糖尿病足病因和诊治的现状及进展
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摘要
糖尿病足(diabetic foot,DF)的发生对患者个人、家庭和社会均造成了严重的经济、心理和医疗负担,目前这已成为一个全球性问题。DF是糖尿病性神经病变、血管病变和感染等多种因素共同作用的结果。其中,糖尿病性神经病变是DF发生的最重要因素;跖骨头下组织变薄、心理障碍可促进DF的发生;生长因子和蛋白酶表达和活性的变化延缓糖尿病足溃疡(diabetic foot ulcer,DFU)的愈合,这一发现为在分子水平治愈慢性难治性DFU提供了依据。临床处理时首先要明确其主要病因并进行相应的治疗;控制感染、局部减压和改善缺血是DF治疗的关键措施;高压氧、干细胞移植、生长因子和基质金属蛋白酶抑制剂的使用等为其治疗提供了更广阔的前景。DF重在预防,其关键在于识别高危患者并控制危险因素。
Diabetic foot (DF) problems are common throughout the world, resulting in major economic, psychological and medical consequences for the patients, their families and society. DF results from the interaction of several contributory factors including diabetic neuropathy, peripheral vascular disease and infection , etc. Among these , neuropathy is the most important contributory cause in the pathway to DF. The reduction of subcutaneous tissue under the metatarsal heads and psychological dysfunction are associated with diabetic foot ulcer(DFU). Changes of their expression and activity of growth factors and proteases are relevant for the pathogenesis of the maintaining chronicity of DFU,which provides ways to correct the molecular defects that have reulted in its chronicity. The key measure to treat DFU is to control infection,to remedy ischemia and to relieve high foot pressure . Hyperbaric oxygen therapy , stem cell therapy , the use of growth factors and inhibitors of matrix-metalloproteinases supply us with a broader perspective.Early recognition and management of independent risk factors for DF are the basic key to prevent it.
Diabetic foot (DF) problems are common throughout the world, resulting in major economic, psychological and medical consequences for the patients, their families and society. DF results from the interaction of several contributory factors including diabetic neuropathy, peripheral vascular disease and infection , etc. Among these , neuropathy is the most important contributory cause in the pathway to DF. The reduction of subcutaneous tissue under the metatarsal heads and psychological dysfunction are associated with diabetic foot ulcer(DFU). Changes of their expression and activity of growth factors and proteases are relevant for the pathogenesis of the maintaining chronicity of DFU,which provides ways to correct the molecular defects that have reulted in its chronicity. The key measure to treat DFU is to control infection,to remedy ischemia and to relieve high foot pressure . Hyperbaric oxygen therapy , stem cell therapy , the use of growth factors and inhibitors of matrix-metalloproteinases supply us with a broader perspective.Early recognition and management of independent risk factors for DF are the basic key to prevent it.
引文
1 许樟荣,敬华译.国际糖尿病足工作组编写:糖尿病足国际临床指南.北京:人民军医出版社,2003,6-45
2 Boulton AJM. The diabetic foot: from art to science. Diabetologia, 2004, 47: 1343-1353
3 Levy MJ, Valabhji J. The diabetic foot. Surgery(oxford), 2008,26(1): 25-28
4 American Diabetes Association. Preventive Foot Care in Diabetes. Diabetes Care, 2004, 27: Suppl 1, S63-64
5 Khammash MR, Obeidat KA. Prevalence of Ischemia in Diabetic Foot Infection. World J. Surg,2003, 27: 797–799
6 Rathur HM, Boulton AJM. The diabetic foot. Clinics in Dermatology,2007,25:109–120
7 Abouaesha F, Van Schie CHM, Armstrong DG, et al. Plantar soft tissue thickness predicts high peak plantar pressure in the diabetic foot. J Am Podiatr Med Assoc , 2004,94:39–42
8 Vileikyte L, Rubin RR, Leventhal H. Psychological aspects of diabetic neuropathy and its late sequelae. Diab Metab Res Rev ,2004,20 :Suppl 1,S13–S18
9 Boulton AJM, Kirsner RS, Vileikyte L. Neuropathic diabetic foot ulcers. N Engl J Med, 2004, 351:48–55
10 Kiecolt-Glaser J, Preacher JK, MacCallum RC, et al. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci USA, 2003, 100: 9090 –9095
11 Yang EV, Bone CM, MacCallum RC, et al. Stress related modulation of matrix metalloproteinase expression. J Neuroimmunol , 2002,133:144–150
12 Lobmann R, Schultz G ,Lehnert H. Proteases and the Diabetic Foot Syndrome: Mechanisms and Therapeutic Implications. Diabetes Care, 2005, 28: 461-467
13 Lobmann R, Ambrosch A, Schultz G, et al. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia, 2002,45:1011–1016
14 Boulton AJM. The diabetic foot. Medicine, 2006, 34(3):87-90
15 Foster AVM, EdmondsME. The simple staging system: a new diabetic foot classification validated to guide therapy. In: Neurodiab and DFSG of EASD Joint Meeting(AbstrctsBook) Hungary, 2002. 112
16 许障荣. 老年糖尿病患者足病变的诊断与防治. 老年医学与保健杂志,2005,11(3):138-141
17 Miranda-Palma B, Basu S, Mizel MS, et al. monofilament as the gold standard for foot ulcer screening: a reappraisal. Diabetes ,2003, 53 :Suppl 1,A63
18 Carrington AL, Shaw JE, Van Schie CHM, et al. Can motor nerve conduction velocity predict foot problems in diabetes over a six year outcome period? Diabetes Care , 2002, 25:2010–2015
19 Lavery LA, Armstrong DG, Wunderlich RP, et al. Predictive value of foot pressure assessment when part of a population-based diabetes disease management program. Diabetes Care,2003, 26:1069–1073
20 Juha H.A. Niinikoski, M.D. Clinical Hyperbaric Oxygen Therapy, Wound Perfusion, and Transcutaneous Oximetry. World J. Surg, 2004,28: 307–311
21 Strauss MB, Bryant BJ, Hart GB. Transcutaneous oxygen measurements under hyperbaric oxygen conditions as a predictor for healing of problem wounds. Foot Ankle Int,2002,23:933-937
22 于德民,王鹏华译. 溃疡足. 见:Edmonds ME, Foster AVM, Sanders LJ 编著:糖尿病足诊治实践彩色图解. 天津:天津科技翻译出版公司,2006,80
23 Feldmeier J, ed. Hyperbaric oxygen 2003: indications and results: Hyperbaric Oxygen Therapy Committee report. Kensington, Md.: Undersea & Hyperbaric Medical Society, 2003:41-55
24 Piaggesi A, Viacava P, Rizzo L, et al. Semi-quantitative analysis of the histopathological features of the neuropathic foot ulcer—effects of pressure relief. Diabetes, 2003,26: 3123–3128
25 Lavery LA , Baranoski S , Ayello EA. Options for off-loading the diabetic foot . Advances in Skin & Wound Care, 2004 ,17 (4) :181- 186
26 Van Schie CHM, Whalley A, Armstrong DG, et al. The effect of silicone injections in diabetic foot on peak plantar pressure and plantar tissue thickness: a 2 year follow-up. Arch Phys Med Rehabil, 2002, 83:919–923
27 Van Schie CHM, Whalley A, Vileikyte L, et al. Efficacy of injected liquid silicone is related to peak plantar foot pressures in the neuropathic diabetic foot. Wounds , 2002, 14:26–30
28 Van Schie CHM, Whalley A , Vileikyte L , et al. Efficacy of injected liquid silicone in diabetic foot to ruduce risk factors for ulceration: a randomized double-blind placebo-controlled trial [J ] . Diabetes Care , 2000 , 23 :634-638
29 Loot MA, Kenter SB, van Galen WJ, et al. Fibroblasts derived from chronic diabetic ulcers differ in their response to stimulation with EGF, IGF-I, bFGF and PDGF-AB compared to controls. Eur J Cell Biol ,2002,81:153–160
30 Mandracchia VJ, Sanders SM, Frerichs JA. The use of becaplermin (rhPDGFBB) gel for chronic nonhealing ulcers: a retrospective analysis. Clin Podiatr Med Surg, 2001, 18:189 –209
31 Chin GA,Thigpin TG,Perrin KJ,et al.Treatment of chronic ulcers in diabetic patients with a topical metalloproteinase inhibitor,doxycycline. Wounds, 2003, 15:315–323
32 Frykberg RG, Zgonis T,.Armstrong DG,et al.Diabetic foot disoreders:a clinical practice guideline(2006 revision). The Journal of Foot&Ankle Surgery,2006,45:s1-65
33 Bello YM, Falabella AF, Eaglstein WH. Tissue-engineered skin:Current status in wound healing. Am J Clin Dermatol 2001,2:305-313
34 Kastenbauer T ,Hornlein B ,Sokol G, et al. Evaluation of granulocyte - colony stimulating factor in infected diabetic foot ulcers. Diabetologia,2003,46: 27-30
35 Martínez-Sánchez G, Al-Dalain SM, et al. Therapeutic efficacy of ozone in patients with diabetic foot. European Journal of Pharmacology,2005,523:151-161
36 Sigala F, Menenakos Ch, Sigalas P, et al. Transluminal angioplasty of isolated crural arterial lesions in diabeticswith critical limb ischemia1.Vasa,2005,34: 186-191
37 Feiring AJ, Wesolowski AA, Lade S. Primary stent-supported angioplasty for treatment of below-knee critical limb ischemia and severe claudication: early and one-year outcomes. J Am Coll Cardiol,2004,44:2307-2314
38 曾明, 董扬. 糖尿病足的手术治疗.中华医学杂志,2006, 86(45):3230-3232
39 Badiavas EV, Falanga V . Treatment of chronic wounds with bone marrow-derived cells. Arch Dermatol, 2003, 139:510– 516
40 Eriko TY, Hiroaki M, Toyoaki M, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cell: a pilot study and a randomized controlled trial [ J ]. Lancet,2002,360:427-435
41 黄平平, 李尚珠, 韩明哲, 等. 自体外周血干细胞移植治疗下肢动脉硬化闭塞症. 中华血液学杂志, 2003, 24: 308 - 311
42 杨晓凤, 吴雁翔, 王红梅, 等. 自体外周血干细胞移植治疗62例缺血性下肢血管病临床研究. 中华内科杂志, 2005, 44 (2) : 95 - 98
43 王富军,谷涌泉,杨艳辉,等. 自体外周血干细胞移植治疗糖尿病足1例.临床荟萃杂志, 2006, 21(15):1128- 1129
44 杨晓凤.干细胞血管新生与糖尿病足.中国实用内科杂志,2006,26(17):1319-1321
45 Reyes M, Dudek A , Jahagirdar B , et al . Origin of endothelial progenitors in human postnatal bone marrow. JClin Invest , 2002 ,109 :337-346
46 Asahara T, Isner JM. Endothelial progenitor cells for vascular regeneration. J Hematother Stem Cell Res,2002,11:171-178
47 Iba O, Matsubara H , Nozawa Y, et al. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs. Circulation, 2002,106: 2019-2025
48 Kobayashi T, Hamano K, Li TS, et al . Angiogenesis induced by the injection of peripheral leukocytes and platelets. J Surg Res , 2002 ,103 :279-286
2 Boulton AJM. The diabetic foot: from art to science. Diabetologia, 2004, 47: 1343-1353
3 Levy MJ, Valabhji J. The diabetic foot. Surgery(oxford), 2008,26(1): 25-28
4 American Diabetes Association. Preventive Foot Care in Diabetes. Diabetes Care, 2004, 27: Suppl 1, S63-64
5 Khammash MR, Obeidat KA. Prevalence of Ischemia in Diabetic Foot Infection. World J. Surg,2003, 27: 797–799
6 Rathur HM, Boulton AJM. The diabetic foot. Clinics in Dermatology,2007,25:109–120
7 Abouaesha F, Van Schie CHM, Armstrong DG, et al. Plantar soft tissue thickness predicts high peak plantar pressure in the diabetic foot. J Am Podiatr Med Assoc , 2004,94:39–42
8 Vileikyte L, Rubin RR, Leventhal H. Psychological aspects of diabetic neuropathy and its late sequelae. Diab Metab Res Rev ,2004,20 :Suppl 1,S13–S18
9 Boulton AJM, Kirsner RS, Vileikyte L. Neuropathic diabetic foot ulcers. N Engl J Med, 2004, 351:48–55
10 Kiecolt-Glaser J, Preacher JK, MacCallum RC, et al. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci USA, 2003, 100: 9090 –9095
11 Yang EV, Bone CM, MacCallum RC, et al. Stress related modulation of matrix metalloproteinase expression. J Neuroimmunol , 2002,133:144–150
12 Lobmann R, Schultz G ,Lehnert H. Proteases and the Diabetic Foot Syndrome: Mechanisms and Therapeutic Implications. Diabetes Care, 2005, 28: 461-467
13 Lobmann R, Ambrosch A, Schultz G, et al. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia, 2002,45:1011–1016
14 Boulton AJM. The diabetic foot. Medicine, 2006, 34(3):87-90
15 Foster AVM, EdmondsME. The simple staging system: a new diabetic foot classification validated to guide therapy. In: Neurodiab and DFSG of EASD Joint Meeting(AbstrctsBook) Hungary, 2002. 112
16 许障荣. 老年糖尿病患者足病变的诊断与防治. 老年医学与保健杂志,2005,11(3):138-141
17 Miranda-Palma B, Basu S, Mizel MS, et al. monofilament as the gold standard for foot ulcer screening: a reappraisal. Diabetes ,2003, 53 :Suppl 1,A63
18 Carrington AL, Shaw JE, Van Schie CHM, et al. Can motor nerve conduction velocity predict foot problems in diabetes over a six year outcome period? Diabetes Care , 2002, 25:2010–2015
19 Lavery LA, Armstrong DG, Wunderlich RP, et al. Predictive value of foot pressure assessment when part of a population-based diabetes disease management program. Diabetes Care,2003, 26:1069–1073
20 Juha H.A. Niinikoski, M.D. Clinical Hyperbaric Oxygen Therapy, Wound Perfusion, and Transcutaneous Oximetry. World J. Surg, 2004,28: 307–311
21 Strauss MB, Bryant BJ, Hart GB. Transcutaneous oxygen measurements under hyperbaric oxygen conditions as a predictor for healing of problem wounds. Foot Ankle Int,2002,23:933-937
22 于德民,王鹏华译. 溃疡足. 见:Edmonds ME, Foster AVM, Sanders LJ 编著:糖尿病足诊治实践彩色图解. 天津:天津科技翻译出版公司,2006,80
23 Feldmeier J, ed. Hyperbaric oxygen 2003: indications and results: Hyperbaric Oxygen Therapy Committee report. Kensington, Md.: Undersea & Hyperbaric Medical Society, 2003:41-55
24 Piaggesi A, Viacava P, Rizzo L, et al. Semi-quantitative analysis of the histopathological features of the neuropathic foot ulcer—effects of pressure relief. Diabetes, 2003,26: 3123–3128
25 Lavery LA , Baranoski S , Ayello EA. Options for off-loading the diabetic foot . Advances in Skin & Wound Care, 2004 ,17 (4) :181- 186
26 Van Schie CHM, Whalley A, Armstrong DG, et al. The effect of silicone injections in diabetic foot on peak plantar pressure and plantar tissue thickness: a 2 year follow-up. Arch Phys Med Rehabil, 2002, 83:919–923
27 Van Schie CHM, Whalley A, Vileikyte L, et al. Efficacy of injected liquid silicone is related to peak plantar foot pressures in the neuropathic diabetic foot. Wounds , 2002, 14:26–30
28 Van Schie CHM, Whalley A , Vileikyte L , et al. Efficacy of injected liquid silicone in diabetic foot to ruduce risk factors for ulceration: a randomized double-blind placebo-controlled trial [J ] . Diabetes Care , 2000 , 23 :634-638
29 Loot MA, Kenter SB, van Galen WJ, et al. Fibroblasts derived from chronic diabetic ulcers differ in their response to stimulation with EGF, IGF-I, bFGF and PDGF-AB compared to controls. Eur J Cell Biol ,2002,81:153–160
30 Mandracchia VJ, Sanders SM, Frerichs JA. The use of becaplermin (rhPDGFBB) gel for chronic nonhealing ulcers: a retrospective analysis. Clin Podiatr Med Surg, 2001, 18:189 –209
31 Chin GA,Thigpin TG,Perrin KJ,et al.Treatment of chronic ulcers in diabetic patients with a topical metalloproteinase inhibitor,doxycycline. Wounds, 2003, 15:315–323
32 Frykberg RG, Zgonis T,.Armstrong DG,et al.Diabetic foot disoreders:a clinical practice guideline(2006 revision). The Journal of Foot&Ankle Surgery,2006,45:s1-65
33 Bello YM, Falabella AF, Eaglstein WH. Tissue-engineered skin:Current status in wound healing. Am J Clin Dermatol 2001,2:305-313
34 Kastenbauer T ,Hornlein B ,Sokol G, et al. Evaluation of granulocyte - colony stimulating factor in infected diabetic foot ulcers. Diabetologia,2003,46: 27-30
35 Martínez-Sánchez G, Al-Dalain SM, et al. Therapeutic efficacy of ozone in patients with diabetic foot. European Journal of Pharmacology,2005,523:151-161
36 Sigala F, Menenakos Ch, Sigalas P, et al. Transluminal angioplasty of isolated crural arterial lesions in diabeticswith critical limb ischemia1.Vasa,2005,34: 186-191
37 Feiring AJ, Wesolowski AA, Lade S. Primary stent-supported angioplasty for treatment of below-knee critical limb ischemia and severe claudication: early and one-year outcomes. J Am Coll Cardiol,2004,44:2307-2314
38 曾明, 董扬. 糖尿病足的手术治疗.中华医学杂志,2006, 86(45):3230-3232
39 Badiavas EV, Falanga V . Treatment of chronic wounds with bone marrow-derived cells. Arch Dermatol, 2003, 139:510– 516
40 Eriko TY, Hiroaki M, Toyoaki M, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cell: a pilot study and a randomized controlled trial [ J ]. Lancet,2002,360:427-435
41 黄平平, 李尚珠, 韩明哲, 等. 自体外周血干细胞移植治疗下肢动脉硬化闭塞症. 中华血液学杂志, 2003, 24: 308 - 311
42 杨晓凤, 吴雁翔, 王红梅, 等. 自体外周血干细胞移植治疗62例缺血性下肢血管病临床研究. 中华内科杂志, 2005, 44 (2) : 95 - 98
43 王富军,谷涌泉,杨艳辉,等. 自体外周血干细胞移植治疗糖尿病足1例.临床荟萃杂志, 2006, 21(15):1128- 1129
44 杨晓凤.干细胞血管新生与糖尿病足.中国实用内科杂志,2006,26(17):1319-1321
45 Reyes M, Dudek A , Jahagirdar B , et al . Origin of endothelial progenitors in human postnatal bone marrow. JClin Invest , 2002 ,109 :337-346
46 Asahara T, Isner JM. Endothelial progenitor cells for vascular regeneration. J Hematother Stem Cell Res,2002,11:171-178
47 Iba O, Matsubara H , Nozawa Y, et al. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs. Circulation, 2002,106: 2019-2025
48 Kobayashi T, Hamano K, Li TS, et al . Angiogenesis induced by the injection of peripheral leukocytes and platelets. J Surg Res , 2002 ,103 :279-286