Diabetic Food

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An MWC Publication July 20 04

© 20 04 UMDNJ-Center for Continuingand Outreach Education andRomain e Pierson Publishers, Inc.

CME-CE Certified ActivitySponsored by the University of Medicine & Dentistry of New

Jersey (UM D NJ)–Center for Co ntinuing and Outreach Education

The Diabetic Foot Ulcer:

Management and Prevention

Strategies in Primary Care

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grant from

www.residentandstaff.com

Release Date: July 2004Expiration Date: June 30, 2005Nursing credit for this activity will beprovided through June 30, 2005.



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The Diabetic Foot Ulcer: Management andPrevention Strategies in Primary Care

©

I r a A .

G r u n t h e r

PROJ R 163



The Diabetic Foot Ulcer: Management and Prevention Strategies in Primary Care

CME-CE Certified Activity Sponsored by the

University o f M edicine & D entistry of New Jersey (UMD NJ)–

Center for Continuing and Outreach Education

Release Da te: July 2004 • Expiration D ate: June 30, 2005

This activity is supported b y a n unrestricted educationa l grant from No vo N ordisk.

Introduction:

The purpose of this activity is to educate health care providers on the management and prevention of

diabetic foot ulcer.

Target Audi ence:

This activity is designed for primary care practitioners, nurses, and pharmacists.

Learni ng O bjecti ves:

Upon compl etion of this activi ty, part icipants 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 a pplication o f a ppropriate treatment• D escribe measures to prevent occurrence of foo t ulcer

M ethod of I nstruction:

Participants should read the learning objectives and review the activity in its entirety. After reviewing the

ma teria l, complete the post-test/self-assessment test consisting of a series of mult iple-choice questions.

Upon completing this activity as designed and achieving a passing score of 70% or more on the post-test,

part icipants w ill receive a CM E-CE credit letter aw arding AMA/PR A category 1 credit, nursing continuing ed-

ucation credit, pharmacy continuing education credit, and the test answer key four (4) to six (6) weeks after re-

ceipt of the post-test, registration, and evaluation materials.

Estimated time to complete this activity as designed is 1.0 hour.Physician Accreditat ion :

UMDNJ–Center for Continuing and Outreach Education is accredited by the Accreditation Council for

C ontinuing Medical Education to provide continuing medical education fo r physicians.

UMDNJ–Center for Continuing and Outreach Education designates this educational activity for a maximum

of 1.0 category 1 credit tow ard the AM A Physician’s Recognition Aw ard . Each physician should claim o nly

tho se credits tha t he/she actua lly spent in the act ivity.

The activity w as prepared in a ccordance with the AC CM E Essentials.

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UMDNJ–Center for Continuing and Outreach Education is an approved provider of continuing education

by the New Jersey Sta te Nurses Associat ion (NJ SNA), P rovider N umber P173-9/2003-2006. Pro vider Approval

is valid through June 30, 2005. NJSNA is accredited by the ANCC Commission on Accreditation. This activity

is approved fo r 1.0 contact hours.Provider approved by the Ca lifornia Boa rd of Registered N ursing, Provider Number CEP 13780 for 1.0

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UM D NJ is accredited by the American C ouncil on Pharma ceutical Education as a provider of

continuing pharmaceutical education. This course 374-000-04-017-H01 qualifies for 1.0 contact hour

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six (6) w eeks after successful completion of the progra m. Release Da te: July 2004 • Expira tion

D ate: June 30, 2005.

This activity was reviewed for relevance, accuracy of content, balance of presentation, and time required for

participation by Azeez Farooki, M D ; Anne M arie Van H oven, MD ; M s. Lorna Austin, C PhT; M s. Jennifer

Nishioka, RPh; Ms. Helene Mitzi Dolese, RN, CIM; Joanne Librie, RN; and Irina Lipets, RN, BSN.



The Diabetic Foot Ulcer

Faculty:

M ark Angelo, M D Arthur Nam, M D , M S

Assistant Faculty, Internal M edicine Resident

University of M edicine & D entistry of New Jersey D epartment of Surgery

Robert Wood Johnson M edical School G eorge Washington University M edical C enter

C ooper H ealth System Washington, D C

Camden, NJ

Program D ir ectors:

Dorothy Caputo, M A, APRN , BC-ADM , CDE D iana Vamos, PharmD

D irector of Special Initia tives C linical O ncology Pharmacist

C ontinuing and Outreach Education The C ancer Institute of New Jersey

Assistant Professor, New Brunsw ick, NJ

UM DN J–School of H ealth Related Prof essions

New Brunswick, NJ

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In accordance with the disclosure policies of UMDNJ and to conform with ACCME, ACPE, ANCC-COA,

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providers of co mmercial services, tha t relat e to the content o f their presentat ion/material, o r the commercial

contributors of this activity, that could be perceived as a real or apparent conflict of interest; and (2) the identi-

ficat ion of a commercial prod uct/device tha t is unlab eled for use or a n investiga tiona l use of a product /device

not y et a pproved.

Faculty D isclosure Declarati ons:

D rs Angelo, N am, and Vamo s, and M s Ca puto have no significant fina ncial relationships to disclose.

Field Tester D isclosure Declar ati ons:

D rs Van H oven and Farooki a nd M s Austin, Do lese, Librie, Lipets, a nd N ishioka ha ve no significant

financial interests to disclose.

O ff -L abel Usage D isclosur e: This activity d oes not conta in informa tion o f commercial pro ducts/devices that are unlab eled for use or

investigational uses of products not yet approved.

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Pierson Pub lishers, Inc.

Accreditation refers to recognition of continuing nursing education activities only and does not imply the

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participants are urged to consult the full prescribing information on any agent(s) presented in this activity for

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scribing any medication. This is particularly important when a drug is new or infrequently prescribed.

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July 2004 •Resident & Staff Physician 3

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 ulcer—commonly re-

ferred to as “ diabetic foot” —in their

lifetime.2 Frequently limb threaten-

ing, as many as 14% to 24% of di-

abetic patients w ith a foot ulcer will

require amputation.3 The vast ma-

jority 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 sys-

tems and is present in approximate-

ly 30% of the diabetic population.2

The economic impact of the compli-

cations of diabetic neuropathy is

considerable. In 2001, approxi-

mately $10.9 billion was spent on

diabetic neuropathy and associat-

ed complicat ions, up to 27% of to-

tal 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 man-

agement and prevention strategies.

Who Is at Risk for DiabeticFoot Ulcer?

Factors associated with an in-

creased 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-relat-

ed condit ions a lso increase the risk

for foot ulcerations, including pe-

ripheral neuropathy with loss of

protective sensation, altered foot

biomechanics in the presence of

neuropathy, bony deformity, sig-

nificant peripheral vascular dis-

ease, history of ulcers or amputa-

tion, and severe nail pathology.

Pathogenesis of DiabeticNeuropathy

The pathogenesis of diabetic neu-

ropathy involves a complex interre-

The Diabetic Foot Ulcer: Management andPrevention Strategies in Primary Care

M a r k An ge lo , M DAssistant Faculty, Internal M edicineUniversity of M edicine & Dentistry

of N ew JerseyRobert Wood Johnson Medical SchoolCooper Health SystemCamden, NJ

A rt hu r Na m , M D , M SResidentDepartment of SurgeryGeorge Washington University

M edical Center

Washington, DC

Foot ulcers are a major cause of morbidity and mortality in

pat ients w ith diabetes. Health care providers who a ppreciate 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 w ound characteristics,

causative organisms, and comorbidities and may require topical

or systemic antimicrobial therapy and/or surgical intervention.

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4 Resident & Staff Physician


lationship between metabolic and

ischemic factors and nerve repair

mechanisms (Figure 1). Major em-

phasis has been placed on the poly-

ol pathway, as depicted in Figure 2.

Sorbitol, w hich a ppears to function

as a tissue toxin, has been implicat-

ed in the development of neuropa-

thy, retinopathy, nephropathy, and

aortic disease.4,5 Under physiologic

concentrations of substrate, aldose

reductase has a low affinity for glu-

cose, and little sorbitol is produced.

However, in the presence of pro-

found and chronic hyperglycemia,

much greater amounts of sorbitol

are produced. In an experimental

model of diabetic neuropathy, sor-

bitol accumulation was associated

with a decrease in myoinositol con-

tent, abnormal phosphoinositide

metabolism, and a decrease in Na + -

K+ -ATPa se act ivity.4 The primacy of

the polyol pathw ay in the initiation

of neuropathy is supported by evi-

dence showing that inhibition of al-

dose 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 se-

rum and tissue proteins—such as

plasma albumin, lens protein, fi-

brin, collagen, and lipoproteins—

from chronic hyperglycemia.7 In

this process, excess glucose com-

bines with free amino acids on

serum or tissue proteins, initially

forming reversible, early glycated

products and later, irreversible,

advanced glycation end products

(AG E).7,8 Receptors for AG E are

present on macrophages and en-

dothelial cells, and the binding of

AGE to its receptors may induce

the synthesis and release of cyto-

kines, va scular ad hesion molecules,

endothelin-1, and tissue factor.

AGE may a lso decrease endothe-

lial-derived nitric oxide as well as

alter b asement membrane proteins,

lipoproteins, and cellular mat rix.

Activation of vascular protein

kinase C (PKC) isoforms also ap-

pears to be important to the devel-

opment 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 dia-

cylglycerol (DAG), a major endoge-

nous 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 UlcerPathophysiologic factors in-

volved in the development of dia-

betic foot ulcers are neuropathy, ar-

terial insufficiency, musculoskeletal

abnormalities, and poor wound

healing (Figure 3). Microbial path-

ogens, w hich w ill be discussed la ter,

also play a key role. Additionally,

poor nutrition compromises the

healing process. Therefore, espe-

cially in elderly patients or those

with other comorbidities, a nutri-

Figure 1—Pathogenesis of diabetic neuropathy.Adapt ed from Rose BD, McCulloch DK.

Glycemic control and vascular complications in type 1 diabetes mellitus. UpToDate .

www.uptodate .com.

Increased aldosereductase activity Glycation ofproteins, AGE

Cytotoxicity of neural, glial, andvascular component of peripheral

nerve; nerve damage

AGE = ad vanced g lycat ion end products; DAG = diacylglycerol; PKC = prot ein kina se C.

Hyperglycemia

Diabetic complications

Increased DAG,PKC activity

Sorbitol accumula-tion,neural

myoinositol deple-tion, decreasedNa+-K +-ATPase

activity

Activation of endo-thelial macrophage

AGE receptors; alteredbasement membrane

proteins, lipoproteins,matrix proteins

Altered endothelial cell

permeability; alteredsignal transduction andhormone responsiveness

of vascularsmooth muscle





tionist should be consulted to pro-

vide guidance and assist with food

choices and supplements as needed.

Neuropathy The cytotox ic, 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 de-

myelinization process in type-A sen-

sory fibers, which are involved with

proprioception and the sensations of

light touch, pressure, and vibration.

The type-C sensory fibers, w hich

are associated with free nerve end-

ings that sense noxious, painful,

and thermal stimuli, are similarly

affected.11 Damage to these fibers

may initially result in pathologic

activation of signal transduction

along these pathways, leading to

the pain and paresthesias of diabet-

ic neuropathy, w hich, coupled w ith

lack of sensation, leaves the patient

with an ataxic gait. The clinical

consequence of these disrupted

fibers is the loss of crucial protec-

tive sensat ion, w hich heightens sus-

ceptibility to mechanical, chemical,

or t hermal injury.11 The trauma can

remain undetected, resulting in in-

flamma tion, further mechanical in-

jury, and ulceration.12

In persons with diabetic neuropa-

thy, the small intrinsic muscles of the

foot atrophy as a result of demyelin-

ization 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 metata rsal heads become more

prominent. The metatarsal-pha-

langeal joints can become unstable

secondary to wasting of the lumbri-

cal and interosseous muscles, and

overpow ering extrinsic muscles can

depress the metatarsal heads, contract

the digits, and cock up the toes.11

These changes increase weightbear-

ing on the metatarsal heads and are

manifested by a dysfunctional gait.

As the patho logic process continues,

the soft tissue covering the bones is

exposed to abnormal compressive

and shearing stress as it rubs against

footwear during walking. With con-

tinuing exposure to shearing stress,

the skin forms callus. Although this

is initially a protective response, as

time progresses, all that remains be-

tween 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 peripher-

al circulation in the extremities by

supplying the sympathetic ad-

renergic fibers that regulate arteri-

ole vasomotor tone and blood flow

through arteriovenous shunts.15

Failure of sympathetic control re-

sults in arteriolar vasodilatation,

w hich reduces periphera l resis-

tance, increases arteriovenous

shunt flow, and increases cutaneous

blood flow at the expense of perfu-

sion of the deeper structures. The

greater cutaneous flow is responsi-

ble for the frequently encountered

elevated foot temperatures and dis-

tended dorsal veins observed in pa-

tients with diabetic neuropathy.

Blood that is bypassing the capil-

Figure 2—Role of sorbitol in diabetic microvascular disease. Adapt ed from Frank RN.

On the pathogenesis of diabetic retinopathy. A 1990 update. Ophthalmology. 1991;98:586-593.

GlucoseFructose

NAD = n icotina mide ad enine dinucleotide; NADH = the reduced fo rm of nicoti-na mide ad enine dinucleotide; NADP = nicotina mide ad enine dinucleotide ph os-pha te; NADPH = the reduced fo rm of nicotina mide ade nine dinucleotide phosphat e.

NADPH NADP NAD NADH

Sorbitol

Osmoticeffects

Other?Decreasedcell myoinositol

Aldose reductase Sorbitol dehydrogenase

I n persons with diabetic neuropathy,

the small intrinsic muscles of the foot

atrophy as a result of demyelinizationin distal motor nerves.





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 con-

tribute to ulcerat ion.

Adding to the problems caused

by autonomic dysfunction is dia-

betic anhidrosis. This represents a

sudomotor impairment character-

ized by decreased sweating that re-

sults in dry, scaly, cracked skin,

which facilitates the introduction

of infectious agents.18

Ar teri al insuff i ciency 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 foo t is decreased, prima rily be-

cause of atherosclerotic obstruc-

tion of the major conduit vessels,

characteristically involving the tib-

ial and peroneal vessels, while

sparing those in the pedal arch.

M icrovascular dysfunction a dds to

the vascular problems.20 Defective

hyperemic responses a nd endothe-

lial dysfunction may also be im-

portant in the pathogenesis of fo ot

ulcers in patients with diabetic

neuropathy. A gradient of oxygen

tissue pressure is required for fi-

broblast growth and the initiation

of angiogenesis, while chronic hy-

poxia impairs w ound healing.2

Musculoskeletal abnormali ti es Diabetic patients are susceptible

to musculoskeletal abnormalities of

the foot, such as neuropathic ar-

thropathy, previously known as

Charcot’s foot. Neuropathic ar-

thropathy is characterized by

chronic, progressive, degenerative

disease of 1 or more joints and is

identified by sw elling, bleeding, in-

creased 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 ab-

normalities is improper loading of

the joints, uneven weight distribu-

tion, and repeated trauma.21

Poor wound heali ng 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, ex-

posing matrix proteins and lead ing

to platelet aggregation, clot forma-

tion, and hemostasis.2 Platelets re-

lease 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. Subse-

quently, monocytes are activated to

form tissue macrophages, which

play a critical role in suppressing

bacterial growth and clearing exis-

Figure 3—Pathophysiology of foot ulcers from diabetic neuropathy.Adapted from

Zang ara GA, Hull MM. Diab etic neuropat hy: patho physiology and prevention of foot

ulcers. Clin Nu rse Spec. 1999;13:57-65.

Sensory dysfunction Autonomic dysfunction

Foot ulcer

Motor dysfunction

Decreased sensoryperception of:

• Pain

• Vibration

• Temperature

• Touch

Smallmuscle atrophy

Decreasedsweating

Arterio-venous shunt

Imbalance of flexorand extensor muscles

Dry, scalyskin

Decreasedcapillary pressure

Clawed toes Fissures Edema

Prominentmetatarsal heads

Altered gait

Callus

Injury:

• Mechanical

• Thermal

• Chemical

Infection Poor woundhealing





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 in-

jury.2 The clonal expansion of cells,

particularly fibroblasts, appears to

define wound healing. Wound clo-

sure, occurring from the rim of the

wound inward, is characterized by

complete epithelialization. The end

of healing is heralded by the migra-

tion of keratinocytes to the wound

site. During this remodeling phase,

tensile strength and cellular organi-

zation improve, skin integrity re-

turns, and the wound contracts.2

Chronic hyperglycemia in dia-

betic patients disrupts the normal

cellular and inflammatory path-

ways involved in wound healing

and increases susceptibility to in-

fection.4 Individuals with diabetes

have been found to have abnorma l

cellular function, particularly of fi-

broblasts and neutrophils.2 In ad-

dition, AG E a lters endothelial a nd

macrophage activation, which in-

terferes with cytokine production

and cellular migration. AG E may

also be detrimental to basement

membrane proteins, extracellular

matrix production, and endothe-

lial-derived nitric oxide produc-

tion. There is also evidence to sug-

gest that increased D AG a nd PKC

activity changes endothelial cell

permeability, signal transduction,

and the hormone responsiveness

of vascular smooth muscle.9,10

Clinical PresentationCommon sites of foot ulcers are

the metatarsal heads and distal

phalanx, medial and lateral mid-

foot, and the heel. Various methods

of grading the severity of diabetic

foot infection have been used. Joshi

and colleagues recently described a

useful classification system that di-

vides ulcers into those that do and

do no t threaten loss of limb.23

M ild ul cers Mild, non–limb-threatening ul-

cers are often shallow lesions with a

clean base and less than 2 cm of sur-

rounding cellulitis, w ith no evidence

of fasciitis, abscess, or osteomyeli-

tis. No ischemic process is involved,

and the patient has good blood glu-

cose control. Initial treatment in-

cludes oral antibiotics and wound

care. The causative organisms for

these ulcers are primarily aerobic

gram-positive cocci (eg, Staphylo-

coccus aureus and streptococci ).23

Severe ul cers Limb-threatening ulcers are

those characterized by deep infec-

tion and more than 2 cm of celluli-

tis. 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

w ith a metal probe w ould also sig-

nify osteomyelitis. If the situation

is unclear as to the presence of an

infectious process involving the

bone, an MRI should be obtained.

Diabetic patients presenting

with this type of ulcer should be

hospitalized immediately for intra-

venous antibiotic therapy and sur-

gical consultation. The causative

organisms of such ulcerations are

characteristically polymicrobial—

aerobic gram-positive cocci, strict

anaerobes (eg, Bacteroides frag-

il is ), or gram-negative bacilli (eg,

Escherichia col i ).

TreatmentLocalized care

Localized care of diabetic foot ul-

cers consists of topical antimicrobial

therapy, appropriate dressing appli-

cation, foot elevation, debriding

agents, and limitation of weight-

bearing a ctivities.24 The success of lo-

calized care depends on a high de-

gree of compliance by the patient

and caregiver. Topical ant imicrobial

agents, such as silver sulfadiazine (eg,

Silvadene cream, Thermazene) and

mupirocin (Bactroban), can stimu-

late wound healing by eliminating

bacteria on the wound surface. They

should be used, however, only as ad-

Severe ulcer.

Mild ulcer.

C o u r t e s y o f J o h n

S .

S t e i n b e r g ,

D P M

C o u r t e s y o f J o h n

S . S

t e i n b e r g ,

D P M





junctive therapy. The use of povi-

dine-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 pa tients with

mild ulcers (as defined above) or

those who refuse surgical debride-

ment. Options for topical debriding

agents include collagenase (Santyl)

or papa in-urea (Accuzyme, Pana fil).

Becaplermin gel (Regranex) ha s

been found to significantly in-

crease the incidence of complete

wound closure and significantly

reduce the time to complete clo-

sure of diabetic foot ulcers. 25

A moist environment is most

conducive to formation of a nas-

cent tissue matrix. Several existing

products promote maintenance of

a moist w ound. A recent Cochrane

Review examining 3 randomized

controlled trials of hydrogel dress-

ing products found a significant

improvement over saline dressings

alone. 26

Larval therapy with sterile mag-

gots has been described in patients

failing other types of therapy for

debridement of necrotic tissue.27

Surgical intervent ion Surgery, which can consist of

drainage, debridement, and often

amputation, is important for pre-

serving tissue, maximizing revas-

cularization, and promoting heal-

ing.28 The goal of early, aggressive

debridement and drainage is to re-

move all necrotic soft tissue and

bone.2 Even for pa tients w ith poor

circulatory status, it is important

to establish dependent drainage to

prevent poo ling of pus. There is no

evidence to support soaking an ul-

cerated foot in a whirlpool or oth-

er hydrotherapies.2 In fact, such

measures could result in macera-

tion, infection, or burns. The deci-

sion to perform surgery must be

made with caution because, while

the intervention can remove the

source of infection, too much ma-

nipulation can impair healing by

further damaging the tissues. 28

Systemic antimicrobial therapy The choice of antimicrobial

agent is ba sed on t he suspected ba c-

terial flora, appearance of the in-

fected site, history o f the lesion, a nd

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 antimicro-

bial therapy can be used to treat

mild, superficia l lesions when the

infection is in the early stages,

drainage is minimal, gangrene is

absent, and the patient does not

have systemic symptoms. M ore se-

vere ulcerat ions w ill req uire intra -

venous antimicrobial therapy.29

Recommended oral agents in-

clude cephalexin (Biocef, Keflex),

clindamycin (Cleocin), and am-

ox icillin/pot a ssium clavu lan a te

(Augmentin).29

Intraveneous antimicrobial ther-

apy is initiated when systemic or

extensive infection is suspected,

most commonly in patients who

have developed septicemia or os-

teomyelitis. 29 The recommended

agents include a beta-lactam plus a

beta-lactamase inhibitor (eg, am-

picillin sodium/sulbacta m sod ium

[Unasyn]) or clindamycin plus a

gram-negative drug (eg, a third-

generation cephalosporin, a fluo-

roquinolone, or aztreonam [Azac-

ta m]). Caution should be used w ith

fluoroquinolones in diabetic pa-

tients because these medications

may w orsen glycemic control. Van-

comycin (Vancocin, Vancoled) plus

imipenem-cilastatin (Primaxin) is

used for life-threatening infec-

tions.29 Linezolid has been recently

evaluated and has shown promise

as a n alternat ive therapy. Ho w ever,

there appears to be no benefit of

linezolid over a mpicillin/sulba c-

tam. 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 w eeks, for o steomyelitis it is

4 to 6 weeks.24,31 Ultimately, the

length of t reatment depends on the

severity of the infection, the

causative organism, and the clini-

D iabetic patients must be instructed

about proper and consistent foot care.Feet should be kept clean and dry

at all t imes. Patients w ith neuropathy

should not walk barefoot, even in the

home. Properly f itted shoes are essent ial.





cal response to the chosen medica-

tion. It is important to continue

antibiotic therapy until an infec-

tion has been eliminated.

Prevention Is KeyG lycemic control is para mount

in the prevention of diabetic neu-

ropathy and the development of

diabetic foot ulcers. A chronically

elevated blood glucose concentra-

tion is the initial factor that sets in

motion the pathogenic process of

neuropathy.

Diabetic patients must be in-

structed about proper and consis-

tent foot care to prevent ulcers.

Feet should be kept clean and dry

at all times. Patients with neuropa-

thy should not walk barefoot,

even in the home. Properly fitted

shoes are essential. This is a par-

ticular problem w ith w omen, since

an a dequat e shoe is not oft en styl-

ish. Patients should be told to in-

spect their feet carefully daily for

callus, infection, abrasions, for-

eign bodies, or blisters and to con-

sult the physician about any po-

tentially troub lesome lesion.

The National Diabetes Educa-

tion Program recommends that all

patients with diabetes have a thor-

ough foot examination at least an-

nually to assess the condition o f the

skin and nails and to evaluate for

the presence of any sensory or

skeletal abnormalities.32 Proprio-

ception and standardized sensory

evaluation should be performed to

help identify patients at risk. Stan-

da rdized sensory eva luat ion is best

accomplished with the Semmes-

Weinstein monofilament at vari-

ous locations of the foot, includ-

ing the toes, the metatarsal head

area, and the heel. “ High-risk” pa-

tients 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 ap-

propriate foot care specialist.

Pat ients w ith diabetes and high-

risk foot conditions should be ed-

ucated regarding their risk factors

and appropriate management. A

nonjudgmental assessment of a

person’s current knowledge and

care practices should be obtained

first. Patients at risk should under-

stand the implications of the loss

of protective sensation, the impor-

tance of foot monitoring on a dai-

ly basis, the proper care of the

foot, including nail and skin care,

and the selection of appropriate

footwear. The patient’s under-

standing of these issues and their

physical ability to conduct proper

foot surveillance and care should

be assessed. Patients with neu-

ropathy should be advised to

break in new shoes gradually to

minimize the formation of blisters

and ulcers. Patients with visual

difficulties, physical constraints

preventing mo vement, or cognitive

problems that impair their ability

to assess the condition of the foot

and to institute appropriate re-

sponses 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 footw ear.33

ConclusionPeripheral diabetic neuropathy

affects nearly one third of all pa-

tients with diabetes. Foot ulceration

is a preventable complication in

those w ith peripheral neuropathy.

Better understanding of the patho-

physiologic basis of foot ulcers can

assist health care providers in the

evaluation, diagnosis, and treatment

of diabetic foot ulcers. It is also criti-

cal to provide thorough, regular foot

assessments with standardized sen-

sory evaluations, skin assessment,

and bony alignment evaluation as

well as patient and family educa-

tion. If begun early, these interven-

tions for health promotion a nd dis-

ease prevention can help patients

identify the early signs and symp-

toms of diabetic foot ulcers before

extensive complications occur,

thereby improving their quality of

life, preventing pain and amputa-

tion, and reducing the health care

costs of this chronic disease. ■

References1. Centers for Disease Control and Preven-tion. National diabetes fact sheet: generalinformation and national estimates on dia-betes in the United Sta tes, 2003. Rev ed. At-lanta, Ga: U.S. Department of Health andHuman Services, Centers for Disease Con-trol and Prevention, 2004.2. http://www.diabetes.org/info/diabetesinfo. jsp.3. G ordo is A, Scuffham P, Shearer A, et al.

The health care costs of diabetic peripheralneuropathy in the U.S. D iabetes Care .2003;26:1790-1795.4. G reene DA, La ttimer SA, Sima AA. Sor-bitol, phosphoinositides, and sodium-potas-sium-ATPa se in the pa thog enesis of diab eticcomplications. N Engl J M ed. 1987;316:599-606.5. Kador PF, Kinoshita JH. Role of aldosereductase in the development of diabetes-associated complications. Am J M ed. 1985;79(suppl 5A):8-12.6. G reene DA, La ttimer SA. Action ofsorbinil in diabetic peripheral nerve. Rela-tionship of polyol (sorbitol) pathw ay inhibi-tion to a myoinositol-mediated defect in

sodium-potassium ATPase activity. D iabetes.1984;33:712-716.7. Vlassara H. Protein glycation in the kid-ney: role in diabetes and aging. Kidney Int.1996;49:1795-1804.8. Brow nlee M. Lilly Lecture 1993. G lyca-tion and diabetic complications. D iabetes.1994;43:836-841.9. Inoguchi T, Ba ttan R, H andler E, et al.Preferential elevation of protein kinase Cisoform βII and diacylglycerol levels in theaorta and heart of diabetic rats: differentialreversibility to glycemic control by islet celltransplantation. Proc N atl A cad Sci U S A.1992;89:11059-11063.10. Wolf BA, Williamson JR, Eamon RA, et





al. D iacylglycerol a ccumulation and microvas-cular abnormalities induced by elevated glu-cose levels. J Cli n Invest. 1991;87:31-38.11. Sumpio BE. Foot ulcers. N Engl J M ed.

2000;343:787-793.12. Boulton AJM. The pathogenesis of dia-betic foot problems: an overview. D iabet M ed . 1996;13(suppl 1):S12-S16.13. Collier JH, Brodbeck CA. Assessing thediabetic foot: plantar callus and pressuresensation. D iabetes Educ. 1993;19:503-508.14. Stess RM, Jensen SR, Mirmiran R. Therole of dynamic plantar pressures in diabeticfoo t ulcers. D iabetes Care. 1997;20:855-858.15. Bornmyr S, Svensson H, Lilja B, et al.Cutaneous vasomotor responses in youngtype I diabetic patients. J D iabetes Compli - cations. 1997;11:21-26.16. Purewa l TS, Go ss DE, Wat kins PJ, et al.Lower limb venous pressure in diabetic neu-ropathy. D iabetes Care. 1995;18:377-381.17. Uccioli L, Ma ncini L, G iordano A, et al.Lower limb arterio-venous shunts, auto-

nomic neuropathy and diabetic foot. Dia- betes Res Cl in Pr act. 1992;16:123-130.18. Spallone V, Uccioli L, M enzinger G .Diabetic autonomic neuropathy. D iabetes M etab Rev. 1995;11:227-257.19.Singer AJ, Clark RAF. Cutaneous wound

healing. N Engl J M ed. 1999;341:738-746.20. Kamal K, Powell RJ, Sumpio BE. Thepathobiology of diabetes mellitus: implica-tions for surgeons. J Am Co ll Surg. 1996;183:271-289.21. Brower AC, Allman RM. Pathogenesisof the neurotrophic joint: neurotraumaticvs. neurovascular. Radiology. 1981;139:349-354.22. Witte M B, Ba rbul A. G eneral principlesof wound healing. Surg Clin N orth Am .1997;77:509-528.23. Joshi N, Caputo M, Weitekamp MR,et al. Infections in patients with diabetesmellitus. N Engl J M ed. 1999;341:1906-1912.24. Joseph WS, LeFrock JL. The pat hogene-sis of diabetic foot infections—immuno-pathy, angiopathy, and neuropathy. J Foot Surg. 1987;26(suppl):S7-S11.25.Wieman TJ, Smiell JM, Su Y. Efficacy andsafety of a topical gel formulation of recom-binant human platelet-derived growth factor-

BB (becaplermin) in patients w ith chronicneuropathic diabetic ulcers. A phase III ran-domized placebo-controlled double-blindstudy. D iabetes Care . 1998;21:822-827.26. Smith J. Debridement of diabetic footulcers. Cochrane Database Syst Rev . 2002;

(4):CD003556.27. Stoddard SR, Sherman RA, Mason BE,et al. Maggot debridement therapy. An alter-native treatment for nonhealing ulcers. J Am Podiatr M ed Assoc . 1995;85:218-221.28. Hollingshead TS. Pathophysiology andtreatment of diabetic foot ulcer. Clin Podia- tr M ed Surg. 1991;8:843-855.29. Joseph WS. Treatment o f low er extremi-ty infections in diabetics. D rugs. 1991;42:984-996.30. Lipsky BA, Itani K, Norden C. LinezolidDiabetic Foot Infections Study Group.Treating foot infections in diabetic patients:a randomized, multicenter, open-label trialof linezolid versus ampicillin-sulbactam/amoxicillin-clavulanate. Clin Infect Dis .2004;38:17-24.31. Kapor-Drezgic J, Zhou X , Ba bazono T,et al. Eff ect of high glucose on mesangial cellprotein kinase C-σ and -ε is polyol pathway-dependent. J Am Soc N ephrol . 1999;10:1193-1203.

32. National Diabetes Education Program.ht tp://ndep.nih.gov.33. Ma yfield JA, Reiber GE, Sand ers LJ, etal. American Diabetes Association. Positionstatement. Preventive foot care in diabetes.D iabetes Care . 2004;27(suppl 1):S63-S64.

CM E-CE Questions for The D iabe tic Foot Ulcer

1. During a routine examination, it is determined

that Mr Smith, a patient w ith long-standing diabetes,

has developed a foot ulcer. It is a 1-cm shallow ulcer

on the plantar aspect of the foot under the firstmetatarsal 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

mana gement fo r 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 ha d va riable control over her diabetes in the past,

although her hemoglobin A1c has been excellent for

the past 4 years. Which of the follow ing would clas-

sify this patient as “ high risk” for development of a

diabetic foot ulcer?

a. absence of palpable pedal pulses

b. abnorma lities of sensation via t he Semmes-

Weinstein monofilament test

c. presence of musculoskeleta l foot deformities

d. previous history of foot ulcers

e. all of the above

3. The patient in question 2 is determined to have

“ low-risk” feet by your history and physical exami-

nation. In the absence of other complaints, the most

appropriate management o f this pat ient is:a. arterial evaluat ion via the ankle-brachial index

b. proper education of the patient regarding ap-

propriate footwear, daily foot inspection, ap-

propriate 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 a ll of the follow ing EXC EPT:

a. singular microbial organism predominance

b. more than 2 cm of surrounding cellulitis

c. deep w ounds with evident fa sciitis

d. arterial insufficiency

e. abscess formation




CM E-CE Questio ns CONTINUED

6. When choosing an antimicrobial agent for the

treatment of a diabetic foot ulcer, it is important to

consider:

a. history of the ulcerb. 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 topi-

cal treatments often results in hospitalization of pa-

tients with diabetic foot ulcers. A multidisciplinary ap-

proach to these recalcitrant infections is best. Which of

the following is NOT part o f the initial evaluation a nd

management of the severe diabetic foot ulcer?

a. x-rays of the affected footb. surgical debridement to uncover the extent of

the infection

c. arterial evaluation of the low er extremity

d. single-drug therapy w ith cefazolin

e. All of the abo ve 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 dia betic foot ulcers EXC EPT:

a. Mild ulcers may respond to chemical or enzy-

matic debriding agents such as papain-urea.

b. Topical ant imicrobials (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 promotewound healing.

d. Localized care is most successful w hen pat ients

and caregivers are extremely compliant in their

use.

e. Pa tients should be restricted from weightbear-

ing activities and appropriate footwear should

be assessed.

9. Patients with diabetes complicated by neuropathy

should be ta ught:a. to visually inspect their feet daily

b. never to w alk barefoot, even in the housec. 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 a ppropriate footw ear

e. all of the above




University of Medicine & Dentistry of New JerseyCenter for Continuing and Outreach Education


REGISTRATION FORMThere is no charge for this CME-CE activity.

In order to o bta in credit, pa rticipants a re req uired to :

(1) Read the learning objectives, review the activity, and complete the self-assessment q uiz.

(2) Co mplete this registrat ion form and the activity evaluation form on the follow ing page, and record your

test answers in the box below.

(3) Send the registrat ion and evaluation forms to:

UMDNJ-Center for Continuing and Outreach Education

via ma il: PO Box 1709, New a rk, NJ 07101-1709

via fax: 973-972-7128

(4) Retain a copy of yo ur test a nswers. Your answ er sheet will be graded and if a passing score of 70% or

more is achieved, a C M E-C E credit letter aw arding AMA/PR A category 1 credit, nursing continuing edu-

cation credit, pharmacy continuing educat ion credit, a nd the test a nswer key w ill be mailed to you w ithinfour (4) to six (6) weeks. Individuals who fail to attain a passing score will be notified and offered the op-

portunity to complete the activity aga in.

SELF-ASSESSMENT TEST

Circle the best answer for each question on pages 10-11.

1. A B C D E 6. A B C D E




5. A B C D E 10. A B C D E

REGISTRATION

First Na me M.I. Last Na me Degree

D aytime Phone Evening Phone

Fax E-mail

Preferred Mailing Address ■ Home ■ Business

City State Zip Code

Affiliation, Specialty

I attest that I have completed the acti vit y “ The D iabeti c Foot Ul cer: M anagement and Prevent ion Str ategies in

Primary Care” as designed and I am claiming 1.0 AM A/PRA category 1 credit .

Signature Date

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

UMDNJ–Center for Continuing and Outreach Education

PO Box 1709, New ark, N J 07101-1709

Phone: 973-972-4267 or 800-227-4852

Activity Code: 05MC36




University of Medicine & Dentistry of New JerseyCenter for Continuing and Outreach Education


ACTIVITY EVALUATION FORM

The planning and execution of useful and educationally sound continuing education activities are guided inlarge part b y input from pa rticipant s. To assist us in evalua ting the effectiveness of this act ivity and to ma ke rec-

ommendations 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 par-

ticipants. Please note: CE credit letters and long-term credit retention information will only be issued upon re-ceipt of this completed evaluation form.Thank you for your cooperation!

Strongly StronglyPROGRAM OBJECTIVES: H aving completed this activity, a re you better able to: Agree Disagree

• D iscuss the causes and risk factors of foot ulcer in diabetic patients 5 4 3 2 1

• D etermine the severity of foot ulcer in a particula r pa tient 5 4 3 2 1

• List applica tion of appropria te treatment 5 4 3 2 1

• D escribe measures to prevent occurrence of foot ulcer 5 4 3 2 1

Strongly StronglyOVERALL EVALUATION: Agree Disagree

The informa tion presented increa sed my a w areness/understa nding of the subject. 5 4 3 2 1

The information presented w ill influence how I practice. 5 4 3 2 1

The information presented w ill help me improve pa tient ca re. 5 4 3 2 1

The faculty demonstra ted current know ledge of the subject. 5 4 3 2 1

The program w as educa tiona lly sound and scientifica lly balanced. 5 4 3 2 1

The program avoided commercia l bias or influence. 5 4 3 2 1

O verall, the program met my expecta tions. 5 4 3 2 1

I w ould recommend this program to my colleagues. 5 4 3 2 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 t o 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 effective-

ness and ability to communicat e w ith and co uncil pat ients and /or monit or pat ient disease stat us.

Please list any specific areas of the activity that could be improved to assist us in providing valuable education

to t he pharmacy community.

Activity code : 05MC36



Documents

Diabetic Food