scholarly journals Substantially Altered Expression Profile of Diabetes/Cardiovascular/Cerebrovascular Disease Associated microRNAs in Children Descending from Pregnancy Complicated by Gestational Diabetes Mellitus—One of Several Possible Reasons for an Increased Cardiovascular Risk

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1557 ◽  
Author(s):  
Ilona Hromadnikova ◽  
Katerina Kotlabova ◽  
Lenka Dvorakova ◽  
Ladislav Krofta ◽  
Jan Sirc

Gestational diabetes mellitus (GDM), one of the major pregnancy-related complications, characterized as a transitory form of diabetes induced by insulin resistance accompanied by a low/absent pancreatic beta-cell compensatory adaptation to the increased insulin demand, causes the acute, long-term, and transgenerational health complications. The aim of the study was to assess if alterations in gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases are present in whole peripheral blood of children aged 3–11 years descending from GDM complicated pregnancies. A substantially altered microRNA expression profile was found in children descending from GDM complicated pregnancies. Almost all microRNAs with the exception of miR-92a-3p, miR-155-5p, and miR-210-3p were upregulated. The microRNA expression profile also differed between children after normal and GDM complicated pregnancies in relation to the presence of overweight/obesity, prehypertension/hypertension, and/or valve problems and heart defects. Always, screening based on the combination of microRNAs was superior over using individual microRNAs, since at 10.0% false positive rate it was able to identify a large proportion of children with an aberrant microRNA expression profile (88.14% regardless of clinical findings, 75.41% with normal clinical findings, and 96.49% with abnormal clinical findings). In addition, the higher incidence of valve problems and heart defects was found in children with a prior exposure to GDM. The extensive file of predicted targets of all microRNAs aberrantly expressed in children descending from GDM complicated pregnancies indicates that a large group of these genes is involved in ontologies of diabetes/cardiovascular/cerebrovascular diseases. In general, children with a prior exposure to GDM are at higher risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases, and would benefit from dispensarisation as well as implementation of primary prevention strategies.

2018 ◽  
Vol 27 (1) ◽  
pp. 51-56
Author(s):  
Ferdousi Hossain Poly ◽  
Syeda Afroza ◽  
Hasanur Rahman ◽  
Md Imran Hassan

A congenital heart defect is a heart problem which is present at birth, caused by improper development of the heart during fetal development. In majority of cases there is no known reason for the heart to develop improperly. Some type of congenital heart defects are related to chromosomal abnormality(5-6%), some are to single gene defect(3-5%) or environmental factors(2%). In 85-90% of cases there is no identifiable cause and are generally considered to be caused by multifactorial inheritance. There are some maternal factors which have some role in cardiovascular malformations. These include high maternal age(above 30 years), maternal obesity, consanguinity among the parents, fever during pregnancy, gestational diabetes mellitus, smoking, alcohol consumption, ingestion of any teratogenic drug including homeopathy and herbal medicine. Objective of the study: To evaluate the risk factors associated with congenital heart disease. Methodology: A case control study was conducted at paediatric department of Sir Salimullah Medical College & Mitford Hospital following approval of the protocol from 1st January 2013 to 30th June 2014. Children fulfilling the inclusion criteria-(0-5 year old children of both sexes admitted in paediatric units of Mitford Hospital with any type of congenital heart disease confirmed by echocardiography) were considered as cases. A similar number of age and sex matched children admitted in Mitford Hospital without any cardiac defect were considered as controls. Data were collected by questionnaire. Results: The results show that majority of the cases are male. Maternal age (27.09 ± 4.63) and BMI (24.10 ± 2.28) both are significantly higher in cases than those of controls. Among the cases 31.8% mothers had consanguineous marriage (p=0.001) and 27.1% mothers had history of fever during pregnancy whereas it was present in 9.3% mothers of controls, the difference is significant statistically (p=0.001). Among the cases 34.6% mothers had history of gestational diabetes mellitus and only 18.9% controls had so and the difference is significant statistically (p=0.014). Conclusion: Relatively old age and more weight during pregnancy, consanguinity between parents, fever during pregnancy, history of gestational diabetes mellitus are the main risk factors of congenital heart defects in children J Dhaka Medical College, Vol. 27, No.1, April, 2018, Page 51-56


2020 ◽  
Vol 21 (21) ◽  
pp. 8413
Author(s):  
Ilona Hromadnikova ◽  
Katerina Kotlabova ◽  
Ladislav Krofta ◽  
Jan Sirc

The goal was to assess how a history of any kind of pregnancy-related complication altered expression profile of microRNAs played a role in the pathogenesis of diabetes, cardiovascular and cerebrovascular diseases in the peripheral blood leukocytes of children at the age of 3–11 years. The prior exposure to gestational hypertension, preeclampsia, fetal growth restriction, gestational diabetes mellitus, preterm prelabor rupture of membranes or spontaneous preterm birth causes that a significant proportion of children (57.42% to 90.0% specifically) had a substantially altered microRNA expression profile, which might be the origin of a lifelong cardiovascular risk. A total of 23 out of 29 tested microRNAs were upregulated in children born from such complicated gestation. The occurrence of overweight, obesity, valve problems and heart defects even intensified upregulation of microRNAs already present in children exposed to such pregnancy complications. The occurrence of overweight/obesity (miR-92a-3p, and miR-210-3p) and valve problems or heart defects (miR-342-3p) induced microRNA upregulation in children affected with pregnancy complications. Overall, 42.86% overweight/obese children and 27.36% children with valve problems or heart defects had even higher microRNA levels than children with normal clinical findings after complicated pregnancies. In addition, the microRNA expression profile was also able to differentiate between children descending from normal gestation in relation to the occurrence of overweight and obesity. Screening on the base of the combination of 19 microRNAs identified 70.0% overweight/obese children at 90.0% specificity. In general, children after complicated pregnancies, just as children after normal pregnancies, with abnormal findings are at a higher risk of the onset of cardiovascular complications, and their dispensarization, with the aim to implement primary prevention strategies, would be beneficial.


2019 ◽  
Vol 66 (5) ◽  
pp. 431-441 ◽  
Author(s):  
Huiyan Wang ◽  
Guangtong She ◽  
Wenbai Zhou ◽  
Kezhuo Liu ◽  
Jun Miao ◽  
...  

2020 ◽  
Vol 21 (7) ◽  
pp. 2437 ◽  
Author(s):  
Ilona Hromadnikova ◽  
Katerina Kotlabova ◽  
Lenka Dvorakova ◽  
Ladislav Krofta

Mothers with a history of gestational diabetes mellitus (GDM) have an increased risk of developing diabetes in the future and a lifelong cardiovascular risk. Postpartal expression profile of cardiovascular/cerebrovascular disease associated microRNAs was assessed 3–11 years after the delivery in whole peripheral blood of young and middle-aged mothers with a prior exposure to GDM with the aim to identify a high-risk group of mothers at risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases who would benefit from implementation of early primary prevention strategies and long-term follow-up. The hypothesis of the assessment of cardiovascular risk in women was based on the knowledge that a series of microRNAs play a role in the pathogenesis of diabetes mellitus and cardiovascular/cerebrovascular diseases. Abnormal expression profile of multiple microRNAs was found in women with a prior exposure to GDM (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and-miR-574-3p). Postpartal combined screening of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p showed the highest accuracy for the identification of mothers with a prior exposure to GDM at a higher risk of later development of cardiovascular/cerebrovascular diseases (AUC 0.900, p < 0.001, sensitivity 77.48%, specificity 93.26%, cut off >0.611270413). It was able to identify 77.48% mothers with an increased cardiovascular risk at 10.0% FPR. Any of changes in epigenome (upregulation of miR-16-5p, miR-17-5p, miR-29a-3p, and miR-195-5p) that were induced by GDM-complicated pregnancy are long-acting and may predispose mothers affected with GDM to later development of diabetes mellitus and cardiovascular/cerebrovascular diseases. In addition, novel epigenetic changes (upregulation of serious of microRNAs) appeared in a proportion of women that were exposed to GDM throughout the postpartal life. Likewise, a previous occurrence of either GH, PE, and/or FGR, as well as a previous occurrence of GDM, is associated with the upregulation of miR-1-3p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-29a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p. On the other hand, upregulation of miR-16-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-103a-3p, miR-195-5p, miR-342-3p, and miR-574-3p represents a unique feature of aberrant expression profile of women with a prior exposure to GDM. Screening of particular microRNAs may stratify a high-risk group of mothers with a history of GDM who might benefit from implementation of early primary prevention strategies.


2019 ◽  
Author(s):  
Ya Xiao ◽  
Weihao Chen ◽  
Ruixue Chen ◽  
Anling Luo ◽  
Dayi Chen ◽  
...  

Abstract Background Gestational diabetes mellitus (GDM) is a pathological condition, affecting an increasing number of pregnant women worldwide. Safe and effective treatment for GDM is very important for the public health. In this study, we utilized a high-fat diet induced GDM model to evaluate the effects of LBP on GDM and examined the changes of exosomal microRNA expression profiling to decipher the potential underlying mechanism of LBP.Methods Female C57BL/6J mice were fed a control diet, HFD, or 150 mg/kg LBP- supplemented HFD for 6 weeks before conception and throughout gestation. Oral glucose tolerance test and plasma lipid levels were determined and liver histopathology was assessed. Sequencing was used to define the microRNA expression profiling of plasma exosomes in the three groups of mice and proteins expression levels of the candidate target genes were analyzed.Results LBP significantly relieved glucose intolerance, abnormal plasma lipid levels and pathomorphological changes of liver histopathology in HFD induced GDM mice. Moreover, we found that this effect of LBP was mediated by down-regulation of the increase of 6 miRNAs (miR-93-3p, miR-188-5p, miR-466k, miR-1188-5p, miR-7001-3p and miR-7115-5p) and reversing the increase protein expression of CPT1A, which is the target gene of miR-188-5p.Conclusions Our findings provide novel insights into the biological activities of LBP in the treatment of GDM.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Ya Xiao ◽  
Weihao Chen ◽  
Ruixue Chen ◽  
Anling Luo ◽  
Dayi Chen ◽  
...  

Objective. Gestational diabetes mellitus (GDM) is a pathological condition, affecting an increasing number of pregnant women worldwide. Safe and effective treatment for GDM is very important for the public health. In this study, we utilized a high-fat diet-induced GDM model to evaluate the effects of LBP on GDM and examined the changes of exosomal microRNA expression profiling to decipher the potential underlying mechanism of LBP. Methods. Female C57BL/6J mice were fed a control diet, HFD, or 150 mg/kg LBP-supplemented HFD for 6 weeks before conception and throughout gestation. Oral glucose tolerance test and plasma lipid levels were determined, and liver histopathology was assessed. Sequencing was used to define the microRNA expression profiling of plasma exosomes in the three groups of mice, and protein expression levels of the candidate target genes were analyzed. Results. LBP significantly relieved glucose intolerance, abnormal plasma lipid levels, and pathomorphological changes of liver histopathology in HFD-induced GDM mice. Moreover, we found that this effect of LBP was mediated by downregulation of the increase of 6 miRNAs (miR-93-3p, miR-188-5p, miR-466k, miR-1188-5p, miR-7001-3p, and miR-7115-5p) and reversing the increase of the protein expression of CPT1A, which is the target gene of miR-188-5p. Conclusions. Our findings provide novel insights into the biological activities of LBP in the treatment of GDM.


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