1、糖尿病與發炎指標糖尿病與發炎指標CRPCRP 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.Phosphochlorin
2、e 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 wit
3、h 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 (a)Negatively stained electron micrograph showi
4、ng the typical pentameric disc-like structure face-on and side-on(arrows).(b)Ribbon diagram of the crystal structure,showing the lectin fold and the two calcium atoms(spheres)in the ligand-binding site of each protomer.(c)Space-filling model of the CRP molecule,showing a single phosphocholine molecu
5、le 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 t
6、o 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
7、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
8、2004;27:1680-1687.140 180 mg/dL 051015PravastatinPlaceboWOSCOPS:Overlap Analysis Frequency per 100 On treatment LDL n Events 1120 108 1071 67 Placebo Pravastatin RR on Pravastatin =0.65 Log rank p=0.002 Adjust for on-treatment LDL,HDL,VLDL,TG&baseline covariates.RR on Pravastatin=0.64,p=0.014 77 155
9、 116 194 232 mg/dL 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 betwee
10、n 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),-40,-40,-55,-55,-33,-33,-36,-36,-49,-49,-
11、40,-40-60-60-50-50-40-40-30-30-20-20-10-100 0Median=Median=MedianP0.01 P0.01 P30)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 Associa
12、ted 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 020406080100120140295050100150200250300350100
13、120140160180200Hypertension 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
14、(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.x3.0 x2.2x1.40.00.51.01.52.02.53.03.5Relative Risk of DevelopingFatal CVDDyslipidemia Hypertension Dyslipidemia/Hyper
15、tension 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 56*2244*2078*5766*5601020304050607080HypertensionHigh cholesterolObesityLow physical activityWith diabetes(%)Witho
16、ut diabetes(%)Archives of Internal Medicine 2002;162:427-433*P0.001 Hypertension and Dyslipidemia Commonly Occurs in Diabetes in Taiwan TADE 2002 Prevalence(%)26.6%40.9%52.6%64.9%0%10%20%30%40%50%60%70%High uric acid Dyslipidemia Obesity Hypertension C C反應蛋白反應蛋白 (CRP)(CRP)可加強可加強 TC/HDLTC/HDL比值預估首度心比值預估首度心肌梗塞發生之風險肌梗塞發生之風險 0 01 12 23 34 4高高中中低低低低中中高高Ridkor PM.Circulation 1996;97:2007-11.冠冠 心心 病病 風風 險險 TC/HDL 比值比值 CRP 0 1 2 3 4 N=1,008 代謝異常數目代謝異常數目 代謝異常包括：代謝異常包括：肥胖肥胖 高血壓高血壓 高三酸甘油脂症高三酸甘油脂症 低低HDL-C 高
