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

Background Gestational diabetes is associated with an increased risk of coronary artery disease and adverse cardiovascular events in later life. Coronary microvascular dysfunction is a common precursor of coronary after disease. Although microvascular dysfunction is common in GDM, the exact mechanisms remain unknown. Aim To study the associations between coronary flow reserve (CFR) with common biomarkers of hyperglycemia, insulin resistance, inflammation and oxidative stress. Methods Measurement of CFR was performed noninvasively using echocardiography in all patients. Results 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,BF ₁₀ :785) and uric acid (r=-0.29,p < 0.001,BF ₁₀ :113) and moderate to strong evidence for HOMA-IR (r=-0.21,p = 0.006,BF ₁₀ :20). 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). Conclusions 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 GDM rappears as the most likely cause for reduced CFR.