Circulating Surfactant Protein A (SP-A), a Marker of Lung Injury, Is Associated With Insulin Resistance

Fernández-Real, José Manuel; Chico, B. N. Diaz; Shiratori, Masanori; Nara, Yoshiharu; Takahashi, Hiroki; Ricart, Wifredo

doi:10.2337/dc07-2173

Cited by 29 publications

(25 citation statements)

References 27 publications

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“…When the alveolocapillary barrier is damaged, surfactant proteins leak into the bloodstream. A recent population-based random sample has described how increased circulating levels of surfactant protein A, the major surfactant-associated protein, were associated with altered glucose tolerance and insulin resistance [17]. Therefore, surfactant defects in diabetic individuals may also lead to an increase in airway resistance and to a reduction in FEV 1 , FEF and FEV 1 / FVC ratio, as observed in our patients.…”

Section: Discussionsupporting

confidence: 50%

“…This is undeniably significant, because airflow limitation is an independent predictor of death in type 2 diabetes [12]. The available data suggest that the appearance of structural changes in respiratory muscle associated with insulin resistance [13,14], non-enzymatic glycosylation of the connective tissue [15,16], defects in the stimulation of pulmonary surfactant production [17] and the presence of a low-grade chronic inflammation state [18] should be considered among the possible mechanisms involved in this relationship. In support of these findings, thickening of the alveolar epithelia and pulmonary capillary basal lamina, fibrosis, centrilobular emphysema and pulmonary microangiopathy have been described in autopsy findings from diabetic individuals [19].…”

Section: Introductionmentioning

confidence: 99%

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Type 2 diabetes impairs pulmonary function in morbidly obese women: a case–control study

et al. 2010

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Aims/hypothesis To determine whether the presence of type 2 diabetes and the degree of metabolic control are related to reduced pulmonary function in obese individuals. Conclusions/interpretation The presence of diabetes and the degree of glycaemic control are related to respiratory function impairment in morbidly obese women. Therefore, the impact of type 2 diabetes on pulmonary function should be taken into consideration by those providing care for obese people.

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Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Type 2 diabetes impairs pulmonary function in morbidly obese women: a case–control study

et al. 2010

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“…Another possible mechanism may involve SP-A. Levels of SP-A in the blood have been reported to be associated with insulin resistance [17] and may possibly be associated with a lower VC because SP-A is a marker of interstitial lung injury.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to impaired restrictive lung function, impaired obstructive lung function is not associated with diabetes [12][13][14][15][16]. The underlying mechanisms of the association between a lower VC and diabetes are not known, but insulin resistance is thought to play a role [9][10][11][12][13] and, recently, blood levels of surfactant protein A (SP-A) have been reported to be associated with insulin resistance [17]. SP-A, which is a marker of interstitial lung injury, may be a possible link between lower VC and insulin resistance.…”

Section: Introductionmentioning

confidence: 99%

A cross-sectional relationship between vital capacity and metabolic syndrome and between vital capacity and diabetes in a sample Japanese population

Oda

Kawai

2009

Environ Health Prev Med

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Objectives A lower vital capacity (VC) has been reported to be an independent predictor of diabetes in Western countries. The aim of this study was to examine the relationships between VC and diabetes and between VC and metabolic syndrome (MS) in Japanese individuals. Methods Stepwise multiple linear regressions with fasting glucose as a dependent variable and age, metabolic risk factors, and percentage vital capacity (%VC) as independent variables were performed using data obtained from 1651 men and 957 women. Area under the receiver operating characteristic curve (AUC) of -%VC for diagnosing diabetes, MS, and Japanese MS (JMS) were calculated, and stepwise logistic regressions using diabetes, MS, and JMS as dependent variables were performed. Results Percentage vital capacity was independently associated with fasting glucose in men, but not in women. The AUC of -%VC for diagnosing diabetes, MS, and JMS were 0.647, 0.606, and 0.598, respectively (all p \ 0.0001) in men and 0.639 (p = 0.065), 0.513 (p = 0.732), and 0.668 (p = 0.01), respectively, in women. Age, waist circumference (WC), and %VC in men and WC and %VC in women were independently associated with diabetes. Age and %VC in men and only age in women were independently associated with MS, and age and %VC in both men and women were independently associated with JMS. Conclusions Among a representative Japanese population, a lower VC was significantly associated with diabetes and MS in men, but the relationships were not conclusive in women.

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“…Surfactant protein and message were either reduced (39) or delayed (20,21) in fetal and neonatal lungs of offspring of streptozotocin-treated rats. In contrast to T1DM, circulating SP-A level was significantly higher in patients with insulin resistance compared with normal subjects (16). Surfactant dysregulation also occurs in diet-induced obesity.…”

Section: Summary Of Findingsmentioning

confidence: 92%

Fatty diabetic lung: altered alveolar structure and surfactant protein expression

Foster

Ravikumar

Bellotto

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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nary dysfunction develops in type 2 diabetes mellitus (T2DM) in direct correlation with glycemia and is exacerbated by obesity; however, the associated structural derangement has not been quantified. We studied lungs from obese diabetic (fa/fa) male Zucker diabetic fatty (ZDF) rats at 4, 12, and 36 wk of age, before and after onset of T2DM, compared with lean nondiabetic (ϩ/ϩ) rats. Surfactant proteins A and C (SP-A and SP-C) immunoexpression in lung tissue was quantified at ages 14 and 18 wk, after the onset of T2DM. In fa/fa animals, lung volume was normal despite obesity. Numerous lipid droplets were visible within alveolar interstitium, lipofibroblasts, and macrophages, particularly in subpleural regions. Total triglyceride content was 136% higher. By 12 wk, septum volume was 21% higher, and alveolar duct volume was 36% lower. Capillary basement membrane was 29% thicker. Volume of lamellar bodies was 45% higher. By age 36 wk, volumes of interstitial collagen fibers, cells, and matrix were respectively 32, 25, and 80% higher, and capillary blood volume was 18% lower. ZDF rats exhibited a strain-specific increase in resistance of the air-blood diffusion barrier with age, which was exaggerated in fa/fa lungs compared with ϩ/ϩ lungs. In fa/fa lungs, SP-A and SP-C expression were elevated at age 14 -18 wk; the normal age-related increase in SP-A expression was accelerated, whereas SP-C expression declined with age. Thus lungs from obese T2DM animals develop many qualitatively similar changes as in type 1 diabetes mellitus but with extensive lipid deposition, altered alveolar type 2 cell ultrastructure, and surfactant protein expression patterns that suggest additive effects of hyperglycemia and lipotoxicity. diabetes mellitus; lung morphometry; lipid deposition; collagen; surfactant-associated proteins THE LUNG IS A RECOGNIZED TARGET of diabetic microangiopathy, manifested by modest restrictions of ventilatory capacity, lung volume, and diffusing capacity (12,24,41). Because alveolar microvascular reserves are extensive, pulmonary dysfunction is usually not the presenting complaint in diabetes mellitus, although modest pulmonary dysfunction may become overtly debilitating under physiological stress (e.g., high-altitude exposure or exercise) or following the loss of alveolar microvascular reserves brought on by aging or disease (23,24). In patients with type 1 diabetes mellitus (T1DM), we have found a significant restrictive defect associated with decreased lung diffusing capacity for carbon monoxide (DL CO ) at a given pulmonary blood flow, mainly due to a reduction of membrane conductance compared with age-matched nondiabetic healthy subjects (41, 52). Structural abnormalities observed at autopsy in diabetic human lungs include thickened epithelial and capillary basement membranes (72, 77), alveolar septal destruction, and enlarged air spaces (32). In streptozotocin-induced T1DM, volumes of basal laminae, extracellular matrix, and interstitial connective tissue are increased in diabetic lungs compared with contr...

show abstract

Circulating Surfactant Protein A (SP-A), a Marker of Lung Injury, Is Associated With Insulin Resistance

Cited by 29 publications

References 27 publications

Type 2 diabetes impairs pulmonary function in morbidly obese women: a case–control study

Type 2 diabetes impairs pulmonary function in morbidly obese women: a case–control study

A cross-sectional relationship between vital capacity and metabolic syndrome and between vital capacity and diabetes in a sample Japanese population

Fatty diabetic lung: altered alveolar structure and surfactant protein expression

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