Performance of the lower limb musculoskeletal system in patients with different degree of diabetic ulcer risk

Background The objective of the study was to determine the correlation between the biomechanical parameters: ankle and foot muscle strength, range of motion (ROM) at ankle joint (AJ), subtalar joint (SJ) and rst metatarsophalangeal joint (I MTP) in patients with different diabetic ulcer risk assessed by IWGDF 2019 Guidance risk stratication system. Method A cross-sectional study included 100 diabetic patients. The patients were classied into 4 risk categories of development of diabetic foot ulcer (DFU) applying IWGDF Guidelines 2019 stratication risk system. The function of ten foot and ankle muscles was evaluated by manual muscle testing and application of the Michigan Diabetic Neuropathy Score (MDNS) system. The range of motion ROM at the ankle, subtalar and rst metatarsophalangeal joint was measured with a goniometer. The risk assessment was done applying IWGDF Guidelines 2019 stratication risk system. To test the statistical signicance the ANOVA test was applied.


Background
Diabetic foot ulcer (DFU), as one of the most severe diabetic complications of the lower extremities, will be developed in up to 34% of persons with diabetes during their lifetime [1]. Amputation, as the most serious complication of diabetes in the lower extremities, takes place every 20 seconds somewhere in the world [2]. Although the data on the burden of diabetes mellitus are very obvious, this complication is underestimated in scienti c and clinical practice compared to other diabetes complications [3].
DFU is usually developed as a result of several risk factors present in people with diabetes, with diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) usually playing a central role in this process [4]. DFU development is related to an abnormal pattern of plantar pressure distribution caused by alterations in the foot rollover process due to loss of foot-ankle muscular strength, range of motion (ROM), and nervous function, as their integrity is needed to enable proper load absorption on the plantar surface [5][6][7][8][9]. The ROM at joints is altered in diabetes [10] and can result in abnormally high intrinsic plantar pressures and lead to plantar ulceration, but only as a contributor to other risk factors [11]. There is evidence that elevated hyperglycaemia accelerates the loss in muscle size and strength, especially in the distal muscles of the lower leg [13]. Weakness evaluated by manual testing has been reported to be an independent risk factor for the development of foot ulcers, probably because muscle weakness at the ankle and knee in DPN leads to the abnormal application of pressure at the sole during gait due to alterations of the biomechanics of the feet [13,14].
Considering the above facts about the DFU burden, the health care profession's noble quote is worth stating: "prevention is better than the treatment of the disease," the earlier the intervention, the better the outcome. [15]. Unfortunately, prevention does not receive top priority when it comes to diabetes. Two cornerstones of the preventative foot care are 1) to implement knowledge in daily foot care, and b) to improve treatment adherence [16]. According to the recommendations outlined in the Guidelines on the prevention and management of diabetic foot disease published by the International Working Group on the Diabetic Foot (IWGDF), identifying patients who are at risk for ulceration is the rst step in prevention [4]. For the purpose of at-risk patient identi cation, the IWGDF has established a strati cation system that also directs care interventions. Key risk factors include loss of protective sensation (LOPS), PAD, and foot deformity, history of foot ulceration, and any level of lower extremity amputations [17].
Relationship between the performances of the musculoskeletal system of the lower limb and the assessed DFU risk in diabetic patients has not yet been explored, however, it was assumed that the overall DFU risk is positively correlated with the decline of the lower extremity muscle performance. If there is a positive relationship between these two variables, it might be possible to establish an additional set of preventative measures to decrease the complications of DM of the lower extremities by using an active rehabilitative approach with the goal of muscle strengthening and increasing the mobility at the joint.

Objective
The objective of the study was to determine the correlation between the biomechanical parameters: ankle and foot muscle strength, ROM at ankle, subtalar and rst metatarsophalangeal joint in patients with different diabetic ulcer risk assessed by IWGDF 2019 Guidance risk strati cation system.

2.1.Design and subjects
Patients with both types of diabetes mellitus who are registered with primary health care physicians during 2014 were the subject of this cross-sectional study. The sample of 100 patients who entered the study consecutively consisted of patients from ten primary health care clinics who were seen for their insulin needs or for their oral hypoglycemic medication management. The survey included medical records review, interview for the sake of detailed with the medical history , as well as measurement and testing of the patients. Medical records were the source of personal data, data on the type of DM, duration and management of the disease up to date, and HbA1c values not older than six months. [18,19]. The clinical examinations were performed routinely by the same examiner.

2.2.Diabetc foot risk assessment
Using the data obtained from comprehensive examinations and the history taking, the patients were classi ed into risk categories applying IWGDF Guidelines 2019 strati cation risk system as follows: the risk category 0 -patients with normal ndings; the risk category 1 (low risk) -patients with LOPS or PAD; the risk category 2 (moderate risk) -patients with LOPS + PAD, or LOPS + foot deformity or PAD + foot deformity; the risk category 3 (high risk) -patients who had LOPS or PAD, and one or more of the following: history of a foot ulcer, lower-extremity amputation, and end-stage renal disease [17].
LOPS was assessed as follows: vibration testing using a 128-Hz tuning fork, tests of pinprick sensation on the dorsum of foot, tactile sensation test using cotton wool on the dorsum of foot, and Achilles ankle re ex assessment [20,21]. Vibratory sensation was tested over the tip of the great toe bilaterally.
Abnormal vibratory sensation was de ned as a situation when the patient loses vibratory sensation while the examiner still perceives it with a 128-Hz tuning fork on the tip of the toe. A disposable pin was applied just proximal to the toenail on the dorsal surface of the hallux, with just enough pressure to deform the skin. The inability to perceive pinprick over either hallux was considered to be an abnormal test result. Ankle re exes were tested using the tendon hammer, with the patient kneeling on a chair. Absence of ankle re ex either at rest or upon the reinforcement, was regarded as an abnormal result [22]. Inability to perceive the cotton wool touch on the dorsal surface of the foot was regarded as an abnormal test result. One or more abnormal tests would suggest LOPS, while at least two regular tests (and no abnormal test) would rule out LOPS [20].
Vascular examination included palpation of the posterior tibial and dorsalis pedis pulses bilaterally, which was characterized as either "present" or "absent" [22][23][24]. The presence of two or less of the four pedal pulses indicated PAD [23]. In patients with amputations, the result on the one leg counted twice.

2.3.Foot strenght assessment
Foot and ankle muscle function were evaluated with manual muscle testing (MMT) on the dominant leg. The same scoring system, which is used in the MDNS, was applied [18,25,26]. MMT indicates the ability of the tested muscle to produce an active movement against the examiner's resistance. MMT was done on a dominant leg. Score 0 was for normal muscle strength, 1 for mild, 2 for severe muscle weakness, and 3 for complete loss of muscle strength. As described, the muscle score (MS) was obtained for each set of muscles that were examined. The minimum score was 0 (normal strength in 10 muscles) and the maximum score was 30 (complete loss of strength in 10 muscles). Higher scores indicated increased muscle weakness [25,27]. In described testing positions, the manual clinical assessment [28] was performed for the following muscles: triceps surae, tibialis anterior, interosseus, lumbrical, exor hallucis brevis, extensor digitorum brevis, extensor digitorum longus, exor digitorum brevis, extensors hallucis longus, and extensor hallucis brevis [8].

2.4.Range of motion measurement
The joint mobility at the ankle joint (AJ), subtalar joint (SJ), and rst metatarsophalangeal joint (I MTP) was determined using a goniometer on the dominant lower limb [29,30]. ROM at the AJ was measured with the patient in a supine position. The passive maximum range of talar exion and extension were measured and the sum of the two values was recorded as ROM at the AJ [29]. The ROM at SJ was measured with the patient in a prone position. The maximum range of calcaneal inversion and eversion were measured and added up to indicate the ROM at the SJ. The range of passive extension to plantar exion at the I MTP was measured with the patient supine and the ROM at the I MTP was recorded as the sum of those two values [29,30].

2.5.Foot deformities assessment
The presence of deformities such as hammer toes, claw toes, prominent metatarsal heads, and high medial arch were assessed using a foot deformity score. Hammer toes were de ned as "a hyperextended metatarsophalangeal joint with a exion deformity of the proximal interphalangeal joint and hyperextension of the distal interphalangeal joint". Claw toes were de ned as "hyperextension of the metatarsophalangeal joints and exion of the proximal and distal interphalangeal joints". Prominent metatarsal heads were de ned as "any palpable plantar prominences of the metatarsal site of the foot".
Lastly, high medial arch was de ned as "an abnormally high medial longitudinal arch". A point was given for each deformity present to whatever degree, with a maximum score of 6 (3 for one leg) because subject could only score for one of the toe deformities. In patients with amputations, the result on the one leg counted twice [25,27]. Patient was de ned as having a deformity if he/she had a score of 2 or more.

Statistical analyses
The statistical analyses were done using the software package "IBM SPSS Statistics". For a statistical analysis continuous data were presented as means and standard deviations. To test the statistical signi cance between variables, the one-way ANOVA test were applied. The cut off for the signi cance of the results was p<0.05.

Results
In the sample of the 100 patients, there were more women (53%) than men (47%). The average age of the group was 61.91 years, SD ± 10.74, and the average diabetes duration was 12.25 years, SD ± 8.60. Based on the IWGDF Guidelines 2019 strati cation risk system, patients were classi ed into one of the risk categories. The largest number (51%) of patients were classi ed into risk category 0. 16% of patients were classi ed into risk category 1, 21% into risk category 2, and 12% of patients were classi ed into risk category 3. The average muscle strength in the patients who were classi ed into risk category 0 was 9.2, 13.9 for those in the risk category 1, 13.3 in the risk category 2, and 15.2 in the risk category 3, all of which are shown in Figure 1. The strength of ankle and foot muscles signi cantly declines with risk progression (F=9.37551, p=.0000).

ROM at ankle joint
The average ROM at AJ in the group of patients classi ed into risk category 0 was 49.3°, risk category 1 was 48.8°, risk category 2 was 45.5° and the risk category 3 was 44.6°, as shown in Figure 2. The average ROM at AJ in the groups of patients classi ed into different risk categories is not signi cantly different (F=.98757,p= .4020).

ROM at subtalar joint
The average ROM at SJ in the group of patients classi ed into risk category 0 was 37.8°, risk category 1 was 31.3°, risk category 2 was 35°, and the risk category 3 was 28.7°. The average ROM at SJ signi cantly declines with risk progression (F=5.53021, p=.0015), as shown in Figure 3 The presence of the LOPS is due to the presence of a certain degree of DPN and many studies proved a strong association between DPN and the loss of muscle strength [32][33][34][35]. The muscle atrophy in diabetic patients is most pronounced in distal parts of the lower leg indicating a length-dependent neuropathic process [10]. The presence of PAD is also one of the determining factors for classifying patients into risk category 1 and 2. Regensteiner found the correlation between the PAD with chronic changes in affected muscle morphology and its function. Muscles in the region affected by PAD has demonstrated denervation and a reduction in the cross-sectional area of type II muscle bers. In patients with PAD there is also a decrease in oxidative enzyme activities, more pronounced with increasing disease severity [36].
McDermott also con rmed that the PAD affects muscle strength, especially the distal lower extremity muscles [37]. Certain number of authors believe that there is a relationship between intrinsic foot muscle weakness caused by motor neuropathy and the development of foot deformities such as pes cavus, claw toe deformity, hammer toe deformity, and hallux valgus, however, this relationship has not been su ciently explored, especially regarding the muscle weakness level that affects the development of the deformities [38,39]. Patients classi ed into risk category 3 had ulcer or amputation in the history and the lowest muscular strength compared to patients classi ed into lower risk categories. Ulcers are most commonly of the neuropathic or neuro-ischemic origin [40] which means that the loss of muscle strength in patients classi ed in this risk category is primarily in uenced by a neuropathic [14,32,34] and/or ischemic process [36].The average ulcer healing time is 8 weeks [23] to 78 days [41], and in many cases the ulcer does not heal and pass into chronic wounds, which affects the mobility, loss of muscle bers, and consequently loss of muscle strength. As 80% of the cases of amputations are preceded by an ulcer, the period of inactivity in patients with an amputation can be very prolonged and affects accelerated muscle loss, strength reduction, and functional capacity [42].
The mean ROM value at AJ in the study group is not statistically signi cant, but it is worth noting that the average value of the ROM at AJ drops from the lower to the higher risk category. The average value of ROM at SJ in patients classi ed into risk category 0 is 37.8°, and in patients classi ed into risk category 3 is 28.75°. It has been proven that there is a statistically signi cant difference in the mean values of the ROM at SJ between risk categories. The average value of ROM at the I MTP joint in patients classi ed into risk category 0 is 78.6°, and in patients classi ed into risk category 3 is the smallest, and it is 57.92°. This study has proved a strong relationship between the average values of ROM at I MTP joint in patients classi ed into different risk categories. There are no studies that explored the relationship between the values of ROM in different risk categories for development of DM complications at lower extremities. The limited joint mobility (LJM) at AJ and I MTP joint have been identi ed as a causing factor of local pressure increase and ulcer formation in patients with DPN [43]. LJM and reduction of the elasticity of the ankle in diabetic patients develop due to three mechanisms: (1) collagen glycosylation based on the hyperglycemic state; (2) shortening of triceps bers, and (3) qualitative changes in connective tissue because of increasing in brous versus contractile tissue [44]. Lower ROM in patients classi ed into category 2 compared to the patients classi ed into the risk category 1 can be explained by the presence of additional qualitative changes in muscle tissue and formation of connective tissue due to ischemia in patients with PAD [36]. The lowest ROM in patients classi ed into category 3 characterized by history of ulcer or amputation can be explained by adaptive changes in the tissues resulting from the long-term inactivity of patients during the ulcer healing process, and more intensive tissue changes caused by hyperglycemia which primarily led to the onset of ulceration or amputation in these patients.
The main goals of physical therapy interventions in DM patients are to prevent complications, to reduce the effects of immobilization, to maintain functional capacity, and to minimize the onset of complications. Presently, in the majority of cases, physical therapies are applied when DFU and amputation have already occurred and only occasionally are used as preventative procedures [5][6][7]. This research highlights the signi cance of the continued surveillance and screening, along with some elements of biomechanical assessment of the feet in a primary care setting, intending to identify factors that can be in uenced by active measures to reduce the incidence of diabetic complications on the lower extremities [45].
The limitation of this study is the fact that overall physical activity and tness were not individually assessed as both parameters have impact on muscle strength. Assessment of the muscle strength is done using MMT which is more or less a subjective evaluation method. This weak spot in measurement objectivization is alleviated by utilization of a qualitative system used in MDNS which offers four grades of strength and measuring by the same examiner. The range of motion measurement is also performed by an examiner; however, the human error was minimized through high-quality preparation, including drawing lines from joint center using prongs. The use of subjective measure in the assessment of musculoskeletal system performance is justi ed when it is used meticulously and by a single examiner. Although many studies have shown a correlation between diabetes and some functions of the musculoskeletal system [25,27,29,30], there are no studies that evaluated the total risk for DFU development and performance, which presents another limitation in the area of methodology and the results themselves.

Conclusion
The risk for diabetic foot ulcer signi cantly correlates with decreased ankle and foot muscle strength, as well as decreased range of motion at the subtalar joint and rst metatarsophalangeal joint, but it does not correlate with the range of motion at the ankle. It is a huge scienti c and professional challenge to explore if an active approach through targeted physical therapy and rehabilitation procedures enhances the performance of the lower limb musculoskeletal system and thus slows down -or even stops progression of DM complications and reduces the risk of amputations. In conclusion, the simplicity and low cost of the assessment of the lower limb musculoskeletal performance could be an additional screening tool for of risk of developing DFU, mainly because its results could be the basis for another active preventative approach. Written informed consent was obtained from all participants.

Availability of data and material
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Funding
The authors received no nancial support for the research, authorship, and publication of this article.
Authors' contributions SNB and SJ made the conception and design of the study. SNB performed data acquisition and statistical analysis and drafted the manuscript. SJ and NT revised the manuscript. GT contributed to the study design and coordination and revised the manuscript. Co-authors agreed with the nalized submission. All authors read and approved the nal manuscript. Figure 1 Muscle strength and risk for diabetic foot ulceration Score 0 was for normal muscle strength, 1 for mild, 2

Figures
for severe muscle weakness and 3 for complete muscle loss of strength. Minimum score was 0 (normal strength in 10 muscles) and maximum score was 30. Muscle strength in groups of patients classi ed into different diabetic foot ulcer risk categories signi cantly declines with risk progression; p<0.05. Points represent the average muscle strength in the groups of diabetic patients classi ed into certain risk category followed by straight lines that represent their SDs.

Figure 2
The range of motion at the ankle joint and risk for diabetic foot ulceration The average range of motion (ROM) at ankle joint (AJ) in groups of patients classi ed into different diabetic foot ulcer risk categories does not signi cantly differ; p>0.05. Points represent the average ROM at AJ in the groups of diabetic patients classi ed into certain risk category followed by straight lines that represent their SDs.

Figure 3
The range of motion at the subtalar joint and risk for diabetic foot ulceration The average range of motion (ROM) at subtalar joint (SJ) in groups of patients classi ed into different diabetic foot ulcer risk categories signi cantly declines with risk progression; p<0.05. Points represent the average ROM at SJ in the groups of diabetic patients classi ed into certain risk category followed by straight lines that represent their SDs.

Figure 4
The range of motion at rst metatarsophalangeal joint and risk for diabetic foot ulceration The average range of motion (ROM) at rst metatarsophalangeal joint (I MTP) in groups of patients classi ed into different diabetic foot ulcer risk categories signi cantly declines with risk progression; p<0.05. Points represent the average ROM at I MTP in the groups of diabetic patients classi ed into certain risk category followed by straight lines that represent their SDs.