prevalence of gestational diabetes mellitus and mild gestational hyperglycemia, newborns large for gestational age, macrosomia, first cesarean delivery, and newborn hospital stay. Statistical analysis was performed using Poisson regression, the Student’s t test, the Chi square or Fisher’s exact test and risk estimate. The statistical significance threshold was set at 95% (p < 0.05).ResultsThe new protocol resulted in an 85% increase in the number of women with GDM, but failed to identify 17.3% of pregnant women classified as having mild gestational hyperglycemia, despite a normal 75-g OGTT. The new guidelines did not affect perinatal outcome.ConclusionsThese results support the validity of maintaining the glycemic profile as part of the diagnostic protocol at our hospital. Large multicenter studies with an adequate sample size are required for conclusive evidence on the cost-effectiveness of the new protocol.

Validation of a symphysis-fundal height chart developed for pregnancy complicated by diabetes and hyperglycemia: an observational study.

BackgroundThe present study validates a symphysis-fundal height chart (SFH-chart) for pregnant women with type 2 diabetes mellitus (DM2), gestational diabetes mellitus (GDM) and mild gestational hyperglycemia (MGH) attending at the Diabetes and Pregnancy Reference Service of the Botucatu Medical School, UNESP, Brazil.MethodsA cross-sectional study was carried out to evaluate the performance of the specific FHC in predicting small (SGA) and large (LGA) for gestational age newborns (NB). We evaluated 206 pregnant women with DM2, GDM or MGH and their NB. The last symphysis-fundal height measure, taken at birth, was used to determine the sensitivity index (Sens), specificity index (Spe), positive prediction value (PPV), negative prediction value (NPV) and accuracy in predicting SGA and LGA. The gold standard was the Lubchenco birth weight/gestational age ratio evaluated at birth.ResultsThe mothers showed adequate glycemic control; 91.3 % of all pregnant women achieved HbA1c < 6,5 % in the third trimester. The SFH-chart tested achieved 100 % of Sens and NPV in predicting both SGA and LGA, with accuracy of 90.3 % (85.5; 93.6) and 91.8 % (87.2; 94.8), respectively, for predicting SGA and LGA newborns.ConclusionsThe Basso SFH-chart showed high performance in predicting both SGA and LGA newborns of DM-2, GDM and MGH mothers, with better performance than the national reference SFH-chart. These findings support the internal validation of the Basso SFH-chart, which may be implemented in the prenatal care of the Diabetes and Pregnancy Reference Service-Botucatu Medical School/UNESP.

Increased DNA Damage is Related to Maternal Blood Glucose Levels in the Offspring of Women With Diabetes and Mild Gestational Hyperglycemia.

This study aimed at correlating maternal blood glucose levels with DNA damage levels in the offspring of women with diabetes or mild gestational hyperglycemia (MGH). Based on oral glucose tolerance test results and glycemic profiles, 56 pregnant women were allocated into 3 groups: nondiabetes, MGH, and diabetes. The offspring of these women (56 infants) were also evaluated. Maternal peripheral blood and umbilical cord blood samples were collected and processed for biochemical and DNA damage analysis by the comet assay. A positive correlation between maternal blood glucose mean and increased offspring DNA damage levels was observed. Hyperglycemia played a role in offspring DNA damage, but other diabetes-induced complications were also involved. Increased maternal blood glucose levels can lead to increased offspring DNA damage levels. Therefore, the monitoring, control, and treatment of pregnant women with diabetes and MGH are highly important to ensure a risk-free pregnancy and healthy infants.

Characterization of Natural Killer Cells and Cytokines in Maternal Placenta and Fetus of Diabetic Mothers.

The present study characterized natural killer cells and cytokines in diabetic mothers, their placenta, and fetus. In the maternal blood from the hyperglycemic groups, the CD16+CD56− NK cells increased, whereas that of CD16+CD56+ decreased in gestational diabetes mellitus [GDM] group. Cord blood from type 2 diabetes [DM-2] showed a higher proportion of CD16+CD56− and CD16−CD56+. The placental extravillous layer of GDM and DM-2 showed an increase of CD16+CD56− cells and, irrespective of region, the proportion of CD16−CD56+ cells was higher in mild gestational hyperglycemia [MGH] and GDM and lower in DM-2. IL-2 was lower in maternal blood and IFN-γ higher in maternal and cord blood from the GDM group. IL-17 was higher in maternal and cord blood from the DM-2 group. The placental extravillous layer of the MGH showed high levels of IL-4, IL-6, IL-10, IL-17, and IFN-γ and low levels of IL-1β and IL-8, whereas the placental villous layer contained high levels of IL-17 and IFN-γ. The GDM group, irrespective of region, showed higher levels of IL-8. The DM-2 group, irrespective of region, placenta showed high levels of TNF-α, IL-17, and IFN-γ. The hyperglycemia produces an inflammatory environment with a high content of inflammatory cytokines and cells expressing CD16+.

Health related quality of life in pregnant women with diabetes or mild hyperglycemia

ABSTRACT Background: Diabetes mellitus (DM) is a public health concern spread worldwide. Maternal diabetes in pregnancy increases risk of adverse perinatal and maternal outcomes; therefore; affecting the women´s quality of life (QOL). Objective: To evaluate quality of life in pregnant women with diabetes mellitus, gestational diabetes or mild gestational hyperglycemia. Study Design: This is a prospective and longitudinal study. The sample comprised 105 pregnant women, i.e. 66 Hyperglycemic (HG) and 39 Normoglycemic (NG). The validated WHOQOL–BREF/ QUALITY of LIFE ASSESSMENT questionnaire was applied at the first prenatal appointment or at time of disease diagnosis; and re-applied at delivery admission or at 36-37 weeks’ gestation. Results: Most pregnant women considered good QOL at early pregnancy, but not at late pregnancy. In general, they were satisfied with their quality of life. NG pregnant women were more satisfied than their HG counterparts. At the onset of the gestational period the HG group obtained lower scores in the physical domain than the NG group. At the end of the gestational period, the scores on physical, psychological and environmental domains were significant lower in pregnant women with diabetes or hyperglycemia. Conclusion: The study demonstrated that pregnant women with diabetes or hyperglycemia were compromised in certain aspects of quality of life. Keywords: Pregnancy, Diabetes mellitus, hyperglycemia, life quality, outpatient treatment, hospital

Hyperglycemia Differentially Affects Maternal and Fetal DNA Integrity and DNA Damage Response.

Objective: Investigate the DNA damage and its cellular response in blood samples from both mother and the umbilical cord of pregnancies complicated by hyperglycemia. Methods: A total of 144 subjects were divided into 4 groups: normoglycemia (ND; 46 cases), mild gestational hyperglycemia (MGH; 30 cases), gestational diabetes mellitus (GDM; 45 cases) and type-2 diabetes mellitus (DM2; 23 cases). Peripheral blood mononuclear cell (PBMC) isolation and/or leukocytes from whole maternal and umbilical cord blood were obtained from all groups at delivery. Nuclear and mitochondrial DNA damage were measured by gene-specific quantitative PCR, and the expression of mRNA and proteins involved in the base excision repair (BER) pathway were assessed by real-time qPCR and Western blot, respectively. Apoptosis was measured in vitro experiments by caspase 3/7 activity and ATP levels. Results: GDM and DM2 groups were characterized by an increase in oxidative stress biomarkers, an increase in nuclear and mitochondrial DNA damage, and decreased expression of mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1) involved in BER. The levels of hyperglycemia were associated with the in vitro apoptosis pathway. Blood levels of DNA damage in umbilical cord were similar among the groups. Newborns of diabetic mothers had increased expression of BER mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1, POLβ and FEN1). A diabetes-like environment was unable to induce apoptosis in the umbilical cord blood cells. Conclusions: Our data show relevant asymmetry between maternal and fetal blood cell susceptibility to DNA damage and apoptosis induction. Maternal cells seem to be more predisposed to changes in an adverse glucose environment. This may be due to differential ability in upregulating multiple genes involved in the activation of DNA repair response, especially the BER mechanism. However if this study shows a more effective adaptive response by the fetal organism, it also calls for further studies to determine the limit of this response that definitely changes the fate of a fetus under these conditions of cellular stress.

IRS-1 gene polymorphism and DNA damage in pregnant women with diabetes or mild gestational hyperglycemia.

BackgroundPregnant women with mild gestational hyperglycemia present a high risk for hypertension and obesity, and appear to reproduce the model of metabolic syndrome in pregnancy, including hyperinsulinemia and insulin resistance. Diabetic patients have a higher frequency of the IRS-1 Gly972Arg variant and this polymorphism is directly related to insulin resistance and subsequent hyperglycemia. In diabetes, hyperglycemia and other associated factors generate reactive oxygen species that increase DNA damage. The aims of this study were to evaluate the presence of the IRS-1 Arg972 polymorphism in pregnant women with diabetes or mild gestational hyperglycemia, and in their newborns. Additionally, we evaluated the level of primary DNA damage in lymphocytes of Brazilian pregnant women and the relationship between the amount of genetic damage and presence of the polymorphism.MethodsA based on the oral glucose tolerance test (OGTT) results and on glycemic profiles (GP), as follows: non-diabetic group, mild gestational hyperglycemia (MGH) and diabetic group. Eighty-five newborns were included in the study. Maternal peripheral blood samples and umbilical cord blood samples (5–10 mL) were collected for genotyping by PCR-RFLP and for comet assays.ResultsThe prevalence of genotype Gly/Arg in pregnant women groups was not statistically significant. In newborns, the frequency of Gly/Arg was significantly higher in the MGH and diabetic groups than in the non-diabetic group. Taken together, groups IIA and IIB (IIA + IIB; diabetes) presented lower amounts of DNA damage than the non-diabetic group (p = 0.064). No significant association was detected between genetic damage and the presence of the Arg972 genotype in pregnant women.ConclusionThe polymorphism was more prevalent in newborns of diabetic and MGH women. We believe that it is necessary to increase the number of subjects to be examined in order to better determine the biological role of the Arg972 polymorphism in these patients. Despite being classified as low-risk, pregnant women with mild gestational hyperglycemia characterize a population of maternal and perinatal adverse outcomes, and that, together with their newborns, require better monitoring by professionals and health services.

Impact of gestational hypothyroidism on uterine implantation and reproductive performance in the rat

Impact of gestational hypothyroidism on uterine implantation and reproductive performance in the rat

Changes in the TNF-alpha/IL-10 ratio in hyperglycemia-associated pregnancies

AimsTNF-α is a diabetogenic cytokine associated with adverse outcomes during pregnancy that can be counterbalanced by IL-10. We have investigated IL-10 and TNF-α balance at maternal and placental levels in hyperglycemia-associated pregnancies. MethodsOne hundred and ninety-two pregnant women participated, which included normoglycemic women (ND) and women with mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM2). Maternal plasma and placental tissue IL-10 and TNF-α levels were measured by ELISA and placental TNF-α was also immunolocalized. ResultsMaternal plasma TNF-α levels were highest in GDM (p=0.0190), whereas TNF-α levels were highest in placental tissues in DM2 (p=0.0095). Immunohistochemistry also showed strong reactivity with anti-TNF-α antibody in the villous structures in the DM2 group. Conversely, IL-10 levels were lowest in maternal plasma of the DM2 group (p=0.0228). The TNF-α/IL-10 ratio in maternal plasma progressively increased with the severity of hyperglycemia (p<0.0001), being highest in placenta of the DM2 group (p=0.0150). In both, plasma and placenta, TNF-α/IL-10 ratio were correlated with mean maternal glycemia and HbA1c levels. ConclusionsAlterations of placenta and serum TNF-α/IL-10 balance with predominance of TNF-α were correlated with the severity of hyperglycemia during gestation. This association may offer insight into the pathogenesis of gestational hyperglycemia and associated pregnancy outcomes.