老年糖尿病患者的治療策略

1、老年糖尿病患者的治療策略,李詩(shī)洋,糖尿病患病人數(shù) (20-79歲) 排名前10位的國(guó)家/地區(qū) 單位:百萬(wàn),最新IDF流行病學(xué)數(shù)據(jù)顯示： 20102030年糖尿病在全球迅速流行,中國(guó)糖尿病患病人數(shù)已居世界第一,Diabetes Atlas, 5th edition, IDF, 2011.,China in 2010,11.6% prevalence of diabetes in adults in China in 2010 based on cross-sectional study of 98,658 adults in China in 2010 estimated prevalence

2、any diabetes in 11.6% (12.1% in men and 11% in women) prediabetes in 50.1% Reference - JAMA 2013 Sep 4;310(9):948, editorial can be found in JAMA 2013 Sep 4;310(9):916,我國(guó)老年人群糖尿病患病率顯著增加,我國(guó)老年人的標(biāo)準(zhǔn)大于等于60歲,中華內(nèi)科雜志. 2014;53(3):243-251,Background,Diabetes mellitus type 2 is a common endocrine disorder chara

3、cterized by variable degrees of insulin resistance and deficiency, resulting in hyperglycemia. It is often identified through routine screening beginning in middle age, or through targeted screening of adults with risk factors such as obesity, metabolic syndrome, polycystic ovary syndrome, a history

4、 of gestational （妊娠期的）diabetes, or other concerning familial, clinical, or demographic characteristics.,Also called,diabetes mellitus type II type 2 diabetes type II diabetes non-insulin-dependent diabetes mellitus (NIDDM) adult-onset diabetes（成人型） insulin-resistant diabetes,Who is most affected,per

5、sons with obesity(2) mean age at diagnosis of type 2 diabetes in United Stated decreased from 52 years in 1988-1994 to 46 years in 1999-2000 (Ann Fam Med 2005 Jan-Feb;3(1):60 full-text) diabetes prevalence similar in men and women globally, but slightly higher in men 60 years old and in women at old

6、er ages (Diabetes Care 2004 May;27(5):1047 full-text) American Indians/Alaska Natives (AI/ANs) have higher prevalence of diabetes from 1994 to 2002, age-adjusted prevalence of diabetes among United States adults increased from 4.8% to 7.3%, but among AI/AN adults, from 11.5% to 15.3% (MMWR Morb Mort

7、al Wkly Rep 2003 Aug 1;52(30):702 full-text) from 1994 to 2004, age-adjusted prevalence of diagnosed diabetes in AI/ANs 35 years old increased from 0.85% to 1.71%; prevalence in 2004 increased with age from 0.22% at age 15 years to 4.68% at ages 25-34 years (MMWR Morb Mortal Wkly Rep 2006 Nov 10;55(

8、44):1201 full-text),Likely risk factors,Prediabetes impaired fasting glucose（空腹血糖受損） - plasma glucose 110-125 mg/dL (6.1-6.9 mmol/L) using WHO criteria, or 100-125 mg/dL (5.6-6.9 mmol/L) using ADA criteria impaired glucose tolerance （糖耐量減低）- 2-hour plasma glucose 140-199 mg/dL (7.8-11 mmol/L) during

9、 75 g oral glucose tolerance test (WHO and ADA criteria) HbA1c 5.7%-6.4% (ADA criteria),Likely risk factors,obesity metabolic syndrome polycystic ovary syndrome（多囊卵巢綜合征） gestational diabetes mellitus (GDM)（妊娠期糖尿?。?Diagnostic criteria,fasting plasma glucose 126 mg/dL (7 mmol/L) (after no caloric inta

10、ke for 8 hours) symptoms of hyperglycemia（高血糖） with random plasma glucose 200 mg/dL (11.1 mmol/L) 2-hour plasma glucose 200 mg/dL (11.1 mmol/L) during a 75 g oral glucose tolerance test HbA1c 6.5% (HbA1c may not be accurate for diagnosis if there is pregnancy, hemoglobinopathy(血紅色異常), certain anemia

11、s（貧血）, or abnormal erythrocyte（紅細(xì)胞） loss or replacement) Repeat testing for confirmation in the absence of unequivocal （明確的）hyperglycemia. (WHO/IDF 2006 PDF) WHO Consultation Report 2011 PDF,Additional testing and evaluation,a fasting lipid profile liver transaminases serum creatinine, estimated glo

12、merular filtration rate, spot urine microalbumin（微量蛋白） to creatinine ratio a dilated eye exam to detect retinopathy（視網(wǎng)膜）a Semmes-Weinstein monofilament （震動(dòng)閾值）exam to detect peripheral neuropathy （周圍神經(jīng)病變）,Individualize glycemic goals,Strong recommendation targets in adults with type 2 diabetes are Hb

13、A1c 7% in most nonpregnant adults and 6% in pregnant women with preexisting（既往） diabetes,Consider individualized lipid goals and blood pressure goals; generally recommended targets in adults with type 2 diabetes are low-density lipoprotein (LDL) cholesterol 100 mg/dL (2.6 mmol/L) and blood pressure

14、130/80 mm Hg or 50% of adults with coronary artery disease may have diabetes or impaired glucose metabolism 32% of patients scheduled for coronary angiography may have diabetes, almost half of which may be undiagnosed 17% of adults may have had silent myocardial infarction by time of diagnosis with

15、type 2 diabetes postural hypotension and postural dizziness may be associated with diabetes mellitus type 2 insulin use may be associated with higher risk of hypertension in adults with type 2 diabetes 10%-48% adults with type 2 diabetes may have obstructive sleep apnea (OSA) type 2 diabetes may be

16、associated with vitamin D deficiency,臨床問(wèn)題,誰(shuí)是老年糖尿病的理想管理對(duì)象？ 如何進(jìn)行功能評(píng)估和危險(xiǎn)分層： 建立個(gè)體化控制目標(biāo)的依據(jù) 如何確定治療方案,2012 ADA老年糖尿病人群分類, 健康，幾乎沒(méi)有并發(fā)的慢性疾病，認(rèn)知功 能和功能狀態(tài)完好； 病情復(fù)雜/ 中等健康，存在多種慢性合并疾病，或 2 項(xiàng)日?；顒?dòng)受限，或輕- 中度認(rèn)知功能受損； 非常復(fù)雜/ 健康較差，需長(zhǎng)期護(hù)理，或伴有終末期慢性疾病，或中- 重度認(rèn)知功能受損，或 2項(xiàng)日常活動(dòng)無(wú)法自理。,2013IDF 老年DM人群功能分類,CATEGORY 1: FUNCTIONALLY INDEPENDEN

17、T CATEGORY 2: FUNCTIONALLY DEPENDENT Subcategory A: Frail Subcategory B: Dementia CATEGORY 3: END OF LIFE CARE,2012 ADA以HbA1c為參考的策略,HbA1c 與死亡率呈 U 型曲線 HbA1c 在 7.5% 死亡風(fēng)險(xiǎn)比率最 低（IQR 7.5% 7.6%） HbA1c6.0% 或 11.0% 死亡風(fēng)險(xiǎn)均增加。 (2012ADA),2013ACCE,The A1c target must be individualized, based on numerous factors,

18、such as age, co-morbid conditions, duration of diabetes, risk of hypo-glycemia, patient motivation, adherence, life expectancy, etc. An A1c of 6.5% or less is still considered optimal if it can be achieved in a safe and affordable manner, but higher tar-gets may be appropriate and may change in a gi

19、ven individual over time.,根據(jù)功能狀況，老年2型糖尿病患者的常規(guī)血糖目標(biāo),INTERNATIONAL DIABETES FEDERATION MANAGING OLDER PEOPLE WITH TYPE 2 DIABETES GLOBAL GUIDELINE（2013年）,老年2型糖尿病患者的HbA1c目標(biāo)值,2016 ADA,老年糖尿病治療策略的優(yōu)化新觀點(diǎn)： 美國(guó)糖尿病協(xié)會(huì)(ADA)和美國(guó)老年病學(xué)會(huì)(AGS)發(fā)表的共識(shí),個(gè)性化控制目標(biāo)的制定 健康，極少伴隨其他慢性疾病，無(wú)認(rèn)知障礙，功能狀態(tài)無(wú)受損。糖化血紅蛋白控制目標(biāo)可定為75 病情復(fù)雜，伴多種慢性疾病，或日?；顒?dòng)

20、能力有2項(xiàng)或更多項(xiàng)受損，或輕中度認(rèn)知障礙。目標(biāo)可能需要放寬到8以降低低血糖和跌倒風(fēng)險(xiǎn) 病情非常復(fù)雜健康狀況很差，或伴終末期慢性疾病，或中重度認(rèn)知障礙，或2項(xiàng)或更多項(xiàng)日常生活不能自理。目標(biāo)定為85,Diabetes in Older Adults: A Consensus Report Journal of the American Geriatrics Society; v:60 i:12 p:2342-2356; 12/2012,老年糖尿病治療策略的優(yōu)化,（三）個(gè)性化控制目標(biāo)的制定 老年糖尿病診療措施專家共識(shí)（年版） 中國(guó)老年學(xué)學(xué)會(huì)老年醫(yī)學(xué)會(huì)老年內(nèi)分泌代謝專業(yè)委員會(huì) （） HbAlc7.5%

21、：相應(yīng)FPG7.5mmol/L和2hPG10.Ommol/L。 適用于預(yù)期生存期10年、較輕并發(fā)癥及伴發(fā)疾病，有一定低血糖風(fēng)險(xiǎn)，應(yīng)用胰島素 促泌劑類降糖藥物或以胰島素治療為主的2型和1型糖尿病患者。 （2）HbAlc8.O%：對(duì)應(yīng)的FPG8.Ommol/L和2hPG11.Immol/L。 適用于預(yù)期生存期5年、中等程度并發(fā)癥及伴發(fā)疾病，有低血糖風(fēng)險(xiǎn)，應(yīng)用胰島素促泌劑類降糖藥物或以多次胰島素注射治療為主的老年糖尿病患者。 （3）HbAlc8.5%： 如有預(yù)期壽命5年、完全喪失自我管理能力等情況,中華內(nèi)科雜志. 2014;53(3):243-251,臨床問(wèn)題,誰(shuí)是老年糖尿病的理想管理對(duì)象？ 如何進(jìn)

22、行功能評(píng)估和危險(xiǎn)分層： 建立個(gè)體化控制目標(biāo)的依據(jù) 如何確定治療方案,治療理念：重視基礎(chǔ)治療,（一）重視基礎(chǔ)治療 1 糖尿病教育 2 飲食 3 運(yùn)動(dòng) 其中，糖尿病教育是公認(rèn)的提高糖尿病治療水平的重要措施。而飲食和運(yùn)動(dòng)治療則應(yīng)貫穿于糖尿病治療的始終,中華內(nèi)科雜志. 2014;53(3):243-251,2013 IDF老年2型糖尿病藥物治療路徑,生活方式干預(yù),此后，在每一步驟，如果未達(dá)到個(gè)體化的HbA1c 目標(biāo),考慮一線治療,考慮二線治療：在一線藥物基礎(chǔ)上增加為兩藥治療,考慮三線治療：三種口服藥物治療、胰島素或GLP-1RA,后續(xù)治療選擇,二甲雙胍,磺脲或 DPP-4抑制劑,二甲雙胍 （若未作為一

23、線用藥）,磺脲 或 DPP-4抑制劑,DPP-4抑制劑 或磺脲,基礎(chǔ)胰島素 或預(yù)混胰島素,或,GLP-1RA,GLP-1RA,基礎(chǔ)+餐時(shí) 胰島素,替換口服藥物或 基礎(chǔ)胰島素或 預(yù)混胰島素,常規(guī)治療路徑,備選治療路徑,其它治療選擇 （按字母排序）,阿卡波糖或 格列奈類或 胰島素或 SGLT2抑制劑或 噻唑烷二酮,阿卡波糖或 格列奈類或 GLP-1RA或 胰島素或 SGLT2抑制劑或 噻唑烷二酮,阿卡波糖或 格列奈類或 SGLT2抑制劑或 噻唑烷二酮,需考慮的患者因素： 身體功能 虛弱 癡呆 疾病終末期,藥物選擇考慮因素： 腎功能 磺脲的低血糖風(fēng)險(xiǎn) 藥物副作用 藥物所致體重降低的潛在危害 費(fèi)用 可

24、獲得性 當(dāng)?shù)靥幏椒ㄒ?guī) 停用無(wú)效藥物,2013 IDF Global Guideline for Managing Older People with Type 2 Diabetes. /guidelines/managing-older-people-type-2-diabetes,中國(guó)老年醫(yī)學(xué)會(huì)老年糖尿病診療措施 專家共識(shí)（2013年版）降糖治療路徑,中華內(nèi)科雜志. 2014;53(3):243-251,2016 ADA,2016 ADA,所有的治療均需建立在以下項(xiàng)目基礎(chǔ)上,綜合評(píng)估和危險(xiǎn)分層 functional status 功能狀態(tài) Hypoglyca

25、emia 低血糖 Hyperglycaemia and their consequences 高血糖及結(jié)果 Falls 跌倒 pain 疼痛 medicine related adverse events 藥物相關(guān)不良反應(yīng) Cost consideration and cost benefit analysis (if available) 經(jīng)濟(jì) Level of comorbid illness and/or frailty 共病/衰弱 Life expectancy including when to implement palliative care 預(yù)期壽命/姑息,IDF 2型糖尿病老

26、年患者管理指南,一線治療推薦： 二甲雙胍（沒(méi)有腎功能減退和其他禁忌時(shí)） 低血糖發(fā)生風(fēng)險(xiǎn)低的磺脲類（避免使用格列本脲）,International Diabetes Federation. Global Guideline for Managing Older People with Type 2 Diabetes (2013). Available at ,老年糖尿病患者低血糖發(fā)生風(fēng)險(xiǎn)高,一項(xiàng)在德國(guó)進(jìn)行的研究，對(duì)2009年6月至2010年3月間口服降糖藥物治療的3810名糖尿病患者低血糖事件進(jìn)行回顧性分析，老年糖尿病患者低血糖發(fā)生率高,Bramlage et al. Ca

27、rdiovascular Diabetology 2012, 11:122,老年患者更易發(fā)生嚴(yán)重低血糖,動(dòng)脈血糖（mmol/L）,年輕患者,感知低血糖閾值,發(fā)生嚴(yán)重低血糖閾值,老年人不僅對(duì)低血糖感知閾值下降 而且嚴(yán)重低血糖的閾值高于年輕人,Diabetes Care. 1997 Feb;20（2）:135-41.,老年患者,0.80.1,ACCORD： 低血糖可能抵消2型糖尿病患者控制血糖獲得的受益,研究第1年，強(qiáng)化治療組和標(biāo)準(zhǔn)治療組糖化血紅蛋白穩(wěn)定的中位水平分別為6.4%和7.5%。但是發(fā)現(xiàn)強(qiáng)化治療組的死亡率更高，導(dǎo)致平均隨訪3.5年后中止強(qiáng)化治療（強(qiáng)化治療組和標(biāo)準(zhǔn)治療組的死亡率分別為5.0%和4.0%，P=0.04）。,ACCORD：治療對(duì)血糖控制的影響,ACCORD：治療對(duì)全因死亡率的影響,HbA1c(%),時(shí)間(年),時(shí)間(年),強(qiáng)化治療,強(qiáng)化治療,標(biāo)準(zhǔn)治療,標(biāo)準(zhǔn)治療,發(fā)生事件的患者(%),Accord Study Group NEJM 2008 358 24 2545,DPP-4抑制劑治療的特點(diǎn),通過(guò)延長(zhǎng)體內(nèi)自身GLP-1的作用改善糖代謝 主要降低餐后血糖 對(duì)于老年患者