Diabetes In Offspring Research Articles

Cerium Oxide Nanozymes Improve Skeletal Muscle Function in Gestational Diabetic Offspring by Attenuating Mitochondrial Oxidative Stress.

Gestational diabetes mellitus (GDM) is a significant complication during pregnancy that results in abnormalities in the function of multiple systems in the offspring, which include skeletal muscle dysfunction and reduced systemic metabolic capacity. One of the primary causes behind this intergenerational effect is the presence of mitochondrial dysfunction and oxidative stress in the skeletal muscle of the offspring due to exposure to a high-glucose environment in utero. Cerium oxide (CeO2) nanozymes are antioxidant agents with polymerase activity that have been widely used in the treatment of inflammatory and aging diseases. In this study, we synthesized ultrasmall particle size CeO2 nanozymes and applied them in GDM mouse offspring. The CeO2 nanozymes demonstrated an ability to increase insulin sensitivity and enhance skeletal muscle motility in GDM offspring by improving mitochondrial activity, increasing mitochondrial ATP synthesis function, and restoring abnormal mitochondrial morphology. Furthermore, at the cellular level, CeO2 nanozymes could ameliorate metabolic dysregulation and decrease cell differentiation in adult muscle cells induced by hyperglycemic stimuli. This was achieved through the elimination of endogenous reactive oxygen species (ROS) and an improvement in mitochondrial oxidative respiration function. In conclusion, CeO2 nanozymes play a crucial role in preserving muscle function and maintaining the metabolic stability of organisms. Consequently, they serve to reverse the negative effects of GDM on skeletal muscle physiology in the offspring.

Effect of individualised nutritional intervention on the postpartum nutritional status of patients with gestational diabetes mellitus and the growth and development of their offspring: a quasi-experimental study

This study explored the effect of individualised nutritional intervention on the postpartum nutritional status of patients with the growth and development of their offspring. This study included pregnant women with gestational diabetes mellitus (GDM) at Hangzhou Women’s Hospital in 2019. At 42 days after childbirth, the HbA1c (95% CI: 0.44-0.56%, p < 0.001), the FPG (95% CI: 0.01–0.26 mmol/L, p < 0.05), 2HPG (95% CI: −0.01–0.73 mmol/L, p < 0.05) and TCH (95% CI: −0.34–0.00 mmol/L, p < 0.05) level of the control group were 0.14, 0.36, and 0.17 mmol/L higher than in the intervention group. There were no differences in TG and HGB between the two groups (all p > 0.05). There were significant differences in the number of macrosomia and neonatal weight between the two groups (both p < 0.05). Differences in WHZ after childbirth were not statistically significant between the two groups (all p > 0.05). Individualised nutritional intervention could improve blood glucose levels 42 days after childbirth and reduce macrosomia incidence in pregnant women with GDM. Impact statement What is already known on this subject? Individualised nutrition intervention can improve blood glucose status and complications during pregnancy, thus improving pregnancy outcomes. What the results of this study add? Individual nutrition intervention improved the blood glucose and nutritional status of patients at 42 days postpartum, but there was no difference in the growth and development indicators of their offspring at 0–24 months. What the implications are of these findings for clinical practice and/or further research? Improve nutritional intervention programs for gestational diabetes, improve blood glucose during pregnancy and postpartum, to improve pregnancy outcomes and reduce the occurrence of type 2 diabetes and other metabolic diseases; Extend the monitoring range of the growth and development of the offspring of gestational diabetes, find the problems and timely carry out the nutritional intervention, to improve the development of the offspring.

Association of parental cardiovascular risk factors with offspring type 1 diabetes mellitus insulin sensitivity

AimThis study aimed to determine whether the insulin resistance (IR) and lipid profiles in Type 1 Diabetes (T1D) offspring are associated with IR and other cardiovascular risk factors in their parents. MethodsThis study included 99 T1D patients (19.6 ± 4.0 yrs.), 85 mothers and 60 fathers. Parents' IR was assessed by HOMA-IR, and the insulin sensitivity in T1D patients was assessed by the estimated Glucose Disposal Rate (eGDR). ResultsThe eGDR in the T1D offspring was negatively related to age (p = 0.023), weight (p = 0.004), LDL (p = 0.026), and microalbuminuria (p = 0.019). Maternal Type 2 Diabetes (p < 0.001) and HOMA-IR (p = 0.029) were negatively related to eGDR in their T1D offspring. The maternal HOMA-IR and the proband's eGDR were positively (p = 0.012) and negatively (p = 0.042) associated with the birth weight of the T1D offspring, respectively. We didn't find an association with the fathers' profiles. ConclusionsIn a cohort of offspring with T1D the insulin sensitivity was related to the IR, lipid profile, and the presence of T2D only in their mothers. Precocious screening and treatment of these risk factors beyond glycemic control will benefit T1D with this background.

Nephron deficit and low podocyte density increase risk of albuminuria and glomerulosclerosis in a model of diabetes.

Podocytes are terminally differentiated epithelial cells in glomeruli. Podocyte injury and loss are features of many diseases leading to chronic kidney disease (CKD). The developmental origins of health and disease hypothesis propose an adverse intrauterine environment can lead to CKD later in life, especially when a second postnatal challenge is experienced. The aim of this study was to examine whether a suboptimal maternal environment would result in reduced podocyte endowment, increasing susceptibility to diabetes-induced renal injury. Female C57BL/6 mice were fed a low protein diet (LPD) to induce growth restriction or a normal protein diet (NPD) from 3 weeks before mating until weaning (postnatal Day 21, P21) when nephron and podocyte endowment were assessed in one male and one female offspring per litter. Littermates were administered streptozotocin or vehicle at 6 weeks of age. Urinary albumin excretion, glomerular size, and podometrics were assessed following 18 weeks of hyperglycemia. LPD offspring were growth restricted and had lower nephron and podocyte number at P21. However, by 24 weeks the podocyte deficit was no longer evident and despite low nephron endowment neither albuminuria nor glomerulosclerosis were observed. Podocyte number was unaffected by 18 weeks of hyperglycemia in NPD and LPD offspring. Diabetes increased glomerular volume reducing podocyte density, with more pronounced effects in LPD offspring. LPD and NPD diabetic offspring developed mild albuminuria with LPD demonstrating an earlier onset. LPD offspring also developed glomerular pathology. These findings indicate that growth-restricted LPD offspring with low nephron number and normalized podocyte endowment were more susceptible to alterations in glomerular volume and podocyte density leading to more rapid onset of albuminuria and renal injury than NPD offspring.

Novel circRNA-miRNA-mRNA networks regulated by maternal exercise in fetal hearts of pregestational diabetes

BackgroundMaternal exercise lowers the incidence of congenital heart defects (CHDs) induced by pregestational diabetes. However, the molecular mechanisms underlying the beneficial effects of maternal exercise remain unclear. The present study aimed to identify circular RNA (circRNA), microRNA (miRNA) and mRNA networks that are regulated by maternal exercise in fetal hearts of pregestational diabetes. MethodsPregestational diabetes was induced in adult C57BL/6 female mice by streptozotocin. The expression profiles of circRNAs, miRNAs and mRNAs in E10.5 fetal hearts of offspring of control and diabetic mothers with or without exercise were analyzed using next generation sequencing. circRNA-miRNA-mRNA networks in fetal hearts were mapped and key candidate transcripts were verified by qPCR analysis. ResultsPregestational diabetes dysregulated the expression of 206 circRNAs, 66 miRNAs and 391 mRNAs in fetal hearts. Maternal exercise differentially regulated 188 circRNAs, 57 miRNAs and 506 mRNAs in fetal hearts of offspring of pregestational diabetes. A total of 5 circRNAs, 12 miRNAs, and 28 mRNAs were incorporated into a final maternal exercise-associated regulatory network in fetal hearts of offspring of maternal diabetes. Notably, maternal exercise normalized the dysregulated circ_0003226/circ_0015638/miR-351-5p and circ_0002768/miR-3102-3p.2-3p pairs in fetal hearts of pregestational diabetes. ConclusionMaternal exercise reverses the dysregulated circ_0003226/circ_0015638/miR-351-5p and circ_0002768/miR-3102-3p.2-3p pairs, and partially normalizes circRNA, miRNA, and mRNA expression profiles in fetal hearts of pregestational diabetes. These findings shed new light on the potential mechanisms of the beneficial effects of maternal exercise on the developing heart in diabetic pregnancies.

Variations in Anthropometric Parameters in Offspring of Type 2 Diabetes Patients

Background: The risk of developing diabetes mellitus for an individual with a positive family history of the disease is two-to fourfold higher in an offspring of a diabetic compared with offspring of non-diabetic. Objectives: This study aimed to assess the anthropometric parameters of offspring of type 2 diabetes mellitus (T2DM) patients in Sagamu, Nigeria. Methods: Study subjects were 100 offspring of consecutive T2DM patients’ attending a hospital endocrinology clinic. Diabetic offspring were exempted from the study. FBS was determined employing enzymatic hexokinase method. Height, weight, waist circumference (WC), and hip circumference (HC) were measured utilizing standard methods while body mass index (BMI) and waist-hip ratio (WHR) were calculated. Results: There were 50 males and 50 females study subjects, aged 16 to 65 years. The most populated aged group was 16 to 25 years of which 48.6% (n=36) were males and 51.4% (n=38) were females. Totally, 18 subjects were either obese or overweight. Significantly, male subjects had a greater mean weight compared to females (P=0.021) while females had greater mean BMI (P=0.037). Mean WHR was significantly higher among male subjects (P=0.018). Conclusion: Common Anthropometric parameters are normal, female subjects tend to have higher BMI while males have higher weight and WHR.

Patterns of Hba1c Levels in Normoglycemic Offspring of T2 Diabetes Mellitus Patients

Background: The risk of developing diabetes mellitus for an individual with a positive family history of the disease is two- to fourfold higher in an offspring of a diabetic compared with offspring of non-diabetic shown by serum glycated hemoglobin (HbA1c) levels. There is paucity of data on pre-diabetes in our environment. Objectives: This study was designed to determine the baseline HbA1c levels of normoglycemic offspring of type 2 diabetes mellitus (T2DM) patients in Ijebu-ode, Nigeria. Methods: This is a cross-sectional study of offspring of T2DM patients (ODP) and those of offspring of non-diabetic parents (ONDP). Diabetic offspring were exempted from the study. FBS was determined using enzymatic hexokinase method to determine glucose concentrations and exclude diabetes. Serum HbA1c was measured using standard method. Height and weight were measured using standard methods. Body mass index (BMI) was calculated. Results: There were 100 ODP and 100 ONDP aged 16 to 40 years. The most populated aged group was 21 to25 years which is 44% (n=88). 6% (n=12) of the study group were obese. 19% were overweight (n=38). The mean weight of ODP was significantly higher than that of ONDP (P=0.020). Also, the mean HBA1c of ODP was significantly higher than that of ONDP (P&lt;0.001). Conclusion: The serum HbA1c level was significantly higher among ODP than ONDP. The mean weight was significantly higher in ODP than ONDP.

Insulin Resistance in Type II Diabetes Mellitus Patients and Their First Degree Relatives- An Observational Study

Type II diabetes (T2DM) is caused by environmental, genetic, metabolic, and unknown variables. In diabetics, insulin resistance is the most of prolonged hyperglycemia. T2DM is induced by insulin resistance and cell dysfunction. The interaction of genetics and environment further complicates T2DM development. Insulin resistance and beta cell dysfunction are two of the most common Type 2 Diabetes Mellitus symptoms. A vicious triangle of cell failure (80% cell function) and insulin resistance in the muscles and liver causes major physiological issues. A group of diabetes patients (Group I), non-diabetic first-degree relatives of diabetic patients (Group II), and a non-diabetic healthy control group (Group III) were studied. The diabetes patients had the greatest systolic and diastolic blood pressures, followed by first degree relatives and healthy controls. We found that people with diabetes had higher fasting (FBS) and postprandial sugar, glycated haemoglobin (HbA1c) than diabetic offsprings and control group. Moreover, fasting insulin levels are higher in first degree relatives than in diabetes patients in the control group. The HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) levels of diabetics and their progeny do not differ much. The HOMA-IR measures insulin resistance severity. Common reference levels for HOMA-IR insulin resistance range from 0.7 - 2. Insulin resistance in diabetics and their first-degree relatives is evident from the results.

Diabetic pregnancy as a novel risk factor for cardiac dysfunction in the offspring\u2014the heart as a target for fetal programming in rats

Aims/hypothesisThe impact of diabetic pregnancy has been investigated extensively regarding offspring metabolism; however, little is known about the influence on the heart. We aimed to characterise the effects of a diabetic pregnancy on male adult offspring cardiac health after feeding a high-fat diet in an established transgenic rat model.MethodsWe applied our rat model for maternal type 2 diabetes characterised by maternal insulin resistance with hyperglycaemia and hyperinsulinaemia. Diabetes was induced preconceptionally via doxycycline-induced knock down of the insulin receptor in transgenic rats. Male wild-type offspring of diabetic and normoglycaemic pregnancies were raised by foster mothers, followed up into adulthood and subgroups were challenged by a high-fat diet. Cardiac phenotype was assessed by innovative speckle tracking echocardiography, circulating factors, immunohistochemistry and gene expression in the heart.ResultsWhen feeding normal chow, we did not observe differences in cardiac function, gene expression and plasma brain natriuretic peptide between adult diabetic or normoglycaemic offspring. Interestingly, when being fed a high-fat diet, adult offspring of diabetic pregnancy demonstrated decreased global longitudinal (−14.82 ± 0.59 vs −16.60 ± 0.48%) and circumferential strain (−23.40 ± 0.57 vs −26.74 ± 0.34%), increased relative wall thickness (0.53 ± 0.06 vs 0.37 ± 0.02), altered cardiac gene expression, enlarged cardiomyocytes (106.60 ± 4.14 vs 87.94 ± 1.67 μm), an accumulation of immune cells in the heart (10.27 ± 0.30 vs 6.48 ± 0.48 per fov) and higher plasma brain natriuretic peptide levels (0.50 ± 0.12 vs 0.12 ± 0.03 ng/ml) compared with normoglycaemic offspring on a high-fat diet. Blood pressure, urinary albumin, blood glucose and body weight were unaltered between groups on a high-fat diet.Conclusions/interpretationDiabetic pregnancy in rats induces cardiac dysfunction, left ventricular hypertrophy and altered proinflammatory status in adult offspring only after a high-fat diet. A diabetic pregnancy itself was not sufficient to impair myocardial function and gene expression in male offspring later in life. This suggests that a postnatal high-fat diet is important for the development of cardiac dysfunction in rat offspring after diabetic pregnancy. Our data provide evidence that a diabetic pregnancy is a novel cardiac risk factor that becomes relevant when other challenges, such as a high-fat diet, are present.Graphical abstract

Elevated MST1 leads to apoptosis via depletion of YAP1 in cardiomyocytes exposed to high glucose

BackgroundGestational diabetes mellitus is a risk factor for congenital heart defects. The article aimed to investigate the expression and roles of MST1, YAP1, Last1/2 and Survivin in modulating HG-induced cardiomyocyte apoptosis and maternal diabetes-induced heart abnormality.MethodsDiabetes mellitus was induced in rats using streptozotocin. The protein expression and phosphorylation analysis in fetal heart tissue was assessed by western blot and immunohistochemical staining. Hoechst 33342 staining assay was performed to explore H9C2 apoptosis. The gene and protein expression in H9C2 cells was assessed by quantitative PCR and western blot. Knockdown of gene expression was assessed by RNA interference.ResultsOur results revealed that increased MST1 protein levels in the heart tissues of the offspring of diabetic rats in vivo and in H9C2 cardiomyocytes under HG treatment in vitro, respectively. Knockdown and overexpression experiments showed that MST1 played a key role in mediating HG-induced apoptosis in cardiomyocytes. Downregulation of YAP1 was associated with HG-induced, MST1-mediated cardiomyocyte apoptosis. Further study showed that MST1 downregulated the protein level of YAP1 through mediation of YAP1 phosphorylation on Ser127 and Ser397; this process also required LATS1/2 participation. MST1 overexpression increased the phosphorylation levels of LATS1/2, which were also shown to be increased in the heart tissues of diabetic offspring. We also found that YAP1 mediated the expression of Survivin during HG-induced apoptosis, and the Survivin-inhibitor YM155 partially inhibited the role of YAP1 in suppressing apoptosis induced by HG in cardiomyocytes.ConclusionThese findings reveal a regulatory mechanism of MST1/YAP1/Survivin signaling in modulating cardiomyocyte apoptosis in vitro and maternal diabetes-induced congenital heart defects in vivo.

Evaluation of cardiac autonomic functions of non diabetic offsprings of diabetic parents

Occurrence of autonomic imbalance is not very uncommon in diabetic patients and evidences of subclinical autonomic imbalance in their offsprings are also reported. Objective: To study the effect of parental diabetes on cardiac autonomic functions of their non diabetic children. aterials and Methods: The study was conducted in the department of Physiology SSIMS and RC, Davangere, after the approval of the institutional ethical committee, on 100 subjects. 50 non diabetic offsprings of diabetic parents (cases) and 50 non diabetic offsprings of non diabetic parents (controls). The subjects were in the age group of 18-25 years and were selected on the basis of predetermined inclusion exclusion criteria. The study protocol was explained and informed written consent was taken from the subjects. Battery of six conventional cardiac autonomic function tests were done which included, resting HR, HR response to deep breathing, HR response to Valsalva, DBP response to IGHT, BP and HR response to change in posture, BP response to CPT. Statistical analysis was done using Student’s unpaired t test. Result: Our results show decreased parasympathetic activity as indicated by increased basal HR (p Conclusion: Our results show that there is a state of sympathovagal imbalance in the non diabetic offsprings of diabetic parents that can be inferred from an increased sympathetic activity and decreased parasympathetic activity. Keywords: Diabetes mellitus, Autonomic function.

Downregulation of SOX11 in fetal heart tissue, under hyperglycemic environment, mediates cardiomyocytes apoptosis.

Gestational diabetes mellitus is one of the causes of abnormal embryonic heart development, but the mechanism is still poor. This study investigated the regulatory mechanism and role of SOX11 in congenital heart abnormality in a hyperglycemic environment. Immunohistochemistry, Western blotting, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed decreased SOX11 protein and messenger RNA (mRNA) levels in the heart tissue of diabetic offspring compared with the control group. A Sequenom EpiTYPER MassArray showed that methylation sites upstream in SOX11 region 1 were increased in the diabetic group compared with the control group. Luciferase reporter assays and qRT-PCR showed that Dnmt3b overexpression decreased SOX11 promoter activity and its mRNA level, whereas Dnmt3a had little effect on regulating SOX11 expression. Furthermore, we found that Dnmt3L cooperated with Dnmt3b to regulate SOX11 gene expression. Additionally, the function of SOX11 silencing was analyzed by using small interfering RNA-mediated knockdown. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and apoptotic assays showed that SOX11 downregulation inhibited cell viability and induced apoptosis in cardiomyocytes. Overexpression of the SOX11 gene suppressed cardiomyocytes apoptosis after high glucose treatment. We identified a novel epigenetic regulatory mechanism of SOX11 during heart development in a hyperglycemic environment and revealed a distinct role of SOX11 in mediating cardiomyocytes viability and apoptosis.

Study of Prevalence of Metabolic Syndrome in Offspring of Type 2 Diabetic Population

Metabolic Syndrome is defined as Syndrome X is a cluster of co-existing metabolic abnormalities likeobesity, hypertension and dyslipidemia leading to a marked increase inDiabetes mellitus and a five fold increase in CVD thereby imposing a great burden on public health andclinical practice. Metabolic syndrome encompasses a set of conditions of which obesity in particularvisceral obesity, is an important component. Obesity has a positive correlation with incidence and severityof diabetes. Aim of the study is to estimate the prevalence of Metabolic syndrome in offspring of Type 2diabetic population. This study was conducted to estimate the prevalence of metabolic syndrome and itscomponents in offsprings of type 2 diabetes Mellitus population and it includes 100 subjects who werediabetic and presenting to Osmania General Hospital, Hyderabad. Offspring of type II diabetes parentsexhibits higher prevalence of metabolic syndrome . Normoglycemic offspring exhibits higher prevalence ofhypertriglyceridemia indicating precedence of lipid abnormalities to glucose intolerance. Diabetic offspringhave a statistically significant prevalence of metabolic syndrome than the non diabetic offspring.

A comparison of tetrad and triangle test: case study on sweetener products using consumer panels

The development of sensory test methods in the food industry is increasing with the need for product development to meet consumer acceptance. The food industry examine the presence or absence of production differences using appropriate sensory tests is discriminatory tests (different tests). The most popular and widely used different test in the food industry is the triangle test, but it has the disadvantage of developing a tetrad test that is supposed to have a more powerful statistical advantage. The study aimed to compare triangle test with tetrad test on sweetener products. The panelists used in this research were consumer panelists of sweetener product aged 20–65 years old based on medical history catagorised into 3 groups: (1) non-diabetic without diabetic offspring, (2) non-diabetic with diabetic offspring, (3) and diabetic. Total panelists were 100 with duplicate. Different tests were analyzed with the concept of signal detection theory and Thurstonian models (Proportion correct response, Pc, d’, p value, perceptual noise, and test power). The result showed that tetrad test can replace triangle test on sweetener product A and C using non-diabetic panelists without diabetic offspring and combination of all panelists group, as well as sweetener B with combination of all panelist group, because having perceptual noise less than 50% (1.64–32.09%), and is supported by power value that stated strength of tetrad test is more powerful (test power triangle: 0.215–0.994, test power of tetrad test: 0.445–1.000).

Molecular Insight into Odontogenesis in Hyperglycemic Environment: A Systematic Review.

ABSTRACTDiabetes mellitus is an endocrinal disorder affecting worldwide and the disease incidence is rising alarmingly high. The effects of diabetes on tooth development are explored by limited studies and their molecular insights are very rarely studied. This systematic review is aimed to provide the best scientific literature source on the molecular insights into odontogenesis in hyperglycemic environment caused by diabetes mellitus or by maternal diabetes on the offspring. The literature search was conducted on the databases, namely PubMed, PubMed Central, Cochrane, and Scopus. The original studies exploring the alterations in the molecular pathways of odontogenesis in diabetes mellitus were selected. Data were extracted, chosen, and evaluated by two independent researchers. At the end of thorough data search, four articles were eligible for the review. Three articles brought out the molecular pathways involved in the offspring of gestational diabetes through animal models. Fourth article was an in vitro study, which treated the stem cells in hyperglycemic environment and drafted the molecular pathway. The altered molecular pathways in dental epithelial stem cells (DESCs), dental papilla cells (DPCs), and stem cells from apical papilla were studied and empowered with statistical analysis. Thus with this systematic review, we conclude that apurinic/apyrimidinic endonuclease1 downregulation causing deoxyribonucleic acid hypermethylation and Oct4, Nanog gene silencing, activation of toll-like receptor-4/nuclear factor kappa B (TLR4/NF-κB) pathway are involved in suppressing cell proliferation and accelerated apoptosis in DESCs in high glucose environment. DPCs are suppressed from odonto differentiation by activation of TLR4 signaling and resulting inhibition of SMAD1/5/9 phosphorylation in diabetic condition. NF-κB pathway activation causes decreased cell proliferation and enhanced differentiation in apical papilla stem cells in hyperglycemia. Further studies targeting various stages of odontogenesis can reveal more molecular insight.

Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: population based cohort study with 40 years of follow-up

ObjectiveTo evaluate the associations between maternal diabetes diagnosed before or during pregnancy and early onset cardiovascular disease (CVD) in offspring during their first four decades of life.DesignPopulation based cohort study.SettingDanish...

Gestational diabetes mellitus affects odontoblastic differentiation of dental papilla cells via Toll-like receptor 4 signaling in offspring.

Gestational diabetes mellitus (GDM) is an important factor involved in the pathogenesis of organ development in the offspring. Here, we analyzed the effects of GDM on odontoblastic differentiation of dental papilla cells (DPCs) and dentin formation in offspring and investigated their underlying mechanisms. A GDM rat model was induced by intraperitoneal injection of streptozotocin and offspring were collected. The results showed that GDM significantly affected odontoblast differentiation and dentin formation in offspring tooth. GDM activated the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-ĸB) signaling pathway and inhibited SMAD1/5/9 signaling to modulate the odontoblastic differentiation of DPCs in offspring. Inhibition of TLR4 signaling by treated with TAK-242 significantly reverses the suppression of odonto-differentiation of DPCs in diabetic offspring. Taken together, these data indicate GDM activated the offspring DPCs TLR4/NF-ĸB signaling, which suppressed the SMAD1/5/9 phosphorylation and then inhibited odontoblasts differentiation and dentin formation.

Sapropterin reduces coronary artery malformation in offspring of pregestational diabetes mice

Endothelial nitric oxide synthase (eNOS) and oxidative stress are critical to embryonic coronary artery development. Maternal diabetes increases oxidative stress and reduces eNOS activity in the fetal heart. Sapropterin (Kuvan®) is an orally active, synthetic form of tetrahydrobiopterin (BH4) and a co-factor for eNOS with antioxidant properties. The aim of the present study was to examine the effects of sapropterin on fetal coronary artery development during pregestational diabetes in mice. Diabetes was induced by streptozotocin to adult female C57BL/6 mice. Sapropterin (10 mg/kg/day) was orally administered to pregnant mice from E0.5 to E18.5. Fetal hearts were collected at E18.5 for coronary artery morphological analysis. Sapropterin treatment to diabetic dams reduced the incidence of coronary artery malformation in offspring from 50.0% to 20.6%. Decreases in coronary artery luminal diameter, volume and abundance in fetal hearts from diabetic mothers, were prevented by sapropterin treatment. Maternal diabetes reduced epicardial epithelial-to-mesenchymal transition (EMT) and expression of transcription and growth factors critical to coronary artery development including hypoxia-inducible factor 1a (Hif1a), Snail1, Slug, β-catenin, retinaldehyde dehydrogenase 2 (Aldh1a2), basic fibroblast growth factor (bFGF) and vascular endothelial group factor receptor 2 (Vegfr2) in E12.5 hearts. Additionally, eNOS phosphorylation was lower while oxidative stress was higher in E12.5 hearts from maternal diabetes. Notably, these abnormalities were all restored to normal levels after sapropterin treatment. In conclusion, sapropterin treatment increases eNOS activity, lowers oxidative stress and reduces coronary artery malformation in offspring of pregestational diabetes. Sapropterin may have therapeutic potential in preventing coronary artery malformation in maternal diabetes.

Maternal voluntary exercise mitigates oxidative stress and incidence of congenital heart defects in pre-gestational diabetes.

Women with pre‐gestational diabetes have a higher risk of producing children with congenital heart defects (CHDs), caused predominantly by hyperglycemia‐induced oxidative stress. In this study, we evaluated if exercise during pregnancy could mitigate oxidative stress and reduce the incidence of CHDs in the offspring of diabetic mice. Female mice were treated with streptozotocin to induce pre‐gestational diabetes, then mated with healthy males to produce offspring. They were also given access to running wheels 1 week before mating and allowed to exercise voluntarily until E18.5. Heart morphology, gene expression, and oxidative stress were assessed in foetal hearts. Maternal voluntary exercise results in a significantly lower incidence of CHDs from 59.5% to 25%. Additionally, diabetes‐induced defects in coronary artery and capillary morphogenesis were also lower with exercise. Myocardial cell proliferation and epithelial‐mesenchymal transition at E12.5 was significantly lower with pre‐gestational diabetes which was mitigated with maternal exercise. Cardiac gene expression of Notch1, Snail1, Gata4 and Cyclin D1 was significantly higher in the embryos of diabetic mice that exercised compared to the non‐exercised group. Furthermore, maternal exercise produced lower reactive oxygen species (ROS) and oxidative stress in the foetal heart. In conclusion, maternal exercise mitigates ROS and oxidative damage in the foetal heart, and results in a lower incidence of CHDs in the offspring of pre‐gestational diabetes. Exercise may be an effective intervention to compliment clinical management and further minimize CHD risk in mothers with diabetes.

Recent advances in the antepartum management of diabetes.

Gestational and pre-gestational diabetes are frequent problems encountered in obstetrical practice and their complications may influence both the mother (such as hypertension, pre-eclampsia, increased caesarean rates) and the foetus (such as macrosomia, shoulder dystocia, respiratory distress, hypoglycaemia, or childhood obesity and diabetes). Given the important implications for mothers and their offspring, screening and appropriate management of diabetes during pregnancy are essential. This is a review of articles published between 2015 and 2018 on Medline via Ovid that focus on advances in the management of diabetes in pregnancy. Recent data have concentrated predominantly on optimising glycaemic control, which is key for minimising the burden of maternal and foetal complications. Lifestyle changes, notably physical exercise and diet adjustments, appear to have beneficial effects. However, data are inconclusive with respect to which diet and form of exercise provide optimal benefits. Oral glycaemic agents—in particular, metformin—are gaining acceptance as more data indicating their long-term safety for the foetus and newborn emerge. Recent reviews present inconclusive data on the efficacy and safety of insulin analogues. New technologies such as continuous insulin pumps for type 1 diabetes and telemedicine-guided management of diabetes are significantly appreciated by patients and represent promising clinical tools. There are few new data addressing the areas of antenatal foetal surveillance, the timing and need for induction of delivery, and the indications for planned caesarean section birth.