The potential interaction between impaired adipose tissue function, systemic inflammation, and COPD may provide insight into the pathogenesis and reversibility of the systemic pathology in the disease. mechanisms by which these effects may affect lung disease patients. RESULTS: Our results suggest that diabetes can affect the severity and clinical course of several lung diseases. CONCLUSIONS: Although the diabetes-lung association is epidemiologically and clinically well-established, especially in asthma, the underlying mechanism and pathophysiology are not been fully understood. Several mechanisms have been suggested, mainly associated with the pro-inflammatory and proliferative properties of diabetes, but also in relation to micro- and macrovascular effects of diabetes on the pulmonary vasculature. Also, hypoglycemic drugs may influence lung diseases in different ways. For example, metformin was considered a potential therapeutic agent in lung diseases, while insulin was shown to exacerbate lung diseases; this suggests that their effects extend beyond their hypoglycemic properties. [35], in diabetic animal models [36], and in humans [25]. Therefore, the most investigated pathway in the pathogenesis of the diabetes-asthma association is chronic inflammation such as RAGE. RAGE signaling has been shown to be highly expressed in the lung and to induce chronic airway and vascular inflammation [13, 37]. RAGE has a regulatory role in T-cell proliferation and differentiation of both Th1 and Th2 cells [38]. Diabetes-prone non-obese diabetic (NOD) mice have been shown to give rise to enhanced Th2-mediated responses and contribute to a Th2-predominant asthma phenotype. Increased systemic interleukin 6 as an inflammatory and metabolic dysfunction biomarker in diabetes has been associated with more severe asthma [39, 40]. In this context, monocyte chemoattratant protein (MCP) 1, which recruits monocytes to inflammation sites, has been shown to play a significant role in diabetic patients with asthma via airway remodeling and predicts a poorer prognosis [41]. Matrix metallopreinase (MMP) 9 mediates sputum overproduction secondary to airway epithelial barrier dysfunction caused by hyperglycemia, especially during exacerbation, and cause airway inflammation in airway epithelial cells [30, 42]. 2.5 Summary The diabetes-asthma association is well-established epidemiologically and clinically. Diabetes is a risk factor for more severe and complicated asthma. The main pathogenesis of this association is inflammation and pro-inflammatory cytokines. However, the pathogenesis has yet to be fully understood and more research is necessary to establish a strong biological basis. 3. Chronic obstructive pulmonary disease (COPD) and diabetes 3.1 Introduction COPD is a preventable and treatable disease characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities, which are often secondary to significant exposure to noxious particles or gases [43]. It is currently the fourth leading cause of death worldwide. It has been increasingly recognized that the presence of common factors in COPD and in other chronic extra-pulmonary diseases, such as diabetes mellitus, together with the frequent coexistence of these conditions in the same adult individual, supports the hypothesis of common processes sharing their pathogeneses within the same patient [44]. 3.2 Epidemiology Metabolic syndrome has been recognized as one of the most relevant clinical comorbidities associated with COPD patients [45]. However, the link between COPD and diabetes is much less clear. Diabetes is more prevalent in COPD than in the general population. Prevalence estimates of diabetes among COPD patients range between 10.1-23.0% [46, 47]. 3.3 Clinical presentation The risk of diabetes in COPD patients has been Flufenamic acid found to be higher in more severe phenotypes (level 3-4 according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline). This risk was independent of BMI, smoking, and other confounding factors. Moreover, the presence of diabetes among those with COPD has been shown to be associated with worse outcomes, such as Flufenamic acid mortality and hospitalization [48]. 3.4 Mechanisms The mechanisms by which diabetes influences lung function have not yet been fully determined. The correlation between COPD and diabetes may depend on several mutual risk factors and physiological alterations. COPD patients are primarily.In fact, most pulmonology literature does not address diabetes as an influencing factor for lung diseases. Growing evidence suggests that diabetes and the widely used hypoglycemic drugs may impact the pathogenesis, development, and progression of several lung diseases and their prognosis and clinical outcome, suggesting that diabetes should be considered as a relevant factor in the clinical approach to lung disease patients. metformin was regarded as a potential restorative agent in lung diseases, while insulin was shown to exacerbate lung diseases; this suggests that their effects lengthen beyond their hypoglycemic properties. [35], in diabetic animal models [36], and in humans [25]. Therefore, probably the most investigated pathway in the pathogenesis of the diabetes-asthma association is definitely chronic swelling such as RAGE. RAGE signaling offers been shown to be highly indicated in the lung and to induce chronic airway and vascular swelling [13, 37]. RAGE has a regulatory part in T-cell proliferation and differentiation of both Th1 and Th2 cells [38]. Diabetes-prone non-obese diabetic (NOD) mice have been shown to give rise to enhanced Th2-mediated reactions and contribute to a Th2-predominant asthma phenotype. Improved systemic interleukin 6 as an inflammatory and metabolic dysfunction biomarker in diabetes has been associated with more severe asthma [39, 40]. With this context, monocyte chemoattratant protein (MCP) 1, which recruits monocytes to swelling sites, has been shown to play a significant part in diabetic patients with asthma via airway redesigning and predicts a poorer prognosis [41]. Matrix metallopreinase (MMP) 9 mediates sputum overproduction secondary to airway epithelial barrier dysfunction caused by hyperglycemia, especially during exacerbation, and cause airway swelling in airway epithelial cells [30, 42]. 2.5 Summary The diabetes-asthma association is well-established epidemiologically and clinically. Diabetes is definitely a risk element for more severe and complicated asthma. The main pathogenesis of this association is definitely swelling and pro-inflammatory cytokines. However, the pathogenesis offers yet to be fully recognized and more study is necessary to establish a strong biological basis. 3. Chronic obstructive pulmonary disease (COPD) and diabetes 3.1 Intro COPD is a preventable and treatable disease characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities, which Flufenamic acid are often secondary to significant exposure to noxious particles or gases [43]. It is currently the fourth leading cause of death worldwide. It has been progressively recognized that the presence of common factors in COPD and in additional chronic extra-pulmonary diseases, such as diabetes mellitus, together with the frequent coexistence of these conditions in the same adult individual, helps the hypothesis of common processes posting their pathogeneses within the same patient [44]. 3.2 Epidemiology Metabolic syndrome has been recognized as probably one of the most relevant clinical comorbidities associated with COPD individuals [45]. However, the link Rabbit polyclonal to GST between COPD and diabetes is much less obvious. Diabetes is definitely more prevalent in COPD than in the general population. Prevalence estimations of diabetes among COPD individuals range between 10.1-23.0% [46, 47]. 3.3 Clinical demonstration The risk of diabetes in COPD individuals has been found to be higher in more severe phenotypes (level 3-4 according to the Global Initiative for Chronic Obstructive Lung Disease (Platinum) guideline). This risk was self-employed of BMI, smoking, and additional confounding factors. Moreover, the presence of diabetes among those with COPD has been shown to be associated with worse results, such as mortality and hospitalization [48]. 3.4 Mechanisms The mechanisms by which diabetes influences lung function have not yet been fully determined. The correlation between COPD and diabetes may depend on several mutual risk factors and physiological alterations. COPD individuals are primarily former or active smokers. Smoking may lead to concomitant comorbidity, but it is definitely progressively evident that individuals with COPD also have a high burden of comorbidity self-employed of smoking [49]. In the large COPD Gene cohort, diabetes subjects Flufenamic acid with a history of smoking experienced worse lung function actually if they experienced no established analysis of COPD [50]. Recently, there has been increasing desire for the relationship between obesity and COPD, although the Flufenamic acid nature of this association remains unfamiliar. It has been proposed that reduced oxidative capacity and systemic hypoxia may play a role in the pathogenesis of COPD in obese individuals [51]. The potential connection between impaired adipose cells function, systemic swelling, and COPD may provide insight into the pathogenesis and reversibility of the systemic pathology in the disease. The effects of obesity.