Can Weight Bearing Aerobic Exercise be Done Safely with an Active Diabetic Plantar Foot Ulcer and Can It Improve Healing Time

Catherine Fall, BSc (HONS) [Student]

Salford University, Manchester, UK; E-mail: C.Fall1@edu.salford.ac.ukv

INTRODUCTION

The diabetic foot (DF) is one of the most feared complications of diabetes due to its devastating effects; caused by a combination of diabetic neuropathy (DN) and peripheral arterial disease (PAD) which results in diabetic foot ulcers (DFU’s), critical ischemia, and infection.¹ The economic burden of the DF on the National Health Service (NHS) in the UK is rising, with an estimated expenditure of over £837 million being cost on ulcer treatment and amputation during 2014-2015² to nearly one billion in 2022.³

DFU’s are one of the leading causes of lower limb amputation (LLA) in the UK⁴ with up to 85% of amputations caused by diabetes preceded by a DFU.³ DFU’s often arise due to infrequent foot checks by specialist physicians⁵ and/or due to the symptoms of DF being hard to recognise by the patient due to sensory loss combined with being under educated on what to look out for at home during a personal foot check.⁶ Recurrence of DFU’s is common; Armstrong et al⁷ states that ‘around 40% of DFU patients have a recurrence within 1-year after ulcer healing, almost 60% within 3-years, and 65% within 5-years’ and Moulik et al⁸ categorises the reported 5-year mortality rate as 45%, 18% and 55% for neuropathic, neuroischemic and ischemic ulcers, respectively.

Many diabetics have vascular complications and comorbidities⁹ and in general lead sedentary lives, which leads to the worsening of these co-morbidities.¹⁰ Research on the benefits of aerobic exercise on the vascular system in diabetics is vast with many studies indicating a reduced mortality rate and improved quality of life from exercising.¹¹ However, research on the benefits of aerobic exercise on diabetics with active DFU’s is slim, making it difficult to assess whether aerobic exercise can be done safely in these patients. The general guidelines from the International Working Group on the DF is to offload the foot and make weight bearing minimal whilst recovering from a DFU¹² but this therefore worsens the sedentary behaviour and contributes to the already bleak outcome of having a DFU,¹⁰ with between 15-20% of patients with DFU getting worse, leading to amputation.¹ Staggeringly, 70% of people with DFU’s die within 10-years, with most of these deaths being vascular related.¹³

Study Selection

A total of 22 studies were found with keywords “active foot ulcer” AND “aerobic physical activity” AND “diabetic ulcer healing” via search databases PubMed, Elsevier, Academia and ResearchGate. After careful deselection of studies lasting less than 10-weeks and those that exclude PAD; 5 papers were included in the review (Table 1) (Appendix Table 2).

CRITIQUE OF THE LITERATURE

Participants

Suryani et al,¹⁴ LeMasters et al¹⁵ and Nwankwo et al^16,17 included between 50-80 mixed gender participants split into an invention group and control, whereas Lindberg et al¹⁸ only included 5 male participants with no control. Holdcroft¹⁹ found that studies with mixed gender have been shown to be more accurate and states that ‘research funding for coronary artery disease in men is far greater than for women, yet the at-risk population of women, which is an older age group, suffers more morbidity and mortality’. Suryani et al¹⁴ and LeMasters et al¹⁵ used randomised selection methods but Nwankwo used own clinical judgement to recommend the participants, which has proven to increase bias.²⁰

Age was slightly lower in the Suryani et al¹⁴ study with an average of 55-years, compared to other papers average of between 65-69-years, which coincides with the average age of most diabetes patients in the UK today.²¹ Lower age at disease onset correlated with participants having the longest duration of diabetes. Nwankwo’s et al^16,17 average duration was considerably higher than other papers at 21.77-years. Song²² found that duration of diabetes has been shown to be an indicator of progression of diabetic comorbidities with ‘stroke and peripheral vascular disease levels becoming significantly higher in type 2 diabetics (T2D) after 20-years duration’ and Brownrigg et al²³ found that increased peripheral vascular disease has a diminishing effect on the rate of healing.

Lindberg’s et al¹⁸ participants had a prevalence of 80% T2D, whereas LeMaster et al¹⁵ had T2 prevalence of 95% in the experimental group and 93.5% in both groups. Sunyani only included T2D and Nwankwo et al^16,17 failed to mention which type the participants were. T2D is more heavily associated with obesity and peripheral vascular disease than T1, therefore excess plantar pressures and dyslipidaemia may be more prevalent in this study.^24,25 However, recent findings are suggesting that obesity is a major predictor of T1D in children due to the ‘accelerator hypothesis’ by Wilkins.²⁶

Body mass index (BMI) was higher for participants in LeMasters¹⁵ study, with an average BMI of 36.55 (SD), putting these patients in the obese class 2 category.²⁷ Obesity has been proven to delay healing time due to vasculogenic impairment.28 In the experimental groups, Lindberg’s et al18 average BMI was 28.7 and Nwankwo’s et al1^6,17 27.66 but Nwankwo’s et al^16,17 non-experimental group was 22.96, indicating a significant difference amongst the control and intervention group in this study. BMI was slightly lower in Suryani’s et al¹⁴ at 24.5, putting this group of participants in normal BMI range.²⁷

Blood pressure (BP) allowance to participate in the exercise programmes also differed, whereby Lindberg et al18 did not signify the systolic/diastolic value but referred to advice from the responsible physician. However, Nwankwo’s et al^16,17 systolic inclusion value was < 165 mmHg and LeMasters et al15< 200 mmHg to take part; this is a significant difference and above the recommended BP value of< 180/110 mmHg for completing light-moderate exercise in which no further evaluation is needed.²⁹

Lindberg et al¹⁸ had a 60% non-smoker statistic, LeMasters et al¹⁵ had a 95% non-smoker statistic in the intervention group and a 91% accumulative percentage including control, but Nwankwo et al^16,17  and Suryani et al¹⁴ failed to identify which participants were smokers. Smoking increases the risk of diabetic foot amputation and is the leading cause of PAD (Appendix Table 3).³⁰

Method

All papers were randomized controlled trials (RCT) apart from Lindberg’ et al¹⁸ which was a research paper. RCT’s have been proven to be more accurate than research papers.³¹ Duration of exercise programmes ranged from 10-weeks to 12-months. Lindberg et al18 LeMaster et al¹⁵ and Suryani et al¹⁴ were mixed aerobic and resistance-based, whereas Nwankwo et al^16,17  solely aerobic. A mixture of aerobic/resistance exercise has been proven to have more benefits on the cardiovascular system and overall fitness than one category alone.³²

Lindberg et al¹⁸ and Nwankwo et al^16,17  were fully supervised trials, whereas LeMaster et al¹⁵ was supervised for only the first 3-months and thereafter home based. Suryani et al¹⁴ was entirely home based with tri-weekly monitoring over the phone and exercises recorded in a logbook. Regular monitoring improves adherence and inaccuracy’s have been found when recording home exercise diaries.¹¹ Adherence has been noticeably poor in diabetics when asked to exercise, supervision has been known to increase adherence and enhance the benefits of an exercise programme.³³

Sessions during Lindberg’s et al¹⁸ study were not progressive and there was no pre-scheduled programme with an aim to encourage self-management and improve adherence, therefore it is impossible to determine the number of sessions each individual patient took part in per week. The study included a patient satisfaction survey form report (PSSF) but no motivational interviewing or counselling. Counselling and motivational interviewing have proven to improve patient adherence to exercise.³⁴ Patients wore a removable air cast walker or orthopaedic shoe, completed 12-minute cardiovascular exercise plus light-moderate elastic band resistance exercises but many sessions were not completed due to adherence issues. Ulcer wound was evaluated by Wilcoxon Signed Ranks test, but the study did not mention if the wound was evaluated during the programme or just pre and post programme.

Nwankwo et al^16,17  included counselling in a structured, progressive exercise programme. A systematic review by Irvine et al³⁵ showed that progressive exercise programmes help increase adherence, motivation and reduce pain amongst diabetics. Variation in a programme can also have great purpose in motivating the participant.³⁶ Nwankwo’s et al^16,17  experimental group wounds were checked bi-weekly by the nurse, measured with a transparent ruler. Regular checks from the diabetic nurse improve patient ulcer outcome rates.³⁷

LeMaster et al¹⁵ was the only full weight bearing walking programme that included at home daily living activity monitoring via accelerometer at ^{3, 6} and 12-month intervals. The patients performed 3×30 minute aerobic sessions per week in orthotic prescribed footwear, steps were recorded via pedometer throughout. The type of terrain the exercise was performed on was not mentioned. Even with the correct shoes, different terrain can cause sheer stresses and pressure38 and although patients had access to an ongoing dermatologist if needed, they self-managed footcare at home. Home examinations have proven poor in diabetic patients due to being uneducated on what to recognise as potential harm.⁶

Statistics amongst all papers were analysed to a p<0.05 significance using statistical package for social sciences (SPSS) or statistical analysis system (SAS) software. SPSS has been found to be more commonly used amongst RCT’s, with over 52.1% of studies using this software. However, SAS can be more useful for comparison graphs but can be time consuming (Appendix Table 4).³⁹

Results

Lindberg showed that no DFU’s worsened during the programme, proving safety and feasibility towards this variable. However, there were many adverse events with delayed onset muscle soreness (DOMS) being reported in 3 out of 5 participants. DOMS is partly due to a build-up of lactic acid accumulating when tissues become oxygen deprived during exercise,⁴⁰ which can be detrimental to diabetics because of their risk of lactic acidosis, often due to taking the popular medication metformin.⁴¹ Progression of the programme was halted amongst individuals suffering from DOMS. However, patient satisfaction survey scores (PSSF) and performing daily living activities improved following the programme which is highly beneficial in a diabetic patient who is depressed due to pain.⁴² One patient’s ulcer increased in size during a holiday where he was walking regularly, highlighting that weight bearing may increase ulcer size.

Nwankwo et al¹⁶proved at 12-weeks there was a reduction in fasting plasma glucose. Exercise has shown to reduce fasting glucose levels in diabetics, decreasing the risk of cardiovascular disease.¹¹ Wound size percentage reduction was larger in the intervention group, however there was a large difference between baseline wound size in both groups, whereby the experimental groups size was 26.45+9.46 mm and the control 17.70+7.23 mm, indicating that results may be influenced by this. There was no difference in cholesterol levels at 12-weeks.

Nwankwo et al¹⁷ showed an increase in SPO2 in both groups, with greater increase in experimental group than the control. In the experimental group, ankle brachial index (ABI) levels also increased, wound size decreased with no correlation to BMI after 4-weeks but had a large connection to BMI level at 12-weeks, indicating that BMI is a large indicator in the duration of ulcers.²³ However, there was no correlation between BMI, wound size and SPO2 in the control group.

LeMaster et al¹⁵ suggested there was no additional risk in weight bearing exercise on DFU’s in diabetics with DN. However, although he proved that there was no additional risk in plantar only ulcers, there was a significant increase in other types of lesions in the intervention group. Lesions on the dorsal toes or other areas of lower limb are associated with poor outcome in diabetics due to infection.⁴³ Healing time was slower in the intervention group indicating that weight bearing exercise may have an adverse outcome on healing. Step count increased in the intervention group for the first 6-months but not in the control, however, both groups’ steps declined by 12-months, indicating a poorer adherence rate as time went on.

Suryani et al¹⁴ proved there was less reoccurrence of ulcers overall in the intervention group but on the contrary to Nwankwo et al^16,17  ABI levels did not significantly improve. However, DN scores decreased in the intervention group and walking speed increased, even after 24-weeks, indicating that improved strength/ flexibility has an influence on walking speed.⁴⁴ HBA1C remained unchanged after this study correlating with Nwanko’s et al^16,17  study (Appendix Table 5).

Discussion

The level of bias in Nwankwo’s et al^16,17  study was high, ulcer size was higher in the intervention group at baseline than the control, leading to obscured results. Suryani et al¹⁴ was less biased, with even parameters, making for a more viable outcome²⁰ but only included seated exercises therefore less pressure was applied to the foot. Lindberg et al¹⁸ had no comparison control group and adherence was poor, therefore making conclusions on the relevance of the study is difficult. LeMasters et al¹⁵ ulcer healing time and non-plantar lesions were much greater in the intervention group than the control, indicating that weight bearing exercise on diabetic patients with DN is perhaps not the best intervention to reduce diabetic complications.

Outcome measures varied amongst these papers with no identical testing strategies or assessments. However, it is acceptable to predict that Hemoglobin A1C (HBA1C) is not a viable assessment tool due to it remaining unchanged in 2 of the studies. HBA1C is a percentage of glucose levels over an 8-12-week time frame,⁴⁵ therefore changes in HBA1C level may not have changed for up to 3-months following an exercise programme. There was a contradiction between ABI measurement significance, however Nwankwo et al^16,17  devised a more aerobic programme, which may indicate that aerobic exercise has a more significant effect on ABI measures than resistance-based exercise such as Suryani’s et al¹⁴ programme. These papers did not indicate smoking status, smoking alone is a major cause of PAD which can lower ABI levels. Smoking also influences a person’s ability to reach maximal cardiovascular benefits through hypercoagulation and respiratory distress.⁴⁶ Cholesterol levels may also be influenced by this; therefore, cholesterol may still be a viable tool in assessing the benefits of a short-term 12-week exercise programme.⁴⁷

A raised BMI is a huge indicator in recurrence of DFUs23 and aerobic exercise can decrease BMI. Flexibility exercises can improve cutaneous perfusion response.⁴⁸ Resistance exercises can improve neuropathy sensation,¹⁴ which in turn increases balance, walking stability⁴⁴ and may also increase healing.²³

Based on this review it is fair to say that non-weight bearing or semi-weight bearing exercise in the presence of DFU alongside severe DN is safer and more feasible in the aim to try and stop the regression of diabetic complications. It has not been concluded whether aerobic exercise improves ulcer healing time.

The purpose is to devise a safe and feasible aerobic/resistance exercise programme for diabetics with an active plantar DFU associated with PN and/or mild to moderate ischemia, to increase healing time, improve cardiovascular health and ultimately reduce amputation/mortality rates. The proposal aims to increase adherence and sustainability of exercise by not exhausting participants interest and keeping participants motivated, in the hope of improving quality of life and encouraging better lifestyle choices following the programme.

The study will be a RCT, comprised of a 12-week exercise programme which will be individually tailored to the patient including two types of semi weight bearing aerobic methods alongside a variety of non-weight bearing resistance exercises to keep the participants engaged. Patients with mild-moderate PAD will be allowed to participate, on the contrary to other related studies whereby PAD is amongst the exclusion criteria,^49,50 in a bid to improve patient’s circulation and oxygenise lower extremities. The programme will be gradually progressive to avoid any adverse effects caused by excess pressure which can be predicted under the physical stress theory⁵¹ which will avoid any extreme muscular fatigue following exercise.

Background and Significance

Statistics by Mottolini³ report that ‘7957 major diabetic LLA were reported in England between 2017-2020’. Prognosis is poor for diabetics with PAD who have undergone first minor amputation, with 23% of patients undergoing subsequent major amputation approximately 1-year later.⁵² Quality of life following this loss is reduced markedly.⁵³ Aerobic exercise can decrease the devastating effects of cardiovascular associated problems in diabetics, lower glucose levels54 and improve quality of life, which is of the upmost importance as 1 in 4 of the diabetic population suffer from depression.⁵⁵ Recent studies on diabetic ulcers, using near infrared spectroscopy show that peripheral HbO2 and total Hb levels are increased following resistance-based exercise resulting in reduced ischemia.56 However, there are few studies on aerobic combined with resistance-based exercise amongst patients with an active DFU.

The current guidelines on treatment of an active DFU are to offload the foot, reducing weight bearing activity to a minimum for the ulcer to heal.¹² However, being more sedentary worsens PAD, raises HBA1C levels and increases BMI, which has a negative effect on healing.²³ It seems that a greater amount of time is spent on treating the DF, rather than preventing the co-morbidities. For patients with stable ischemic heart disease, exercise programmes are currently prescribed; Boden et al⁵⁷ has shown that these programmes ‘reduce total mortality by 20%, cardiac mortality by 26%, and non-fatal myocardial infarction by 21%’, yet there is no current exercise prescription in place for diabetics when they share many of the same problems.

RESEARCH DESIGN

Participants

Participants are to give written informed consent and the study is to be approved by Manchester University Foundation Trust and Ethical approval given by the NHS research Ethics Committee (REC). Thirty (30) participants, 15 male, 15 female with T2D, active plantar DFU will be recruited to the study from the Peter Mount, Manchester Royal Infirmary Diabetes and Endocrine clinic. Prior to the trial, the participants will be signed off by their primary physician and randomized using simple randomisation software into an evenly split intervention group/control group. The intervention group will take part in the exercise programme whereas the control group will continue to have the usual wound care from the diabetic clinic (Appendix Table 6).

Pre-programme Assessments

Participants will complete a pre activity level form, however due to the progressive nature of the programme – any level of pre activity will be accepted. Participants will be asked to record their morning resting heart rate before rising on 3 consecutive days before the study begins to determine mean resting heart rate, from this maximum heart rate and heart rate reserve levels will be calculated via the Karvonen method,⁵⁸ giving an indicator of patient’s fitness level. Workload will be set to 40-60% HRR to avoid patients undertaking physical exercise challenges that cannot be achieved wearing a removable cast walker such as the Astrand cycle test18 and follows the recommended cardiovascular guidelines of moderate exercise for diabetes with PAD complications (Appendix Table 7).⁵⁹

Method

The programme will be fully supervised by Register for Exercise Professionals (REPs) Level 4 Advanced Exercise Trainer at the rehabilitation gym at Manchester Royal Infirmary (MRI). The trainer will provide monthly motivational interviewing. A band 7 diabetic nurse will complete foot checks biweekly. A band 5 Orthotist will prescribe new diabetic footwear for the participant once ulcer heals and will monitor removable walker’s condition.

Baseline, 6 and 12-weekly assessments include transparent ruler measurement, toe brachial pressure index (TBPI) toe pressures, SPo2, ABI, fasting blood glucose (FBG), blood cholesterol levels, Semmes monofilament test, BP, BMI. A polar heart rate monitor will be worn during exercise. Adverse events will be recorded. 2222 will be phoned for emergency care. An ankle pedometer will be worn by both groups to monitor steps at home to provide comparisons on activity levels and determine any correlation between higher activity/ulcer healing times outside of the programme. Whilst at home the guidelines on offloading devices will be advised.⁶⁰ Results will be statistical analysed by SPSS version 28 with an accuracy of p<0.05 (Appendix Tables 8 and 9).

Limitations and Difficulties

Claudication may occur because of ischemia; breaks need to be taken and exercise restarted once pain subsides. Patient needs to be reassured that the pain experienced is not dangerous and the pain should subside further into the programme as fitness level improves.⁶¹ Hypoglycaemia should be managed appropriately with juice and snacks onsite if symptoms do occur. However, pre-exercise blood sugar checks will be taken prior to exercise; if levels are below 90 mg/dL, guidelines by Zaharieva et al⁶² will be followed (Appendix Table 1).

Adherence to the participant wearing the removable walker at home may be a problem, with patients choosing not to wear their walkers. However, the motivational interviewing is to encourage participants to follow the guidelines because removable walkers have a better outcome on healing when used appropriately.⁶⁰

BUDGET AND JUSTIFICATION

Budget and Justification (Appendix Table 10). Total expenditure is £29413.09. However, costs of treatment/amputation are reaching nearly £1billion.3 Preventing the cause will be more cost effective in the long run.

FUNDING

The author received no financial support for the research and authorship of this research article and proposal.

DECLARATION OF CONFLICT OF INTEREST

The author declares that there are no potential conflicts of interest with respect to the research and authorship of this article. If the proposal is to be undertaken as a study, it would need permission from the Manchester Foundation Trust and would need ethical approval from the Health Research Authority’s (HSA) NHS RECS.

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APPENDICES

Table 3. Participant Compatibles Nr*=Non-recorded

Table 4. Methods