1.

Qory Aulia Dana Lubis (2008320060)

2. Marshella Brenda S. Nasution (2008320067)
3. Ainun Ulfah Sa’adiah Harahap (2008320068)
4. Lathifah Ardhian (2008320070)
5. Kaisar Balemun Harahap (2008320074)

Pembimbing :
dr. Asri Ludin Tambunan, M. Ked(PD), SpPD, FINASIM
● Title :
Risk factors for the recurrence of diabetic foot ulcers among
diabetic patients : a meta analysis.

● Authors :
Ze Hao Huang, Si Qing Li, Yan Kou, Lei Huang, Ting Yu,
Ailing Hu.

● Journal Name :
International Wiley Journal

● Date of Issue :
16 Juni 2019
ABSTRACT
INTRODUCTION : This study aimed to systematically review and identify the risk factors
for the recur- rence of diabetic foot ulcers (DFUs) among diabetic patients. PUBMED,
EMBASE, Web of Science, Cochrane Library, China Biology Medicine (CBM), China
National Knowledge Infrastructure (CNKI), WanFang, and VIP databases were
electronically searched to identify eligible studies updated to January 2019 to collect case-
control studies or cohort studies on the risk factors for the recurrence of DFUs.

METHOD : Two reviewers independently screened the literature, extracted data, and
assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. A meta-
analysis was performed using RevMan 5.3. Nine retrospective cohort studies were included,
in which 1426 patients were enrolled, 542 in the DFU recurrence group and 884 in the non-
recurrent DFU group.
RESULT : Risk factors for the recurrence of DFUs included male gender (odds ratio [OR]
= 1.38, 95% confidence interval [CI], 1.07-1.78, P < .05), smoking (OR = 1.66, 95% CI,
1.26-2.20, P = .0004), duration of diabetes (OR = 4.43, 95% CI, 1.96-6.90, P = .0004),
duration of past DFUs (OR = 1.02, 95% CI, 1.00-1.03, P = .006), plantar ulcers (OR = 5.31,
95% CI, 4.93-5.72, P <.00001), peripheral artery disease (OR = 1.65, 95% CI, 1.20-2.28, P
= .002), and diabetic peripheral neuropathy (OR = 2.15, 95% CI, 1.40-3.30, P = .0005).

CONCLUSION : No significant differences were found in age, body mass index, total
cholesterol, diabetic nephropathy, diabetic retinopathy, or hypertension. Health care staff
should pay attention to the identified risk factors for the recurrence of DFUs. Because of the
limited quality and quantity of the included studies, rigorous studies with adequate sample
sizes are needed to verify the conclusion.
INTRODUCTION
 According to the International Diabetes Federation (IDF), the
number of global diabetic patients reached 41.5 billion in 2015 and is
expected to reach 64.2 billion in 2040.

75% of those with diabetes were living in low- and middle-

income countries. Diabetic foot ulcers (DFUs) are one of the most
serious complications in diabetic patients as they are perhaps the most
common cause of diabetes-related hospitalisation and may lead to
amputation.
 Approximately 40% of patients with DFUs experience a
recurrence within 1 year after the ulcer has healed, nearly 60%
within 3 years, and 65% within 5 years.

Recurrent foot ulcerations result from various factors that

have adverse effects on patients' physiological condition, mental
health, and social functioning. In addition, these recurrent ulcers
increase the patient's medical burden because of long-term costs
related to wound management.
 There are few studies on the risk factors for the
recurrence of DFUs, and the identification of the risk factors has
still failed to reach a consensus. According to previous study of
Khalifa and Qian et al., with the former study indicating that
patients with a long duration of diabetes were at high risk of
recurrent foot ulcers, while the latter study did not show a
significant difference.

Research conducted by Diouri et al., showed that males

were more prone to recurrences of DFUs than females, but the
results from Dubský et al., did not show a significant difference
between males and females. In addition, there is still no meta-
analysis available to help synthesise these data and provide
vigorous evidence for the prevention of DFU recurrence.
MATERIALS AND
METHODS
 Studies :
o Case-control
o Cohort
Search terms :
o Diabetic foot ulcer
Databases :
o Foot ulcer
o PUBMED
o Recurrence
o EMBASE
Literature Search Strategy o Reulceration
o Web of Science
o Recurrent ulceration
o Cochrane Library
o Risk factor
o China Biology Medicine
o Predicted factor
o China National Knowledge
Infrastructure
o WangFang
o VIP Databases
Study Inclusion and Exclusion Criteria

o Diabetic patients with healed foot

ulcerations
o Case-control study or cohort study
1
o Comparison groups of recurrence and non-
Study Inclusion
Criteria: recurrence
o Data on the risk factors for recurrence of
2 DFUs reported as odds ratios (ORs) with
95% confidence intervals (95% CI)
o English or Chinese article.
3
o Editorials
Study Exclusion o Reviews
4 Criteria: o
o
Letters
Comments
 The following data were independently extracted by two
researchers :
 First author
 Year of publication
 Location of study
 Type of study
Data Abstraction and  Design
Quality Appraisal  Population size (recurrence/non-recurrence)
 Sample ages
 Follow-up time
 Risk factors

The methodological quality of included studies was independently

assessed using the validated Newcastle–Ottawa Scale (NOS).
 Statistical Analysis

All statistical analyses were performed using the Publication bias was assessed by using a funnel
Review Manager Software (RevMan5.3, plot
Microsoft, Redmond, Washington)
RESULTS
Search Process
Characteristics of the Included Studies
 Demographic Factors for The Recurrence of DFUs

Age
Two studies has reported that there is a relationship
between age and the risk of DFU recurrenc. And also no
significant difference was found in estimate of the study
effect size.

Gender
Seven strudies with 1207 patients provided eligible data
for demonstrating the relationship between gender and
DFU recurrence, The pooled results showed that males
had a higher risk of developing DFU recurrence than
females 
 Smoking
Six studies with ncluded a total of 973 patients
provided available data on the association
between smoking and DFU recurrence. The
results is  showed that smoking was associated
with an increased incidence of DFU recurrence

Body Mass Index

Three studies provided available data on the
association between BMI and DFU recurrence.
 Duration Of Diabetes Duration of past DFUs

The fixed-effects model showed that patients with a long Patients with a long duration of past DFUs were at a
duration of diabetes were at a significant risk of DFU higher risk of DFU recurrence (OR = 1.02, 95% CI, 1.00-
recurrence. 1.03, P = .006)
Clinical Factors for The Recurrence of DFUs

Peripheral Artery Disease

Patients with PAD were at a significant risk of DFU recurrence (OR =
1.65, 95% CI, 1.20-2.28, P = .002)

Diabetic Peripheral Neuropathy

Total of 534 patients provided available data on the association between
DPN and DFU recurrence. The pooled results suggested that DPN was
associated with an increased incidence of DFU recurrence (OR = 2.15,
95% CI, 1.40-3.30, P = .0005).

Diabetic Nephropathy
Total of 718 patients provided available data on the association between
DN and DFU recurrence. However, no significant difference was found
between the combined estimates (OR = 1.32, 95% CI, 0.95-1.82, P
= .10)
 Diabetic Retinopathy
Total of 645 patients pro- vided available data on the association
between DR and DFU recurrence. However, no significant difference
was found between the combined estimates (OR = 1.08, 95% CI, 0.77-
1.52, P = .65)

Hypertension
Total of 729 patients pro- vided available data on the association
between hypertension and DFU recurrence. However, no significant
difference was found between the combined estimates. (OR = 1.23, 95%
CI, 0.90-1.68, P = .20)

Total Cholesterol
Two studies reported the relationship between TC and the risk of DFU
recurrence. However, distinct heterogeneity was found among the
included studies (I2 = 73%, P < .05), and no significant difference was
found in the estimate of the study effect size (OR = 1.34, 95% CI, 0.57-
3.14, P = .50)
DISCUSSION
 Meta-analysis results showed that the
risk of DFU recurrence in male patients
was 1.38 times higher than that in
female, which was consistent with the
results of a previous study. However,
among the studies included in this study,
Male Gender Dubský et al and Khalifa found that
DFU recurrence was not related to
gender, but the authors did not give any
explanation for this negative result,
possibly because of the small sample
size.
 Some reported a higher risk of DFU recurrence in
patients with a history of smoking. Our result is
consistent with these studies. Although several
studies reported that smoking was not a risk factor
of DFU recurrence, these studies were limited in
their small sample size, while our result was based
on six studies, in which 44.2% of patients in the
DFU recurrence group had a history of smoking
Smoking compared with 34.2% in DFU non-recurrence group,
and low heterogeneity was identified among them.
According to previous studies, smoking affects
the control of blood glucose in diabetic patients,
which is closely related to the occurrence of DFUs.
In addition, smoking can cause vasoconstriction and
blood flow obstruction, leading to ischaemia and
affecting the repair of ulcers.
 Our study also found that, with the
progression of diabetes, the risk of DFU
recurrence increases, which is consistent
with the studies of Qian et al and Hu et al,
Long Duration but studies conducted by Chang et al and
Khalifa found that the duration of diabetes
of Diabetes was not an independent risk factor for
DFU recurrence; however, the authors did
not give any explanation for this negative
result.
 DFU patients with DPN were at a higher risk
of DFU recurrence, which was consistent with the
results of a previous study. DFU patients with
DPN may experience feelings of abnormal
temperature or pain sensations in their feet, and
their perception of external stimuli will be
Diabetic weakened and easily damaged. Furthermore,
sweat glands will be demineralized in case of
Peripheral autonomic neuropathy, which will make the skin
on the foot dry, chapped, and prone to ulcers. In
Neuropathy motor neuropathy, foot muscle atrophy leads to
foot malformations, and foot compression
imbalance is also prone to damage.

The results of this study indicated that DPN

is a risk factor for the recurrence of DFUs, and the
recognition of DPN should be evaluated as early
as possible in clinical practice.
Limitations

1. Some of the research data needed to be recalculated and extracted, and there may be errors in the data
conversion.
2. Because of limitations of the included data, we did not conduct subgroup analyses and funnel plots.
Some of our results show significant heterogeneity, and it is difficult to identify the possible causes of
heterogeneity.
3. Only the Chinese and English literature was retrieved, and there may be incomplete retrieval.
4. Another potential limitation is the number of existing studies; hence, further research should be
conducted to validate our conclusion.
CONCLUSION
 The results of this meta-analysis showed that gender, smoking, duration of
diabetes, duration of past DFUs, plantar ulcers, PAD, and DPN were risk
factors for DFU recurrence. By identifying these factors, health care staff
could focus on the identified risk factors for the recurrence; hence, patients
with a relatively higher risk of DFU recurrence could be treated in a more
timely manner. However, because of the limited quantity and quality of the
included studies, the research evidence of risk factors for DFU recurrence is
still insufficient. The above conclusions may be biased, and more studies are
needed to verify the correlation between the above risk factors and DFU
recurrence.
 DAFTAR PUSTAKA

Huang Z.H., Li S.Q., Kou Y., Huang L., Yu T., Hu A. Risk Factors For The Recurrence of
Diabetic Foot Ulcers Among Diabetic Patients : A Meta Analysis. International Wiley Journal :
Guangzhou. 16 June 2019. Page 1-10.
 THANKS!

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