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Effects Of Statin Treatment On The Inflammation-Related Factors In Type 2 Diabetes With Or Without Macro-Vascular Complications

Posted on:2007-11-05Degree:MasterType:Thesis
Country:ChinaCandidate:C Y WangFull Text:PDF
GTID:2144360242963443Subject:Internal cardiovascular disease
Abstract/Summary:PDF Full Text Request
An increasing number of epidemiological studies have shown that type 2 diabetes or impaired glucose tolerance is an independent risk factor of cardiovascular diseases. A seven-year-long prospective epidemiological study of middle and old-aged Americans showed that risk of myocardial infraction or death for Type 2 Diabetic patients without a history of myocardial infarction is similar to that of non-Type 2 Diabetic patients with previous myocardial infarction. American Heart Association (AHA), therefore, acknowledged in the 1999's proclamation that Diabetes is a CHD risk equivalent; in the 2001 NCEP-ATP III made by American cholesterol education project experts about the screening, evaluation, and treatment of the adults Hypercholesterolemia, it is pointed out that diabetes is the CHD risk equivalents and it is proposed to treat the type 2 diabetics by active statins.Statins is one class of important medicines for both primary and secondary prevention and treatments for coronary heart diseases and stroke. While statins inhibit the rate-limiting enzyme (HMGCOA) in the process of cholesterol composition and disturb anabolism of cholesterol and reduce the plasma cholesterol level. The basic researches found that Statins has the effect of anti-inflammatory action as well as anti- atherosclerotic action through the pleiotropic effects. In vivo studies also showed that statins could down-regulate inflammatory markers and mediators, C reactive protein (CRP), reduce the secretion of other inflammatory factors and chemical factors and inhibit the expression of major histocompatibility complex-II inγ-interferon to regulate immunity. The clinical studies also showed that statins could reduce the level of inflammatory factors in patients with cardiovascular diseases with the multiple risk factors, attenuate the inflammatory state of the patients.The diabetes subgroup analysis in Heart Protection Study(HPS)proved that taking 40 mg simvastatin every day would reduce the risk of cardiovascular incidents by 25% in diabetic patients. The protective effects would not be influenced by the levels of blood glucose and cholesterol of the patients. Recently published CARDS'study shows that taking 10 mg atovastatin could dramatically reduce incidence of the cardiovascular and cerebrovascular events and mortality in patients with type 2 diabetes with inconspicuous increase in plasma cholesterol level, suggesting that pleiotropic effects of statins, such as anti-inflammation, endothelial function modulation, anti-coagulation and anti-thrombus, play an important role in cardiovascular protection.Even if type 2 diabetes is associated with a marked increase in the risk of cardio-cerebral vascular diseases, most high risk population and patients with CHD risk equivalents have not be prescribed statins regularly. Therefore, we carried out this study to explore anti-inflammation effects of simvarstatin in type 2 diabetic patients in order to provide theoretical foundation for clinical diabetic patients to take statins for prevention of cardio-cerebral vascular diseases.Method: Patients'collection in the study was carried out as complete matching principle according to age, gender, level of fasting blood glucose and plasma lipids, pancreatic island function, body weight index, blood pressure, as well as course of macrovascular complications. Twenty-eight type 2 diabetic patients were collected in stable condition from July 2004 to May 2005 in Tongji Hospital excluding acute and chronic infections, tumor, and immune diseases. All the patients prescribed oral simvastatin (Germany merck company) 40 mg for the consecutive two weeks and vein blood was drawn from the selected patients in early morning (fasting for 10 to 12 hours) exactly before and after oral simvarstatin. Blood mononuclear cells was separated to test the activity of nuclear transcription factor kappa B (NF-κB P65) and plasma inflammatory factors TNF-α,IL-6,IL-1βand the level of anti-inflammatory factors IL-4,IL-10,hs-CRP were measured with specific kits.Results:①Statins therapy could reduce the general levels of inflammatory cytokines IL- 6,TNF–α,IL - 1βin the Type 2 diabetic patients with and without macrovascular complications but reduce the levels of anti-inflammatory cytokines IL-4 and IL-10;②The levels of inflammation-related factors are closely related with NF-κB P65 activity in peripheral blood mononuclear cells.Conclusion:Type 2 diabetic patients have remarkable increase in inflammatory cytokines and reduction in anti-inflammatory cytokines, which suggest the patients are in an inflammatory state and Statins treatment could remarkably reduce the inflammatory cytokines and increase the level of anti-inflammatory cytokines, suggesting that oral statin attenuate inflammatory status. This preliminary data from diabetic patients provide an insight into relation between diabetes and imflammation as well as a scientific foundation for diabetic patients to take statins for the sake of preventing cardio-cerebral vascular diseases.
Keywords/Search Tags:nucleus factor kappa B, Type 2 diabetes, inflammatory factors, anti-inflammatory factors, CHD risk equivalents
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