Gestational Diabetes Can Increase CVD Risk

Gestational diabetes history is linked with coronary artery calcification (CAC) in women, an indicator of atherosclerotic CVD, and a predictor of CVD clinical events. 

Gestational diabetes (GD) is a significant risk factor for cardiovascular disease, leading to early-onset and an increased risk of type 2 diabetes. It is unknown whether achieving normoglycemia will mitigate the excess risk of CVD associated with GD history. This study aimed to assess GD history related to coronary artery calcification (CAC) in women. Confirmation is unclear about whether GD history increases CVD risk separate from T2D diagnosis. Although it may seem that maintaining normoglycemic levels reduces CVD risk, women with a history of GD who did not advance to T2D had a 30% to 56% higher CVD risk based on a pooled risk estimate from a meta-analysis. According to previous studies, the risk is still present regardless of glycemic levels post-pregnancy. This analysis evaluated GD history’s relationship across the reproductive years to the presence of coronary artery calcium in women during midlife, a strong predictor of atherosclerotic CVD (ASCVD). 

From 1985 to 1986 (baseline), 5,115 participants (2,787 women) 18 to 30 years of age (52% Black) were recruited across the US. The CARDIA (Coronary Artery Risk Growth in Young Adults) study was a multicenter, longitudinal observational study evaluating the determinants of CHD risk factors in young Black and White men and women. 1,133 parous women had 2,066 births after baseline in the analytical sample, and researchers measured metabolic risk factors before the first pregnancy. After the baseline test, non-contrast cardiac computed tomography was performed using standard protocols in years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011). CAC scores were combined from 2 consecutive scans for years 15 and 20. This study hypothesized that after pregnancy, deteriorating glucose tolerance, including prediabetes, would increase the risk of CAC independently of other risk factors for CVD. In addition, GD’s history will be associated with a higher risk of CAC even among women who are subsequently normoglycemic.

Worsening glucose tolerance among women without GD was correlated with higher CAC scores (P=0.003), but women with GD had more comparable proportions across the glucose tolerance groups. Over time, the overall CAC levels increased, with higher ratios obtaining scores >10 in examination year 25 relative to years 15 and 20. The results indicate that even sustained post-pregnancy normoglycemia in women with a GD history was associated with an increased CAC risk. The risk of CAC was ~2 times higher for women with a history of GD across all glucose tolerance levels relative to women without GD and with normoglycemia, irrespective of sociodemographic, clinical, and lifestyle behavioral risk factors. Apart from glucose tolerance, GD history can adversely affect CVD risk. The findings were that women with prior gestational diabetes were more likely to develop prediabetes or event diabetes than to sustain post-pregnancy normoglycemia (36%, 25.9%, or 38.1%) relative to women without gestational diabetes (35%, 9%, or 56%), overall P<0.001.

In this analysis, for all subsequent glucose tolerance measures, including normoglycemia, in women with previous GD, coronary calcified plaque calculated by CAC was approximately two times higher than in women without GD and normoglycemia. Thus, GD history may represent a constellation of risk factors that promote atherosclerotic plaque development in the absence of hyperglycemia. Insulin resistance and perhaps higher inflammation amongst women with prior GD who remained normoglycemic at follow-up in this study are coherent with the hypothesis, but there were limitations. This investigation’s fundamental limitation is the lack of routine biochemical testing for diabetes or CVD risk factors among young women of childbearing age. Higher ASCVD risk among women with GD history has been primarily attributed to their younger generation at T2D onset and a several-fold more increased risk of progression to T2D.

Furthermore, this analysis did not account for other risk factors that they may have been experiencing, potentially causing heart disease and coronary artery calcification. Altogether, the analysis conducted highlights the necessity for early intervention and prevention of gestational diabetes. Clinicians can encourage women of childbearing age to eat healthy, exercise, and maintain a healthy weight to prevent the development of gestational diabetes and subsequent increased CVD risk.

Practice Pearls:

• Women with a history of gestational diabetes have a two-fold risk of developing coronary artery calcification compared to those who do not.
• It is essential to regularly assess heart disease after being diagnosed with gestational diabetes and type 2 diabetes post-pregnancy.
• It is advised to maintain a healthy lifestyle during pregnancy to decrease women’s chances of developing gestational diabetes.

References for “Gestational Diabetes Can Increase CVD Risk”:
Gunderson, Erica P., et al. “Gestational Diabetes History and Glucose Tolerance After Pregnancy Associated With Coronary Artery Calcium in Women During Midlife  Circulation, Jan 21, 2021

DeSisto, Carla L et al. “Prevalence estimates of gestational diabetes mellitus in the United States, Pregnancy Risk Assessment Monitoring System (PRAMS), 2007-2010.” Preventing chronic disease vol. 11 E104. Jun 19. 2014

Shalonda Kimble, PharmD Candidate, South College School of Pharmacy

Oluwatayo Ishola, PharmD. Candidate, South College, School of Pharmacy

Macrina Ghali, PharmD Candidate 2021, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences