Intensive therapy for diabetes through influence on innate immune system

Steno-2 Study has previously shown that original intensive therapy reduced the risk of cardiovascular and microvascular events to about 50% of that of conventional treatment in type 2 diabetic patients. Further, in the subsequent follow-up study, intensive therapy was found to have sustained beneficial effects on cardiovascular events and death rate in this population. Another clinical trial, China Da Qing Diabetes Prevention Study, has recently reported that group-based lifestyle interventions over six years could prevent or delay the development of diabetes in patients with impaired glucose tolerance (IGT). The two famous intervention trials have demonstrated a consistent salutary effect of intensive therapy on the development and progression of diabetes and its complications. However, the exact mechanisms of the sustained beneficial effects remain to be elusive. There is a growing body of evidence to suggest that type 2 diabetes is associated with a general activation of the innate immune system, in which there is a chronic, cytokine-mediated state of low-grade inflammation. Some diabetic treatment agents with anti-inflammatory properties may lower both acute-phase reactants which are components of the innate immune system independent of their anti-hyperglycemic actions or lipid-lowering effects. The immunomodulatory effects of regular exercise, and in particular resistance training, may have positive effects on innate immunity and so may provide benefits for the profile of type 2 diabetes in addition to improving strength and functional abilities. Therefore, we speculate that the effects on the innate immune system through pharmacologic therapy or lifestyle modification such as exercise training are able to account - at least amongst others - for carry-over beneficial effects of multifactorial intervention on insulin resistance and type 2 diabetes. This hypothesis, if proved to be valid, might provide a new therapeutic option for the management of type 2 diabetes. (C) 2009 Elsevier Ltd. All rights reserved.