The relation between insulin resistance and lung function: a cross sectional study

Sagun, Gul; Gedik, Canan; Ekiz, Esra; Karagoz, Engin; Takır, Mümtaz; Oğuz, Aytekin

doi:10.1186/s12890-015-0125-9

Cited by 31 publications

(21 citation statements)

References 32 publications

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“…To the best of our knowledge, no clear links have been explored between diabetes and the CCSP. However, it is intriguing to speculate that reductions in CCSP in diabetics may be a mechanism underlying human epidemiology studies suggesting associations between diabetes (Klein et al 2010), insulin resistance (Sagun et al 2015), and the metabolic syndrome (Chen et al 2014) and reduced lung function (FEV1 and FVC) and increased incidence of restrictive lung disease (Sonoda et al 2018).…”

Section: Discussionmentioning

confidence: 99%

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Repetitive Ozone Exposures and Evaluation of Pulmonary Inflammation and Remodeling in Diabetic Mouse Strains

Wagner

Barkauskas

Vose

et al. 2020

Environ Health Perspect

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BACKGROUND: Epidemiological studies support the hypothesis that diabetes alters pulmonary responses to air pollutants like ozone (O 3). The mechanism(s) underlying these associations and potential links among diabetes, O 3 , and lung inflammation and remodeling are currently unknown. OBJECTIVES: The goal was to determine whether pulmonary responses to repetitive ozone exposures are exacerbated in murine strains that are hyperglycemic and insulin resistant. METHODS: Normoglycemic and insulin-sensitive C57BL/6J mice; hyperglycemic, but mildly insulin-resistant, KK mice; and hyperglycemic and markedly insulin-resistant KKAy mice were used for ozone exposure studies. All animals were exposed to filtered air (FA) or repetitive ozone (0:5 ppm O 3 , 4 h/d, for 13 consecutive weekdays). Tissue analysis was performed 24 h following the final exposure. This analysis included bronchoalveolar lavage (BAL) for cell and fluid analysis, and tissue for pathology, immunohistology, mRNA, and hydroxyproline. RESULTS: Following repetitive O 3 exposure, higher bronchoalveolar lavage fluid inflammatory cells were observed in all mice (KKAy >KK >C57BL=6), with a notable influx of neutrophils and eosinophils in KK and KKAy mice. Although the lungs of O 3-exposed C57BL/6J and KK mice had minimal centriacinar histological changes without fibrosis, the lungs of O 3-exposed KKAy mice contained marked epithelial hyperplasia in proximal alveolar ducts and adjacent alveoli with associated centriacinar fibrosis. Fibrosis in O 3-exposed KKAy lungs was confirmed with immunohistochemistry, tissue hydroxyproline content, and tissue mRNA expression of fibrosis-associated genes (Ccl11, Il13, and Mmp12). Immunofluorescence staining and confocal microscopy revealed alterations in the structure and composition of the airway and alveolar epithelium in regions of fibrosis. DISCUSSION: Our results demonstrate that in diabetic animal strains repetitive ambient ozone exposure led to early and exaggerated pulmonary inflammation and remodeling. Changes in distal and interstitial airspaces and the activation of Th2 inflammatory and profibrotic pathways in experimental animals provide a preliminary, mechanistic framework to support the emerging epidemiological associations among air pollution, diabetes, and lung disease.

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Section: Discussionmentioning

confidence: 99%

“…However, it is intriguing to speculate that reductions in CCSP in diabetics may be a mechanism underlying human epidemiology studies suggesting associations between diabetes ( Klein et al. 2010 ), insulin resistance ( Sagun et al. 2015 ), and the metabolic syndrome ( Chen et al.…”

Section: Discussionmentioning

confidence: 99%

Repetitive Ozone Exposures and Evaluation of Pulmonary Inflammation and Remodeling in Diabetic Mouse Strains

Wagner

Barkauskas

Vose

et al. 2020

Environ Health Perspect

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“…However, the pathophysiological mechanisms underlying the development of this deleterious effect of type 2 diabetes mellitus (T2DM) and its aggravation are still mostly unclear, with conflicting evidence. Among the well-recognized mechanisms, the metabolic pathways related to insulin resistance and low-grade chronic inflammation, inherent in T2DM pathophysiology, have been emphasized [ 5 , 6 ]. In addition, the effect of metabolic control on pulmonary function is also controversial.…”

Section: Introductionmentioning

confidence: 99%

Non-linear association between diabetes mellitus and pulmonary function: a population-based study

et al. 2020

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Background There is increasing evidence that the lung is a target organ of diabetes. This study aimed to examine in detail the association between diabetes mellitus and pulmonary function using a national cohort. We also aimed to explore the non-linear association between pulmonary function and blood glucose, insulin resistance, and C-reactive protein (CRP). Methods A total of 30,442 participants from the National Health and Nutrition Examination Survey from the period between 2007 and 2012 were included. The cross-sectional association between diabetes mellitus and pulmonary function was assessed using multiple linear regression. Where there was evidence of non-linearity, we applied a restricted cubic spline with three knots to explore the non-linear association. Partial mediation analysis was performed to evaluate the underlying mechanism. All analyses were weighted to represent the US population and to account for the intricate survey design. Results A total of 8584 people were included in the final study population. We found that diabetes was significantly associated with reduced forced expiratory volume in one second (FEV1) and forced vital capacity. We further found L-shaped associations between hemoglobin A1c (HbA1c) and pulmonary function. There was a negative association between HbA1c and FEV1 in diabetes participants with good glucose control (HbA1c < 7.0%), but not in patients with poor glucose control. A non-linear association was also found with fasting plasma glucose, 2 h-plasma glucose after oral glucose tolerance test, insulin resistance, and CRP. Finally, we found that diabetes duration did not affect pulmonary function, and the deleterious effect of diabetes on pulmonary function was mediated by hyperglycemia, insulin resistance, low-grade chronic inflammation (CRP), and obesity. Conclusions Diabetes mellitus is non-linearly associated with pulmonary function. Our finding of a negative association between HbA1c and FEV1 in diabetes patients with good glucose control but not in patients with poor glucose control indicates that a stricter glycemic target should be applied to diabetic patients to improve pulmonary function. Given, the cross-sectional nature of this research, a longitudinal study is still needed to validate our findings.

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“…In an Australian cohort, the increased prevalence of self-reported asthma in PCOS remained significant after adjustment for age, BMI and smoking (13); this may indicate an independent effect of PCOS on asthma. Additionally, an association between impaired glucose regulation and decreased lung function has been described in non-diabetic populations (14,15). In a large cross-sectional study, oligomenorrhea, one of three criteria of PCOS diagnosis, was associated with increased prevalence of asthma symptoms and decreased forced vital capacity (FVC) at all values of BMI above 25kg/m 2 (16).…”

Section: Introductionmentioning

confidence: 99%

Impaired Respiratory Function in Women With PCOS Compared With Matched Controls From a Population-Based Study

Underdal

Salvesen

Henriksen

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Increased prevalence of asthma has been reported from epidemiological studies in women with polycystic ovary syndrome (PCOS). Objective To investigate respiratory function in women with PCOS compared with controls in a clinical setting. Design An 8-year clinical follow-up study including self-reported asthma diagnoses and spirometry of women with PCOS randomized to metformin or placebo during pregnancy in the original studies (the Pilot and the PregMet-study), compared with matched controls from a population-based cohort study (The HUNT Study). Setting Secondary and tertiary care centers. Participants A total of 145 women with PCOS (54% of original cohort) were matched 1:3 to controls, on gender, age, and smoking-status. Main outcomes and measures Self-reported doctor-diagnosed asthma (DDA), percentage of predicted forced expiratory volume in the first second of expiration (FEV1 % predicted), percentage of predicted forced vital capacity (FVC % predicted). Results Women with PCOS reported more DDA compared with controls (19% vs 9%; P < 0.01). Spirometry indicated a combined obstructive (FEV1 % predicted, 93.7 vs 102.0; P < 0.01) and restrictive (FVC % predicted, 94.5 vs 103.7; P < 0.01) respiratory impairment in PCOS compared with controls. Metformin in pregnancy did not affect respiratory function at follow-up. Conclusion Women with PCOS reported higher prevalence of DDA compared with controls matched for age and smoking status. In addition, respiratory function was decreased, with both obstructive and restrictive components. Further insight to the underlying pathogenesis of these observations is needed. Clinical trial registration ClinicalTrials.gov: The PregMet study: NCT00159536. The Pilot study: NCT03259919.

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The relation between insulin resistance and lung function: a cross sectional study

Cited by 31 publications

References 32 publications

Repetitive Ozone Exposures and Evaluation of Pulmonary Inflammation and Remodeling in Diabetic Mouse Strains

Repetitive Ozone Exposures and Evaluation of Pulmonary Inflammation and Remodeling in Diabetic Mouse Strains

Non-linear association between diabetes mellitus and pulmonary function: a population-based study

Impaired Respiratory Function in Women With PCOS Compared With Matched Controls From a Population-Based Study

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