Endothelin‐1 receptor antagonists reduce HbA1c in obese patients with pulmonary hypertension

Abstract

Obesity is associated with insulin resistance and type II diabetes. Our lab has recently shown that blockade of endothelin‐1 (ET‐1) receptors attenuates insulin resistance in a mouse model of diet induced obesity. Currently, ET‐1 receptor blockers are FDA approved to treat patients with pulmonary hypertension. We hypothesized that patients taking ET‐1 receptor antagonists (ERA) have improvements in insulin sensitivity. Electronic health record data were extracted from EPIC (Epic) at the University of Mississippi Medical Center. Data from 2013‐2020 were retrieved from patients ≥18 years old with a clinical diagnosis of pulmonary hypertension and at least two clinical visits within 2 years. Patients that were prescribed ERAs (n=12) were similar in age (61±14 vs. 60±14 yr), BMI (34±8 vs. 35±11 kg/m2), diabetes prevalence (73% vs. 80%, p=0.59), and follow‐up time (209±74 vs. 283±180 days) as compared to control patients (n=137). Additionally, there was a similar decrease in BMI at follow‐up in the control (‐1.6±5 kg/m2) and ERA patients (‐1.9±3 kg/m2). Interestingly, at follow‐up, HbA1c significantly decreased ‐12±11% in patients taking ERA while control patients were associated with a 2±20% increase in HbA1c. In the ERA patients, circulating LDL and total cholesterol tended to decrease (‐6±23% and ‐6±13%, respectively) and HDL tended to increase (‐9±32%) after ERA but did not reach statistical significance. These data suggest a potential anti‐diabetic effect of ERAs in patients with obesity and insulin resistance.