scholarly journals Trans-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes

2021 ◽  
Author(s):  
Natalia Pervjakova ◽  
Gunn-Helen Moen ◽  
Maria-Carolina Borges ◽  
Teresa Ferreira ◽  
James P Cook ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Increased Risk ◽  
In Pregnancy

Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in a total of 5,485 women with GDM and 347,856 without GDM. Through trans-ancestry meta-analysis, we identified five loci with genome-wide significant association (p<5×10-8) with GDM, mapping to/near MTNR1B (p=4.3×10-54), TCF7L2 (p=4.0×10-16), CDKAL1 (p=1.6×10-14), CDKN2A-CDKN2B (p=4.1×10-9) and HKDC1 (p=2.9×10-8). Multiple lines of evidence pointed to genetic contributions to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D; and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomisation analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.

scholarly journals Genetics and Epigenetics: New Insight on Gestational Diabetes Mellitus

2020 ◽  
Vol 11 ◽  
Author(s):  
Maria Grazia Dalfrà ◽  
Silvia Burlina ◽  
Gloria Giovanna Del Vescovo ◽  
Annunziata Lapolla
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Gestational Diabetes ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Maternal Metabolism

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.

scholarly journals The Pathophysiology of Gestational Diabetes Mellitus

2018 ◽  
Vol 19 (11) ◽  
pp. 3342 ◽  
Author(s):  
Jasmine Plows ◽  
Joanna Stanley ◽  
Philip Baker ◽  
Clare Reynolds ◽  
Mark Vickers
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Overweight And Obesity ◽  
Chronic Hyperglycemia ◽  
Increased Risk

Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

scholarly journals Gestational Diabetes Mellitus (GDM): Current concept and a short Review

1970 ◽  
Vol 24 (1) ◽  
pp. 16-20 ◽  
Author(s):  
MT Rahman ◽  
T Tahmin ◽  
S Ferdousi ◽  
SN Bela
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Later Life ◽  
Short Review ◽  
Current Concept ◽  
Increased Risk ◽  
Develop Type

Gestational Diabetes Mellitus (GDM) is a very common and important disease occurring during pregnancy and has detrimental effect on both the mother and the baby. The mother is at increased risk of developing obstetric complications like prolonged labour, prone to develop type 2 diabetes in future and the baby is born with overweight, cause of childhood obesity and later life development of type 2 diabetes. A short review and current concept of GDM is discussed. Key words: GDM, Type 2 diabetes, Obesity, Macrosomia, Complications   doi: 10.3329/bjpath.v24i1.2877 Bangladesh J Pathol 24 (1) : 16-20

scholarly journals Gestational diabetes mellitus and the role of intercurrent type 2 diabetes on long-term risk of cardiovascular events

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiyu Sun ◽  
Gyu Ri Kim ◽  
Su Jin Lee ◽  
Hyeon Chang Kim
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Cardiovascular Events ◽  
Cvd Risk ◽  
Increased Risk ◽  
Incident Cases

AbstractRecent studies have shown that gestational diabetes mellitus (GDM) is associated with an increased risk for cardiovascular disease. GDM has also been shown to be a risk factor for type 2 diabetes (T2DM) after pregnancy. However, there is limited evidence regarding the role of intercurrent T2DM on the relationship between GDM and future CVD. Thus, we investigated the risks of incident cardiovascular events among women with GDM during pregnancy compared to women without GDM and whether the increased CVD risk is dependent on intercurrent development of T2DM. We conducted a population-based retrospective cohort study using the Korean National Health Insurance Service claims database. Outcomes were the first occurrence of any CVD (myocardial infarction, treatment with coronary revascularization, heart failure, and cerebrovascular disease). Cox proportional hazard models were used to assess the association between GDM and incident CVD events, using landmark analysis at 4 years. A total of 1,500,168 parous women were included in the analysis, of which 159,066 (10.60%) had GDM. At a median follow-up of 12.8 years, 13,222 incident cases of total CVD were observed. Multivariable-adjusted hazard ratio for total CVD among women with prior GDM, compared with those without GDM, was 1.08 (95% CI 1.02–1.14). Further classifying GDM by progression to T2DM in relation to total CVD risk indicated a positive association for GDM with progression to T2DM vs no GDM or T2DM (HR 1.74; 95% CI 1.40–2.15), and no statistically significant association for GDM only (HR 1.06; 95% CI 1.00–1.12). GDM with subsequent progression to T2DM were linked with an increased risk of cardiovascular diseases. These findings highlight the need for more vigilant postpartum screening for diabetes and the implementation of diabetes interventions in women with a history of GDM to reduce future CVD risk.

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