Coronary microvascular dysfunction in gestational diabetes: insights on possible mechanism from a large institutional registry.

Gestational diabetes is associated with an increased risk of coronary artery disease (CAD) and adverse cardiovascular events in later life. Coronary microvascular dysfunction is a common precursor of CAD. Although microvascular dysfunction is common in gestational diabetes (GDM), the exact mechanisms remain unknown. We aimed to study the associations between coronary flow reserve (CFR) with common biomarkers of hyperglycemia, insulin resistance, inflammation and oxidative stress. Measurement of CFR was performed noninvasively using echocardiography in all patients. Patients with a low CFR (≤ 2.5) had higher HbA1c%, HOMA-IR, triglyceride-glucose index, uric acid, and total and non-HDL cholesterol as compared to those with a normal CFR (> 2.5). On univariate analysis, there was strong evidence favoring an association between CFR with HbA1c% (r=-0.32, p < 0.001, BF10:785) and uric acid (r=-0.29, p < 0.001, BF10:113) and moderate evidence for HOMA-IR (r=-0.21, p = 0.006, BF10:9.1). Final linear regression model included HbA1c% (β=-0.31, p < 0.001); HOMA-IR (β=-0.25, p = 0.001); uric acid (β=-0.19, p = 0.007) and waist circumference (β = 0.25, p < 0.001). GDM patients with higher HbA1c%, HOMA-IR, hyperuricemia and lower waist circumference are at a higher risk for coronary microvascular dysfunction. However, most of the variance in CFR is not related to any biomarkers and a past history of transient hyperglycemia during pregnancy appears as the most likely explanation for reduced CFR.