Insulin resistance in pulmonary arterial hypertension, is it a novel disease modifier?

Recent studies have introduced glucose intolerance and insulin resistance (IR) as novel risk factors in patients with pulmonary arterial hypertension (PAH).

We aimed to investigate the prevalence of glucose intolerance and IR in patients with PAH and their correlation with functional capacity and prognostic factors.

Sixty-nine patients with pulmonary arterial hypertension (class I Pulmonary hypertension in accordance with updated clinical classification of pulmonary hypertension) scheduled for right heart catheterization were enrolled. FBS, HbA1c, lipid profile, pro -BNP and hs-CRP were measured along with a 6-minute walk test (6-MWT) and obtaining demographic, functional and hemodynamic data. Fasting triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) was used as a surrogate of insulin sensitivity. Using published criteria, HbA1c ≤ 5.9% defined as normal, 6.0-6.4% as glucose intolerance, and ≥ 6.5% as diabetes. All patients were followed for a year regarding development of any cardiovascular event (mortality and/or hospitalization).

In total, 76.8% of patients were female: 61% of them had idiopathic PAH, 33% Eisenmenger syndrome, and 6% PAH secondary to a connective tissue disease. With respect to TG/HDL-C, 43.5% of patients had IR and 47.8% of patients had HbA1c > 6. There was no difference between IR and insulin sensitive (IS) group or glucose intolerance and sensitive group regarding NYHA class, 6MWT, Pro BNP, hs-CRP and hemodynamic data and there was no correlation between IR or glucose intolerance and any event.

Unrecognized glucose intolerance and IR are common in PAH. However, further studies are needed to show whether glucose or insulin dysregulation plays any role in PAH pathogenesis or it is secondary to advanced PAH.