2型糖尿病

疾病

2型糖尿病(Type 2 diabetes 或 Type 2 diabetes mellitus,简称 T2DT2DM,或称第2型糖尿病[注 1],旧称非胰岛素依赖型糖尿病(英语:noninsulin-dependent diabetes mellitus,NIDDM)或成人发病型糖尿病(英语:adult-onset diabetes),是一种慢性代谢疾病,患者特征为高血糖、相对缺乏胰岛素、有胰岛素抗性[6]。常见症状有烦渴频尿、不明原因的体重减轻[3] ,可能还包括多食、疲倦、或有治不好的酸痛[3],以上症状通常会慢慢出现[6]。高血糖带来的长期并发症包括心脏病中风糖尿病视网膜病变,这可能导致失明肾脏衰竭、甚至四肢血流不顺而需要截肢[1] ;2型糖尿病患者可能突然发生高渗性高血糖状态,但却不太会并发糖尿病酮症酸中毒[4][5]

2型糖尿病
又称非胰岛素依赖型糖尿病(Noninsulin-dependent diabetes mellitus,NIDDM)
成人糖尿病(adult-onset diabetes)[1]
空心蓝圈为糖尿病的国际象征符号[2]
读音
症状烦渴多尿症、不明原因体重下降多食症[3]
并发症高渗性高血糖状态糖尿病酮症酸中毒心血管疾病中风糖尿病视网膜病变肾功能衰竭截肢[1][4][5]
起病年龄中年或老年[6]
病程终身[6]
类型糖尿病荷尔蒙失调
病因肥胖症、缺乏运动、遗传[1][6]
诊断方法血糖测量[3]
预防维持正常体重、体能锻炼、均衡饮食[1]
治疗饮食调整英语diabetic diet二甲双胍、胰岛素、代谢手术[1][7][8][9]
预后预期寿命缩短约10年[10]
患病率3.92亿(2015年)[11]
分类和外部资源
医学专科内分泌学
ICD-115A11
ICD-10E11
OMIM125853、​601283、​601407、​603694、​608036
DiseasesDB3661
MedlinePlus000313
eMedicine117853
Orphanet181376、​181376
[编辑此条目的维基数据]

2型糖尿病主要发生在肥胖而又缺乏运动的人[1],具有先天基因遗传者风险也较高[6]。2型糖尿病占了糖尿病患者约九成的病例,另外一成为1型糖尿病妊娠糖尿病患者[1]。1型糖尿病患者因胰脏β细胞自身免疫破坏,而有绝对性胰岛素缺乏的问题[12][13]。糖尿病确诊需经由血液检查而定,如检测空腹血糖值英语fasting plasma glucose口服葡萄糖耐量试验(OGTT)或检测糖化血红蛋白(HbA1c[3]

部分的2型糖尿病可经由保持正常体重、规律运动及适当饮食来预防[1],治疗方式有运动和改变饮食英语Diabetic diet[1]。如果没有经常性血糖偏低,建议的治疗药物选择包含:双胍类[7][14]磺酰脲类(sulfonylureas)、噻唑烷二酮类(thiazolidinedione)、GLP-1类似物DPP-4抑制剂SGLT2抑制剂及复方药物、胰岛素,但许多患者最终都必须使用胰岛素治疗[9]。使用胰岛素的患者必须定期测量血糖,口服降血糖药的患者则不一定需要[15]。对肥胖的患者而言,接受减肥手术对改善糖尿病亦十分有效[8][16]

自1960年起,2型糖尿病病例就随着肥胖率逐渐升高[17]。1985年时全球仅有约3000万人罹患糖尿病,到了2015年患者增至3.92亿人[11][18]。糖尿病好发于中高龄层[6],但现今青年人罹患2型糖尿病的比率逐渐增加[19][20]。2型糖尿病患者可能减损长达约十年的寿命[10]。糖尿病是最早被描述的疾病之一[21],1920年代科学家就发现了胰岛素对它的重要性[22]

台湾健保数据库10年追踪研究发现,65岁以上新确诊糖尿病病人,于男性族群之死亡相对风险为非糖尿病患者的1.2倍;于女性族群则为1.27倍。糖尿病患者中,10 年内发生心血管并发症相对风险也高于非糖尿病患者 (8.9%vs.5.8%),而男性和女性的相对风险分别为1.54及1.70。[23]

糖尿病讲解影片(英文)

病征与症状

 
糖尿病显著症状概述

糖尿病的典型症状为多尿症烦渴多食症Polyphagia)以及体重减轻[24]。诊断时其他常见的症状包括视野模糊皮肤瘙痒周围神经病变、反复阴道炎疲劳等病史[13]。然而,很多人在最初数年间不会出现病征,一般在常规体检中才被诊断出来[13]。在少部分的患者会出现高渗性高血糖状态,此类患者会产生高血糖伴有意识水平下降英语decreased level of consciousness,以及低血压的病况[13]

并发症

2型糖尿病是慢性疾病,患者的预期寿命可减少长达10年[10]。导致预期寿命减少的部分原因是相关的并发症,包括:患上心血管疾病的风险是健康人群的二至四倍,其中包括缺血性心脏病中风等等。下肢截肢率会增加20倍,住院率亦相对增高[10]。在发达国家及越来越多的其他地区里,2型糖尿病是导致非创伤性失明肾衰竭的首要原因[25]。在发病过程中,患者罹患认知功能障碍英语cognitive dysfunction痴呆风险也会增高,如阿兹海默病血管性痴呆等等[26]。其他并发症还包括黑棘皮症性功能障碍,以及容易发生感染[24]

糖尿病患相较于正常族群会增加2到4倍的心血管疾病风险,约32%的糖友合并有心血管疾病[27],而心血管疾病是全世界糖尿病患者最重要的并发症及主要死因,近6成的糖尿病患者死于心血管疾病。[28]

研究显示,糖化血色素(HbA1c)每增加1%会增加16%心衰竭发生率[29],近15%的糖友合并有心衰竭[27],增加60-80%心血管死亡风险。[30][31]男性心衰竭比例高2.5倍,女性心衰竭比例高4.1倍[32],30%-50%心衰竭患者有糖尿病[33],五年存活率仅剩12.5%。另外,约10%的2型糖尿病患会发生肾病变(约20万人),40%末期肾脏疾病原因来自于糖尿病。[34]

糖尿病血管并发症可分为小血管并发症(Microvascular disease)及大血管并发症(Macrovascular disease)且随着并发症逐渐加重常会导致患的器官、身体功能的丧失。[35]

小血管病变包括视网膜病变、神经病变与肾病变等等,由糖尿病引起的小血管疾病;大血管病变则包括冠状动脉心脏病(冠心症)、中风、周边血管疾病等,糖尿病病患因为常合并患有高血压、血脂异常及代谢综合征,这些因素也会促进冠状动脉粥状硬化的产生[36]

2型糖尿病人的血脂异常特征为,三酸甘油脂酯增高、高密度脂蛋白胆固醇下降,低密度脂蛋白胆固醇略上升。[37]高密度脂蛋白胆固醇下降,会增加糖尿病老年患者的心血管疾病及缺血性中风风险。[38]

另外,高血压是在糖尿病很常见的共病症,相较于非糖尿病患者族群,糖尿病族群的高血压发生率可高出1.5–3 倍之多。[39]约有 6–8 成的糖尿病患者死于心血管并发症,而这些心血管并发症的发生有高达 75% 可以归咎于高血压所造成。[40]除了心血管并发症,与高血压相关的糖尿病并发症还包括了肾脏病变、视网膜病变、中风等。[37]

病因

2型糖尿病的发生与患者的生活方式与遗传因素有关[25][41]。有些因素如饮食习惯和肥胖症等是人为可控制的,但其他如年纪增长、性别为女性、遗传等因素则不然[10]。睡眠不足也与2型糖尿病有关[42],因为睡眠不足会使致身体的新陈代谢有所改变,进而诱发2型糖尿病[42]。孕妇在胎儿发育过程中的营养状况对胎儿未来罹患糖尿病的几率也占有一席之地,其中DNA甲基化改变是造成此种影响的可能机制之一[43]。此外,肠道细菌如肠道普氏菌Prevotella copri)和普通拟杆菌Bacteroides vulgatus)也可能和2型糖尿病有关[44]

生活方式

目前认为有不少生活方式都是引致2型糖尿病的重要因素,其中包括肥胖症超重BMI高于25)、身体活动量不足、不健康的饮食、压力过大以及城市化的生活等[10]。30%的华裔与日裔患者体脂过高,欧裔和非裔患者则有60%至80%,印第安人和太平洋岛民患者则100%都体脂过高[13]。至于非肥胖症的2型糖尿病患则常有过高的腰臀比[13]。吸烟似乎也会增加罹患2型糖尿病的机会[45]

饮食也是影响2型糖尿病发病风险的重要因素。饮用过量的含饮料可增加患病风险[46][47]。饮食里摄取的脂肪也是很重要的因素,饱和脂肪反式脂肪均会增加患病风险,而多元不饱和脂肪单元不饱和脂肪则有助于降低风险[41]。摄取大量白米似乎也会使致病风险增加[48]。也有学者相信,7%的病例可能是缺乏运动所致[49]持久性有机污染物可能也和糖尿病相关[50]

遗传因素

大多数糖尿病个案涉及多种基因,而这些不同的基因都可能会使患上2型糖尿病的几率上升[10]。如果同卵双胞胎的其中一人有糖尿病,另一人患上糖尿病的机会高于90%,然而非同卵的兄弟姐妹的几率只有25%至50%[13]。到2011年为止,共发现了超过36个基因都可能增加罹患2型糖尿病的风险[51]。然而,即使全部这些基因加在一起,亦只占诱发糖尿病的整体遗传因素中的10%[51]。举例来说,可使发病风险增加1.5倍的等位基因TCF7L2英语TCF7L2为常见基因变异中拥有最高风险的基因[13]。多数与糖尿病有关的基因都与β细胞英语beta cells功能有关[13]

在一部分罕见的糖尿病个案中,发病原因是因单个基因出现异常而引起的(称为单基因型糖尿病或“其他特殊类型糖尿病”)。[13][10]其中包括年轻人成人型糖尿病英语maturity onset diabetes of the young(简称MODY)、矮妖精貌综合征英语LeprechaunisRabson-Mendenhall综合征等等[10]。其中年轻人成人型糖尿病占年轻糖尿病患者个案总和的1%至5%[52]

健康状况

许多药物和健康问题都会使人较易患糖尿病[53]。这些药物包括:糖皮质激素噻嗪类利尿剂β受体阻滞剂非典型抗精神病药物[54]他汀类药物[55]。曾患妊娠糖尿病的人患上2型糖尿病的风险较高[24],而其他和2型糖尿病相关的健康问题还包括肢端肥大症皮质醇增多症甲状腺功能亢进症嗜铬细胞瘤及某些癌症胰高血糖素瘤英语glucagonoma[53]。另外,睾酮缺乏与2型糖尿病也有很密切的关联[56][57]

病理生理学

2型糖尿病的病因复杂,对于单一病患而言,难以确认引发疾病的原因,往往环境和遗传因素中的一种或者多种均有可能与发病相关[58]。胰岛β细胞功能失常和胰岛素抵抗引发了2型糖尿病[59]:尽管在1980年代,人们普遍认为仅靠胰岛素抵抗即可引发糖尿病,但后来的研究表明,在没有β细胞功能失常的情况下,糖尿病不可能发生[60]。在这两种症状的程度方面,患者表现出的胰岛素抵抗和相对胰岛素不足的程度有所差异:有些人以胰岛素抵抗为主、轻微的胰岛素分泌缺陷为次;而其他人可能只有轻微的胰岛素抵抗,而以胰岛素分泌不足为主[13]

在2型糖尿病中,胰岛素抵抗和高血浆胰岛素水平的发生往往先于疾病发生[58]:尽管过去曾认为高胰岛素水平是胰岛素抵抗引起的代偿,但后来的研究表明,血浆中的高胰岛素水平不一定是代偿胰岛素抵抗的后果,亦有可能是产生胰岛素抵抗的原因[61]。再者,在肥胖诱导的炎症等各种因素作用下,胰岛β细胞的生产或者分泌胰岛素的功能受损。[58]

其他可能与2型糖尿病和胰岛素抵抗、胰岛功能受损有关的重要机制还包括:脂肪细胞脂质的分解增加、对肠泌素英语incretin的抵抗或缺乏、血液中胰高血糖素水平过高、肾脏积蓄的盐份和水分上升,及中枢神经系统的代谢调节异常[10]

胰岛素抵抗

胰岛素抵抗被认为是2型糖尿病的主要特征之一[59]。在胰岛素抵抗的情况下,应当对胰岛素进行响应的组织或器官(如肌肉、肝脏及脂肪组织)无法对正常浓度的胰岛素作出适当响应[62]——例如:具体到肝脏而言,指的是肝脏无法正常响应胰岛素信号,致使糖原分解和葡萄糖异生不能被抑制,血糖被不当增加[63];具体到肌肉而言,指的是肌肉组织无法无法正常响应胰岛素信号,致使肌肉吸收的血糖减少,血糖下降变缓[64]。并不只有葡萄糖在这一过程受到影响:2型糖尿病患者的肝脏和肌肉常见异位脂肪沉积,其氧化过程和葡萄糖形成底物竞争,抑制了葡萄糖的氧化英语Randle cycle,亦被用来解释胰岛素抵抗的形成。此类的脂肪累积早于2型糖尿病的发病。[65]

欧洲胰岛素阻抗研究组织(EGIR)研究发现胰岛素敏感度会依年龄增加而下降,不过两者关联性会因身体质量指数(body mass index, BMI)校正而消失。[66]老化后胰岛素阻抗性的现象可能来自于腹部脂肪组织增生、骨骼肌肉量降低、生理活动减少、线粒体功能不全、荷尔蒙分泌减退、氧化压力和慢性发炎等。[67][68]

动物实验显示,单独的胰岛素抵抗并不一定引起糖尿病:消耗大量能量的大脑和肌肉之中存在的胰岛素抵抗并未在引起胰岛素抵抗,有鉴于此,肝脏和胰岛中的胰岛素抵抗可能是借由其它途径诱导。双基因敲除则提示胰岛素抵抗的多基因型,如IRS-1和GK双基因敲除可以诱导小鼠糖尿病,而单基因敲除不能。胰岛素抵抗往往会与高血压、高血脂等心血管风险因子聚集,形成所谓的“代谢综合征”。[58]

β细胞功能异常

然而,并非所有出现胰岛素抵抗的人士都会患上糖尿病,患者的胰岛β细胞需同时有胰岛素分泌障碍时才会发病[13]。胰岛β细胞功能失常是1型糖尿病和2型糖尿病的共同特征之一,但在2型糖尿病中,胰岛功能常常被忽视。2型糖尿病中的β细胞功能下降往往在糖类不耐受发生以前就已经发生[59]。确诊时,胰岛功能通常已经是正常水平的三成左右;英国前瞻性糖尿病研究中显示,胰岛的功能衰减无法透过饮食,磺脲类、二甲双胍或胰岛素治疗等单一治疗手段进行控制。目前用药选择中,DPP4i抑制剂、GLP-1类似物观察到针对2型糖尿病患者β细胞功能的改善[69]

1型糖尿病的胰岛素分泌不足主要是因为自体免疫引起的β细胞死亡,而2型糖尿病中的β细胞功能下降或者死亡的原因则较为复杂,与氧化应激、炎症等相关[59]。如以脂质毒性的角度而言,在肝脏和肌肉中异位累积的过量脂肪难以被有效氧化,透过非氧化途径生成反应性脂肪,诱导脂质的凋亡亦纠正脂肪过载的情形;在这一过程生成的神经酰胺等物质可介导胰腺细胞的衰亡[65]。由于饮食和遗传因素等原因,亚裔群体,特别是印度人,易于产生在器官内累积大量脂肪的腹部肥胖;尽管亚裔人群较西方群体纤瘦,也有较高的糖尿病流行率可能与之相关[70][71]。但这一过程不仅仅和脂质毒性有关,还和糖类引发的氧化应激有关[72]:过量的糖类与脂质在能量循环中会形成竞争,糖类的氧化往往受到抑制[73]

诊断

世界卫生组织糖尿病诊断标准[74][75]  编辑
条件 餐后两小时血糖 空腹血糖 HbA1c
mmol/l(mg/dl) mmol/l(mg/dl) %
正常 <7.8(<140) <6.1(<100) <5.7
空腹血糖障碍英语Impaired fasting glucose <7.8(<140) ≥6.1(≥100)& <7.0(<126) 5.7–6.4
糖耐量受损英语Impaired glucose tolerance ≥7.8(≥140) <7.0(<126) 5.7–6.4
糖尿病 ≥11.1(≥200) ≥7.0(≥126) ≥6.5

世界卫生组织定义糖尿病(包括1型和2型)为有症状之单次血糖值上升,或两次血糖值上升达到以下标准[76]

  • 空腹血糖≥7.0 mmol/l(126 mg/dl)
  • 作出糖耐力测试,口服两小时之后,血糖≥11.1 mmol/l(200 mg/dl)。

随机血糖高于11.1 mmol/l (200 mg/dl )且出现典型症状[24]糖化血红蛋白(HbA1c)高于6.5%是也一种诊断糖尿病的方法[10]。2009年,一个由美国糖尿病协会(American Diabetes Association,简称ADA)、国际糖尿病联合会(International Diabetes Federation,简称IDF)和欧洲糖尿病研究协会(European Association for the Study of Diabetes,简称EASD)之专家代表组成的国际专家委员会建议糖尿病诊断应使用48 mmol/mol作为临界值(相当于 HbA1c 6.5%)[77],美国糖尿病协会于2010年采用此建议[78]。只有病患出现典型症状和血糖>11.1  mmol/l(>200  mg/dl)才应该重复进行阳性检验[77]

糖尿病诊断之临界阈根据的是糖耐力测试、空腹血糖或HbA1c,和并发症(如视网膜病变)的关系[10]。比起糖耐力测试,空腹或随机血糖因为比较方便而被广泛使用[10]。HbA1c的优点是不需禁食且结果较稳定,但缺点是检验较血糖测量昂贵[79]。估计美国有20%的糖尿患者不知道自己患有糖尿病[10]

2型糖尿病的特征是在胰岛素抵抗胰岛素相对缺乏所造成的高血糖[80],这与1型糖尿病中的绝对胰岛素缺乏大不相同,后者是因为胰岛细胞损坏所导致的。而妊娠期糖尿病则是在怀孕时新发生的高血糖[13]。1型和2型糖尿病通常可以根据临床表现来区分[77]。如果对诊断存在疑问,抗体试验可能有助于判定1型糖尿病,C-胜肽英语C-peptide水平则有助于判定2型糖尿病[81]

台湾诊断标准

诊断标准包括以下4项,非怀孕状况下“只要符合其中1项”即可诊断为糖尿病(前三项需重复验证2次以上)[82]
(一) 糖化血色素(HbA1c)≧ 6.5%
(二) 空腹血浆血糖 ≧ 126 mg/dL
(三) 口服葡萄糖耐受试验第2小时血浆血糖 ≧ 200 mg/dL
(四) 典型的高血糖症状(多吃、多喝、多尿与体重减轻)且 随机血浆血糖 ≧ 200 mg/dL

中国大陆诊断标准

 

[83]

筛检

由于没有证据证明大规模糖尿病筛检英语Screening (medicine)可改善最终结果,因此没有大型组织或部门建议进行全面筛检[84][85]美国预防服务任务小组英语United States Preventive Services Task Force(USPSTF)建议对没有症状且血压高于 135/80 毫米水银柱的成年人进行筛检[86]。对于血压较低的人,并没有充分证据显示能够降低此群体的风险和死亡率[86][85]。USPSTF也建议40至70岁之间的过重者进行筛检[87]

世界卫生组织(WHO)和USPSTF皆建议高风险者进行筛检[84][88]。在美国,高风险者包含年龄超过45岁、一等亲英语first degree relative(包含手足)有糖尿病、部分族裔(如拉美裔、非裔,以及美洲原住民)、有妊娠糖尿病多囊卵巢综合征病史、过重,或是患有代谢综合征等等[24]美国糖尿病学会英语American Diabetes Association建议BMI超过25者进行筛检(亚裔则建议23以上就应该筛检)[89]。也建议,45 岁以上成人应每 1–3 年检查一次空腹血糖、HbA1C 或口服葡萄糖耐受试验。[90]卫生福利部国民健康署亦提供整合性筛检,筛检项目也包含糖尿病,40–64 岁的民众,建议每 3 年筛检一次;而针对 65 岁以上的民众,建议每年筛检一次。[91]

预防

适当营养和经常运动可以延缓或防止2型糖尿病的发病[92][93],严格执行生活方式控制可以降低超过一半的风险[25][94]。无论原始体重多寡或后来的体重是否减轻,运动皆有益处[95]。但单靠调整饮食便能降低风险的证据却十分有限[96],一些证据支持多摄取绿色蔬菜[97],也有一些证据支持限制含糖饮料[46]。对于葡萄糖耐受不良英语impaired fasting glucose的人士,只改变饮食习惯和运动,或同时使用二甲双胍阿拉伯糖,可以降低罹患糖尿病的风险[25][98],改变生活方式比服用二甲双胍还有效[25]。一份2017年的回顾文献指出,长期的生活方式改造能降低28%罹病风险,但糖尿病药物在停药后将无助于减低风险[99]。血中的维生素D含量较低会增加糖尿病的风险,但口服补充维生素D3无法改善罹病风险[100]

管理

2型糖尿病的疾病管理着重于调整生活型态、减低其他心血管风险因素,以及将血糖维持在正常值[25]英国国民保健署建议2型糖尿病初诊人士进行血糖自我监测[101],但是对于没有使用多剂量胰岛素的人士,自我监测的益处仍有争议[25][102]。管理其他心血管风险因素如高血压高胆固醇微量白蛋白尿能改善预期余命[25]。将收缩压控制于 140 mmHg 以下能够降低死亡风险,并改善预后[103],更高积极的血压管理(低于130/80 mmHg)相较于标准血压管理(140/85–100 mmHg)虽能使中风风险轻微减低,但对总体死亡风险并没有影响[104]

相对于标准血糖控制(HbA1C7-7.9%),更积极的血糖控制(HbA1C<6%)似乎并未改善死亡率[105][106]。2型糖尿病的治疗目标通常是HbA1C低于7%至8%或空腹血糖低于7.2 mmol/L(130 mg/dl);但若将低血糖症和预期余命等特定风险纳入考量,这些目标在专业临床会诊后可以改变[107][108]。尽管临床指引建议医师须衡量血糖控制的长期好处和立即伤害,许多人仍被过度治疗,例如对预期余命小于9年的患者进行强化血糖控制便没有好处[109]

所有患有2型糖尿病的人士都应定期进行眼科检查[13]。有限的证据显示以刮除牙结石和牙根整平术治疗牙周病或许可以短期改善糖尿病患者的血糖[110],但没有证据显示这样的改善能持续超过4个月[110]。目前并没有证据表示治疗牙周病的药物有助于改善血糖[110]

生活方式

适当的饮食和运动是糖尿病治疗的基础[24],运动量越充足效果越佳[111]。运动能改善血糖控制,降低体脂和血脂,这些效果即使在没有体重减轻的情形下也都有证据支持[112]有氧运动可使HbA1c下降并改善胰岛素敏感性[113]阻力训练也有改善的效果,若能同时进行有氧运动及阻力训练效果尤佳[113]

能促进减重的饮食英语diabetic diet调整相当重要[114]。目前最理想的饮食配方为何仍有争议[114],但目前已知低升糖指数饮食英语low glycemic index diet低碳水化合物饮食可以改善血糖[115][116]。在2型糖尿病发病后短时间内开始超低卡路里饮食英语Very-low-calorie diet能使疾病缓解[117]素食者相对来说罹患糖尿病的机会较低,但荤食摄取适量者效果则与素食无异[118]。目前尚无证据支持肉桂可以改善2型糖尿病患者的血糖[119]

适当的卫教也能协助患者控制血糖,效果最佳可维持到24个月[120]。若轻度糖尿病患者的血糖无法借由调整生活型态改善,则可能需要考虑配合药物治疗[24]。目前仍尚无足够证据说明调整生活型态对于患者死亡率的影响[94]

药物

 
二甲双胍500mg片剂

目前有数类抗糖尿病药,如双胍类、磺酰脲类(sulfonylureas)、噻唑烷二酮类thiazolidinedione)、GLP-1类似物DPP-4抑制剂SGLT2抑制剂等。遵照医师建议使用药物能有效控制病况,病患应定时用药并定时回诊追踪,以降低血糖波动,达到最好控制效果。

  • 双胍类
    • 由于有证据表明二甲双胍metformin)可降低死亡率,因此通常将其作为第一线治疗药物[7][25][121]。然而目前有关此议结论仍有疑问[122],且并非所有第二线糖尿病患者都能一体适用,如有低血氧或是肾、肝、心脏疾病者,不建议使用二甲双胍[24]。若二甲双胍metformin)不足以控制病情,则可使用另一个类的口服制剂或注射胰岛素辅助控制[107]
  • 磺酰脲类
    • 用于2型糖尿病的抗糖尿病药,主要作用是促进胰脏β细胞分泌胰岛素。目前较常用的为格列美脲,为第二代磺酰脲类药物。[123]
  • 噻唑烷二酮类
    • 用于2型糖尿病的抗糖尿病药,主要作用是增进胰岛素的感受性,改善血糖控制。[124]目前有吡格列酮(Pioglitazone)、罗格列酮(Rosiglitazone)药物。吡格列酮(Pioglitazone)因有报导指出此药物会增加膀胱癌的风险,法国跟德国已经暂时停止销售这个药物。[125]罗格列酮(Rosiglitazone)过去曾有心脏副作用疑虑[126][127][128],2010年FDA曾限制使用条件,并要求药商执行药品风险评估暨管控计划[129][130],台湾亦跟进管制措施,直到2016年才解除限制。[131]
  • DPP-4抑制剂
  • SGLT2抑制剂
    • 用于2型糖尿病的抗糖尿病药,主要作用是抑制葡萄糖在肾脏的再吸收而使葡萄糖由尿液排除的抗糖尿病药[136], SGLT2抑制剂可以降低血糖水平和体重,并且可以降低舒张压与收缩压。[137]常见药物如达格列净卡纳格列净英语Canagliflozin曲格列净英语Ertugliflozin恩格列净,恩格列净是首支SGLT2抑制剂类降糖药有完成心血管预后研究的药品,目前唯一口服降糖药被研究证实有控糖、护心、保肾及减重等效果。[138]SGLT2抑制剂为第2型糖尿病的治疗药物,国际临床研究结果显示,恩格列净(Empagliflozin)在管理心脏衰竭部分亦有成效,因此除糖尿病适应症外,同时具有心衰竭适应症,据2021年发表的国际临床试验证明,可以降低25%心衰竭住院或心血管死亡风险,并且延缓4倍肾丝球过滤率(eGFR)下降速率。SGLT2抑制剂同时被纳入心脏衰竭的治疗指引[139]
  • GLP-1类似物(肠泌素)
    • 用于2型糖尿病的抗糖尿病药,主要作用是提升胰岛素分泌,并抑制餐后升糖素的分泌,达到降低血糖的效果。常见药物有艾塞那肽、 利拉鲁肽…等,需要用注射方式使用。[140]

2018年医学期刊The Lancet分析指出SGLT2抑制剂效果优于GLP-1与DDP-4可以降低心衰竭住院的风险、减少心肌梗死、中风、心血管死亡等心血管不良总和事件,甚至可以减少45%肾脏病变风险。[141] SGLT2抑制剂达格列净恩格列净都经实验证实可降低心脏衰竭病患因心血管因素而死亡或入院的风险[142],2020年SGLT2抑制剂也通过美国FDA认证可用于治疗心脏衰竭[143]

截至2015年为止研究指出,二甲双胍(Metformin)因为其效果、价钱、安全性总和而言仍然是一线的最佳药物,但因其副作用不建议肾功能衰竭者使用。[144] 除一线用药外,其余糖尿病药物的选择基于降低血糖、最少副作用,以及患者的喜好、用药习惯,各种患者自身疾病(如自身心血管疾病、慢性肾病)、用药后不适应症(低血糖症)…等。[145]

2016年的研究指出糖尿病患者的血压最好控制于140至150 mmHg之间[146]

胰岛素可以单独使用,也可以配合其他口服药剂一起使用[25],大多数人最初都无需注射胰岛素[13]。当使用时,通常在夜间采用一种长效制剂,同时继续口服药物[24][25]。剂量会过一段时间才起效,达到控制血糖的效果[25]。当夜间胰岛素不足,每日两次胰岛素可达到更好的控制[24]。长效胰岛素,甘精胰岛素glargine)和地特胰岛素效果及安全性相同[147],其效果并不优于中效胰岛素(NPH insulin),且价格又较贵,因此截至2010年的研究并无发现其实质效益[148]。对于怀孕的患者,胰岛素通常是治疗选择[24]

过去谣传补充维生素D可预防糖尿病,根据2019年美国糖尿病学会年会最新研究指出,针对糖尿病前期的患者补充维生素D无法预防患者恶化成糖尿病,该研究同步发表在新英格兰医学期刊。[149]

复方药物

目前糖尿病口服药物亦有复方药物,如Glyxambi(糖顺平)其限用于已接受过最大耐受剂量的二甲双胍(Metformin),且并用恩格列净(Empagliflozin, Jardiance,恩排糖) 或利拉利汀(Linagliptin Trajenta,糖渐平) 治疗,糖化血色素值(HbA1c)仍未低于8.5%者,亦有其他不同类型的复方药物例如DPP-4抑制剂西格列汀(Sitagliptin, Januvia,佳糖维)与二甲双胍(Metformin) 的复方药物JANUMET(捷糖稳)、利拉利汀(Linagliptin, Trajenta,糖渐平)与二甲双胍(Metformin) 的复方药物Trajenta Duo(糖倍平)、维格列汀( Vildagliptin, Galvus,高糖优适) 与二甲双胍(Metformin) 的复方药物Galvus Met(高糖优美)。SGLT2抑制剂复方药物也有恩格列净(Empagliflozin, Jardiance,恩排糖) 与二甲双胍(Metformin) 的复方药物 Jardiance Duo(恩美糖)、达格列净(Dapagliflozin, Forxiga,福适佳) 与二甲双胍(Metformin) 的复方药物Xigduo XR(释多糖)。复方药物可提高患者服药顺从性,也可降低口服药物的复杂程度,如Glyxambi(糖顺平)综合Empagliflozin 、Linagliptin优点,能降糖、降低体重、降低心血管疾病、保肾、不易低血糖多重功效。[150]

外科手术

对于超重的患者,代谢手术(减肥手术)是治疗糖尿病的有效措施[151]。许多人手术后,能够维持正常的血糖水平并服用很少或根本不服用药物[152],且长期死亡率也会降低了[153]。不过仍存在低于1%的短期手术死亡风险[154]。目前建议身高体重指数(BMI)大于35的糖尿病患者进行代谢手术[155][156]。BMI介于30-35之间的若血糖控制不佳或有高度胰岛素阻抗者,也建议进行[155][156]

流行病学

 
2014年全球糖尿病患病率(每1000个居民),世界平均为9.2%。

2015年,全球2型糖尿病患者约有3.92亿人,占糖尿病患者的90%[10][11],约相当于世界成人人口的6%[11]。糖尿病是发达国家发展中国家常见的疾病[10]。在经济欠发达地区仍然相当罕见[13]

糖尿病是台湾人十大死因之一,根据2021年卫福部统计,台湾现行糖尿病患人数约200多万人,并以每年25,000名的速率持续增加中,对国人的健康影响不容小觑[157]

女性在某些族裔中似乎罹病风险较高[10][158],如南亚裔太平洋岛民Pacific Islander)、拉美裔Latino),和美洲原住民等族裔群体似乎有更高的患病风险[24]。这可能是由于这些群体对西方的生活方式更为敏感[159]。传统上,2型糖尿病归类为成人疾病,然而随着儿童肥胖率英语Childhood obesity的增加,越来越多的儿童也被诊断罹患2型糖尿病[10]。美国青少年被诊断为2型糖尿病的频率与1型糖尿病同样频繁[13]

糖尿病患者在1985年的数量估计在3000万,在1995年增至1.36亿,2005年增加至2.17亿[18]。增加的原因主要是全球人口老龄化、运动减少,和肥胖率增加[18]。至2000年为止,糖尿病患者数最多的五个国家是印度(3170万)、中国(2080万)、美国(1770万)、印度尼西亚(840万)和日本(680万)[160]。糖尿病被世界卫生组织确认为一种全球性流行病[1]

历史

糖尿病是最早被记录的疾病之一[21],早在公元前约1500年的埃及手稿将其称为“尿液过多”[161]。据信首个有记载的病例被认为是1型糖尿病[161]。同时期,古印度的医生在同期也发现了该病,由于患者的尿液会引来蚂蚁,因此将其归称为“蜜糖尿”(madhumeha[161]。而现今所使用的医学术语“diabetes”一词源自希腊文的“siphon”(虹吸管),意思是“在弯管中流动”,描述其多尿的症状。该词是由希腊人孟菲斯阿波罗尼奥斯英语Apollonius (physician)Apollonius of Memphis)在公元前230年首次使用[161]。根据盖伦的描述,在罗马帝国时期,该病可能属罕见病,在其生涯中仅见两例[161]

公元400-500年,印度医生妙闻揭罗迦英语Charaka首次将1型和2型糖尿病区分开来,认为1型与青年有关,而2型与体重过重有关[161]。“mellitus”一词由英国人约翰·罗尔(John Rolle)于1700年代末期首次使用,用于与频繁排尿的尿崩症相区分[161]。虽然有关糖尿病的纪述相当古老,但该病一直没有有效的治疗。直到20世纪初,加拿大人弗雷德里克·班廷查尔斯·贝斯特在1921年和1922年发现胰岛素[161]。随后又在1940年代开发出长效NPH胰岛素[161]

备注

  1. ^ 对于本条目名称的用词解释:自从1997年,美国糖尿病学会(ADA)与世界卫生组织(WHO)的专家共同开会决定糖尿病的重新命名,废弃了原来的 NIDDM、误用的Type II(罗马数字),而指定使用 Type 2(阿拉伯数字)。主要是由于医学的新进展以及避免混淆(Type II 近似 Type 11,eleven);并且不使用“Diabetes mellitus Type 2”而是使用“Type 2 diabetes mellitus”(T2DM,其后简称T2D)。台湾国健署及糖尿病学会亦使用“第2型”,非“第二型”,而且不用“第II型”;顺序亦有规定:“2型糖尿病”,非“糖尿病第2型”。参考来源见讨论页。

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