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 proliferator-activated 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.
From the Department of Medicine, Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, Connecticut (SH); and the Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai School of Medicine, New York (MNG).
Dr. Gong received grant support from NIH (RO1 HL084060, RO1 HL086667, and RO1 HL60710). Dr. Honiden has not disclosed any potential conflicts of interest.
For information regarding this article, E-mail: Michelle.Gong@mssm.edu