糖尿病神经病变是糖尿病最常见的并发症。在美国,DN 是导致糖尿病足部问题和溃疡的主要原因,后两者是糖尿病患者入院和非外伤性截肢的主要原因。[5]Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, et al. The global burden
of diabetic foot disease. Lancet. 2005;366:1719-1724.http://www.ncbi.nlm.nih.gov/pubmed/16291066?tool=bestpractice.com大约 50% 的糖尿病患者在其一生中会出现糖尿病神经病变,尽管根据曾使用的诊断标准,这个比例从 10% 至 90% 不等。[6]Thomas PK, Tomlinson DR. Diabetic and hypoglycemic neuropathy. In: Dyck P, Thomas P, Griffin J, et al, eds. Peripheral Neuropathy. 3rd ed. Philadelphia, PA: WB Saunders; 1993:1219-1250.虽然 1 型和 2 型糖尿病间的神经病理学无显著不同,但在成人隐匿性自身免疫性糖尿病 (LADA) 患者中,小纤维神经病变可能更为严重。[7]Alam U, Asghar O, Petropoulos IN, et al. Small fiber neuropathy in patients with latent autoimmune diabetes in adults. Diabetes Care. 2015;38:e102-e103.http://www.ncbi.nlm.nih.gov/pubmed/26106229?tool=bestpractice.com
早期 1 型糖尿病患者发生糖尿病神经病变的几率很低。但是,在糖尿病控制和并发症试验 (DCCT) 的受试者(认为其在基线时无神经性检查异常)中,经过约 5 年随访后,对于接受常规治疗和接受强化治疗的受试者,神经系统检查异常的发生率分别接近 20% 和 10%。[8]The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86.http://www.nejm.org/doi/full/10.1056/NEJM199309303291401#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/8366922?tool=bestpractice.comDCCT 队列糖尿病干预和并发症的流行病学 (EDIC) 研究在观察随访期间,远端对称性多发性神经病 (DSPN) 和心血管自主神经病变 (CAN) 的患病率均增加。在 2013 至 2014 年 EDIC 研究,1 型糖尿病平均病程达到 26 年,对于上文提及的强化治疗组和常规对照治疗组,报告的糖尿病周围神经病变 (DPN) 患病率分别为 25% 和 35%,CAN 在两组患病率分别为 29% 和 35%。[9]Albers JW, Herman WH, Pop-Busui R, et al; Diabetes Control and Complications Trial /Epidemiology of Diabetes Interventions and Complications Research Group. Effect of prior intensive insulin treatment during the Diabetes Control and Complications Trial (DCCT) on peripheral neuropathy in type 1 diabetes during the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Diabetes Care. 2010;33:1090-1096.http://care.diabetesjournals.org/content/33/5/1090.longhttp://www.ncbi.nlm.nih.gov/pubmed/20150297?tool=bestpractice.com[10]Pop-Busui R, Low PA, Waberski BH, et al; DCCT/EDIC Research Group. Effects of prior
intensive insulin therapy on cardiac autonomic nervous system function in type 1
diabetes mellitus: the Diabetes Control and Complications Trial/Epidemiology of
Diabetes Interventions and Complications study (DCCT/EDIC). Circulation. 2009;119:2886-2893.http://circ.ahajournals.org/cgi/content/full/119/22/2886http://www.ncbi.nlm.nih.gov/pubmed/19470886?tool=bestpractice.comEURODIAB IDDM 并发症研究发现,16 个欧洲国家随机选择的 1 型糖尿病患者中,糖尿病神经病变的患病率为 28%,且没有明显的地域差异。[11]Tesfaye S, Stevens LK, Stephenson JM, et al. Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study. Diabetologia. 1996;39:1377-1384.http://www.ncbi.nlm.nih.gov/pubmed/8933008?tool=bestpractice.com匹兹堡糖尿病并发症流行病学研究对 1 型糖尿病患者进行跟踪发现,在 5.3 年的时间内糖尿病周围神经病变的累计发生率为 29%。[12]Maser RE, Steenkiste AR, Dorman JS, et al. Epidemiological correlates of diabetic neuropathy. Report from Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes. 1989;38:1456-1461.http://www.ncbi.nlm.nih.gov/pubmed/2620781?tool=bestpractice.com
一项针对 1 型或 2 型糖尿病门诊患者的前瞻性研究发现,在诊断出糖尿病 25 年后,DN 患病率从诊断时的 10% 增加到 50%。[13]Pirart J, Lauvaux JP, Rey W. Blood sugar and diabetic complications. N Engl J Med. 1978;298:1149.http://www.ncbi.nlm.nih.gov/pubmed/643042?tool=bestpractice.com美国罗彻斯特糖尿病研究也报告了类似的患病率,59% 的 2 型糖尿病患者和 66% 的 1 型糖尿病患者患有糖尿病神经病变。[14]Dyck PJ, Kratz KM, Karnes JL, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology. 1993 Apr;43(4):817-24.http://www.ncbi.nlm.nih.gov/pubmed/8469345?tool=bestpractice.com英国的一项针对 1 型糖尿病和 2 型糖尿病患者的大型横断面研究发现,糖尿病神经病变的患病率为 29%。[15]Young MJ, Boulton AJ, MacLeod AF, et al. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993;36:150-154.http://www.ncbi.nlm.nih.gov/pubmed/8458529?tool=bestpractice.com对于因筛查诊断出 2 型糖尿病而接受多因素干预的患者,对 DN 发病率无益处。[16]Sandbæk A, Griffin SJ, Sharp SJ, et al. Effect of early multifactorial therapy compared with routine care on microvascular outcomes at 5 years in people with screen-detected diabetes: a randomized controlled trial: the ADDITION-Europe study. Diabetes Care. 2014;37:2015-2023.http://care.diabetesjournals.org/content/37/7/2015.longhttp://www.ncbi.nlm.nih.gov/pubmed/24784827?tool=bestpractice.com[17]Charles M, Ejskjaer N, Witte DR, et al. Prevalence of neuropathy and peripheral arterial disease and the impact of treatment in people with screen-detected type 2 diabetes: the ADDITION-Denmark study. Diabetes Care. 2011;34:2244-2249.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177734/http://www.ncbi.nlm.nih.gov/pubmed/21816977?tool=bestpractice.com在一项对 2300 多名 2 型糖尿病受试者(平均病程约为 10 年,且确认存在冠状动脉疾病)进行的大型研究中,DPN 的患病率约为 50%。[18]Pop-Busui R, Lu J, Lopes N, et al; BARI 2D Investigators. Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort. J Peripher Nerv Syst. 2009;14:1-13.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692660/?tool=pubmedhttp://www.ncbi.nlm.nih.gov/pubmed/19335534?tool=bestpractice.com[19]Pop-Busui R, Lu J, Brooks MM, et al; BARI 2D Study Group. Impact of glycemic control strategies on the Progression of Diabetic Peripheral Neuropathy in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Cohort. Diabetes Care. 2013;36:3208-3215.http://care.diabetesjournals.org/content/36/10/3208.longhttp://www.ncbi.nlm.nih.gov/pubmed/23757426?tool=bestpractice.com 对于基线无糖尿病周围神经系统检查异常的患者,4 年随访期内糖尿病周围神经病变的累积发病率为 69%。[19]Pop-Busui R, Lu J, Brooks MM, et al; BARI 2D Study Group. Impact of glycemic control strategies on the Progression of Diabetic Peripheral Neuropathy in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Cohort. Diabetes Care. 2013;36:3208-3215.http://care.diabetesjournals.org/content/36/10/3208.longhttp://www.ncbi.nlm.nih.gov/pubmed/23757426?tool=bestpractice.com在两项 1 型糖尿病纵向研究中,约 18% 的患者在 3 年内发生 DPN。[20]Pritchard N, Edwards K, Russell AW, et al. Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in type 1 diabetes. Diabetes Care. 2015;38:671-675.http://care.diabetesjournals.org/content/38/4/671.longhttp://www.ncbi.nlm.nih.gov/pubmed/25573881?tool=bestpractice.com[21]Lovblom LE, Halpern EM, Wu T, et al. In vivo corneal confocal microscopy and prediction of future-incident neuropathy in type 1 diabetes: a preliminary longitudinal analysis. Can J Diabetes. 2015;39:390-397.http://www.ncbi.nlm.nih.gov/pubmed/25936902?tool=bestpractice.com 在全国 NHANES 研究中,痛性 DPN 的患病率为 27%。[6]Thomas PK, Tomlinson DR. Diabetic and hypoglycemic neuropathy. In: Dyck P, Thomas P, Griffin J, et al, eds. Peripheral Neuropathy. 3rd ed. Philadelphia, PA: WB Saunders; 1993:1219-1250.
纵向研究显示,在 2 型和 1 型糖尿病,CAN 患病率年增长率分别约为 6% 和 2%。[22]Spallone V, Ziegler D, Freeman R, et al; Toronto Consensus Panel on Diabetic Neuropathy. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011;27:639-653.http://onlinelibrary.wiley.com/doi/10.1002/dmrr.1239/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21695768?tool=bestpractice.com患病率随年龄(40-70 岁:1 型达 38%,2 型达 44%)和糖尿病病程(对于长期糖尿病患者,1 型达 35%,2 型达 65%)的增加而增加。[22]Spallone V, Ziegler D, Freeman R, et al; Toronto Consensus Panel on Diabetic Neuropathy. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011;27:639-653.http://onlinelibrary.wiley.com/doi/10.1002/dmrr.1239/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21695768?tool=bestpractice.com
由于其显著的临床表现和高发病率,DN 会明显降低生活质量。[23]Vileikyte L, Leventhal H, Gonzalez JS, et al. Diabetic peripheral neuropathy and depressive symptoms: the association revisited. Diabetes Care. 2005;28:2378-2383.http://care.diabetesjournals.org/cgi/content/full/28/10/2378http://www.ncbi.nlm.nih.gov/pubmed/16186266?tool=bestpractice.com[24]Vileikyte L, Rubin RR, Leventhal H. Psychological aspects of diabetic neuropathic foot complications: an overview. Diabetes Metab Res Rev. 2004;20:S13-18.http://www.ncbi.nlm.nih.gov/pubmed/15150807?tool=bestpractice.com青少年糖尿病 SEARCH 研究中获得的证据报告,在 1 型糖尿病青少年患者中发现心血管自主神经病变和 DPN 迹象。[25]Jaiswal M, Urbina EM, Wadwa RP, et al. Reduced heart rate variability among youth with type 1 diabetes: the SEARCH CVD study. Diabetes Care. 2013;36:157-162.http://care.diabetesjournals.org/content/36/1/157.longhttp://www.ncbi.nlm.nih.gov/pubmed/22961570?tool=bestpractice.com研究还显示了糖耐量受损人群中发生小纤维神经病变的证据。[26]Asghar O, Petropoulos IN, Alam U, et al. Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance. Diabetes Care. 2014;37:2643-2646.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140158/http://www.ncbi.nlm.nih.gov/pubmed/24969581?tool=bestpractice.com[27]Zilliox LA, Ruby SK, Singh S, et al. Clinical neuropathy scales in neuropathy associated with impaired glucose tolerance. J Diabetes Complications. 2015;29:372-377.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558101/http://www.ncbi.nlm.nih.gov/pubmed/25690405?tool=bestpractice.com