Diabetic foot ulcers--effects on QOL, costs, and mortality and the role of standard wound care and advanced-care therapies.

Abstract

Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes mellitus. A review of the literature confirms that the presence of an unhealed DFU negatively affects several domains of patient quality of life (daily and social activities) and increases the risk of infection, amputation, and death. Patients with diabetes mellitus and DFUs also have higher healthcare utilization rates than patients without DFUs and reported healing rates vary from 24% to 82% after 12 weeks of care. Guidelines for the expeditious healing of DFUs are available and include debridement, infection control, offloading, and the use of dressings that maintain a moist wound bed. Wound measurements to determine progress toward healing must be obtained because percent reduction in wound area during the first 4 weeks of care is a predictor of treatment outcome. If a wound fails to respond to standard care, the use of advanced treatment approaches such as cytokines, negative pressure therapy, and living skin equivalents may be beneficial. Clinical studies to further elucidate the effects of topical, systemic, and supportive regimens of care on outcomes and costs are needed.

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diabetes.1Diabetic foot ulcers (DFUs), one of the most com-
mon complications of diabetes, have an annual incidence rate
of 1% to 4% and a lifetime risk of 15% to 25%.2-5Peripheral
neuropathy is a major contributing factor in the development
of DFUs, along with deformity, callus, trauma, and vascular
insufficiency.1,3,4,6,7DFUs are often recalcitrant to treatment
and associated with serious medical complications, such as
osteomyelitis and lower limb amputation. Approximately 15%
of DFUs result in lower extremity amputation.5,7More than
85% of lower extremity amputations in patients with diabetes
are precipitated by a foot ulcer.6,8
he prevalence of diabetes mellitus is increasing worldwide;
by the year 2025, an estimated 300 million people will have
The ultimate goal of DFU management is complete wound
healing. Standard management strategies for healing DFUs typ-
ically have included debridement, infection control, offloading,
and the use of dressings to maintain a moist wound bed. Despite
the use of standard management strategies, healing rates of DFUs
remain low.
The purpose of this review is to enhance understanding of the
effect of DFUs on quality of life (QoL), costs, morbidity, and mor-
tality and to describe current management approaches to opti-
mize outcomes of care.
The Effects of Diabetic Foot Ulcers
Quality of life.DFUs can be painful and limit daily and social
Diabetic Foot Ulcers — Effects on Quality
of Life, Costs, and Mortality and the Role
of Standard Wound Care and Advanced-
Care Therapies in Healing: A Review
Robert J. Snyder, DPM, CWS; Jason R. Hanft, DPM, FACFAS
Abstract
Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes mellitus. A review of the literature confirms
that the presence of an unhealed DFU negatively affects several domains of patient quality of life (daily and social activities)
and increases the risk of infection, amputation, and death. Patients with diabetes mellitus and DFUs also have higher health-
care utilization rates than patients without DFUs and reported healing rates vary from 24% to 82% after 12 weeks of care.
Guidelines for the expeditious healing of DFUs are available and include debridement, infection control, offloading, and the
use of dressings that maintain a moist wound bed. Wound measurements to determine progress toward healing must be
obtained because percent reduction in wound area during the first 4 weeks of care is a predictor of treatment outcome. If
a wound fails to respond to standard care, the use of advanced treatment approaches such as cytokines, negative pressure
therapy, and living skin equivalents may be beneficial. Clinical studies to further elucidate the effects of topical, systemic,
and supportive regimens of care on outcomes and costs are needed.
Key Words: diabetic foot ulcer, wound care, healthcare costs, quality of life, review
Index: Ostomy Wound Management 2009;55(11):28–38
Potential Conflicts of Interest: Dr. Snyder and Dr. Hanft disclose they have received speaker honoraria and served as a consultant
or paid advisory board member, Advanced BioHealing, LaJolla, CA. Editorial assistance in the writing of this article, funded by
Advanced BioHealing, Inc, was provided by Tracey Fine, MS, ELS, and Amy Horton, PharmD, CMPP, The JB Ashtin Group,
Inc., Plymouth, MI.
Dr. Snyder is the Medical Director, Wound Healing and Hyperbaric Center at University Hospital, Tamarac, FL; Professor (Adjunct), Temple University College of
Podiatric Medicine, Philadelphia, PA; and in private practice in Tamarac, FL. Dr. Hanft is Director of Research, Podiatric Residency Program; and Director, Podiatric
Education, South Miami (FL) Hospital; and in private practice, The Foot and Ankle Institute of South Florida, South Miami, FL. Please address correspondence
to: Robert J. Snyder, DPM, CWS, 7301 N. University Drive, Suite 305, Tamarac, FL 33321; email:drwound@aol.com.

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DIABETIC FOOT ULCERS
activities, leading to reduced QoL. Goodridge et al9compared
QoL parameters in 104 patients with healed and unhealed DFUs
(defined as having a history of DFU ≥6 months) who received
care in a tertiary foot care clinic. The results of each DFU group
also were compared with patients with diabetes and no history
of a foot ulcer, patients with hypertension, and persons in the
general population. Results using the Medical Outcomes Survey
Short Form 12 questionnaire showed the unhealed DFU group
had a greater reduction in overall physical health compared with
patients with diabetes and no history of ulcer, patients with hy-
pertension, and persons in the general population than the healed
DFU group. Additionally, significantly reduced QoL scores were
found in the unhealed DFU group compared with the healed
DFU group in several measures of physical health (P<0.002 to P
<0.04). Patients with unhealed DFUs experienced significantly
greater physical limitations and pain that affected their daily ac-
tivities and interfered with their social lives (see Figure 1). Results
of the Cardiff Wound Impact Scale showed patients with un-
healed ulcers experienced frustration and anxiety associated with
their wounds, had difficulties with activities of daily living and
footwear, and complained of having a limited social life.
Costs. A retrospective cohort study7using data collected from
a health maintenance organization from 1993 to 1995 found that
patients with DFUs (N = 514) used significantly more healthcare
resources (P<0.001) than age- and sex-matched control subjects
with diabetes and no history of foot ulcers. In the first year after
DFU diagnosis, patients with ulcers had 0.24 more emergency
room visits, 22 more outpatient visits, and 4.6 more inpatient
days than the control patients. In the second year, emergency
room visits remained unchanged for the DFU group, but outpa-
tient visits and inpatient days declined. The year 2 data for the
control group remained unchanged in all categories. Of the 514
patients with DFUs in the study, 15% developed osteomyelitis
and 15.6% had a lower limb amputated. At 36 months postdiag-
nosis, survival was significantly decreased for the DFU group
compared with the diabetic control group (72% versus 87%, re-
spectively; P<.0001).
The study7also found the attributable cost of treating a new
DFU for the 2-year period after diagnosis was $27,987 (in 1995
US dollars). Based on the medical care component of the US con-
sumer price index, which measures the average change in prices
over time of goods and services purchased by households, that
cost has increased to $45,301 (in 2008 US dollars).10The high cost
of treatment is linked to the high rate of healthcare utilization
among patients with DFUs.7
Mortality. The high rate of mortality in patients with DFUs
is well known, but how it compares with other serious medical
conditions is less well understood. Armstrong et al11discussed the
relatively high 5-year mortality rates for patients with neuropathic
and ischemic DFUs and diabetes-related amputations compared
with serious medical conditions, including
several common types of cancer, using data
gathered from multiple sources. By 5 years,
45% to 55% of patients with neuropathic and
ischemic DFUs, respectively, will die. These
common complications of diabetes have
higher mortality rates than cancers of the
prostate, breast, and colon, as well as
Hodgkin’s disease (see Figure 2). Peripheral
arterial disease itself, a primary contributor to
the development of ischemic DFU, is associ-
ated with a high mortality rate.
A recent 10-year, prospective, population-
based study12has found a history of DFU to
be a significant independent predictor of
mortality in patients with diabetes. Findings
are based on data from 1,339 patients with di-
abetes with a history of DFU, 155 patients
with diabetes without a history of DFU, and
63,632 nondiabetic participants in the Nord-
Trøndelag Health Study in Norway. The 10-
year mortality rate for patients with diabetes
with a history of DFU was 49% compared
Key Points
• The personal, physical, and economic burden of di-
abetic foot ulcers remains substantial but evidence
about optimal protocols of care is increasing.
• The authors of this review emphasize the impor-
tance of following currently available guidelines (in-
cluding offloading) and assessing progress towards
healing to optimize outcomes of care.
Ostomy Wound Management 2009;55(11):28–38
Figure 1. Quality-of-life scores in adult patients with healed (n = 47) and
unhealed (n = 57) diabetic foot ulcers.
DFU = Diabetic foot ulcer
SF-12 = Medical Outcomes Survey Short Form 12
Adapted with permission9
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with 35.2% for patients with diabetes and no history of DFU and
10.5% for nondiabetics. Among the diabetic subjects, DFU his-
tory was associated with a 38% increased risk of death. The as-
sociation between DFU history and mortality did not change
substantially after accounting for cardiovascular disease, microal-
buminuria, anxiety, or depression.
Healing rates.According to the 1999 American Diabetes As-
sociation13consensus statement on DFU care, DFUs are believed
to become chronic wounds because of predisposing factors of di-
abetes, such as peripheral neuropathy, abnormal cellular function,
and vascular disease leading to tissue hypoxia. The reason some
ulcers do not progress from an inflammatory/proliferative phase
is not well understood, but studies of chronic ulcers have found
excessive activity of the matrix metalloproteinases collagenase
and elastase that results in premature degradation of collagen and
growth factors.
DFU healing rate was examined in a meta-analysis14of 10 con-
trol groups from US Food and Drug Administration (FDA)-ap-
proved clinical trials that used standard wound care, defined as
debriding, offloading, and saline-moistened gauze dressings or
placebo gel and gauze dressings. The weighted mean rates of neu-
ropathic ulcer healing were 24.2% (95% confidence interval [CI]
19.5%, 28.8%) over 12 weeks and 30.9% (95% CI 26.6%, 35.1%)
over 20 weeks. These data offer clinicians and patients realistic
expectations of the chance of healing neuropathic ulcers during
12 and 20 weeks of care. Furthermore, these data demonstrate
that even with standard wound care, healing neuropathic foot ul-
cers in patients with diabetes is a challenge.
Standard of Wound Care for Diabetic Foot Ulcers
To better address the challenges of healing DFUs, in 2006 the
Wound Healing Society (WHS)15published evidence-based
treatment guidelines. These guidelines were written using existing
medical literature databases as well as the Medicare/Center for
Medicare and Medicaid Services (CMS) con-
sensus guidelines for chronic wounds and in-
clude clinical as well as pre-clinical studies.
Additionally, each guideline is graded by the
strength of the supporting evidence — ie, a
Level I guideline, the highest grade, is based
on a meta-analysis of multiple randomized
controlled trials (RCT) or at least two RCTs
and a Level II is based on at least one RCT and
two significant clinical series or expert opin-
ion papers.
The WHS guidelines comprise eight cate-
gories beginning with diagnosis of the ulcer
and ending with prevention of recurrences.
Optimal DFU therapy includes debridement
of necrotic and devitalized tissue, use of moist
dressings, controlling infection, and using of-
floading techniques to reduce pressure on the
wound. These standard principles are ubiq-
uitous in DFU guidelines.3,13,15However, the
WHS guidelines15and other recent reviews3,16 advocate a re-eval-
uation of the treatment regimen and considering the use of ad-
vanced-care agents (topical, device, or systemic) for wounds with
a 4-week treatment history of standard wound care resulting in
<50% overall wound area reduction.15
Debridement. Removing necrotic and devitalized tissues is
an important first step in the treatment process. In addition
to debris removal, debriding helps rid the wound of bacteria.
Surgical debridement with a sharp instrument (eg, a scalpel)
is considered the gold standard technique (Level I evidence)
but more than one debridement technique (eg, ultrasound,
pulsed lavage, and autolytic and topical enzymatic ointments)
may be appropriate.15
Debridement is thought to change the wound physiology
from chronic to acute. There is evidence that frequent surgical
debridement of wound necrotic tissue and callus surrounding
DFUs leads to higher rates of healing.17A prospective, random-
ized, double-blind multicenter, clinical trial evaluated patients
with chronic (defined as ≥8 weeks duration), neuropathic DFUs
(N = 118) treated with recombinant human platelet-derived
growth factor-beta beta or placebo.17All patients had aggressive
sharp debridement of DFUs before randomization and repeat
debridement of callus and necrotic tissue as needed. Across the
six treatment centers, patients who received frequent debride-
ment experienced a higher rate of healing than patients who re-
ceived less frequent debridement, regardless of whether they
received active treatment or placebo (see Table 1). Results from
these studies demonstrate that frequent debridement is an im-
portant first step in wound care for DFUs, irrespective of other
wound treatments used.
Proper debridement technique is necessary for optimal re-
duction of bacteria, debris, and devitalized tissue (Level II evi-
dence).15,18During debridement, the necrotic tissue is excised
to the level of healthy, bleeding tissue. Encompassing callus or
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Figure 2. Reported 5-year mortality rates.
CA = Carcinoma
PAD = Peripheral arterial disease
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