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 Neuropathic and Biomechanical Etiology of Foot Ulceration in Diabetics

1. Classification of diabetic neuropathy

  • Mononeuropathies (isolated and multiple, cranial mononeuropathies).
  • Polyneuropathies (diabetic sensory polyneuropathy, proximal motor polyneuropathy, autonomic neuropathies).

2. Pathogenesis of diabetic neuropathy

  • Sorbitol accumulation.
  • The activated polyol pathway theory.
  • Changes in perineural and endoneurial vasculature and resultant ischemia of the nerve.
  • Hyperglycemia-related nonenzymatic glycosylation of the vasoneurosum and the endoneural matrix.
  • The role of insulin.

3. Foot changes as they relate to neuropathy

  • Consequences of sensory dysfunction.
  • Consequences of motor dysfunction.
  • Consequences of autonomic dysfunction.

4. Foot biomechanics

  • Normal gait (stance and swing phases).
  • Abnormal foot biomechanics.
  • Charcot deformity.
  • Biomechanical changes caused by segmental amputations of the foot (hallux amputation, toe amputation, transmetatarsal ray amputations, Lisfranc and Chopart amputations).

5. Pathophysiology of diabetic foot ulceration

  • The role of the loss of protective sensation.
  • The role of the structural deformity of the foot.


Simmons Z, Feldman EL. Update on diabetic neuropathy. Curr Opin Neurol 2002;15:595-603.

The pathogenesis of diabetic neuropathy is multifactorial. There is increasing evidence to link abnormalities in the polyol pathway to the pathogenesis of diabetic neuropathy. In addition, there appear to be abnormalities of nerve regeneration and of sodium and calcium channels. Aldose reductase inhibitors, neurotrophic factors and vascular endothelial growth factor have shown promise for reversing neuropathy. Lamotrigine and bupropion represent new treatments for neuropathic pain. All this new information about the pathogenesis and treatment of diabetic neuropathy is summarized in this article.

Guyton GP, Saltzman CL. The diabetic foot: basic mechanisms of disease. Instr Course Lect 2002;51:169-181.

This article addresses the many synergistic factors that cause both ulceration and neuroarthropathy. These include dramatic alterations in all components of the peripheral nerves, the mechanical characteristics of bones and soft tissues, gait kinematics, the vasculature at both a microscopic and a macroscopic level, the immune system, and the fundamental processes of wound healing.

Cavanagh PR, Ulbrecht JS, Caputo GM. New developments in the biomechanics of the diabetic foot. Diabetes Metab Res Rev 2000;16 Suppl 1:S6-S10.

Biomechanical issues are now widely recognized as being important in the treatment of diabetic foot disease. This article summarizes recent advances in the understanding of the association between foot deformity and plantar pressure, the measurement of shear stress and the importance of neuropathy and callus in the pathogenesis of ulceration. Recent data on the biomechanical evaluation of surgery as well as the efficacy of unloading devices is also presented.

Frykberg RG, Armstrong DG, Giurini J, Edwards A, Kravette M, Kravitz S, Ross C, Stavosky J, Stuck R, Vanore J. Diabetic foot disorders: a clinical practice guideline. American College of Foot and Ankle Surgeons. J Foot Ankle Surg 2000;39(5 Suppl):S1-60.

The underlying pathophysiology and treatment of diabetic foot ulcers, infections, and the diabetic Charcot foot are thoroughly reviewed. Based on currently available evidence, the authors present a Clinical Practice Guideline for diabetic foot disorders.

Laing P. The development and complications of diabetic foot ulcers. Am J Surg 1998;176(2A Suppl):11S-19S.

Neuropathy and ischemia, two common complications of diabetes mellitus, are the primary underlying risk factors for the development of foot ulcers and their complications. However, an initiating factor, such as physical or mechanical stress, is also required for an ulcer to develop. In addition to increasing the risk of ulceration, diabetes mellitus also increases the risk of infection by impairing the body's ability to eliminate bacteria. The complex processes by which diabetic ulcers develop are reviewed in this article.

Posted June 2010