Plantar Pressure Changes and Correlating Risk Factors in Chinese Patients with Type 2 Diabetes: Preliminary 2-year Results of a Prospective Study.

I NTRODUCTION

In 2013, 382 million patients were suffering from diabetes worldwide, and it has been estimated that this number may surpass 592 million by 2035.[ 1 ] Previous studies have shown that lower leg amputations in diabetes patients account for more than 50% of all amputations and that two-thirds of these amputations may result from foot ulcerations.[ 2 ] As diabetic foot ulcerations constitute a major cause of lower leg amputations, ulcerations must be treated at early stages. Various factors may lead to ulceration development.[ 3 4 ] Several studies have shown that plantar pressure plays a major role in predicting foot ulcerations in diabetes patients.[ 3 5 6 7 ] The higher the peak plantar pressure level, the higher the commensurate risk of foot ulceration.[ 8 ] Diabetes patients have a different plantar pressure distribution than individuals without diabetes. We previously studied risk factors correlated with plantar pressure levels in Chinese patients with type 2 diabetes in a cross-sectional study which demonstrated that high plantar pressure levels in diabetes patients were correlated with weight, height, neuropathy symptom score (NSS), ankle-brachial index (ABI), sex, history of ulcer and callus, intima-media membrane of the lower limb blood vessels, and fasting blood glucose (FBG).[ 9 ] However, few prospective studies have examined plantar pressure changes in diabetes patients. In addition, there is little information available on correlating risk factors in Chinese patients with type 2 diabetes. This study aims to examine plantar pressure changes in Chinese patients with type 2 diabetes and to identify prospective factors related to plantar pressure changes in this patient population.

M ETHODS

Participant selection

This study was conducted based on Declaration of Helsinki principles and was approved by ethical committees of the local hospital. Written informed consent was obtained from all of the participants. According to preexperimental requirements, we should require at least 48 patients to participate in this study. Sixty-five diabetes patients were enrolled in the study from March of 2012 to August of 2012. These individuals were invited to participate in the second wave of the study 2 years later. The diabetes patients completed identical examinations at the baseline point and 2 years later. The inclusion criteria included: (1) Adults (aged ≥18 years); (2) diagnosis of type 2 diabetes; (3) no obvious gait abnormalities by visual inspection. Diagnosis of type 2 diabetes was confirmed through a review of laboratory data and medical records or via communication with the participants’ primary care physicians. The exclusion criteria included: (1) An active foot ulcer, foot deformity, foot surgical history, or individuals who were unable to walk unaided; (2) serious circulatory system disease (New York Heart Association functional Class III or IV), nephropathy (chronic kidney disease Class IV or V), hepatopathy (alanine transaminase or aspartate transaminase of higher than five times of the normal level), or hematopathy (leucocythemia, lymphadenoma, multiple myeloma and other diseases that impair quality of life and movement); (3) neuropathy, with the exception of diabetic neuropathy; and (4) severe mental illness (patients who could not complete the study examinations). Prior the study, the participants were questioned about their medical history and were subjected to a physical examination to exclude the presence of neurological disorders, with the exception of diabetic neuropathy. When a diagnosis could not be confirmed, we conducted electromyography, computed tomography, or magnetic resonance imaging tests. In addition to imaging studies, we invited doctors in a related clinical department to make diagnoses.

Data collection

We interviewed the participants to collect data on their demographic, height, and weight characteristics. We surveyed the participants regarding the presence or absence of several selected symptoms related to neuropathy to determine their NSS.[ 10 ] We recorded the height of shoe heels they always worn over the course of the study and noted the appearance of infections, ulcers, calluses, or blisters in the 2 years.

Dynamic plantar pressure levels were measured using the footscan gait system (RSscan International, Olen, Belgium). The participants walked barefoot across the sensor platform at 90–110% speed of the established speed before conducting our measurements. The plantar pressure data included the maximum force, maximum pressure, impulse, pressure-time integral and loading rate values under each region. These data were obtained from 10 parts of the foot (toe 1, the hallux; toe 2–5, the second to fifth toes; meta 1, the first metatarsal head; meta 2, the second metatarsal head; meta 3, the third metatarsal head; meta 4, the fourth metatarsal head; meta 5, the fifth metatarsal head; midfoot; medial heel, the medial portion of the heel; and lateral heel, the lateral portion of the heel).[ 9 ] No parameter difference between the left and right foot was found via the Wilcoxon signed ranks test ( P > 0.05). Therefore, only the left foot plantar pressure data were used for the following data analysis.

A portable continuous-wave Doppler device (ACC113; Huntleigh, Cardiff, Wales, United Kingdom) was used to measure systolic blood pressure levels for ABI.[ 11 ] A diagnostic iU22 ultrasound system (Philips Medical Systems, Bothell, WA, USA) was used to detect the intima-media membrane of lower limb blood vessels. Each sonography was performed by three operators who had more than 10 years of professional experience. Foot sensations were evaluated using a Semmes–Weinstein monofilament (10 g) test kit (SENSELab Aesthesiometer, Hörby, Sweden).[ 12 ] Sensory and motor nerve conduction velocities of the common peroneal nerve (SCV/MCV) measurements were carried out on a Nicolet Viking II electromyography (Nicolet Company, Madison, Wisconsin, USA) by two operators with more than 15 years of professional experience.

Hemoglobin A1c (HbA1c) levels were measured using a DCA Vantage analyzer (Siemens Medical Solutions Diagnostics, NY, USA). FBG, plasma cholesterol, and triglyceride concentrations were measured using an AU-2700 automated analyzer (Olympus, Mishima, Japan).

Statistical analysis

The data analysis was performed using SAS version 9.1.3 software (SAS Institute Inc., Cary, NC, USA). After testing for normality levels via Kolmogorov–Smirnov testing, all normally distributed data were expressed as the mean ± standard deviation, and other continuous data were expressed as median (interquartile range). Rank data and categorical data are expressed with numbers. A paired-samples t -test was used to evaluate any potential data differences between the normally distributed results at the baseline point and 2 years later, and a related-samples Wilcoxon Signed Rank test was used for abnormally distributed data and ranked data. A McNemar test was selected to evaluate any potential differences between categorical variables at the baseline point and 2 years later. Spearman's bivariate correlation was used to analyze the correlation between the significant plantar pressure variable changes and the significant clinical characteristics changes (including continuous data and ranked data). To evaluate the association between the plantar pressure changes and the categorical variables of clinical characteristics, a Mann–Whitney U -test for independent samples was used to compare the means of significant plantar pressure changes in different groups divided by the categorical variables. A value of P < 0.05 was considered as statistically significant.

Multiple linear regression analyses were conducted to analyze the correlation between clinical characteristic changes and plantar pressure variable changes. Low, weak, strong, and very strong correlations were denoted by β coefficient values of 0.00–0.25, 0.26–0.5, 0.51–0.75, and 0.76–1.00, respectively.[ 13 ]

R ESULTS

Sixty-five participants with type 2 diabetes were recruited to participate in this study. The clinical characteristics of the participants are summarized in Table 1 . The sample consisted of 36 women and 29 men, with a mean age of 59 years (range, 40–78 years) and a mean disease course of 8.20 years (range, 0.04–27.00 years).

Table 2 summarizes the plantar pressure parameters at the baseline point and 2 years later. Maximum force and pressure levels of the first to the fourth metatarsal head increased over the course of the 2 year study. The impulse of the third metatarsal head and the pressure-time integral value of the second to the fourth metatarsal head also increased. Impulse levels in the medial and lateral portions of the heel declined. The pressure-time integral of the lateral portion of the heel decreased as well. The participants showed no progression in the loading rate of each plantar region by the end of the 2 year study.

Correlations between the significant plantar pressure variable changes and the significant clinical characteristic changes (including continuous data and ranked data) are summarized in Table 3 , and the data without significant changes have been excluded. The plantar pressure variable changes showed a correlation with body mass index (BMI), HbA1c, FBG, cholesterol, triglyceride, the intima-media membrane of lower limb blood vessels, NSS, ABI, and SCV changes.

The results of Mann–Whitney U -tests for evaluating the association between the significant plantar pressure changes and the categorical variables of clinical characteristics are summarized in Table 4 . The plantar pressure changes showed association with the appearance of blisters, calluses, infections, and ulcers over the course of the study.

Multiple linear regressions that could explain the changes of the plantar pressure parameters are summarized in Table 5 . Plantar pressure parameters increased with BMI levels. HbA1c changes were positively correlated with maximum force and maximum pressure changes in the first metatarsal head. Cholesterol changes were positively correlated with impulse changes in the lateral portion of the heel and pressure-time integral changes in the second metatarsal head. ABI changes were positively correlated with maximum force changes in the first metatarsal head. NSS and SCV changes were positively correlated with some plantar pressure changes. Plantar pressure changes also had a correlation with the appearance of infections, blisters, and calluses over the course of the study.

D ISCUSSION

Our previous study showed that the sampled patients with type 2 diabetes exhibited higher maximum force, maximum pressure, impulse, and pressure-time integral levels in certain forefoot regions and lower maximum pressure levels under the lateral portion of the heel than the sample of participants without diabetes.[ 9 ] This complemented the conclusions of Pataky et al .[ 14 ] which showed an anterior displacement of weight-bearing during walking in the patients with diabetes. In the present study, we explored plantar pressure changes in patients with type 2 diabetes in 2 years, and found significant increases in plantar pressure levels in some forefoot portions, especially in the second to forth metatarsal heads. A decrease in heel impulse and pressure-time integral levels was also found. In addition, the diabetes patients exhibited an increase in plantar pressure levels and were at a risk of foot ulceration.[ 3 7 ] Ledoux et al .[ 15 ] previously reported that higher peak plantar pressure levels in metatarsals was significantly associated with greater ulcer risk. Our current study revealed high plantar pressure levels in the metatarsal heads. Based on these results, more attention should be paid to high plantar pressure levels and to increased plantar pressure level. Moreover, some associated precautions (e.g., the provision of suitable footwear, appropriate insoles, and hosiery) should be taken immediately.[ 16 17 ]

In our previous cross-sectional association study, weight was identified as a determining factor of high plantar pressure levels.[ 9 ] Flynn et al .[ 18 ] supported 20% of a participant's body weight using a Zuni exercise system and reported that plantar pressure levels can be reduced with weight loss. Arnold et al .[ 19 ] achieved an increase in weight through the application of a weighted vest and found that peak and mean plantar pressure levels increase depending on the plantar region involved. These two studies described immediately obtained weight changes through the use of instruments and found that planter pressure increased with weight increase. In the present study, we studied spontaneous changes in weight with no statistical significance and chose the variable of BMI to reflect the heaviness and lightness. We found that plantar pressure parameters increase with BMI levels. All of the above findings illustrate plantar pressure responses to an increase in weight or BMI. These results suggest that body weight management plays a critical role in preventing the development of high plantar pressure levels in diabetes patients. Accordingly, weight loss may play a role in reducing risks of developing foot ulcerations.

Ahroni et al .[ 20 ] demonstrated that HbA1c was not an independent factor of plantar pressure. In this study, FBG changes showed no correlation with plantar pressure variable changes. HbA1c changes were only positively correlated with maximum force and maximum pressure changes in the first metatarsal head, and the β was lower than 0.5. Therefore, the elevation of blood glucose concentrations above normal levels for patients with type 2 diabetes may not significantly and directly contribute to plantar pressure changes. However, the indirect impact of blood glucose levels remains unclear. Changes in cholesterol levels were related to impulse changes in the lateral portion of the heel and pressure-time integral changes in the second metatarsal head. However, triglyceride level changes were not correlated with plantar pressure changes. Few studies have been conducted on the association between the lipid and plantar pressure parameters. The correlation between blood glucose or lipid and plantar pressure warrants additional exploration.

Existing evidence suggests that diabetic neuropathy and high plantar pressure levels are closely related.[ 21 ] Patients with mild diabetic neuropathy show an increase in pressure-time integral levels in the forefoot, and plantar pressure changes are aggravated during later stages.[ 17 ] Payne et al .[ 22 ] reported that neuropathy-related variables played a key role in plantar pressure levels in a diabetic foot, and especially in the hallux, in the first metatarsal head, and in the heel region. The present study showed that NSS and SCV level changes were positively correlated with plantar pressure changes in diabetes patients. NSS and SCV measures are used to assess diabetic neuropathy from neuropathic symptoms and conduction velocities of large-diameter neurons, respectively.[ 23 24 ] However, no remarkable correlation was found between plantar pressure changes and foot sensation changes identified via our Semmes–Weinstein monofilament test, which serves as another method of diabetic neuropathy diagnosis.[ 25 ] The results of this study were consistent with those of our previous study, which demonstrated that NSS was associated with plantar pressure levels, but that foot sensations were not related to plantar pressure levels.[ 9 ] Based on the above findings, NSS and SCV may play more pivotal role in predicting plantar pressure changes than foot sensations.

Doppler arterial pressure and ABI levels are used to evaluate peripheral arterial diseases.[ 9 26 ] Pataky et al .[ 26 ] reported a relationship between plantar pressure and Doppler arterial pressure levels of both the tibial posterior and dorsalis pedis artery. In the present study, ABI changes were found to be related to maximum force changes in the first metatarsal head. Peripheral vascular diseases may also contribute to high plantar pressure levels. In this study, changes in the intima-media membrane of lower limb blood vessels showed no correlation with plantar pressure changes. The inconformity was attributed to several causes. First, the data were not primed to address the correlation, as the intima-media membrane examined in this study was the thickest intima-media membrane of lower limb blood vessels. Hence, an inevitable personal error resulted without a fixed position for measuring thickness levels, though all of participants were examined by the same expert operator. Second, the intima-media membrane of the lower limb blood vessels may play a less important role than the above peripheral vascular disease variables in predicting high plantar pressure levels.

Our preceding study proved that a history of foot ulcers was unrelated to plantar pressure levels.[ 20 ] We monitored the appearance of ulcers over the course of the study and showed that ulcers had no correlation with plantar pressure changes. These results indicated that the appearance of ulcers may not play a key role in the formation of high plantar pressure levels. One of Potter's studies noted that participants without calluses showed 25% lower pressure levels than those with calluses.[ 27 ] In this study, the appearance of calluses over the course of the study showed a relationship with plantar pressure changes in the second to the fourth metatarsal head. We must pay more attention to plantar pressure levels in diabetes patients with calluses. Moreover, we also studied the relationship between planter pressure changes and the appearance of blisters and infections over the course of the study. The appearance of blisters was related to the pressure-time integral in the second metatarsal head. The appearance of infections was correlated with maximum force and pressure-time integral changes in the second metatarsal head, maximum pressure changes in the second and third metatarsal head, and impulse changes in the medial and lateral portions of the heel. The appearance of blisters or infections may serve as an indicator of plantar pressure changes.

It is unfortunate that we did not examine walking behavior variables. There was inevitable personal error in the sonography detecting intima-media membrane of the lower limb blood vessels. In addition, none of the participants wore shoes with ≥5 cm heels daily. Furthermore, two participants had ulcers and three participants developed blisters over the course of the study, and this may have contributed to the development of bias in the data analysis, affecting our conclusions. It is a pity that MCV changes had no statistical significance. All of the blood samples were collected from the participants at 7 AM on a regular weekday morning after 12 h of fasting and limited activity to make the data relatively stable, and blood glucose, cholesterol, and triglyceride concentrations after the fasting period may reflect a rough change trend. However, the data are unstable and susceptible, and cannot reflect exact changes in concentrations over the 2 years and may include a degree of bias.

Overall, plantar pressure changes showed a remarkable correlation with BMI, HbA1c, cholesterol, ABI, SCV, NSS changes and with the appearance of infections, blisters, and calluses over the course of the study. While the ultimate result of diabetic foot ulceration is devastating, foot ulcerations can be prevented. We must pay more attention to factors that are correlated with plantar pressure changes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Edited by: Ning-Ning Wang

R EFERENCES

1 Guariguata L Whiting DR Hambleton I Beagley J Linnenkamp U Shaw JE Global estimates of diabetes prevalence for 2013 and projections for 2035 Diabetes Res Clin Pract 2014 103 137 49 24630390 10.1016/j.diabres.2013.11.002

2 Larsson J Apelqvist J Towards less amputations in diabetic patients. Incidence, causes, cost, treatment, and prevention - A review Acta Orthop Scand 1995 66 181 92 7740955 10.3109/17453679508995520

3 Frykberg RG Lavery LA Pham H Harvey C Harkless L Veves A Role of neuropathy and high foot pressures in diabetic foot ulceration Diabetes Care 1998 21 1714 9 9773736 10.2337/diacare.21.10.1714

4 Apelqvist J Elgzyri T Larsson J Löndahl M Nyberg P Thörne J Factors related to outcome of neuroischemic/ischemic foot ulcer in diabetic patients J Vasc Surg 2011 53 1582 8.e2 21515021 10.1016/j.jvs.2011.02.006

5 Viswanathan V Snehalatha C Sivagami M Seena R Ramachandran A Association of limited joint mobility and high plantar pressure in diabetic foot ulceration in Asian Indians Diabetes Res Clin Pract 2003 60 57 61 12639766 10.1016/s0168-8227(02)00272-3

6 van Schie CH Slim FJ Keukenkamp R Faber WR Nollet F Plantar pressure and daily cumulative stress in persons affected by leprosy with current, previous and no previous foot ulceration Gait Posture 2013 37 326 30 22947998 10.1016/j.gaitpost.2012.07.022

7 Stess RM Jensen SR Mirmiran R The role of dynamic plantar pressures in diabetic foot ulcers Diabetes Care 1997 20 855 8 9135955 10.2337/diacare.20.5.855

8 Armstrong DG Peters EJ 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 37 303 7 9710782 10.1016/s1067-2516(98)80066-5

9 Qiu X Tian DH Han CL Chen W Wang ZJ Mu ZY Risk factors correlated with plantar pressure in Chinese patients with type 2 diabetes Diabetes Technol Ther 2013 15 1025 32 23984803 10.1089/dia.2013.0085

10 Dyck PJ Thomas PK Diabetic Neuropathy 1999 2nd ed Philadelphia W.B. Saunders Co

11 Mukherjee D Cho L Peripheral arterial disease: Considerations in risks, diagnosis, and treatment J Natl Med Assoc 2009 101 999 1008 19860299 10.1016/s0027-9684(15)31066-x

12 Bakker K Apelqvist J Schaper NC International Working Group on Diabetic Foot Editorial Board Practical guidelines on the management and prevention of the diabetic foot 2011 Diabetes Metab Res Rev 2012 28 Suppl 1 225 31 22271742 10.1002/dmrr.2253

13 Pett MA Ruth D Crawford J Nonparametric Statistics in Health Care Research: Statistics for Small Samples and Unusual Distributions 1997 Thousand Oaks Sage Publications

14 Pataky Z Assal JP Conne P Vuagnat H Golay A Plantar pressure distribution in type 2 diabetic patients without peripheral neuropathy and peripheral vascular disease Diabet Med 2005 22 762 7 15910629 10.1111/j.1464-5491.2005.01520.x

15 Ledoux WR Shofer JB Cowley MS Ahroni JH Cohen V Boyko EJ Diabetic foot ulcer incidence in relation to plantar pressure magnitude and measurement location J Diabetes Complications 2013 27 621 6 24012295 10.1016/j.jdiacomp.2013.07.004 PMC4227535

16 Masson EA What causes high foot pressures in diabetes: How can they be relieved? Proceedings of the IDF satellite symposium on the diabetic foot, Washington 1991 Foot 1992 2 212 7

17 Sacco IC Hamamoto AN Tonicelli LM Watari R Ortega NR Sartor CD Abnormalities of plantar pressure distribution in early, intermediate, and late stages of diabetic neuropathy Gait Posture 2014 40 570 4 25086801 10.1016/j.gaitpost.2014.06.018

18 Flynn TW Canavan PK Cavanagh PR Chiang JH Plantar pressure reduction in an incremental weight-bearing system Phys Ther 1997 77 410 6 9105343 10.1093/ptj/77.4.410

19 Arnold JB Causby R Pod GD Jones S The impact of increasing body mass on peak and mean plantar pressure in asymptomatic adult subjects during walking Diabet Foot Ankle 2010 1 5518 25 10.3402/dfa.v1i0.5518 PMC3284282 22396809

20 Ahroni JH Boyko EJ Forsberg RC Clinical correlates of plantar pressure among diabetic veterans Diabetes Care 1999 22 965 72 10372250 10.2337/diacare.22.6.965

21 Fernando M Crowther R Lazzarini P Sangla K Cunningham M Buttner P Biomechanical characteristics of peripheral diabetic neuropathy: A systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure Clin Biomech (Bristol, Avon) 2013 28 831 45 10.1016/j.clinbiomech.2013.08.004 24035444

22 Payne C Turner D Miller K Determinants of plantar pressures in the diabetic foot J Diabetes Complications 2002 16 277 83 12126786 10.1016/s1056-8727(01)00187-8

23 Arezzo JC New developments in the diagnosis of diabetic neuropathy Am J Med 1999 107 9 16 10.1016/s0002-9343(99)00008-x 10484040

24 Dyck PJ Detection, characterization, and staging of polyneuropathy: Assessed in diabetics Muscle Nerve 1988 11 21 32 3277049 10.1002/mus.880110106

25 Feng Y Schlösser FJ Sumpio BE The Semmes Weinstein monofilament examination as a screening tool for diabetic peripheral neuropathy J Vasc Surg 2009 50 675 82 682.e1 19595541 10.1016/j.jvs.2009.05.017

26 Pataky Z Golay A Bounameaux H Bobbioni-Harsch E Assal JP Relationship between peripheral vascular disease and high plantar pressures in diabetic neuro-ischaemic patients Diabetes Metab 2003 29 489 95 14631325 10.1016/s1262-3636(07)70062-9

27 Potter J Potter MJ Effect of callus removal on peak plantar pressures Foot 2000 10 23 26