Is type II diabetes mellitus a disease of the innate immune system?
Type II (non-insulin-dependent) diabetes mellitus is associated with increased blood concentrations of markers of the acute-phase response, including sialic acid, alpha-1 acid glycoprotein, serum amyloid A, C-reactive protein and cortisol, and the main cytokine mediator of the response, interleukin-6. The dyslipidaemia common in Type II diabetes (hypertriglyceridaemia and low serum levels of HDL cholesterol) is also a feature of natural and experimental acute-phase reactions. We review evidence that a long-term cytokine-mediated acute-phase reaction occurs in Type II diabetes and is part of a wide-ranging innate immune response. Through the action of cytokines on the brain, liver, endothelium, adipose tissue and elsewhere, this process could be a major contributor to the biochemical and clinical features of metabolic syndrome X (glucose intolerance, dyslipidaemia, insulin resistance, hypertension, central obesity, accelerated atherosclerosis) but also provides a mechanism for many other abnormalities seen in Type II diabetes, including those in blood clotting, the reproductive system, metal ion metabolism, psychological behaviour and capillary permeability. In the short-term, the innate immune system restores homeostasis after environmental threats; we suggest that in Type II diabetes and impaired glucose tolerance long-term lifestyle and environmental stimulants, probably in those with an innately hypersensitive acute-phase response, produce disease instead of repair.
Pickup
J C
JC
Department of Chemical Pathology, United Medical School, Guy's Hospital, London, UK.
Crook
M A
MA
D000210:Acute-Phase Reaction; D000818:Animals; D016207:Cytokines / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology*; D006801:Humans; D007109:Immunity; D008954:Models, Biological
D016207:Cytokines