ADVERTISEMENT
Current Insights On Biomechanics And The Diabetic Ulcerative Functional Foot
Changes in fat pad thickness, compromised mobility and the development of neuropathy can have a profound effect on the biomechanics of the diabetic foot. This author emphasizes how a strong understanding of the biomechanical forces upon the diabetic foot can lead to more effective treatment and prevention of further complications.
Much has been written about the devastating effects of diabetes on the foot. As the plague of diabetes continues to spread throughout the world, the number of foot-related complications from diabetes continues to grow.
Podiatric medicine has taken a leading role in the immediate treatment of the diabetic foot ulcer to the point of healing. However, the relapse rate for diabetic ulcers is extremely high with reports averaging about 40 percent in the first 12 months following healing of the initial ulcer.1 In 1993, in an effort to decrease the risk of patients with diabetes developing ulcerations, the Centers for Medicare and Medicaid Services added diabetic shoes as a benefit to qualified individuals. Certainly, this has decreased the incidence of pain and callus formation.2
However, diabetic shoes alone are not sufficient to actually decrease the number of ulcers and the costs of treating those ulcers continues to soar. Clinicians not only need to consider and address the mechanical factors that contribute to diabetic foot ulcers, they also need to be aware of and evaluate the well-known risks for disabilities and injuries that are common to patients with diabetes. By recognizing the early development of problems, one may develop strategies to try to prevent the devastating consequences in this high-risk patient population.
What You Should Know About Changes In The Metatarsal Fat Pad With Diabetes
A great many diabetic ulcers occur in the forefoot, under the metatarsal heads and under the digits, especially the hallux. Since the bottom of each metatarsal head is round, when the metatarsal head makes contact with the ground, it only contacts at a single point. Thus, if half the body weight is on the metatarsal heads, it means that under the point of contact, there is a significant amount of pressure unless there is some way for the weight to transfer away from the single point of bone contact.
The metatarsal fat pad is the structure that is responsible for dissipating the pressure from the lowest points of the metatarsal heads to the sides of the metatarsal heads, to the intermetatarsal spaces and to points proximal and distal to the metatarsal heads.3 Podiatrists are very familiar with calluses forming under metatarsal heads where the metatarsal fat pad is thinner and many physicians have attempted to treat calluses by increasing the thickness of the metatarsal fat pad.4–6
Patients with diabetes, whether or not they have neuropathy, generally have decreased thickness of the metatarsal fat pads, and the thinner the metatarsal fat pad, the higher the risk of developing ulcers.7,8 Abouaesha and colleagues noted the following respective minimum thicknesses of metatarsal fat pad necessary to ensure that peak pressures under the first through fifth metatarsal heads do not exceed 700 kPa: 11.05 mm, 7.85 mm, 6.65 mm, 6.55 mm and 5.05 mm.9 Since the easiest way to measure fat pad thickness under the metatarsal heads is with ultrasound, the day may not be too far distant when diabetic foot screenings may include ultrasound examination of the fat pad thickness under each of the five metatarsal heads.10
Whether diabetes itself causes fat pad atrophy is still under debate. In a small sample of computed tomography (CT) exams of patients with diabetes who had had prior ulcers, Robertson and colleagues showed no difference in the thickness of the fat pads in comparison with healthy, age-matched controls.11 However, the authors did note that there was a decrease in the fat pad thickness that correlated with age.
Waldecker and Lehr also challenged the concept that the fat pad atrophies in patients with diabetes with a histological study showing no evidence of fat pad atrophy in patients with diabetes in comparison with control patients.12 Wang and coworkers also supported this challenge, showing an increase in the thickness of the septal fibers that separated the adipocytes in the metatarsal fat pad in patients with diabetes.13,14 Chao and colleagues showed that patients with diabetic foot ulcers had a 15 percent thinner epidermis than control patients.15 The authors found that in patients with diabetes with no neuropathy or foot ulcers, there was actually a 6 percent increase in the epidermal thickness in comparison to patients with diabetic neuropathy and control patients.
Less controversial has been the repeated finding that the metatarsal fat pad migrates forward in the patient with diabetic neuropathy. This causes a functional decrease in the thickness of the soft tissues between the metatarsal heads and the ground, and an increase in the thickness of the pad under the proximal phalanges.16 Mickle and coworkers measured the total thickness of the soft tissue under the metatarsals and just the fat component of the soft tissue.17 The authors noted that those with hammertoes had a total decrease in the soft tissue but not in the thickness of the adipose layer of the metatarsal fat pad.
While the thickness of the fat pad may be more age dependent, researchers have shown the migration of the cushioning pad forward due to the development of hammertoes increases pressure under the metatarsal heads.18 In fact, the presence of hammertoes was the most important predictor of peak plantar pressure in a study by Mueller and colleagues.19 At any age, dorsiflexion of the metatarsophalangeal joint (MPJs) causes tightening of the vertical fibers in the fat pad under the metatarsal heads, which increases the stiffness of the pad and allows push-off force to transfer to the forefoot.20 As people age, the metatarsal cushion becomes even stiffer, which means that corresponding dorsiflexion angles of the MPJs have even greater stiffness in the elderly than in the young.21 Therefore, a hammertoe deformity in the young has less of an impact on the cushioning under the metatarsal heads than the same hammertoe deformity in the elderly.
How Collagen And AGEs Affect The Stiffness Of The Fat Pad
As one studies the etiologies of diabetic foot problems, the problem of advanced glycation end products (AGEs) becomes ever more important.22 The AGE buildup occurs normally in the aging process but higher blood sugar levels markedly increase the level of AGEs.23,24 Of great concern in the past few years is the relationship between AGEs and vascular disease. With elevated AGEs, numerous mechanisms cause increased endothelial dysfunction, elevated low-density lipoprotein (LDL) levels, an increased instability of plaques and decreased vascular repair in response to injury.25
Future research into diabetic angiopathy points to approaches (such as AGE crosslink “breakers”) to decrease the AGE levels.26 Collagen is a very important protein highly affected by increased levels of AGEs. These AGEs cause biochemical modification, in which glucose binding to amino acids on the surface of the collagen convert enzymatically to non-reversible crosslinks between the fibers.27 The greater the number of crosslinks between the collagen fibers, the less the fibers can slide against each other, which increases the stiffness of the fibers.28,29 Therefore, it is not surprising that research has found the fat pad under the metatarsal heads in patients with diabetes is stiffer than in those without diabetes.30–32
Why is a stiffer fat pad a problem? The first result of a stiffer fat pad is that the softer pad increases the shock absorption of the forefoot hitting the ground. A stiffer fat pad decreases shock absorption, which means that greater energy imparts to the soft tissues during the landing on the forefoot.33 The second result is that the stiffer fat pad means the stress disperses less medially and laterally away from the lowest points of the metatarsal heads. Subsequently, more stress acts on the soft tissue pads directly under the metatarsal heads and less stress affects the portion of the fat pad between the metatarsal heads.34 The third result is that as the collagen fibers become stiffer, they strain less before they break. Whereas healthy, non-glycated tissues can normally withstand strain values, when the collagen fibers are stiffer, these tissues start breaking with the same amount of strain.
Therefore, we see that in the literature, authors have recorded a great variety of minimum stress values as necessary to produce a diabetic foot ulcer.35–38 The future standard for diabetic shoe prescriptions may be to actually measure the stiffness of the soft tissues under the foot and select the right insole from a variety of insoles with various degrees of cushioning.39,40
A Closer Look At Compromised Mobility With The Diabetic Foot
The collagen in the plantar fat pad is not the only tissue that stiffens. The collagen tissues throughout the body all stiffen with diabetes. One of the results of this stiffening of all the collagen tissues is the stiffening of all the ligaments, which causes loss of mobility in all of the joints.41 This can be extremely problematic in many portions of the gait cycle.
For example, during the contact period of gait, the rearfoot starts in a mildly inverted state and then everts. The forefoot lands first on the fifth metatarsal and then each of the metatarsals land in succession from lateral to medial. By the end of the contact period, the rearfoot is mildly everted and the forefoot is mildly inverted to the rearfoot so all the metatarsal heads are on the ground.
Loss of eversion mobility in the subtalar joint can be problematic as it increases the load on the lateral side of the forefoot. This may be extremely problematic in patients with genu varum or in patients with a natural inverted forefoot.
Loss of mobility in the midtarsal joint can be problematic in a couple of ways. If the patient with diabetes exhibits a normal amount of rearfoot eversion during contact, the forefoot may have difficulty in compensating by inverting at the midtarsal joint. This may cause an increase in pressure under the first and/or second metatarsal heads. On the other hand, if the forefoot cannot invert adequately to allow subtalar joint pronation, one may see an increase in pressure under the fourth and/or fifth metatarsal heads.
In addition to frontal plane restrictions in motion, sagittal plane motion is also decreased in all the metatarsals with stiffer collagen tissues.42 This also decreases shock absorption during forefoot loading and decreases surface adaptation by the foot, especially when changing directions. Evaluation of available motion of the rearfoot as well as available motion in the midtarsal joint can be an important part of assessing why calluses or ulcers are developing in the forefoot. It can also be invaluable in helping to design the diabetic orthotic.43
One of the most documented losses of range of motion is in the ankle joint. This is largely attributable to the glycation of the Achilles tendon, which increases the tendon’s thickness and stiffness.44,45 This causes several changes in the diabetic foot, including earlier forefoot loading at contact as well as an increased load on the forefoot during the stance phase of gait.46,47 Measuring the Achilles tendon length will show the tendon shortens with time due to glycation.48
Accordingly, the peak pressures as well as the force-time integral increase on the forefoot during gait, which increases the risk of ulceration.49,50 This increase in forefoot pressure increases the dorsiflexion on the midtarsal and tarsometatarsal joints. Almost all cases of Charcot joint development involve Achilles tendon shortening.
In conjunction with Achilles tendon thickening is the thickening of the plantar fascia.51 This increase in thickness decreases the effect of the windlass mechanism of the foot, which causes a decrease in digital dorsiflexion, decreased time in the propulsive period of gait and a decrease in supination of the rearfoot during propulsion.52,53 Achilles tendon stretching is certainly one of the modalities that may increase the dorsiflexion flexibility during gait and decrease the risk of adverse effects created by Achilles glycation.54
Understanding The Effects Of Diabetic Neuropathy On Biomechanics
Besides the glycation of the collagen tissues creating increased trauma to the foot when standing and walking, diabetic neuropathy has an equal if not greater adverse effect on the foot. Certainly, research has shown tissue glycation to be a predictor of other diabetic complications including neuropathy.55 A common test for neuropathy utilized by most insurance companies to determine qualification for diabetic shoes is the 10 g Semmes-Weinstein monofilament test.56,57 Inability of the patient to detect the 10 g monofilament is often known as loss of protective sensation.58
However, the sensitivity and specificity of the Semmes-Weinstein test may be inadequate for detecting diabetic neuropathy and assessing if the patient’s gait pattern has changed.59 Some researchers believe that by the time a patient loses 10 g of sensitivity, there has already been significant loss of much neurological function in the lower extremity, and that 1 g or 2 g sensitivity loss is a better measure of the presence of diabetic neuropathy.60–62 Certainly, the Semmes-Weinstein monofilament depends on the stimulation of the light touch sensation, which is a function of the small myelinated afferent nerves. However, it does not address large myelinated afferent nerve fibers nor does it address unmyelinated nerve fibers, efferent motor nerve fibers, or autonomic nerve fibers.
There is little literature to guide physicians as to when various nerve fiber types are compromised in the progression of the diabetic neuropathy. The fact that a great many patients with diabetes are insensate to the 10 g monofilament and yet continue to suffer diabetic nerve pain in the most distal aspect of the feet is highly suggestive to me that myelinated nerve fibers are often affected by neuropathy before unmyelinated fibers.
Diabetic motor neuropathy has had much more research and recognition in recent years. Authors have documented a direct relationship between the plantar muscle volume loss, as measured by magnetic resonance imaging (MRI) and ultrasound studies, and the amount of actual neuropathy.63 Significant plantar foot muscle atrophy occurs very early in the process, long before standard screening tests detect the loss of sensation.64 The loss of interosseous muscle strength and medial head of the flexor hallucis brevis precedes decreases in strength of the lateral flexor hallucis brevis, which may increase the likelihood of hallux valgus development.65
Since lumbrical malfunction has long been implicated in the development of hammertoes and because the lumbricals are an important part of digital stabilization during the propulsive period, researchers commonly conclude that there is a direct cause and effect relationship between hammertoes and diabetic neuropathy.66 Certainly, the ratio of extensor to flexor toe strength increases in hammertoe, which would accentuate the hammering of the toes if both the extensors and flexors contract simultaneously.67 However, though the risk of hammertoes is greater with diabetic neuropathy, not everyone with diabetic neuropathy has hammertoes. Therefore, the creation of hammertoes is still multifactorial and depends on other biomechanical factors.68,69
Researchers have found the incidence of pronated feet to be greater in those with diabetic neuropathy.70 The early loss of plantar foot musculature will definitely decrease supination torque around the midtarsal joint, affecting the propulsive phase of gait when the midtarsal joint has to plantarflex in order for the windlass mechanism to work. Therefore, propulsion is decreased in early stages of peripheral neuropathy. In addition, as the plantar muscles start deteriorating, a loss of stability of the medial column of the foot starts occurring. As the neuropathy continues, the lower leg muscles start showing the replacement of muscle tissue with adipose tissue.71 Loss of strength of the deep posterior muscles of the lower leg, including the posterior tibial and the long flexors, causes decreased stability of the medial column. The decreased stability of the medial column is directly related to an increase in Meary’s angle (the dorsiflexion angle of the first metatarsal to the talar neck bisection on lateral weightbearing X-rays).72 By assessing medial column instability of the foot early, it may be possible to delay the onset of the symptoms associated with abnormal pronation of the foot.
Not only does muscle mass decrease in the leg with diabetic neuropathy, the timing of muscle activation is also delayed when walking. Overall, patients with diabetes slow their walking speed and also decrease their step length.73,74 This decrease in walking speed actually increases the metabolic cost of walking.75 Factors that decrease walking speed include delayed motor nerve conduction velocity as well as the decreased muscle fiber conduction velocity.76 This means that the initiation of muscle contraction is delayed and then once contraction starts, the time to maximum contraction force is also delayed.
This results in not only decreased strength of the anterior tibialis but delayed activation of the anterior tibialis during the toe-off period and during swing.77,78 This results in a combination of decreased ankle joint dorsiflexion during swing and decreased knee flexion in early swing, thus making those with diabetic neuropathy much more susceptible to falling due to failure of the foot to clear small obstacles.79 The weakness of the anterior tibial tendon also decreases its eccentric contraction function during the contact period of gait. This, along with the increased tightness of the Achilles tendon, causes the forefoot to hit the ground earlier and decreases the shock absorption of the forefoot hitting the ground.80 Weakness of the anterior tibial tendon may increase extensor substitution, which accentuates the hammering of the digits.
One of the aspects of diabetic neuropathy that we often do not think about is the loss of proprioception. Patients lose ankle joint proprioception fairly early in the development of diabetic neuropathy, which results in patients overestimating their degree of ankle joint dorsiflexion.81 This may result in ankle joint plantarflexors activating to correct for too much lean forward, which could cause patients to tend to fall backwards more easily.82 Loss of joint position sense also markedly increases postural sway. Balance, therefore, is markedly decreased and the incidence of falls is much greater in patients with diabetes.83
One may utilize various pedobarographic and balance assessment tools for assessment of balance on a regular basis. Strategies to improve balance include passive shoe, orthotic and brace therapy. Experiments with insoles that add somatosensory input have also shown promise in improving balance although much development remains to be done.84,85 Authors also recommend that when there is detectable balance deterioration, the patient begin an active balance training program with a physical medicine specialist.86,87
Final Notes
Changes in mechanical properties of all of the lower extremity tissues cause abnormal forces that are at the root of the formation of ulcers and resultant infections that plague the patient with diabetes. These abnormal forces are compounded by changes in every aspect of neurological function. Muscle mass degeneration as well as abnormal muscle firing patterns change gait patterns and increase the formation of common foot deformities including hallux valgus, hammertoes and flatfoot. Loss of other proprioception and stretch reflexes have marked effects on postural stability and increase the injuries due to falling in patients with diabetes.
The podiatrist, therefore, finds that the diabetic foot can present with the most complicated biomechanical challenge. By assessing the many aforementioned biomechanical factors, the podiatrist is better able to recommend not just better shoe therapy but better orthotic or brace therapy, more vigorous physical therapy as well as closer monitoring of the patient as the various biomechanical factors will continue to change.
Dr. Phillips is affiliated with the Orlando Veterans Affairs Medical Center in Orlando, Fla. He is a Diplomate of the American Board of Foot and Ankle Surgery, and the American Board of Podiatric Medicine. Dr. Phillips is a Professor of Podiatric Medicine with the College of Medicine at the University of Central Florida. He is also a member of the American Society of Biomechanics.
References
1. Armstrong DG, Boulton AJM, Bus SA. Diabetic foot ulcers and their recurrence. New Engl J Med. 2017; 376(24):2367-2375.
2. Menz HB, Auhl M, Ristevski S, et al. Effectiveness of off-the-shelf, extra-depth footwear in reducing foot pain in older people: a randomized controlled trial. J Gerontol. 2014; 70(4):511-517.
3. Bojsen-Møller F. Anatomy of the forefoot, normal and pathologic. Clinical Orthop Rel Res. 1979; 142:10-18.
4. Van Schie CHM, Whalley A, Vileikyte L, et al. Efficacy of injected liquid silicone in the diabetic foot to reduce risk factors for ulceration: a randomized double-blind placebo-controlled trial. Diabetes Care. 2000; 23(5):634-638.
5. Colen LB, Replogle SL, Mathes SJ. The VY plantar flap for reconstruction of the forefoot. Plast Reconstr Surg. 1988; 81(2):220-227.
6. Rocchio TM. Augmentation of atrophic plantar soft tissue with an acellular dermal allograft: a series review. Clin Podiatr Med Surg. 2009; 26(4):545-557.
7. Gooding GA, Stess RM, Graf PM, et al. Sonography of the sole of the foot: evidence for loss of foot pad thickness in diabetes and its relationship to ulceration of the foot. Investigative Radiol. 1986; 21(1):45-48.
8. Abouaesha F, van Schie CHM, Griffths GD, et al. Plantar tissue thickness is related to peak plantar pressure in the high-risk diabetic foot. Diabetes Care. 2001; 24(7):1270-1274.
9. Abouaesha F, Van Schie CHM, Armstrong DG, Boulton AJM. Plantar soft-tissue thickness predicts high peak plantar pressure in the diabetic foot. J Am Podiatr Med Assoc. 2004; 94(1):39-42.
10. Cavanagh PR. Plantar soft tissue thickness during ground contact in walking. J Biomech. 1999; 32(6):623-628.
11. Robertson DD, Mueller MJ, Smith KE, et al. Structural changes in the forefoot of individuals with diabetes and a prior plantar ulcer. J Bone Joint Surg. 2002; 84(8):1395-1404.
12. Waldecker U, Lehr HA. Is there histomorphological evidence of plantar metatarsal fat pad atrophy in patients with diabetes? J Foot Ankle Surg. 2009; 48(6):648-52
13. Wang YN, Lee K, Ledoux WR. Histomorphological evaluation of diabetic and non-diabetic plantar soft tissue. Foot Ankle Int. 2011; 32(8):802-810.
14. Wang YN, Lee K, Shofer JB, Ledoux WR. Histomorphological and biochemical properties of plantar soft tissue in diabetes. Foot. 2017; 33:1–6.
15. Chao CYL, Zheng YP, Cheing GLY. Epidermal thickness and biomechanical properties of plantar tissues in diabetic foot. Ultrasound Med Biol. 2011; 37(7):1029-1038.
16. Bus SA, Maas M, Cavanagh PR, et al. Plantar fat-pad displacement in neuropathic diabetic patients with toe deformity. Diabetes Care. 2004; 27(10):2376-2381
17. Mickle KJ, Munro BJ, Lord SR, et al. Soft tissue thickness under the metatarsal heads is reduced in older people with toe deformities. J Orthoped Res. 2011; 29(7):1042-1046.
18. Bus SA, Maas M, de Lange A, et al. Elevated plantar pressures in neuropathic diabetic patients with claw/hammer toe deformity. J Biomech. 2005; 38(9):1918-1925.
19. Mueller MJ, Hastings M, Commean, PK, et al. Forefoot structural predictors of plantar pressures during walking in people with diabetes and peripheral neuropathy. J Biomech. 2003; 36(7):1009-1017.
20. Garcia CA, Hoffman SL, Hastings MK, et al. Effect of metatarsal phalangeal joint extension on plantar soft tissue stiffness and thickness. Foot. 2008; 18(2):61-67.
21. Teoh JC, Shim VPW, Lee T. Quantification of plantar soft tissue changes due to aging in various metatarsophalangeal joint angles with realistic tissue deformation. J Biomech. 2014; 47(12):3043-3049.
22. Huijberts MSP, Schaper NC, Schalkwijk CG. Advanced glycation end products and diabetic foot disease. Diabetes/Metab Res Rev. 2008; 24(Suppl 1):S19–24.
23. Lee AT, Cerami A. Role of glycation in aging. Ann New York Acad Sci. 1992; 663(1):63-70.
24. Kilhovd BK, Julsrud Berg T, Birkeland KI, et al. Serum levels of advanced glycation end products are increased in patients with type 2 diabetes and coronary heart disease. Diabetes Care. 1999; 22(9):1543-1548.
25. Goh SY, Cooper ME. The role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab. 2008; 93(4):1143-1152.
26. Wolffenbuttel BHR, Boulanger CM, Crijns FRL, et al. Breakers of advanced glycation end products restore large artery properties in experimental diabetes. Proceed Nat Acad Sci. 1998; 95(8):4630-4634.
27. Fu MX, Wells-Knecht KJ, Blackledge JA, et al. Glycation, glycoxidation, and cross-linking of collagen by glucose: kinetics, mechanisms, and inhibition of late stages of the Maillard reaction. Diabetes. 1994; 43(5):676-683.
28. Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2001; 44(2):129-146.
29. Li Y, Fessel G, Georgiadis M, Snedeker JG. Advanced glycation end-products diminish tendon collagen fiber sliding. Matrix Biol. 2013; 32(3):169-177.
30. Klaesner JW, Hastings MK, Zou D, et al. Plantar tissue stiffness in patients with diabetes mellitus and peripheral neuropathy. Arch Phys Med Rehab. 2002; 83(12):1796-1801.
31. Pai S, Ledoux WR. The compressive mechanical properties of diabetic and non-diabetic plantar soft tissue. J Biomech. 2010; 43(9):1754-1760.
32. Sun JH, Cheng BK, Zheng YP, et al. Changes in the thickness and stiffness of plantar soft tissues in people with diabetic peripheral neuropathy. Arch Phys Med Rehab. 2011; 92(9):1484-1489.
33. Jan YK, Lung CW, Cuaderes E, et al. Effect of viscoelastic properties of plantar soft tissues on plantar pressures at the first metatarsal head in diabetics with peripheral neuropathy. Physiol Measurement. 2012; 34(1):53.
34. Hsu CC, Tsai WC, Shau YW, et al. Altered energy dissipation ratio of the plantar soft tissues under the metatarsal heads in patients with type 2 diabetes mellitus: a pilot study. Clin Biomech. 2007; 22(1):67-73.
35. Armstrong DG, Peters EJG, Athanasiou KA, Lavery LA. Is there a critical level of plantar foot pressure to identify patients at risk for neuropathic foot ulceration? J Foot Ankle Surg. 1998; 37(4):303-307.
36. Lavery LA, Armstrong DG, Wunderlich RP, et al. Predictive value of foot pressure assessment as part of a population-based diabetes disease management program. Diabetes Care. 2003; 26(4):1069-1073.
37. Owings TM, Apelqvist J, Stenström A, et al. Plantar pressures in diabetic patients with foot ulcers which have remained healed. Diabetic Medicine. 2009; 26(11):1141-1146.
38. Barn R, Waaijman R, Nollet F, et al. Predictors of barefoot plantar pressure during walking in patients with diabetes, peripheral neuropathy and a history of ulceration. PLOS One. 2015; 10(2):e0117443.
39. Zheng YP, Choi YKC, Wong K, et al. Biomechanical assessment of plantar foot tissue in diabetic patients using an ultrasound indentation system. Ultrasound Med Biol. 2000; 26(3):451-456.
40. Chen WM, Shim VPW, Park SB, Lee T. An instrumented tissue tester for measuring soft tissue property under the metatarsal heads in relation to metatarsophalangeal joint angle. J Biomech. 2011; 44(9):1801-1804.
41. Deschamps K, Matricali GA, Roosen P, et al. Comparison of foot segmental mobility and coupling during gait between patients with diabetes mellitus with and without neuropathy and adults without diabetes. Clin Biomech. 2013; 28(7):813-819.
42. DiLiberto FE, Tome J, Baumhauer JF, et al. Individual metatarsal and forefoot kinematics during walking in people with diabetes mellitus and peripheral neuropathy. Gait Posture. 2015; 42(4):435-441.
43. Molines-Barroso RJ, Lázaro-Martínez JL, Aragón-Sánchez FJ, et al. Forefoot ulcer risk is associated with foot type in patients with diabetes and neuropathy. Diabetes Res Clin Pract. 2016; 114:93-98.
44. Cheing GLY, Chau RMW, Kwan RLC, et al. Do the biomechanical properties of the ankle–foot complex influence postural control for people with Type 2 diabetes? Clinical Biomech. 2013; 28(1):88-92.
45. Guney AF, Karaman VI, Kafadar IH, et al. Biomechanical properties of Achilles tendon in diabetic vs. non-diabetic patients. Exper Clin Endocrin Diabetes. 2015; 123(7):428-432.
46. Caselli A, Pham H, Giurini JM, et al. The forefoot-to-rearfoot plantar pressure ratio is increased in severe diabetic neuropathy and can predict foot ulceration. Diabetes Care. 2002; 25(6):1066-1071.
47. Guldemond NA, Leffers P, Walenkamp GHIM, et al. Prediction of peak pressure from clinical and radiological measurements in patients with diabetes. BMC Endocrine Disorders. 2008; 8(1):16.
48. Cronin NJ, Peltonen J, Ishikawa M, et al. Achilles tendon length changes during walking in long-term diabetes patients. Clin Biomech. 2010; 25(5):476-482.
49. Giacomozzi C, D’ambrogi E, Uccioli L, Macellari V. Does the thickening of Achilles tendon and plantar fascia contribute to the alteration of diabetic foot loading? Clin Biomech. 2005; 20(5):532-539.
50. Evranos B, Idilman I, Ipek A, et al. Real-time sonoelastography and ultrasound evaluation of the Achilles tendon in patients with diabetes with or without foot ulcers: a cross sectional study. J Diabetes Complications. 2015; 29(8):1124-1129.
51. D’ambrogi E, Giacomozzi C, Macellari V, Uccioli L. Abnormal foot function in diabetic patients: the altered onset of Windlass mechanism. Diabetic Med. 2005; 22(12):1713-1719.
52. Courtemanche R, Teasdale N, Boucher P, et al. Gait problems in diabetic neuropathic patients. Arch Phys Med Rehab. 1996; 77(9):849-855.
53. Kwon OY, Minor SD, Maluf KS, Mueller MJ. Comparison of muscle activity during walking in subjects with and without diabetic neuropathy. Gait Posture. 2003; 18(1):105-113.
54. Macklin K, Healy A, Chockalingam N. The effect of calf muscle stretching exercises on ankle joint dorsiflexion and dynamic foot pressures, force and related temporal parameters. Foot. 2012; 22(1):10-17.
55. Craig ME, Duffin AC, Gallego PH, et al. Plantar fascia thickness, a measure of tissue glycation, predicts the development of complications in adolescents with type 1 diabetes. Diabetes Care. 2008; 31(6):1201-1206.
56. Mueller MJ. Identifying patients with diabetes mellitus who are at risk for lower-extremity complications: use of Semmes-Weinstein monofilaments. Phys Ther. 1996; 76(1):68-71.
57. Dahmen R, Haspels R, Koomen B, Hoeksma AF. Therapeutic footwear for the neuropathic foot: an algorithm. Diabetes Care. 2001; 24(4):705-709.
58. Wunderlich RP, Armstrong DG, Husain KS, Lavery LA. Defining loss of protective sensation in the diabetic foot. Adv Skin Wound Care. 1998; 11(3):123-128.
59. Feng Y, Schlösser FJ, Sumpio BE. The Semmes Weinstein monofilament examination as a screening tool for diabetic peripheral neuropathy. J Vasc Surg. 2009; 50(3):675-682.
60. Kamei N, Yamane K, Nakanishi S, et al. Effectiveness of Semmes–Weinstein monofilament examination for diabetic peripheral neuropathy screening. J Diabetes Complications. 2005; 19(1):47-53.
61. Bourcier ME, Ullal J, Parson HK, et al. Diabetic peripheral neuropathy: how reliable is a homemade 1-g monofilament for screening? A case-control study of sensitivity, specificity, and comparison with standardized sensory modalities. J Family Practice. 2006; 55(6):505-509.
62. Wang F, Zhang J, Yu J, et al. Diagnostic accuracy of monofilament tests for detecting diabetic peripheral neuropathy: a systematic review and meta-analysis. J Diabetes Res. 2017; epub Oct. 8.
63. Andersen H, Gjerstad MD, Jakobsen J. Atrophy of foot muscles. A measure of diabetic neuropathy. Diabetes Care. 2004; 27(10):2382-2385.
64. Greenman RL, Khaodhiar L, Lima C, et al. Foot small muscle atrophy is present before the detection of clinical neuropathy. Diabetes Care. 2005; 28(6):1425-1430.
65. Lin YC, Wu J, Baltzis D, et al. MRI assessment of regional differences in phosphorus-31 metabolism and morphological abnormalities of the foot muscles in diabetes. J Magnetic Resonance Imaging. 2016; 44(5):1132-1142.
66. Van Schie CHM, Vermigli C, Carrington AL, Boulton AJM. Muscle weakness and foot deformities in diabetes. Diabetes Care. 2004; 27(7):1668-1673.
67. Kwon OY, Tuttle LJ, Johnson JE, Mueller MJ. Muscle imbalance and reduced ankle joint motion in people with hammer toe deformity. Clin Biomech. 2009; 24(8):670-675.
68. Ledoux WR, Shofer JB, Smith DG, et al. Relationship between foot type, foot deformity, and ulcer occurrence in the high-risk diabetic foot. J Rehab Res Devel. 2005; 42(5):665-672.
69. Bus SA, Maas M, Michels RPJ, Levi M. Role of intrinsic muscle atrophy in the etiology of claw toe deformity in diabetic neuropathy may not be as straightforward as widely believed. Diabetes Care. 2009; 32(6):1063-1067.
70. De Camargo Neves SI, Crema Noguera G, Almeida Bacarin T, et al. Medial longitudinal arch change in diabetic peripheral neuropathy. Acta Ortopédica Brasileira. 2009; 17(1):13-16.
71. Bittel DC, Bittel AJ, Tuttle LJ, et al. Adipose tissue content, muscle perfor-mance and physical function in obese adults with type 2 diabetes mellitus and peripheral neuropathy. J Diabetes Complications. 2015; 29(2):250-257.
72. Hastings MK, Mueller MJ, Woodburn J, et al. Acquired midfoot deformity and function in individuals with diabetes and peripheral neuropathy. Clin Biomech. 2016; 32:261-267.
73. Paul L, Ellis BM, Leese GP, et al. The effect of a cognitive or motor task on gait parameters of diabetic patients, with and without neuropathy. Diabetic Med. 2009; 26(3):234-239.
74. Malindu Eranga F, Crowther RG, Lazzarini PA, et al. Gait parameters of people with diabetes-related neuropathic plantar foot ulcers. Clin Biomech. 2016; 37:98-107.
75. Petrovic M, Deschamps K, Verschueren SM, et al. Is the metabolic cost of walking higher in people with diabetes? J Appl Physiol. 2016; 120(1):55-62.
76. Strotmeyer ES, De Rekeneire N, Schwartz AV, et al. The relationship of reduced peripheral nerve function and diabetes with physical performance in old-er white and black adults. Diabetes Care. 2008; 31(9):1767-1772.
77. Eneida Yuri S, Gomes AA, Butugan MK, Sacco ICN. Muscle fiber conduction velocity in different gait phases of early and late-stage diabetic neuropathy. J Electromyogr Kinesiol. 2016; 30:263-271.
78. Allen MD, Major B, Kimpinski K, et al. Skeletal muscle morphology and contractile function in relation to muscle denervation in diabetic neuropathy. J Appl Physiol. 2014; 116(5):545–552.
79. Hsu WC, Liu MW, Lu TW. Biomechanical risk factors for tripping during obstacle—Crossing with the trailing limb in patients with type II diabetes mellitus. Gait Posture. 2016; 45:103-109.
80. Abboud RJ, Rowley DI, Newton RW. Lower limb muscle dysfunction may contribute to foot ulceration in diabetic patients. Clin Biomech. 2000; 15(1):37-45.
81. Hsu WC, Lu TW, Liu MW. Lower limb joint position sense in patients with type II diabetes mellitus. Biomed Engin. 2009; 21(4):271-278.
82. Paxton RJ, Feldman-Kothe C, Trabert MK, et al. Postural steadiness and ankle force variability in peripheral neuropathy. Motor Control. 2016; 20(3):266-284.
83. Lim KB, Kim DJ, Noh JH, et al. Comparison of balance ability between patients with type 2 diabetes and with and without peripheral neuropathy. PM&R. 2014; 6(3):209-214.
84. Priplata AA, Patritti BL, Niemi JB, et al. Noise‐enhanced balance control in patients with diabetes and patients with stroke. Ann Neurol. 2006; 59(1):4-12.
85. Geertzen JHB. Effects of vibrating insoles on standing balance in diabetic neuropathy. J Rehabil Res Devel. 2008; 45(9):1441.
86. Morrison S, Colberg SR, Mariano M, et al. Balance training reduces falls risk in older individuals with type 2 diabetes. Diabetes Care. 2010; 33(4):748-750.
87. Allet L, Armand S, De Bie RA, et al. The gait and balance of patients with diabetes can be improved: a randomised controlled trial. Diabetologia. 2010; 53(3):458-466.
