Genetics of Gestational Diabetes Mellitus - The Indian Perspective.
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ABSTRACT:
SUBMITTER: Madhu SV
PROVIDER: S-EPMC9302408 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite years of investigation, very little is known about the genetic predisposition for gestational diabetes mellitus (GDM). However, the advent of genome-wide association and identification of loci contributing to susceptibility to type 2 diabetes mellitus has opened a small window into the genetics of GDM. More importantly, the study of the genetics of GDM has not only illuminated potential new biology underlying diabetes in pregnancy, but has also provided insights into fetal outcomes. Here, I review some of the insights into GDM and fetal outcomes gained through the study of both rare and common genetic variation. I also discuss whether recent testing of type 2 diabetes mellitus susceptibility loci in GDM case-control samples changes views of whether GDM is a distinct form of diabetes. Finally, I examine how the study of susceptibility loci can be used to influence clinical care, one of the great promises of the new era of human genome analysis.
| S-EPMC3092103 | biostudies-literature
Project description:Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy, with a prevalence that has increased significantly in the last decade, coming to affect 12-18% of all pregnancies. GDM is believed to be the result of a combination of genetic, epigenetic and environmental factors. Following the identification of susceptibility genes for type 2 diabetes by means of genome-wide association studies, an association has also been demonstrated between some type 2 diabetes susceptibility genes and GDM, suggesting a partial similarity of the genetic architecture behind the two forms of diabetes. More recent genome-wide association studies, focusing on maternal metabolism during pregnancy, have demonstrated an overlap in the genes associated with metabolic traits in gravid and non-gravid populations, as well as in genes apparently unique to pregnancy. Epigenetic changes-such as DNA methylation, histone modifications and microRNA gene silencing-have also been identified in GDM patients. Metabolomics has been used to profile the metabolic state of women during pregnancy, based on the measurement of numerous low-molecular-weight metabolites. Measuring amino acids and conventional metabolites has revealed changes in pregnant women with a higher insulin resistance and high blood glucose levels that resemble the changes seen in non-gravid, insulin-resistant populations. This would suggest similarities in the metabolic profiles typical of insulin resistance and hyperglycemia whether individuals are pregnant or not. Future studies combining data obtained using multiple technologies will enable an integrated systems biology approach to maternal metabolism during a pregnancy complicated by GDM. This review highlights the recent knowledge on the impact of genetics and epigenetics in the pathophysiology of GDM and the maternal and fetal complications associated with this pathology condition.
| S-EPMC7736606 | biostudies-literature
Project description:We compared the plasma miRNA expression profiles between healthy and GDM women by microarray analysis.Our study offers new insights into circulating biomarkers of GDM and thus provides a valuable resource for future investigations.
2017-04-22 | GSE98043 | GEO
Project description:Background Non-communicable diseases such as cardiovascular diseases, respiratory diseases and diabetes contribute to the majority of deaths in India. Public health programmes on non-communicable diseases (NCD) prevention primarily target the behavioural risk factors of the population. Hereditary is known as a risk factor for most NCDs, specifically, type 2 diabetes mellitus (T2DM), and hence, understanding of the genetic markers of T2DM may facilitate prevention, early case detection and management. Main body We reviewed the studies that explored marker–trait association with type 2 diabetes mellitus globally, with emphasis on India. Globally, single nucleotide polymorphisms (SNPs) rs7903146 of Transcription Factor 7-like 2 (TCF7L2) gene was common, though there were alleles that were unique to specific populations. Within India, the state-wise data were also taken to foresee the distribution of risk/susceptible alleles. The findings from India showcased the common and unique alleles for each region. Conclusion Exploring the known and unknown genetic determinants might assist in risk prediction before the onset of behavioural risk factors and deploy prevention measures. Most studies were conducted in non-representative groups with inherent limitations such as smaller sample size or looking into only specific marker–trait associations. Genome-wide association studies using data from extensive prospective studies are required in highly prevalent regions worldwide. Further research is required to understand the singular effect and the interaction of genes in predicting diabetes mellitus and other comorbidities.
| S-EPMC9438889 | biostudies-literature
Project description:ObjectiveSince Asians are particularly vulnerable to the risk of gestational diabetes mellitus (GDM), the lifecourse health implications of which are far beyond pregnancy, we aimed to summarize the literature to understand the research gaps on current GDM research among Asians.MethodsWe systematically searched the articles in PubMed, Web of Science, Embase, and Scopus by 30 June 2021 with keywords applied on three topics, namely "GDM prevalence in Asians", "GDM and maternal health outcomes in Asians", and "GDM and offspring health outcomes in Asians".ResultsWe observed that Asian women (natives and immigrants) are at the highest risk of developing GDM and subsequent progression to type 2 diabetes among all populations. Children born to GDM-complicated pregnancies had a higher risk of macrosomia and congenital anomalies (i.e. heart, kidney and urinary tract) at birth and greater adiposity later in life.ConclusionThis review summarized various determinants underlying the conversion between GDM and long-term health outcomes in Asian women, and it might shed light on efforts to prevent GDM and improve the lifecourse health in Asians from a public health perspective.Systematic review registrationProspero, CRD42021286075.
| S-EPMC9245567 | biostudies-literature
Project description:BACKGROUND:Numerous genes have been reported in relation with gestational diabetes mellitus (GDM), but the findings were not consistently replicated across populations, or there have been no detailed studies on them. Previous literatures suggested that, out of all angiotensin converting enzyme (ACE) gene polymorphisms, only ACE insertion/deletion (I/D) gene polymorphism has a strong association with GDM in Asian Indian women. AIM:This study was devoted to evaluate the association of four single nucleotide polymorphisms (SNPs) ACE A240T, C1237T, G2350A and I/D with GDM and Type 2 diabetes mellitus. MATERIALS AND METHODS:This study recruited 105 GDM cases, 119 Type 2 diabetes mellitus subjects and 120 controls. PCR-RFLP was used for identifying genotypes of ACE A240T, C1237T and G2350A and PCR was performed in the case of ACE I/D. RESULTS:Significant associations of ACE SNP's, C1237T, and G2350A with GDM were observed. Haplotype analysis revealed the remarkably significant evidence of association with SNP combination ACE A240T, C1237T, G2350A, and I/D with GDM patients (P = 0.024). Individuals possessing haplotype "TTAI" (frequency 30% in GDM and 0 in controls) derived from these SNPs had 185 fold increased risk of developing GDM (95% of confidence interval: 11.13-3102.15), which was highest when compared with other 15 haplotypes. CONCLUSION:Shorter-range haplotypes were also significant, but the only consistently associated alleles were found to be in ACE C1237T, G2350A, and I/D. These results suggested that the variant in close proximity to ACE C1237T, G2350A and/or I/D modulates susceptibility to GDM and noninsulin dependent diabetes mellitus in Indian women.
| S-EPMC4765272 | biostudies-literature
Project description:Circular RNA can regulate blood glucose levels by targeting mRNA expression, but the role of circRNA in GDM is still unknown. Therefore, a joint microarray analysis of circRNAs and their targeting mRNAs using the peripheral blood of GDM patients and healthy pregnant women was carried out for the first time. In our study, high-throughput microarray sequencing technique was used to analyze the expression profile of circRNA and transcripts mRNA in the peripheral blood of GDM patients, in order to comprehensively evaluate the role of circRNAs targets and their parents genes in the signal pathways related to the pathogenesis of GDM. Some of the discovered circRNAs and their linear transcript mRNAs related to T cell receptor signaling pathway were further verified in larger samples by droplet digital PCR(ddPCR) and quantitative real-time PCR(qRT-PCR), respectively. The verification results confirmed the initial microarray results.
2021-08-27 | GSE182737 | GEO
Project description:tsRNA profiles of gestational diabetes mellitus and healthy control groups were generated by deep sequencing using Illumina NextSeq 500.
2024-05-12 | GSE267259 | GEO
Project description:The hemochorial placenta provides a critical barrier at the maternal-fetal interface to modulate maternal immune tolerance and enable gas and nutrient exchange between mother and conceptus. Pregnancy outcomes are adversely affected by gestational diabetes mellitus (GDM); however, the effects of GDM on placental formation, and subsequently fetal development, are not fully understood. In this report, streptozotocin was used to induce hyperglycemia in pregnant rats for the purpose of investigating the impact of GDM on placental formation and fetal development. GDM caused placentomegaly and placenta malformation, decreasing placental efficiency and fetal size. Elevated glucose disrupted rat trophoblast stem (TS) cell differentiation in vitro. Evidence of altered trophoblast differentiation was also observed in vivo, as hyperglycemia affected the junctional zone transcriptome and interfered with intrauterine trophoblast invasion and uterine spiral artery remodeling. When exposed to hypoxia, rats with GDM showed decreased proliferation and ectoplacental cone development on gestation day (gd) 9.5 and complete pregnancy loss by gd 13.5. Furthermore, elevated glucose concentrations inhibited TS cell responses to hypoxia in vitro. Overall, these results indicate that alterations in placental development, efficiency, and plasticity could contribute to the suboptimal fetal outcomes in offspring from pregnancies complicated by GDM.
2020-07-07 | GSE144276 | GEO
Project description:Gestational diabetes mellitus (GDM) is a growing public health problem worldwide. The condition is associated with perinatal complications and an increased risk for future metabolic disease in both mothers and their offspring. In recent years, molecular biomarkers received considerable interest as screening tools for GDM. The purpose of this review is to provide an overview of the current status of single-nucleotide polymorphisms (SNPs), DNA methylation, and microRNAs as biomarkers for GDM. PubMed, Scopus, and Web of Science were searched for articles published between January 1990 and August 2018. The search terms included "gestational diabetes mellitus", "blood", "single-nucleotide polymorphism (SNP)", "DNA methylation", and "microRNAs", including corresponding synonyms and associated terms for each word. This review updates current knowledge of the candidacy of these molecular biomarkers for GDM with recommendations for future research avenues.
| S-EPMC6213110 | biostudies-literature