Unrecognized glucose intolerance is common in pulmonary arterial hypertension

Abstract

BACKGROUND Animal and human data suggest insulin resistance is common in pulmonary arterial hypertension (PAH). Although routine assessment of insulin resistance is difficult, hemoglobin A1c (HbA1c) is a sensitive test to detect diabetes mellitus (DM) and those at high risk for diabetes. We aimed to define the prevalence of elevated HbA1c in PAH patients and to correlate HbA1c with functional assessment. METHODS HbA1c was measured in 41 PAH patients without a diagnosis of DM, along with demographic, functional, and hemodynamic data. Using published criteria, HbA1c ≤ 5.9% defined normal, 6.0–6.4% glucose intolerance, and ≥ 6.5% diabetes. RESULTS Twenty-three patients (56%) had HbA1c ≥ 6.0%, 6 patients (15%) had unrecognized DM (HbA1c ≥ 6.5%). Age and body mass index were similar in patients with HbA1c ≥ 6.0% versus HbA1c < 6.0%. There was a trend towards lower mean six-minute walk distance in patients with elevated HbA1c (331.0 ± 126.6 meters versus 413.6 ± 74.9 meters, p=0.07). Six-month event-free survival was not significantly different in patients with elevated HbA1c. CONCLUSIONS Unrecognized glucose intolerance as assessed by HbA1c is common in PAH. Further studies are needed to discern if glucose or insulin dysregulation mediates PAH pathogenesis or is secondary to advanced PAH.

SIRT3–AMP-Activated Protein Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction

“…The effects of SU5416-induced pulmonary endothelial injury and elevated pulmonary pressure in rats with metabolic syndrome observed in this study provides support for the proposed role of metabolic syndrome as a risk factor for the development of PH-HFpEF 52–55 . Epidemiological studies indicate that PH-HFpEF patients are older and have a higher prevalence of hypertension, diabetes, obesity, and coronary artery disease than patients with PAH 3–6 .…”

HbA1c in pulmonary arterial hypertension: A marker of prognostic relevance?

“…12 In another study, HbA 1c level did not influence short-term event-free survival in PAH. 13 In our PAH patient group, no association between HbA 1c level and anthromorphometric parameters, gender, hemodynamic or functional parameters was observed. This is in accordance with recent findings by Pugh et al 13 Importantly, we found that PAH patients with HbA 1c Ͻ5.7% had a significantly better prognosis in long-term follow-up at 1, 3, and 5 years compared with patients presenting with initial HbA 1c Ն5.7% (Figure 1), even after correction for PHrelated death.…”

“…12 Increased glucose intolerance-assessed by the concentration of glycosylated hemoglobin A 1c (HbA 1c )-has been noted in patients with PAH, but without effect on 6-month event-free survival. 13 In the present study, we assessed HbA 1c concentrations in patients newly diagnosed with PAH prior to commencement of therapy and correlated HbA 1c values with the longterm survival of these patients.…”

Impact of Diabetes in Patients with Pulmonary Hypertension

“…It is interesting to note that insulin resistance and undiagnosed diabetes may be relatively common in patients with PAH. 22,23 In fact, a few of the patients in our cohort who were defined as nondiabetic were later found to have HbA 1c values high enough to be classified as insulin resistant or even diabetic. Future studies involving diabetic patients with PH should follow the trends of HbA 1c to help determine the utility of this biomarker with regard to prognosis.…”