1、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(fnm)新陳代謝科,第一页，共二十六页。,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.Phosphochlo
2、rine 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
3、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.,第二页，共二十六页。,Molecular Structure and Morphology of Human CRP,Negatively stained electron micr
4、ograph 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
5、molecule located in the ligand-binding site of each protomer).,Pepys MB,et al.Clin Invest 2003;111:1805-1812.,第三页，共二十六页。,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 de
6、tection 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,
7、AHA):CRP 1 mg/l is low CVD riskCRP 1 to 3 mg/l is moderate CVD riskCRP 3 to 10 mg/l is high CVD risk CRP levels 10 mg/l generally indicates bacterial infection,第四页，共二十六页。,Demographic and Descriptive Characteristics of the US Population Without a Previous Diagnosis of Hypertension From NHANES III,Mat
8、thias B.et al.Diabetes Care 2004;27:1680-1687.,第五页，共二十六页。,WOSCOPS:Overlap Analysis,Frequency per 100,On treatment LDL,WOSCOPS Group.Circulation.1998;97:1440-45,第六页，共二十六页。,第七页，共二十六页。,The Effects of Atorvastatin versus Simvastatin on Atherosclerosis Progression Study(ASAP),Atorvastatin reduced CRP lev
9、els 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,-1
10、9.7,第八页，共二十六页。,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,第九页，共二十六页。,Effects of Switching Pravastatin to Cerivastatin on C-Reactive Protein,Butyrylcholinesterase,
11、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 cerivastat
12、in,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
13、and CRP.,Shinn AH,et al Curr Med Res Opin.2005;(2):207-213.,第十页，共二十六页。,Risk Factors for CHD,ModifiableHypertensionHigh LDL cholesterolLow HDL cholesterolCigarette smokingPhysical inactivityDiabetesObesity(BMI 30)Thrombogenic/hemostatic stateAtherogenic diet,Non-modifiableAgeMale sexFamily history of
14、 premature CHD,National Cholesterol Education Program Adult Treatment Panel III.2002.NIH Publication No.02-5215.,第十一页，共二十六页。,Factors Associated with Increased or Decreased CRP,Higher CRPHypertensionHyperglycemiaLow HDL/high TGSmokingObesityMetabolic syndromeEstrogen/progesterone useChronic infection
15、,Lower CRPIncrease exerciseAlcohol consumptionWeight lossMedication:StatinFibrate,第十二页，共二十六页。,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/1
16、000,Probability of CVD/1000,Age,40,50,60,70,Framingham study,SBP(mm Hg)in men,TC(mg/dL)in men,第十三页，共二十六页。,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,第十四页，共二十六页。,Hypertension and High Cholesterol are Twice as Prevalent in Adults with DM Compared to
