Diminished Alveolar Microvascular Reserves In Type-2 Diabetes Mellitus Reflect Systemic Microangiopathy

Abstract

Objective: Alveolar microvascular function is moderately impaired in type-1, manifested by restriction of lung volume and diffusing capacity (DL_CO). We examined whether similar impairment develops in type-2 (T2DM), defined the physiologic sources of impairment as well as the relationships to glycemia and systemic microangiopathy.

Research Design and Methods: A cross-sectional study was conducted at a University-affiliated Diabetes Treatment Center and outpatient Diabetes Clinic, involving 69 non-smoking T2DM patients without overt cardiopulmonary disease. Lung volume, pulmonary blood flow (Q̇), DL_CO, membrane diffusing capacity (measured from nitric oxide uptake, DL_NO), and pulmonary capillary blood volume (Vc) were determined at rest and exercise for comparison with that in 45 healthy non-smokers as well as normal reference values.

Results: In T2DM patients, peak levels of oxygen uptake, Q̇ and DL_CO, DL_NO and Vc at exercise were 10-25% lower compared to control subjects. In non-obese patients (BMI<30 kg/m²), reduction in DL_CO, DL_NO and Vc was fully explained by the lower lung volume and peak Q̇, but these factors did not fully explain the impairment in obese patients (BMI>30 kg/m²). The slope of the increase in Vc with respect to Q̇ was reduced ∼20% in patients regardless of BMI, consistent with impaired alveolar-capillary recruitment. Functional impairment was directly related to glycosylated hemoglobin level, retinopathy, neuropathy and microalbuminuria in a gender-specific manner.

Conclusions: Alveolar microvascular reserves are reduced in T2DM, reflecting restriction of lung volume, alveolar perfusion and capillary recruitment. Reduction correlates with glycemic control and extra-pulmonary microangiopathy, and is aggravated by obesity.