课件：糖尿病与发炎指标CR.ppt

糖尿病與發炎指標CRP,吳達仁 醫師 成大醫學院附設醫院內科部 內分泌新陳代謝科,CRP : From Acute Phase Protein to Cardiovascular disease,CRP is a symmetrical ring molecule that consists of 5 noncovalent but associate protomers. Each protomer has 2 calcium ions responsible for the specific binding of phosphochlorine. Phosphochlorine is a common constituent of many bacterial and fungal polysaccharides and most biologic cell membranes, such as the phosphochlorine residues of C (or capsular)-polysaccharide of Streptococcus pneumoniae. The protein was named “C-reactive” because of this reaction. A stable pentameric protein-compound with a half-life of 19 hours, without diurnal variation, CRP is a pathogenic marker and a nonspecific marker of inflammation.CRP is synthesized in response to the acute phase of a bacterial or fungal infection.,Molecular Structure and Morphology of Human CRP,Negatively stained electron micrograph showing the typical pentameric disc-like structure face-on and side-on (arrows). Ribbon diagram of the crystal structure, showing the lectin fold and the two calcium atoms (spheres) in the ligand-binding site of each protomer . Space-filling model of the CRP molecule, showing a single phosphocholine molecule located in the ligand-binding site of each protomer).,Pepys MB, et al. Clin Invest 2003;111:1805-1812.,Assays of CRP and Reference Ranges,During the acute phase of infection, serum CRP levels were measured by rate nephelometry (“serum CRP assay”). These assays have a lower limit of detection of only 6 to 10 mg/l. A more sensitive latex particle-enhanced immunoturbidimetric assay (“high sensitivity hs-CRP assay”) has been developed that has a lower limit of detection (or sensitivity) of about 0.15 mg/l. It is used to assess for cardiovascular risk. The risk factors by hs-CRP levels (CDC, AHA): CRP 1 mg/l is low CVD risk CRP 1 to 3 mg/l is moderate CVD risk CRP 3 to 10 mg/l is high CVD risk CRP levels 10 mg/l generally indicates bacterial infection,Demographic and Descriptive Characteristics of the US Population Without a Previous Diagnosis of Hypertension From NHANES III,Matthias B. et al. Diabetes Care 2004;27:1680-1687.,WOSCOPS: Overlap Analysis,Frequency per 100,On treatment LDL,WOSCOPS Group. Circulation. 1998;97:1440-45,The Effects of Atorvastatin versus Simvastatin on Atherosclerosis Progression Study ( ASAP),Atorvastatin reduced CRP levels to a greater extent than simvastatin,van Wissen S, et al. Atherosclerosis. 2002;165:361-366.,*P0.001 for difference between groups; * P=0.02 for difference between groups,*,*,-50,-45,-40,-35,-30,-25,-20,-15,-10,-5,0,1 Year,2 Years,Atorvastatin,Simvastatin,Percent change in hs-CRP,-44.9,-14.0,-40.1,-19.7,Influence of Baseline BMI on Ability of Atorvastatin to Modify CV Risk Factors (REVERSAL Study ),P0.01,P0.01,P0.05,%,Nicholls SJ, et al. Am J Cardiol 2006;97:1553-7.,Total Ch LDL-C CRP,Effects of Switching Pravastatin to Cerivastatin on C-Reactive Protein, Butyrylcholinesterase, and Lipids,Patients were eligible for inclusion if they had an active prescription for pravastatin for at least 3 months. Subjects were converted from pravastatin 10 mg-40 mg daily to cerivastatin 0.2 mg-0.8 mg daily at equipotent doses. Median CRP levels at the pravastatin phase, 6 weeks of cerivastatin, and 12 weeks of cerivastatin, were 0.380 mg/dL, 0.403 mg/dL, and 0.364 mg/dL p = 0.772), respectively. Conclusion: Median CRP remained stable with pravastatin and cerivastatin use, although TC and LDL decreased. The further decline observed with LDL, but not CRP suggests differing effects of statins on LDL and CRP.,Shinn AH, et al Curr Med Res Opin. 2005; (2): 207-213.,Risk Factors for CHD,Modifiable Hypertension High LDL cholesterol Low HDL cholesterol Cigarette smoking Physical inactivity Diabetes Obesity (BMI 30) Thrombogenic/hemostatic state Atherogenic diet,Non-modifiable Age Male sex Family history of premature CHD,National Cholesterol Education Program Adult Treatment Panel III. 2002. NIH Publication No. 02-5215.,Factors Associated with Increased or Decreased CRP,Higher CRP Hypertension Hyperglycemia Low HDL/ high TG Smoking Obesity Metabolic syndrome Estrogen/progesterone use Chronic infection,Lower CRP Increase exercise Alcohol consumption Weight loss Medication: Statin Fibrate,Hypertension and Dyslipidaemia Are Major Risk Factors for CHD,Kannel W. In: Hypertension: Pathophysiology and Treatment. New York: McGraw-Hill, Inc.; 1977:888-909; Castelli WP. Am J Med. 1984;76:4-12.,CHD incidence/1000,Probability of CVD/1000,Age,40,50,60,70,Framingham study,SBP (mm Hg) in men,TC (mg/dL) in men,Concomitant Hypertension and Dyslipidemia Increase the Risk of Developing Fatal CVD,Adapted from De Backer G et al. Eur J Cardiovasc Prev Rehabil. 2003;10 (suppl 1):S1-S78.,Dyslipidemia,Hypertension,Dyslipidemia/ Hypertension,TC 271 mg/dL (7 mmol/L),SBP 180 mm Hg,TC 271 mg/dL (7 mmol/L) SBP 180 mm Hg,Hypertension and High Cholesterol are Twice as Prevalent in Adults with DM Compared to those without DM,Archives of Internal Medicine 2002; 162: 427-433,* P0.001,Hypertension and Dyslipidemia Commonly Occurs in Diabetes in Taiwan,TADE 2002,Prevalence (%),High uric acid,Dyslipidemia,Obesity,Hypertension,C反應蛋白 (CRP)可加強 TC/HDL比值預估首度心肌梗塞發生之風險,Ridkor PM. Circulation 1996;97:2007-11.,冠 心 病 風 險,TC/HDL 比值,CRP,C-RP (mg/L),0 1 2 3 4,N=1,008,代謝異常數目,代謝異常包括： 肥胖 高血壓 高三酸甘油脂症 低HDL-C 高胰島素血症,Festa et al. Circulation 2000;102:42-7.,C反應蛋白 (CRP)與代謝異常數目 Insulin Resistance Atherosclerosis Study,5 4 3 2 1,P0.001,Albert MA, et al. Circulation. 2003;107:443,Alcohol Consumption and Plasma C-RP,Many Assays Developed Before hs-CRP Are More Sensitive Than “hs-CRP Assay”,As early as 1981, a solid-phase single-antibody competitive radioimmunoassay with a single rabbit anti-CRP antibody directly immobilized onto a magnetic particle had a sensitivity of 0.05 mg/l. With use of a double-antibody competitive radioimmunoassay, the sensitivity was increased further to 0.003 mg/l. An in-house ELISA CRP assay developed in 1997 has a sensitivity of 0.007 mg/l and was used in 1999 to evaluate the hs-CRP test for clinical use. In 2000, an immunoradiometric assay (IRMA) was developed with polyclonal antibodies of CRP immobilized on microtiter plates and monoclonal antibodies of CRP labeled with 125I. IRMA had a sensitivity of 0.05 mg/l,-36.4*,Atorvastatin,-5.2,Pravastatin,Change in CRP levels from baseline,Change (%),*P0.001 vs pravastatin,-40,-30,-20,-10,0,1.8,2.9,18 Months,2.8,3.0,Baseline,Atorvastatin,Pravastatin,CRP (mg/L),Relationship Between Adiponectin and Glycemic Control, Blood Lipids, and Inflammatory Markers in Men With Type 2 Diabetes,Matthias B. et al. Diabetes Care 2004;27:1680-1687.,The correlation matrix among changes of lipid profile and studied cardiovascular risk factors at the end of 12-week fenofibrate treatment (n=39),Changes of the Studied Risk Factors at the End of 12-week Fenofibrate Treatment (n=39),Binding and Internalization of C-reactive Protein by Fcgamma Receptors on Human Aortic Endothelial Cells (HAEC) Mediates Biological Effects,Several reports showed that CRP binds to Fcgamma receptors on leukocytes. CRP (100 microg/mL) significantly upregulated surface expression of Fcgamma receptors, CD32, as well as CD64 on HAECs (P0.01). Preincubation wit