July 2004

An MWC Publication

The Diabetic Foot Ulcer:

Management and Prevention
Strategies in Primary Care

CME-CE Certified Activity

Sponsored by the University of Medicine & Dentistry of New
Jersey (UMDNJ)Center for Continuing and Outreach Education

Release Date: July 2004

Expiration Date: June 30, 2005
Nursing credit for this activity will be
provided through June 30, 2005.

www.residentandstaff.com
2004 UMDNJ-Center for Continuing
and Outreach Education and
Romaine Pierson Publishers, Inc.

This activity is supported by

an unrestricted educational
grant from

 Ira A. Grunther

The Diabetic Foot Ulcer: Management and

Prevention Strategies in Primary Care

MWC Publishing Staff

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PROJ R163

The Diabetic Foot Ulcer: Management and Prevention Strategies in Primary Care
CME-CE Certified Activity Sponsored by the
University of Medicine & Dentistry of New Jersey (UMDNJ)
Center for Continuing and Outreach Education
Release Date: July 2004 Expiration Date: June 30, 2005
This activity is supported by an unrestricted educational grant from Novo Nordisk.
Introduction:
The purpose of this activity is to educate health care providers on the management and prevention of
diabetic foot ulcer.
Target Audience:
This activity is designed for primary care practitioners, nurses, and pharmacists.
Learning Objectives:
Upon completion of this activity, participants should be able to:
Discuss the causes and risk factors of foot ulcer in diabetic patients
Determine the severity of foot ulcer in a particular patient
List application of appropriate treatment
Describe measures to prevent occurrence of foot ulcer
Method of Instruction:
Participants should read the learning objectives and review the activity in its entirety. After reviewing the
material, complete the post-test/self-assessment test consisting of a series of multiple-choice questions.
Upon completing this activity as designed and achieving a passing score of 70% or more on the post-test,
participants will receive a CME-CE credit letter awarding AMA/PRA category 1 credit, nursing continuing education credit, pharmacy continuing education credit, and the test answer key four (4) to six (6) weeks after receipt of the post-test, registration, and evaluation materials.
Estimated time to complete this activity as designed is 1.0 hour.
Physician Accreditation:
UMDNJCenter for Continuing and Outreach Education is accredited by the Accreditation Council for
Continuing Medical Education to provide continuing medical education for physicians.
UMDNJCenter for Continuing and Outreach Education designates this educational activity for a maximum
of 1.0 category 1 credit toward the AMA Physicians Recognition Award. Each physician should claim only
those credits that he/she actually spent in the activity.
The activity was prepared in accordance with the ACCME Essentials.
Nursing Accreditation:
UMDNJCenter for Continuing and Outreach Education is an approved provider of continuing education
by the New Jersey State Nurses Association (NJSNA), Provider Number P173-9/2003-2006. Provider Approval
is valid through June 30, 2005. NJSNA is accredited by the ANCC Commission on Accreditation. This activity
is approved for 1.0 contact hours.
Provider approved by the California Board of Registered Nursing, Provider Number CEP 13780 for 1.0
contact hours.
Pharmacy Accreditation:
UMDNJ is accredited by the American Council on Pharmaceutical Education as a provider of
continuing pharmaceutical education. This course 374-000-04-017-H01 qualifies for 1.0 contact hour
(0.100 CEU) of continuing pharmacy credit, which will be awarded via mail within four (4) to
six (6) weeks after successful completion of the program. Release Date: July 2004 Expiration
Date: June 30, 2005.
This activity was reviewed for relevance, accuracy of content, balance of presentation, and time required for
participation by Azeez Farooki, MD; Anne Marie Van Hoven, MD; Ms. Lorna Austin, CPhT; Ms. Jennifer
Nishioka, RPh; Ms. Helene Mitzi Dolese, RN, CIM; Joanne Librie, RN; and Irina Lipets, RN, BSN.

The Diabetic Foot Ulcer

Faculty:
Mark Angelo, MD
Assistant Faculty, Internal Medicine
University of Medicine & Dentistry of New Jersey
Robert Wood Johnson Medical School
Cooper Health System
Camden, NJ

Arthur Nam, MD, MS

Resident
Department of Surgery
George Washington University Medical Center
Washington, DC

Program Directors:
Dorothy Caputo, MA, APRN, BC-ADM, CDE
Director of Special Initiatives
Continuing and Outreach Education
Assistant Professor,
UMDNJSchool of Health Related Professions
New Brunswick, NJ

Diana Vamos, PharmD

Clinical Oncology Pharmacist
The Cancer Institute of New Jersey
New Brunswick, NJ

Disclosure:
In accordance with the disclosure policies of UMDNJ and to conform with ACCME, ACPE, ANCC-COA,
and FDA guidelines, all program faculty are required to disclose to the activity participants: (1) the existence of
any financial interest or other relationships with the manufacturers of any commercial products/devices, or
providers of commercial services, that relate to the content of their presentation/material, or the commercial
contributors of this activity, that could be perceived as a real or apparent conflict of interest; and (2) the identification of a commercial product/device that is unlabeled for use or an investigational use of a product/device
not yet approved.
Faculty Disclosure Declarations:
Drs Angelo, Nam, and Vamos, and Ms Caputo have no significant financial relationships to disclose.
Field Tester Disclosure Declarations:
Drs Van Hoven and Farooki and Ms Austin, Dolese, Librie, Lipets, and Nishioka have no significant
financial interests to disclose.
Off-Label Usage Disclosure:
This activity does not contain information of commercial products/devices that are unlabeled for use or
investigational uses of products not yet approved.
Disclaimer:
The views expressed in this activity are those of the faculty. It should not be inferred or assumed that they
are expressing the views of Novo Nordisk, any other manufacturer of pharmaceuticals, UMDNJ, or Romaine
Pierson Publishers, Inc.
Accreditation refers to recognition of continuing nursing education activities only and does not imply the
University of Medicine and Dentistry of New JerseyCenter for Continuing and Outreach Education, NJSNA,
California Board of Registered Nursing or ANCC Commission on Accreditation approval or endorsement of
any commercial product.
The drug selection and dosage information presented in this activity are believed to be accurate. However,
participants are urged to consult the full prescribing information on any agent(s) presented in this activity for
recommended dosage, indications, contraindications, warnings, precautions, and adverse effects before prescribing any medication. This is particularly important when a drug is new or infrequently prescribed.
Copyright 2004 UMDNJCenter for Continuing and Outreach Education and Romaine Pierson
Publishers, Inc. All rights reserved including translation into other languages. No part of this activity may
be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying,
recording, or any information storage and retrieval systems, without permission in writing from UMDNJ
Center for Continuing and Outreach Education and Romaine Pierson Publishers, Inc.

 Ira A. Grunther

The Diabetic Foot Ulcer: Management and

Prevention Strategies in Primary Care
Foot ulcers are a major cause of morbidity and mortality in
patients with diabetes. Health care providers who appreciate the
scope of the problem and have a thorough understanding of the
pathophysiology of diabetic neuropathy and known risk factors
can prevent many of these foot ulcers and their complications.
Instructing patients to observe for first signs of foot ulcers can
lead to early intervention and prevention of complications.
Treatment of established lesions depends on wound characteristics,
causative organisms, and comorbidities and may require topical
or systemic antimicrobial therapy and/or surgical intervention.
Mark Angelo, MD
Assistant Faculty, Internal Medicine
University of Medicine & Dentistry
of New Jersey
Robert Wood Johnson Medical School
Cooper Health System
Camden, NJ

Arthur Nam, MD, MS

Resident
Department of Surgery
George Washington University
Medical Center
Washington, DC

Most recent estimates by the

Centers for Disease Control and
Prevention in Atlanta point to a
prevalence of 18.2 million people
in the United States with diabetes,1
approximately 15% of whom will
have a foot ulcercommonly referred to as diabetic footin their
lifetime.2 Frequently limb threatening, as many as 14% to 24% of diabetic patients with a foot ulcer will
require amputation.3 The vast majority of diabetic foot ulcers are
caused by vascular and mechanical
factors in conjunction with diabetic
neuropathy. Diabetic neuropathy is
apparent as damage to the sensory,
motor, and autonomic nervous systems and is present in approximately 30% of the diabetic population.2
The economic impact of the compli-

cations of diabetic neuropathy is

considerable. In 2001, approximately $10.9 billion was spent on
diabetic neuropathy and associated complications, up to 27% of total medical costs of diabetes.3 This
article discusses risk factors for the
development of foot ulcers, the
pathogenesis of diabetic neuropathy,
foot ulcer classification, and management and prevention strategies.

Who Is at Risk for Diabetic

Foot Ulcer?
Factors associated with an increased risk for foot ulcers include
having diabetes for more than 10
years, male gender, poor blood
glucose control, and coexistent
cardiovascular, retinal, or renal
complications.3 Specific foot-related conditions also increase the risk
for foot ulcerations, including peripheral neuropathy with loss of
protective sensation, altered foot
biomechanics in the presence of
neuropathy, bony deformity, significant peripheral vascular disease, history of ulcers or amputation, and severe nail pathology.

Pathogenesis of Diabetic
Neuropathy
The pathogenesis of diabetic neuropathy involves a complex interre-

July 2004 Resident & Staff Physician

The Diabetic Foot Ulcer

lationship between metabolic and

ischemic factors and nerve repair
mechanisms (Figure 1). Major emphasis has been placed on the polyol pathway, as depicted in Figure 2.
Sorbitol, which appears to function
as a tissue toxin, has been implicated in the development of neuropathy, retinopathy, nephropathy, and
aortic disease.4,5 Under physiologic
concentrations of substrate, aldose
reductase has a low affinity for glucose, and little sorbitol is produced.
However, in the presence of profound and chronic hyperglycemia,
much greater amounts of sorbitol
are produced. In an experimental
model of diabetic neuropathy, sorbitol accumulation was associated
with a decrease in myoinositol content, abnormal phosphoinositide
metabolism, and a decrease in Na+K+-ATPase activity.4 The primacy of
the polyol pathway in the initiation
of neuropathy is supported by evidence showing that inhibition of aldose reductase corrects the level of
myoinositol in nerves and restores
full Na+-K+-ATPase activity.6
Another factor of pathogenic
importance is the glycation of serum and tissue proteinssuch as
plasma albumin, lens protein, fibrin, collagen, and lipoproteins
from chronic hyperglycemia.7 In
this process, excess glucose combines with free amino acids on
serum or tissue proteins, initially
forming reversible, early glycated
products and later, irreversible,
advanced glycation end products
(AGE).7,8 Receptors for AGE are
present on macrophages and endothelial cells, and the binding of
AGE to its receptors may induce
the synthesis and release of cytokines, vascular adhesion molecules,
endothelin-1, and tissue factor.
AGE may also decrease endothe-

4 Resident & Staff Physician

Hyperglycemia

Increased aldose
reductase activity

Sorbitol accumulation, neural

myoinositol depletion, decreased
Na+-K+-ATPase
activity

Increased DAG,
PKC activity

Altered endothelial cell

permeability; altered
signal transduction and
hormone responsiveness
of vascular
smooth muscle

Glycation of
proteins, AGE

Activation of endothelial macrophage

AGE receptors; altered
basement membrane
proteins, lipoproteins,
matrix proteins

Cytotoxicity of neural, glial, and

vascular component of peripheral
nerve; nerve damage

Diabetic complications
AGE = advanced glycation end products; DAG = diacylglycerol; PKC = protein kinase C.

Figure 1Pathogenesis of diabetic neuropathy. Adapted from Rose BD, McCulloch DK.
Glycemic control and vascular complications in type 1 diabetes mellitus. UpToDate.
www.uptodate.com.

lial-derived nitric oxide as well as

alter basement membrane proteins,
lipoproteins, and cellular matrix.
Activation of vascular protein
kinase C (PKC) isoforms also appears to be important to the development of diabetic neuropathy.
PKC activities are increased in the
glomeruli, retina, aorta, and heart
of diabetic animals.9 Heightened
activity is thought to be caused by
enhanced de novo synthesis of diacylglycerol (DAG), a major endogenous activator of PKC.10 Evidence
shows that activated PKC increases
levels of messenger ribonucleic acid
encoding matrix components in

glomeruli and produces many of

the vascular abnormalities induced
by high glucose levels.8

Causes of Foot Ulcer

Pathophysiologic factors involved in the development of diabetic foot ulcers are neuropathy, arterial insufficiency, musculoskeletal
abnormalities, and poor wound
healing (Figure 3). Microbial pathogens, which will be discussed later,
also play a key role. Additionally,
poor nutrition compromises the
healing process. Therefore, especially in elderly patients or those
with other comorbidities, a nutri-

The Diabetic Foot Ulcer

NADPH

NADP

NAD

Sorbitol

Glucose
Aldose reductase

Osmotic
effects

NADH

Fructose
Sorbitol dehydrogenase

Decreased
cell myoinositol

Other?

NAD = nicotinamide adenine dinucleotide; NADH = the reduced form of nicotinamide adenine dinucleotide; NADP = nicotinamide adenine dinucleotide phosphate; NADPH = the reduced form of nicotinamide adenine dinucleotide phosphate.

Figure 2Role of sorbitol in diabetic microvascular disease. Adapted from Frank RN.
On the pathogenesis of diabetic retinopathy. A 1990 update. Ophthalmology. 1991;98:
586-593.

tionist should be consulted to provide guidance and assist with food

choices and supplements as needed.

Neuropathy
The cytotoxic, ischemic/hypoxic
effects of sorbitol, AGE, and DAG/
PKC are thought to disrupt signal
transduction in the peripheral nerves.
Malfunction of the sensory nervous
system leads to a segmental demyelinization process in type-A sensory fibers, which are involved with
proprioception and the sensations of

activation of signal transduction

along these pathways, leading to
the pain and paresthesias of diabetic neuropathy, which, coupled with
lack of sensation, leaves the patient
with an ataxic gait. The clinical
consequence of these disrupted
fibers is the loss of crucial protective sensation, which heightens susceptibility to mechanical, chemical,
or thermal injury.11 The trauma can
remain undetected, resulting in inflammation, further mechanical injury, and ulceration.12

In persons with diabetic neuropathy,

the small intrinsic muscles of the foot
atrophy as a result of demyelinization
in distal motor nerves.
light touch, pressure, and vibration.
The type-C sensory fibers, which
are associated with free nerve endings that sense noxious, painful,
and thermal stimuli, are similarly
affected.11 Damage to these fibers
may initially result in pathologic

In persons with diabetic neuropathy, the small intrinsic muscles of the

foot atrophy as a result of demyelinization in distal motor nerves. This
leads to an imbalance of the flexor
and extensor muscles and clawing
or curling of the toes. Clawing, a

typical foot posture in peripheral

neuropathy, shifts the foot position
so that the toes bear less weight and
the metatarsal heads become more
prominent. The metatarsal-phalangeal joints can become unstable
secondary to wasting of the lumbrical and interosseous muscles, and
overpowering extrinsic muscles can
depress the metatarsal heads, contract
the digits, and cock up the toes.11
These changes increase weightbearing on the metatarsal heads and are
manifested by a dysfunctional gait.
As the pathologic process continues,
the soft tissue covering the bones is
exposed to abnormal compressive
and shearing stress as it rubs against
footwear during walking. With continuing exposure to shearing stress,
the skin forms callus. Although this
is initially a protective response, as
time progresses, all that remains between the callus and the affected
bone is a thin layer of tissue that is
subjected to additional shearing
stress that may destroy tissue and
cause inflammation, bleeding, and
eventual ulcer formation.12-14
Finally, the autonomic nervous
system directly influences peripheral circulation in the extremities by
supplying the sympathetic adrenergic fibers that regulate arteriole vasomotor tone and blood flow
through arteriovenous shunts.15
Failure of sympathetic control results in arteriolar vasodilatation,
which reduces peripheral resistance, increases arteriovenous
shunt flow, and increases cutaneous
blood flow at the expense of perfusion of the deeper structures. The
greater cutaneous flow is responsible for the frequently encountered
elevated foot temperatures and distended dorsal veins observed in patients with diabetic neuropathy.
Blood that is bypassing the capil-

July 2004 Resident & Staff Physician

The Diabetic Foot Ulcer

lary bed via the arterio-venous

shunting may increase capillary
pressure and neuropathic edema in
the foot.16,17 This edema can further
exacerbate foot pressures and contribute to ulceration.
Adding to the problems caused
by autonomic dysfunction is diabetic anhidrosis. This represents a
sudomotor impairment characterized by decreased sweating that results in dry, scaly, cracked skin,
which facilitates the introduction
of infectious agents.18

Sensory dysfunction

Motor dysfunction

Decreased sensory
perception of:

Small
muscle atrophy

Decreased
sweating

Imbalance of flexor
and extensor muscles

Dry, scaly
skin

Clawed toes

Fissures

Edema

Prominent
metatarsal heads

Infection

Poor wound
healing

Autonomic dysfunction

Arteriovenous shunt

Pain
Vibration
Temperature

Decreased
capillary pressure

Touch

Injury:

Arterial insufficiency

Mechanical

In diabetes, ischemia secondary

to vascular disease interferes with
healing by limiting the supply of
oxygen, nutrients, and the cellular
and soluble mediators involved in
the repair process.19 Blood flow to
the foot is decreased, primarily because of atherosclerotic obstruction of the major conduit vessels,
characteristically involving the tibial and peroneal vessels, while
sparing those in the pedal arch.
Microvascular dysfunction adds to
the vascular problems.20 Defective
hyperemic responses and endothelial dysfunction may also be important in the pathogenesis of foot
ulcers in patients with diabetic
neuropathy. A gradient of oxygen
tissue pressure is required for fibroblast growth and the initiation
of angiogenesis, while chronic hypoxia impairs wound healing.2

Thermal

Musculoskeletal abnormalities
Diabetic patients are susceptible
to musculoskeletal abnormalities of
the foot, such as neuropathic arthropathy, previously known as
Charcots foot. Neuropathic arthropathy is characterized by
chronic, progressive, degenerative
disease of 1 or more joints and is

6 Resident & Staff Physician

Chemical
Altered gait

Callus

Foot ulcer
Figure 3Pathophysiology of foot ulcers from diabetic neuropathy. Adapted from
Zangara GA, Hull MM. Diabetic neuropathy: pathophysiology and prevention of foot
ulcers. Clin Nurse Spec. 1999;13:57-65.

identified by swelling, bleeding, increased temperature, bone changes,

and joint instability. This disease
process likely stems from recurring
trauma secondary to loss of pain
and proprioception or from the
previously described autonomic
neuropathy that shunts blood to
the skin away from the deep tissues
and results in osteopenia.21 The end
result of these musculoskeletal abnormalities is improper loading of
the joints, uneven weight distribution, and repeated trauma.21

Poor wound healing

The biology of wound healing
can be thought of as a succession of

unique cellular and physiologic

events.22 Normally, at the time of
injury, blood vessels rupture, exposing matrix proteins and leading
to platelet aggregation, clot formation, and hemostasis.2 Platelets release cytokines and growth factors
that stimulate further proliferation
of the clot and the recruitment and
mitogenesis of cellular elements.2
Neutrophils are recruited within
minutes to hours of the injury, and
more mediators and chemotactic
substances are released. Subsequently, monocytes are activated to
form tissue macrophages, which
play a critical role in suppressing
bacterial growth and clearing exis-

The Diabetic Foot Ulcer

Clinical Presentation
Common sites of foot ulcers are
the metatarsal heads and distal
phalanx, medial and lateral midfoot, and the heel. Various methods

Mild ulcers
Mild, nonlimb-threatening ulcers are often shallow lesions with a
clean base and less than 2 cm of surrounding cellulitis, with no evidence
of fasciitis, abscess, or osteomyelitis. No ischemic process is involved,
and the patient has good blood glucose control. Initial treatment includes oral antibiotics and wound
care. The causative organisms for
these ulcers are primarily aerobic
gram-positive cocci (eg, Staphylococcus aureus and streptococci).23

infectious process involving the

bone, an MRI should be obtained.
Diabetic patients presenting
with this type of ulcer should be
hospitalized immediately for intravenous antibiotic therapy and surgical consultation. The causative
organisms of such ulcerations are
characteristically polymicrobial
aerobic gram-positive cocci, strict
anaerobes (eg, Bacteroides fragilis), or gram-negative bacilli (eg,
Escherichia coli).

Courtesy of John S. Steinberg, DPM

of grading the severity of diabetic

foot infection have been used. Joshi
and colleagues recently described a
useful classification system that divides ulcers into those that do and
do not threaten loss of limb.23

Courtesy of John S. Steinberg, DPM

tent bacteria and necrotic tissue.2

Macrophages continue releasing
cytokines and growth factors, which
bring fibroblasts and endothelial
cells to the wound.2 Reperfusion
depends on angiogenesis, which, in
turn, depends on the migration of
endothelial cells to the site of injury.2 The clonal expansion of cells,
particularly fibroblasts, appears to
define wound healing. Wound closure, occurring from the rim of the
wound inward, is characterized by
complete epithelialization. The end
of healing is heralded by the migration of keratinocytes to the wound
site. During this remodeling phase,
tensile strength and cellular organization improve, skin integrity returns, and the wound contracts.2
Chronic hyperglycemia in diabetic patients disrupts the normal
cellular and inflammatory pathways involved in wound healing
and increases susceptibility to infection.4 Individuals with diabetes
have been found to have abnormal
cellular function, particularly of fibroblasts and neutrophils.2 In addition, AGE alters endothelial and
macrophage activation, which interferes with cytokine production
and cellular migration. AGE may
also be detrimental to basement
membrane proteins, extracellular
matrix production, and endothelial-derived nitric oxide production. There is also evidence to suggest that increased DAG and PKC
activity changes endothelial cell
permeability, signal transduction,
and the hormone responsiveness
of vascular smooth muscle.9,10

Severe ulcer.

Treatment

Mild ulcer.

Localized care

Severe ulcers
Limb-threatening ulcers are
those characterized by deep infection and more than 2 cm of cellulitis. Such ulcers involve ischemia,
and their metabolic control is poor.
At presentation these foot ulcers
often have evidence of fasciitis or
frank abscess formation. X-ray
films of the foot may demonstrate
periosteal lifting associated with
osteomyelitis. Palpation of bone
with a metal probe would also signify osteomyelitis. If the situation
is unclear as to the presence of an

Localized care of diabetic foot ulcers consists of topical antimicrobial

therapy, appropriate dressing application, foot elevation, debriding
agents, and limitation of weightbearing activities.24 The success of localized care depends on a high degree of compliance by the patient
and caregiver. Topical antimicrobial
agents, such as silver sulfadiazine (eg,
Silvadene cream, Thermazene) and
mupirocin (Bactroban), can stimulate wound healing by eliminating
bacteria on the wound surface. They
should be used, however, only as ad-

July 2004 Resident & Staff Physician

The Diabetic Foot Ulcer

junctive therapy. The use of povidine-iodine solutions (Betadine) and

ointments (Betadine ointment) on
healing tissue remains controversial.
Foot soaks and lubricating lotions
have been recommended in the past,
but their efficacy has not been
proven in controlled trials.
Chemical or enzymatic debriding
agents are reserved for patients with
mild ulcers (as defined above) or
those who refuse surgical debridement. Options for topical debriding
agents include collagenase (Santyl)
or papain-urea (Accuzyme, Panafil).
Becaplermin gel (Regranex) has
been found to significantly increase the incidence of complete
wound closure and significantly
reduce the time to complete closure of diabetic foot ulcers.25
A moist environment is most
conducive to formation of a nascent tissue matrix. Several existing
products promote maintenance of
a moist wound. A recent Cochrane
Review examining 3 randomized
controlled trials of hydrogel dressing products found a significant
improvement over saline dressings
alone.26
Larval therapy with sterile maggots has been described in patients
failing other types of therapy for
debridement of necrotic tissue.27

Surgical intervention
Surgery, which can consist of
drainage, debridement, and often
amputation, is important for preserving tissue, maximizing revascularization, and promoting healing.28 The goal of early, aggressive
debridement and drainage is to remove all necrotic soft tissue and
bone.2 Even for patients with poor
circulatory status, it is important
to establish dependent drainage to
prevent pooling of pus. There is no

8 Resident & Staff Physician

evidence to support soaking an ulcerated foot in a whirlpool or other hydrotherapies.2 In fact, such
measures could result in maceration, infection, or burns. The decision to perform surgery must be
made with caution because, while
the intervention can remove the
source of infection, too much manipulation can impair healing by
further damaging the tissues.28

Intraveneous antimicrobial therapy is initiated when systemic or

extensive infection is suspected,
most commonly in patients who
have developed septicemia or osteomyelitis.29 The recommended
agents include a beta-lactam plus a
beta-lactamase inhibitor (eg, ampicillin sodium/sulbactam sodium
[Unasyn]) or clindamycin plus a
gram-negative drug (eg, a third-

Diabetic patients must be instructed

about proper and consistent foot care.
Feet should be kept clean and dry
at all times. Patients with neuropathy
should not walk barefoot, even in the
home. Properly fitted shoes are essential.
Systemic antimicrobial therapy
The choice of antimicrobial
agent is based on the suspected bacterial flora, appearance of the infected site, history of the lesion, and
general condition of the patient. It
is important to use drugs that are
bactericidal, since diabetic patients
have poor immune defenses, and if
the pathogen is not eliminated, the
infection will recur. Oral antimicrobial therapy can be used to treat
mild, superficial lesions when the
infection is in the early stages,
drainage is minimal, gangrene is
absent, and the patient does not
have systemic symptoms. More severe ulcerations will require intravenous antimicrobial therapy.29
Recommended oral agents include cephalexin (Biocef, Keflex),
clindamycin (Cleocin), and amoxicillin/potassium clavulanate
(Augmentin).29

generation cephalosporin, a fluoroquinolone, or aztreonam [Azactam]). Caution should be used with

fluoroquinolones in diabetic patients because these medications
may worsen glycemic control. Vancomycin (Vancocin, Vancoled) plus
imipenem-cilastatin (Primaxin) is
used for life-threatening infections.29 Linezolid has been recently
evaluated and has shown promise
as an alternative therapy. However,
there appears to be no benefit of
linezolid over ampicillin/sulbactam. The cost of linezolid often
will limit its availability, especially
in an outpatient setting.30
The recommended length of
therapy for soft tissue infection is
2 to 3 weeks, for osteomyelitis it is
4 to 6 weeks.24,31 Ultimately, the
length of treatment depends on the
severity of the infection, the
causative organism, and the clini-

The Diabetic Foot Ulcer

cal response to the chosen medication. It is important to continue

antibiotic therapy until an infection has been eliminated.

Prevention Is Key
Glycemic control is paramount
in the prevention of diabetic neuropathy and the development of
diabetic foot ulcers. A chronically
elevated blood glucose concentration is the initial factor that sets in
motion the pathogenic process of
neuropathy.
Diabetic patients must be instructed about proper and consistent foot care to prevent ulcers.
Feet should be kept clean and dry
at all times. Patients with neuropathy should not walk barefoot,
even in the home. Properly fitted
shoes are essential. This is a particular problem with women, since
an adequate shoe is not often stylish. Patients should be told to inspect their feet carefully daily for
callus, infection, abrasions, foreign bodies, or blisters and to consult the physician about any potentially troublesome lesion.
The National Diabetes Education Program recommends that all
patients with diabetes have a thorough foot examination at least annually to assess the condition of the
skin and nails and to evaluate for
the presence of any sensory or
skeletal abnormalities.32 Proprioception and standardized sensory
evaluation should be performed to
help identify patients at risk. Standardized sensory evaluation is best
accomplished with the SemmesWeinstein monofilament at various locations of the foot, including the toes, the metatarsal head
area, and the heel. High-risk patients are defined as those who lack
palpable pedal pulses, have abnor-

malities of protective sensation,

foot deformities, and a history of
foot ulcers or amputations; they
should have a visual foot inspection
at every visit. High-risk patients
should also be referred to the appropriate foot care specialist.
Patients with diabetes and highrisk foot conditions should be educated regarding their risk factors
and appropriate management. A
nonjudgmental assessment of a
persons current knowledge and
care practices should be obtained
first. Patients at risk should understand the implications of the loss
of protective sensation, the importance of foot monitoring on a daily basis, the proper care of the
foot, including nail and skin care,
and the selection of appropriate
footwear. The patients understanding of these issues and their
physical ability to conduct proper
foot surveillance and care should
be assessed. Patients with neuropathy should be advised to
break in new shoes gradually to
minimize the formation of blisters
and ulcers. Patients with visual
difficulties, physical constraints
preventing movement, or cognitive
problems that impair their ability
to assess the condition of the foot
and to institute appropriate responses will need other people,
such as family members, to assist
in their care. Patients at low risk
may benefit from education on
foot care and footwear.33

Conclusion
Peripheral diabetic neuropathy
affects nearly one third of all patients with diabetes. Foot ulceration
is a preventable complication in
those with peripheral neuropathy.
Better understanding of the pathophysiologic basis of foot ulcers can

assist health care providers in the

evaluation, diagnosis, and treatment
of diabetic foot ulcers. It is also critical to provide thorough, regular foot
assessments with standardized sensory evaluations, skin assessment,
and bony alignment evaluation as
well as patient and family education. If begun early, these interventions for health promotion and disease prevention can help patients
identify the early signs and symptoms of diabetic foot ulcers before
extensive complications occur,
thereby improving their quality of
life, preventing pain and amputation, and reducing the health care
costs of this chronic disease.

References

1. Centers for Disease Control and Prevention. National diabetes fact sheet: general
information and national estimates on diabetes in the United States, 2003. Rev ed. Atlanta, Ga: U.S. Department of Health and
Human Services, Centers for Disease Control and Prevention, 2004.
2. http://www.diabetes.org/info/diabetesinfo.jsp.
3. Gordois A, Scuffham P, Shearer A, et al.
The health care costs of diabetic peripheral
neuropathy in the U.S. Diabetes Care.
2003;26:1790-1795.
4. Greene DA, Lattimer SA, Sima AA. Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic
complications. N Engl J Med. 1987;316:
599-606.
5. Kador PF, Kinoshita JH. Role of aldose
reductase in the development of diabetesassociated complications. Am J Med. 1985;
79(suppl 5A):8-12.
6. Greene DA, Lattimer SA. Action of
sorbinil in diabetic peripheral nerve. Relationship of polyol (sorbitol) pathway inhibition to a myoinositol-mediated defect in
sodium-potassium ATPase activity. Diabetes.
1984;33:712-716.
7. Vlassara H. Protein glycation in the kidney: role in diabetes and aging. Kidney Int.
1996;49:1795-1804.
8. Brownlee M. Lilly Lecture 1993. Glycation and diabetic complications. Diabetes.
1994;43:836-841.
9. Inoguchi T, Battan R, Handler E, et al.
Preferential elevation of protein kinase C
isoform II and diacylglycerol levels in the
aorta and heart of diabetic rats: differential
reversibility to glycemic control by islet cell
transplantation. Proc Natl Acad Sci U S A.
1992;89:11059-11063.
10. Wolf BA, Williamson JR, Eamon RA, et

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al. Diacylglycerol accumulation and microvascular abnormalities induced by elevated glucose levels. J Clin Invest. 1991;87:31-38.
11. Sumpio BE. Foot ulcers. N Engl J Med.
2000;343:787-793.
12. Boulton AJM. The pathogenesis of diabetic foot problems: an overview. Diabet
Med. 1996;13(suppl 1):S12-S16.
13. Collier JH, Brodbeck CA. Assessing the
diabetic foot: plantar callus and pressure
sensation. Diabetes Educ. 1993;19:503-508.
14. Stess RM, Jensen SR, Mirmiran R. The
role of dynamic plantar pressures in diabetic
foot ulcers. Diabetes Care. 1997;20:855-858.
15. Bornmyr S, Svensson H, Lilja B, et al.
Cutaneous vasomotor responses in young
type I diabetic patients. J Diabetes Complications. 1997;11:21-26.
16. Purewal TS, Goss DE, Watkins PJ, et al.
Lower limb venous pressure in diabetic neuropathy. Diabetes Care. 1995;18:377-381.
17. Uccioli L, Mancini L, Giordano A, et al.
Lower limb arterio-venous shunts, autonomic neuropathy and diabetic foot. Diabetes Res Clin Pract. 1992;16:123-130.
18. Spallone V, Uccioli L, Menzinger G.
Diabetic autonomic neuropathy. Diabetes
Metab Rev. 1995;11:227-257.
19. Singer AJ, Clark RAF. Cutaneous wound

healing. N Engl J Med. 1999;341:738-746.

20. Kamal K, Powell RJ, Sumpio BE. The
pathobiology of diabetes mellitus: implications for surgeons. J Am Coll Surg. 1996;
183:271-289.
21. Brower AC, Allman RM. Pathogenesis
of the neurotrophic joint: neurotraumatic
vs. neurovascular. Radiology. 1981;139:
349-354.
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of wound healing. Surg Clin North Am.
1997;77:509-528.
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et al. Infections in patients with diabetes
mellitus. N Engl J Med. 1999;341:19061912.
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Surg. 1987;26(suppl):S7-S11.
25. Wieman TJ, Smiell JM, Su Y. Efficacy and
safety of a topical gel formulation of recombinant human platelet-derived growth factorBB (becaplermin) in patients with chronic
neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind
study. Diabetes Care. 1998;21:822-827.
26. Smith J. Debridement of diabetic foot
ulcers. Cochrane Database Syst Rev. 2002;

(4):CD003556.
27. Stoddard SR, Sherman RA, Mason BE,
et al. Maggot debridement therapy. An alternative treatment for nonhealing ulcers. J Am
Podiatr Med Assoc. 1995;85:218-221.
28. Hollingshead TS. Pathophysiology and
treatment of diabetic foot ulcer. Clin Podiatr Med Surg. 1991;8:843-855.
29. Joseph WS. Treatment of lower extremity infections in diabetics. Drugs. 1991;42:
984-996.
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1193-1203.
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Diabetes Care. 2004;27(suppl 1):S63-S64.

CME-CE Questions for The Diabetic Foot Ulcer

1. During a routine examination, it is determined
that Mr Smith, a patient with long-standing diabetes,
has developed a foot ulcer. It is a 1-cm shallow ulcer
on the plantar aspect of the foot under the first
metatarsal head. There appears to be a clean base
with 1.5 cm of surrounding cellulitis. Which of the
following is NOT an appropriate initial choice of
management for this patient?
a. cephalexin
b. clindamycin
c. linezolid
d. mupirocin topical
e. amoxicillin/clavulanate
2. Ms Johnson is a 52-year-old female diagnosed
with type 2 diabetes 7 years ago. She notes that she
has had variable control over her diabetes in the past,
although her hemoglobin A1c has been excellent for
the past 4 years. Which of the following would classify this patient as high risk for development of a
diabetic foot ulcer?
a. absence of palpable pedal pulses
b. abnormalities of sensation via the SemmesWeinstein monofilament test
c. presence of musculoskeletal foot deformities
d. previous history of foot ulcers
e. all of the above

10 Resident & Staff Physician

3. The patient in question 2 is determined to have

low-risk feet by your history and physical examination. In the absence of other complaints, the most
appropriate management of this patient is:
a. arterial evaluation via the ankle-brachial index
b. proper education of the patient regarding appropriate footwear, daily foot inspection, appropriate nail care, and foot hygiene
c. thorough annual foot examination
d. all of the above
e. b and c only
4. Of the 18.2 million patients in the United States
with diabetes mellitus, what percentage exhibit signs
or symptoms of peripheral neuropathy?
a. 5%
b. 15%
c. 30%
d. 45%
e. greater than 50%
5. Severe or limb-threatening diabetic foot ulcers are
characterized by all of the following EXCEPT:
a. singular microbial organism predominance
b. more than 2 cm of surrounding cellulitis
c. deep wounds with evident fasciitis
d. arterial insufficiency
e. abscess formation

The Diabetic Foot Ulcer

CME-CE Questions CONTINUED

6. When choosing an antimicrobial agent for the
treatment of a diabetic foot ulcer, it is important to
consider:
a. history of the ulcer
b. bacterial flora
c. appearance of the wound site
d. overall health of the patient
e. all of the above
7. Failure of appropriate oral antimicrobials and topical treatments often results in hospitalization of patients with diabetic foot ulcers. A multidisciplinary approach to these recalcitrant infections is best. Which of
the following is NOT part of the initial evaluation and
management of the severe diabetic foot ulcer?
a. x-rays of the affected foot
b. surgical debridement to uncover the extent of
the infection
c. arterial evaluation of the lower extremity
d. single-drug therapy with cefazolin
e. All of the above are appropriate for the initial
evaluation and management of patients with a
severe diabetic foot ulcer.
8. All of the following are true regarding localized
care for diabetic foot ulcers EXCEPT:
a. Mild ulcers may respond to chemical or enzymatic debriding agents such as papain-urea.

b. Topical antimicrobials (eg, silver sulfadiazine)

stimulate wound healing by eliminating bacteria.
c. Foot soaks have proved to be effective for the
treatment of foot ulcers because they promote
wound healing.
d. Localized care is most successful when patients
and caregivers are extremely compliant in their
use.
e. Patients should be restricted from weightbearing activities and appropriate footwear should
be assessed.
9. Patients with diabetes complicated by neuropathy
should be taught:
a. to visually inspect their feet daily
b. never to walk barefoot, even in the house
c. to soak their feet to aid in healing foot ulcers
d. options a and b
e. all of the above
10. Patients with diabetes at risk for foot ulcers
should understand:
a. the implications of the loss of protective sensation
b. the importance of foot monitoring on a daily basis
c. the proper care of the foot, including nail and
skin care
d. the selection of appropriate footwear
e. all of the above

The Diabetic Foot Ulcer

University of Medicine & Dentistry of New Jersey

Center for Continuing and Outreach Education

The Diabetic Foot Ulcer: Management and Prevention Strategies in Primary Care
REGISTRATION FORM
There is no charge for this CME-CE activity.
In order to obtain credit, participants are required to:
(1) Read the learning objectives, review the activity, and complete the self-assessment quiz.
(2) Complete this registration form and the activity evaluation form on the following page, and record your
test answers in the box below.
(3) Send the registration and evaluation forms to:
UMDNJ-Center for Continuing and Outreach Education
via mail:
PO Box 1709, Newark, NJ 07101-1709
via fax:
973-972-7128
(4) Retain a copy of your test answers. Your answer sheet will be graded and if a passing score of 70% or
more is achieved, a CME-CE credit letter awarding AMA/PRA category 1 credit, nursing continuing education credit, pharmacy continuing education credit, and the test answer key will be mailed to you within
four (4) to six (6) weeks. Individuals who fail to attain a passing score will be notified and offered the opportunity to complete the activity again.
SELF-ASSESSMENT TEST
Circle the best answer for each question on pages 10-11.
1.
A
B
C
D
E
6.
2.
A
B
C
D
E
7.
3.
A
B
C
D
E
8.
4.
A
B
C
D
E
9.
5.
A
B
C
D
E
10.

A
A
A
A
A

B
B
B
B
B

C
C
C
C
C

D
D
D
D
D

E
E
E
E
E

REGISTRATION
First Name
Daytime Phone
Fax

M.I.

Last Name

Degree

Evening Phone
E-mail

Preferred Mailing Address Home Business

City

State

Zip Code

Affiliation, Specialty

I attest that I have completed the activity The Diabetic Foot Ulcer: Management and Prevention Strategies in
Primary Care as designed and I am claiming 1.0 AMA/PRA category 1 credit.
Signature

Date

Credit for this activity is available until June 30, 2005.

UMDNJCenter for Continuing and Outreach Education
PO Box 1709, Newark, NJ 07101-1709
Phone: 973-972-4267 or 800-227-4852

Activity Code: 05MC36

The Diabetic Foot Ulcer

University of Medicine & Dentistry of New Jersey

Center for Continuing and Outreach Education

The Diabetic Foot Ulcer: Management and Prevention Strategies in Primary Care
ACTIVITY EVALUATION FORM
The planning and execution of useful and educationally sound continuing education activities are guided in
large part by input from participants. To assist us in evaluating the effectiveness of this activity and to make recommendations for future educational offerings, please take a few moments to complete this evaluation form.
Your response will help ensure that future programs are informative and meet the educational needs of all participants. Please note: CE credit letters and long-term credit retention information will only be issued upon receipt of this completed evaluation form. Thank you for your cooperation!
PROGRAM OBJECTIVES: Having completed this activity, are you better able to:
Discuss the causes and risk factors of foot ulcer in diabetic patients
Determine the severity of foot ulcer in a particular patient
List application of appropriate treatment
Describe measures to prevent occurrence of foot ulcer
OVERALL EVALUATION:
The information presented increased my awareness/understanding of the subject.
The information presented will influence how I practice.
The information presented will help me improve patient care.
The faculty demonstrated current knowledge of the subject.
The program was educationally sound and scientifically balanced.
The program avoided commercial bias or influence.
Overall, the program met my expectations.
I would recommend this program to my colleagues.

Strongly
Agree

5
5
5
5

Strongly
Disagree

4
4
4
4

3
3
3
3

2
2
2
2

Strongly
Agree

5
5
5
5
5
5
5
5

1
1
1
1
Strongly
Disagree

4
4
4
4
4
4
4
4

3
3
3
3
3
3
3
3

2
2
2
2
2
2
2
2

1
1
1
1
1
1
1
1

If you anticipate changing one or more aspects of your practice as a result of your participation in this activity,
please provide us with a brief description of how you plan to do so.

Please provide any additional comments pertaining to this activity (positives and negatives) and suggestions for
improvement:

Please list any topics that you would like to be addressed in future educational activities:

FOR PHARMACY PROFESSIONALS ONLY:

Please explain how this activity did or did not meet the needs of the pharmacy community for this disease.

Please comment on the aspects of this activity that contributed toward improving your professional effectiveness and ability to communicate with and council patients and/or monitor patient disease status.

Please list any specific areas of the activity that could be improved to assist us in providing valuable education
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Activity code : 05MC36