Diabetes, insulin, and development of acute lung injury

Abstract

Objectives-Recently, many studies have investigated the immunomodulatory effects of insulin and glucose control in critical illness. This review examines evidence regarding the relationship between diabetes and the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), reviews studies of lung injury related to glycemic and nonglycemic metabolic features of diabetes, and examines the effect of diabetic therapies.Data Sources and Study Selection-A MEDLINE/PubMed search from inception to August 1, 2008, was conducted using the search terms acute lung injury, acute respiratory distress syndrome, hyperglycemia, diabetes mellitus, insulin, hydroxymethylglutaryl-CoA reductase inhibitors (statins), angiotensin-converting enzyme inhibitor, and peroxisome proliferatoractivated receptors, including combinations of these terms. Bibliographies of retrieved articles were manually reviewed.Data Extraction and Synthesis-Available studies were critically reviewed, and data were extracted with special attention to the human and animal studies that explored a) diabetes and ALI; b) hyperglycemia and ALI; c) metabolic nonhyperglycemic features of diabetes and ALI; and d) diabetic therapies and ALI.Conclusions-Clinical and experimental data indicate that diabetes is protective against the development of ALI/ARDS. The pathways involved are complex and likely include effects of hyperglycemia on the inflammatory response, metabolic abnormalities in diabetes, and the interactions of therapeutic agents given to diabetic patients. Multidisciplinary, multifaceted studies, involving both animal models and clinical and molecular epidemiology techniques, are essential. Keywordsacute respiratory distress syndrome; acute lung injury; hyperglycemia; diabetes mellitus; insulin Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a devastating condition defined by the American-European Consensus Committee on ARDS as an acute syndrome of lung inflammation and increased permeability associated with severe hypoxia and bilateral infiltrates on chest radiographs with no evidence of left heart failure (1). Decades of animal and clinical studies have identified several pathophysiologic mechanisms important in the development of ALI/ARDS. Acute inflammation is a key feature, as evidenced by the central role of neutrophil recruitment and activation and the increased expression and release of inflammatory mediators, such as proinflammatory and antiinflammatory cytokines and chemokines. Disturbances in surfactant function and edema Copyright © 2009 clearance are present, and ample evidence supports imbalances in oxidant/antioxidant activity (2), coagulation/fibrinolysis, and fibrosis/repair. The relative balance of these interacting pathways either exacerbates or ameliorates further lung injury (3,4).ALI/ARDS is a commonly encountered condition, with 190,600 cases of ALI per year in the United States and an associated 74,500 deaths and 3.6 million hospital days (5). Of the predisposing injuries for ALI/ARDS, ...

Respiratory Dysfunction in Patients With Sepsis: Protective Effect of Diabetes Mellitus

“…9 In an observational cohort study 6 of 375 patients treated with mechanical ventilation for more than 48 hours, higher glucose levels in the first 24 hours of respiratory failure were associated with a decreased risk for acute respiratory distress syndrome (ARDS; P = .025). In another large cohort of 688 critically ill patients at risk for ARDS from sepsis, trauma, massive transfusion, and aspiration, diabetes protected against the development of ARDS, even after adjustments for potential confounders such as age, clinical risk for ARDS, severity of illness, and transfusion (adjusted odds ratio, 0.58; 95% confidence interval, 0.36-0.92).…”

“…Clinical and epidemiological studies [6][7][8][9] have indicated that respiratory dysfunction is less likely in patients who have both sepsis and diabetes mellitus than in patients who have sepsis but no diabetes. Possible explanations for this difference include the effects of hyperglycemia on the inflammatory response, metabolic abnormalities in diabetes, and interactions of agents used to treat diabetes mellitus.…”

“…Possible explanations for this difference include the effects of hyperglycemia on the inflammatory response, metabolic abnormalities in diabetes, and interactions of agents used to treat diabetes mellitus. 7,9 Compared with other ethnic groups, Asian patients, especially those from South Asian countries, have a 4-to 6-fold greater risk for type 2 diabetes mellitus and a higher risk for renal, cardiovascular, and cerebrovascular complications. 10 Knowledge of differences in the pattern of organ failure would be useful in monitoring and managing patients with diabetes mellitus in whom sepsis develops.…”

Variation in the Incidence and Timing of Acute Lung Injury

“…First, the authors appropriately adjusted for racebased differences in the prevalence of diabetes across race groups, a comorbidity that may reduce the risk of ALI. 9 Second, the authors adjusted for tidal volume delivered to patients before ALI was present. It is becoming increasingly recognized that lower tidal volumes may protect individuals who are mechanically ventilated from developing ALI.…”

Effect of oxidative stress on respiratory epithelium from children with Down syndrome

“…Both pulmonary and extrapulmonary triggers, for example, pneumonia and aspiration or sepsis and neurotrauma, can induce ARDS. Patient characteristics, such as the presence of chronic disease or genetic make-up, can modulate the risk for developing ARDS [4].…”