Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
David M. Kendall, MD
Medical Director and Chief,
Clinical and Professional Services
International Diabetes Center at Park Nicollet
Minneapolis, MN
Richard M. Bergenstal, MD
Executive Director,
International Diabetes Center at Park Nicollet
Minneapolis, MN
Chapter 4:
Diabetic Neuropathy/
The Diabetic Foot
Andrew JM Boulton, MD, DSc (Hon), FRCP
Agbor Ndip, MD
Contents
• Assessment of Diabetic
Neuropathy
6. Complications of Diabetic
Neuropathy
7. Conclusion
8. References
Contents
1. Introduction
3. Pathophysiology
• Clinical Presentation
• Differential Diagnosis of
Diabetic Sensorimotor
Neuropathy
• Assessment of Diabetic
Neuropathy
6. Complications of Diabetic
Neuropathy
7. Conclusion
8. References
Although the history of diabetic neuropathy can be are not uncommon in people with diabetes. This is
traced as far back as that of diabetes, it was not exemplified by the Rochester Diabetic Neuropathy
until the 18th century that Western scientists start- Study, in which up to 10% of peripheral neuropa-
ed studying the complications of diabetes with the thy in diabetic patients was deemed to be of non-
recognition of neuropathy as a common complica- diabetic causation.2
tion and the subject of scientific interest and sys-
tematic studies. Marshall de Calvi, a French physi- However, for research, epidemiologic and clinical
cian, was the first to correctly identify the relation- trial purposes, a more detailed definition that
ship between diabetes and the nervous system. His includes subclinical neuropathy is required.3 The
works were supported by those of Althaus, who San Antonio Consensus defined diabetic neuropa-
further emphasized the nocturnal character of the thy as “a demonstrable disorder either clinically
pain in 1884. But it is Frederick William Pavy, the evident or subclinical, occurring in the setting of
19th century British physician to whom credit is diabetes without nondiabetic causes, including
given for first describing neuropathic symptoms manifestations in the somatic and/or autonomic
and associating these with diabetes. Pavy also parts of the peripheral nervous system.”4 This
pointed out that the onset of neuropathic symp- chapter will focus on the epidemiology, etiology,
toms may precede those of clinical diabetes. Later, diagnosis and management of diabetic somatic
Charcot extended these observations as well as peripheral sensorimotor neuropathy.
described the neuroarthropathy that is now named
after him. Davies-Pryce, a resident surgeon of
Nottingham Dispensary in England, was the first
to describe the micro- and macroscopic changes in
the peripheral nerves of people with diabetes and
to recognize the link between “diabetic neuritis
and perforating foot ulcers”. The awareness of
neuropathy as a common diabetes complication
was such that in the late 19th century, Purdy was
able to assert; “It is rare to meet with a case of
diabetes in which there is not more or less nervous
disturbance.”
Definition
continued
mechanisms include:
• Hyperglycemic neuropathy
• Generalized symmetrical polyneuropathies
• Inflammation
demyelinating neuropathy
• Genetic factors
Hyperglycemia
This concept maintains that hyperglycemia- lism and can cause disturbances in the desatura-
induced endothelial dysfunction results in reduced tion of gamma-linolenic acid (GLA), resulting in
nerve blood flow (NBF), vascular reactivity and reduced production of vasodilatory compounds
endoneural hypoxia, thus causing functional and with a consequent decrease in nerve blood flow.26
structural changes in the nerve.15 The endothelial Treatment with gamma-linolenic acid has been
changes in the vasa nervorum have been attributed shown to improve nerve function in diabetes.27
to increased aldose reductase activity, non-enzy- Carnitine deficiency has been found in patients
matic glycation and glycoxidation, activation of with microvascular complications of diabetes,
protein kinase C, oxidative-nitrosative stress and including neuropathy. In streptozotocin-induced
changes in arachidonic acid and prostaglandin diabetic rats, carnitine deficiency has been associ-
metabolism.15 More recently, other mechanisms ated with hyperactivation of polyol pathway, while
have been implicated and include: in human studies, replacement therapy with
Acetyl- L-carnitine has been shown to improve
• Decreased expression of the vanilloid receptor 1 painful neuropathy symptoms.28
in vasa nervorum16
This concept essentially rests on the premise that human studies differs in type 1 and type 2 dia-
the same mechanisms involved in the vascular the- betes. The neuropathy in type 1 diabetes shows a
ory are not exclusive to the endothelium of vasa more rapid progression with more severe function-
nervorum but may also affect the neural elements al and structural changes.29 Such differences are
of the peripheral nervous system (PNS), such as accounted for by impaired insulin action and sig-
Schwann cells, spinal cord oligodendrocytes and nal transduction in type 1 diabetes, whereas hyper-
dorsal root ganglion neurons. It further proposes glycemia per se contributes equally to neuropathy
that other pathobiochemical abnormalities can in the 2 types of diabetes. There are 2 types of
directly affect the nerve cell, namely: insulin receptors – type A (IR-A) and type B (IR-
B). Glucose metabolism is regulated by insulin via
• Metabolic derangements (down regulation of IR-B. However, the central and peripheral nervous
Na+K+ATP-ase activity21; changes in fatty acid systems contain more IR-A than IR-B, but at nor-
and phospholipid metabolism22) mal serum insulin levels, the insulin affinities of
both these receptors are similar. Thus, it is very
• Impaired secretion of nerve growth factors23 possible that correction of insulin levels in treat-
ments for type 1 diabetes or insulin-sensitizing
• Abnormal signal transduction24 therapy in the case of type 2 diabetes, not only
There is also evidence, albeit limited, that suggest • Occasionally involves the hands in a glove dis-
subclinical inflammation is associated with and tribution
perhaps causative of DN and neuropathic impair-
ments. However, this association appears rather • Mostly, symptoms are gradual (chronic), but
specific, as only certain immune mediators are may be acute
involved. In a recent study, high levels of C-reac-
tive protein and interleukin-6 were found to be
consistently associated with DPN, high MNSI • Onset is insidious and symptoms are intermit-
- Chronic sensory symptoms
Table 2
Motor Sensory
Non-painful Painful
Asleep Knife-like
Squeezing
Burning
Freezing
Throbbing
Allodynia
Hyperalgesia
Some authorities believe that there exists a specif- that small-fiber dysfunction is present early in the
ic small-fiber neuropathy with neuropathic pain, course of neuropathy. Nonetheless, it remains
sometimes together with autonomic dysfunction clear that there is gradual loss of nerve function in
but few signs. However, this shares many similari- diabetic patients that is more rapid than that in
ties with the acute sensory neuropathy, but symp- age-matched non-diabetic subjects. This rate of
toms tend to be more persistent. It is believed to loss is related to the level of glycemic control.44-46
represent an early stage in the development of One consequence of this progressive loss of nerve
chronic sensorimotor neuropathy. function is an increasing risk of insensitive foot
ulceration.47
These painful sensory neuropathies should not be
confused with hyperglycemic neuropathy, which
may occur in newly diagnosed patients and is
Differential Diagnosis of Diabetic Sensory
of nerve function and, occasionally, transient The diagnosis of diabetic neuropathy is essentially
symptoms. clinical and rarely is recourse made to further
investigations. However, diabetic neuropathy
remains a diagnosis of exclusion; therefore, the
presentation of neuropathic symptoms in a patient
Psychological Aspects of Diabetic
Diabetic neuropathy can cause devastating effects other non diabetes-related causes of neuropathy.
on psychosocial functioning and quality of life.40 Conversely, the absence of specific symptoms can-
Depression and anxiety are the most commonly not be taken as the absence of diabetic neuropathy.
recognized psychosocial maladaptation in patients It is not uncommon for the same patient to have 2
with diabetic neuropathy41 and clinicians must rec- or more aetiologies for neuropathy. In the United
ognize them as these can affect adherence and out- States, diabetes and alcoholism are the 2 most
come. Any underlying psychosocial disorder must common causes of peripheral neuropathy. The fol-
Sensory score
Vibration sense
128Hz tuning fork
at apex of the hallux Normal=0
Temperature
Perception on the Reduced/abnormal=1
dorsum of the foot
Pinprick
Reflex Ankle reflex Present=0
score Present with
reinforcement=1
Absent=2
This is a specialist tool used in the investigation of used to follow response to treatment. CCM meas-
diabetic neuropathies. In distal sensorimotor neu- ures correlates well with electrophysiologic and
ropathy, they provide a measure of the following: morphologic nerve assessment. Longer term stud-
ies are ongoing that would determine their utility
• Nerve conduction velocity (NCV) in clinical evaluation of neuropathy.58
• F-waves
• Distribution of velocities
• Excitability
Figure 1
Descending fibers
TCAs / SSRIs / SNRIs
α2 antag / Tramadol
Fluoxetine 5HT
Opioid Dextromethorphan
α2
Substance P
DRG
Ca channels Substantia
NMDA gelatinosa
C-fiber
Glutamate AMPA
mGlur
Glutamate Capsaicin
Clonidine
Aδ fiber GABA A
GABA
GABA B
Na channels
Interneuron
Topiramate
Pregabalin
Carbamazepine
Topiramate
TCAs / Insulin
Gabapentin
C-fibers are modulated by sympathetic input with spontaneous firing of different neurotransmitters to the dor-
sal root ganglia (DRG), spinal cord and cerebral cortex. Sympathetic blockers (clonidine) and depletion of
axonal SP used by C-fibers as their neurotransmitter (capsaicin) may improve pain. In contrast, Aδ fibers uti-
lize NA+ channels for their conduction and agents that inhibit Na+ exchange, such as antiepileptic drugs, tri-
cyclic antidepressants and insulin, may ameliorate this form of pain. Anticonvulsants (carbamazepine,
gabapentin, pregabalin, topiramate) potentiate GABA activity, inhibit Na+ and Ca channels and inhibit
NMDA and AMPA receptors. Dextromethorphan blocks NMDA receptors in the spinal cord. TCA, SSRIs and
SNRIs inhibit serotonin and norepinephrine reuptake, enhancing their effect in endogenous pain-inhibitory
systems in the brain. Abbreviations: SP: substance P; TCA: tricyclic antidepressants; SSRIs: selective sero-
tonin reuptake inhibitors; SNRIs: serotonin and norepinephrine reuptake inhibitors; NMDA: N-methyl-D-aspar-
tate; AMPA: amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; GABA: gamma-aminobutyric acid
Opioids
Treatment Options for painful diabetic neuropathy (Adapted from McQuay et al, Zeigler and Dobecki et al)79-81
118
Compound/ Starting Dose Remarks Side NNT
measure dose per day Effects
SSNRI
Treatment Options for Painful Diabetic Neuropathy (Adapted from McQuay et al, Zeigler and Dobecki et al)79-81
SSRIs
Paroxetine 40 +++
Citalopram 40 +++
Anticonvulsants
Weak opioids
Local treatment
Strong opioids
119
Table 4
120
Treatment Options for Painful Diabetic Neuropathy (Adapted from McQuay et al, Zeigler and Dobecki et al)79-81
Balneotherapy,
relaxation therapy
Acupuncture No AE
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Contents
4. Foot Ulcers
6. Conclusions
7. References
8. Questions
resent the commonest cause of hospital admission Foot ulceration and amputation will be considered
amongst diabetic patients in Western countries, are together in this section, as they are closely interre-
responsible for much morbidity, and even mortali- lated. A selection of epidemiologic data for diabet-
ty, and are a major economic drain on the health ic foot ulceration and amputation, originating from
care system. The global term “diabetic foot” is studies from a number of different countries, is
used to refer to a variety of pathologic conditions provided in Table 1. As can be seen in Table 1,
that might affect the feet of diabetic patients. reported frequencies of amputation and ulceration
Whereas neuropathy is a major contributory factor do vary considerably as a consequence of different
in the etiopathogenesis of foot ulceration and diagnostic criteria used, as well as regional differ-
Charcot Neuroarthropathy (CN), it can all too ences. However, diabetes remains a major cause of
often be implicated in the causal chain ultimately non-traumatic amputation across the world, with
resulting in amputation. However, in recent years, rates being as great as 15 times higher than in the
neuroischemic and ischemic ulcers have become non-diabetic population. It is not possible to do
increasingly more common, possibly because neu- direct comparisons between studies and countries
ropathic ulcers are easier to prevent.1 because of methodological issues and, additional-
ly, surveys invariably include only patients with
A number of facts also attest to the increasing previously diagnosed diabetes, whereas in type 2
importance of diabetic foot disease: diabetes, foot problems may be a presenting fea-
ture. In the United Kingdom Prospective Diabetes
• Foot ulceration is common, affecting up to 25% Study, for example, 13% of patients had neuropa-
of diabetic patients during their lifetime, and thy at diagnosis of diabetes of sufficient severity
over 85% of lower limb amputations are preced- to put them at major risk for foot problems.
ed by foot ulcers: diabetes remains the common-
est cause of non-traumatic amputation in Western
countries.2,3
A thorough understanding of the pathways that Peripheral vascular disease (PVD) is also more
result in the development of foot lesions is essen- common in patients with diabetes, tends to occur
tial if we are to be successful in reducing the high at an earlier age and is more likely to involve dis-
incidence of foot ulcers and ultimately amputa-
tions in diabetes. Ulceration does not occur spon-
taneously, rather, it is the combination of causative
Table 2
Figure 1.
• Somatic
• Autonomic
Table 1
warm foot. It must be remembered that the warm, It is most common that a combination of 2 or
insensitive foot is just as much at risk for foot more risk factors ultimately contribute to the
problems as the cool foot secondary to PVD. development of diabetic foot lesions. In a prospec-
tive study on the causation of foot ulceration,
It has been increasingly recognized in recent years Reiber et al8 identified a number of causal path-
that patients with end-stage renal disease (ESRD), ways, with the commonest triad of component
particularly those on dialysis, have a much greater causes being neuropathy, deformity and trauma
risk of developing foot lesions. Similarly, (present in nearly 2 out of 3 incident foot ulcer
retinopathy (especially with disturbed vision) has cases). Edema and ischemia were also common
been shown to increase the risk of foot lesions. component causes. Thus, the patient with insensi-
Figure 1
Neurological
Vascular
• Foot pulses
• Ankle Brachial Pressure Index, if indicated
As noted above, it has been stated that the vast with an extensive shoe-induced ulcer. The expla-
majority of foot problems in diabetes are poten- nation, however, is simple: with reduced sensa-
tially preventable: the first step in prevention must tion, a very tight fit stimulates the remaining pres-
be the identification of the at-risk population. It is sure nerve endings and is then interpreted by the
now accepted that every patient with diabetes patient as a normal fit. In order to successfully
should be screened for major complications, reduce the risk of foot ulcers and amputations, we
including risk of foot ulcers, at least annually, and must realize that with the loss of pain there is also
such a review can be carried out either in the pri- diminished motivation in the healing and, more
mary care or hospital setting. A task force of the importantly, the prevention of injury.
American Diabetes Association (ADA) recently
addressed the question of what should be included It may be for this reason that there is little evi-
for foot screening in the comprehensive diabetic dence to actually support the use of preventative
foot examination (CDFE).9 Wherever possible, education in first foot ulcers in diabetes. Patients
recommendations were made according to evi- clearly need to be informed of the risk of having
dence-based medicine, and emphasis was placed insensate feet, the need for regular self-inspection,
on a simple clinical examination, as up to 50% of foot hygiene and podiatry treatment and, addition-
foot ulcer patients have no history of any neuro- ally, they must be told what action to take in the
pathic or vascular symptoms. There is a strong event of an injury or the discovery of a foot ulcer.
evidence base to support the use of simple clinical However, it has been shown that patients often
tests as predictors of foot ulcers.9,10 A summary of possess distorted beliefs about neuropathy,12 think-
the key components of the CDFE is provided in ing that it is a circulatory problem and subsequent-
Table 3. 2 simple clinical assessments, the 10 g ly do not link foot ulcers and amputation. Thus, an
pressure perception using the 10 g monofilament educational program that focuses on reducing foot
and 1 of 4 other tests was recommended for neu- ulcers will be doomed to failure and, therefore,
ropathy, whereas foot pulse palpation remains the much work is required in the area of preventative
mainstay in the assessment of the peripheral vas- education. Sadly, a recent study of a focused foot
culature. The ankle brachial index should also be care education program in patients with a history
tested in patients with diabetes over 50 years of of ulcers could find no evidence that such targeted
age, if possible.11 education was associated with a reduced incidence
of foot ulceration.13
Interventions for High-risk Patients
would place a patient into a group at higher risk of Regular nail and skin care, callus trimming and
ulceration, and potential interventions will be dis- education by a podiatrist are all essential in the
cussed under a number of sub-headings, the most management of the high-risk diabetic foot.
important of which is education. Attempted self-care has been reported in several
cases to cause ulceration and, similarly, self-care
Education of calluses must be discouraged.
insensitive feet have lost their warning signal — Whereas inappropriate footwear is often a com-
pain—that ordinarily brings the patient to their mon cause of foot ulceration in insensitive feet,
doctor. Thus, the care of the patient with no pain good footwear has been shown in more than 1
sensation or other peripheral sensations is a new study to reduce the incidence of recurrent ulcera-
challenge, for which we have little training. It is tion.5,7
difficult for us to comprehend, for example, that
an intelligent patient would buy and wear a pair of
shoes 3 sizes too small and come to our clinic
For many years, it has been recognized that prior The principles of management of foot ulceration
to ulceration and skin breakdown, the involved in diabetic patients depend upon a careful assess-
area of the foot tends to warm up as a conse- ment of the causative factors, the presence or
quence of local inflammation. In a seminal ran- absence of infection, the degree of neuropathy
domized, controlled trial, Lavery et al14 random- and/or ischemia and the site of the lesion.
ized patients with a history of neuropathic foot Numerous classification systems for diabetic foot
ulceration to 1 of 3 groups, the main intervention ulcers have been proposed, but for the purposes of
being self-monitoring of skin temperature of both this chapter, the University of Texas (UT) Wound
feet. If a maintained difference in temperature was Classification System will be described and used
observed between the 2 feet, the patients were in this discussion (Table 4). This system assesses
advised to rest or see their podiatrist. This study the depth of the ulcer and the presence or absence
clearly showed that those patients who performed of ischemia and/or infection. This classification
self-monitoring of skin temperatures and followed system has been shown to be useful in predicting
the advice had a markedly and significantly the outcome of several longitudinal studies.
reduced incidence of recurrent ulceration (8% vs.
30%). Thus, self-monitoring of skin temperature
may well be helpful in the reduction of recurrent
Offloading
ulcers, but has yet to be shown to be helpful in the A normal individual with a foot wound will gener-
primary prevention of foot ulceration. ally limp, as putting pressure on the ulcer would
be painful. The presence of sensory loss as a con-
sequence of neuropathy permits weight bearing on
an ulcer which can maintain the chronicity of the
lesion. The gold standard, in terms of offloading,
has therefore been the total contact cast (TCC)
which redistributes the pressure under the plantar
area of the foot. Several randomized, controlled
trials have compared the TCC with other offload-
ing devices and, invariably, healing is most rapid
in those randomized to TCC management.5
Table 4
Stage Grade
0 1 2 3
The danger of dressings and bandages is that some Clinically infected ulcers – non-limb-threatening
health care professionals may draw from them a infected ulcers (UT1B, 1D, 2B, 2D [see Table 3])
false sense of security, believing that by dressing can generally be treated on an outpatient basis,
an ulcer they are curing it. Nothing could be fur- and oral broad-spectrum antibiotics should be used
ther from the truth for a neuropathic ulcer. The 3 initially until results of wound bacterial sensitivi-
most important factors in the healing of a foot ties are obtained. With respect to microbiological
ulcer are freedom from pressure (offloading), free- analysis, whereas superficial wound swabs are
dom from infection and good vascularity. commonly taken, deep (preferably tissue) speci-
Dressings simply protect the wound from local mens are much preferred in terms of accuracy of
trauma, minimize the risk of infection and opti- diagnosis.16,17 In common with dressings, there is
mize the wound environment, which should be little evidence base to guide the specific choice of
moist in most cases. The evidence base to help in antibiotic therapy. It is clear that local investiga-
the choice of dressings is woefully inadequate, tion and tissue analysis for microbiological
with the very few trials that have been performed pathogens should include an x-ray of the affected
hampered by small numbers, inappropriate com- foot, along with tissue culture. If no osteomyelitis
parators and poor study design. There is little evi- is identified, a non-limb-threatening foot ulcer
dence to support the use of any particular dressing. with clinical infection should be treated with a
broad-spectrum antibiotic. When sensitivities are
known, targeted appropriate narrow-spectrum
agents should be prescribed. Suitable initial broad-
Management of Infection
Initial management of foot ulcers is guided by spectrum cover might include agents such as an
Patients with a limb-threatening infection general- amongst these, probing to bone has been shown to
ly display systemic systems and signs, and require have the greatest predictive value, whereas plain
hospitalization and parenteral antibiotics. Deep radiographs are insensitive in early states in the
wound and blood cultures should be obtained, the natural history of osteomyelitis. Whereas the diag-
circulation assessed with non-invasive studies and nosis is ultimately made in most cases using a
metabolic control should be optimized. Early sur- plain radiograph of the foot, magnetic resonance
gical debridement is indicated in such cases and, imaging (MRI) is playing an increasing role in the
as above, antibiotic regimens should be broad- diagnosis, as it has high sensitivity. The most
spectrum until sensitivities are known. For such recent review on this topic suggests that a combi-
serious infections, a combination of clindamycin nation of clinical and laboratory findings can sig-
and ciprofloxacin, or flucloxacillin, ampicillin and nificantly improve diagnostic accuracy for
metronidazole may be suitable. osteomyelitis in the diabetic foot. Most helpful is
the combination of ulcer depth with serum inflam-
An increasing concern with diabetic foot clinics is matory markers.19 Contrary to traditional teaching,
the identification and isolation of antibiotic-resist- it is increasingly recognized that some cases of
ant pathogens, such as Methicillin-resistant localized osteomyelitis, particularly those not
Staphylococcus Aureus (MRSA). In most cases, involving a joint space, can be managed by long-
such organisms are opportunistic colonizers rather term antibiotic therapy. Despite this, localized
than true pathogens, and are secondary to the often bony resection after appropriate antibiotic therapy
inappropriate use of long duration broad-spectrum remains the most common approach to care. It is
antibiotics. Anti-MRSA specific therapies are clear that further research is needed in this area, as
rarely indicated. the evidence base for diagnosis and management
of osteomyelitis remains very limited.20
Adjunctive Therapies
growth factors, bioengineered skin substitutes and Ulcers in which there is a major ischemic compo-
others have been studied in the last decade. nent are generally graded C or D (with or without
However, there is little evidence to support their infection) under the UT wound classification sys-
regular use in the management of diabetic foot tem. All patients presenting with foot ulcers in
lesions. Many of these have recently been which any degree of ischemia is suspected should
reviewed by the international working group on have a non-invasive vascular assessment and be
the diabetic foot.18 There is some evidence for the considered for arteriography. In addition to
use of hyperbaric oxygen, but this is generally of offloading and the management of infection,
benefit only in ischemic ulcers with infection, patients with significant arterial lesions warrant
when there is no possibility of distal bypass or assessment by vascular surgery, and bypass should
angioplasty. There is stronger evidence to support be considered, if appropriate. In the presence of
the use of negative pressure wound therapy osteomyelitis (UT 3D), ischemia can significantly,
(NPWT) using vacuum-assisted closure in the adversely influence the outcome. If possible, pro-
management of complex diabetic foot wounds.2 cedures to improve arterial inflow should be car-
Recent randomized, controlled trials suggest that ried out prior to any surgical treatment of
this modality might lead to more rapid appearance osteomyelitis, and all patients should be on appro-
of granulation tissue, with a lesser chance of priate antibiotic therapy. There is reasonable evi-
recurrent ulceration or even amputation.7 dence that patients with significant arterial impair-
ment, as confirmed by a low transcutaneous oxy-
gen tension (TCOT), may experience delayed CN was first described in the mid-19th century by
healing and an increased risk of amputation. Jean-Martin Charcot, a Parisian neurologist. In the
Western world, diabetes is now the most common
cause of this largely preventable and common
clinical problem. An accepted definition of a
Charcot joint is one in which there is simultaneous
presence of bone and joint destruction, fragmenta-
tion and remodeling: this condition is generally a
painless, progressive and destructive arthropathy.
offloading the affected foot using TCC (as an Diabetic foot disease causes significant morbidity
example), is an effective means to reduce disease and is associated with increased mortality. It
activity during this acute phase. Use of the cast should be clear that the spectrum of diabetic foot
should continue until swelling and hyperemia have problems requires the involvement of individuals
resolved and the skin temperature differential is from many specialties. The diabetic foot cannot be
1° C or less, at which time custom-molded shoes regarded as the sole responsibility of the diabetol-
with appropriate insoles are indicated. ogist alone, and a number of reports in the past
Bisphosphonates, potent inhibitors of osteoclast decade have promoted the benefits of multi-disci-
activation, have been suggested as useful adjunc- plinary management of the diabetic foot. There is
tive therapy in reducing disease activity in acute increasing evidence from long-term studies that
CN in a randomized trial. However, further confir- support the adoption of a multi-disciplinary
mation is needed and trials are ongoing. approach, not only in the hospital, but in the com-
munity setting, and this approach is associated
The management of advanced CN with bony with a reduced incidence of foot complications.24
deformity requiring reconstructive surgery is There is substantial evidence that a sustained
beyond the scope of this chapter and the reader is reduction in major amputations can be achieved
referred to a recent review by Robinson et al for and maintained over 20 years, and all these data
additional detail.23 suggest that an aggressive approach to screening
and management of diabetic foot problems in the
future is likely to be associated with improved
outcomes.25
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Complexity of factors related to outcome of arterial disease in people with diabetes.
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aspects of diabetic foot lesions. Curr Diab
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WJ. Education for secondary prevention of
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SE, Wrobel JS, Armstrong DG. Combined
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