1、老年糖尿病患者的治疗策略,李诗洋,糖尿病患病人数 (20-79岁) 排名前10位的国家/地区 单位:百万,最新IDF流行病学数据显示：20102030年糖尿病在全球迅速流行,中国糖尿病患病人数已居世界第一,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 2010estimated prevalenceany
2、 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,我国老年人群糖尿病患病率显著增加,我国老年人的标准大于等于60岁,中华内科杂志. 2014;53(3):243-251,Background,Diabetes mellitus type 2 is a common endocrine disorder characteri
3、zed 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 of ge
4、stational （妊娠期的）diabetes, or other concerning familial, clinical, or demographic characteristics.,Also called,diabetes mellitus type IItype 2 diabetestype II diabetesnon-insulin-dependent diabetes mellitus (NIDDM)adult-onset diabetes（成人型）insulin-resistant diabetes,Who is most affected,persons with o
5、besity(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):60full-text)diabetes prevalence similar in men and women globally, but slightly higher in men 60 years old and in women at older ages (Diabe
6、tes Care 2004 May;27(5):1047full-text)American Indians/Alaska Natives (AI/ANs) have higher prevalence of diabetesfrom 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 Mortal Wkly Rep 2003
7、Aug 1;52(30):702full-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(44):1201full-text),
8、Likely risk factors,Prediabetes impaired fasting glucose（空腹血糖受损） - 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 criteriaimpaired glucose tolerance （糖耐量减低）- 2-hour plasma glucose 140-199 mg/dL (7.8-11 mmol/L) during 75 g oral glucose to
9、lerance test (WHO and ADA criteria)HbA1c 5.7%-6.4% (ADA criteria),Likely risk factors,obesitymetabolic syndromepolycystic ovary syndrome（多囊卵巢综合征）gestational diabetes mellitus (GDM)（妊娠期糖尿病）,Diagnostic criteria,fasting plasma glucose 126 mg/dL (7 mmol/L) (after no caloric intake for 8 hours)symptoms o
10、f 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 testHbA1c 6.5% (HbA1c may not be accurate for diagnosis if there is pregnancy, hemoglobinopathy(血红色异常), certain anemias（贫血）, or abnormal erythroc
11、yte（红细胞） loss or replacement)Repeat testing for confirmation in the absence of unequivocal （明确的）hyperglycemia.(WHO/IDF 2006 PDF)WHO Consultation Report 2011 PDF,Additional testing and evaluation,a fasting lipid profile liver transaminases serum creatinine, estimated glomerular filtration rate, spot
12、urine microalbumin（微量蛋白） to creatinine ratioa dilated eye exam to detect retinopathy（视网膜）a Semmes-Weinstein monofilament （震动阈值）exam to detect peripheral neuropathy （周围神经病变）,Individualize glycemic goals,Strong recommendation targets in adults with type 2 diabetes are HbA1c 7% in most nonpregnant adul
13、ts 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 130/80 mm Hg or 50% of adults w
14、ith 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 type 2 diabetes postural hypote
15、nsion 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 associated with vitamin D defic
16、iency,临床问题,谁是老年糖尿病的理想管理对象？如何进行功能评估和危险分层：建立个体化控制目标的依据如何确定治疗方案,2012 ADA老年糖尿病人群分类, 健康，几乎没有并发的慢性疾病，认知功能和功能状态完好； 病情复杂/ 中等健康，存在多种慢性合并疾病，或 2 项日常活动受限，或轻- 中度认知功能受损； 非常复杂/ 健康较差，需长期护理，或伴有终末期慢性疾病，或中- 重度认知功能受损，或 2项日常活动无法自理。,2013IDF 老年DM人群功能分类,CATEGORY 1: FUNCTIONALLY INDEPENDENTCATEGORY 2: FUNCTIONALLY DEPENDENT
17、 Subcategory A: Frail Subcategory B: DementiaCATEGORY 3: END OF LIFE CARE,2012 ADA以HbA1c为参考的策略,HbA1c 与死亡率呈 U 型曲线HbA1c 在 7.5% 死亡风险比率最 低（IQR 7.5% 7.6%） HbA1c6.0% 或 11.0% 死亡风险均增加。 (2012ADA),2013ACCE,The A1c target must be individualized, based on numerous factors, such as age, co-morbid conditions, dur
18、ation 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 given individual over time.,根据功能状况，老年2型糖
19、尿病患者的常规血糖目标,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目标值,2016 ADA,老年糖尿病治疗策略的优化新观点：美国糖尿病协会(ADA)和美国老年病学会(AGS)发表的共识,个性化控制目标的制定 健康，极少伴随其他慢性疾病，无认知障碍，功能状态无受损。糖化血红蛋白控制目标可定为75病情复杂，伴多种慢性疾病，或日常活动能力有2项或更多项受损，或轻中度认知障碍。目标可能需要放宽到8以降低低血糖和跌倒
20、风险病情非常复杂健康状况很差，或伴终末期慢性疾病，或中重度认知障碍，或2项或更多项日常生活不能自理。目标定为85,Diabetes in Older Adults: A Consensus ReportJournal of the American Geriatrics Society; v:60 i:12 p:2342-2356; 12/2012,老年糖尿病治疗策略的优化,（三）个性化控制目标的制定 老年糖尿病诊疗措施专家共识（年版） 中国老年学学会老年医学会老年内分泌代谢专业委员会（） HbAlc7.5%：相应FPG7.5mmol/L和2hPG10.Ommol/L。适用于预期生存期10年、
21、较轻并发症及伴发疾病，有一定低血糖风险，应用胰岛素促泌剂类降糖药物或以胰岛素治疗为主的2型和1型糖尿病患者。（2）HbAlc8.O%：对应的FPG8.Ommol/L和2hPG11.Immol/L。适用于预期生存期5年、中等程度并发症及伴发疾病，有低血糖风险，应用胰岛素促泌剂类降糖药物或以多次胰岛素注射治疗为主的老年糖尿病患者。（3）HbAlc8.5%：如有预期寿命5年、完全丧失自我管理能力等情况,中华内科杂志. 2014;53(3):243-251,临床问题,谁是老年糖尿病的理想管理对象？如何进行功能评估和危险分层：建立个体化控制目标的依据如何确定治疗方案,治疗理念：重视基础治疗,（一）重视基
22、础治疗1 糖尿病教育2 饮食3 运动其中，糖尿病教育是公认的提高糖尿病治疗水平的重要措施。而饮食和运动治疗则应贯穿于糖尿病治疗的始终,中华内科杂志. 2014;53(3):243-251,2013 IDF老年2型糖尿病药物治疗路径,生活方式干预,此后，在每一步骤，如果未达到个体化的HbA1c 目标,考虑一线治疗,考虑二线治疗：在一线药物基础上增加为两药治疗,考虑三线治疗：三种口服药物治疗、胰岛素或GLP-1RA,后续治疗选择,二甲双胍,磺脲或 DPP-4抑制剂,二甲双胍（若未作为一线用药）,磺脲或 DPP-4抑制剂,DPP-4抑制剂或磺脲,基础胰岛素或预混胰岛素,或,GLP-1RA,GLP-1
23、RA,基础+餐时胰岛素,替换口服药物或基础胰岛素或预混胰岛素,常规治疗路径,备选治疗路径,其它治疗选择（按字母排序）,阿卡波糖或格列奈类或胰岛素或SGLT2抑制剂或噻唑烷二酮,阿卡波糖或格列奈类或GLP-1RA或胰岛素或SGLT2抑制剂或噻唑烷二酮,阿卡波糖或格列奈类或SGLT2抑制剂或噻唑烷二酮,需考虑的患者因素：身体功能虚弱痴呆疾病终末期,药物选择考虑因素：肾功能磺脲的低血糖风险药物副作用药物所致体重降低的潜在危害费用可获得性当地处方法规停用无效药物,2013 IDF Global Guideline for Managing Older People with Type 2 Diabet
24、es.http:/www.idf.org/guidelines/managing-older-people-type-2-diabetes,中国老年医学会老年糖尿病诊疗措施专家共识（2013年版）降糖治疗路径,中华内科杂志. 2014;53(3):243-251,2016 ADA,2016 ADA,所有的治疗均需建立在以下项目基础上,综合评估和危险分层functional status 功能状态Hypoglycaemia 低血糖Hyperglycaemia and their consequences 高血糖及结果Falls 跌倒 pain 疼痛medicine related adverse
25、 events 药物相关不良反应Cost consideration and cost benefit analysis (if available) 经济Level of comorbid illness and/or frailty 共病/衰弱Life expectancy including when to implement palliative care 预期寿命/姑息,IDF 2型糖尿病老年患者管理指南,一线治疗推荐：二甲双胍（没有肾功能减退和其他禁忌时）低血糖发生风险低的磺脲类（避免使用格列本脲）,56,International Diabetes Federation. Glo
26、bal Guideline for Managing Older People with Type 2 Diabetes (2013). Available at www.idf.org,老年糖尿病患者低血糖发生风险高,一项在德国进行的研究，对2009年6月至2010年3月间口服降糖药物治疗的3810名糖尿病患者低血糖事件进行回顾性分析，老年糖尿病患者低血糖发生率高,Bramlage et al. Cardiovascular Diabetology 2012, 11:122,老年患者更易发生严重低血糖,动脉血糖（mmol/L）,年轻患者,感知低血糖阈值,发生严重低血糖阈值,老年人不仅对低血糖
27、感知阈值下降而且严重低血糖的阈值高于年轻人,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获得的受益,研究第1年，强化治疗组和标准治疗组糖化血红蛋白稳定的中位水平分别为6.4%和7.5%。但是发现强化治疗组的死亡率更高，导致平均随访3.5年后中止强化治疗（强化治疗组和标准治疗组的死亡率分别为5.0%和4.0%，P=0.04）。,ACCORD：治疗对血糖控制的影响,ACCORD：治疗对全因死亡率的影响,HbA1c(%),时间(年),时间(年),强化治疗,强化治疗,标准治疗,标准治疗,发生事件的
28、患者(%),Accord Study Group NEJM 2008 358 24 2545,DPP-4抑制剂治疗的特点,通过延长体内自身GLP-1的作用改善糖代谢主要降低餐后血糖对于老年患者有较多获益（A*）低血糖风险很小耐受性和安全性比较好不增加体重,60,中国老年学学会老年医学会老年内分泌代谢专业委员会,老年糖尿病诊疗措施专家共识编写组.中华内科杂志 2014,53(3):243-251.,*A级 多个随机对照试验的Meta分析或系统评价；多个随机对照试验或1个样本量足够的高质量随机对照研究,2012 ADA/EASD 立场声明DPP-4抑制剂作用机制与特点,2012 ADA/EASD共
29、识指出，DPP-4抑制剂机制与特点如下1： 口服DPP-4抑制剂增加活性GLP-1及GIP水平1,2DPP-4抑制剂主要作用为胰岛素与胰高糖素双调节DPP-4抑制剂不增加体重肠促胰素类药物自身不会引起低血糖,Inzucchi SE, et al. Diabetes Care. 2012 Jun;35(6):1364-79.Deacon CF, Diabetes Obes Metab 2011;13:718.,合并多种代谢异常的治疗,1.控制高血压 目标值：140/80mmHg. 药物选择：ACEI/ARB CCB -B 2.控制血脂 大血管危险因素 LDL-C 2.6mmol/L 心脑血管危险
30、 LDL-C 1.8mmol/L3.缺血性脑梗死,Recommendations for Statin and CombinationTreatment in Persons With Diabetes,Cardiovascular risk management,Blood pressure BP 10% men and women over 50 years of age who have at least one additional major risk factor (family history of cardiovascular disease; hypertension; smoking; dyslipidaemia; or albuminuria).,
