GD May Increase Heart Disease Risk Despite Achieving Normal Blood Glucose Levels

Results of a prospective cohort study suggest history of gestational diabetes (GD) may promote development of atherosclerotic plaque, potentially increasing the risk of future heart disease among women, even in the absence of hyperglycemia.

The findings, published in Circulation, indicate “A history of gestational diabetes may entail underlying vascular changes and adversely affect development of cardiovascular disease [CVD] through pathways such as insulin resistance and impaired insulin secretion that promote atherogenic plaques independent of dysglycemia,” the authors said.

GD affects between 8% and 9% of all US pregnancies and between 17% to 20% of pregnancies worldwide, according to the researchers. Prior to pregnancy, women who develop GD may present with impaired glucose tolerance, or prediabetes, and dyslipidemia. Following pregnancy, women who develop GD are 4 to 7 times more likely to develop type 2 diabetes (T2D)—a contributing factor to CVD and coronary artery disease.

However, “evidence is mixed about whether GD history increases CVD risk independent of subsequent T2D, with relative risks ranging from a null association among older European women, to a 1.25- to 2-fold higher risk among younger women,” the authors explained.

Routine diabetes testing generally is not recommended in adults under the age of 45, and previously studies have failed to distinguish between prediabetes and normoglycemia, which combined “represent the lowest risk group with highest relevance as the referent group for younger populations.”

To evaluate the relationship between GD history and subsequent transitions in glucose tolerance across reproductive years, the researchers analyzed data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. The longitudinal, multicenter observational study began in 1985 and recruited 5115 participants at baseline from 4 US geographic areas. Originally intended to examine the determinants of coronary heart disease risk factors in young Black and White men and women, for current analysis, the researchers evaluated the presence of coronary artery calcium (CAC)—a strong predictor of atherosclerotic CVD (ASCVD)—in women enrolled in CARDIA during midlife.

Of the surviving cohort, retention at follow-up years 15, 20, and 25 was 74%, 72%, and 72%, respectively. Deidentified data of 1133 parous women who had 2066 births after baseline were included in the analysis. Fifty-one percent of women identified as White. All participants had metabolic risk factors measured and recorded before their first pregnancy, while medical and clinical attributes, sociodemographic factors, and lifestyle behaviors were collected during subsequent in-person examinations.

CAC scores, measured via noncontrast cardiac CT, were measured at years 15, 20, and 25. Biochemical testing of glucose tolerance took place at baseline and years 7, 10, 15, 20, and 25, and were used to classify women as having normoglycemia, prediabetes, and incident diabetes.

A total of 139 (12.3%) women reported GD during pregnancy (6.7 per 100 pregnancies), with a mean (SD) time of 14.7 (5.9) years since last birth to end of follow-up, at which time the mean age was 47.6 (4.8) years. Data showed CAC was present in 25% (34/139) of women with GD and 15% (149/994) of women with no GD.

In comparison with no GD/normoglycemia, analyses revealed the following adjusted HRs:

• 1.54 (95% CI, 1.06-2.24) for no GD/prediabetes
• 2.17 (95% CI, 1.30-3.62) for no GD/incident diabetes
• 2.34 (95% CI, 1.34-4.09) for GD/normoglycemia
• 2.13 (95% CI, 1.09-4.17) for GD/prediabetes
• 2.02 (95% CI, 0.98-4.19) for GD/incident diabetes

Older age, smoking, metabolic syndrome, and hypertension were all associated with CAC presence.

Results show sustained normoglycemia after pregnancy among women who had GD was still associated with increased risk of CAC, and risk associations were not confounded by the use of lipid-lowering medications.

“In comparison with women without GD and with normoglycemia, the risk of CAC was [approximately] 2 times higher for women with a history of GD across all levels of glucose tolerance, independent of sociodemographic, clinical, and lifestyle behavioral risk factors,” the authors wrote.

Impaired insulin secretion and resistance may explain increased coronary artery atherogenesis in the absence of glucose intolerance observed in the study. In addition, data showed that in women without a history of GD, average weight gain was inversely correlated with glucose tolerance, but not in women with previous GD. “A history of GD may confer additional underlying risk for ASCVD through obesity-related cardiometabolic pathways without apparent clinical manifestations,” the researchers hypothesized.

Lack of data on CAC measurements prior to pregnancy and the use of CAC scores as a surrogate for heart disease risk (as opposed to cardiovascularcardiovascular events) mark limitations to the study.

"Risk assessment for heart disease should not wait until a woman has developed prediabetes or T2D," said study author Erica P Gunderson, PhD, in a statement. "Diabetes and other health problems that develop during pregnancy serve as early harbingers of future chronic disease risk, particularly heart disease. Health care systems need to integrate the individual's history of GD into health records and monitor risk factors for heart disease, as well as the recommended testing for T2D in these women at regular intervals, which is critical to target prevention efforts."

Reference

Gunderson EP, Sun B, Catov JM, et al. Gestational diabetes history and glucose tolerance after pregnancy associated with coronary artery calcium in women during midlife. Circulation. Published online February 1, 2021. doi:10.1161/CIRCULATIONAHA.120.047320