Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension

Abstract

Background: Diabetes mellitus is associated with left ventricular hypertrophy and dysfunction. Parallel studies have also reported associations between diabetes mellitus and right ventricular dysfunction and reduced survival in patients with pulmonary arterial hypertension. However, the impact of diabetes mellitus on the pulmonary vasculature has not been well characterized. We hypothesized that diabetes mellitus and hyperglycemia could specifically influence right ventricular afterload and remodeling in patients with Group I pulmonary arterial hypertension, providing a link to their known susceptibility to right ventricular dysfunction.

Methods: Using an adjusted model for age, sex, pulmonary vascular resistance, and medication use, associations of fasting blood glucose, glycated hemoglobin, and the presence of diabetes mellitus were evaluated with markers of disease severity in 162 patients with pulmonary arterial hypertension.

Results: A surrogate measure of increased pulmonary artery stiffness, elevated pulmonary arterial elastance (P = .012), along with reduced log(pulmonary artery capacitance) (P = .006) were significantly associated with the presence of diabetes mellitus in patients with pulmonary arterial hypertension in a fully adjusted model. Similar associations between pulmonary arterial elastance and capacitance were noted with both fasting blood glucose and glycated hemoglobin. Furthermore, right ventricular wall thickness on echocardiography was greater in pulmonary arterial hypertension patients with diabetes, supporting the link between right ventricular remodeling and diabetes.

Conclusion: Cumulatively, these data demonstrate that an increase in right ventricular afterload, beyond pulmonary vascular resistance alone, may influence right ventricular remodeling and provide a mechanistic link between the susceptibility to right ventricular dysfunction in patients with both diabetes mellitus and pulmonary arterial hypertension.

Keywords: Diabetes mellitus; Pulmonary arterial capacitance; Pulmonary arterial elastance; Pulmonary arterial hypertension.

Figure 1. Correlation plots between indices of hyperglycemia and measures of pulmonary arterial hypertension severity

The figures below depict the significant associations between glycated hemoglobin levels and pulmonary arterial capacitance, pulmonary arterial elastance, as well as pulmonary artery saturation in the pulmonary arterial hypertension cohort. Similarly, significant but weaker associations are evident between fasting blood glucose levels and pulmonary artery saturation and six-minute walk distance including trends toward associations with right ventricular wall thickness.