1、國立成功大學醫學院附設醫院內科部內分泌新陳代謝科吳達仁 醫師Hypertension occurs with twice the frequency in the diabetic population as compared with the general,non-diabetic population.50%of patients diagnosed with diabetes eventually become hypertensive.Christlieb AR.Diabetes 1981：30(Suppl 2):90The age-and sex-adjusted prevalen
2、ce of hypertension among diabetic subjects was twice that of non-diabetic subjects(39.6%vs 16.4%)in TAIWAN.2.Hypertensive subjects had a higher prevalence of diabetes than normotensive subjects(10.2%vs 4.9%).Tai TY,et al.Diabetes Care 1991:14:1031.T-J WU高血壓病患有較高的糖尿病發生率高血壓病患有較高的糖尿病發生率0102030追蹤之追蹤之8 8
3、年發生率年發生率 (每每10001000人年人年發生案例發生案例)Gress TW et al.N Engl J Med.2000;342:905-912.T-J WU010203040506070無糖尿病無糖尿病有糖尿病有糖尿病每每10001000人人-年發生年發生心血管病事件心血管病事件1.SHEP Cooperative Research Group.JAMA.1991;265:3255-3264.2.Staessen JA et al.Lancet.1997;350:1757-1764.3.Wang JG et al.Arch Intern Med.2000;160:221-228.S
4、HEP1 SYST-EUR2 SYST-CHINA3高血壓在糖尿病病患的重要性高血壓在糖尿病病患的重要性高血壓是糖尿病患極為常見之共犯結構。約2060%糖尿病患患有高血壓。在第2型糖尿病患之高血壓，經常是以胰島素抗性為特徵之代謝症候群(metabolic syndrome)的主要成員之一。在第1型糖尿病患之高血壓則經常是反應著糖尿病腎臟病變(diabetic nephropathy)的開始。高血壓會增加糖尿病患大血管併發症(macrovascular)與 微細血管併發症(microvascular complications)之風險包括腦卒中、冠心病、週邊血管病變、網膜病變、及腎臟病變。由最近
5、幾年累積下來嚴謹的RCT(randomized clinical trials)資料証實：積極治療糖尿病患之高血壓是可以改善大血管與微細血管病變。T-J WU降低血壓有助減低糖尿病相關併發症之風險降低血壓有助減低糖尿病相關併發症之風險嚴密控制嚴密控制血壓血壓(144/82 mm Hg)相對於一般血壓控制相對於一般血壓控制(154/87mm Hg)減低糖尿病相關併發症風險之比率減低糖尿病相關併發症風險之比率其功效甚於降血糖其功效甚於降血糖 (HbA1c(HbA1c 由由 7.9%7.9%降至降至 7%)7%)降血壓降血壓 降血糖降血糖-32%*10%-24%*12%-44%*NA-56%*NA-
6、37%*25%UK Prospective Diabetes Study Group.BMJ.1998;317:703-713.糖尿病相關死亡糖尿病相關死亡糖尿病相關併發症糖尿病相關併發症腦卒中腦卒中(Stroke(Stroke)心臟衰竭心臟衰竭(Heart failureHeart failure)糖尿病微細血管併發症糖尿病微細血管併發症T-J WU05101520253010510095908580達成之舒張壓mm Hg%危險性減少危險性減少HOT Study 理想的舒張壓理想的舒張壓HOT Study 顯示降血壓可降低顯示降血壓可降低心血管意外之危險性達心血管意外之危險性達 30%30%
7、Hansson et al 19980510152025908580 mm Hg目標舒張壓目標舒張壓重大心血管意外重大心血管意外 /1000 /1000病人病人/年年Hansson et al 1998p=0.005 for trend糖尿病人積極降血壓可有效降低糖尿病人積極降血壓可有效降低之心血管意外之心血管意外 (HOT Study)平均舒張壓平均舒張壓基礎腎臟功能與基礎腎臟功能與重大心血管意外和舒張壓間之關係重大心血管意外和舒張壓間之關係J Hypertens 1999;17(Suppl 3):S1460510152025303540757080859095100105理想舒張壓理想舒張
8、壓:High creatinine=71.9 mmHg Low creatinine=80.9 mmHg重大心血管意外重大心血管意外/1000/1000病人病人/年年Creatinine 1.5 mg/dlCreatinine 1.5 mg/dl Working Group on Hypertension in定140/90 mmHg 為糖尿病患目標血壓 。JNC VI,1997 定130/85 mmHg 為糖尿病患目標血壓。125/75 mmHg為蛋白尿(1 g/day)病患目標血壓。UKPDS 與 Hypertension Optimal Treatment(HOT)研究，兩者皆顯示以血壓
9、以血壓130/80mmHg130/80mmHg為目標值的治療成效，確實顯著優於較寬鬆目標值的治療。由流行病學研究資料顯示糖尿病患血壓120/70 mmHg 以上，就與心血管事件以及死亡率增加息息相關。因此，在無特殊安全顧慮下，設定血壓目標值 50 mg/L at 9 y 1.210.31Urine albumin 300 mg/L at 9 y0.480.09Relative risk*(95%CI)Favors ACE inhibitorFavors-blocker0.512UKPDS Group.BMJ.1998;317:713-720.T-J WU以血管張力素轉化酵素抑制劑治療高血壓以血
10、管張力素轉化酵素抑制劑治療高血壓之糖尿病患的效果之糖尿病患的效果風險減少風險減少(%)HOPE study investigators.Lancet.2000;355:253-259.T-J WUEffects of ACEI on BP in Hypertensive Type 2 Diabetics with Incipient Nephropathy BRILLIANTAgardh C-D,et al.J Hum Hypertens 1996;10:185-192LisinoprilNifedipine180160140120100 80Month of Treatment0 1 3 6
11、 9 12Agardh C-D,et al.J Hum Hypertens 1996;10:185-192Lisinopril Nifedipine p0.0006 vs.placebo at 12 monthsT-J WUAlbumin Excretion(g/min)Baseline 6 month 12 month70605040302010BRILLIANTACEI Improves Albumin Excretion Rate in Microalbuminuric Patients with T1DM：EUrodiab Controlled trial of Lisinopril
12、in Insulin dependent Diabetes(EUCLID)EUCLID Study Group.Lancet 1997;349:1787-1792AER(g/min)Time(months)706050403020106 12 18 24PlaceboLisinoprilTreatment difference=38.5g/min,p=0.001T-J WUMalaise and fatigueEdemaGI tract Diseases Renal Failure Cough Erectile dysfunctionHeadacheDepressionRashAllergic
13、 reaction Intermittent claudication BronchospasmCold and numb handHypokalemiaHyponatremia)Side Effect ACEI CCB Diuretics -blockersNo.(%)(n=635)(n=235)(n=283)(n=358)高血壓糖尿病患高血壓糖尿病患降血壓治療之主要不良反應降血壓治療之主要不良反應Data Sources:ACEI:ABCD,UKPDS;CCB:ABCD;Diuretics:SHEP;-blockers:UKPDS TJ WU21(3.3)11(1.7)9(1.4)6(0.
14、9)29(4.6)3(0.5)2(0.3)1(0.2)1(0.2)7(1.1)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)20(8.5)4(1.7)2(0.9)8(3.4)2(0.9)10(4.3)0(0.0)1(0.4)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)13(4.6)0(0.0)34(11.9)0(0.0)11(3.9)0(0.0)0(0.0)0(0.0)0(0.0)70(24.8)6(2.3)22(7.9)16(4.5)0(0.0)5(1.4)0(0.0)0(0.0)6(1.7)3(0.8
15、)1(0.3)0(0.0)2(0.6)15(4.2)22(6.2)0(0.0)0(0.0)0(0.0)Diuretic Beta-blockersACE inhibitorCCBAlpha-blockers血糖血糖中性中性中性中性中性中性血脂肪血脂肪中性中性中性中性中性中性電解質電解質干擾干擾中性中性中性中性中性中性中性中性胰島素抗性胰島素抗性中性中性併發症併發症 冠心病冠心病保護保護(A)保護保護(A)保護保護(A)未評未評未定未定 腎病變腎病變未評未評保護保護(A)保護保護(A)保護保護*(C)未評未評 腦卒中腦卒中保護保護(A)保護保護(A)保護保護(A)保護保護*(A)未評未評降血壓藥
16、物對高血壓糖尿病患之影響降血壓藥物對高血壓糖尿病患之影響Nephroprotective Role of Angiotensin II Receptor Antagonists in Type 2 Diabetes The Irbesartan Diabetic Nephropathy Trial(IDNT)and the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan(RENAAL)trial.Both trials showed a significant reduction in the pr
17、imary pre-specified end-point of death,or worsening of renal function(doubling of serum creatinine)or the development of end-stage renal disease.The Irbesartan Microalbuminuria Study(IRMA)-2 and the Microalbuminuria Reduction with Valsartan study(MARVAL)-were trials conducted in patients with type 2
18、 diabetes with microalbuminuria.These trials demonstrated an angiotensin receptor blocker(ARB)interfere with the natural history of diabetic nephropathy in a blood pressure-independent fashion.The Effect of Irbesartan on The Development of Diabetic Nephropathy in Patients with T2DM 0 04 48 812121616
19、2020Onset of Diabetic Nephropathy(%)Relative risk*(95%CI)Favors ARBs0.51210/19419/19530/201300mg/dayP300 mg/day),and renal insufficiency,an ARB should be strongly considered.(A)T-J WU0.5Siebenhofer A,et al.Diabet Med 2004;21:18-25.Favors ARBs Favors StandardOdds ratio (95%CI)12Total mortalityCombine
20、dCardiovasxccular events CombinedEnd-stage renal diseaseCombinedLewisLindholmLewisLindholmLewis0.5Favors ARBsOdds ratio (95%CI)12Favors PlaceboBrennerLewisBrennerLewisBrennerLewisT-J WUARB and Renal Disease in Patients With Type 2 Diabetes An Asian perspective from the RENAAL study A total of 252 As
21、ian patients were enrolled in the RENAAL study,which compared losartan to placebo in addition to conventional antihypertensive medications in type 2 diabetic patients with nephropathy.Mean follow-up was 3.2 years.Losartan reduced the risk of the primary composite end point composed of a doubling of
22、serum creatinine,end-stage renal disease,or all-cause mortality in Asian patients by 35%(P=0.02).No difference between losartan and placebo was observed for the cardiovascular composite outcomes.Losartan reduced the level of proteinuria by 47%(P 0.001)and rate of decrease in renal function by 31%(P=
23、0.0074).Chan JC,et al Diabetes Care 2004:27:874-879.中危險層級中危險層級超高或高超高或高危險層級危險層級低危險層級低危險層級監測血壓與監測血壓與危險因素危險因素3-63-6個月個月監測血壓與監測血壓與危險因素危險因素6-126-12個月個月立即藥物治療立即藥物治療收縮壓收縮壓 140140或或舒張壓舒張壓 9090開始開始藥物治療藥物治療收縮壓收縮壓 150150或或舒張壓舒張壓 9595開始開始藥物治療藥物治療未超出則未超出則繼續監測繼續監測未超出則未超出則繼續監測繼續監測高血壓處理對策高血壓處理對策生活型態調整生活型態調整:戒煙戒煙,減肥
24、減肥,適酒量適酒量,限鹽限鹽,運動等運動等依危險因子依危險因子,靶器官受損靶器官受損,與關聯狀況評估危險層級與關聯狀況評估危險層級1999 WHO-ISH HYPERTENSION PRACTICE GUIDELINES FOR PRIMARY CARE PHYSICIANSBP classification SBP*mmHg DBP*mmHg Lifestyle modification Initial drug therapy Without compelling indication With compelling indicationsNormal 120 and 160 or 100
25、 Yes Two-drug combination for most(usually thiazide-type diuretic and ACEI or ARB or BB or CCB).*Treatment determined by highest BP category.Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.Treat patients with chronic kidney disease or diabetes to BP go
26、al of 20/10 mmHg above goal,initiate therapy with 2 agents.Certain high-risk conditions are compelling indications for other drug classes.美國糖尿病學會對糖尿病人血壓控制美國糖尿病學會對糖尿病人血壓控制的建議的建議(ADA 2004)目標血壓應控制在收縮壓小於130mmHg、舒張壓小於80mmHg。收縮壓於130 139 mmHg、或舒張壓於80 90mmHg的糖尿病病人，經3個月非藥物療法的行為介入治療未達目標血壓，也即須加上降血壓藥物治療。收縮壓140
27、mmHg、或舒張壓 90mmHg的糖尿病病人，非藥物療法的行為介入治療同時，也須即加上降血壓藥物治療。ADA position statement.Diabetes Care 2004;27(suppl 1):565-7美國糖尿病學會對糖尿病抗高血壓藥物治療的建議美國糖尿病學會對糖尿病抗高血壓藥物治療的建議 血管張力素轉化酵素抑制劑(ACE-Is)、血管張力素接受器阻斷劑(ARBs)、乙型阻斷劑(-blockers)、或 利尿劑(Diuretics)均可做起始治療的選項。大多數的糖尿病患要控制到理想血壓之目標，兩種以上的降血壓藥物並用是不能少的；須要三種以上的降血壓藥物並用也很常見。大多數的糖
28、尿病患，尤其具其他危險因子，不論高血壓輕重，不論第1、2型，建議以ACE-Is為首選藥物。對併糖尿病腎病變(顯微蛋白尿或蛋白尿)，ACE-Is(第1、2型)與 ARBs(第2型)皆可減少尿蛋白排出量，可延緩腎功能的惡化。所以均被推薦為首選藥物。如果糖尿病患合併近期心肌梗塞，加上-blockers，可減少心血管併發症死亡率。長效型鈣離子通道阻斷劑也是可用的，一般作二線使用。糖尿病抗高血壓藥物治療，須考慮comorbidities,tolerability,personal preferences,and cost。Position Statement of ADA.Diabetes Care 2004;27:S565-7Capoten 25 9.3Tritace 2.5 20.8Zestrii 10 18.0Renitec 10 20.5Renitec 20 20.5Acertil 4 24.9Coraar 50 27.6Diovan 80 27.1Aprovel 150 27.6Micardis 40 27.6T-J WUThank you for your attention!
