Pulmonary diffusing capacity, serum angiotensin-converting enzyme activity and the angiotensin-converting enzyme gene in Japanese non-insulin-dependent diabetes mellitus patients

doi:10.1016/S0168-8227(99)00006-6

Diabetes Research and Clinical Practice

Volume 43, Issue 3, March 1999, Pages 173-177

https://doi.org/10.1016/S0168-8227(99)00006-6 Get rights and content

Abstract

We investigated the independent change in pulmonary diffusing capacity (DLCO) as one manifestation of pulmonary microangiopathy and to analyze the correlation between DLCO and serum ACE. We also examined the association between DLCO and the ACE genes. We examined pulmonary functions, especially %DLCO/VA (DLCO corrected by alveolar volume, percent predicted) in 54 NIDDM patients and 34 age-matched normal control subjects. Subjects were subdivided according to the degree of retinopathy. Serum ACE level was assayed by a colorimetric method in 54 patients and an insertion/deletion polymorphism in the ACE gene was amplified using the polymerase chain reaction in 52 of the 54 patients. There was a significant reduction of %DLCO/VA (percent predicted P<0.05) in diabetic patients. In the proliferative retinopathy (PDR) group, %DLCO/VA was significantly (P<0.05) lower than in the no diabetic retinopathy (NDR) and simple diabetic retinopathy (SDR) groups. Although the levels of serum ACE were within normal ranges in all diabetic groups, %DLCO/VA was negatively correlated with serum ACE values (r=0.49, P<0.0002, y=−1.4x+109.3). Differences among DD, ID and II type of the ACE gene, with respect to the incidence of abnormal values of each clinical parameter, were not significant. DLCO was significantly reduced in patients with PDR and the serum ACE was significantly related to impaired DLCO. Our study suggests the existence of microangiopathic involvement of pulmonary vessels in NIDDM patients.

Introduction

The pathogenesis of the major long-term complications of diabetes mellitus is thought to involve a microvascular process [1], probably involving the lung [2]. On the other hand, a possible relation between elevated serum angiotensin-converting enzyme (ACE) and diabetes mellitus was reported by Lieberman et al. [3], especially in the investigation of diabetic retinopathy patients. However, since the lungs have the largest capillary bed of any organ in the body, they appear to be the site where serum ACE acts on circulating substrates [4]. The aim of this study was, therefore, to assess the possible association between the degree of retinopathy as a vascular complication of NIDDM and changes in pulmonary diffusing capacity (DLCO), as one manifestation of pulmonary microangiopathy and subsequently to analyze the correlation between DLCO and serum ACE. Furthermore, we also examined the association between DLCO and the ACE genes [5].

Section snippets

Subjects and methods

The subjects consisted of 54 Japanese NIDDM patients and 34 age-matched normal volunteers. The clinical characteristics of the patients, subdivided according to the degree of retinopathy and of the control group are shown in Table 1. Nine of the patients were under dietary therapy, 17 under oral medication therapy and 28 under insulin therapy. Patients with cardiopulmonary disorders or having smoked were excluded. Furthermore, patients having hypertension according to conventional criteria

Results

Pulmonary function data are summarized in Table 2 with normalized values in percentages. The FEV₁% and %VC showed no significant changes between controls and both groups of diabetic patients. However, as compared with controls, there was a significant reduction of %DLCO/VA (percent predicted P<0.05) in diabetic patients. In the proliferative retinopathy (PDR) group, %DLCO/VA was significantly (P<0.05) lower than in the no diabetic retinopathy (NDR) and simple diabetic retinopathy (SDR) groups.

Discussion

This study showed that DLCO was significantly reduced in patients with PDR. In addition, the serum ACE levels were significantly related to impaired DLCO.

Although previous studies concerning pulmonary dysfunctions in both IDDM and NIDDM patients have been reported [9], [10], [11], all of them estimated the pulmonary diffusion without regard to the abnormality of the flow volume curve, which influences DLCO and ventilation–perfusion inequalities [6]. As we had excluded the patients with abnormal

Acknowledgements

The authors wish to thank Dr Hitoshi Murao (Central Clinical Laboratory, Osaka Medical College) for his valuable advice about pulmonary function tests.

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Pulmonary diffusing capacity, serum angiotensin-converting enzyme activity and the angiotensin-converting enzyme gene in Japanese non-insulin-dependent diabetes mellitus patients

Abstract

Introduction

Section snippets

Subjects and methods

Results

Discussion

Acknowledgements

Chest

Diabetes Res. Clin. Pract.

Newer aspects of diabetic microangiopathy

Ann. Rev. Med.

Is the lung a ‘target organ’ in diabetes mellitus?

Arch. Intern. Med.

Serum angiotensin-converting enzyme: evaluations in diabetes mellitus

Ann. Intern. Med.

Serum angiotensin converting enzyme in pulmonary disease

Lung

PCR deletion of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase1)

Nucl. Acids Res.

Effect of low hemoglobin levels on the diffusing capacity of the lungs for CO

Respiration