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2型糖尿病

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2型糖尿病
同義詞 非胰島素依賴型糖尿病(Noninsulin-dependent diabetes mellitus,NIDDM)
成人糖尿病(adult-onset diabetes)[1]
Blue circle for diabetes.svg
空心蓝圈為糖尿病的國際象徵符號[2]
發音
醫學專科 內分泌學
症状 煩渴英语polydipsia多尿症、不明原因體重下降多食症[3]
併發症 高渗性高血糖状态英语Hyperosmolar hyperglycemic state糖尿病酮症酸中毒心血管疾病中風糖尿病视网膜病变腎功能衰竭截肢[1][4][5]
常見始發於 中年或老年[6]
病程 終身[6]
肇因 肥胖症、缺乏運動、遺傳[1][6]
診斷方法 血糖測量[3]
預防 維持正常體重、體能鍛煉、均衡飲食[1]
治療 飲食調整英语diabetic diet二甲双胍、胰島素、代謝手術[1][7][8][9]
預後 预期寿命縮短約10年[10]
盛行率 3.92億(2015年)[11]

2型糖尿病英语:Diabetes mellitus type 2,简称T2DM,台湾称为第二型糖尿病),大陆旧称為非胰岛素依赖型糖尿病英语:noninsulin-dependent diabetes mellitus,简称NIDDM)或成人发病型糖尿病adult-onset diabetes),是一种慢性代謝疾病,患者特徵為高血糖、相對缺乏胰島素、有胰島素抗性[6]。常見症狀有煩渴英语Polydipsia頻尿、不明原因的體重減輕[3] ,可能還包括多食、疲倦、或有治不好的痠痛[3],以上症狀通常會慢慢出現[6]。高血糖帶來的長期併發症包括心臟病中風糖尿病視網膜病變,這可能導致失明腎臟衰竭、甚至四肢血流不順而需要截肢[1] ;第二型糖尿病患者可能突然發生高渗性高血糖状态英语Hyperosmolar hyperglycemic state,但卻不太會併發糖尿病酮酸血症[4][5]

第二型糖尿病主要發生在肥胖而又缺乏運動的人[1],具有先天基因遺傳者風險也較高[6]。2型糖尿病佔了糖尿病患者約九成的病例,另外一成為第一型糖尿病妊娠糖尿病患者[1]。一型糖尿病患者因胰臟β細胞英语beta cells自體免疫英语autoimmune破壞,而有絕對性胰島素缺乏的問題[12][13]。糖尿病確診需經由血液檢查而定,如檢測空腹血糖值英语fasting plasma glucose口服葡萄糖耐量試驗(OGTT)或檢測糖化血紅蛋白(HbA1c[3]

部分的第二型糖尿病可經由保持正常體重、規律運動及適當飲食來預防[1],治療方式有運動和改變飲食英语Diabetic diet[1]。如果沒有經常性血糖偏低,建議的治療藥物為二甲双胍[7][14],但許多患者最終都必須使用胰島素治療[9]。使用胰島素的患者必須定期測量血糖,口服降血壓藥的患者則不一定需要[15]。對肥胖的患者而言,接受减肥手术對改善糖尿病亦十分有效[8][16]

自1960年起,第二型糖尿病病例就隨著肥胖率逐漸升高[17]。1985年時全球僅有約3000萬人罹患糖尿病,到了2015年患者增至3.92億人[11][18]。糖尿病好發於中高齡層[6],但現今青年人罹患2型糖尿病的比率逐漸增加[19][20]。第二型糖尿病患者可能減損長達約十年的壽命[10]。糖尿病是最早被描述的疾病之一[21],1920年代科學家就發現了胰島素對它的重要性[22]

糖尿病講解影片(英文)

病征与症状[编辑]

糖尿病显著症状概述

糖尿病的典型症状为多尿症煩渴英语polydipsia多食症Polyphagia)以及体重减轻[23]。诊断时其他常见的症状包括視野模糊英语blurred vision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]。在少部分的患者會出現高渗性高血糖状态英语hyperosmolar hyperglycemic state,此類患者會產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]

併发症[编辑]

2型糖尿病是慢性疾病,患者的预期寿命可减少長達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。下肢截肢率會增加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[24]。在发病过程中,患者罹患认知功能障碍英语cognitive dysfunction失智症风险也会增高,如阿兹海默病血管性痴呆等等[25]。其他并发症還包括黑棘皮症性功能障碍,以及容易发生感染[23]

病因[编辑]

2型糖尿病的發生與患者的生活方式与遗传因素有關[24][26]。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[27],因為睡眠不足会使致身体的新陈代谢有所改变,進而诱发2型糖尿病[27]。孕妇在胎儿发育过程中的营养状况對胎兒未來罹患糖尿病的機率也佔有一席之地,其中DNA甲基化改變是造成此種影響的可能機制之一[28]。此外,腸道細菌如腸道普氏菌英语PrevotellaPrevotella copri)和普通擬桿菌Bacteroides vulgatus)也可能和2型糖尿病有關[29]

生活方式[编辑]

目前認為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)、身體活动量不足、不健康的飲食、压力過大以及城市化的生活等[10]。30%的華裔與日裔患者體脂過高,欧裔和非裔患者則有60%至80%,印第安人和太平洋岛民患者則100%都體脂過高[13]。至於非肥胖症的2型糖尿病患則常有過高的腰臀比[13]。吸菸似乎也會增加罹患2型糖尿病的機會[30]

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[31][32]。饮食裡摄取的脂肪也是很重要的因素,饱和脂肪反式脂肪均會增加患病风险,而多元不饱和脂肪单元不饱和脂肪則有助於降低风险[26]。攝取大量白米似乎也会使致病风险增加[33]。也有學者相信,7%的病例可能是缺乏运动所致[34]持久性有機污染物可能也和糖尿病相關[35]

遗传因素[编辑]

大多数糖尿病个案涉及多種基因,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[36]。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%[36]。舉例來說,可使发病风险增加1.5倍的等位基因TCF7L2英语TCF7L2为常见基因变异中擁有最高风险的基因[13]。多数与糖尿病有关的基因都与β細胞英语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]其中包括年輕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]。其中年輕人成人型糖尿病占年轻糖尿病患者个案总和的1%至5%[37]

健康状况[编辑]

許多药物和健康问题都会使人較易患糖尿病[38]。這些药物包括: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英语atypical antipsychotic[39]他汀类药物[40]。曾患妊娠糖尿病的人患上2型糖尿病的风险较高[23],而其他和2型糖尿病相关的健康问题還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英语pheochromocytoma及某些癌症胰高血糖素瘤英语glucagonoma[38]。另外,睾酮缺乏与2型糖尿病也有很密切的关联[41][42]

空气污染[编辑]

美国华盛顿大学的研究小组对二氧化碳与糖尿病之间的联系做了大型研究,根据研究结果,2016年全球糖尿病病例中,有14%病例是跟空气污染有关系。[43]

病理生理学[编辑]

胰島素阻抗(圖右)會使血糖較高。

从病理生理学的角度来说,2型糖尿病導因於在胰岛素抵抗的情况下,β细胞无法制造足够的胰岛素[13]。胰岛素抵抗意指细胞无法对正常濃度的胰岛素作出适当反应,這種現象主要發生在肌肉、肝脏及脂肪组织[44]。正常情况下,胰岛素会抑制肝臟葡萄糖的释出;但出现胰岛素抵抗时,肝脏会不适当地把葡萄糖释放到血液中[10]。每位患者岛素抵抗和β细胞功能障碍的比率都有所不同,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]

其他可能与2型糖尿病和胰岛素抵抗有关的重要机制還包括:脂肪细胞脂质的分解增加、对腸泌素英语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份上升,及中枢神经系统的代谢調節異常[10]。然而,并非所有出现胰岛素抗体的人士都会患上糖尿病,患者的胰岛β细胞需同時有胰岛素分泌障碍時才会发病[13]

诊断[编辑]

世界卫生组织糖尿病诊断标准[45][46]  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(<110) <6.0
空腹血糖障碍英语Impaired fasting glucose <7.8(<140) ≥6.1(≥110)& <7.0(<126) 6.0–6.4
糖耐量受损英语Impaired glucose tolerance ≥7.8(≥140) <7.0(<126) 6.0–6.4
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,或两次血糖值上升達到以下標準[47]

  • 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 )且出現典型症狀[23]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)之專家代表組成的国际专家委员会建议糖尿病诊断应使用48 mmol/mol作為臨界值(相當於 HbA1c 6.5%)[48],美国糖尿病协会于2010年采用此建议[49]。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[48]

糖尿病診斷之临界阈根據的是糖耐力测试、空腹血糖或HbA1c,和并发症(如視網膜病變)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廣泛使用[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[50]。估计美國有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對缺乏所造成的高血糖[51],这与1型糖尿病中的绝对胰岛素缺乏大不相同,後者是因為胰岛细胞损坏所導致的。而妊娠期糖尿病則是在懷孕時新發生的高血糖[13]。1型和2型糖尿病通常可以根据臨床表現来区分[48]。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[52]

筛檢[编辑]

由于没有证据证明大規模糖尿病篩檢英语Screening (medicine)可改善最终结果,因此没有大型組織或部门建议进行全面篩檢[53][54]美國預防服務任務小組英语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檢[55]。对于血压较低的人,并没有充分证据顯示能夠降低此群體的風險和死亡率[55][54]。USPSTF也建議40至70歲之間的過重者進行篩檢[56]

世界卫生组织(WHO)和USPSTF皆建議高風險者進行篩檢[53][57]。在美國,高風險者包含年齡超過45歲、一等親英语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綜合症病史、過重,或是患有代謝症候群等等[23]美國糖尿病學會英语American Diabetes Association建議BMI超過25者進行篩檢(亞裔則建議23以上就應該篩檢)[58]

预防[编辑]

适当营养和经常运动可以延缓或防止2型糖尿病的发病[59][60],強力的執行生活方式控制可以降低超過一半的風險[24][61]。無論原始體重多寡或后来的体重是否减轻,运动皆有益处[62]。但单靠調整饮食便能降低風險的证据卻十分有限[63],一些证据支持多攝取綠色蔬菜[64],也有一些证据支持限制含糖饮料[31]。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,或同時使用二甲双胍阿拉伯糖,可以降低罹患糖尿病的风险[24][65],改变生活方式比服用二甲双胍还有效[24]。一份2017年的回顧文獻指出,長期的生活方式改造能降低28%罹病風險,但糖尿病藥物在停藥後將無助於減低風險[66]。血中的維生素D含量較低會增加糖尿病的風險,但口服補充維生素D3無法改善罹病風險[67]

管理[编辑]

2型糖尿病的疾病管理着重于調整生活型態、减低其他心血管风险因素,以及將血糖維持在正常值[24]英国國民保健署建议2型糖尿病初诊人士进行血糖自我监测[68],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爭議[24][69]。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餘命[24]。將收縮壓控制於 140 mmHg 以下能夠降低死亡風險,並改善預後[70],更高積極的血壓管理(低于130/80 mmHg)相較於標準血壓管理(140/85–100 mmHg)雖能使中风风险轻微减低,但对总体死亡风险并没有影响[71]

相对于标准血糖控制(HbA1C7-7.9%),更積極的血糖控制(HbA1C<6%)似乎并未改善死亡率[72][73]。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);但若將低血糖症和预期餘命等特定风险納入考量,这些目标在专业临床会诊后可以改变[74][75]。儘管臨床指引建議醫師須衡量血糖控制的長期好處和立即傷害,許多人仍被過度治療,例如對預期餘命小於9年的患者進行強化血糖控制便沒有好處[76]

所有患有2型糖尿病的人士都應定期进行眼科检查[13]。有限的證據顯示以刮除牙結石和牙根整平術治療牙周病或許可以短期改善糖尿病患者的血糖[77],但沒有證據顯示這樣的改善能持續超過4個月[77]。目前並沒有證據表示治療牙周病的藥物有助於改善血糖[77]

生活方式[编辑]

适当的饮食和运动是糖尿病治疗的基础[23],运动量越充足效果越佳[78]。運動能改善血糖控制,降低體脂和血脂,這些效果即使在沒有體重減輕的情形下也都有證據支持[79]有氧运动可使HbA1c下降并改善胰岛素敏感性[80]阻力训练也有改善的效果,若能同時進行有氧運動及阻力训练效果尤佳[80]

能促進減重的飲食英语diabetic diet調整相當重要[81]。目前最理想的飲食配方為何仍有爭議[81],但目前已知低升糖指數飲食英语low glycemic index diet低碳水化合物飲食可以改善血糖[82][83]。在第二型糖尿病發病後短時間內開始超低卡路里飲食英语Very-low-calorie diet能使疾病緩解[84]素食者相對來說罹患糖尿病的機會較低,但葷食攝取適量者效果則與素食無異[85]。目前尚無證據支持肉桂可以改善第二型糖尿病患者的血糖[86]

適當的衛教也能協助患者控制血糖,效果最佳可維持到24個月[87]。若輕度糖尿病患者的血糖無法藉由調整生活型態改善,則可能需要考慮配合藥物治療[23]。目前仍尚無足夠證據說明調整生活型態對於患者死亡率的影響[61]

药物[编辑]

二甲双胍500mg片剂

目前有几类抗糖尿病药。由于有证据表明二甲双胍metformin)可降低死亡率,因此通常将其作為第一线治疗药物[7][24][88]。然而目前有關此議結論仍有疑問[89],且並非所有第二線糖尿病患者都能一體適用,如具有嚴重腎臟或肝臟疾病者,不應使用二甲双胍[23]

如二甲双胍不足以控制病情,则可使用另一个类的口服制剂或注射胰島素辅助控制[74]。其他类别的药物包括有磺酰脲类(sulfonylureas)、噻唑烷二酮类药物英语Thiazolidinedionethiazolidinedione)、DPP-4抑制剂SGLT2抑制剂以及GLP-1类似物[74]。截至2015年為止,目前研究仍無法表明不同製劑間的效果是否有顯著差異[74]。一份2018年的回顧性文章表示SGLT2抑制剂的效果優於GLP-1类似物及DDP-4抑制剂[90]

罗格列酮(Rosiglitazone)為一種噻唑烷二酮类药物,該藥物被發現可以改善長期預後,並可以改善血糖值[91],但同時他也有導致心臟疾病的風險[92]血管紧张肽I转化酶抑制剂(ACEIs)可以預防腎臟疾病,並可以改善糖尿病的預後[93][94]。但類似藥物血管紧张素II受体拮抗剂(ARBs)則無此效果[94]。一份2016年的回顧性文章指出糖尿病患者的血壓最好控制於140至150 mmHg之間[95]

胰岛素可以單獨使用,也可以配合其他口服藥劑一起使用[24],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[23][24]。劑量會過一段時間才起效,達到控制血糖的效果[24]。当夜间胰岛素不足,每日两次胰岛素可达到更好的控制[23]。长效胰岛素,甘精胰岛素英语Insulin glargineglargine)和地特胰岛素效果及安全性相同[96],其效果並不優於中效胰岛素(NPH insulin),且價格又較貴,因此截至2010年的研究並無發現其實質效益[97]。对于怀孕的患者,胰岛素通常是治疗选择[23]

補充维生素D可能也可以改善胰島素阻抗的問題,以及降低HbA1c[98]

外科手术[编辑]

对于超重的患者,代謝手術(减肥手术)是治疗糖尿病的有效措施[99]。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[100],且长期死亡率也會降低了[101]。不过仍存在低于1%的短期手术死亡风险[102]。目前建議身高體重指數(BMI)大於35的糖尿病患者進行代謝手術[103][104]。BMI介於30-35之間的若血糖控制不佳或有高度胰島素阻抗者,也建議進行[103][104]

流行病学[编辑]

2000年全球糖尿病患病率(每1000个居民)。世界平均为2.8%。
  无数据
  ≤ 7.5
  7.5–15
  15–22.5
  22.5–30
  30–37.5
  37.5–45
  45–52.5
  52.5–60
  60–67.5
  67.5–75
  75–82.5
  ≥ 82.5

2015年,全球2型糖尿病患者約有3.92亿人,占糖尿病患者的90%[10][11],約相当于世界成人人口的6%[11]。糖尿病是已開發國家发展中国家常见的疾病[10]。在经济欠发达地区仍然相當罕见[13]

女性在某些族裔中似乎罹病風險較高[10][105],如南亚裔太平洋岛民英语Pacific IslanderPacific 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[23]。这可能是由于這些群体对西方的生活方式更为敏感[106]。传统上,2型糖尿病歸類為成人疾病,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年為止,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)[107]。糖尿病被世界卫生组织确认为一种全球性流行病[1]

历史[编辑]

糖尿病是最早被記錄的疾病之一[21],早在公元前约1500年的埃及手稿将其称为“尿液過多”[108]。據信首个有记载的病例被认为是1型糖尿病[108]。同時期,古印度的医生在同期也發現了该病,由於患者的尿液會引來螞蟻,因此將其歸稱为“蜜糖尿”(madhumeha[108]。而現今所使用的醫學術語「diabetes」一詞源自希臘文的「siphon」(虹吸管),意思是「在彎管中流動」,描述其多尿的症狀。該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[108]。根據蓋倫的描述,在罗马帝国时期,该病可能属罕见病,在其生涯中僅見兩例[108]

公元400-500年,印度医生妙聞揭羅迦英语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型与體重過重有关[108]。“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[108]。雖然有關糖尿病的紀述相當古老,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[108]。随后又在1940年代开发出长效NPH胰岛素[108]

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