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The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer
DIAB-6346; No. of Pages 7 diabetes research and clinical practice xxx (2015) xxx–xxx
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Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer Piergiorgio Francia a,*, Giuseppe Seghieri b, Massimo Gulisano a, Alessandra De Bellis c, Sonia Toni d, Anna Tedeschi c, Roberto Anichini c a
Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy Tuscany Regional Health Agency (ARS), Florence, Italy c Diabetes Unit, USL 3, St. Jacopo Hospital, Pistoia, Italy d Diabetes Unit, Meyer Children’s Hospital, Florence, Italy b
article info
abstract
Article history:
Aims: Evaluation of how ankle joint mobility (AJM) can be useful in the identification of
Received 16 December 2014
patients with diabetes at risk of foot ulcer (FU).
Received in revised form
Methods: Plantar and dorsal flexion of foot were evaluated using an inclinometer in 87
19 February 2015
patients (54 type 2 and 33 type 1), and 35 healthy sex- and age-matched control subjects.
Accepted 3 April 2015
Patients with diabetes were followed up for diagnosis of FU over the next 8 years and
Available online xxx
subsequently, patients were subdivided into: those without a history of FU (18 type 1 and 33 type 2), those who had a history of FU detected before baseline evaluation (14 type 2)
Keywords:
and those who had history of first ulceration detected by the 8th year of the evaluation
Diabetic foot
period (7 type 2).
Ankle range of motion
Results: Aging and diabetes caused a significant reduction in mobility of each of the move-
Limited joint mobility
ments investigated ( p < 0.001), whereas after adjusting for the confounding effect of age,
Foot ulcer risk scale
diabetes specifically reduced plantar flexion ( p < 0.0001). AJM was significantly lower in those with history of previous FU compared to all the other groups ( p < 0.001). The first ulceration was detected in the same foot presenting lower AJM in 17 of the 22 subjects with diabetes with history of ulcer (77.27%). Conclusions: Diabetes and aging reduce AJM although diabetes seems to reduce plantar flexion to a more specific extent. Reduced AJM is mostly associated with a previous history of FU. The evaluation of AJM is a valid and reliable ulcer risk scale that indicates which foot is at higher ulcer risk. # 2015 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author at: Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy. Tel.: +39 0557944577; fax: +39 0557944586. E-mail address: [email protected] (P. Francia). http://dx.doi.org/10.1016/j.diabres.2015.04.001 0168-8227/# 2015 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Francia P, et al. The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer. Diabetes Res Clin Pract (2015), http://dx.doi.org/10.1016/j.diabres.2015.04.001
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1.
Introduction
Diabetic foot is one of the most ominous complications of diabetes [1]. Neuropathy, vasculopathy, minor foot trauma and foot deformities are individually or altogether the main etiological factors of diabetic foot ulcers. However, other factors, such as limited joint mobility (LJM) of the ankle, may contribute to the genesis of diabetic foot ulcer [2–5]. LJM is an important risk factor for plantar foot ulcer because it may induce abnormal distribution of foot plantar pressure in static and dynamic conditions [5–9]. In particular, diabetes may exacerbate reduced joint mobility that typically occurs with aging [10–12]. In clinical practice, the effect of diabetes on joint mobility may be difficult to prevent because it can induce a painless deficit in joint range of motion (ROM) with an insidious onset followed by asymptomatic progressive deterioration [5,7,13]. At the same time, it is well known that LJM can occur a few years after diagnosis, even in young patients [10,13–15]. It has been reported that LJM increases in relation to the diabetic peripheral neuropathy level in patients with diabetes and is related to the increase in peak plantar foot pressure, integral pressure–time and shear forces [5–7,9,16,17]. The significant correlation of LJM of the first metatarso-phalangeal, subtalar and ankle joints and diabetes is well known [7,16,18]. The overall thickening and stiffness in the main tendons and ligaments of the foot-ankle complex, i.e. the plantar fascia and Achilles tendons, can influence joint function and limit ankle ROM and foot joint mobility [19,20]. Reduced joint ROM can impair the performance of large movements such as gait in subjects with diabetes. [8,9,21,22]. Ankle and metatarsophalangeal LJM alter foot propulsion and increase the load at the metatarsal heads [7,22]. The accumulation of forefoot loads in orthostatic posture and during the whole stance phase increases the risk of tissue breakdown [5–8,17,23]. Since LJM and ROM alterations can be evident in subjects with diabetes prior to the development of clinical neuropathy [7,9,24], it has been suggested for many years that the assessment of ankle and foot joint mobility can help to define
the risk of ulcer and to monitor a patient’s condition [6,7,9,18,25–28]. The aim of this study was to verify joint mobility changes during the lifetime of patients with diabetes and to use ankle joint mobility (AJM) to monitor the risk of foot ulcer. In addition, we investigated the presence of a direct relationship between limited AJM and a higher risk of foot ulcer in the same patient.
2.
Patients and methods
Patients attending the St. Jacopo Hospital of Pistoia, Italy were consecutively recruited for evaluation of AJM in plantar and dorsal flexion by means of an inclinometer. A total of 87 patients with diabetes, 14 young and 73 adults, of whom 54 type 2 and 19 type 1, were evaluated and compared with 35 healthy control subjects, of whom 21 were adults and 14 were youths. Both young groups (patients with diabetes and control subjects) ranged in age from 11 to 17 years. The detailed clinical characteristics of the study participants are shown in Tables 1 and 2. Exclusion criteria were: presence of current foot ulcer at baseline, orthopedic and/or surgical complications or Charcot foot. Data were collected regarding type of diabetes, diabetes duration, and presence of neuropathy. The physical examination included foot inspection, evaluation of neuropathy by means of vibration perception threshold (VPT), 10 G Semmens Weinstein monofilament, and evaluation of patellar and ankle reflexes. Evaluation of vasculopathy included determination of peripheral pulses and transcutaneous oxygen tension (TcpO2). Hemoglobin A1c was measured at baseline by high performance liquid chromatography HPLC method. Weight, height and body mass index (BMI) were measured. BMI was expressed as body weight in kilograms divided by height in meters squared (kg/m2). When patients had foot ulcers in the past or during follow-up, they were graded according to the University of Texas Wound Classification System [29]. Patients with diabetes were followed up from the diagnosis of foot ulcer and for 8 years thereafter. The adult group was
Table 1 – Main characteristics and dorsal, plantar and total AJM (expressed as degrees) in type 1 patients with diabetes compared to age- and sex-matched controls. Type 1 diabetes mellitus patients
Controls
Age (yrs) Diabetes duration (yrs) Gender (M/F) HbA1c (% – mmol/mol) BMI (kg/m2) Neuropathy at baseline no. (%) Plantar flexion (8 – degree) Dorsal flexion (8) Total AJM (8) D Right–left (8)
Youths (n = 14)
Adults (n = 21)
Youths (n = 14)
Adults (n = 19)
14.4 1.8 – 6/8 – 21.5 2.7a – 38.5 4.2a 114.4 10.8a 152.9 13.2a 2.7 1.9
61.3 4.7 – 10/11 – 26.6 3.7b – 37.6 7.4 94.5 18.1a 131.6 19.2a 6.5 4.3
14.1 1.0 6.1 4.6a 7/7 7.2 0.7 to 56 6a 20.4 2.5a 0 28.0 5.6b 91.2 12.3b 120.8 15.3b 5.0 3.7
52.1 12.8 26.5 11.0b 10/9 8.3 1.4 to 67 11.b 28.1 3.5b 6 (31) 32.7 9.8 76.7 22.8b 109.4 27.3b 5.8 6.3
p-Value*
<0.0001 <0.0001 <0.02 <0.0001 – <0.0005 <0.0001 <0.0001 NS
Values are mean SD. By one-way ANOVA. a vs. b in young and adult groups: p < 0.001. *
Please cite this article in press as: Francia P, et al. The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer. Diabetes Res Clin Pract (2015), http://dx.doi.org/10.1016/j.diabres.2015.04.001
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Table 2 – Dorsal, plantar and total AJM (expressed as degrees) in controls and in type 2 diabetes mellitus patients.
Age (yrs) Diabetes duration (yr) Gender (M/F) HbA1c (% – mmol/mol) BMI (kg/m2) Neuropathy at baseline No. (%) Plantar flexion (8 – degree) Dorsal flexion (8) Total AJM (8) D Right/left (8)
Controls (n = 21)
Type 2 diabetes mellitus patients (n = 54)
p-Value
61.3 4.7 – 10/11 – 26.6 3.7 – 37.6 7.4 94.5 18.1 131.6 19.2 6.6 4.3
63.7 6.6 14.2 9.6 30/24 7.7 1.1 to 61 9 28.7 4.3 25 (46) 25.7 10 73.3 21.4 99.0 26.0 6.5 6.1
NS – – – <0.05 – <0.001 <0.001 <0.001 <0.001
subdivided into: patients without history of foot ulcer (18 adults with T1DM, and 33 adults with type 2 diabetes), 14 patients with type 2 diabetes had history of foot ulcer detected before baseline evaluation and 7 adults with type 2 diabetes had history of first ulceration detected by the 8th year of the evaluation period. Only one patient with type 1 diabetes had the first ulceration during the follow-up period. Nine patients with prior history of ulcer had digital ulcers, three had metatarsal and two had plantar heel ulcers. Of those patients who developed ulcers at follow-up, five had digital ulcers, one had metatarsal and one had heel ulcer.
2.1.
Determination of joint mobility
AJM was evaluated using an inclinometer (Fabrication Enterprises Inc, White Plains, NY, USA) [30–32] with the patient lying supine, the subtalar joint in neutral position and the feet over the edge of the bed. The knee, corresponding to the evaluated ankle, was extended and put over a rigid 5-cm high support. The maximum range of dorsal and plantar flexion was determined after drawing with the demographic pen the fifth metatarsal bone and positioning the inclinometer along the diaphysis of the bone, with one extremity put on the distal condylus. All measurements were performed by the same observer, recording the mean of three consecutive readings. All participants and parents or guardians of the young subjects were informed of the purpose of the study and its experimental procedures before obtaining written informed consent and enrollment in the study. The protocol and consent form were approved by the Ethics committees of the local Health Area Unit of Pistoia Hospital. The study was performed in accordance with the declaration of Helsinki.
2.2.
Statistical analysis
Data were reported as mean SD or percentage, as appropriate. ROM values were expressed in degree and reported as mean SD. Comparisons between groups were analyzed by ANOVA, using the Bonferroni correction for multiple comparisons. Comparisons between frequencies were performed using the Chi-square method. Multiple regression analysis was performed using the presence of foot ulcer as the dependent variable and all variables which appeared to be significantly correlated with foot ulceration as confounding factors for univariate analysis. A two-tailed p value of <0.05 was regarded as statistically significant. All calculations were
performed using the SPSS system for Windows Version 16.0 (SPSS Inc., Chicago, IL, USA).
3.
Results
As shown in Table 1, in young and adult patients with type 1 diabetes, total AJM and dorsal flexion were significantly higher than in respective controls while plantar flexion was not significantly different between adult groups. Plantar, dorsal and total AJM were significantly reduced in patients with type 2 diabetes (Table 2). Analysis of data about development of foot ulcer at follow-up demonstrated that, when compared to matched controls, the reduction in plantar flexion and total AJM were evident in patients with no ulceration, those with foot ulcer and those with history of previous ulceration at baseline (Table 3). Dorsal flexion was reduced in those who developed foot ulcer by the 8-year follow up and in those with history of previous foot ulcer, with these latter having the most evident reduction in plantar flexion (Table 3). No differences were noted as to D – right–left difference. Since age and body weight had, as expected, a major effect on reduction of plantar and dorsal flexion as well as on total AJM, we performed a multivariate analysis with ankle joint mobility as dependent variable and age, presence of diabetes, sex and BMI as covariates in both type 1 and type 2 patients with diabetes and in controls. From this analysis, diabetes remained significantly associated with dorsal, plantar and total AJM reduction in both types of diabetes. Female gender was associated with a significant reduction in both dorsal flexion and total AJM, while age was not significantly associated with a plantar flexion decrease in either group of diabetic patients, after adjusting for body weight (Table 4). Finally, considering the whole cohort of diabetic patients (type 1 and type 2), age was the only variable significantly associated ( p < 0.001) with reduction of dorsal, plantar flexion and total AJM, in a model with BMI, Hba1c and diabetes duration as other covariates (data not shown).
4.
Discussion
The etiopathogenesis of LJM in diabetes has not been fully explained, although the main causal factor seems to be the effect of metabolic disorders on the increased stiffness of skin, joint capsule, ligaments and tendons [13,33].
Please cite this article in press as: Francia P, et al. The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer. Diabetes Res Clin Pract (2015), http://dx.doi.org/10.1016/j.diabres.2015.04.001
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Table 3 – Main characteristics and dorsal, plantar and total AJM (expressed as degrees) in type 2 diabetic patients compared to age- and sex-matched controls. FU: follow-up period. Controls (n = 21)
Age (yrs) Gender (M/F) Diabetes duration (yr) HbA1c (% – mmol/mol) BMI (kg/m2) Neuropathy at baseline no. (%) Plantar flexion (8 – degree) Dorsal flexion (8) Total AJM (8) D Right/left (8)
61.3 4.7 10/11 – – 26.6 3.7 – 37.6 7.4a 94.5 18.1a 131.6 19.2a 6.6 4.3
Type 2 diabetes mellitus patients (n = 54) No foot ulceration (n = 33)
Foot ulceration at final FU (n = 7)
History of previous ulceration (n = 14)
62.5 5.8 17/16 12.9 8.1a 7.6 1.1 to 59 9 29.3 4.5a 9 (27)a 27.1 11.0b 80.8 21.4d 107.9 26.1b,d 5.4 6.0
65.3 6.6 4/3 22.4 12.5b 7.9 1.2 to 63 10 25.5 2.4b 4 (57) 26.9 7.3b 66.7 10.4b 93.6 9.3b 8.8 5.7
65.5 8.3 9/5 13.4 10.0 7.9 1.3 to 63 11 28.8 4.1 12 (86)b* 21.7 7.7b 58.9 17.5b,c 80.6 21.1b,c 7.9 6.4
p-Value
NS – <0.04 NS <0.04 <0.001 <0.0001 <0.0001 <0.0001 NS
a vs. b; c vs. d: p < 0.001. By Chi-square method.
*
Table 4 – Multivariate analysis considering dorsiflexion, plantar flexion and total AJM (expressed as degrees) as dependent variables and age, BMI, diabetes and sex as independent variables in type 1 (a) or type 2 (b) patients with diabetes. b-Regression coefficient (a) Ankle dorsal flexion Intercept Age Diabetes (Y/N) BMI Sex Ankle plantar flexion Intrercept Age Diabetes (Y/N) BMI Sex Total AJM Intercept Age Diabetes (Y/N) BMI Sex (b) Ankle dorsal flexion Intercept Age Diabetes (Y/N) BMI Sex Ankle plantar flexion Intercept Age Diabetes (Y/N) BMI Sex Total AJM Intercept Age Diabetes (Y/N) BMI Sex
p-Value
p-Model
97.46 0.48 21.22 0.28 12.14
0.0001 0.0001 0.0001 NS 0.002
0.0001
33.66 0.02 7.14 0.17 0.52
0.0001 NS 0.0005 NS NS
0.012
134.89 0.49 27.28 0.26 12.86
0.0001 0.0006 0.0001 NS 0.005
0.0001
135.04 0.77 19.25 0.07 3.28
0.0002 0.05 0.0008 NS NS
0.0008
16.73 0.16 13.54 0.53 1.95
NS NS 0.0001 NS NS
0.0001
152.11 0.61 32.30 0.58 1.12
0.0003 NS 0.0001 NS NS
0.0001
The main biochemical abnormality in joint tissue of diabetic patients is the excess of non-enzymatic glycosylation of collagen, with production of advanced glycation and products (AGEs), which in turn lead to an increase in collagen cross-links. The increase in inter- and intra-molecular crosslinking of collagen fibers alters, in turn, the mechanical properties of these tissues with a decrease in elasticity and tensile strength, causing mechanical stiffness [13,34,35]. As a matter of fact, a deficit of AJM is often present in subjects with diabetes, even without clinically relevant complications, who are matched for age and compared with healthy controls [5,7,9]. At the same time it is well known that joint mobility decreases as individuals grow older [12]. Thus, the reduction of AJM in older patients, when compared to young healthy subjects, is the result of at least two main factors: aging and diabetes [12,13,36]. To verify the joint mobility changes over time in a population with diabetes and to define how AJM can be useful in the monitoring of foot ulcer risk we have studied a cohort of 87 patients with diabetes and monitored the occurrence of foot ulcers over the next 8 years. The population with diabetes, both youths and adults, had significantly reduced AJM in flexion–extension compared to healthy, age-matched subjects. A comparison of all adults with diabetes with age-matched healthy adults shows that the population with diabetes has a strong and significant AJM reduction in each movement evaluated. Nonetheless, the young subjects with diabetes have significantly reduced mobility of each of the movements investigated when compared to the young control group. This result suggests that diabetes, even in young people, has important negative effects on AJM, and indicates that although the proper management of young patients with type 1 diabetes can be difficult, it is important for the prevention of chronic complications of the disease. Furthermore, female patients with type 1 diabetes are more inclined to impairment in both dorsal and total AJM than males, probably due to the other gender risk factors such as women’s tendency to wear high-heeled shoes. The method we used in this study indicates that aging particularly affects ankle dorsal
Please cite this article in press as: Francia P, et al. The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer. Diabetes Res Clin Pract (2015), http://dx.doi.org/10.1016/j.diabres.2015.04.001
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flexion in comparison with ankle plantar flexion, which was significantly associated only with diabetes. In addition, within the type 2 diabetic group, plantar flexion was significantly lower in patients with type 2 diabetes than in those with type 1. This result may further reinforce the finding that diabetes, even if it has a later onset, induces a more severe deficit of plantar flexion mobility which may be due to the simultaneous shortening of the Achilles tendon and thickening of the plantar fascia, both of which are present in diabetes [37]. In other words, diabetes would primarily cause the known alterations in the connective tissue, i.e., of the Achilles tendon and plantar fascia, which seem to act together in altering foot loading and ultimately inducing the typical foot posture in plantar flexion [38,39]. Other than to verify the presence of a typical negative trend in AJM in the population with diabetes, a further aim of this study was to evaluate the presence of mobility values critical to foot ulcer risk. Our results, in patients with history of foot ulcer detected before or after baseline evaluation, show that AJM decreases in the population at high risk of ulcer. Nonetheless, the group which developed foot ulceration, in contrast with those who did not, had significantly reduced AJM in dorsal flexion compared to the non-diabetic adult control group. This result suggests that AJM reduction in dorsal flexion could be considered as an additional indicator of foot ulcer risk. Plantar flexion mobility rather than dorsiflexion was already strongly reduced, even in elderly diabetic patients who did not develop an ulcer over the next 8 years, confirming the strong relationship of this parameter to diabetes. The possible negative effect on reduced AJM possibly exerted by prior immobilization or offloading maneuvers in patients with previous foot ulcer, can be excluded by the similar D right–left differences in AJM observed in all patients’ groups, indicating that any impairment in AJM was bilaterally uniform (see Table 3). The results of this study indicate, moreover, that there is a significant mobility difference in dorsal and total ankle flexion between patients with type 2 diabetes with a history of ulcer and those without. A history of previous foot ulceration is associated with an even higher reduction in plantar and dorsal mobility, compared with those who will develop an ulcer in the next 8 years after the measurement. This suggests an earlier impairment in AJM among those with past history of foot ulceration. It is interesting to note that previous history of foot ulceration is associated with the highest rate of peripheral neuropathy. The small number of patients in our study did not allow us to draw plausible correlations between the location of ulcers developed at follow-up and the type of reduction in AJM. Peripheral neuropathy was present only in adult patients, independently of the type of diabetes, and mostly in those with previous history of foot ulcers, suggesting that it is strongly associated with limited LJM. In the total population, 25 of 54 patients with type 2 diabetes (46.3%) had neuropathy at baseline according to described criteria. This is not so different from the expected rate [39–41]. The prevalence increased to 57% in the group of patients who developed foot ulcers and to 86% in those with previous foot ulcer, from baseline. The relatively low prevalence of neuropathy at baseline in patients who later developed foot ulcer, compared to those who had previously experienced it, can be explained
5
by the fact that the detrimental effect of AJM reduction as well as of muscle strength abnormalities can occur even before the appearance of clinical neuropathy [9,42,43]. In this study, aging seems to affect the difference in mobility between the two ankles as evidenced by the significant difference in young and elderly non-diabetic subjects, while diabetes does not seem to have as important an effect. This does not mean that the different joint mobility between the two ankles is a less interesting parameter. In agreement with Mueller’s [6] retrospective analysis, 17 out of 22 of our cases (77.27%) with a history of ulceration and who had a subsequent foot ulcer, had the first episode in the same foot with lower AJM. For this reason, an evaluation of joint mobility difference between the two ankles in a single patient may help to indicate which foot is at higher risk.
4.1.
Limitations and strengths of the study
Our study has some limitations: AJM was determined with a unique method without using other methodological imaging approaches which are useful for excluding the occurrence of possible concomitant joint pathologies. In addition, our study has the limitation of being observational and not designed in a time-course manner. In spite of these limitations, however, our study has some important strengths: it covers a population of patients with both type 1 and type 2 diabetes. Finally, our patients are well matched as to sex and age and we have followed them up for 8 years, which is a relatively lengthy time.
5.
Conclusion
Ankle joint mobility in flexion–extension is significantly lower in adult and young patients with diabetes than in healthy controls. Diabetes seems to affect particularly ankle plantar flexion while dorsal flexion seems to be mostly affected by aging. Within the diabetic population investigated, ankle joint mobility decreases as the risk of ulceration increases: however, the group at highest risk seems to be those with a history of previous foot ulceration, indicating that reduced AJM represents an early risk factor of foot ulceration, at least in people with type 2 diabetes mellitus. All this suggests that ankle joint mobility is a useful indicator for monitoring ulcerative risk in patients with diabetes, other than being able to indicate which foot is at higher ulcerative risk. In conclusion, measuring AJM should be performed early in individuals with diabetes.
Conflict of interest None.
Acknowledgements The authors thanks Mrs G. Iannone for technical and administrative support and Mary Forrest for revising the English.
Please cite this article in press as: Francia P, et al. The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer. Diabetes Res Clin Pract (2015), http://dx.doi.org/10.1016/j.diabres.2015.04.001
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on ankle muscle performance in people with diabetes mellitus and a neuropathic plantar ulcer. Phys Ther 2005;85:34–43; (b) Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 1993;43:817–24. [40] Abbott CA, Carrington AL, Ashe H, Bath S, Every LC, Griffiths J, et al. The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort. Diabet Med 2002;19:377–84.
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Contents available at ScienceDirect
Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer Piergiorgio Francia a,*, Giuseppe Seghieri b, Massimo Gulisano a, Alessandra De Bellis c, Sonia Toni d, Anna Tedeschi c, Roberto Anichini c a
Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy Tuscany Regional Health Agency (ARS), Florence, Italy c Diabetes Unit, USL 3, St. Jacopo Hospital, Pistoia, Italy d Diabetes Unit, Meyer Children’s Hospital, Florence, Italy b
article info
abstract
Article history:
Aims: Evaluation of how ankle joint mobility (AJM) can be useful in the identification of
Received 16 December 2014
patients with diabetes at risk of foot ulcer (FU).
Received in revised form
Methods: Plantar and dorsal flexion of foot were evaluated using an inclinometer in 87
19 February 2015
patients (54 type 2 and 33 type 1), and 35 healthy sex- and age-matched control subjects.
Accepted 3 April 2015
Patients with diabetes were followed up for diagnosis of FU over the next 8 years and
Available online xxx
subsequently, patients were subdivided into: those without a history of FU (18 type 1 and 33 type 2), those who had a history of FU detected before baseline evaluation (14 type 2)
Keywords:
and those who had history of first ulceration detected by the 8th year of the evaluation
Diabetic foot
period (7 type 2).
Ankle range of motion
Results: Aging and diabetes caused a significant reduction in mobility of each of the move-
Limited joint mobility
ments investigated ( p < 0.001), whereas after adjusting for the confounding effect of age,
Foot ulcer risk scale
diabetes specifically reduced plantar flexion ( p < 0.0001). AJM was significantly lower in those with history of previous FU compared to all the other groups ( p < 0.001). The first ulceration was detected in the same foot presenting lower AJM in 17 of the 22 subjects with diabetes with history of ulcer (77.27%). Conclusions: Diabetes and aging reduce AJM although diabetes seems to reduce plantar flexion to a more specific extent. Reduced AJM is mostly associated with a previous history of FU. The evaluation of AJM is a valid and reliable ulcer risk scale that indicates which foot is at higher ulcer risk. # 2015 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author at: Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy. Tel.: +39 0557944577; fax: +39 0557944586. E-mail address: [email protected] (P. Francia). http://dx.doi.org/10.1016/j.diabres.2015.04.001 0168-8227/# 2015 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Francia P, et al. The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer. Diabetes Res Clin Pract (2015), http://dx.doi.org/10.1016/j.diabres.2015.04.001
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1.
Introduction
Diabetic foot is one of the most ominous complications of diabetes [1]. Neuropathy, vasculopathy, minor foot trauma and foot deformities are individually or altogether the main etiological factors of diabetic foot ulcers. However, other factors, such as limited joint mobility (LJM) of the ankle, may contribute to the genesis of diabetic foot ulcer [2–5]. LJM is an important risk factor for plantar foot ulcer because it may induce abnormal distribution of foot plantar pressure in static and dynamic conditions [5–9]. In particular, diabetes may exacerbate reduced joint mobility that typically occurs with aging [10–12]. In clinical practice, the effect of diabetes on joint mobility may be difficult to prevent because it can induce a painless deficit in joint range of motion (ROM) with an insidious onset followed by asymptomatic progressive deterioration [5,7,13]. At the same time, it is well known that LJM can occur a few years after diagnosis, even in young patients [10,13–15]. It has been reported that LJM increases in relation to the diabetic peripheral neuropathy level in patients with diabetes and is related to the increase in peak plantar foot pressure, integral pressure–time and shear forces [5–7,9,16,17]. The significant correlation of LJM of the first metatarso-phalangeal, subtalar and ankle joints and diabetes is well known [7,16,18]. The overall thickening and stiffness in the main tendons and ligaments of the foot-ankle complex, i.e. the plantar fascia and Achilles tendons, can influence joint function and limit ankle ROM and foot joint mobility [19,20]. Reduced joint ROM can impair the performance of large movements such as gait in subjects with diabetes. [8,9,21,22]. Ankle and metatarsophalangeal LJM alter foot propulsion and increase the load at the metatarsal heads [7,22]. The accumulation of forefoot loads in orthostatic posture and during the whole stance phase increases the risk of tissue breakdown [5–8,17,23]. Since LJM and ROM alterations can be evident in subjects with diabetes prior to the development of clinical neuropathy [7,9,24], it has been suggested for many years that the assessment of ankle and foot joint mobility can help to define
the risk of ulcer and to monitor a patient’s condition [6,7,9,18,25–28]. The aim of this study was to verify joint mobility changes during the lifetime of patients with diabetes and to use ankle joint mobility (AJM) to monitor the risk of foot ulcer. In addition, we investigated the presence of a direct relationship between limited AJM and a higher risk of foot ulcer in the same patient.
2.
Patients and methods
Patients attending the St. Jacopo Hospital of Pistoia, Italy were consecutively recruited for evaluation of AJM in plantar and dorsal flexion by means of an inclinometer. A total of 87 patients with diabetes, 14 young and 73 adults, of whom 54 type 2 and 19 type 1, were evaluated and compared with 35 healthy control subjects, of whom 21 were adults and 14 were youths. Both young groups (patients with diabetes and control subjects) ranged in age from 11 to 17 years. The detailed clinical characteristics of the study participants are shown in Tables 1 and 2. Exclusion criteria were: presence of current foot ulcer at baseline, orthopedic and/or surgical complications or Charcot foot. Data were collected regarding type of diabetes, diabetes duration, and presence of neuropathy. The physical examination included foot inspection, evaluation of neuropathy by means of vibration perception threshold (VPT), 10 G Semmens Weinstein monofilament, and evaluation of patellar and ankle reflexes. Evaluation of vasculopathy included determination of peripheral pulses and transcutaneous oxygen tension (TcpO2). Hemoglobin A1c was measured at baseline by high performance liquid chromatography HPLC method. Weight, height and body mass index (BMI) were measured. BMI was expressed as body weight in kilograms divided by height in meters squared (kg/m2). When patients had foot ulcers in the past or during follow-up, they were graded according to the University of Texas Wound Classification System [29]. Patients with diabetes were followed up from the diagnosis of foot ulcer and for 8 years thereafter. The adult group was
Table 1 – Main characteristics and dorsal, plantar and total AJM (expressed as degrees) in type 1 patients with diabetes compared to age- and sex-matched controls. Type 1 diabetes mellitus patients
Controls
Age (yrs) Diabetes duration (yrs) Gender (M/F) HbA1c (% – mmol/mol) BMI (kg/m2) Neuropathy at baseline no. (%) Plantar flexion (8 – degree) Dorsal flexion (8) Total AJM (8) D Right–left (8)
Youths (n = 14)
Adults (n = 21)
Youths (n = 14)
Adults (n = 19)
14.4 1.8 – 6/8 – 21.5 2.7a – 38.5 4.2a 114.4 10.8a 152.9 13.2a 2.7 1.9
61.3 4.7 – 10/11 – 26.6 3.7b – 37.6 7.4 94.5 18.1a 131.6 19.2a 6.5 4.3
14.1 1.0 6.1 4.6a 7/7 7.2 0.7 to 56 6a 20.4 2.5a 0 28.0 5.6b 91.2 12.3b 120.8 15.3b 5.0 3.7
52.1 12.8 26.5 11.0b 10/9 8.3 1.4 to 67 11.b 28.1 3.5b 6 (31) 32.7 9.8 76.7 22.8b 109.4 27.3b 5.8 6.3
p-Value*
<0.0001 <0.0001 <0.02 <0.0001 – <0.0005 <0.0001 <0.0001 NS
Values are mean SD. By one-way ANOVA. a vs. b in young and adult groups: p < 0.001. *
Please cite this article in press as: Francia P, et al. The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer. Diabetes Res Clin Pract (2015), http://dx.doi.org/10.1016/j.diabres.2015.04.001
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Table 2 – Dorsal, plantar and total AJM (expressed as degrees) in controls and in type 2 diabetes mellitus patients.
Age (yrs) Diabetes duration (yr) Gender (M/F) HbA1c (% – mmol/mol) BMI (kg/m2) Neuropathy at baseline No. (%) Plantar flexion (8 – degree) Dorsal flexion (8) Total AJM (8) D Right/left (8)
Controls (n = 21)
Type 2 diabetes mellitus patients (n = 54)
p-Value
61.3 4.7 – 10/11 – 26.6 3.7 – 37.6 7.4 94.5 18.1 131.6 19.2 6.6 4.3
63.7 6.6 14.2 9.6 30/24 7.7 1.1 to 61 9 28.7 4.3 25 (46) 25.7 10 73.3 21.4 99.0 26.0 6.5 6.1
NS – – – <0.05 – <0.001 <0.001 <0.001 <0.001
subdivided into: patients without history of foot ulcer (18 adults with T1DM, and 33 adults with type 2 diabetes), 14 patients with type 2 diabetes had history of foot ulcer detected before baseline evaluation and 7 adults with type 2 diabetes had history of first ulceration detected by the 8th year of the evaluation period. Only one patient with type 1 diabetes had the first ulceration during the follow-up period. Nine patients with prior history of ulcer had digital ulcers, three had metatarsal and two had plantar heel ulcers. Of those patients who developed ulcers at follow-up, five had digital ulcers, one had metatarsal and one had heel ulcer.
2.1.
Determination of joint mobility
AJM was evaluated using an inclinometer (Fabrication Enterprises Inc, White Plains, NY, USA) [30–32] with the patient lying supine, the subtalar joint in neutral position and the feet over the edge of the bed. The knee, corresponding to the evaluated ankle, was extended and put over a rigid 5-cm high support. The maximum range of dorsal and plantar flexion was determined after drawing with the demographic pen the fifth metatarsal bone and positioning the inclinometer along the diaphysis of the bone, with one extremity put on the distal condylus. All measurements were performed by the same observer, recording the mean of three consecutive readings. All participants and parents or guardians of the young subjects were informed of the purpose of the study and its experimental procedures before obtaining written informed consent and enrollment in the study. The protocol and consent form were approved by the Ethics committees of the local Health Area Unit of Pistoia Hospital. The study was performed in accordance with the declaration of Helsinki.
2.2.
Statistical analysis
Data were reported as mean SD or percentage, as appropriate. ROM values were expressed in degree and reported as mean SD. Comparisons between groups were analyzed by ANOVA, using the Bonferroni correction for multiple comparisons. Comparisons between frequencies were performed using the Chi-square method. Multiple regression analysis was performed using the presence of foot ulcer as the dependent variable and all variables which appeared to be significantly correlated with foot ulceration as confounding factors for univariate analysis. A two-tailed p value of <0.05 was regarded as statistically significant. All calculations were
performed using the SPSS system for Windows Version 16.0 (SPSS Inc., Chicago, IL, USA).
3.
Results
As shown in Table 1, in young and adult patients with type 1 diabetes, total AJM and dorsal flexion were significantly higher than in respective controls while plantar flexion was not significantly different between adult groups. Plantar, dorsal and total AJM were significantly reduced in patients with type 2 diabetes (Table 2). Analysis of data about development of foot ulcer at follow-up demonstrated that, when compared to matched controls, the reduction in plantar flexion and total AJM were evident in patients with no ulceration, those with foot ulcer and those with history of previous ulceration at baseline (Table 3). Dorsal flexion was reduced in those who developed foot ulcer by the 8-year follow up and in those with history of previous foot ulcer, with these latter having the most evident reduction in plantar flexion (Table 3). No differences were noted as to D – right–left difference. Since age and body weight had, as expected, a major effect on reduction of plantar and dorsal flexion as well as on total AJM, we performed a multivariate analysis with ankle joint mobility as dependent variable and age, presence of diabetes, sex and BMI as covariates in both type 1 and type 2 patients with diabetes and in controls. From this analysis, diabetes remained significantly associated with dorsal, plantar and total AJM reduction in both types of diabetes. Female gender was associated with a significant reduction in both dorsal flexion and total AJM, while age was not significantly associated with a plantar flexion decrease in either group of diabetic patients, after adjusting for body weight (Table 4). Finally, considering the whole cohort of diabetic patients (type 1 and type 2), age was the only variable significantly associated ( p < 0.001) with reduction of dorsal, plantar flexion and total AJM, in a model with BMI, Hba1c and diabetes duration as other covariates (data not shown).
4.
Discussion
The etiopathogenesis of LJM in diabetes has not been fully explained, although the main causal factor seems to be the effect of metabolic disorders on the increased stiffness of skin, joint capsule, ligaments and tendons [13,33].
Please cite this article in press as: Francia P, et al. The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer. Diabetes Res Clin Pract (2015), http://dx.doi.org/10.1016/j.diabres.2015.04.001
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Table 3 – Main characteristics and dorsal, plantar and total AJM (expressed as degrees) in type 2 diabetic patients compared to age- and sex-matched controls. FU: follow-up period. Controls (n = 21)
Age (yrs) Gender (M/F) Diabetes duration (yr) HbA1c (% – mmol/mol) BMI (kg/m2) Neuropathy at baseline no. (%) Plantar flexion (8 – degree) Dorsal flexion (8) Total AJM (8) D Right/left (8)
61.3 4.7 10/11 – – 26.6 3.7 – 37.6 7.4a 94.5 18.1a 131.6 19.2a 6.6 4.3
Type 2 diabetes mellitus patients (n = 54) No foot ulceration (n = 33)
Foot ulceration at final FU (n = 7)
History of previous ulceration (n = 14)
62.5 5.8 17/16 12.9 8.1a 7.6 1.1 to 59 9 29.3 4.5a 9 (27)a 27.1 11.0b 80.8 21.4d 107.9 26.1b,d 5.4 6.0
65.3 6.6 4/3 22.4 12.5b 7.9 1.2 to 63 10 25.5 2.4b 4 (57) 26.9 7.3b 66.7 10.4b 93.6 9.3b 8.8 5.7
65.5 8.3 9/5 13.4 10.0 7.9 1.3 to 63 11 28.8 4.1 12 (86)b* 21.7 7.7b 58.9 17.5b,c 80.6 21.1b,c 7.9 6.4
p-Value
NS – <0.04 NS <0.04 <0.001 <0.0001 <0.0001 <0.0001 NS
a vs. b; c vs. d: p < 0.001. By Chi-square method.
*
Table 4 – Multivariate analysis considering dorsiflexion, plantar flexion and total AJM (expressed as degrees) as dependent variables and age, BMI, diabetes and sex as independent variables in type 1 (a) or type 2 (b) patients with diabetes. b-Regression coefficient (a) Ankle dorsal flexion Intercept Age Diabetes (Y/N) BMI Sex Ankle plantar flexion Intrercept Age Diabetes (Y/N) BMI Sex Total AJM Intercept Age Diabetes (Y/N) BMI Sex (b) Ankle dorsal flexion Intercept Age Diabetes (Y/N) BMI Sex Ankle plantar flexion Intercept Age Diabetes (Y/N) BMI Sex Total AJM Intercept Age Diabetes (Y/N) BMI Sex
p-Value
p-Model
97.46 0.48 21.22 0.28 12.14
0.0001 0.0001 0.0001 NS 0.002
0.0001
33.66 0.02 7.14 0.17 0.52
0.0001 NS 0.0005 NS NS
0.012
134.89 0.49 27.28 0.26 12.86
0.0001 0.0006 0.0001 NS 0.005
0.0001
135.04 0.77 19.25 0.07 3.28
0.0002 0.05 0.0008 NS NS
0.0008
16.73 0.16 13.54 0.53 1.95
NS NS 0.0001 NS NS
0.0001
152.11 0.61 32.30 0.58 1.12
0.0003 NS 0.0001 NS NS
0.0001
The main biochemical abnormality in joint tissue of diabetic patients is the excess of non-enzymatic glycosylation of collagen, with production of advanced glycation and products (AGEs), which in turn lead to an increase in collagen cross-links. The increase in inter- and intra-molecular crosslinking of collagen fibers alters, in turn, the mechanical properties of these tissues with a decrease in elasticity and tensile strength, causing mechanical stiffness [13,34,35]. As a matter of fact, a deficit of AJM is often present in subjects with diabetes, even without clinically relevant complications, who are matched for age and compared with healthy controls [5,7,9]. At the same time it is well known that joint mobility decreases as individuals grow older [12]. Thus, the reduction of AJM in older patients, when compared to young healthy subjects, is the result of at least two main factors: aging and diabetes [12,13,36]. To verify the joint mobility changes over time in a population with diabetes and to define how AJM can be useful in the monitoring of foot ulcer risk we have studied a cohort of 87 patients with diabetes and monitored the occurrence of foot ulcers over the next 8 years. The population with diabetes, both youths and adults, had significantly reduced AJM in flexion–extension compared to healthy, age-matched subjects. A comparison of all adults with diabetes with age-matched healthy adults shows that the population with diabetes has a strong and significant AJM reduction in each movement evaluated. Nonetheless, the young subjects with diabetes have significantly reduced mobility of each of the movements investigated when compared to the young control group. This result suggests that diabetes, even in young people, has important negative effects on AJM, and indicates that although the proper management of young patients with type 1 diabetes can be difficult, it is important for the prevention of chronic complications of the disease. Furthermore, female patients with type 1 diabetes are more inclined to impairment in both dorsal and total AJM than males, probably due to the other gender risk factors such as women’s tendency to wear high-heeled shoes. The method we used in this study indicates that aging particularly affects ankle dorsal
Please cite this article in press as: Francia P, et al. The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer. Diabetes Res Clin Pract (2015), http://dx.doi.org/10.1016/j.diabres.2015.04.001
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flexion in comparison with ankle plantar flexion, which was significantly associated only with diabetes. In addition, within the type 2 diabetic group, plantar flexion was significantly lower in patients with type 2 diabetes than in those with type 1. This result may further reinforce the finding that diabetes, even if it has a later onset, induces a more severe deficit of plantar flexion mobility which may be due to the simultaneous shortening of the Achilles tendon and thickening of the plantar fascia, both of which are present in diabetes [37]. In other words, diabetes would primarily cause the known alterations in the connective tissue, i.e., of the Achilles tendon and plantar fascia, which seem to act together in altering foot loading and ultimately inducing the typical foot posture in plantar flexion [38,39]. Other than to verify the presence of a typical negative trend in AJM in the population with diabetes, a further aim of this study was to evaluate the presence of mobility values critical to foot ulcer risk. Our results, in patients with history of foot ulcer detected before or after baseline evaluation, show that AJM decreases in the population at high risk of ulcer. Nonetheless, the group which developed foot ulceration, in contrast with those who did not, had significantly reduced AJM in dorsal flexion compared to the non-diabetic adult control group. This result suggests that AJM reduction in dorsal flexion could be considered as an additional indicator of foot ulcer risk. Plantar flexion mobility rather than dorsiflexion was already strongly reduced, even in elderly diabetic patients who did not develop an ulcer over the next 8 years, confirming the strong relationship of this parameter to diabetes. The possible negative effect on reduced AJM possibly exerted by prior immobilization or offloading maneuvers in patients with previous foot ulcer, can be excluded by the similar D right–left differences in AJM observed in all patients’ groups, indicating that any impairment in AJM was bilaterally uniform (see Table 3). The results of this study indicate, moreover, that there is a significant mobility difference in dorsal and total ankle flexion between patients with type 2 diabetes with a history of ulcer and those without. A history of previous foot ulceration is associated with an even higher reduction in plantar and dorsal mobility, compared with those who will develop an ulcer in the next 8 years after the measurement. This suggests an earlier impairment in AJM among those with past history of foot ulceration. It is interesting to note that previous history of foot ulceration is associated with the highest rate of peripheral neuropathy. The small number of patients in our study did not allow us to draw plausible correlations between the location of ulcers developed at follow-up and the type of reduction in AJM. Peripheral neuropathy was present only in adult patients, independently of the type of diabetes, and mostly in those with previous history of foot ulcers, suggesting that it is strongly associated with limited LJM. In the total population, 25 of 54 patients with type 2 diabetes (46.3%) had neuropathy at baseline according to described criteria. This is not so different from the expected rate [39–41]. The prevalence increased to 57% in the group of patients who developed foot ulcers and to 86% in those with previous foot ulcer, from baseline. The relatively low prevalence of neuropathy at baseline in patients who later developed foot ulcer, compared to those who had previously experienced it, can be explained
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by the fact that the detrimental effect of AJM reduction as well as of muscle strength abnormalities can occur even before the appearance of clinical neuropathy [9,42,43]. In this study, aging seems to affect the difference in mobility between the two ankles as evidenced by the significant difference in young and elderly non-diabetic subjects, while diabetes does not seem to have as important an effect. This does not mean that the different joint mobility between the two ankles is a less interesting parameter. In agreement with Mueller’s [6] retrospective analysis, 17 out of 22 of our cases (77.27%) with a history of ulceration and who had a subsequent foot ulcer, had the first episode in the same foot with lower AJM. For this reason, an evaluation of joint mobility difference between the two ankles in a single patient may help to indicate which foot is at higher risk.
4.1.
Limitations and strengths of the study
Our study has some limitations: AJM was determined with a unique method without using other methodological imaging approaches which are useful for excluding the occurrence of possible concomitant joint pathologies. In addition, our study has the limitation of being observational and not designed in a time-course manner. In spite of these limitations, however, our study has some important strengths: it covers a population of patients with both type 1 and type 2 diabetes. Finally, our patients are well matched as to sex and age and we have followed them up for 8 years, which is a relatively lengthy time.
5.
Conclusion
Ankle joint mobility in flexion–extension is significantly lower in adult and young patients with diabetes than in healthy controls. Diabetes seems to affect particularly ankle plantar flexion while dorsal flexion seems to be mostly affected by aging. Within the diabetic population investigated, ankle joint mobility decreases as the risk of ulceration increases: however, the group at highest risk seems to be those with a history of previous foot ulceration, indicating that reduced AJM represents an early risk factor of foot ulceration, at least in people with type 2 diabetes mellitus. All this suggests that ankle joint mobility is a useful indicator for monitoring ulcerative risk in patients with diabetes, other than being able to indicate which foot is at higher ulcerative risk. In conclusion, measuring AJM should be performed early in individuals with diabetes.
Conflict of interest None.
Acknowledgements The authors thanks Mrs G. Iannone for technical and administrative support and Mary Forrest for revising the English.
Please cite this article in press as: Francia P, et al. The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer. Diabetes Res Clin Pract (2015), http://dx.doi.org/10.1016/j.diabres.2015.04.001
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