The long term goal of this research is to reduce the incidence of lower extremity amputation in people with diabetes mellitus and peripheral neuropathy. It is hypothesized that muscle, joint, and movement deterioration associated with diabetes and peripheral neuropathy contribute to metatarsophalangeal joint (MTPJ) hyperextension deformity. MTPJ deformity results in excessive plantar stress on the insensitive forefoot, leading to ulceration and amputation. However, the specific cause of MTPJ deformity is not clear. The overall goal of this proposal is to identify the causes of MTPJ deformity and examine the ability of a targeted foot specific intervention to de-couple diabetes related mechanisms from MTPJ deformity and progression, following participants for 3 years. We hypothesizes that the cause of MTPJ deformity is an interaction of the accumulation of advanced glycation end products, muscle deterioration, limited joint mobility and compensatory movement strategies.
The specific aims are to determine: 1) relationships between advanced glycation end products, intrinsic foot muscle volume, limited ankle dorsiflexion joint mobility, MTPJ hyperextension movement pattern, and MTPJ alignment; 2) estimate the effect of a foot specific intervention on the MTPJ extension alignment and 3) determine progression of MTPJ deformity and the predictors of progression over three years. The following will be collected on participants with diabetes mellitus and peripheral neuropathy and monitored over three years to understand the causes and progression of MTPJ deformity: 1) Skin intrinsic florescence to measure advanced glycation end product accumulation which increases collagen cross-linking and is associated with peripheral neuropathy, limited joint mobility, and muscle deterioration. 2) Magnetic resonance images to measure intrinsic foot muscle deterioration that precedes extrinsic foot muscle deterioration as a result of distal to proximal peripheral neuropathy. The muscle imbalance of weak intrinsic foot muscles, the only muscles able to flex the MTPJ, in the presence of relatively stronger extrinsic toe extensors, results in a force couple that hyperextends the MTPJ. 3) Kinematic and computed tomography measurement of foot and ankle joint positions to exam the mobility and movement patterns that contribute to repeated and extreme MTPJ hyperextension during daily activities. We believe advanced glycation end products lead to limited ankle joint dorsiflexion. As a result, there is increased reliance on the extensor digitorum longus to assist in dorsiflexing the stiff ankle joint during activities like si to stand. This study will have profound implications for reducing risk for skin breakdown and amputation by helping to understand and treat the causes of acquired neuropathic foot deformities. A successful foot specific intervention that improves MTPJ alignment will provide a non-invasive option to halt or slow the cascade of events leading to major lower extremity amputation, while improving function and minimizing disability.

Public Health Relevance

One in four of the 26 million people with DM will develop skin breakdown and as many of 85% of those with a history of skin breakdown or amputation has metatarsal phalangeal joint (MTPJ) deformity. MTPJ angle has been found to be the most important variable predicting peak plantar pressure during walking, a key contributor to skin breakdown. Therefore, understanding the causes of MTPJ deformity and the ability of a foot specific intervention to de-couple disease from deformity will improve the strategies used to manage, treat, and prevent diabetic foot deformity, reducing the risk of lower extremity amputation in this high risk population.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Musculoskeletal Rehabilitation Sciences Study Section (MRS)
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Jones, Teresa L Z
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Washington University
Other Health Professions
Schools of Medicine
Saint Louis
United States
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Johnson, Jeffrey E; Paxton, E Scott; Lippe, Julienne et al. (2015) Outcomes of the Bridle Procedure for the Treatment of Foot Drop. Foot Ankle Int 36:1287-96