Professional Documents
Culture Documents
Received 8 August 2006; received in revised form 28 March 2007; accepted 23 April 2007
Abstract
Objectives: The aim of this study was to evaluate the epidemiology of diabetic foot problems (DFP) and predictive factors for major
amputations (below- and above-knee). Methods: This is a prospective study of 202 patients treated in National University Hospital (NUH)
during the period of January 2005 to May 2006. A protocol was designed for documentation including patient profile, type of DFP, presence
of risk factors, comorbidities and complications, clinical presentation, investigations, treatment given, and final outcome. The predictors for
limb loss were determined using univariate and stepwise logistic regression analysis. Results: One hundred ninety-two patients had Type 2
diabetes. Mean age of cohort was 60 years, with male to female ratio of 1:1. Incidence of DFP was significantly higher in Malays ( P=.0015)
and Indians ( P=.036) and significantly lower in Chinese ( Pb.05). Of patients, 72.8% had poor endocrine control (GHb level N7%), and
42.1% of patients had sensory neuropathy based on 5.07 SemmesWeinstein Monofilament test. Common DFP included gangrene (31.7%),
infection (abscess, osteomyelitis) (28.7%), ulcer (27.7%), cellulitis (6.4%), necrotizing fasciitis (3.5%) and Charcots osteoarthropathy
(2.0%). Surgery was performed in 74.8% of patients and major amputation in 27.2% of patients (below-knee in 20.3% and above-knee in
6.9%). Conclusions: This is the first detailed prospective study evaluating predictive factors for major amputations in patients with DFP.
Significant univariate predictive factors for limb loss were age above 60 years, stroke, ischaemic heart disease, nephropathy, peripheral
vascular disease (PVD), sensory neuropathy, glycosylated haemoglobin level, Ankle Brachial Index (ABI) b0.8, gangrene, infection, and
pathogens such as methicillin-resistant Streptococcus aureus (MRSA) and Staphylococcus aereus. Upon stepwise logistic regression
analysis, only PVD and infection were significant.
D 2008 Elsevier Inc. All rights reserved.
Keywords: Diabetes; Amputation; Risk factors; Epidemiology
1. Introduction
The prevalence of diabetes in Singapore is 8.2% in 2004
(Ministry of Health Singapore, 2004). Diabetic foot problems (DFP) are very common in Singapore, accounting for
approximately one fifth of all emergency admissions in
National University Hospital (NUH). Every year, almost
4 Corresponding author. Department of Orthopaedic Surgery, Yong
Loo Lin School of Medicine, National University of Singapore, Singapore.
Tel.: +65 6772 4323; fax: +65 6778 0720.
E-mail address: dosnathe@nus.edu.sg (A. Nather).
1056-8727/08/$ see front matter D 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.jdiacomp.2007.04.004
78
3. Results
The age of patients ranged from 21 to 91 years, with
mean age being 60.0 years. Majority of patients were in
their fifth and sixth decades. Bose (1978) also found the
average age to be about 60 years. The ratio of males to
females was 1:1, although Bose found the ratio of males to
females to be 1:1.5. Racial distribution was 45.5% Chinese,
32.7% Malays, 17.8% Indians, and 4.0% other races. When
compared against the racial distribution of Singapores
national population (Singapore Department of Statistics,
2000), incidence of DFP in our cohort was significantly
higher in Malays ( P=.0015) and Indians ( P=.036) and
significantly lower in Chinese ( Pb.05). Previous studies on
diabetic foot lesions in Singapore (Bose, 1979; Bose, 1978;
Cheah et al., 1985; Lee & Bose, 1985) did not study the
incidence of DFP amongst the different races.
One hundred ninety-two patients had Type 2 diabetes,
and 10 had Type 1. Duration of diabetes ranged from 1 to
48 years. Of patients, 41.6% had diabetes between 1 and
10 years duration, 39.1% between 11 and 20 years, 14.3%
between 21 and 30 years, and 5.0% with more than
30 years duration.
Majority of patients (72.8%) had poor control of
diabetes, as indicated by their GHb levels (N7%).
The most common comorbidities were hypertension
(74.8%), followed by IHD (36.1%) and stroke (8.9%). Risk
factors included smoking (19.3%), alcoholism (9.4%),
obesity (8.4%), and hyperlipidaemia (51.0%). With respect
to the complications of diabetes, 44.1% of patients had
retinopathy, and 51.5% had nephropathy.
The most common DFP were gangrene (31.7%),
infection (abscess and osteomyelitis) (28.7%), and ulcer
(27.7%). Others included cellulitis (6.4%), necrotizing
fasciitis (3.5%), and Charcots osteoarthropathy (2.0%).
Ulcers encountered were Grade 1 in 15 patients, Grade 2 in
27, and Grade 3 in 14.
Infections were encountered in 122 patients (60.4%)
63 patients (31.2%) with monomicrobial infections and
59 patients (29.2%) with polymicrobial infections. This is
based on blood cultures performed for all patients and
swabs for culture in patients with ulcer or discharge. In
patients undergoing operation, tissue from the infected area
was sent for culture. This is rather different to an earlier
study performed by Bose (Bose, 1979), who found
monomicrobial infections in 53.3% and polymicrobial
infections in 46.7%. The commonest pathogens encountered in the group with monomicrobial infections were
Staphylococcus aureus (34.9%), Pseudomonas aeruginosa
(17.5%), Streptococcus agalactiae Group B (11.1%), and
methicillin-resistant Streptococcus aureus (MRSA)
(11.1%). In comparison, Bose (1979) found monomicrobial
infections to consist of Streptococcus aureus (30%),
P. aeruginosa (30%), Proteus (22.5%) and Klebsiella
(17.5%). Fifty-nine patients had polymicrobial infections, and the commonest pathogens encountered were
79
Table 1
Results of evaluation of factors as predictive factors of limb loss
Limb loss
Risk factor
Positive
Age
V60 years
N60 years
19 (18.4)
36 (36.4)
Gender
Male
Female
Race
Chinese
Malay
Indian
Others
Unadjusted
Stepwise analysis
OR (95% CI)
P value
84 (81.6)
63 (63.6)
1.0
2.5 (1.34.8)
26 (25.2)
29 (29.3)
77 (74.8)
70 (70.7)
1.0
1.2 (0.72.3)
25
15
12
3
(27.2)
(22.7)
(33.3)
(37.5)
67
51
24
5
(72.8)
(77.3)
(66.7)
(62.5)
1.0
0.8 (0.41.6)
1.3 (0.63.1)
1.6 (0.47.2)
Yes
No
Yes
No
Yes
No
43
12
28
27
9
46
(28.5)
(23.5)
(38.4)
(20.9)
(50.0)
(25.0)
108
39
45
102
9
138
(71.5)
(76.5)
(61.6)
(79.1)
(50.0)
(75.0)
1.3 (0.62.7)
1.0
2.4 (1.24.4)
1.0
3.0 (1.18.0)
1.0
.493
Yes
No
Yes
No
Yes
No
Yes
No
3
52
3
52
12
43
33
22
(15.8)
(28.4)
(17.6)
(28.1)
(30.8)
(26.4)
(32.0)
(22.2)
16
131
14
133
27
120
70
77
(84.2)
(71.6)
(82.4)
(71.9)
(69.2)
(73.6)
(68.0)
(77.8)
0.5
1.0
0.5
1.0
1.2
1.0
1.7
1.0
(0.11.7)
.249
(0.22.0)
.360
(0.62.7)
.581
(0.93.1)
.119
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
24
31
40
15
45
10
30
25
40
15
(27.0)
(27.4)
(38.5)
(15.3)
(48.4)
(9.2)
(35.3)
(21.4)
(36.7)
(16.1)
65
82
64
83
48
99
55
92
69
78
(73.0)
(72.6)
(61.5)
(84.7)
(51.6)
(90.8)
(64.7)
(78.6)
(63.3)
(83.9)
1.0
1.0
3.5
1.0
9.3
1.0
2.0
1.0
3.0
1.0
(0.51.8)
.941
(1.86.8)
b.001
(4.320.0)
b.001
(1.13.8)
.029
(1.55.9)
.001
Type of DFP
Gangrene
Infection
Ulcer
Cellulitis
Necrotizing fasciitis
Charcots osteoarthropathy
30
6
15
0
4
0
(46.9)
(10.3)
(26.8)
(0.0)
(57.1)
(0.0)
34
52
41
13
3
4
(53.1)
(89.7)
(73.2)
(100.0)
(42.9)
(100.0)
4.0 (2.17.7)
0.2 (0.10.6)
1.0 (0.51.9)
N.A
3.8 (0.817.4)
N.A
b.001
.001
.930
.999
.090
.999
2 (20.0)
53 (27.6)
8 (80.0)
139 (72.4)
1.0
1.5 (0.37.4)
Duration of diabetes
N30 years
110 years
1120 years
2 (20.0)
21 (25.0)
21 (26.6)
8 (80.0)
63 (75.0)
58 (73.4)
1.0
1.3 (0.36.8)
1.4 (0.37.4)
Comorbidities
Hypertension
IHD
Stroke
Risk factors
Alcoholism
Obesity
Smoking
Hyperlipidaemia
Complications
Retinopathy
Nephropathy
PVD
Sensory neuropathy
ABI b0.8
Negative
OR (95% CI)
P value
8.4 (3.918.3)
b.001
0.3 (0.10.7)
.011
.005
.518
.527
.490
.536
.008
.028
.601
.729
.656
(continued on next page)
80
Table 1 (continued)
Limb loss
Risk factor
Duration of diabetes
2130 years
GHb level N7%
Yes
No
Pathogens
MRSA
B. fragilis
Staphylococcus aureus
P. aeruginosa
Streptococcus agalactiae Group B
Unadjusted
Stepwise analysis
Positive
Negative
OR (95% CI)
P value
11 (37.9)
34 (23.1)
21 (38.2)
18 (62.1)
113 (76.9)
34 (61.8)
2.4 (0.413.7)
0.5 (0.30.9)
1.0
.309
.034
7.0
1.5
0.4
1.3
0.5
.006
.413
.042
.578
.249
7
7
7
10
3
(70.0)
(35.0)
(15.2)
(31.3)
(15.8)
3
13
39
22
16
(30.0)
(65.0)
(84.8)
(68.8)
(84.2)
(1.728.1)
(0.64.0)
(0.21.0)
(0.62.9)
(0.11.7)
OR (95% CI)
P value
3.1.2. Sex
Sex was not found to be an important predictive factor in
our study ( P=.518). This is similar to findings by Gurlek
et al. (1998). In contrast, Hamalainen et al. (1999), Tseng
(2006), Resnick et al. (2004), and Hennis et al. (2004) found
sex to be a significant prognostic factorthe male gender
having an increased predisposition to amputation.
3.1.3. Race
Race was not found to be a significant predictive factor
for limb loss in our study. In a study conducted by Young
et al. (2003), Native Americans, African Americans, and
Hispanics were found to have an increased risk of
amputations compared to the whites.
3.1.4. Type of DFP
Gangrene ( Pb.001) and infection ( P=.001) were found
to be predictive factors for limb loss in our study. However,
osteomyelitis was found to be a significant prognostic factor
by Fejfarova et al. (2002) and Gurlek et al. (1998).
3.1.5. Risk factors
Smoking, alcoholism, obesity and hyperlipidaemia were
not found to be predictive factors for limb loss in our study
conducted ( PN.05). Smoking was also not found to be a
significant predictive factor by Gurlek et al. (1998), Lehto
et al. (1996) and Selby & Zhang (1995).
3.1.6. Comorbidities
Both stroke ( P=.028) and IHD ( P=.008) were found to
be predictive factors of limb loss in our cohort while
hypertension was not ( P=.493). Similarly, stroke was found
to be a significant factor by Selby & Zhang (1995), while
hypertension was not found to be a significant factor by
Gurlek et al. (1998). However, hypertension was found to
be a significant factor by Selby and Zhang.
3.1.7. Complications
PVD ( Pb.001) and nephropathy ( Pb.001) were found to
be significant predictive factors for limb loss in our cohort.
Studies conducted by Hamalainen et al. (1999), Young et al.
(2003), Nelson et al. (1988), Resnick et al. (2004), Lehto
4. Conclusions
This is the first prospective study in detail to evaluate the
predictive factors for limb salvage in patients with DFP in
Singapore. Significant univariate predictive factors for limb
loss were age above 60 years, comorbidities (stroke and
IHD), complications of diabetes (nephropathy), PVD,
sensory neuropathy, GHb level, ABI b0.8, DFP such as
81
Acknowledgment
The authors would like to thank all members of the NUH
Multi-Disciplinary Team for DFP, Dr. Vikram David, Dr
V.A. Rajesh, Dr Ajay Nambiar, and the house officers and
medical officers of NUH wards for their commitment in
providing health care to patients with DFP.
References
Bose, K. (1979). A surgical approach for the infected foot. International
Orthopaedics, 3 (3), 177 181.
Bose, K. (1978). Infection in diabetic foot. Annals of the Academy of
Medicine, Singapore, 7, 359 365.
Cheah, J. S., Thai, A. C., Alli, R., Chan, L., Wang, K. W., & Yeo, P. P.
(1985). Infections in diabetes with special reference to diabetics in
Singapore. Annals of the Academy of Medicine, Singapore, 14 (2),
240 246.
Edmonds, M. E., & Foster, A. V. M. (2005). Managing the diabetic foot
(2nd ed.). London7 Blackwell.
Fejfarova, V., Jirkovska, A., Skibova, J., & Petkov, V. (2002). Pathogen
resistance and other risk factors in the frequency of lower limb
amputations in patients with the diabetic foot syndrome. Vnitrni
Lekarstvi, 48 (4), 302 306.
Gurlek, A., Bayraktar, M., Savas, C., & Gedik, O. (1998). Amputation rate
in 147 Turkish patients with diabetic foot: The Hacettepe University
Hospital Experience. Experimental and Clinical Endocrinology &
Diabetes, 106 (5), 404 409.
Hamalainen, H., Ronnemaa, T., Halonen, J. P., & Toikka, T. (1999). Factors
predicting lower extremity amputations in patients with Type 1 or
Type 2 diabetes mellitus: A population-based 7-year follow-up study.
Journal of Internal Medicine, 246 (1), 97 103.
Hennis, A. J. M., Fraser, H. S., Jonnalagadda, R., Fuller, J., & Chaturvedi,
N. (2004). Explanations for the high risk of diabetes-related amputation
in a Caribbean population of Black African descent and potential for
prevention. Diabetes Care, 27, 2636 2641.
Imran, S., Ali, R., & Mahboob, G. (2006). Frequency of lower extremity
amputation in diabetics with reference to glycemic control and Wagner
S grades. Journal of the College of Physicians and SurgeonsPakistan,
16 (2), 124 127.
Lee, E. H., & Bose, K. (1985). Orthopaedic management of diabetic
foot lesions. Annals of the Academy of Medicine, Singapore, 14 (2),
331 333.
Lehto, S., Ronnemaa, T., Pyorala, K., & Laakso, M. (1996). Risk factors
predicting lower extremity amputations in patients with NIDDM.
Diabetes Care, 19, 607 612.
Leung, H. B., Ho, Y. C., Carnett, J., Lam, P. K. W., & Wong, W. C. (2001).
Diabetic foot ulcers in the Hong Kong Chinese population: Retrospective study. Hong Kong Medical Journal, 7, 350 355.
Ministry of Health Singapore. (1993). Central Claims Processing System.
Ministry of Health Singapore. (1999). Clinical Practice Guidelines for
Managing Diabetes Mellitus.
Ministry of Health Singapore. (2004). Details of National Health Survey
2004 Findings.
Miyajima, S., Shirai, A., Yamamoto, S., Okada, N., & Matsushita, T.
(2006). Risk factors for major limb amputations in diabetic foot
gangrene patients. Diabetes Research and Clinical Practice, 71 (3),
272 279.
82
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.