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.
HbA1c levels in patients before and after being prescribed an endothelin receptor antagonist.
