The Pathogenesis of Foot Problems

  • Jonathan E. Shaw
  • Andrew J. M. Boulton
Part of the Contemporary Endocrinology book series (COE, volume 7)


The diabetic foot can present with many different problems, but the most important clinically are ulceration, amputation, and Charcot neuroarthropathy. These will be the focus of this chapter. Many diabetic complications have a great impact on the foot and it is therefore not surprising that diabetic foot problems account for more hospital inpatient days than any other diabetic problem (1). Diabetic neuropathy and peripheral vascular disease are the main etiological factors in foot ulceration, and may act alone, together, or in combination with other factors such as microvascular disease, biomechanical abnormalities, limited joint mobility, and increased susceptibility to infection. A thorough understanding of the contributory factors that lead to foot ulceration and amputation is essential for successful treatment of established pathology. Perhaps more importantly, as the role of education and appropriate footwear in preventing ulceration and amputation is now established, accurate identification of high-risk patients on whom these services can be focused is vital.


Peripheral Vascular Disease Diabetic Neuropathy Diabetic Peripheral Neuropathy Metatarsal Head Lower Extremity Amputation 
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  1. 1.
    Williams DRR. Hospital admissions of diabetic patients: information from hospital activity analysis. Diabetic Med 1985;2:27–32.PubMedCrossRefGoogle Scholar
  2. 2.
    Bell P. Vascular disease: aetiology and presentation. In: Boulton AJM, Connor H, Cavanagh PR, eds. The Foot in Diabetes, 2nd ed. Wiley, Chichester, UK, 1994, pp. 121–135.Google Scholar
  3. 3.
    Fasching P, Waldhausl W, Wagner OF. Elevated circulating adhesion molecules in NIDDM—potential mediators in diabetic macroangiopathy (letter). Diabetologia 1996;39:1242–1244.PubMedCrossRefGoogle Scholar
  4. 4.
    Schmidt AM, Crandall J, Hori O, Cao R, Lakatta E. Elevated plasma levels of vascular cell adhesion molecule-1 (VCAM-1) in diabetic patients with microalbuminuria: a marker of vascular dysfunction and progressive vascular disease. Br J Haematol 1996;92:747–750.PubMedCrossRefGoogle Scholar
  5. 5.
    Abbott RD, Brand FN, Kannel WB. Epidemiology of some peripheral arterial findings in diabetic men and women: experiences from the Framingham Study. Am J Med 1990;88:376–381.PubMedCrossRefGoogle Scholar
  6. 6.
    Walters DP, Gatling W, Mullee MA, Hill RD. The prevalence, detection and epidemiological correlates of peripheral vascular disease: a comparison of diabetic and non-diabetic subjects in an English community. Diabetic Med 1992;9:710–715.PubMedCrossRefGoogle Scholar
  7. 7.
    Strandness DE, Priest RE, Gibbons RE, Seattle MD. Combined clinical and pathological study of diabetic and non diabetic peripheral artery disease. Diabetes 1961;13:366–372.Google Scholar
  8. 8.
    King TA, DePalma RG, Rhodes RS. Diabetes mellitus and atherosclerotic involvement of the profunda femoris artery. Surg Gynecol Obstet 1984;159:553–556.PubMedGoogle Scholar
  9. 9.
    Jude E, Shaw J, Chalmers N, Boulton AJM. Peripheral vascular disease (PVD) in diabetic and non-diabetic patients—a comparison. Diabetic Med 1996;13(suppl 7):S47.Google Scholar
  10. 10.
    Osmundson PJ, O’Fallon WM, Zimmerman BR, Kazmier FJ, Langworthy AL, Palumbo PJ. Course of peripheral arterial occlusive disease in diabetes. Vascular laboratory assessment. Diabetes Care 1990;13:143–152.Google Scholar
  11. 11.
    Edmonds ME. Experience in a multi-disciplinary diabetic foot clinic. In: Boulton AJM, Connor H, Ward JD, eds. The Foot in Diabetes, 1st ed. Wiley, Chichester, UK, 1987, pp. 121–133.Google Scholar
  12. 12.
    Thomson FJ, Veves A, Ashe H, Knowles EA, Gem J, Walker MG, Hirst P, Boulton AJM. A team approach to diabetic foot care: the Manchester experience. The Foot 1991;1:75–82.CrossRefGoogle Scholar
  13. 13.
    Pecoraro RE, Reiber GE, Burgess EM. Pathways to diabetic limb amputation. Basis for prevention. Diabetes Care 1990;13:513–521.Google Scholar
  14. 14.
    Young MJ, Boulton AJM, MacLeod AF, Williams DRR, Sonksen PH. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia 1993;36:150–154.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    Walters DP, Gatting W, Mullee MA, Hill RD. The prevalence of diabetic distal sensory neuropathy in an English community. Diabet Med 1991;9:349–353.CrossRefGoogle Scholar
  17. 17.
    Sosenko JM, Kato M, Soto R, Bild DE. Comparison of quantitative sensory-threshold measures for their association with foot ulceration in diabetic patients. Diabetes Care 1990;13:1057–1061.PubMedCrossRefGoogle Scholar
  18. 18.
    Boulton AJ, Kubrusly DB, Bowker JH, Gadia MT, Quintero L, Becker DM, Skyler JS, Sosenko JM. Impaired vibratory perception and diabetic foot ulceration. Diabet Med 1986;3:335–337.PubMedCrossRefGoogle Scholar
  19. 19.
    Young MJ, Breddy JL, Veves A, Boulton AJM. The prediction of diabetic neuropathic foot ulceration using vibration perception thresholds. A prospective study. Diabetes Care 1994;17:557–560.Google Scholar
  20. 20.
    Rith-Najarian SJ, Stolusky T, Ghodes DM. Identifying diabetic patients at high risk for lower-extremity amputation in a primary care setting. Diabetes Care 1992;15:1386–1389.PubMedCrossRefGoogle Scholar
  21. 21.
    Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, Wilson DM, O’Brien PC, Melton LJ. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy and nephropathy in a population-based cohort. Neurology 1993;43:817–824.PubMedCrossRefGoogle Scholar
  22. 22.
    Uccioli L, Monticone D, Durola J, Russo F, Mormile F, Mennuni G, Menzinger G. Autonomic neuropathy influences great toe blood pressure. Diabetes Care 1994;17:284–287.PubMedCrossRefGoogle Scholar
  23. 23.
    Ctercteko GC, Dhanendran M, Hutton WC, Le Quesne LP. Vertical forces acting on the feet of diabetic patients with neuropathic ulceration. Br J Surg. 1981;68:608–614.PubMedCrossRefGoogle Scholar
  24. 24.
    Boulton AJM, Hardisty CA, Betts RP, Franks CI, Worth RC, Ward JD, Duckworth T. Dynamic foot pressure and other studies as diagnostic and management aids in diabetic neuropathy. Diabetes Care 1983;6:26–33.PubMedCrossRefGoogle Scholar
  25. 25.
    Veves A, Murray HJ, Young MJ, Boulton AJM. The risk of foot ulceration in diabetic patients with high foot pressure: a prospective study. Diabetologia 1992;35:660–663.PubMedCrossRefGoogle Scholar
  26. 26.
    Murray HJ, Young MJ, Hollis S, Boulton AJM. The association between callus formation, high pressures and neuropathy in diabetic foot ulceration Diabetic Med 1996;13:979–982.PubMedCrossRefGoogle Scholar
  27. 27.
    Young MJ, Cavanagh PR, Thomas G, Johnson MM, Murray H, Boulton AJM. The effect of callus removal on dynamic plantar foot pressures in diabetic patients. Diabet Med 1992;9:55–57.PubMedCrossRefGoogle Scholar
  28. 28.
    Young MJ, Coffey J, Taylor PM, Boulton AJM. Weight bearing ultrasound in diabetic and rheumatoid arthritis patients. The Foot 1995;5:76–79.CrossRefGoogle Scholar
  29. 29.
    Masson EA, Hay EM, Stockley I, Veves A, Betts RP, Boulton AJM. Abnormal foot pressures alone may not cause ulceration Diabet Med 1989;6:426–428.PubMedCrossRefGoogle Scholar
  30. 30.
    Fernando DJ, Masson EA, Veves A, Boulton AJM. Relationship of limited joint mobility to abnormal foot pressures and diabetic foot ulceration. Diabetes Care 1991;14:8–11.PubMedCrossRefGoogle Scholar
  31. 31.
    Veves A, Sarnow MR, Giurini JM, Rosenblum BI, Lyons JE, Chrzan JS, Habershaw GM. Differences in joint mobility and foot pressures between black and white diabetic patients. Diabet Med 1995;12:585–589.PubMedCrossRefGoogle Scholar
  32. 32.
    Shaw JE, Boulton AJM. Pressure time integrals may be more important than peak pressures in diabetic foot ulceration. Diabetic Med 1996;13(suppl 7):S22.Google Scholar
  33. 33.
    Landsmann AS, Meaney DF, Cargill RS, Macarak EJ, Thibault LE. High strain rate tissue deformation. J Am Podiatr Med Assoc 1995;85:519–527.Google Scholar
  34. 34.
    Flynn MD, Edmonds ME, Tooke JE, Watkins PJ. Direct measurement of capillary blood flow in the diabetic neuropathic foot. Diabetologia 1988;31:652–656.PubMedCrossRefGoogle Scholar
  35. 35.
    Rayman G, Hassan A, Tooke JE. Blood flow in the skin of the foot related to posture in diabetes mellitus. Br Med J 1986;292:87–90.CrossRefGoogle Scholar
  36. 36.
    Parkhouse N, Le Quesne PM. Impaired neurogenic vascular response in patients with diabetes and neuropathic foot lesions. N Engl J Med 1988;318:1306–1309.PubMedCrossRefGoogle Scholar
  37. 37.
    Nelson RG, Gohdes DM, Everhart JE, Hartner JA, Zwemer FL, Pettitt DJ, Knowler WC. Lowerextremity amputations in NIDDM. 12-yr follow-up study in Pirna Indians. Diabetes Care 1988;11:8–16.PubMedCrossRefGoogle Scholar
  38. 38.
    Siitonen OI, Niskanen LK, Laakso M, Siitonen JT, Pyorala K. Lower-extremity amputations in diabetic and nondiabetic patients. A population-based study in eastern Finland. Diabetes Care 1993;16:16–20.PubMedCrossRefGoogle Scholar
  39. 39.
    Selby JV, Zhang D. Risk factors for lower extremity amputations in persons with diabetes. Diabetes Care 1995;18:509–516.PubMedCrossRefGoogle Scholar
  40. 40.
    Pecoraro RE, Ahroni JH, Boyko EJ, Stensel VL. Chronology and determinants of tissue repair in diabetic lower extremity ulcers. Diabetes 1991;40:1305–1313.PubMedCrossRefGoogle Scholar
  41. 41.
    Vileikyte L, Shaw JE, Kincey J, Carrington AL, Boulton AJM. A Prospective study of neuropathic and psychological factors in foot ulceration. Diabetologia 1996;39(suppl 1):A3.Google Scholar
  42. 42.
    Valway SE, Linkins RW, Gohdes DM. Epidemiology of lower-extremity amputations in the Indian Health Service, 1982-1987. Diabetes Care 1993;16:349–353.PubMedCrossRefGoogle Scholar
  43. 43.
    Lee JS, Lu M, Lee VS, Russell D, Bahr C, Lee ET. Lower-extremity amputation. Incidence, risk factors, and mortality in the Oklahoma Indian Diabetes Study. Diabetes 1993;42:876–882.PubMedCrossRefGoogle Scholar
  44. 44.
    Gujral JS, McNally PG, O’Malley BP, Burden AC. Ethnic differences in the incidence of lower extremity amputation secondary to diabetes mellitus. Diabetic Med 1993;10:271–274.PubMedCrossRefGoogle Scholar
  45. 45.
    Clarke D, Martin K, Kaltas G, Tindall H. Ethnic variation in the diabetic foot clinic. Diabetic Med 1992;9(suppl 1):35A.Google Scholar
  46. 46.
    Most RS, Sinnock P. The epidemiology of lower extremity amputations in diabetic individuals. Diabetes Care 1983;6:87–91.PubMedCrossRefGoogle Scholar
  47. 47.
    Walsh CH, Soler NG, Fitzgerald MG. Association of foot lesions with retinopathy in patients with newly diagnosed diabetes. Lancet 1975;1:878–880.PubMedCrossRefGoogle Scholar
  48. 48.
    Grossi EA, Esposito R, Harris LJ, Crooke GA, Galloway AC, Colvin SB, Culliford AT, Baumann FG, Yao K, Spencer FC. Sternal wound infections and use of internal mammary artery grafts. J Thorac Cardiovasc Surg 1991;102:342–346.PubMedGoogle Scholar
  49. 49.
    Sapico FL, Bessman AN. Diabetic foot infections. In: Frykeberg RG, ed. The High Risk Foot in Diabetes Mellitus. Churchill Livingstone, New York, 1991, pp. 197–211.Google Scholar
  50. 50.
    Pecoraro RE, Chen MS. Ascorbic acid metabolism in diabetes mellitus. Ann NY Acad Sci 1987;498:248–258.PubMedCrossRefGoogle Scholar
  51. 51.
    Shaw JE, Spencer MJ, Herrick SE, Ferguson MWJ, Boulton AJM. Reduced tissue levels of TGFβl may contribute to poor healing in diabetic foot ulcers. Diabetologia 1996;39(suppl 1):A4.Google Scholar
  52. 52.
    Brash PD, Foster JE, Vennart W, Daw J, Tooke JE. Magnetic resonance imaging reveals micro-hemorrhages in the feet of diabetic patients with a history of ulceration. Diabetic Med 1996;13:973–978.PubMedCrossRefGoogle Scholar
  53. 53.
    Cavanagh PR, Young MJ, Adams JE, Vickers KL, Boulton AJM. Radiographic abnormalities in the feet of patients with diabetic neuropathy. Diabetes Care 1994;17:201–209.PubMedCrossRefGoogle Scholar
  54. 54.
    Elloesser L. On the nature of neuropathic affections of the joints. Ann Surg 1917;66:201–217.CrossRefGoogle Scholar
  55. 55.
    Sanders LJ, Frykberg RG. Diabetic neuropathic osteoarthropathy: the Charcot foot. In: Frykberg RG, ed. The High Risk Foot in Diabetes Mellitus. Churchill Livingstone, New York, 1991, pp. 297–338.Google Scholar
  56. 56.
    Edmonds ME, Clarke MB, Newton S, Barrett J, Watkins PJ. Increased uptake of bone radiopharmaceutical in diabetic neuropathy. Q J Med 1985;57:843–855.PubMedGoogle Scholar
  57. 57.
    Young MJ, Marshall A, Adams JE, Selby PL, Boulton AJM. Osteopenia, neurological dysfunction, and the development of Charcot neuroarthropathy. Diabetes Care 1995;18:34–38.PubMedCrossRefGoogle Scholar
  58. 58.
    Shaw JE, Adams JE, Boulton AJM. Peri-articular abnormalities in neuropathic arthropathy. Diabet Med 1995;12(suppl 2):S43.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Jonathan E. Shaw
  • Andrew J. M. Boulton

There are no affiliations available

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