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© 2004 by the American Diabetes Association, Inc.
Reviews/Commentaries/Position Statements |
Inflammation and Activated Innate Immunity in the Pathogenesis of Type 2 Diabetes
From the Metabolic Unit, Guy’s, King’s and St. Thomas’s School of Medicine, Guy’s Hospital, London, U.K.
Address correspondence and reprint requests to John Pickup, Metabolic Unit, Thomas Guy House, GKT School of Medicine, Guy’s Hospital, London SE1 9RT, U.K. E-mail: john.pickup{at}kcl.ac.uk
There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properties lower both acute-phase reactants and glycemia (aspirin and thiazolidinediones) and possibly decrease the risk of developing type 2 diabetes (statins). Among the risk factors for type 2 diabetes, which are also known to be associated with activated innate immunity, are age, inactivity, certain dietary components, smoking, psychological stress, and low birth weight. Activated immunity may be the common antecedent of both type 2 diabetes and atherosclerosis, which probably develop in parallel. Other features of type 2 diabetes, such as fatigue, sleep disturbance, and depression, are likely to be at least partly due to hypercytokinemia and activated innate immunity. Further research is needed to confirm and clarify the role of innate immunity in type 2 diabetes, particularly the extent to which inflammation in type 2 diabetes is a primary abnormality or partly secondary to hyperglycemia, obesity, atherosclerosis, or other common features of the disease.
Abbreviations: AGE, advanced glycation end product • CRP, C-reactive protein • HPA, hypothalamic-pituitary-adrenal • IFG, impaired fasting glucose • IGT, impaired glucose tolerance • IL, interleukin • IRS, insulin receptor substrate • LC-NE, locus coeruleus-norepinephrine • LPS, lipopolysaccharide • NF-
B, nuclear factor-B • PAI-1, plasminogen activator inhibitor 1 • PPAR, peroxisome proliferator-activated receptor • PRR, pattern recognition receptor • TLR, toll-like receptor • TNF, tumor necrosis factor
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|
|
|
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|
|
|
|
 |
|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
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|
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|
|
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|
|
|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|
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|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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