HUMAN MITOCHONDRIAL tRNA MUTATIONS IN MATERNALLY INHERITED DEAFNESS

Mutations in mitochondrial tRNA genes have been shown to be associated with maternally inherited syn-dromic and non-syndromic deafness. Among those, mutations such as tRNALeu(UUR) 3243A>G associated with syndromic deafness are often present in heteroplasmy, and the non-syndromic deafness-associated tRNA mu-tations including tRNASer(UCN) 7445A>G are often in homoplasmy or in high levels of heteroplasmy. These tRNA mutations are the primary factors underlying the development of hearing loss. However, other tRNA mutations such as tRNAThr 15927G>A and tRNASer(UCN) 7444G>A are insufficient to produce a deafness phe-notype, but always act in synergy with the primary mitochondrial DNA mutations, and can modulate their phenotypic manifestation. These tRNA mutations may alter the structure and function of the corresponding mitochondrial tRNAs and cause failures in tRNAs metabolism. Thereby, the impairment of mitochondrial protein synthesis and subsequent defects in respiration caused by these tRNA mutations, results in mitochon-drial dysfunctions and eventually leads to the development of hearing loss. Here, we summarized the deaf-ness-associated mitochondrial tRNA mutations and discussed the pathophysiology of these mitochondrial tRNA mutations, and we hope these data will provide a foundation for the early diagnosis, management, and treatment of maternally inherited deafness.

Heteroplasmy Level of the Mitochondrial tRNA^(Leu(UUR)) A3243G Mutation in a Chinese Family Is Positively Associated with Earlier Age-of-onset and Increasing Severity of Diabetes

Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Methods Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations. Results Family members on the maternal side all harbored the tRNA^Lcu（UUR） A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980（P=0.02）. Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found. Conclusions The main cause of diabetes in this pedigree is the tRNA^Lcu（UUR） A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNA^Lcu（UUR） A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.

Human embryonic stem cells as an in vitro model for studying developmental origins of type 2 diabetes

The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of offspring.Since the theory emerged more than 30 years ago,many epidemiological and animal studies have confirmed that in utero exposure to environmental insults,including hyperglycemia and chemicals,increased the risk of developing noncommunicable diseases(NCDs).These NCDs include metabolic syndrome,type 2 diabetes,and complications such as diabetic cardiomyopathy.Studying the effects of different environmental insults on early embryo development would aid in understanding the underlying mechanisms by which these insults promote NCD development.Embryonic stem cells(ESCs)have also been utilized by researchers to study the DOHaD.ESCs have pluripotent characteristics and can be differentiated into almost every cell lineage;therefore,they are excellent in vitro models for studying early developmental events.More importantly,human ESCs(hESCs)are the best alternative to human embryos for research because of ethical concerns.In this review,we will discuss different maternal conditions associated with DOHaD,focusing on the complications of maternal diabetes.Next,we will review the differentiation protocols developed to generate different cell lineages from hESCs.Additionally,we will review how hESCs are utilized as a model for research into the DOHaD.The effects of environmental insults on hESC differentiation and the possible involvement of epigenetic regulation will be discussed.

Maternal low protein diet and fetal programming of lean type 2 diabetes

Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood.Metabolic diseases have been primarily attributed to impaired maternal nutrition during pregnancy,and impaired nutrition has been an immense issue across the globe.In recent years,type 2 diabetes(T2D)has reached epidemic proportion and is a severe public health problem in many countries.Although plenty of research has already been conducted to tackle T2D which is associated with obesity,little is known regarding the etiology and pathophysiology of lean T2D,a variant of T2D.Recent studies have focused on the effects of epigenetic variation on the contribution of in utero origins of lean T2D,although other mechanisms might also contribute to the pathology.Observational studies in humans and experiments in animals strongly suggest an association between maternal low protein diet and lean T2D phenotype.In addition,clear sex-specific disease prevalence was observed in different studies.Consequently,more research is essential for the understanding of the etiology and pathophysiology of lean T2D,which might help to develop better disease prevention and treatment strategies.This review examines the role of protein insufficiency in the maternal diet as the central driver of the developmental programming of lean T2D.

Parental transmission of type 2 diabetes mellitus in a highly endogamous population

AIM: To determine the parental transmission of diabetes mellitus (DM) and evaluate its influence on the clinical characteristics. METHODS: This was a cross sectional study. The survey was carried out in urban and semi-urban primary health care centers. Of the 2400 registered with diagnosed diabetes, 1980 agreed and gave their consent to take part in this study, thus giving a response rate of 82.5%. Face to face interviews were conducted using a structured questionnaire followed by laboratory tests. DM was defined according to the World Health Organization expert group. A trained nurse performedphysical examinations and measurements. RESULTS: Of the study population, 72.9% reported a family history of DM. Family history of DM was significantly higher in females (54.2%; P = 0.04) and in the age group below 30 years (24%; P < 0.001). The prevalence of diabetes was higher among patients with a diabetic mother (25.4% vs 22.1%) and maternal aunts/uncles (31.2% vs 22.2%) compared to patients with a diabetic father and paternal aunts/ uncles. Family history of DM was higher in patients of consanguineous parents (38.5%) than those of non-consanguineous parents (30.2%). The development of type 2 diabetes mellitus (T2DM) complications was higher in patients with either a paternal or maternal history of DM than in those without. No significant difference was observed in the metabolic characteristics of patients with/without family history of DM except for hypertension. Complications were higher in diabetic patients with a family history of DM. CONCLUSION: The present study found a significant maternal effect in transmission of T2DM. Family history is associated with the increased incidence of diabetes.

Consequences of gestational and pregestational diabetes on placental function and birth weight

Maternal diabetes constitutes an unfavorable environment for embryonic and fetoplacental development. Despite current treatments, pregnant women with pregestational diabetes are at increased risk for congenital malformations, materno-fetal complications, placental abnormalities and intrauterine malprogramming. The complications during pregnancy concern the mother (gravidic hypertension and/or preeclampsia, cesarean section) and the fetus (macrosomia or intrauterine growth restriction, shoulder dystocia, hypoglycemia and respiratory distress). The fetoplacental impairment and intrauterine programming of diseases in the offspring's later life induced by gestational diabetes are similar to those induced by type 1 and type 2 diabetes mellitus. Despite the existence of several developmental and morphological differences in the placenta from rodents and women, there are similarities in the alterations induced by maternal diabetes in the placenta from diabetic patients and diabetic experimental models. From both human and rodent diabetic experimentalmodels, it has been suggested that the placenta is a compromised target that largely suffers the impact of maternal diabetes. Depending on the maternal metabolic and proin ammatory derangements, macrosomia is explained by an excessive availability of nutrients and an increase in fetal insulin release, a phenotype related to the programming of glucose intolerance. The degree of fetal damage and placental dysfunction and the availability and utilisation of fetal substrates can lead to the induction of macrosomia or intrauterine growth restriction. In maternal diabetes, both the maternal environment and the genetic background are important in the complex and multifactorial processes that induce damage to the embryo, the placenta, the fetus and the offspring. Nevertheless, further research is needed to better understand the mechanisms that govern the early embryo development, the induction of congenital anomalies and fetal overgrowth in maternal diabetes.

Some of the experimental and clinical aspects of the effects of the maternal diabetes on developing hippocampus

Diabetes mellitus during pregnancy is associated with an increased risk of multiple congenital anomalies in progeny.There are sufficient evidence suggesting that the children of diabetic women exhibit intellectual and behavioral abnormalities accompanied by modification of hippocampus structure and function.Although,the exact mechanism by which maternal diabetes affects the developing hippocampus remains to be defined.Multiple biological alterations,including hyperglycemia,hyperinsulinemia,oxidative stress,hypoxia,and iron deficiency occur in pregnancies with diabetes and affect the development of central nervous system(CNS) of the fetus.The conclusion from several studies is that disturbance in glucose and insulin homeostasis in mothers and infants are major teratogenic factor in the development of CNS.Insulin and Insulin-like growth factor-1(IGF-1) are two key regulators of CNS function and development.Insulin and IGF-1 receptors(IR and IGF1 R,respectively) are distributed in a highly specific pattern with the high density in some brain regions such as hippocampus.Recent researches have clearly established that maternal diabetes disrupts the regulation of both IR and IGF1 R in the hippocampus of rat newborn.Dissecting out the mechanisms responsible for maternal diabetes-related changes in the development of hippocampus is helping to prevent from impaired cognitive and memory functions in offspring.

Frontiers in research on maternal diabetes-induced neural tube defects:Past,present and future

Diabetes mellitus rightly regarded as a silent-epidemic is continually on the rise and estimated to have a global prevalence of 6.4 % as of 2010.Diabetes during pregnancy is a well known risk factor for congenital anomalies in various organ systems that contribute to neonatal mortality,including cardiovascular,gastrointestinal,genitourinary and neurological systems,among which the neural tube defects are frequently reported.Over the last two to three decades,several groups around the world have focussed on identifying the molecular cues and cellular changes resulting in altered gene expression and the morphological defects and in diabetic pregnancy.In recent years,the focus has gradually shifted to looking at pre-programmed changes and activation of epigenetic mechanisms that cause altered gene expression.While several theories such as oxidative stress,hypoxia,and apoptosis triggered due to hyperglycemic conditions have been proposed and proven for being the cause for these defects,the exact mechanism or the link between how high glucose can alter gene expression/transcriptome and activate epigenetic mechanisms is largely unknown.Although preconceptual control of diabetes,(i.e.,managing glu-cose levels during pregnancy),and in utero therapies has been proposed as an effective solution for managing diabetes during pregnancy,the impact that a fluctuating glycemic index can have on foetal development has not been evaluated in detail.A tight glycemic control started before pregnancy has shown to reduce the incidence of congenital abnormalities in diabetic mothers.On the other hand,a tight glycemic control after organogenesis and embryogenesis have begun may prove insufficient to prevent or reverse the onset of congenital defects.The importance of determining the extent to which glycemic levels in diabetic mothers should be regulated is critical as foetal hypoglycemia has also been shown to be teratogenic.Finally,the major question remaining is if this whole issue is negligible and not worthy of investigation as the efficient management of diabetes during pregnancy is well in place in many countries.

Association of maternal obesity and gestational diabetes mellitus with overweight/obesity and fatty liver risk in offspring

BACKGROUND Childhood obesity and fatty liver are associated with adverse outcomes such as diabetes,metabolic syndrome,and cardiovascular diseases in adulthood.It is very important to identify relevant risk factors and intervene as early as possible.At present,the relationship between maternal and offspring metabolic factors is conflicting.AIM To estimate the association of maternal obesity and gestational diabetes mellitus(GDM)with overweight/obesity and fatty liver risk in offspring at 8 years of age.METHODS The prospective study included mothers who all had a 75-g oral glucose tolerance test at 24-28 wk of gestation and whose offspring completed follow-up at 8 years of age.Offspring birth weight,sex,height,weight,and body mass index(BMI)were measured and calculated.FibroScan-502 examination with an M probe(Echosens,Paris,France)was prospectively conducted in offspring aged 8 years from the Shanghai Prenatal Cohort Study.RESULTS A total of 430 mother-child pairs were included in the analysis.A total of 62(14.2%)mothers were classified as obese,and 48(11.1%)were classified as having GDM.The mean age of the offspring at follow-up was 8 years old.Thirty-seven(8.6%)offspring were overweight,14(3.3%)had obesity,and 60(14.0%)had fatty liver.The prevalence of overweight,obesity and fatty liver in offspring increased significantly across maternal BMI quartiles(all P<0.05).Among offspring of mothers with GDM,12(25.0%)were overweight,4(8.3%)were obese,and 12(25.0%)had fatty liver vs.25(6.5%),10(2.6%)and 48(12.6%),respectively,for offspring of mothers without GDM(all P<0.05).In multiple logistic regression,after adjustment for variables,the OR for fatty liver in offspring was 8.26(95%CI:2.38-28.75)for maternal obesity and GDM.CONCLUSION This study showed that maternal obesity can increase the odds of overweight/obesity and fatty liver in offspring,and GDM status also increases the odds of overweight/obesity in offspring.Weight management and glycemic control before and during pregnancy need to be highlighted in primary prevention of pediatric obesity and fatty liver.

Probiotics for preventing gestational diabetes in overweight or obese pregnant women:A review

Probiotics are live microorganisms that,when administered in adequate amounts,confer a health benefit to the host.Specific probiotics or probiotic foods can be used to reduce the risk of diseases associated with aberrant gut microbiota composition.The incidence of gestational diabetes mellitus(GDM)has increased annually with the proportion of overweight and obese people.Overweight or obese pregnant women are at high risk of GDM and have obvious changes in gut microbiota compared with normal-weight pregnant women.Specific probiotics or probiotic foods may alter gut microbiota in overweight or obese pregnant women and inhibit the expression of inflammatory factors,consequently resulting in weight loss and reduced insulin resistance.This review discusses the mechanism of probiotics on GDM,as well as the dose,method and duration of probiotics use,and summarizes current evidence on probiotics in improving glucose metabolism and other maternal and infant outcomes in overweight/obese pregnant women.

Study of factors influencing susceptibility and age at onset of type 1 diabetes: A review of data from Continental Italy and Sardinia

AIM:To investigate the role of protein tyrosin phosphatase 22(PTPN22),maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes(T1D)in Continental Italy and Sardinian populations.METHODS:Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia.PTPN22 genotype was determined by DNA analysis.Maternal age at conception and age at onset of disease were obtained from clinical records.χ2 test of independence,student t test for differences between means and odds ratio analysis were carried out by SPSS programs.Three way contingency table analysis was carried out according to Sokal and Rohlf.RESULTS:The pattern of association between PTPN22and T1D is similar in Continental Italy and Sardinia:the proportion of*T allele carriers is 13.6%in T1D vs6.7%in controls in Continental Italy while in Sardinia is 7.3%in T1D vs 4.4%in controls.The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy:the proportion of newborn from mother aging more than 32 years is89.3%in T1D vs 32.7%in consecutive newborn in Sardinia(P<10-6)while in Continental Italy is 32.2%in T1D vs 19.1%in consecutive newborns(P=0.005).This points to an important role of ethnicity.A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia.PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia.Maternal age does not influence significantly age at onset in Italy(8.2 years in T1D infants from mothers aging32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years:P=0.824)while in Sardinia a border line effect is observed(5.75 years in T1D infants from mothers aging 32 years or less vs7.54 years in T1D infants from mothers aging more than 32 years:P=0.062).No effect of sex on age at onset is observed in Continental Italy while in Sardinia female show a lower age at onset of T1D as compared to males(8.07 years in males vs 6.3 years in females:P=0.002).CONCLUSION:The present data confirm the importance of ethnicity on susceptibility and on the age at onset of T1D.

Evaluation of Pregnancy Outcomes among Women with Pregnancies Complicated by Diabetes Mellitus in Abakaliki, South-East, Nigeria

Background: Pregnancies complicated by diabetes are associated with significant increase in maternal and perinatal morbidity and mortality. The management of diabetes in pregnancy is a great challenge in a low resource setting because of limited resources and facilities to care for these women. Aim: To determine the maternal and perinatal outcomes of diabetic pregnant women managed at Alex Ekwueme Federal University Teaching Hospital Abakaliki, Southeast, Nigeria. Materials and methods: This was a 7-year retrospective case-control study that compared pregnancy outcomes among women with pregnancies complicated by diabetes and those without diabetes managed at Alex Ekwueme Federal University Teaching Hospital, Abakalikibetween January 1st, 2012 and December 31st, 2018. The statistical analysis was done using SPSS version 22. Results: The incidence of diabetes in pregnancy in this study was 6.6 per 1000 deliveries. Of 126 women in diabetic arm of the study, 81 were diagnosed during pregnancy and 45 were known diabetic prior to conception. Over two-thirds of 126 women with pregnancy complicated by diabetes achieved good blood glucose control during pregnancy. Both groups differ in their mean BMI and women with diabetes in pregnancy were more likely to be obese compared with control (diabetic;30.1 ± 2.5 versus control;23.4 ± 2.1, P < 0.0001). Pregnant women with diabetes were more likely to be delivered by cesarean section when compared with non-diabetic women (86 versus 23, OR = 9.6, 95% CI: 5.35 - 17.32, P < 0.0001). Similarly, the incidence of polyhydramnious was higher in paturients with diabetes when compared with the control groups (26 versus 13, OR = 2.2, 95%CI: 1.10 - 4.63, P = 0.02). There were no differences between both study groups with regards to other maternal outcomes. The incidence of fetal macrosomia, neonatal hypoglycemia and neonatal respiratory distress syndrome were significantly higher among women whose pregnancies were complicated by diabetes when compared with the control [Diabetics;fetal macrosomia (62.7%), neonatal hypoglycemia (44.4%) and neonatal respiratory distress syndrome (22.2%) versus Control;fetal macrosomia (34.1%), neonatal hypoglycemia (7.9%) and neonatal respiratory distress syndrome (5.6%) respectively]. Conclusion: Women with pregnancies complicated by diabetes had a higher incidence of adverse maternal and perinatal outcomes. Clinical recognition of diabetes in pregnancy is important because institution of therapy, and antepartum fetal surveillance can reduce the maternal and perinatal morbidity and mortality associated with the condition.

Maternal Vitamin D Deficiency and Risk of Development of Gestational Diabetes Mellitus: A Scoping Review

Background: Maternal vitamin D status is a critical determinant during pregnancy, because it plays an important role in the body not only in calcium homeostasis and bone remodeling, but also in the glucose metabolism. Vitamin D deficiency is associated with adverse pregnancy outcomes including gestational diabetes mellitus. Objective: To review evidence on the association between maternal vitamin D deficiency and incidence of gestational diabetes mellitus (GDM). Methods: PRISMA for scoping review guideline and scoping review guidelines of Arksey & O’Malley (2005) was followed in methodological process. A comprehensive search strategy was carried out across the Google Scholar and PubMed from January 2012 to December 2022, using the search terms of “gestational diabetes mellitus/pregnancy outcomes” combined with “vitamin D”, “cholecalciferol” or “25-hydroxyvitamin D” and/or “deficiency”. Articles were screened at the title and the abstract level and at full text by three co-investigators of the study independently with a fourth reviewer resolving discrepancies. Research studies published only in English language were selected. Research using pregnant mothers with multiple pregnancy and chronic diseases was excluded. Results: After screening 134 titles and abstracts, finally 55 original research articles were selected. It involved 48 observational studies and 7 Randomized Control Trials (RCT). Only 30 research articles had found an association between maternal vitamin D deficiency and GDM. Conclusion: As results of previous studies are mixed and inconclusive, further research including more RCTs is needed to clarify the exact mechanism of vitamin D on glucose metabolism during pregnancy.

Effect of insulin in combined with Chinese medicine formulae on the serum Mg2+ and visfatin levels, maternal and infant outcome in pregnant women with gestational diabetes mellitus

Objective:To explore the effect of insulin in combined with Chinese medicine formulae on the serum Mg2+ and visfatin levels, maternal and infant outcome in pregnant women with gestational diabetes mellitus (GDM).Methods:A total of 108 pregnant women with GDM who were admitted in our hospital were included in the study and randomized into the observation group (n=55) and the control group (n=53). The patients in the two groups were given diet control, exercise therapy, and subcutaneous injection of insulin. On this basis, the patients in the observation group were given self-made Chinese medicine formulae, continuously for 2 weeks. The blood sugar level, and serum Mg2+ and visfatin (VF) levels before treatment and before delivery in the two groups were detected. The maternal and infant outcome in the two groups was evaluated.Results:The serum HbA1c, FPG, 1 h PBG, 2 h PBG, and VF levels before delivery in the two groups were significantly reduced when compared with before treatment (P<0.05), while the serum Mg2+ level was significantly elevated when compared with before treatment (P<0.05). The improvement of the above indicators before delivery in the observation group was more significant when compared with the control group (P<0.05). The occurrence rate of cesarean section, premature delivery, gestational hypertension, fetal distress, and macrosomia in the observation group was significantly lower than that in the control group (P<0.05).Conclusions:Insulin in combined with self-made Chinese medicine formulae can effectively control the blood sugar level in pregnant women with GDM, and improve the maternal and infant outcome.

Perinatal Morbidity and Mortality Associated with Maternal Diabetes in the Neonatology Department of the Issaka Gazoby Maternity Hospital, Niamey, Niger

Introduction: The association of diabetes and pregnancy is associated with a significantly higher risk of perinatal morbidity and mortality. The aim of this study was to investigate the perinatal morbidity and mortality associated with maternal diabetes at the Issaka Gazoby Maternity Hospital in Niamey. Methodology: This was a prospective case-control study conducted from April to September 2021 at the Issaka Gazoby Maternity Hospital in Niamey. “Cases” were neonates born to diabetic mothers, and “controls” were neonates born to non-diabetic mothers. The main dependent variable was the occurrence of perinatal complications. Analysis was performed using Epi info software 7.2.1. Pearson’s Chi2 test or Fisher’s exact test were used (p Results: Of the 2,225 admissions during the study period, 31 newborns were born to diabetic mothers (1.4%). Diabetic mothers were 2.8 times more likely to have a history of abortion (67.7% vs. 28.6%;OR = 2.82;p = 0.001). Similarly, a history of macrosomia was found in 29.0% of diabetic mothers versus 9.5% of controls (OR = 2.15;p = 0.01). Macrosomia was also more common in newborns of diabetic mothers (38.7% vs. 9.5%;OR = 2.63;p Conclusion: The risks of ante- and perinatal complications such as abortion, fetal macrosomia and stillbirth, as well as neonatal pathological events (macrosomia and malformations) were greater in newborns of diabetic mothers.

High Prevalence of Gestational Diabetes Mellitus in Beijing： Effect of Maternal Birth Weight and Other Risk Factors

Background： Gestational diabetes mellitus （GDM） is associated with both short- and long-term adverse health consequences for both the mother and her offspring. The aim was to study the prevalence and risk factors for GDM in Beijing. Methods： The study population consisted of 15,194 pregnant women attending prenatal care in 15 hospitals in Beijing, who delivered between June 20, 2013, and November 30, 2013, after 28 weeks of gestation. The participants were selected by cluster sampling from the 15 hospitals identified through random systematic sampling based on the number of deliveries in 2012. A questionnaire was designed to collect information. Results： A total of 2987 （19.7%） women were diagnosed with GDM and 208 （1.4%） had diabetes in pregnancy （DIP）, Age （OR： 1.053, 95% CI： 1.033-1.074, P 〈 0.01）, family history of diabetes mellitus （OR： 1.481, 95% CI：1.254 1.748, P 〈 0.01）, prepregnancy body mass index （BMI） （OR： 1.481, 95% CI：1.254 1.748, P 〈 0.01）, BMI gain before 24 weeks （OR： 1.126, 95% CI： 1.075-1.800, P 〈 0.01 ）, maternal birth weight （P 〈 0.01）, and fasting plasma glucose at the first prenatal visit （P 〈 0.01） were identified as risk factors for GDM. In women with birth weight 〈3000 g, GDM rate was significantly higher. Conclusions： One out of every five pregnant women in Beijing either had GDM or DIP and this constitutes a huge health burden for health services. Prepregnancy BMI and weight gain before 24^th week are important modifiable risk factors for GDM. Ensuring birth weight above 3000 g may help reduce risk for future GDM among female offsprings.

Trimester-specific urinary metabolome alterations associated with gestational diabetes mellitus:A study in different pregnancy stages

Gestational diabetes mellitus(GDM),a frequently-occurring disease during pregnancy,may cause some adverse healthy outcome of both mother and offspring.However,the knowledge about metabolite alterations during the pathogenesis and development process is limited.Here,a large longitudinal nontargeted metabolomics study of 195 pregnant women(64 women with subsequently developed GDM and131 healthy controls)was conducted.Each participant provided urine samples at three timepoints during early,middle and late pregnancy,respectively.The metabolic profiles of 585 urine samples(195×3)were measured by using ultra-high performance liquid chromatography coupled with Orbitrap high-resolution mass spectrometry.Among the 56 identified metabolites,the levels of eight metabolites increased and three ones decreased in the first trimester,the concentration of one metabolite increased and those of 20 decreased in the second trimester,as well as the levels of five metabolites increased and two decreased in the third trimester.After false discovery rate correction,the levels of valine and 5-acetamidovalerate in GDM group significantly increased in the first trimester,the levels of 1-methylguanine and 1,3-dihydro-(2 H)-indol-2-one significantly decreased in the second trimester and three metabolites(threonine,OH-octanedioyl-carnitine and pimelylcarnitine)increased and N-acetyltryptophan decreased in the third trimester,respectively.Six metabolites,such as pantothenic acid and threonine,had significant interaction effects between gestational stage(different trimester)and group(GDM or control).The differential metabolites were involved in“tryptophan metabolism”,“purine metabolism”,“valine,leucine and isoleucine degradation”and other pathways.The findings may provide insights into further pathogenesis study of GDM.

Maternal Obesity,Gestational Diabetes,and Fetal Macrosomia:An Incidental or a Mechanistic Relationship?

Gestational diabetes mellitus(GDM)is a well-established risk factor for fetal macrosomia.A significant number of patients with GDM also suffer from obesity,a factor associated with fetal macrosomia.An important question is whether GDM is independently associated with fetal macrosomia,or whether this relationship is merely the result of maternal obesity acting as a confounder.In this review of the literature,we attempt to further elucidate the relationship between GDM,maternal obesity,and fetal macrosomia.

Effect of maternal pregestational diabetes mellitus on congenital heart diseases

Background The increasing population of diabetes mellitus in adolescent girls and women of childbearing age contributes to a large number of pregnancies with maternal pregestational diabetes mellitus.Congenital heart diseases are a common adverse outcome in mothers with pregestational diabetes mellitus.However,there is little systematic information between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring.Data sources Literature selection was performed in PubMed.One hundred and seven papers were cited in our review,includ-ing 36 clinical studies,26 experimental studies,31 reviews,eight meta-analysis articles,and six of other types.Results Maternal pregestational diabetes mellitus poses a high risk of congenital heart diseases in the offspring and causes variety of phenotypes of congenital heart diseases.Factors such as persistent maternal hyperglycemia,oxidative stress,polymorphism of uncoupling protein 2,polymorphism of adiponectin gene,Notch 1 pathway,Nkx2.5 disorders,dysregula-tion of the hypoxia-inducible factor 1,and viral etiologies are associated with the occurrence of congenital heart diseases in the offspring of mothers with pregestational diabetes mellitus.Treatment options including blood sugar-reducing,anti-oxidative stress drug supplements and exercise can help to prevent maternal pregestational diabetes mellitus from inducing congenital heart diseases.Conclusions Our review contributes to a better understanding of the association between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring and to a profound thought of the mechanism,preventive and therapeutic measurements of congenital heart diseases caused by maternal pregestational diabetes mellitus.