1、1,Basic Medical Knowledge基礎(chǔ)醫(yī)學(xué)知識,糖尿病與糖尿病神經(jīng)病變 Diabetes and Diabetic Neuropathy,2,Contents主要內(nèi)容,糖尿病相關(guān)的學(xué)會組織 糖尿病定義 糖尿病流行病學(xué) 糖尿病分類 糖尿病臨床表現(xiàn) 糖尿病診斷標(biāo)準(zhǔn) 糖尿病神經(jīng)病變概述 Neuropathy screening and treatment Standards of Medical Care in Diabetes-2007 ADA Roleplay,3,糖尿病相關(guān)的學(xué)會 Some Association about Diabetes,中華醫(yī)學(xué)會糖尿病學(xué)分會(CDS)

2、“Chinese Diabetes Society” 歐洲糖尿病研究學(xué)會(EASD) “European Association for the Study of Diabetes” 美國糖尿病協(xié)會(ADA) “American Diabetes Association” 美國國家糖尿病資料組(NDDG) “National Diabetes Data Group” 美國國立衛(wèi)生研究院(NIH) “National Institutes of Health” 國際糖尿病聯(lián)盟(IDF) “International Diabetes Federation” 世界衛(wèi)生組織(WHO) “World

3、Health Organization”,4,糖尿病Diabetes mellitus,糖尿病(diabetes, DM) 糖尿病是一組以胰島素分泌缺陷和（或）胰島素生物作用障礙導(dǎo)致的慢性血糖水平增高為主要特征的代謝疾病群，包括糖、蛋白質(zhì)、脂肪、水及電解質(zhì)等的代謝紊亂，嚴(yán)重時(shí)常導(dǎo)致酸堿平衡失常 特征：高血糖、糖尿、葡萄糖耐量減低及胰島素釋放試驗(yàn)異常 三多一少：多食、多飲、多尿、體重減少,*ADA已將原先的Diabetes mellitus簡略為Diabetes,5,糖尿病流行病學(xué)Epidemiology of Diabetes,2003年IDF報(bào)告全球糖尿病患者超過1.94億 2006年IDF

4、第19屆會議報(bào)告全球成年人糖尿病患病率大于5.7%，糖尿病患者超過2.3億 IDF預(yù)計(jì)2025年全球糖尿病患病率接近7%，糖尿病患者可達(dá)3.33億 全球T2DM發(fā)病率最高的是太平洋島國瑙魯(Naura)和美國皮瑪(Pima)印地安人*,*附注：此數(shù)據(jù)摘自,6,目前世界DM人數(shù)最多的3個(gè)國家依次為：印度、中國、美國 中國有超過5千萬糖尿病患者 1996年全國調(diào)查數(shù)據(jù)： 糖尿病患病率3.21% IGT患病率4.81% 2001年CDS全國住院DM患者并發(fā)癥調(diào)查數(shù)據(jù)： T1DM神經(jīng)病變患病率：44.9% T2DM神經(jīng)病變患病率：61.8% 總發(fā)病率：60.3%,糖尿病流行病學(xué)Epidemiology

5、 of Diabetes,附注：此數(shù)據(jù)摘自,7,糖尿病分類Classification of Diabetes,ADA 2007版糖尿病診療標(biāo)準(zhǔn)： 1型糖尿病(T1DM) 2型糖尿病(T2DM) 其他特殊型糖尿病 妊娠糖尿病(GDM) 注：ADA-美國糖尿病學(xué)會,8,臨床表現(xiàn)Clinical manifestations,代謝紊亂癥候群 “三多一少”：多飲、多食、多尿、體重減少 并發(fā)癥和(或)伴發(fā)病 各種急慢性并發(fā)癥，有的以肢端麻木等周圍神經(jīng)病變而就診 神經(jīng)系統(tǒng)損害發(fā)病率為47-91% 反應(yīng)性低血糖 餐后3-5小時(shí)的低血糖 體檢/手術(shù)發(fā)現(xiàn)高血糖,9,診斷標(biāo)準(zhǔn)Criteria for the d

6、iagnosis of diabetes1999年WHO診斷標(biāo)準(zhǔn),1999年WHO診斷標(biāo)準(zhǔn) 1.有糖尿病癥狀和隨機(jī)血糖11.1mmol/L。 “隨意”是指一天內(nèi)任何時(shí)間，無論進(jìn)食與否。 糖尿病癥狀包括多尿、多飲和不可解釋的體重減輕。 2.FPG7.0mmol/L. FPG:空腹血糖，“空腹”是指至少8h未進(jìn)食（未攝入能量） 3.OGTT試驗(yàn)2hPG 11.1mmol/L。 試驗(yàn)需按WHO要求用75g無水葡萄糖溶于水 對無癥狀者應(yīng)隔日復(fù)測,10,診斷標(biāo)準(zhǔn)Criteria for the diagnosis of diabetes1999年WHO診斷標(biāo)準(zhǔn),糖尿病前期(Pre-Diabetes) 空

7、腹血糖受損(IFG) FPG=6.1mmol/L6.9mmol/L and OGTT 2hPG7.8mmol/L 糖耐量減低(IGT) FPG7.0mmol/L and 7.8mmol/L2hPG11.1mmol/L 附注： 以上數(shù)據(jù)出自1999年WHO診斷標(biāo)準(zhǔn) 正常血糖：3.95.6mmol/L 2006年WHO/IDF將糖尿病前期(Pre-Diabetes)改稱為高血糖中間狀態(tài)(Intermediate Hyperglycemia),11,診斷標(biāo)準(zhǔn)Criteria for the diagnosis of diabetes2007年ADA診斷標(biāo)準(zhǔn),糖尿病前期(Pre-Diabetes) 空

8、腹血糖受損(IFG) FPG=5.6mmol/L6.9mmol/L and OGTT 2hPG7.8mmol/L 糖耐量減低(IGT) FPG7.0mmol/L and 7.8mmol/L2hPG11.1mmol/L 附注：以上數(shù)據(jù)出自2007年ADA診斷標(biāo)準(zhǔn) 正常血糖：3.95.6mmol/L,12,IFG診斷標(biāo)準(zhǔn)Criteria for the diagnosis of diabetesbetween WHO and ADA,WHO FPG=6.1mmol/L6.9mmol/L and OGTT 2hPG7.8mmol/L ADA FPG=5.6mmol/L6.9mmol/L and OG

9、TT 2hPG7.8mmol/L,13,IFG診斷標(biāo)準(zhǔn)Criteria for the diagnosis of diabetesfrom Chinese Diabetes Society(CDS),降低IFG的下限診斷切割點(diǎn),即從6.1 mmol/L降至5.6mmol/L IFG = FPG 5.6mmol/L6.9mmol/L IFG上限的診斷切割點(diǎn)不變,仍為 7.0 mmol/L 在下調(diào)空腹血糖受損診斷切割點(diǎn)后,所有空腹血糖5.6 mmol/L的個(gè)體均應(yīng)接受OGTT,以將人群中的IFG + IGT劃分出來,此點(diǎn)至關(guān)重要,本資料摘自中華醫(yī)學(xué)雜志2005年7月27日第85卷第28期 空腹血糖

10、受損下限診斷切割點(diǎn)的建議 中華醫(yī)學(xué)會糖尿病學(xué)分會,14,高血糖中間狀態(tài)和糖尿病 Intermediate Hyperglycemia 還原、再生細(xì)胞內(nèi)主要抗氧化劑,如谷光苷肽( GSH) 、維生素C、維生素E、輔酶Q 等; 鰲合鐵、銅等金屬離子,降低自由基的產(chǎn)生,摘自臨床薈萃2006年12月5日第21卷第23期 糖尿病周圍神經(jīng)病變的治療,46,糖尿病神經(jīng)病的治療Treatment of Diabetic Neuropathy,6、補(bǔ)充神經(jīng)營養(yǎng) 神經(jīng)生長因子(NGF) 神經(jīng)節(jié)苷脂(GS),摘自臨床薈萃2006年12月5日第21卷第23期 糖尿病周圍神經(jīng)病變的治療,47,糖尿病神經(jīng)病的治療Trea

11、tment of Diabetic Neuropathy,7、痛性神經(jīng)病的治療 主要是應(yīng)用三環(huán)類抗抑郁藥(TCAs) 、抗驚厥藥物、麻醉與止痛劑等 苯妥因及卡馬西平通過阻斷鈉離子通道而穩(wěn)定神經(jīng)細(xì)胞膜,緩解疼痛,但療效欠佳,摘自臨床薈萃2006年12月5日第21卷第23期 糖尿病周圍神經(jīng)病變的治療,48,Standards of Medical Care in Diabetes糖尿病診療標(biāo)準(zhǔn),VI. Prevention and Managerment of Diabetes Complications vi.預(yù)防與處理糖尿病并發(fā)癥 D. Neuropathy screening and tre

12、atment (171,172) D.糖尿病神經(jīng)病變篩查與治療,2007 American Diabetes Association 2007 美國糖尿病學(xué)會,References：DIABETES CARE, VOLUME 30, SUPPLEMENT 1, JANUARY 2007,49,50,51,D. Neuropathy screening and treatment (171,172)D.糖尿病神經(jīng)病變篩查與治療Recommendations建議, All patients should be screened for distal symmetric polyneuropathy

13、 (DPN) at diagnosis and at least annually thereafter, using simple clinical tests. (A) 所有病人在被診斷為糖尿病時(shí)必須利用簡單的臨床試驗(yàn)來篩查遠(yuǎn)端對稱性多神經(jīng)病變(DPN)，并且從那時(shí)以后至少每年篩查一次（A） Electrophysiological testing is rarely ever needed, except in situations where the clinical features are atypical. (E) 除非病人的臨床表現(xiàn)不典型而需要神經(jīng)電生理檢查外，其他情形很少需要

14、這種檢查（E） Once the diagnosis of DPN is established, special foot care is appropriate for insensate feet to decrease the risk of amputation. (B) 一旦DPN診斷成立，對于無感覺足的特殊足部護(hù)理是適當(dāng)?shù)牟⑶疫€可以降低其截肢的危險(xiǎn)性,52,Recommendations建議, Simple inspection of insensate feet should be performed at 3- to 6-month intervals. An abnorma

15、lity should trigger referral for special footwear, preventive specialist, or podiatric care. (B) 每3-6個(gè)月必須對病足進(jìn)行一次簡單的檢查。任何一個(gè)異常均需給于病足所需的特殊靴鞋、或者讓預(yù)防專家或足醫(yī)進(jìn)行會診（B） Screening for autonomic neuropathy should be instituted at diagnosis of type 2 diabetes and 5 years after the diagnosis of type 1 diabetes. Spec

16、ial electrophysiological testing for autonomic neuropathy is rarely needed and may not affect management and outcomes.(E) 對于自主神經(jīng)病變的篩查應(yīng)開始于診斷2型糖尿病的同時(shí)和診斷1型糖尿病的5年之后。自主神經(jīng)病變同樣很少需要神經(jīng)電生理檢查，同時(shí)該檢查對自主神經(jīng)病變的治療及結(jié)果可能也沒有太多的影響（E）,53,Recommendations建議, Education of patients about self-care of the feet and referral fo

17、r special shoes/inserts are vital components of patient management. (B) 自我足部護(hù)理的教育和穿著專用鞋的治療是整體治療的重要組成部分（B） A wide variety of medications is recommended for the relief of specific symptoms related to autonomic neuropathy and are recommended, as they improve the quality of life of the patient. (E) 為了改善

18、病人的生活質(zhì)量，只要能緩解自主神經(jīng)病變相關(guān)特殊癥狀的多種治療方法都是被推薦使用的（E）,54,D. Neuropathy screening and treatment (171,172)D.糖尿病神經(jīng)病變篩查與治療,The diabetic neuropathies are heterogeneous with diverse clinical manifestations.They may be focal or diffuse. Most common among the neuropathies are chronic sensorimotor DPN and autonomicneu

19、ropathy. 糖尿病神經(jīng)病變的臨床表現(xiàn)多種多樣，它們可能是局灶的也可能是彌漫的，最常見的糖尿病神經(jīng)病變是慢性遠(yuǎn)端對稱性感覺運(yùn)動性多神經(jīng)病變和自主神經(jīng)病變 Specific treatment for the underlying nerve damage is currently not available,other than improved glycemic control. Effective symptomatic treatments are available for the manifestations of DPN and autonomic neuropathy. 對于

20、潛在的神經(jīng)損傷目前除了良好控制血糖外沒有其他特效療法可以有效治療，對于遠(yuǎn)端對稱性多神經(jīng)病變和自主神經(jīng)病變采用有效的對癥治療是可行的,55,D. Neuropathy screening and treatment (171,172)D.糖尿病神經(jīng)病變篩查與治療Diagnosis of neuropathy神經(jīng)病變的診斷,Patients with diabetes should be screened annually for DPN using tests such as pinprick sensation, temperature and vibration perception (us

21、ing a 128-Hz tuning fork), and 10-g monofilament pressure sensation at the distal plantar aspect of both great toes and ankle reflexes. 糖尿病病人每年必須進(jìn)行遠(yuǎn)端對稱性多神經(jīng)病變的篩查，常用的檢查方法有：針刺痛覺、溫度覺、音叉振動覺（使用128Hz音叉）、10-g單絲壓力覺以及踝反射 Combinations of more than one test have 87% sensitivity in detecting DPN. 聯(lián)合應(yīng)用多于一項(xiàng)以上的臨床檢查

22、方法診斷遠(yuǎn)端對稱性多神經(jīng)病變的敏感性87%,56,D. Neuropathy screening and treatment (171,172)D.糖尿病神經(jīng)病變篩查與治療Diagnosis of neuropathy神經(jīng)病變的診斷,Loss of 10-g monofilament perception and reduced vibration perception predict foot ulcers. 10g單絲壓力覺的喪失和音叉振動覺的降低預(yù)示著足部潰瘍的發(fā)生 A minimum of one clinical test should be carried out annually

23、, and the use of two tests will increase diagnostic ability. 每年必須最少使用一項(xiàng)臨床檢查來檢測神經(jīng)病變，二項(xiàng)臨床檢查可以提高診斷率 Focal and multifocal neuropathy assessment requires clinical examination in the area related to the neurological symptoms. 局灶性和多病灶性神經(jīng)病變的判定需要神經(jīng)系統(tǒng)癥狀相關(guān)區(qū)域的檢查來實(shí)現(xiàn),57,D. Neuropathy screening and treatment (171,

24、172)D.糖尿病神經(jīng)病變篩查與治療Diabetic autonomic neuropathy糖尿病性自主神經(jīng)病變,Major clinical manifestations of diabetic autonomic neuropathy include resting tachycardia, exercise intolerance, orthostatic hypotension,constipation, gastroparesis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular functio

25、n, “brittle diabetes,” and hypoglycemic autonomic failure. 糖尿病自主神經(jīng)病變的常見臨床表現(xiàn)包括：靜息時(shí)心動過速、運(yùn)動不耐受、便秘、胃輕癱、勃起機(jī)能障礙、泌汗功能障礙、神經(jīng)血管功能受損，“脆性糖尿病”、低血糖性自主神經(jīng)功能衰竭 Cardiac autonomic neuropathy may be indicated by resting tachycardia (100 bpm), orthostasis (a fall in systolic blood pressure20 mmHg upon standing), or othe

26、r disturbances in autonomic nervous system function involving the skin, pupils, or gastrointestinal and genitourinary systems. 靜息時(shí)心動過速（100bpm）、靜息狀態(tài)（站立時(shí)收縮壓下降超過20mmHg以上）、或者其他一些自主神經(jīng)功能的紊亂包括皮膚、瞳孔、胃腸和泌尿生殖系統(tǒng)等可能提示心臟自主神經(jīng)病變的存在,58,D. Neuropathy screening and treatment (171,172)D.糖尿病神經(jīng)病變篩查與治療Diabetic autonomic

27、neuropathy糖尿病性自主神經(jīng)病變,Gastrointestinal disturbances (e.g., esophageal enteropathy, gastroparesis, constipation, diarrhea, fecal incontinence) are common, and any section of the gastrointestinal tract may be affected. Gastroparesis should be suspected in individuals with erratic glucose control. 胃腸道功能

28、紊亂(如：食道性腸病、胃輕癱、便秘、腹瀉、大便失禁)是最常見的，同時(shí)胃腸道的任何部位都有受累的可能。血糖控制不穩(wěn)定的病人應(yīng)該首先懷疑胃輕癱的可能 Diabetic autonomic neuropathy is also associated with genitourinary tract disturbances, including bladder and/or sexual dysfunction. 糖尿病自主神經(jīng)病變同樣也可伴隨泌尿生殖系統(tǒng)功能紊亂，包括膀胱功能和性功能障礙 In men, diabetic autonomic neuropathy may cause loss of

29、 penile erection and/or retrograde ejaculation. 在男性，糖尿病自主神經(jīng)病變可能引起陰莖勃起功能障礙和逆行射精,59,D. Neuropathy screening and treatment (171,172)D.糖尿病神經(jīng)病變篩查與治療Symptomatic treatments對癥治療,The first step in management of patients with DPN should be to aim for stable and optimal glycemic control. 治療糖尿病患者遠(yuǎn)端對稱性多神經(jīng)病變的第一步是

30、穩(wěn)定和理想的血糖控制 Most patients will require pharmacological treatment for painful symptoms: many agents have efficacy confirmed in published randomized controlled trials, though none are specifically licensed for the management of painful-DPN. See Table 10 對于疼痛的癥狀絕大多數(shù)患者都需要藥物治療，發(fā)表的隨機(jī)控制試驗(yàn)證實(shí)許多治療方法都是有效的，但是還沒有一種被特別批準(zhǔn)專門用于治療DPN疼痛癥狀的藥物（見表10）,60,D. Neuropathy screening and treatment (171,172)D.糖尿病神經(jīng)病變篩查與治療Symptomatic treatments對癥治療,三環(huán)類藥物,抗驚厥劑,P物質(zhì)抑制劑,5-