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Ann Am Thorac Soc. 2017 Feb;14(2):190-199. doi: 10.1513/AnnalsATS.201608-605OC.

Abnormal Glucose Metabolism and High-Energy Expenditure in Idiopathic Pulmonary Arterial Hypertension.

Author information

1
1 Department of Pulmonary and Critical Care Medicine, Respiratory Institute.
2
2 Department of Pathobiology, Lerner Research Institute, and.
3
3 Metabolic Translational Research Center, Endocrine and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio.

Abstract

RATIONALE:

Insulin resistance has emerged as a potential mechanism related to the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). However, direct measurements of insulin and glucose metabolism have not been performed in patients with IPAH to date.

OBJECTIVES:

To perform comprehensive metabolic phenotyping of humans with IPAH.

METHODS:

We assessed plasma insulin and glucose, using an oral glucose tolerance test and estimated insulin resistance, and β-cell function in 14 patients with IPAH and 14 control subjects matched for age, sex, blood pressure, and body mass index. Body composition (dual-energy X-ray absorptiometry), inflammation (CXC chemokine ligand 10, endothelin-1), physical fitness (6-min walk test), and energy expenditure (indirect calorimetry) were also assessed.

MEASUREMENTS AND MAIN RESULTS:

Patients with IPAH had a higher rate of impaired glucose tolerance (57 vs. 14%; P < 0.05) and reduced glucose-stimulated insulin secretion compared with matched control subjects (IPAH: 1.31 ± 0.76 μU/ml⋅mg/dl vs. control subjects: 2.21 ± 1.27 μU/ml⋅mg/dl; P < 0.05). Pancreatic β-cell function was associated with circulating endothelin-1 (r = -0.71, P < 0.01) and CXC chemokine ligand 10 (r = -0.56, P < 0.05). Resting energy expenditure was elevated in IPAH (IPAH: 32 ± 3.4 vs. control subjects: 28.8 ± 2.9 kcal/d/kg fat-free mass; P < 0.05) and correlated with the plasma glucose response (r = 0.51, P < 0.01). Greater insulin resistance was associated with reduced 6-minute walk distance (r = 0.55, P < 0.05).

CONCLUSIONS:

Independent of age, sex, blood pressure, and body mass index, patients with IPAH have glucose intolerance, decreased insulin secretion in response to glucose, and elevated resting energy expenditure. These abnormalities are associated with circulating markers of inflammation and vascular dysfunction.

KEYWORDS:

energy expenditure; glucose metabolism disorder; pulmonary hypertension

PMID:
27922752
PMCID:
PMC5427733
DOI:
10.1513/AnnalsATS.201608-605OC
[Indexed for MEDLINE]
Free PMC Article

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