Pulmonary capillary permeability and pulmonary microangiopathy in diabetes mellitus

Pulmonary capillary permeability and pulmonary microangiopathy in diabetes mellitus

diabetes research and clinical practice 108 (2015) e56–e59 Contents available at ScienceDirect Diabetes Research and Clinical Practice jou rnal hom ...

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diabetes research and clinical practice 108 (2015) e56–e59

Contents available at ScienceDirect

Diabetes Research and Clinical Practice jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es

Brief Report

Pulmonary capillary permeability and pulmonary microangiopathy in diabetes mellitus Krzysztof Kuziemski a,*, Joanna Pien´kowska b, Wojciech Słomin´ski c, Ewa Jassem a, Michał Studniarek b a

Department of Allergology and Pneumonology, Medical University of Gdansk, ul. Debinki 7, 80-211 Gdansk, Poland Department of Radiology, Medical University of Gdansk, ul. Debinki 7, 80-211 Gdansk, Poland c Comerch S.A., Al. Jana Pawła II 39, Krako´w, Poland b

article info

abstract

Article history:

Significant increase in permeability surface (PS) in patients with diabetes confirms pulmo-

Received 29 April 2014

nary microcirculation damage in these patients.

Received in revised form

# 2015 Elsevier Ireland Ltd. All rights reserved.

8 February 2015 Accepted 22 February 2015 Available online 6 March 2015 Keywords: Perfusion CT Lung microangiopathy Diabetes mellitus Lung function tests

1.

Introduction

The lungs exhibit a complex microcirculation network whose structure and function can be altered in diabetes (pulmonary microangiopathy) [1–3]. Unfortunately, clinical assessments, including pulmonary function test and lung diffusing capacity for carbon monoxide (DLCO) measurement, are insufficient for

a precise diagnosis [4–6]. Perfusion chest computed tomography (pCT) is a non-invasive, sensitive technique that images hemodynamics on the basis of tissue density changes during the flow of contrast agent through the vascular bed of tested structures [7,8]. Recently, we had demonstrated a significant increase of CT perfusion parameters in the course of diabetes mellitus (DM), which seemed to confirm pulmonary microangiopathy [9]. Our

* Corresponding author. E-mail address: [email protected] (K. Kuziemski). Abbreviations: DLCO, lung diffusion capacity for carbon monoxide; DLCO/VA, lung diffusing capacity for carbon monoxide/alveolar volume; FEV1, forced expiratory volume in one second; pCT, perfusion chest computed tomography; MTT, mean transit time; PS, permeability surface; ROI, regions of interest; TLC, total lung capacity; VC, vital capacity; PFT, pulmonary function test. http://dx.doi.org/10.1016/j.diabres.2015.02.033 0168-8227/# 2015 Elsevier Ireland Ltd. All rights reserved.

diabetes research and clinical practice 108 (2015) e56–e59

present goal was to assess which pCT parameters play a significant role in the diagnosis of pulmonary microangiopathy associated with DM.

2.

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In statistical analysis, the x2-test, t-test and the analysis of variance (ANOVA) were applied. Statistical significance was determined at p < 0.05. Data analysis was carried out using Statistica Data Miner + QC software.

Materials and methods 3.

Thirty never-smoking subjects (15 diabetic patients and 15 healthy controls) were enrolled in the study. No participants had been diagnosed with any acute or chronic respiratory diseases affecting pulmonary function. Standard morphological, biochemical and PFT tests were performed. PFTs were performed in accordance with ATS/ERS guidelines [10,11]. pCT tests were performed according to an axial protocol with the use of a 64-row CT scanner (GE-Light Speed VCT, USA). Perfusion was evaluated in a 4 cm in diameter part of the lung situated 2 cm below the carina. During the test, 40 ml of non-iodinated contrast medium was administered intravenously at the rate of 4 ml/s and with a delay of 12 s. In order to minimize breathing artifacts, the test was performed during suspended inspiration and with temporal resolution of 1 s (40 pictures in 40 s). For each 5-mm slice of lung, 40 scans were obtained. Eighteen elliptical regions of interest (ROIs) were chosen (from 3 to 20), for which perfusion measurements were performed. The perfusion between the anterior and posterior part of lungs was assessed (Fig. 1). Reference ROI 1 was located in the pulmonary artery, while ROIs 3–20 were positioned in a similar location in both lungs and classified as front, medial or back. ROI 2 situated in the aorta was not necessarily evaluated during data analysis. The following parameters of local perfusion were determined (CT Perfusion 4, GE Healthcare USA): 1) Blood volume (BV) – the volume of a vascular bed supplied with blood (ml/100 g lung tissue). 2) Blood flow (BF) – the volume of blood flowing through a defined region in 1 min (ml/100 g/min). 3) Permeability surface (PS) – the vascular permeability for contrast medium penetrating from intravascular to extravascular space (ml/100 g/min). 4) Mean transit time (MTT) – the mean time needed for blood to pass vascular bed (s). The study protocol had been approved by a bioethics committee (No. NKEBN/14/2006).

Results

In the DM group 7 patients were diagnosed with type 1 DM and 8 patients with type 2 DM. The mean time since the diagnosis of DM was 16 years (13.2). Macroangiopathy was found in 11 patients: hypertension in 10, cardiac infarction in 1, and diabetic foot in 1. Diabetic microangiopathy was found in 12 patients: nephropathy in 7, retinopathy in 9, and polyneuropathy in 7. There were significant differences in the DM and control subjects in VC ( p = 0.05), TLC ( p = 0.05), and biochemical markers (fibrinogen p = 0.05, HbA1c p = 0.001, CRP p = 0.05) (Table 1). Mean HbA1c in DM was 9.4% (80 mmol/mol) indicating poor glycemia control. In pCT, in ROIs 3–20, no statistically significant differences were revealed in the mean area of ROIs, in BF, BV, and MTT. Similarly, no differences were found between front and back lung parenchyma either in the DM or in the CG. However, significant differences were found for PS in ROIs 3–20 as well as between the front and back ROIs. PS value was significantly higher in the DM compared with the CG (Table 1).

4.

Discussion

The current study demonstrates evidence of a relationship between PS and damage to lung parenchyma. PS was significantly higher in DM patients compared to the CG. The values were higher in all ROIs 3–20 and the front and back ROIs of the assessed lung parenchyma. In particular the permeability of contrast medium in the back ROIs of lungs was significantly higher. It is impossible to determine absolutely whether the increased PS indicates only structural damage to the vessels or altered functionality as well. PS allows quantifying the flow dynamics for capillaries in pulmonary microcirculation and simultaneously (indirectly) reflects structural changes in these vessels. These changes result in increased permeability of capillaries for contrast medium from intravascular to extravascular space. Hence, PS provides information on the

Fig. 1 – Diagram of determining and summing ROIs in pulmonary perfusion assessment.

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diabetes research and clinical practice 108 (2015) e56–e59

Table 1 – Baseline characteristics of diabetic and nondiabetic patients included in the study. Parameter Age (years) Gender: female/male BMI FEV1 (l/min) FEV1 (%) VC (l) VC (%) TLC (l) TLC (%) DLCO (ml/min/HPa) DLCO (%) CRP (mg/l) Fibrynogen (g/l) HbA1c (%) HbA1c (mmol/mol) Microalbuminuria (mg/l) Glucosuria (mg/dl) ROI front (mm2) ROI back (mm2) ROI 3–20 (mm2) BF ROI front BF ROI back BF ROI 3–20 BV ROI front BV ROI back BV ROI 3–20 MTT ROI front MTT ROI back MTT ROI 3–20 PS ROI front PS ROI back PS ROI 3–20 a

DM

CG

p

49.2 (13.16)a 6/9 31.4 (7.9) 2.9 (0.54) 92.7 (11.57) 4.09 (0.68) 103.66 (13.97) 5.84 (1.24) 98.73 (18.00) 8.81 (2.53) 95.33 (23.98) 3.60 (2.82) 3.79 (0.59) 9.44 (1.50) 80 (16.4) 315.05(562.46)

45.7 (10.63) 5/10 27.4 (5.2) 3.44 (0.9) 98.21 (9.72) 5.03 (1.35) 115.35 (13.94) 6.98 (1.58) 107.69 (16.32) 9.77 (2.19) 97.28 (14.85) 1.91 (1.33) 2.88 (0.62) 5.42 (0.30) 36 (3.3) –

ns ns ns ns ns 0.05 0.05 0.05 ns ns ns 0.05 0.001 0.001 0.001 –

800 (273.86) 1747.25 (551.38) 1976.37 (360.27) 2035.51 (462.95) 185.51 (91.49) 278.50 (158.59) 229.57 (121.43) 11.75 (5.40) 16.44 (7.76) 13.86 (6.37) 4.65 (1.51) 4.31 (1.22) 4.43 (1.31) 26.01 (24.16) 30.61 (26.58) 27.60 (24.21)

– 1630.70 (247.35) 1802.28 (273.74) 1847.77 (268.94) 170.65 (55.08) 201.50 (95.99) 184.23 (70.97) 10.45 (3.16) 12.39 (5.62) 11.22 (4.18) 4.39 (0.83) 4.38 (0.93) 4.35 (0.74) 12.74 (8.80) 10.75 (10.52) 12.07 (9.85)

– ns ns ns ns ns ns ns ns ns ns ns ns 0.05 0.01 0.05

are unclear. A possible explanation is appropriate control of glycemia after the pancreas transplant. We also found that glucose management influences lung function in patients with cystic fibrosis. In these patients, the lung function improved significantly because of intensive insulin therapy [15,16]. The results indicate that the damage to the function and structure of lung microvascular endothelial cells resulting from the lack of metabolic compensation of diabetes and from prolonged illness might be easily identified by CT perfusion scanning.

Conflict of interest None declared.

references

(SD).

condition of pulmonary microcirculation. In contrast, in healthy lungs, the perfusion parameters remain unchanged [12]. No limitations of either obstruction- or restriction-type ventilation reserves were found in either group. DLCO results were also normal without any differences between groups. Additionally, in lung parenchyma there are areas that constitute dead space in terms of anatomy and functionality. In this space, the alveoli and their surrounding vessels are physiologically inactive. Some vessels are recruited only because of additional triggers, such as chronic lung or heart disorders [13]. Similarly, progressing diabetes and gradual development of pulmonary microangiopathy seem to be the trigger for recruitment of inactive pulmonary vessels, which results in minimizing ventilation disorders. However, the damaged vessels remain in the parenchyma and function in an altered way, thus allowing the contrast medium to penetrate from the intravascular space. On the other hand, we demonstrated that proper glycemia management results in a significant improvement of lung function and normalization of HbA1c concentration. In patients with type 1 DM, a significant lung function improvement was observed after a pancreas transplant [14]. The mechanisms of the improvement by glucose normalization

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