The effectiveness of methods of off-loading to prevent diabetic foot ulcers in adults with diabetes: A Systematic Review

Review question/objective

The objective of this review is to systematically review the evidence to determine the best available evidence related to methods of off-loading to prevent the development of foot ulcers in adults with diabetes.

More specifically, the review question is to identify:

What is the effectiveness of methods of off-loading to prevent diabetic foot ulcers in adults with diabetes?

Background

Diabetes mellitus (DM) is a chronic disease characterised by unstable blood glucose levels caused by failure of the beta cells in the pancreas to produce adequate or effective insulin.¹ Insulin is necessary to metabolise sugars, fat and protein for use as energy by the body.^1,2,3 There are three main types of diabetes: gestational, type 1 and type 2 diabetes mellitus.

Gestational diabetes arises during pregnancy and usually disappears by itself following delivery of the baby.^1,2,4 Type 1 diabetes mellitus (T1DM), previously known as juvenile diabetes,¹ is characterised by an absence of insulin, most often presentation is acute and life threatening with regular insulin therapy required to sustain life. Its aetiology is unknown and it is not preventable.⁵ Type 2 diabetes mellitus (T2DM), previously called mature onset diabetes, has a more insidious onset and results from a reduction in beta cell production, reduced effectiveness of cells and/or insulin resistance.^2,5 A combination of a strong family history of T2DM, obesity and inadequate physical activity may contribute to the development of T2DM.⁶

The world prevalence of diabetes is expected to reach 366 million by 2030, more than double the 2000 figure of 171 million.⁷ Up to 50% of those with diabetes will develop complications related to the disease.^1,8 Diabetes and related complications in Australia are estimated to cost up to $6 billion per year for T2DM and $570 million per year for T1DM.¹

The morbidity and mortality of the disease is often underestimated, 3% of non-accidental deaths in Australia are attributable to diabetes.¹ It is the 6th leading cause of death in Australia with approximately 275 new cases per day or 100,000 per year.⁹ It is acknowledged that for every person with T2DM, there is another who has the disease which has not yet been diagnosed.⁹ A common misconception concerning diabetes is that reducing dietary sugar intake is all that is needed to control diabetes and many people are ignorant of other physiological changes associated with the disease.^10,11

Raised blood glucose levels associated with diabetes can contribute to the development of vascular and neurological complications. Atherosclerotic changes in the larger blood vessels, (macrovascular disease) can cause limb ischaemia.^11,12 Smaller vessel (microvascular) changes can impair intracellular oxygen perfusion leading to poorer healing responses to trauma.^11,12 The progress of microvascular disease may see the narrowing of the lumen of smaller vessels such as the vasa nervorum which are small arteries supplying blood to the peripheral nerves. This may result in nerve ischaemia affecting myelinisation of the nerve and axonal activity leading to deficiency in nerve transmission.¹³

Whilst vascular and neurological changes in a person with diabetes occur throughout the body, changes in the heart, eyes, kidneys, and lower limbs can be the more debilitating aspects of this disease on the quality of life (QOL) of the individual.¹⁴ Complications arising from diabetes can cause muscle death or infarction in the heart brought about by cardiovascular disease (CVD). Damage to the eyes may cause blindness (retinopathy), changes in the kidneys lead to renal disease (nephropathy) and possible renal failure.¹ Nerve damage (neuropathy) may occur in the lower limb which may be sensory, motor, and/or autonomic.^1,11

In the lower limbs sensory neuropathy results in the loss of the body's protective feedback mechanism in response to pain or touch resulting in non-detection of minor trauma such as blisters or sores.^15,16 Motor neuropathy can affect balance (proprioception) and spatial awareness resulting in changes in gait. In addition changes in foot structure may lead to placement of abnormal forces during gait resulting in the development of friction or pressure related lesions such as callus or corn formation.^11,15,17 In addition, due to the reduction in nerve conductance there is significant loss of muscle volume and muscle strength in the foot and ankle^11,18 whilst autonomic neuropathy contributes to skin becoming dry and thin and more susceptible to damage. Furthermore, microvascular dysfunction contributes to reduced tissue perfusion causing reduction in oxygenation of the tissues which may result in an increased vulnerability to mechanical stress.^11,19 These three areas of neuropathy are major contributors to the development of a diabetic ulcer and subsequent wound healing failure.¹¹

Nelzén et al defines an ulcer as ‘an open wound below the knee (including foot ulcers) that did not heal … within a 6-week period’.^20(p.184) Chronic leg ulcers can be venous, arterial and/or neuropathic in origin. Venous ulcers may respond to interventions to improve venous return e.g. compression bandaging; while arterial ulcers may respond to improved arterial supply to the area e.g. surgical revascularisation. Underlying physiological changes associated with diabetes make a neuropathic ulcer more complex to treat as ischaemia contributes to reduced healing rates and reduced pressure sensation may lead to ongoing undetected trauma.^15,17,21 Diabetic ulcers usually develop in an area of excess pressure on the plantar surface of the foot or on the dorsal surfaces of misshapen toes. They often start below a corn or area of callus and may not be detected until the overlying thickened skin has been debrided. They can be deep and may allow probing of the ulcer to the underlying bone.^12,17,22

Diabetic ulcers are defined by Apelqvist et al as a ‘lesion through the full thickness of the dermis (Wagner grade 1)’.^17(p.486) A study by Robertshaw et al found healing time for diabetic ulcers ranged from two weeks to six months, with an average time of eight weeks.²³ Those living with a diabetic ulcer often experience restriction of activity, mobility and social contact, pain and/or discomfort, unwanted odours from dressings, difficulty fitting footwear around bulky dressings and the regular and frequent attendance at a clinic for dressing changes.²⁴ Non-healing and recurrent foot ulcers often lead to amputations.¹¹ Lepantalo et al found that 85% of diabetes related amputations were the result of a diabetic ulcer.¹¹ Trautner et al found the relative risk of an amputation associated with diabetes is 22 times greater than in a non-diabetic population.²⁵ In addition, Schofield et al determined that following a lower extremity amputation the 5 year survival rate for those with diabetes was as low as 31.9%²⁶ which supported similar findings by Aulivola et al.¹⁹

Suggested management of those at risk of developing a diabetic ulcer includes regular monitoring of skin integrity and neurovascular status, as well as regular debridement of corns and callus.¹⁷ In addition, pressure modulation, commonly referred to as off-loading may be used as a primary intervention to reduce the risk of developing a diabetic ulcer and may contribute to better outcomes if an ulcer occurs.^4,27

Off-loading is defined by Calhoun et al as ‘any measure to eliminate … abnormal pressure points to promote healing or prevent recurrence of diabetic foot ulcers’.^28(p.35) External mechanical interventions to offload high pressure areas include, but are not limited to, padding attached directly to the foot, padded or customised insoles, customised or prefabricated orthotic devices, customised footwear, and rocker-soled shoes.

Use of off-loading methods for ulcer prevention have been previously investigated in primary studies however the results were inconclusive. Eckerle Mize and Gandhi reported commonly used methods by clinicians based on existing guidelines were not evaluated for significance of effects on outcomes.²⁹ Arad et al reported some findings of efficacy however these results were from case-control studies which were later refuted in a subsequent randomised control trial (RCT).³⁰

In overview, the evidence for reliable and practical off-loading to prevent foot ulcers in adults with diabetes is limited.^27,29 A search of The Joanna Briggs Institute Library of Systematic Reviews, The Cochrane Library, PubMed, Scopus, Embase, Science Direct, Google Scholar and CINAHL databases from 2008 was undertaken. The five year limit for the search was based on the assumption that evidence preceding that date would be considered out-dated. The search found five relevant systematic reviews (published in the years 2008, 2009, 2010 and 2011) which considered both prevention and healing of diabetic foot ulcers. Bus et al (2008) investigated effectiveness of footwear and off-loading for prevention and healing of diabetic foot ulcers.²⁷ The systematic review by Paton et al (2009) reviewed the effectiveness of insoles to prevent diabetic foot ulcers.³¹ Cavanagh and Bus (2010) reviewed ulcer prevention and healing related to use of off-loading.³² In 2010 Dorresteijn et al compared complex versus singular interventions to prevent diabetic foot ulcers.³³ The systematic review by Arad et al (2011) discussed mechanical external methods of off-loading as well as surgical interventions and interventions guided by measurement of plantar foot temperatures.³⁰

The purpose of this review is to identify interventions for prevention only, studies which evaluate both prevention and healing methods will be considered, however only results related to prevention will be included. While there is expected to be some overlap in results and discussion with previous systematic reviews further database searches have discovered more recent literature which will contribute to this study which aims to narrow the field to only methods used externally as a primary intervention to prevent the development of diabetic foot ulcers in those at risk.

There is a need to increase awareness regarding prevention of diabetic ulcers in those at risk and to encourage the acceptance of using offloading modalities in clinical settings as a primary intervention. Bus et al report a gap in the literature regarding ‘off-loading interventions other than footwear and surgery’^27(p.24) which ‘must be filled in order to build up an evidence base to properly assess clinical effectiveness and the use of these interventions’.^27(p.24)

Using an external method of off-loading to reduce pressure on areas of skin at risk of damage may be an easily accessible, less costly and relatively simple way of preventing diabetic ulcers. This review aims to evaluate non-surgical off-loading methods used to prevent the development of diabetic neuropathic foot ulcers. The initial search focus will be for literature regarding ‘diabetic foot ulcers’ however if the search returns extensive results, the focus will be modified to ‘neuropathic foot ulcers’.

Inclusion criteria

Types of participants

This review will consider studies that include adults 18 years and older with diabetes mellitus regardless of age, gender, ethnicity, duration of diabetes, type of diabetes in any clinical setting.

Types of intervention(s)/phenomena of interest

This review will consider studies that evaluate all off-loading methods and strategies (excluding surgical interventions such as Achilles tendon lengthening). Interventions to be considered include mechanical external methods of off-loading, used prior to the development of a primary ulcer or break in the skin of the foot or lower leg.

These may include, but are not limited to; padding: in-shoe and attached to the foot, customised insoles, customised orthotic devices, customised footwear and rocker-soled shoes.

Types of outcomes

The primary outcome of interest will be the prevalence of foot ulcers associated with diabetes mellitus.

Secondary outcomes will include measurable changes in pressure on the skin of the foot and may include, but are not limited to; visual, mechanical or computerised methods

Types of studies

This review will consider any experimental and epidemiological study design including randomised controlled trials, non-randomised controlled trials, quasi-experimental and cohort studies for inclusion.

Search strategy

The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilised in this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Studies published in English will be considered for inclusion in this review. Studies published prior to and including 2012 will be considered for inclusion in this review.

The databases to be searched include:

PubMed

CINAHL

EMBASE

SCOPUS

Cochrane CENTRAL

The search for unpublished studies will include:

Cochrane - Protocols, Research and Trials Register

Clinicaltrials.gov

NHS Research Register

REGARD (database of ESRC)

The search of Grey literature search will include:

Google Scholar

SIGLE

MedNar (excluding Google Scholar)

WorlWideScience

Initial keywords to be used will be:

Off-loading

Padding

Adults

Prevention

Diabetes

Foot ulcer

Diabetic ulcer

(MeSH terms of the above)

Assessment of methodological quality

Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardised critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix V). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.

Data collection

Data will be extracted from papers included in the review using the standardised data extraction tool from JBI-MAStARI (Appendix VI). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives.

Data synthesis

Quantitative data will, where possible be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square and also explored using subgroup analyses based on the different study designs included in this review. Where statistical pooling is not possible the findings will be presented in narrative form including tables and figures to aid in data presentation.

Conflicts of interest

No conflicts of interest.

Acknowledgements

This review will form part of a submission for the Masters of Clinical Science and therefore a secondary reviewer (JT) will only be used for critical appraisal.