有关大流行期间诊断和管理共存疾病的最新信息,请参阅专题“COVID-19 共存疾病管理”。
所有 2 型糖尿病患者治疗方法的基石是个性化的管理计划,包括药物治疗以及由糖尿病教育护士或营养师提供的持续性自我管理教育。[61]Sherifali D, Bai JW, Kenny M, et al. Diabetes self-management programmes in older adults: a systematic review and meta-analysis. Diabet Med. 2015 Nov;32(11):1404-14.
http://www.ncbi.nlm.nih.gov/pubmed/25865179?tool=bestpractice.com
[62]Pillay J, Armstrong MJ, Butalia S, et al. Behavioral programs for type 2 diabetes mellitus: a systematic review and network meta-analysis. Ann Intern Med. 2015 Dec 1;163(11):848-60.
https://annals.org/aim/fullarticle/2446188/behavioral-programs-type-2-diabetes-mellitus-systematic-review-network-meta
http://www.ncbi.nlm.nih.gov/pubmed/26414227?tool=bestpractice.com
[63]Chatterjee S, Davies MJ, Heller S, et al. Diabetes structured self-management education programmes: a narrative review and current innovations. Lancet Diabetes Endocrinol. 2018 Feb;6(2):130-42.
http://www.ncbi.nlm.nih.gov/pubmed/28970034?tool=bestpractice.com
糖尿病自我管理教育可改善糖尿病自我护理,并持续推动有益的生活方式改变。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
这要求提供一般营养学教育和健康生活方式知识,以及基于初始评估和治疗目标的个体化营养和运动计划。加强自我管理的干预措施,也能显著降低糖尿病患者的痛苦。[64]Fisher L, Hessler D, Glasgow RE, et al. REDEEM: a pragmatic trial to reduce diabetes distress. Diabetes Care. 2013 Sep;36(9):2551-8.
https://care.diabetesjournals.org/content/36/9/2551.long
http://www.ncbi.nlm.nih.gov/pubmed/23735726?tool=bestpractice.com
大约 80% 的 2 型糖尿病成人患者合并有血脂异常或高血压,70% 的患者超重或肥胖,大约 15% 的患者当前为吸烟者。[9]Preis SR, Pencina MJ, Hwang SJ, et al. Trends in cardiovascular disease risk factors in individuals with and without diabetes mellitus in the Framingham Heart Study. Circulation. 2009 Jul 6;120(3):212-20.
https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.108.846519
http://www.ncbi.nlm.nih.gov/pubmed/19581493?tool=bestpractice.com
通常,成人 2 型糖尿病患者死于卒中或心肌梗死 (myocardial infarction, MI) 的几率可达非糖尿病患者的两倍,并且他们死于糖尿病大血管并发症的几率是死于糖尿病微血管并发症的四十多倍。[65]Hansen MB, Jensen ML, Carstensen B. Causes of death among diabetic patients in Denmark. Diabetologia. 2012 Feb;55(2):294-302.
http://www.ncbi.nlm.nih.gov/pubmed/22127411?tool=bestpractice.com
[66]Tancredi M, Rosengren A, Svensson AM, et al. Excess mortality among persons with type 2 diabetes. N Engl J Med. 2015 Oct 29;373(18):1720-32.
https://www.nejm.org/doi/full/10.1056/NEJMoa1504347
http://www.ncbi.nlm.nih.gov/pubmed/26510021?tool=bestpractice.com
[67]Desai JR, Vazquez-Benitez G, Xu Z, et al. Who must we target now to minimize future cardiovascular events and total mortality? Lessons from the surveillance, prevention and management of diabetes mellitus (SUPREME-DM) cohort study. Circ Cardiovasc Qual Outcomes. 2015 Sep;8(5):508-16.
https://www.ahajournals.org/doi/full/10.1161/circoutcomes.115.001717
http://www.ncbi.nlm.nih.gov/pubmed/26307132?tool=bestpractice.com
但数据表明,即便血糖、血压、血脂、吸烟和体重管理最佳的 2 型糖尿病成年患者也拥有发生主要心血管事件的风险,但这一风险并不明显高于同年龄和同性别非糖尿病人群出现此类事件的风险。[68]Rawshani A, Rawshani A, Franzén S, et al. Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2018 Aug 16;379(7):633-44.
https://www.nejm.org/doi/10.1056/NEJMoa1800256
http://www.ncbi.nlm.nih.gov/pubmed/30110583?tool=bestpractice.com
[69]Berkelmans GF, Gudbjörnsdottir S, Visseren FL, et al. Prediction of individual life-years gained without cardiovascular events from lipid, blood pressure, glucose, and aspirin treatment based on data of more than 500 000 patients with type 2 diabetes mellitus. Eur Heart J. 2019 Sep 7;40(34):2899-906.
http://www.ncbi.nlm.nih.gov/pubmed/30629157?tool=bestpractice.com
因此,对 2 型糖尿病成年患者的治疗必须包括对所有主要心血管危险因素的管理,并达到针对个人的目标。除血糖控制之外,还包括戒烟、血压控制、血脂控制、对已知冠心病患者使用抗血小板药物,以及对慢性肾脏病或蛋白尿患者使用 ACE 抑制剂或血管紧张素 II 受体拮抗剂。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
[41]Cosentino F, Grant PJ, Aboyans V, et al; Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2019 Aug 31 [Epub ahead of print].
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz486/5556890
http://www.ncbi.nlm.nih.gov/pubmed/31497854?tool=bestpractice.com
[70]Cheng J, Zhang W, Zhang X, et al. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis. JAMA Intern Med. 2014 May;174(5):773-85.
http://www.ncbi.nlm.nih.gov/pubmed/24687000?tool=bestpractice.com
此外,使用可降低心血管死亡率、总死亡率或减少心血管事件的抗高血糖药物可能对已确诊心血管疾病的 2 型糖尿病患者尤其有效。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
[41]Cosentino F, Grant PJ, Aboyans V, et al; Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2019 Aug 31 [Epub ahead of print].
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz486/5556890
http://www.ncbi.nlm.nih.gov/pubmed/31497854?tool=bestpractice.com
[71]Zelniker TA, Wiviott SD, Raz I, et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019 Apr 23;139(17):2022-31.
http://www.ncbi.nlm.nih.gov/pubmed/30786725?tool=bestpractice.com
饮食
营养治疗包括限制热量摄入,以达到推荐的体重,同时提供多样化和有吸引力的食物选择菜单。[72]Cradock KA, ÓLaighin G, Finucane FM, et al. Diet behavior change techniques in type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2017 Dec;40(12):1800-10.
https://care.diabetesjournals.org/content/40/12/1800.long
http://www.ncbi.nlm.nih.gov/pubmed/29162585?tool=bestpractice.com
营养建议需要根据每个患者的需要,最好由营养师制定。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
[29]Evert AB, Dennison M, Gardner CD, et al. Nutrition therapy for adults with diabetes or prediabetes: a consensus report. Diabetes Care. 2019 May;42(5):731-54.
https://care.diabetesjournals.org/content/42/5/731.long
http://www.ncbi.nlm.nih.gov/pubmed/31000505?tool=bestpractice.com
碳水化合物、脂肪和蛋白质的最佳组合,取决于肾功能状态、目前血脂水平、体重指数 (body mass index, BMI)和血糖控制程度等因素。低碳水化合物饮食在 2 型糖尿病管理中似乎对血糖控制有效。[73]Ojo O, Ojo OO, Adebowale F, et al. The effect of dietary glycaemic index on glycaemia in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2018 Mar 19;10(3):E373.
https://www.mdpi.com/2072-6643/10/3/373/htm
http://www.ncbi.nlm.nih.gov/pubmed/29562676?tool=bestpractice.com
饱和脂肪占热量的比例应限制为 <10%。[29]Evert AB, Dennison M, Gardner CD, et al. Nutrition therapy for adults with diabetes or prediabetes: a consensus report. Diabetes Care. 2019 May;42(5):731-54.
https://care.diabetesjournals.org/content/42/5/731.long
http://www.ncbi.nlm.nih.gov/pubmed/31000505?tool=bestpractice.com
减少含糖饮料的摄入(包括牛奶、汽水、功能性饮料和果汁)对许多患者都有益。[29]Evert AB, Dennison M, Gardner CD, et al. Nutrition therapy for adults with diabetes or prediabetes: a consensus report. Diabetes Care. 2019 May;42(5):731-54.
https://care.diabetesjournals.org/content/42/5/731.long
http://www.ncbi.nlm.nih.gov/pubmed/31000505?tool=bestpractice.com
包含健康饮食和躯体活动计划的减重管理方案如果能实现能量损失,则有可能缓解 2 型糖尿病。[29]Evert AB, Dennison M, Gardner CD, et al. Nutrition therapy for adults with diabetes or prediabetes: a consensus report. Diabetes Care. 2019 May;42(5):731-54.
https://care.diabetesjournals.org/content/42/5/731.long
http://www.ncbi.nlm.nih.gov/pubmed/31000505?tool=bestpractice.com
[74]Lean ME, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018 Feb 10;391(10120):541-51.
http://www.ncbi.nlm.nih.gov/pubmed/29221645?tool=bestpractice.com
[75]Gregg EW, Chen H, Wagenknecht LE, et al; Look AHEAD Research Group. Association of an intensive lifestyle intervention with remission of type 2 diabetes. JAMA. 2012 Dec 19;308(23):2489-96.
https://jamanetwork.com/journals/jama/fullarticle/1486829
http://www.ncbi.nlm.nih.gov/pubmed/23288372?tool=bestpractice.com
针对在过去 6 年内诊断为 2 型糖尿病且 BMI 为 27-45 kg/m² 的患者进行支持性减重管理的糖尿病缓解临床试验 (Diabetes Remission Clinical Trial, DiRECT)发现,在第 12 个月时,近半数受试者的病情得到了缓解,达到了非糖尿病状态,并停用了抗糖尿病药物。[74]Lean ME, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018 Feb 10;391(10120):541-51.
http://www.ncbi.nlm.nih.gov/pubmed/29221645?tool=bestpractice.com
两年后,超过三分之一的 2 型糖尿病患者实现了持续性缓解。[76]Lean ME, Leslie WS, Barnes AC, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol. 2019 May;7(5):344-55.
http://www.ncbi.nlm.nih.gov/pubmed/30852132?tool=bestpractice.com
运动和睡眠
为改善血糖控制水平,协助维持体重,降低心血管疾病风险,在患者可耐受的情况下推荐患者参与适度体育活动。ACC/AHA 推荐,在一般情况下,成年人应该每周进行 3 至 4 次有氧体力活动,每次活动平均持续 40 分钟,建议中度到剧烈的体力活动。[77]Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2960-84.
http://www.onlinejacc.org/content/63/25_Part_B/2960
http://www.ncbi.nlm.nih.gov/pubmed/24239922?tool=bestpractice.com
建议穿着合适的鞋子经常行走。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
此外,每周在非连续的日子里进行 2 至 3 次针对所有主要肌肉群的轻微力量训练,每次 20 分钟,可能对患者有益。严重或有症状的心脏病的患者增加体力活动水平之前可能需要评估。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
应该鼓励人们减少久坐的时间,避免长时间久坐。
老年人可获益于柔韧性训练和平衡训练,2-3 次/周,(例如,瑜伽或太极)。
应考虑评估睡眠持续时间和质量。肥胖、糖尿病、高血压、心房颤动和男性性别是睡眠呼吸暂停的危险因素,睡眠不足可能影响血糖控制。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
心血管疾病风险的管理
血压
血压指南对于糖尿病患者的推荐目标有所不同。
2017 年美国心脏病学会/美国心脏协会成人高血压(BP)管理指南建议糖尿病患者 BP 控制在<130/80 mmHg,并采用以下标准对 BP 进行分类:[78]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
http://www.onlinejacc.org/content/71/19/e127
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
正常 (<120/80 mmHg)
升高 (120-129/<80 mmHg)
1 期 (130-139/80-89 mmHg)
高血压 2 期 (≥140/90 mmHg)。
美国糖尿病学会的糖尿病医疗护理标准(Standards of Medical Care in Diabetes)建议:糖尿病患者的目标血压为 <140/90 mmHg;对于已确诊高血压和糖尿病以及已确诊心血管疾病或 10 年心血管风险高于 15% 的患者,考虑以血压 <130/80 mmHg 为目标。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
[79]James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507-20.
https://jamanetwork.com/journals/jama/fullarticle/1791497
http://www.ncbi.nlm.nih.gov/pubmed/24352797?tool=bestpractice.com
无论具体的血压目标如何,推荐采用血管紧张素转换酶抑制剂、血管紧张素 II 受体拮抗剂、钙通道阻滞剂或噻嗪类(或噻嗪类)利尿剂进行初步治疗。黑种人可能从噻嗪类利尿剂或钙通道阻滞剂中取得最大获益。[79]James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507-20.
https://jamanetwork.com/journals/jama/fullarticle/1791497
http://www.ncbi.nlm.nih.gov/pubmed/24352797?tool=bestpractice.com
与血管紧张素 II 受体拮抗剂相比,血管紧张素转换酶抑制剂能够更显著地降低死亡率和心血管事件。[70]Cheng J, Zhang W, Zhang X, et al. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis. JAMA Intern Med. 2014 May;174(5):773-85.
http://www.ncbi.nlm.nih.gov/pubmed/24687000?tool=bestpractice.com
通常需要采用联合药物治疗(采用血管紧张素转换酶抑制剂/血管紧张素-II 受体拮抗剂、钙通道阻滞剂、噻嗪类利尿剂)来达到控制血压的目标。不推荐联合使用血管紧张素转换酶抑制剂和血管紧张素-II 受体拮抗剂,因为这样会增加不良事件的风险。[80]Fried LF, Emanuele N, Zhang JH, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013 Nov 14;369(20):1892-903.
https://www.nejm.org/doi/full/10.1056/NEJMoa1303154
http://www.ncbi.nlm.nih.gov/pubmed/24206457?tool=bestpractice.com
但是,大多数慢性肾病 (chronic kidney disease, CKD) 患者均应使用血管紧张素转换酶抑制剂或血管紧张素-II 受体拮抗剂作为降压治疗方案的一部分。[79]James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507-20.
https://jamanetwork.com/journals/jama/fullarticle/1791497
http://www.ncbi.nlm.nih.gov/pubmed/24352797?tool=bestpractice.com
符合以下条件的人群被定义为 CKD 患者:(a)年龄 <70 岁,肾小球滤过率 (GFR)<60 mL/分/1.73 m²,或(b)任何年龄、GFR 为任何水平,且白蛋白尿中白蛋白(g)和肌酐比值 >30 mg/g。
选择降血压药物时,β 受体阻滞剂对糖尿病患者并非禁忌,但倾向于较少选用,[79]James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507-20.
https://jamanetwork.com/journals/jama/fullarticle/1791497
http://www.ncbi.nlm.nih.gov/pubmed/24352797?tool=bestpractice.com
因其可掩盖低血糖的症状。血管紧张素转换酶抑制剂与胰岛素或胰岛素促分泌剂(例如,磺脲类、格列奈类)合用,可能会增加低血糖的风险。[81]Scheen AJ. Drug interactions of clinical importance with antihyperglycaemic agents: an update. Drug Saf. 2005;28(7):601-31.
http://www.ncbi.nlm.nih.gov/pubmed/15963007?tool=bestpractice.com
如果在一线治疗中血压不受控制,应停止或尽量减少非甾体抗炎药(NSAID)等干扰物质、评估高血压继发病因(包括阻塞性睡眠呼吸暂停),并考虑添加盐皮质激素受体激动剂,[82]Williams B, MacDonald TM, Morant S, et al; British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015 Nov 21;386(10008):2059-68.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00257-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/26414968?tool=bestpractice.com
和/或咨询高血压专科医生。
随着更多研究的开展,血压控制目标和指南也在不断变化。收缩压干预试验 (Systolic Blood Pressure Intervention Trial, SPRINT) 提前结项,因为试验发现,在年龄大于 50 岁、至少有一个额外心脏病危险因素的高血压人群中,120 mmHg 这一更低的收缩压目标可减少心血管并发症和死亡。[83]Wright JT Jr, Williamson JD, et al; SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015 Nov 9;373(22):2103-16.
https://www.nejm.org/doi/10.1056/NEJMoa1511939
http://www.ncbi.nlm.nih.gov/pubmed/26551272?tool=bestpractice.com
但糖尿病患者未纳入这项试验。
越来越强调将家庭血压监测应用于包括糖尿病患者在内的成人高血压诊断和管理。[84]Margolis KL, Asche SE, Bergdall AR, et al. Effect of home blood pressure telemonitoring and pharmacist management on blood pressure control: a cluster randomized clinical trial. JAMA. 2013 Jul 3;310(1):46-56.
https://jamanetwork.com/journals/jama/fullarticle/1707720
http://www.ncbi.nlm.nih.gov/pubmed/23821088?tool=bestpractice.com
血脂
美国心脏病学会/美国心脏协会(ACC/AHA)指南建议,对于年龄>21 岁且耐受他汀类药物的成人患者,如果有临床动脉粥样硬化性心血管疾病(atherosclerotic cardiovascular disease, ASCVD)或低密度脂蛋白 (low-density lipoprotein, LDL)胆固醇 ≥4.9 mmol/L(≥190 mg/dL),则应当接受高强度他汀类药物治疗。[85]Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1082-e1143.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000000625
http://www.ncbi.nlm.nih.gov/pubmed/30586774?tool=bestpractice.com
对于无 ASCVD 的 40-75 岁糖尿病患者,应考虑中等强度的他汀类药物治疗。
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Is there randomized controlled trial evidence to support the use of statins for the primary prevention of cardiovascular disease?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.334/full展示答案 对于 10 年 ACC/AHA 心血管风险高于 20% 的糖尿病患者,应考虑在最大可耐受量他汀类药物治疗中加用依折麦布以使 LDL 水平降低 50% 或更多。[85]Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1082-e1143.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000000625
http://www.ncbi.nlm.nih.gov/pubmed/30586774?tool=bestpractice.com
对于 75 岁以上的糖尿病患者,合理的做法是考虑并与患者讨论启动或继续他汀类药物治疗对患者的利弊。[85]Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1082-e1143.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000000625
http://www.ncbi.nlm.nih.gov/pubmed/30586774?tool=bestpractice.com
在 20-39 岁的糖尿病患者中,如果存在白蛋白尿、估算的 GFR <60 mL/分/1.73 m²、视网膜病或神经病变,应开始他汀类药物治疗。[85]Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1082-e1143.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000000625
http://www.ncbi.nlm.nih.gov/pubmed/30586774?tool=bestpractice.com
妊娠期妇女禁用他汀类药物。
美国糖尿病协会 (American Diabetes Association, ADA) 推荐,血脂异常应根据风险状态进行管理,而非低密度脂蛋白胆固醇水平。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
心血管疾病的危险因素包括 LDL-胆固醇 >2.6 mmol/L(>100mg/dL)、高血压、吸烟、超重和肥胖。建议对所有患者进行生活方式干预治疗。对于患有糖尿病和明显的心血管疾病的患者,应在生活方式干预治疗中增加高强度的他汀类药物治疗,无论血脂基线值如何。高强度他汀类药物治疗也被认为适用于 40 岁以上、无明显心血管疾病但有 1 个或多个心血管疾病(CVD)危险因素的人群。对于 40 岁以上且无其他 CVD 危险因素的糖尿病患者,仍可考虑使用中等强度的他汀类药物治疗。对于已确诊冠心病的糖尿病患者,如果在采用最大可耐受量他汀类药物治疗后 LDL 水平仍持续偏高,此时加用依折麦布或前蛋白转化酶枯草溶菌素 9 (proprotein convertase subtilisin/kexin type 9, PCSK9) 抑制剂(例如阿利西尤单抗、依洛尤单抗)可能会带来临床获益。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
[86]Giugliano RP, Cannon CP, Blazing MA, et al; IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) Investigators. Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in patients with versus without diabetes mellitus: results From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation. 2018 Apr 10;137(15):1571-82.
http://www.ncbi.nlm.nih.gov/pubmed/29263150?tool=bestpractice.com
[87]Sabatine MS, Giugliano RP, Keech AC, et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017 May 4;376(18):1713-22.
https://www.nejm.org/doi/10.1056/NEJMoa1615664
http://www.ncbi.nlm.nih.gov/pubmed/28304224?tool=bestpractice.com
[88]Squizzato A, Suter MB, Nerone M, et al. PCSK9 inhibitors for treating dyslipidemia in patients at different cardiovascular risk: a systematic review and a meta-analysis. Intern Emerg Med. 2017 Oct;12(7):1043-53.
http://www.ncbi.nlm.nih.gov/pubmed/28695455?tool=bestpractice.com
戒烟
应为吸烟患者提供戒烟资源,并提供与戒烟有关的援助,例如适当的药物和咨询等。伐尼克兰联合尼古丁替代疗法可能比单用伐尼克兰更有效。[89]Koegelenberg CF, Noor F, Bateman ED, et al. Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: a randomized clinical trial. JAMA. 2014 Jul;312(2):155-61.
http://www.ncbi.nlm.nih.gov/pubmed/25005652?tool=bestpractice.com
ADA 不推荐电子烟替代吸烟或者辅助戒烟。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
抗血小板疗法
患心血管疾病的成年人应接受阿司匹林作为二级预防。阿司匹林过敏或者不耐受患者可考虑使用氯吡格雷作为替代治疗。在急性冠脉综合征发作后最多 12 个月内,进行双联抗血小板治疗是合理的。主要的副作用是胃肠道出血风险增加。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
[90]Squizzato A, Bellesini M, Takeda A, et al. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events. Cochrane Database Syst Rev. 2017 Dec 14;(12):CD005158.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005158.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/29240976?tool=bestpractice.com
美国糖尿病学会(ADA)建议,对于心血管疾病风险较高(早发心血管疾病家族史、高血压、血脂异常、吸烟、慢性肾脏病/白蛋白尿)的 50-70 岁 2 型糖尿病成人患者,应考虑将阿司匹林治疗作为一级预防,除非他们有较高的严重出血风险。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
美国预防服务工作组(USPSTF)对 50-70 岁患者心脏病发作或卒中的一级预防建议与此类似。[91]Bibbins-Domingo K; US Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2016 Jun 21;164(12):836-45.
https://annals.org/aim/fullarticle/2513179/aspirin-use-primary-prevention-cardiovascular-disease-colorectal-cancer-u-s
http://www.ncbi.nlm.nih.gov/pubmed/27064677?tool=bestpractice.com
抗高血糖药物治疗:初始考虑
糖化血红蛋白目标应遵循个体化原则。[92]Laiteerapong N, Cooper JM, Skandari MR, et al. Individualized glycemic control for US adults with type 2 diabetes: a cost-effectiveness analysis. Ann Intern Med. 2018 Feb 6;168(3):170-8.
http://www.ncbi.nlm.nih.gov/pubmed/29230472?tool=bestpractice.com
[93]Ismail-Beigi F, Moghissi E, Tiktin M, et al. Individualizing glycemic targets in type 2 diabetes mellitus: implications of recent clinical trials. Ann Intern Med. 2011 Apr 19;154(8):554-9.
http://www.ncbi.nlm.nih.gov/pubmed/21502652?tool=bestpractice.com
对于许多患者来说,糖化血红蛋白<7% 的目标是恰当的。然而,糖化血红蛋白 7.0%-7.9% 可能对某些患者更为合适,例如年龄较大、预期寿命有限、已知心血管疾病、具有严重低血糖高风险,或者尽管使用多种降糖药物和胰岛素,仍难以实现低糖化血红蛋白目标的患者。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
与统一的严格控制相比,个性化的糖化血红蛋白目标可提高生活质量。[93]Ismail-Beigi F, Moghissi E, Tiktin M, et al. Individualizing glycemic targets in type 2 diabetes mellitus: implications of recent clinical trials. Ann Intern Med. 2011 Apr 19;154(8):554-9.
http://www.ncbi.nlm.nih.gov/pubmed/21502652?tool=bestpractice.com
如果 HbA1c 高于目标,建议进行药物治疗以降低微血管(肾病、视网膜病变、神经病)和大血管(心肌梗死、卒中、外周血管疾病)并发症风险。[94]UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998 Sep 12;352(9131):854-65.
http://www.ncbi.nlm.nih.gov/pubmed/9742977?tool=bestpractice.com
[95]Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89.
https://www.nejm.org/doi/full/10.1056/NEJMoa0806470
http://www.ncbi.nlm.nih.gov/pubmed/18784090?tool=bestpractice.com
数据表明,预防主要心血管事件和糖尿病肾脏并发症可能不仅受 HbA1c 水平的影响,还受特定抗高血糖药物选药方案的影响。一些特定抗高血糖药物可显著减少某些患者亚组中的全因或心血管疾病死亡率,或者主要心血管事件或肾脏并发症,对于此类患者,这些药物可能是首选药物。[71]Zelniker TA, Wiviott SD, Raz I, et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019 Apr 23;139(17):2022-31.
http://www.ncbi.nlm.nih.gov/pubmed/30786725?tool=bestpractice.com
可在某些患者亚组中减少心血管疾病死亡率的抗高血糖药物包括二甲双胍、[96]Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 2017 Sep;60(9):1620-9.
https://link.springer.com/article/10.1007%2Fs00125-017-4337-9
http://www.ncbi.nlm.nih.gov/pubmed/28770324?tool=bestpractice.com
恩格列净、卡格列净和利拉鲁肽。[71]Zelniker TA, Wiviott SD, Raz I, et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019 Apr 23;139(17):2022-31.
http://www.ncbi.nlm.nih.gov/pubmed/30786725?tool=bestpractice.com
在 ACCORD、ADVANCE 和美国退伍军人糖尿病试验 (Veterans Affairs Diabetes Trial, VADT) 等较早的研究中,对于患心血管疾病或有高心血管疾病风险的 2 型糖尿病患者,使用多种药物使 HbA1c 接近正常的治疗方法没有益处或增加了死亡率。[97]Gerstein HC, Miller ME, Genuth S, et al; ACCORD Study Group. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011 Mar 3;364(9):818-28.
http://www.ncbi.nlm.nih.gov/pubmed/21366473?tool=bestpractice.com
[98]Patel A, MacMahon S, et al; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008 Jun 6;358(24):2560-72.
https://www.nejm.org/doi/full/10.1056/NEJMoa0802987
http://www.ncbi.nlm.nih.gov/pubmed/18539916?tool=bestpractice.com
[99]Reaven PD, Emanuele NV, Wiitala WL, et al; VADT Investigators. Intensive glucose control in patients with type 2 diabetes - 15-year follow-up. N Engl J Med. 2019 Jun 6;380(23):2215-24.
http://www.ncbi.nlm.nih.gov/pubmed/31167051?tool=bestpractice.com
[100]Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009 Jan 8;360(2):129-39.
https://www.nejm.org/doi/full/10.1056/NEJMoa0808431
http://www.ncbi.nlm.nih.gov/pubmed/19092145?tool=bestpractice.com
[101]Gerstein HC, Miller ME, Byington RP, et al; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59.
https://www.nejm.org/doi/full/10.1056/NEJMoa0802743
http://www.ncbi.nlm.nih.gov/pubmed/18539917?tool=bestpractice.com
但是,当时没有钠-葡萄糖共转运蛋白 2 (sodium-glucose co-transporter 2, SGLT2)抑制剂,且这些研究很少使用胰高血糖素样肽-1(glucagon-like peptide-1, GLP-1)激动剂。
使用每日多次胰岛素注射或胰岛素泵的 2 型糖尿病患者,应每日进行三次或多次自我血糖监测。对于采用较少次数胰岛素注射或非胰岛素治疗的患者,自我监测可能有助于指导治疗。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
治疗药物应根据个体选择,考虑患者的价值观和偏好、药物降低全因死亡或心血管疾病死亡率的可能性、肾脏影响、不良作用、成本和其他因素。
二甲双胍因其安全性和对心血管的可能益处,对于无禁忌证的患者,是确诊时推荐的首选疗法。[94]UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998 Sep 12;352(9131):854-65.
http://www.ncbi.nlm.nih.gov/pubmed/9742977?tool=bestpractice.com
[96]Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 2017 Sep;60(9):1620-9.
https://link.springer.com/article/10.1007%2Fs00125-017-4337-9
http://www.ncbi.nlm.nih.gov/pubmed/28770324?tool=bestpractice.com
可在估算的肾小球滤过率(eGFR)降低的患者中安全使用二甲双胍,但如果 eGFR <30 mL/分/1.73 m²,应禁用。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
[102]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-701.
https://care.diabetesjournals.org/content/41/12/2669.long
http://www.ncbi.nlm.nih.gov/pubmed/30291106?tool=bestpractice.com
如果 eGFR <45 mL/分/1.73 m²,则不应启动二甲双胍治疗,对于服用二甲双胍且 eGFR 降至 30-45 mL/分/1.73 m² 范围以内的患者,可以考虑继续使用该药物,但需密切监测肾功能并降低剂量。[102]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-701.
https://care.diabetesjournals.org/content/41/12/2669.long
http://www.ncbi.nlm.nih.gov/pubmed/30291106?tool=bestpractice.com
[103]US Food and Drug Administration. FDA drug safety communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function. Apr 2016 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-revises-warnings-regarding-use-diabetes-medicine-metformin-certain
因禁忌证或不耐受而无法服用二甲双胍的患者,可以改为服用替代性非胰岛素药物,或起始胰岛素治疗。基础-餐时胰岛素被用作 2 型糖尿病和初始血糖过高 (>16.6 mmol/L [>300 mg/dL])患者的初始治疗(不给予二甲双胍)。
对于不伴有确诊心血管疾病的糖尿病患者,如果是初次使用二甲双胍且治疗 3 个月后未达到目标,基于对必要的临床益处、安全性、成本和患者偏好的个性化评估,可添加第二种药物:[102]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-701.
https://care.diabetesjournals.org/content/41/12/2669.long
http://www.ncbi.nlm.nih.gov/pubmed/30291106?tool=bestpractice.com
钠-葡萄糖共转运蛋白 2 (Sodium-glucose co-transporter 2, SGLT2)抑制剂:卡格列净、达格列净、恩格列净或 ertugliflozin
胰高血糖素样肽-1 (glucagon-like peptide-1, GLP-1) 激动剂:利拉鲁肽、利西拉肽、索马鲁肽或度拉糖肽
二肽基肽酶-4 (dipeptidyl peptidase-4, DPP-4) 抑制剂:西格列汀、沙格列汀、利格列汀或阿格列汀
磺脲类:格列美脲、格列齐特或格列吡嗪;氯茴苯酸类(例如,瑞格列奈、那格列奈)也可被选用
α-葡萄糖苷酶抑制剂:阿卡波糖或米格列醇
噻唑烷二酮:吡格列酮
胰岛素
对于伴有确诊心血管疾病的糖尿病患者,如果是初次使用二甲双胍且治疗 3 个月后未达到目标,则可添加第二种药物。建议对长期血糖控制欠佳以及伴确诊心血管疾病和/或肾脏疾病的患者,添加 SGLT2 抑制剂或 GLP-1 激动剂。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
[102]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-701.
https://care.diabetesjournals.org/content/41/12/2669.long
http://www.ncbi.nlm.nih.gov/pubmed/30291106?tool=bestpractice.com
[104]Das SR, Everett BM, Birtcher KK, et al. 2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2018 Dec 18;72(24):3200-23.
http://www.onlinejacc.org/content/72/24/3200
http://www.ncbi.nlm.nih.gov/pubmed/30497881?tool=bestpractice.com
SGLT2 抑制剂:可首选卡格列净或恩格列净。
GLP-1 激动剂:可首选利拉鲁肽。
目前有许多合适的三联降糖药物疗法,不含胰岛素。第二种和第三种抗高血糖药物的选择可能会有所不同,具体取决于心血管合并症。[102]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-701.
https://care.diabetesjournals.org/content/41/12/2669.long
http://www.ncbi.nlm.nih.gov/pubmed/30291106?tool=bestpractice.com
当 2 或 3 种药物的非胰岛素治疗方案失败时,可以加用基础胰岛素。如果需要达到或维持足够的血糖控制,可随后加用餐时胰岛素。为了降低低血糖风险,当开始胰岛素治疗时,磺脲类药物通常应逐渐减量。
特定口服抗高血糖药物的临床特性
通常依据与患者就药物利弊的讨论结果来选择药物。降低全因死亡率或心血管死亡率的药物可优先选择。[41]Cosentino F, Grant PJ, Aboyans V, et al; Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2019 Aug 31 [Epub ahead of print].
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz486/5556890
http://www.ncbi.nlm.nih.gov/pubmed/31497854?tool=bestpractice.com
二甲双胍可促进体重减轻,并可降低心血管事件和死亡率。[94]UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998 Sep 12;352(9131):854-65.
http://www.ncbi.nlm.nih.gov/pubmed/9742977?tool=bestpractice.com
[96]Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 2017 Sep;60(9):1620-9.
https://link.springer.com/article/10.1007%2Fs00125-017-4337-9
http://www.ncbi.nlm.nih.gov/pubmed/28770324?tool=bestpractice.com
SGLT2 抑制剂(卡格列净、达格列净、恩格列净、ertugliflozin)可抑制肾脏对葡萄糖的重吸收。将导致糖尿增加,从而改善血糖控制,促进体重减轻,并具有利尿作用,可降低血压。[105]Scheen AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs. 2015 Jan;75(1):33-59.
http://www.ncbi.nlm.nih.gov/pubmed/25488697?tool=bestpractice.com
有证据表明,使用 SGLT2 抑制剂可预防 2 型糖尿病患者出现重大肾病结局(透析、移植或肾病引起的死亡)。[106]Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019 Nov;7(11):845-54.
http://www.ncbi.nlm.nih.gov/pubmed/31495651?tool=bestpractice.com
经证实,恩格列净和卡格列净可降低 CVD 合并 2 型糖尿病患者的心血管风险,并且可能对肾脏有益。[71]Zelniker TA, Wiviott SD, Raz I, et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019 Apr 23;139(17):2022-31.
http://www.ncbi.nlm.nih.gov/pubmed/30786725?tool=bestpractice.com
[107]Neal B, Perkovic V, Mahaffey KW, et al; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017 Aug 17;377(7):644-57.
https://www.nejm.org/doi/full/10.1056/NEJMoa1611925
http://www.ncbi.nlm.nih.gov/pubmed/28605608?tool=bestpractice.com
[108]Cherney DZ, Zinman B, Inzucchi SE, et al. Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017 Aug;5(8):610-21.
http://www.ncbi.nlm.nih.gov/pubmed/28666775?tool=bestpractice.com
[109]Mahaffey KW, Jardine MJ, Bompoint S, et al. Canagliflozin and cardiovascular and renal outcomes in type 2 diabetes mellitus and chronic kidney disease in primary and secondary cardiovascular prevention groups. Circulation. 2019 Aug 27;140(9):739-50.
https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.119.042007
http://www.ncbi.nlm.nih.gov/pubmed/31291786?tool=bestpractice.com
[110]Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019 Jan 5;393(10166):31-39.
http://www.ncbi.nlm.nih.gov/pubmed/30424892?tool=bestpractice.com
经证实,恩格列净和卡格列净可显著降低糖尿病合并确诊心血管疾病患者的心血管或全因死亡率。[111]Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28.
https://www.nejm.org/doi/10.1056/NEJMoa1504720
http://www.ncbi.nlm.nih.gov/pubmed/26378978?tool=bestpractice.com
[112]Mahaffey KW, Neal B, Perkovic V, et al; CANVAS Program Collaborative Group. Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS program (Canagliflozin Cardiovascular Assessment Study). Circulation. 2018 Jan 23;137(4):323-34.
https://www.ahajournals.org/doi/full/10.1161/circulationaha.117.032038
http://www.ncbi.nlm.nih.gov/pubmed/29133604?tool=bestpractice.com
[113]Rådholm K, Figtree G, Perkovic V, et al. Canagliflozin and heart failure in type 2 diabetes mellitus. Circulation. 2018 Jul 31;138(5):458-68.
https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.118.034222
http://www.ncbi.nlm.nih.gov/pubmed/29526832?tool=bestpractice.com
在一项临床试验中,对患有动脉粥样硬化性心血管疾病或有此风险的 2 型糖尿病患者使用达格列净进行治疗,不会降低主要不良心血管事件的发生率,但降低了因心力衰竭而住院的比率。[114]Wiviott SD, Raz I, Bonaca MP, et al; DECLARE–TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019 Jan 24;380(4):347-57.
https://www.nejm.org/doi/full/10.1056/NEJMoa1812389
http://www.ncbi.nlm.nih.gov/pubmed/30415602?tool=bestpractice.com
关于 ertugliflozin 对治疗 CVD 的益处的试验正在进行中。[115]Cinti F, Moffa S, Impronta F, et al. Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date. Drug Des Devel Ther. 2017 Oct 3;11:2905-19.
https://www.dovepress.com/spotlight-on-ertugliflozin-and-its-potential-in-the-treatment-of-type--peer-reviewed-fulltext-article-DDDT
http://www.ncbi.nlm.nih.gov/pubmed/29042751?tool=bestpractice.com
[116]ClinicalTrials.gov. Cardiovascular outcomes following ertugliflozin treatment in type 2 diabetes mellitus participants with vascular disease: the VERTIS CV study (MK-8835-004). NCT01986881. Apr 2019 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT01986881
[117]ClinicalTrials.gov. ERtugliflozin triAl in DIabetes With Preserved or Reduced ejeCtion FrAcTion mEchanistic Evaluation in Heart Failure (ERADICATE-HF). NCT03416270. May 2018 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03416270
不同药物的不良反应包括以下情况的发生率增高:生殖道感染、糖尿病酮症酸中毒、急性肾损伤、骨折和/或截肢。[111]Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28.
https://www.nejm.org/doi/10.1056/NEJMoa1504720
http://www.ncbi.nlm.nih.gov/pubmed/26378978?tool=bestpractice.com
[118]US Food and Drug Administration (FDA). FDA drug safety communication: FDA strengthens kidney warnings for diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). Jun 2016 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-kidney-warnings-diabetes-medicines-canagliflozin
[119]Ueda P, Svanström H, Melbye M, et al. Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ. 2018 Nov 14;363:k4365.
https://www.bmj.com/content/363/bmj.k4365.long
http://www.ncbi.nlm.nih.gov/pubmed/30429124?tool=bestpractice.com
值得注意的是,美国食品药品监督管理局 (Food and Drug Administration, FDA) 已证实使用卡格列净可增加腿、足截肢的风险。[120]US Food and Drug Administration (FDA). FDA drug safety communication: FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR). May 2017 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-confirms-increased-risk-leg-and-foot-amputations-diabetes-medicine
欧洲药品管理局 (European Medicines Agency, EMA) 也警示了 SGLT2 抑制剂可能增加脚趾截肢的风险。[121]European Medicines Agency (EMA). SGLT2 inhibitors: information on potential risk of toe amputation to be included in prescribing information. Feb 2017 [internet publication].
https://www.ema.europa.eu/en/documents/referral/sglt2-inhibitors-previously-canagliflozin-article-20-procedure-sglt2-inhibitors-information_en-0.pdf
对于坎格列净,处方信息还会将下肢截肢列为不常见的副作用。[122]Medicines and Healthcare products Regulatory Agency. MHRA drug safety update: SGLT2 inhibitors: updated advice on increased risk of lower-limb amputation (mainly toes). Mar 2017 [internet publication].
https://www.gov.uk/drug-safety-update/sglt2-inhibitors-updated-advice-on-increased-risk-of-lower-limb-amputation-mainly-toes
FDA 和英国药品和医疗产品监管署 (Medicines and Healthcare products Regulatory Agency, MHRA) 发出警示,称在 SGLT-2 抑制剂上市后的监测中观察到会阴坏死性筋膜炎(也称为 Fournier 坏疽)病例。[123]US Food and Drug Administration (FDA). FDA drug safety communication: FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes. Aug 2018 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-occurrences-serious-infection-genital-area-sglt2-inhibitors-diabetes
[124]Medicines and Healthcare products Regulatory Agency. SGLT2 inhibitors: reports of Fournier’s gangrene (necrotising fasciitis of the genitalia or perineum). Feb 2019 [internet publication].
https://www.gov.uk/drug-safety-update/sglt2-inhibitors-reports-of-fournier-s-gangrene-necrotising-fasciitis-of-the-genitalia-or-perineum
因此,对于存在会增加截肢风险疾病的患者以及易发生尿路或生殖器感染的患者,应避免使用 SGLT2 抑制剂。
GLP-1 受体激动剂(利拉鲁肽、艾塞那肽、利西拉肽、索马鲁肽和度拉糖肽)适用于希望减轻体重且无胃轻瘫的肥胖患者,愿意采用注射用药,能够容忍最初用药时出现的恶心等常见副作用。[125]Htike ZZ, Zaccardi F, Papamargaritis D, et al. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab. 2017 Apr;19(4):524-36.
http://www.ncbi.nlm.nih.gov/pubmed/27981757?tool=bestpractice.com
一篇综述报道,使用 GLP-1 激动剂后,与安慰剂相比患者减重 1.4 kg,与胰岛素相比患者减重 4.8 kg。[126]Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007 Jul 11;298(2):194-206.
http://www.ncbi.nlm.nih.gov/pubmed/17622601?tool=bestpractice.com
GLP-1 激动剂这类药物对 2 型糖尿病患者的心血管、死亡率和肾脏结局具有有益作用。[127]Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019 Oct;7(10):776-85.
http://www.ncbi.nlm.nih.gov/pubmed/31422062?tool=bestpractice.com
在一项随机试验中,利拉鲁肽显著降低了糖尿病、心血管疾病或高 CVD 风险患者的心血管疾病死亡率和全因死亡率。[128]Marso SP, Daniels GH, Brown-Frandsen K, et al; LEADER Steering Committee on behalf of the LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22.
https://www.nejm.org/doi/full/10.1056/NEJMoa1603827
http://www.ncbi.nlm.nih.gov/pubmed/27295427?tool=bestpractice.com
研究表明,度拉糖肽和索马鲁肽均可减少主要心血管事件,但不能降低全因死亡率或心血管疾病死亡率。[129]Gerstein HC, Colhoun HM, Dagenais GR, et al; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019 Jul 13;394(10193):121-30.
http://www.ncbi.nlm.nih.gov/pubmed/31189511?tool=bestpractice.com
[130]Marso SP, Bain SC, Consoli A, et al; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-44.
https://www.nejm.org/doi/full/10.1056/NEJMoa1607141
http://www.ncbi.nlm.nih.gov/pubmed/27633186?tool=bestpractice.com
[131]Kaul S. Mitigating cardiovascular risk in type 2 diabetes with antidiabetes drugs: a review of principal cardiovascular outcome results of EMPA-REG OUTCOME, LEADER, and SUSTAIN-6 trials. Diabetes Care. 2017 Jul;40(7):821-31.
https://care.diabetesjournals.org/content/40/7/821.long
http://www.ncbi.nlm.nih.gov/pubmed/28637887?tool=bestpractice.com
研究显示,艾塞那肽和利司那肽不会减少主要心血管事件。[132]Hu Y. Advances in reducing cardiovascular risk in the management of patients with type 2 diabetes mellitus. Chronic Dis Transl Med. 2019 Mar 15;5(1):25-36.
https://www.sciencedirect.com/science/article/pii/S2095882X18300653
http://www.ncbi.nlm.nih.gov/pubmed/30993261?tool=bestpractice.com
MHRA 警告,在联合使用 GLP-1 受体激动剂和胰岛素的情况下,将合用胰岛素的剂量迅速减少或停用时,2 型糖尿病患者会出现糖尿病酮症酸中毒的情况。[133]Medicines and Healthcare products Regulatory Agency. GLP-1 receptor agonists: reports of diabetic ketoacidosis when concomitant insulin was rapidly reduced or discontinued. Jun 2019 [internet publication].
https://www.gov.uk/drug-safety-update/glp-1-receptor-agonists-reports-of-diabetic-ketoacidosis-when-concomitant-insulin-was-rapidly-reduced-or-discontinued
DPP-4 抑制剂(西格列汀、沙格列汀、利格列汀、阿格列汀)耐受性好,不影响体重,但不能降低死亡率。
磺脲类药物(格列吡嗪、格列美脲和格列本脲)是临床选择的主要药物,并可减少微血管并发症的风险,但在降低死亡率方面没有获益,且可能导致体重增加和低血糖。[102]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-701.
https://care.diabetesjournals.org/content/41/12/2669.long
http://www.ncbi.nlm.nih.gov/pubmed/30291106?tool=bestpractice.com
这些都是费用较低的抗高血糖药物,包括二甲双胍和人胰岛素。[134]World Health Organization. Guidelines on second- and third-line medicines and type of insulin for the control of blood glucose levels in non-pregnant adults with diabetes mellitus. 2018 [internet publication].
https://apps.who.int/iris/bitstream/handle/10665/272433/9789241550284-eng.pdf?ua=1
对于餐后血糖波动较大的人群,可在二甲双胍基础上加用 α-葡萄糖苷酶抑制剂(阿卡波糖、米格列醇),但胃肠胀气增多和胃肠道(gastrointestinal, GI)副作用较常见。目前还没有强有力的证据表明该药物有益于改善全因或心血管疾病死亡率。
噻唑烷二酮类药物(吡格列酮、罗格列酮)能有效降低血糖,但可能使充血性心力衰竭风险增加一倍以上,通常会导致体重增加和水肿。[102]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-701.
https://care.diabetesjournals.org/content/41/12/2669.long
http://www.ncbi.nlm.nih.gov/pubmed/30291106?tool=bestpractice.com
这些药物可能会导致贫血,并增加女性和男性患者骨折的发生率。此外,罗格列酮会增加 LDL-胆固醇水平,并且有各类证据表明罗格列酮可能增加心血管事件风险。[135]Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007 Jun 14;356(24):2457-71.
https://www.nejm.org/doi/full/10.1056/NEJMoa072761
http://www.ncbi.nlm.nih.gov/pubmed/17517853?tool=bestpractice.com
由于存在持续的安全问题,罗格列酮已从欧洲市场上撤市。[136]European Medicines Agency (EMA). Questions and answers on the suspension of rosiglitazone-containing medicines (Avandia, Avandamet and Avaglim). Sep 2010 [internet publication].
https://www.ema.europa.eu/en/documents/medicine-qa/questions-answers-suspension-rosiglitazone-containing-medicines-avandia-avandamet-avaglim_en.pdf
但在 2013 年,美国食品药品监督管理局 (Food and Drug Administration, FDA) 依据更新的数据解除了美国之前对罗格列酮的限制。[137]Bach RG, Brooks MM, Lombardero M, et al; BARI 2D Investigators. Rosiglitazone and outcomes for patients with diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Circulation. 2013 Aug 20;128(8):785-94.
https://ahajournals.org/doi/full/10.1161/circulationaha.112.000678
http://www.ncbi.nlm.nih.gov/pubmed/23857320?tool=bestpractice.com
FDA 根据一份更新的评价结果得出以下结论:使用吡格列酮可能与膀胱癌风险升高有关。[138]US Food and Drug Administration. FDA drug safety communication: updated FDA review concludes that use of type 2 diabetes medicine pioglitazone may be linked to an increased risk of bladder cancer. Dec 2016 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-updated-fda-review-concludes-use-type-2-diabetes-medicine-pioglitazone
溴隐亭和考来维仑在部分国家中是得到批准的降糖口服剂。他们对许多患者血糖影响有限。溴隐亭可引起胃肠道副作用。考来维仑,原本用作胆汁酸螯合剂,需要每日多次给药,可与其他药物联合使用。目前,此类药物均未被广泛用于控糖治疗。
胰岛素治疗
重度高血糖须采用胰岛素治疗,且当二甲双胍单药治疗或多药联合方案疗效不足时,胰岛素治疗亦为一种选择。通常以睡前给予长效基础胰岛素起始治疗。非胰岛素治疗联合基础胰岛素单次注射,可使部分患者血糖得到良好控制。但是,部分患者需给予每日一次长效基础胰岛素(例如地特胰岛素、甘精胰岛素或德谷胰岛素)注射,并在每餐前注射速效胰岛素(例如赖脯胰岛素、门冬胰岛素或谷赖胰岛素)。中效(NPH) 和短效(常规)胰岛素是基础-餐时胰岛素方案的其他选择。对于 2 型糖尿病患者,人胰岛素和胰岛素类似物在血糖控制、重度低血糖风险、死亡率以及心血管事件等方面效能相当。[139]Fullerton B, Siebenhofer A, Jeitler K, et al. Short-acting insulin analogues versus regular human insulin for adult, non-pregnant persons with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2018 Dec 17;(12):CD013228.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013228/full
http://www.ncbi.nlm.nih.gov/pubmed/30556900?tool=bestpractice.com
[
]
How do short‐acting insulin analogues compare with regular human insulin for adults with type 2 diabetes mellitus?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2514/full展示答案 人胰岛素相较于胰岛素类似物价格低一些。预混胰岛素也可用。治疗方案应遵循个体化原则。现已有能够预设的胰岛素给药设备,能够实现设定胰岛素剂量的给药,可以帮助患者达到血糖控制。随着胰岛素剂量的增加,磺脲类药物应逐渐减量,而二甲双胍可以继续使用。
如果血糖水平≥16.6 mmol/L (≥300 mg/dL) 或者如果 HbA1c ≥86 mmol/mol (≥10%),则诊断时应考虑进行胰岛素治疗。这些患者具有明显的高血糖,在没有恶心、呕吐或容量不足的情况下,二甲双胍可用于辅助治疗。
外源性胰岛素是降低血糖和糖化血红蛋白非常有效的方法,但大多数患者必须在定期自我监测血糖的指导下使用。低血糖(血糖≤3.9 mmol/L [≤70 mg/dL])是胰岛素治疗最严重的潜在并发症。另一个显著的副作用是体重增加。不太常见的副作用可能包括饥饿、恶心、出汗、注射部位刺激或全身过敏反应。
胰岛素校正剂量
对于基础餐时胰岛素使用积极熟练和经验丰富的患者,每餐前给予速效胰岛素的剂量可以根据预期的碳水化合物含量予以调整,或调整预期的体力活动。速效胰岛素的校正剂量也可以基于餐前血糖水平(校正算法)给药。确定校正算法的合理方法是,用 1800 除以全天的胰岛素剂量得到每单位胰岛素降低血糖期望值。例如,对于每天注射 60 单位胰岛素的患者,额外 1 个单位胰岛素的预期血糖降低量为 1800/60 = 30 mg/dL (1.7 mmol/L)。
治疗肥胖糖尿病患者的减重手术
随机临床试验表明,2 型糖尿病患者中,与单纯药物治疗相比,减重手术(也称为代谢手术)在短期内(例如,1-3 年)有益于缓解糖尿病、控制血糖、减少降糖药物需求量、提高生活质量和降低心血管风险因素标志物,[140]Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012 Apr 26;366(17):1567-76.
https://www.nejm.org/doi/10.1056/NEJMoa1200225
http://www.ncbi.nlm.nih.gov/pubmed/22449319?tool=bestpractice.com
[141]Schauer PR, Bhatt DL, Kirwan JP, et al; STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes - 5-year outcomes. N Engl J Med. 2017;376:641-51.
https://www.nejm.org/doi/10.1056/NEJMoa1600869
http://www.ncbi.nlm.nih.gov/pubmed/28199805?tool=bestpractice.com
[142]Kashyap SR, Bhatt DL, Wolski K, et al. Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: analysis of a randomized control trial comparing surgery with intensive medical treatment. Diabetes Care. 2013 Aug;36(8):2175-82.
https://care.diabetesjournals.org/content/36/8/2175.long
http://www.ncbi.nlm.nih.gov/pubmed/23439632?tool=bestpractice.com
[143]Ikramuddin S, Korner J, Lee WJ, et al. Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and hyperlipidemia: the Diabetes Surgery Study randomized clinical trial. JAMA. 2013 Jun 5;309(21):2240-9.
https://jamanetwork.com/journals/jama/fullarticle/1693889
http://www.ncbi.nlm.nih.gov/pubmed/23736733?tool=bestpractice.com
[144]Halperin F, Ding SA, Simonson DC, et al. Roux-en-Y gastric bypass surgery or lifestyle with intensive medical management in patients with type 2 diabetes: feasibility and 1-year results of a randomized clinical trial. JAMA Surg. 2014 Jul;149(7):716-26.
https://jamanetwork.com/journals/jamasurgery/fullarticle/1876617
http://www.ncbi.nlm.nih.gov/pubmed/24899464?tool=bestpractice.com
也有利于2型糖尿病的预防[145]Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012 Aug 23;367(8):695-704.
https://www.nejm.org/doi/10.1056/NEJMoa1112082
http://www.ncbi.nlm.nih.gov/pubmed/22913680?tool=bestpractice.com
队列研究表明,Roux en Y 旁路手术和袖状胃切除术可缓解一半以上患者的糖尿病,平均持续约 5 年,还可显著降低 2 型糖尿病患者的死亡率并减少卒中、心肌梗死和微血管并发症。[146]Yska JP, van Roon EN, de Boer A, et al. Remission of type 2 diabetes mellitus in patients after different types of bariatric surgery: a population-based cohort study in the United Kingdom. JAMA Surg. 2015 Dec;150(12):1126-33.
https://jamanetwork.com/journals/jamasurgery/fullarticle/2446843
http://www.ncbi.nlm.nih.gov/pubmed/26422580?tool=bestpractice.com
[147]Fisher DP, Johnson E, Haneuse S, et al. Association between bariatric surgery and macrovascular disease outcomes in patients with type 2 diabetes and severe obesity. JAMA. 2018 Oct 16;320(15):1570-82.
https://jamanetwork.com/journals/jama/fullarticle/2707461
http://www.ncbi.nlm.nih.gov/pubmed/30326126?tool=bestpractice.com
[148]O'Brien R, Johnson E, Haneuse S, et al. Microvascular outcomes in patients with diabetes after bariatric surgery versus usual care: a matched cohort study. Ann Intern Med. 2018 Sep 4;169(5):300-10.
http://www.ncbi.nlm.nih.gov/pubmed/30083761?tool=bestpractice.com
与袖状胃切除术相比,Roux en Y 手术具有明显减轻体重等益处,但在技术上更具挑战性,并且二次手术率和再入院率更高。减重手术的益处与风险也因 2 型糖尿病亚组的不同而明显各异。在观察性研究中,平均获益率最高的患者似乎是相对年轻(年龄在 40-50 岁之间)的患者、患 2 型糖尿病时间较短的患者以及未接受胰岛素治疗的患者。[149]Park JY. Prediction of type 2 diabetes remission after bariatric or metabolic surgery. J Obes Metab Syndr. 2018 Dec 30;27(4):213-22.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513303/
http://www.ncbi.nlm.nih.gov/pubmed/31089566?tool=bestpractice.com
对于 BMI ≥40 kg/m²(亚裔家庭人群 ≥37.5 kg/m²),且血糖控制于任何水平/接受任何复杂降糖方案治疗的成人,可考虑减重手术。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
还可考虑对以下成人进行手术:BMI 达到 35.0-39.9 kg/m²(亚裔家庭人群为 32.5-37.4 kg/m²),且尽管采取了生活方式管理和最佳内科管理,但高血糖控制效果不佳;BMI 达到 30.0-34.9 kg/m²(亚裔家庭人群为 27.5-32.4 kg/m²),且尽管采取了最佳口服或注射药物(包括胰岛素)治疗,但高血糖控制效果不佳。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
最好在手术量大的专科中心进行减重手术。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
妊娠期糖尿病的治疗
孕前和孕期良好控制血糖,并在安全的情况下使 HbA1c 尽可能接近正常水平(理想情况下,HbA1c <6.5% [48 mmol/mol]),能够获得最佳的母婴的健康结局。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
[150]Tieu J, Middleton P, Crowther CA, et al. Preconception care for diabetic women for improving maternal and infant health. Cochrane Database Syst Rev. 2017 Aug 11;(8):CD007776.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007776.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/28799164?tool=bestpractice.com
ADA 指南推荐先前存在 2 型糖尿病的孕妇应达到以下血糖目标(与妊娠期糖尿病相同):空腹状态下<5.3 mmol/L (<95 mg/dL),且餐后 1 小时≤7.8 mmol/L (≤140 mg/dL) 或餐后 2 小时≤6.7 mmol/L (≤120 mg/dL),HbA1c 个体化目标<42-48 mmol/mol(<6% 至<6.5%)或必要时最高<53 mmol/mol (<7%) 以预防低血糖。[2]American Diabetes Association. Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S1-193.
https://care.diabetesjournals.org/content/42/Supplement_1
英国国家卫生与临床优化研究所指南推荐,如果安全的话,则孕妇的目标血糖值为:餐前葡萄糖 5.3 mmol/L (95 mg/dL),餐后 1 小时葡萄糖低于 7.8 mmol/L (140 mg/dL),餐后 2 小时葡萄糖低于 6.4 mmol/L (115 mg/dL)。[18]National Institute for Health and Care Excellence. Diabetes in pregnancy: management from preconception to the postnatal period. Aug 2015 [internet publication].
https://www.nice.org.uk/guidance/ng3
[证据 C]4efe3e6f-336e-471b-b4bd-bb6de160be6aguidelineC在患妊娠糖尿病的孕妇中,更严格的血糖控制对比相对宽松的血糖控制,效果如何?[18]National Institute for Health and Care Excellence. Diabetes in pregnancy: management from preconception to the postnatal period. Aug 2015 [internet publication].
https://www.nice.org.uk/guidance/ng3
在临床实践中,营养治疗未能实现这些目标时则通常使用胰岛素。NPH 胰岛素可与短效人造胰岛素或速效胰岛素类似物联合使用。长效胰岛素类似物(甘精胰岛素、地特胰岛素或德谷胰岛素)尚未获批用于妊娠期。不建议在妊娠期间使用血管紧张素转换酶抑制剂、血管紧张素-II 受体拮抗剂和 β 受体阻滞剂,并且应避免使用。孕妇禁用他汀类药物。孕前患糖尿病的患者应在孕前、孕期和产后接受视网膜检查。在可能的情况下,接受专科中心的医疗监护对希望妊娠或已妊娠的糖尿病女性患者有益。
医疗保健服务模式
平均而言,在过去的 20 年中,针对糖尿病的医疗水平已显著提升,糖尿病成人患者的死亡率、心血管疾病死亡率和心血管事件发生率降低了 50%。[13]National Institute of Diabetes and Digestive and Kidney Diseases. Diabetes in America. 3rd edition. Bethesda, MD: National Institutes of Health, NIH Pub No. 17-1468; 2018.
https://www.niddk.nih.gov/about-niddk/strategic-plans-reports/diabetes-in-america-3rd-edition
许多因素促进了糖尿病诊治水平的提升,并使患者的临床结局得到改善。[151]Ali MK, Bullard KM, Saaddine JB, et al. Achievement of goals in U.S. diabetes care, 1999-2010. N Engl J Med. 2013 Apr 25;368(17):1613-24.
https://www.nejm.org/doi/full/10.1056/NEJMsa1213829
http://www.ncbi.nlm.nih.gov/pubmed/23614587?tool=bestpractice.com
制定这些策略的主要模式是慢性病照护模式。[152]Bodenheimer T, Wagner E, Grumbach K. Improving primary care for patients with chronic illness: the chronic care model. JAMA. 2002 Oct 9;288(14):1775-9.
http://www.ncbi.nlm.nih.gov/pubmed/12365965?tool=bestpractice.com
该模式包括 6 个核心要素:医疗保健服务系统设计、自我管理支持、决策支持、临床信息系统、社区资源和政策、卫生系统。
证据普遍支持以下医疗护理改善策略。
一个多学科团队对于患者护理的策略,包括训练有素的糖尿病自我管理教育工作者、药剂师和案例管理者的参与。[153]Bongaerts BW, Müssig K, Wens J, et al. Effectiveness of chronic care models for the management of type 2 diabetes mellitus in Europe: a systematic review and meta-analysis. BMJ Open. 2017 Mar 20;7(3):e013076.
https://bmjopen.bmj.com/content/7/3/e013076.long
http://www.ncbi.nlm.nih.gov/pubmed/28320788?tool=bestpractice.com
[154]McLean DL, McAlister FA, Johnson JA, et al. A randomized controlled trial of the effect of community pharmacist and nurse care on improving blood pressure management in patients with diabetes mellitus: study of cardiovascular risk intervention by pharmacists - hypertension (SCRIP-HTN). Arch Intern Med. 2008 Nov 24;168(21):2355-61.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/414649
http://www.ncbi.nlm.nih.gov/pubmed/19029501?tool=bestpractice.com
高级且整合的电子病历临床决策支持系统(其功能不仅仅是简单的提醒和警报)。[155]Sperl-Hillen JM, Crain AL, Margolis KL, et al. Clinical decision support directed to primary care patients and providers reduces cardiovascular risk: a randomized trial. J Am Med Inform Assoc. 2018 Sep 1;25(9):1137-46.
https://academic.oup.com/jamia/article/25/9/1137/5048778
http://www.ncbi.nlm.nih.gov/pubmed/29982627?tool=bestpractice.com
[156]O’Connor PJ, Sperl-Hillen JM, Rush WA, et al. Impact of electronic health record clinical decision support on diabetes care: a randomized trial. Ann Fam Med. 2011 Jan-Feb;9(1):12-21.
http://www.annfammed.org/content/9/1/12.full
http://www.ncbi.nlm.nih.gov/pubmed/21242556?tool=bestpractice.com
针对临床医生进行基于案例的模拟学习干预。[157]Sperl-Hillen J, O'Connor P, Ekstrom H, et al. Using simulation technology to teach diabetes care management skills to resident physicians. J Diabetes Sci Technol. 2013 Sep 1;7(5):1243-54.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876368/
http://www.ncbi.nlm.nih.gov/pubmed/24124951?tool=bestpractice.com
[158]Sperl-Hillen JM, O'Connor PJ, Rush WA, et al. Simulated physician learning program improves glucose control in adults with diabetes. Diabetes Care. 2010 Aug;33(8):1727-33.
https://care.diabetesjournals.org/content/33/8/1727.long
http://www.ncbi.nlm.nih.gov/pubmed/20668151?tool=bestpractice.com
[159]O'Connor PJ, Sperl-Hillen JM, Johnson PE, et al. Simulated physician learning intervention to improve safety and quality of diabetes care: a randomized trial. Diabetes Care. 2009 Apr;32(4):585-90.
https://care.diabetesjournals.org/content/32/4/585.long
http://www.ncbi.nlm.nih.gov/pubmed/19171723?tool=bestpractice.com
对医疗提供系统的其他改良设计,例如替选报销方法、支持更健康生活方式的公共政策变化、以患者为中心的医疗之家以及移动健康 (mHealth) 技术等,可能有机会进一步改善医疗水平,目前正在经受评估。[160]Kim EK, Kwak SH, Jung HS, et al. The effect of a smartphone-based, patient-centered diabetes care system in patients with type 2 diabetes: a randomized, controlled trial for 24 weeks. Diabetes Care. 2019 Jan;42(1):3-9.
https://care.diabetesjournals.org/content/42/1/3.long
http://www.ncbi.nlm.nih.gov/pubmed/30377185?tool=bestpractice.com
[161]Fu H, McMahon SK, Gross CR, et al. Usability and clinical efficacy of diabetes mobile applications for adults with type 2 diabetes: a systematic review. Diabetes Res Clin Pract. 2017 Sep;131:70-81.
http://www.ncbi.nlm.nih.gov/pubmed/28692830?tool=bestpractice.com
糖尿病管理决策应及时做出、依据循证指南并与患者协同制定。