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

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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The Pathophysiology of Gestational Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms19113342 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3342 ◽

Cited By ~ 112

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.

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Previous Gestational Diabetes Mellitus and Markers of Cardiovascular Risk

International Journal of Endocrinology ◽

10.1155/2012/458610 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 32

Author(s):

Nikolaos Vrachnis ◽

Areti Augoulea ◽

Zoe Iliodromiti ◽

Irene Lambrinoudaki ◽

Stavros Sifakis ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Current Knowledge ◽

Normal Pregnancy ◽

Metabolic Abnormalities ◽

Cvd Risk ◽

Maternal Complications

The prevalence of gestational diabetes mellitus (GDM) in the developed world has increased at an alarming rate over the last few decades. GDM has been shown to be associated with postpartum diabetes, insulin resistance, hypertension, and dyslipidemia. A history of previous GDM (pGDM), associated or not with any of these metabolic abnormalities, can increase the risk of developing not only type 2 diabetes mellitus but also cardiovascular disease (CVD) independent of a diagnosis of type 2 diabetes later in life. In this paper we discuss the relationship among inflammatory markers, metabolic abnormalities, and vascular dysfunction in women with pGDM. We also review the current knowledge on metabolic modifications occurring in normal pregnancy and the link between alterations of a normal metabolic state with the long-term maternal complications that may result in increased CVD risk. Our review of studies on pGDM prompts us to recommend that these women be considered a population at risk for later CVD events, which however could be avoided via the use of specially designed follow-up programs in the future.

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Type 2 Diabetes mellitus genetic risk variant T in TCF7L2 rs 7903146 in women is associated with an increased risk for the development of gestational diabetes mellitus (GDM) with necessity of insulin therapy

Diabetologie und Stoffwechsel ◽

10.1055/s-0034-1375153 ◽

2014 ◽

Vol 9 (S 01) ◽

Author(s):

L Potasso ◽

N Perakakis ◽

A Lamprinou ◽

E Polyzou ◽

D Kassanos ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Genetic Risk ◽

Risk Variant ◽

Increased Risk ◽

Genetic Risk Variant

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Role of Type 2 Diabetes in Determining Retinal, Renal, and Cardiovascular Outcomes in Women With Previous Gestational Diabetes Mellitus

Diabetes Care ◽

10.2337/dc16-1400 ◽

2016 ◽

Vol 40 (1) ◽

pp. 101-108 ◽

Cited By ~ 53

Author(s):

Ravi Retnakaran ◽

Baiju R. Shah

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Cardiovascular Outcomes ◽

Previous Gestational Diabetes Mellitus ◽

Previous Gestational Diabetes

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

Bangladesh Journal of Pathology ◽

10.3329/bjpath.v24i1.2877 ◽

1970 ◽

Vol 24 (1) ◽

pp. 16-20 ◽

Cited By ~ 1

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

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

10.1101/2021.10.11.21264235 ◽

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.

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High pre-pregnancy BMI with a history of gestational diabetes mellitus is associated with an increased risk of type 2 diabetes in Korean women

PLoS ONE ◽

10.1371/journal.pone.0252442 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252442

Author(s):

Dayeon Shin ◽

Kyung Won Lee

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Healthy Weight ◽

Korean Women ◽

Increased Risk ◽

The Future ◽

History Of

Despite the importance of pre-pregnancy body mass index (BMI) and a history of gestational diabetes mellitus (GDM) in the progression of GDM to type 2 diabetes, few studies have evaluated the combined effect of high pre-pregnancy BMI and GDM status on the future development of type 2 diabetes in Korean women. This study aimed to examine the relationship of pre-pregnancy BMI and GDM history with the risk of type 2 diabetes among Korean women. In addition, the effects of pre-pregnancy BMI and current BMI on the risk of type 2 diabetes were evaluated. Women who gave birth in the Health Examinees Study of the Korean Genome and Epidemiology Study from 2004 to 2013 (n = 59,258) were included in this study. Multivariable logistic regression was used to examine the association of pre-pregnancy BMI categories (underweight: <18.5 kg/m2; normal: 18.5–22.9 kg/m2; overweight: 23.0–24.9 kg/m2; obese: ≥25.0 kg/m2) and GDM history with the risk of type 2 diabetes after controlling for the following covariates: age, education, income, smoking status before the first pregnancy, alcohol consumption, regular exercise, menarche age, first pregnancy age, and first pregnancy outcome. Compared to women with normal pre-pregnancy BMIs, women with overweight and obese pre-pregnancy BMIs had higher odds of developing type 2 diabetes (adjusted odds ratio [AOR]: 1.13, 95% confidence interval [CI]: 1.02–1.25 and AOR: 1.29, 95% CI: 1.10–1.50, respectively) after controlling for covariates. Women with pre-pregnancy BMIs <23 kg/m2 and current BMIs ≥23 kg/m2 had increased odds of developing type 2 diabetes (AOR: 1.64, 95% CI: 1.51–1.78) compared to those with pre-pregnancy BMIs <23 kg/m2 and current BMIs <23 kg/m2. Among women without a history of GDM, those with overweight and obese pre-pregnancy BMIs had increased odds of developing type 2 diabetes compared to those with normal pre-pregnancy BMIs (AOR: 1.12, 95% CI: 1.01–1.24 and AOR: 1.23, 95% CI: 1.05–1.44, respectively). Among women with GDM, those with obese pre-pregnancy BMIs had increased odds of developing type 2 diabetes (AOR: 3.84, 95% CI: 1.52–9.87). This study showed that there was a higher likelihood of developing type 2 diabetes in women who were overweight or obese before pregnancy with a history of GDM compared to their counterparts without a history of GDM. Furthermore, high pre-pregnancy BMI or high current BMI increased the risk of type 2 diabetes in Korean women, regardless of GDM history. This emphasizes the importance of maintaining a healthy weight status before and after pregnancy to prevent the future risk of type 2 diabetes.

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High Prevalence of Type 2 Diabetes and Pre-Diabetes in Adult Offspring of Women With Gestational Diabetes Mellitus or Type 1 Diabetes: The role of intrauterine hyperglycemia

Diabetes Care ◽

10.2337/dc07-1596 ◽

2007 ◽

Vol 31 (2) ◽

pp. 340-346 ◽

Cited By ~ 370

Author(s):

T. D. Clausen ◽

E. R. Mathiesen ◽

T. Hansen ◽

O. Pedersen ◽

D. M. Jensen ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Adult Offspring ◽

High Prevalence

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Long-Term Metabolic Consequences in Patients with a History of Gestational Diabetes

Current Pharmaceutical Design ◽

10.2174/1381612826666201106092423 ◽

2020 ◽

Vol 26 (43) ◽

pp. 5564-5572

Author(s):

Eleni Kousta ◽

Adamantia Kontogeorgi ◽

Stephen Robinson ◽

Desmond G. Johnston

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Increased Risk ◽

Metabolic Complication ◽

History Of

Gestational diabetes mellitus is a common metabolic complication of pregnancy. Universal guidelines on gestational diabetes have been impeded by the long-term controversies on its definition and screening strategies. The prevalence of gestational diabetes is rising all over the world, is significantly influenced by ethnicity and its rise is mainly attributed to increasing maternal obesity and age. Gestational diabetes mellitus has important long-term implications, including gestational diabetes recurrence, increased risk for developing type 2 diabetes, metabolic syndrome and cardiovascular disease for the mother. Gestational diabetes mellitus may be viewed as a chronic metabolic disorder that is identified in women during gestation and may provide a unique opportunity for the early identification and primary prevention of type 2 diabetes mellitus and cardiovascular disease in these women. In this mini-review, the evolution of screening tests for gestational diabetes and guidelines are briefly described and metabolic and cardiovascular long-term consequences of women with a history of gestational diabetes are summarized. A summary of our own St. Mary’s Hospital-UK Research series on long-term metabolic consequences of 368 women with a history of gestational diabetes of 3 different ethnic groups and 482 control women is also included. We found that approximately 2 years following delivery, 37% of women with a history of gestational diabetes had abnormal glucose concentrations, but, most importantly, even those who were normoglycaemic, postpartum displayed metabolic abnormalities on detailed testing. Future research needs to focus on the prevention of gestational diabetes long-term complications, but also in identification of pre-pregnancy predictors and risk reduction before conception.

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