- Email: [email protected]
Patients’ clinical charecteristics and predictors for diabetic foot amputation
p r i m a r y c a r e d i a b e t e s 1 3 ( 2 0 1 9 ) 247–251
Contents lists available at ScienceDirect
Primary Care Diabetes journal homepage: http://www.elsevier.com/locate/pcd
Original research
Patients’ clinical charecteristics and predictors for diabetic foot amputation Z.A. Sayiner a,∗ , F.I. Can b , E. Akarsu a a b
Department of Endocrinology and Metabolism, Gaziantep University School of Medicine, Gaziantep, Turkey Department of Internal Medicine, Gaziantep University School of Medicine, Gaziantep, Turkey
a r t i c l e
i n f o
a b s t r a c t
Article history:
Introduction: Medical and surgical treatment options are available for patients with dia-
Received 11 July 2018
betic foot ulcers. In more severe cases, amputation decisions are determined by patient
Received in revised form
comorbidities, performance, imaging studies, and clinical examination results. However, an
6 December 2018
objective indicator that predicts how this amputation process will end has not yet been
Accepted 9 December 2018
clarified. This study identifiies clinical characteristics that can be predictors of the need for
Available online 29 December 2018
diabetic foot amputation among patients. Methods: In this retrospective observational study, a total of 400 patients with type 2 diabetes who were over the age of 18 and possessed diabetic foot ulcers were examined. The clinical, radiological, and scintigraphic profiles of these patients including age, gender, duration of diabetes, smoking history, previous diabetic foot amputation, presence of hypertension (HT), coronary artery disease (CAD), peripheral artery disease (PAD), cerebrovascular disease, cardiovascular disease, retinopathy, neuropathy and nephropathy were analyzed. Results: Of the 400 patients with diabetic foot ulcers, 143 (35.75%) underwent foot amputation. Moreover, the frequency of proteinuria in amputees was significantly higher than in non-amputees (p < 0,05). Amputees also exhibited significantly longer smoking histories (p < 0,001), and the frequency of reamputation was significantly higher in those who possesed histories of previous amputation (p = 0.038). After multivariate analysis PAD presence and previous diabetic ulcer history were the significant factors to determine the amputation decision. Conclusion: The following patient characteristics were determined as being effective for predicting the need for amputation: male sex, CAD, PAD, HT, proteinuria, ulcers with Wagner Stages 4–5, smoking histories, previous diabetic ulcer histories, and previous amputation histories. The specificity of the model with these variables was determined as 86% in the patients who did not need amputation. Significant determinants were peripheral artery disease presence and diabetic foot ulcer history. Still, further and more extensive research with higher numbers of patients is necessary for determining more precisely the need for amputation. © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
∗ Corresponding author at: Gaziantep University, School of Medicine, Division of Endocrinology & Metabolism, 27100 Sahinbey, Gaziantep, Turkey. E-mail address: [email protected] (Z.A. Sayiner). https://doi.org/10.1016/j.pcd.2018.12.002 1751-9918/© 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
248
1.
p r i m a r y c a r e d i a b e t e s 1 3 ( 2 0 1 9 ) 247–251
Introduction
With the development of many drugs for diabetes, the life span of patients have been prolonged and the frequency of diabetic complications has increased. Diabetic Foot Syndrome is one of the most important complication of DM. The diabetic foot is one of the most important public health problems in the world because of the length of stay in hospital, high health care cost, increased mortality and morbidity. Diabetic Foot Syndrome occurs when diabetic neuropathy and vascular insufficiency are accompanied by infection. There is a risk of developing diabetic foot ulcers in 10%–25% of all diabetic patients. Besides the cause of 60% of non traumatic foot amputations is diabetic foot ulcer [1,2]. In patients with diabetic foot syndrom, amputation decision is taken with presence of comorbid factors, daily performance of patients, doppler ultrasonography findings, other imaging modalities and clinical examination results. There is no objective amputation criteria developed in this respect yet [3]. Medical and surgical treatment options are available for diabetic foot ulcers. There is no objective predictor of how this process will end. Early or unnecessary amputation may lead increased morbidity, loss of work force loss and high health care cost on the other hand delayed amputation may lead major amputation, prolonged treatment duration [1,4]. In this study, we aimed to reveal the clinical differences between the amputated and non-amputated groups of the patients who were diagnosed with diabetic foot ulcer between 2012–2017 in the Department of Endocrinology and Metabolism Diseases of Gaziantep University Medical Faculty Hospital.
2.
Material and method
The study included patients who were followed up with a diagnosis of diabetic foot ulcer in the Department of Endocrinology and Metabolism of the Faculty of Medicine of Gaziantep University between the years of 2012–2017. A total of 400 patients with type 2 diabetes who completed the age of 18 and had diabetic foot ulcers were identified. Clinical, radiological and scintigraphic findings of 400 patients were retrospectively reviewed. Patients age, gender, duration of diabetes, smoking history, previous diabetic foot amputation, presence of hypertension, coronary artery disease, peripheral artery disease, cerebrovascular disease, cardiovascular disease, retinopathy, neuropathy and nephropathy were noted. Records of diabetic foot ulcers were classified according to the Wagner classification. The presence of peripheral artery disease was determined by examining the results of lower extremity arterial doppler reports in patient files and the clinical symptoms of the patients. The diagnosis of osteomyelitis was made by laboratory, microbiological, radiological and clinical evaluations, and with he probe to bone test in appropriate patients. Lower extremity radiographs, lower extremity scintigraphy, sedimentation rate and C-reactive protein levels and magnetic resonance imaging were used if needed. [5] The presence of neuropathy was concluded by examining the symptoms and EMG results in patient files. Patients were divided into two groups as amputated and non amputated. Gaziantep Univer-
sity Medical Faculty Ethics Committee was approved for the study. (Decision no. 2017/214).
3.
Statistical analysis
Statistical analysis was performed using the IBM SPSS Statistics 22 program. P value of less than 0.05 was considered statistically significant. The Kolmogorov Smirnov test was used to determine whether the data is normal distribution or not. The Chi-square test was used to examine the relationship of clinical data, and the Mann–Whitney U test was used to determine the association of some clinical and laboratory data. Univariate binary logistic regression test was used to calculate the odds ratio of the variables. Comparisons of clinical data with amputations of 400 patients included in the study were performed by Chi square test. For Multivariate binary logistic regression analysis, Variance Inflation Factors (VIF) were calculated to evaluate multicollinearity among variables included to model. Among statistically significant variables according to univariate analysis only variables without collinearity were included to model.
4.
Results
Table 1 shows the comparison of patient groups with amputation and without amputation with clinical data. Of the 400 patients with diabetic foot ulcers, 143 (35.75%) were amputed. Of the amputees, 101 (70.6%) were male and 42 (29.4%) female. There was a cerebrovascular event in 15 (10.5%) of the amputees patients and no SVO in 128 patients (89.5%). In 243 (94.6%) of the 257 diabetic foot ulcers without amputation, SVO was absent and in 14 (5.4%) was present. There was no significant relationship between amputation patients and SVO (p = 0.067). The frequency of proteinuria in amputee patients was statistically significantly higher than in non-amputee patients (p < 0,05). There was no significant difference in terms of neuropathy between patients who were not amputated and amputated (p = 0,053). When the relation between amputation and retinopathy was examined, retinopathy data of many patients could not be reached. A total of 241 of 400 patients were informed of retinopathy. There was no significant difference in retinopathy between amputation patients and non-amputated patients (p = 0.065). 55 (38.5%) of the amputated patients were classified as stage 1–3 and 88 (61.5%) patients as stage 4–5 according to the Wagner classification. The frequency of amputation was higher in patients diabetic foot ulcer with wagner stage 4–5 (p < 0.001). Smoking history was found in 65 (45.5%) of the amputees and there was no smoking history in 78 (54.5%) of the amputees. In patients with amputation, smoking history was significantly higher (p < 0,001). The frequency of reamputation was significantly higher in those who had previous amputation historiey (p = 0.038). After determining the variables that affect the amputation decision, we tried to create a model with these variables. Variance Inflation Factors (VIF) were calculated to evaluate multicollinearity among variables included to model. Model determinants were shown in Table 2. Among statistically
249
p r i m a r y c a r e d i a b e t e s 1 3 ( 2 0 1 9 ) 247–251
Table 1 – The comparison of the clinical charecteristics of the patients with amputation and without amputation. Amputees
Non-Amputees
Number Gender CAD presence PAD presence HT presence CVE presence
Proteinuria presence Neuropathy presence Retinopathy presence Wagner stage Smoking history Diabetic foot ulcer history Previous amputation history
%
Number
OR (%95 GA)
P
%
Female Male No Yes No Yes No Yes No Yes
42 101 38 105 38 105 43 100 128 15
29.4 70.6 26.6 73.4 26.6 73.4 30.1 69.9 89.5 10.5
102 155 105 152 141 116 104 153 243 14
39.7 60.3 40.9 59.1 54.9 45.1 40.5 59.5 94.6 5.4
1 1.58 (1.02–2.45) 1 1.9 (1.22–2.98) 1 3.35 (2.15–5.24) 1 1.58 (1.02–2.44) 1 2.03 (0.95–4.34)
0.039
No Yes No Yes Yok Var 1–3 4–5 No Yes No Yes No Yes
44 99 5 138 15 69 55 88 78 65 70 73 116 27
30.8 69.2 3.5 96.5 17,9 82,1 38.5 61.5 54.5 45.5 49 51 81.8 18.9
116 141 22 235 45 112 251 6 184 73 195 62 228 29
45.1 54.9 8.6 91.4 28,7 71,3 97.7 2.3 71.6 28.4 75.9 24.1 88.7 11.3
1 1.85 (1.20–2.85) 1 2.58 (0.95–6.97) 1.84 (0.95–3.56) 1 1 66.93(27.84–160.87) 1 2.10 (1.37–3.21) 1 3.28 (2.12–5.06) 1 1.83 (1.03–3.23)
0.005
0.004 <0.001 0.039 0.067
0.053 0.065 <0.001
<0.001 <0.001 0.038
P sig with <0,05. CAD: Coronary artery Disease, PAD: Peripheral artery Disease, HT: Hypertension, CVE: Cerebrovascular event.
Table 2 – Multivariate binary logistic regression result and variables in equation. P
Gender PAD presence Hypertension presence CVE presence Neuropathy presence Proteinuria presence Retinopathy presence Smoking history Diabetic foot ulcer history Previous amputation history
,257 ,000 ,673 ,655 ,133 ,312 ,815 ,307 ,000 ,632
OR
1,336 2,978 1,113 1,215 2,292 1,303 1,073 1,292 2,567 1,160
95% C.I.for OR Lower
Upper
,810 1,858 ,676 ,518 ,777 ,780 ,597 ,790 1,592 ,631
2,206 4,771 1,833 2,849 6,762 2,177 1,928 2,115 4,141 2,134
P sig with <0,05. CAD: Coronary artery Disease, PAD: Peripheral artery Disease, CVE: Cerebrovascular event.
significant variables according to univariate analysis only variables without collinearity were included to model. Specificity of the model was 86% and the accuracy of the model was found to be 70% in determining the patients who did not require amputation in patients with diabetic ulcer. Significant determinants were peripheral artery disease presence and diabetic foot ulcer history.
5.
Discussion
The most common comorbid diseases in patients with diabetic foot ulcers are; hypertension, cardiovascular disease,
cerebrovascular disease and peripheral artery disease [6]. In a meta analysis study by Shin and colleagues analyzing 33 articles and found that the rate of amputation of male gender was higher than female patients [7]. This finding is compatible with our study. In our study male patients had higher amputation rates. However, the reason for the amputation being more prevalent in the male gender and being the predisposing factor for the risk of amputation is not fully understood [8]. Differences in male and female behavior were frequently used to explain this situation. Men are often under more physical burden and social pressure than women, and may be a cause for them to force them to feel healthy and strong. Studies have suggested the hormonal protective effect of estrogen. This hormonal effect, which is especially true for cardiovascular diseases, is perhaps caused by differences in immune system function among genders [9,10]. However, there are also studies suggesting that there is no gender difference for diabetic foot amputation [11]. In a study by Adler and colleagues, PAH was shown to be a risk factor for diabetic foot ulcer and PAH presence increased the lower extremity amputation three fold [6]. On the contrary, there are also studies in which there is no significant relationship between PAD and diabetic foot amputation [12]. In our study, amputation was more frequent in patients with PAD. The frequency of PAH in major amputated patients was significantly higher. Peripheral arterial disease is known to be an effective factor in the development of diabetic foot ulcers, progression and delayed healing. Wound progression due to vascular insufficiency and delay of healing can lead to major amputation [13]. It will be important to detect an PAD to achieve permenant treatment.
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p r i m a r y c a r e d i a b e t e s 1 3 ( 2 0 1 9 ) 247–251
Findings in studies examining the relation between amputation frequency and coronary artery disease presence generally indicate that the presence of coronary artery disease increases amputation progression [14–17]. Likewise our study supports these findings. When the relationship between amputation and CVE is examined, different results are seen in the literature. Nather and his colleagues found that CVE increased the risk of amputation [14]. Hamalainen and his colleagues did not find any relationship between amputation and CVE [18]. In patients with amputation we had more CAD in our study. However, there was no statistically significant relationship between amputation and cerebrovascular disease. Hypertension causes arterial wall thickening and thus causes arterial stiffness. Hypertension is the most important cause like diabetes. The combination of DM and hypertension will cause more severe PAD. In the study performed by Jean et al. the duration of hypertension was evaluated and the relationship between diabetic lower limb amputation and long duration of hypertension presence was determined (p = 0.02) [17]. There are also studies in which there is no relationship between diabetic foot amputation and hypertension [9,12,13,19]. In our study, patients with amputation had more hypertension. This information points to the importance of blood pressure regulation in diabetic patients. Patients with amputation had higher proteinuria level at a statistically significant level. On the other hand, there was no significant relationship between amputation and neuropathy. This was because neuropathy was quite high in patients with diabetic foot ulcers, which required both amputates and non amputated. (Respectively 96.5% − 91.4%) Besides there was no significant correlation between amputation and retinopathy. There are studies showing the relationship between amputation and previous diabetic foot ulser presence. In a study by Adler et al. increased amputation risk was found when diabetic foot ulcers develop in patients with diabetic foot ulcer history. It is also shown in this study that the risk of reamputation is increased in patients with amputation history [6,20]. When we analyze the data in our study; the presence of a history of diabetic foot ulcer has been shown to increase the risk of amputation. The diabetic lower extremity amputation history also caused increased reamputation risk. This may be related to poor self care of the patient, lack of foot care training. The presence of Wagner stage 4–5 significantly increases the risk of amputation compared to stage 1–2–3 ulcers. It is seen that Wagner’s disease on the first visit of the patient is the main determinant of clinical course. When we look at studies that examine the relationship between amputation and smoking, we see different results. Hamalainen et al. found that the smoking history increased the frequency of amputation [18]. Li et al. did not find a significant relationship between amputation and smoking history [21]. In our study, smoking history was found to be significantly higher in amputation. Important limitation of the study was the use of the wagner classification instead of the texas and sinbad classifications as the diabetic foot classification. Wagner classification, especially group 3, has a wide range of patients. This situation reduces the power of the study.
As a result; the criteria for amputation in patients with diabetic foot syndrome are still unclear. However, male sex, presence of coronary artery disease, peripheral arterial disease, hypertension, proteinuria, ulcer with wagner stage 4–5, smoking, previous diabetic ulcer history and previous amputation history seem to be effective factors in predicting amputation. The specificity of the model with these variables was determined as 86% in the patients who did not need amputation. Significant determinants were peripheral artery disease presence and diabetic foot ulcer history. It is clear that there is a need for more extensive work with higher numbers of patients to be able to make the amputation decision more eloquently.
Conflict of Interest None.
Funding There is no funding in this study.
references
[1] A. Misuri, G. Lucertini, A. Nanni, A. Viacava, P. Belardi, Predictive value of transcutaneous oximetry for selection of the amputation level, J. Cardiovasc. Surg. 41 (1) (2000) 83–87. [2] G.E. Rayber, J.H. Bowker, M.A. Pfeifer, Epidemiology of foot ulcers and amputations in the diabetic foot, in: The Diabetic Foot, 6th ed., Mosby Inc, St louis, Missouri, 2001, pp. 13–32. [3] S. Akcay, E. Harman, I˙. Safa, Rates and risk factors of diabetic foot reamputations, Med. Sci. 1 (4) (2012) 283–291. [4] R.H. Linger, D.W. Foster, Diabetes mellitus, in: Williams Textbook of Endocrinology, 9th ed., WB Saunders Company, 1988, p. 1017. [5] L. Giurato, M. Meloni, V. Izzo, L. Uccioli, Osteomyelitis in diabetic foot: a comprehensive overview, World J. Diabetes 8 (April (4)) (2017) 135–142. [6] A.I. Adler, E.J. Boyko, J.H. Ahroni, D.G. Smith, Lower-extremity amputation in diabetes. The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers, Diabetes Care 22 (7) (1999) 1029–1035. [7] J.Y. Shin, S.G. Roh, N.H. Lee, K.M. Yang, Influence of epidemiologic and patient behavior-related predictors on amputation rates in diabetic patients: systematic review and meta-analysis, Int. J. Low. Extrem. Wounds 16 (March (1)) (2017) 14–22. ˘ [8] N. Bas¸kal, S. Güllü, S¸.D. Ilgın, M.F. Erdogan, N. Kamel, G. ˘ Erdogan, Evaluation of the patients with diabetic foot ulcerations, Turk. J. Endocrinol. Metab. 1 (2) (1998) 31–35. [9] A. Tivesten, D. Mellstrom, H. Jutberger, Low serum testosterone and high serum estradiol associate with lower extremity peripheral arterial disease in elderly men. The MrOS Study in Sweden, J. Am. Coll. Cardiol. 50 (2007) 1070–1076. [10] A. Nather, C.S. Bee, C.Y. Huak, J.L. Chew, C.B. Lin, S. Neo, E.Y. Sim, Epidemiology of diabetic foot problems and predictive factors for limb loss, J. Diabetes Complications 22 (2) (2008) 77–82. [11] Y. Jiang, X. Ran, L. Jia, C. Yang, P. Wang, J. Ma, H. Yin, Epidemiology of type 2 diabetic foot problems and predictive
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factors for amputation in China, Int. J. Low. Extrem. Wounds 14 (1) (2015) 19–27. A.M. Mantovani, C.E. Fregonesi, M.R. Palma, F.E. Ribeiro, R.A. Fernandes, D.G. Christofaro, Relationship between amputation and risk factors in individuals with diabetes mellitus: a study with Brazilian patients, Diabetes Metab. Syndr. Clin. Res. Rev. 11 (1) (2017) 47–50. B.T. Rodrigues, V.N. Vangaveti, U.H. Malabu, Prevalence and risk factors for diabetic lower limb amputation: a clinic-based case control study, J. Diabetes Res. 2016 (2016). A. Nather, C.S. Bee, C.Y. Huak, J.L. Chew, C.B. Lin, S. Neo, E.Y. Sim, Epidemiology of diabetic foot problems and predictive factors for limb loss, J. Diabetes Complications 22 (2) (2008) 77–82. M.H. Criqui, R.D. Langer, A. Fronek, H.S. Feigelson, M.R. Klauber, Large vessel and isolated small vessel disease, in: F.G.R. Fowkes (Ed.), Epidemiology of Peripheral Vascular Disease, Springer-Verlag, London, 1991, pp. 85–96. M.T. Quilici, S. Del Fiol Fde, A.E. Vieira, M.I. Toledo, Risk factors for foot amputation in patients hospitalized for diabetic foot infection, J. Diabetes Res. 2016 (2016) 8931508.
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[17] B.J. Jeon, H.J. Choi, J.S. Kang, M.S. Tak, E.S. Park, Comparison of five systems of classification of diabetic foot ulcers and predictive factors for amputation, Int. Wound J. 14 (3) (2017) 537–545. [18] H. Hämäläinen, T. Rönnemaa, J.P. Halonen, T. Toikka, Factors predicting lower extremity amputations in patients with type 1 or type 2 diabetes mellitus: a population-based 7-year follow-up study, J. Intern. Med. 246 (1) (1999) 97–103. [19] Y.J. Lai, H.Y. Hu, C.H. Lin, S.T. Lee, S.C. Kuo, P. Chou, Incidence and risk factors of lower extremity amputations in people with type 2 diabetes in Taiwan, 2001–2010, J. Diabetes 7 (2) (2015) 260–267. [20] H.B. Leung, Y.C. Ho, J. Carnett, P.K. Lam, W.C. Wong, Diabetic foot ulcers in the Hong Kong Chinese population: retrospective study, Hong Kong Med. J. 7 (4) (2001) 350–355. [21] X. Li, T. Xiao, Y. Wang, H. Gu, Z. Liu, Y. Jiang, Z. Xu, Incidence, risk factors for amputation among patients with diabetic foot ulcer in a Chinese tertiary hospital, Diabetes Res. Clin. Pract. 93 (1) (2011) 26–30.
Contents lists available at ScienceDirect
Primary Care Diabetes journal homepage: http://www.elsevier.com/locate/pcd
Original research
Patients’ clinical charecteristics and predictors for diabetic foot amputation Z.A. Sayiner a,∗ , F.I. Can b , E. Akarsu a a b
Department of Endocrinology and Metabolism, Gaziantep University School of Medicine, Gaziantep, Turkey Department of Internal Medicine, Gaziantep University School of Medicine, Gaziantep, Turkey
a r t i c l e
i n f o
a b s t r a c t
Article history:
Introduction: Medical and surgical treatment options are available for patients with dia-
Received 11 July 2018
betic foot ulcers. In more severe cases, amputation decisions are determined by patient
Received in revised form
comorbidities, performance, imaging studies, and clinical examination results. However, an
6 December 2018
objective indicator that predicts how this amputation process will end has not yet been
Accepted 9 December 2018
clarified. This study identifiies clinical characteristics that can be predictors of the need for
Available online 29 December 2018
diabetic foot amputation among patients. Methods: In this retrospective observational study, a total of 400 patients with type 2 diabetes who were over the age of 18 and possessed diabetic foot ulcers were examined. The clinical, radiological, and scintigraphic profiles of these patients including age, gender, duration of diabetes, smoking history, previous diabetic foot amputation, presence of hypertension (HT), coronary artery disease (CAD), peripheral artery disease (PAD), cerebrovascular disease, cardiovascular disease, retinopathy, neuropathy and nephropathy were analyzed. Results: Of the 400 patients with diabetic foot ulcers, 143 (35.75%) underwent foot amputation. Moreover, the frequency of proteinuria in amputees was significantly higher than in non-amputees (p < 0,05). Amputees also exhibited significantly longer smoking histories (p < 0,001), and the frequency of reamputation was significantly higher in those who possesed histories of previous amputation (p = 0.038). After multivariate analysis PAD presence and previous diabetic ulcer history were the significant factors to determine the amputation decision. Conclusion: The following patient characteristics were determined as being effective for predicting the need for amputation: male sex, CAD, PAD, HT, proteinuria, ulcers with Wagner Stages 4–5, smoking histories, previous diabetic ulcer histories, and previous amputation histories. The specificity of the model with these variables was determined as 86% in the patients who did not need amputation. Significant determinants were peripheral artery disease presence and diabetic foot ulcer history. Still, further and more extensive research with higher numbers of patients is necessary for determining more precisely the need for amputation. © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
∗ Corresponding author at: Gaziantep University, School of Medicine, Division of Endocrinology & Metabolism, 27100 Sahinbey, Gaziantep, Turkey. E-mail address: [email protected] (Z.A. Sayiner). https://doi.org/10.1016/j.pcd.2018.12.002 1751-9918/© 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
248
1.
p r i m a r y c a r e d i a b e t e s 1 3 ( 2 0 1 9 ) 247–251
Introduction
With the development of many drugs for diabetes, the life span of patients have been prolonged and the frequency of diabetic complications has increased. Diabetic Foot Syndrome is one of the most important complication of DM. The diabetic foot is one of the most important public health problems in the world because of the length of stay in hospital, high health care cost, increased mortality and morbidity. Diabetic Foot Syndrome occurs when diabetic neuropathy and vascular insufficiency are accompanied by infection. There is a risk of developing diabetic foot ulcers in 10%–25% of all diabetic patients. Besides the cause of 60% of non traumatic foot amputations is diabetic foot ulcer [1,2]. In patients with diabetic foot syndrom, amputation decision is taken with presence of comorbid factors, daily performance of patients, doppler ultrasonography findings, other imaging modalities and clinical examination results. There is no objective amputation criteria developed in this respect yet [3]. Medical and surgical treatment options are available for diabetic foot ulcers. There is no objective predictor of how this process will end. Early or unnecessary amputation may lead increased morbidity, loss of work force loss and high health care cost on the other hand delayed amputation may lead major amputation, prolonged treatment duration [1,4]. In this study, we aimed to reveal the clinical differences between the amputated and non-amputated groups of the patients who were diagnosed with diabetic foot ulcer between 2012–2017 in the Department of Endocrinology and Metabolism Diseases of Gaziantep University Medical Faculty Hospital.
2.
Material and method
The study included patients who were followed up with a diagnosis of diabetic foot ulcer in the Department of Endocrinology and Metabolism of the Faculty of Medicine of Gaziantep University between the years of 2012–2017. A total of 400 patients with type 2 diabetes who completed the age of 18 and had diabetic foot ulcers were identified. Clinical, radiological and scintigraphic findings of 400 patients were retrospectively reviewed. Patients age, gender, duration of diabetes, smoking history, previous diabetic foot amputation, presence of hypertension, coronary artery disease, peripheral artery disease, cerebrovascular disease, cardiovascular disease, retinopathy, neuropathy and nephropathy were noted. Records of diabetic foot ulcers were classified according to the Wagner classification. The presence of peripheral artery disease was determined by examining the results of lower extremity arterial doppler reports in patient files and the clinical symptoms of the patients. The diagnosis of osteomyelitis was made by laboratory, microbiological, radiological and clinical evaluations, and with he probe to bone test in appropriate patients. Lower extremity radiographs, lower extremity scintigraphy, sedimentation rate and C-reactive protein levels and magnetic resonance imaging were used if needed. [5] The presence of neuropathy was concluded by examining the symptoms and EMG results in patient files. Patients were divided into two groups as amputated and non amputated. Gaziantep Univer-
sity Medical Faculty Ethics Committee was approved for the study. (Decision no. 2017/214).
3.
Statistical analysis
Statistical analysis was performed using the IBM SPSS Statistics 22 program. P value of less than 0.05 was considered statistically significant. The Kolmogorov Smirnov test was used to determine whether the data is normal distribution or not. The Chi-square test was used to examine the relationship of clinical data, and the Mann–Whitney U test was used to determine the association of some clinical and laboratory data. Univariate binary logistic regression test was used to calculate the odds ratio of the variables. Comparisons of clinical data with amputations of 400 patients included in the study were performed by Chi square test. For Multivariate binary logistic regression analysis, Variance Inflation Factors (VIF) were calculated to evaluate multicollinearity among variables included to model. Among statistically significant variables according to univariate analysis only variables without collinearity were included to model.
4.
Results
Table 1 shows the comparison of patient groups with amputation and without amputation with clinical data. Of the 400 patients with diabetic foot ulcers, 143 (35.75%) were amputed. Of the amputees, 101 (70.6%) were male and 42 (29.4%) female. There was a cerebrovascular event in 15 (10.5%) of the amputees patients and no SVO in 128 patients (89.5%). In 243 (94.6%) of the 257 diabetic foot ulcers without amputation, SVO was absent and in 14 (5.4%) was present. There was no significant relationship between amputation patients and SVO (p = 0.067). The frequency of proteinuria in amputee patients was statistically significantly higher than in non-amputee patients (p < 0,05). There was no significant difference in terms of neuropathy between patients who were not amputated and amputated (p = 0,053). When the relation between amputation and retinopathy was examined, retinopathy data of many patients could not be reached. A total of 241 of 400 patients were informed of retinopathy. There was no significant difference in retinopathy between amputation patients and non-amputated patients (p = 0.065). 55 (38.5%) of the amputated patients were classified as stage 1–3 and 88 (61.5%) patients as stage 4–5 according to the Wagner classification. The frequency of amputation was higher in patients diabetic foot ulcer with wagner stage 4–5 (p < 0.001). Smoking history was found in 65 (45.5%) of the amputees and there was no smoking history in 78 (54.5%) of the amputees. In patients with amputation, smoking history was significantly higher (p < 0,001). The frequency of reamputation was significantly higher in those who had previous amputation historiey (p = 0.038). After determining the variables that affect the amputation decision, we tried to create a model with these variables. Variance Inflation Factors (VIF) were calculated to evaluate multicollinearity among variables included to model. Model determinants were shown in Table 2. Among statistically
249
p r i m a r y c a r e d i a b e t e s 1 3 ( 2 0 1 9 ) 247–251
Table 1 – The comparison of the clinical charecteristics of the patients with amputation and without amputation. Amputees
Non-Amputees
Number Gender CAD presence PAD presence HT presence CVE presence
Proteinuria presence Neuropathy presence Retinopathy presence Wagner stage Smoking history Diabetic foot ulcer history Previous amputation history
%
Number
OR (%95 GA)
P
%
Female Male No Yes No Yes No Yes No Yes
42 101 38 105 38 105 43 100 128 15
29.4 70.6 26.6 73.4 26.6 73.4 30.1 69.9 89.5 10.5
102 155 105 152 141 116 104 153 243 14
39.7 60.3 40.9 59.1 54.9 45.1 40.5 59.5 94.6 5.4
1 1.58 (1.02–2.45) 1 1.9 (1.22–2.98) 1 3.35 (2.15–5.24) 1 1.58 (1.02–2.44) 1 2.03 (0.95–4.34)
0.039
No Yes No Yes Yok Var 1–3 4–5 No Yes No Yes No Yes
44 99 5 138 15 69 55 88 78 65 70 73 116 27
30.8 69.2 3.5 96.5 17,9 82,1 38.5 61.5 54.5 45.5 49 51 81.8 18.9
116 141 22 235 45 112 251 6 184 73 195 62 228 29
45.1 54.9 8.6 91.4 28,7 71,3 97.7 2.3 71.6 28.4 75.9 24.1 88.7 11.3
1 1.85 (1.20–2.85) 1 2.58 (0.95–6.97) 1.84 (0.95–3.56) 1 1 66.93(27.84–160.87) 1 2.10 (1.37–3.21) 1 3.28 (2.12–5.06) 1 1.83 (1.03–3.23)
0.005
0.004 <0.001 0.039 0.067
0.053 0.065 <0.001
<0.001 <0.001 0.038
P sig with <0,05. CAD: Coronary artery Disease, PAD: Peripheral artery Disease, HT: Hypertension, CVE: Cerebrovascular event.
Table 2 – Multivariate binary logistic regression result and variables in equation. P
Gender PAD presence Hypertension presence CVE presence Neuropathy presence Proteinuria presence Retinopathy presence Smoking history Diabetic foot ulcer history Previous amputation history
,257 ,000 ,673 ,655 ,133 ,312 ,815 ,307 ,000 ,632
OR
1,336 2,978 1,113 1,215 2,292 1,303 1,073 1,292 2,567 1,160
95% C.I.for OR Lower
Upper
,810 1,858 ,676 ,518 ,777 ,780 ,597 ,790 1,592 ,631
2,206 4,771 1,833 2,849 6,762 2,177 1,928 2,115 4,141 2,134
P sig with <0,05. CAD: Coronary artery Disease, PAD: Peripheral artery Disease, CVE: Cerebrovascular event.
significant variables according to univariate analysis only variables without collinearity were included to model. Specificity of the model was 86% and the accuracy of the model was found to be 70% in determining the patients who did not require amputation in patients with diabetic ulcer. Significant determinants were peripheral artery disease presence and diabetic foot ulcer history.
5.
Discussion
The most common comorbid diseases in patients with diabetic foot ulcers are; hypertension, cardiovascular disease,
cerebrovascular disease and peripheral artery disease [6]. In a meta analysis study by Shin and colleagues analyzing 33 articles and found that the rate of amputation of male gender was higher than female patients [7]. This finding is compatible with our study. In our study male patients had higher amputation rates. However, the reason for the amputation being more prevalent in the male gender and being the predisposing factor for the risk of amputation is not fully understood [8]. Differences in male and female behavior were frequently used to explain this situation. Men are often under more physical burden and social pressure than women, and may be a cause for them to force them to feel healthy and strong. Studies have suggested the hormonal protective effect of estrogen. This hormonal effect, which is especially true for cardiovascular diseases, is perhaps caused by differences in immune system function among genders [9,10]. However, there are also studies suggesting that there is no gender difference for diabetic foot amputation [11]. In a study by Adler and colleagues, PAH was shown to be a risk factor for diabetic foot ulcer and PAH presence increased the lower extremity amputation three fold [6]. On the contrary, there are also studies in which there is no significant relationship between PAD and diabetic foot amputation [12]. In our study, amputation was more frequent in patients with PAD. The frequency of PAH in major amputated patients was significantly higher. Peripheral arterial disease is known to be an effective factor in the development of diabetic foot ulcers, progression and delayed healing. Wound progression due to vascular insufficiency and delay of healing can lead to major amputation [13]. It will be important to detect an PAD to achieve permenant treatment.
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Findings in studies examining the relation between amputation frequency and coronary artery disease presence generally indicate that the presence of coronary artery disease increases amputation progression [14–17]. Likewise our study supports these findings. When the relationship between amputation and CVE is examined, different results are seen in the literature. Nather and his colleagues found that CVE increased the risk of amputation [14]. Hamalainen and his colleagues did not find any relationship between amputation and CVE [18]. In patients with amputation we had more CAD in our study. However, there was no statistically significant relationship between amputation and cerebrovascular disease. Hypertension causes arterial wall thickening and thus causes arterial stiffness. Hypertension is the most important cause like diabetes. The combination of DM and hypertension will cause more severe PAD. In the study performed by Jean et al. the duration of hypertension was evaluated and the relationship between diabetic lower limb amputation and long duration of hypertension presence was determined (p = 0.02) [17]. There are also studies in which there is no relationship between diabetic foot amputation and hypertension [9,12,13,19]. In our study, patients with amputation had more hypertension. This information points to the importance of blood pressure regulation in diabetic patients. Patients with amputation had higher proteinuria level at a statistically significant level. On the other hand, there was no significant relationship between amputation and neuropathy. This was because neuropathy was quite high in patients with diabetic foot ulcers, which required both amputates and non amputated. (Respectively 96.5% − 91.4%) Besides there was no significant correlation between amputation and retinopathy. There are studies showing the relationship between amputation and previous diabetic foot ulser presence. In a study by Adler et al. increased amputation risk was found when diabetic foot ulcers develop in patients with diabetic foot ulcer history. It is also shown in this study that the risk of reamputation is increased in patients with amputation history [6,20]. When we analyze the data in our study; the presence of a history of diabetic foot ulcer has been shown to increase the risk of amputation. The diabetic lower extremity amputation history also caused increased reamputation risk. This may be related to poor self care of the patient, lack of foot care training. The presence of Wagner stage 4–5 significantly increases the risk of amputation compared to stage 1–2–3 ulcers. It is seen that Wagner’s disease on the first visit of the patient is the main determinant of clinical course. When we look at studies that examine the relationship between amputation and smoking, we see different results. Hamalainen et al. found that the smoking history increased the frequency of amputation [18]. Li et al. did not find a significant relationship between amputation and smoking history [21]. In our study, smoking history was found to be significantly higher in amputation. Important limitation of the study was the use of the wagner classification instead of the texas and sinbad classifications as the diabetic foot classification. Wagner classification, especially group 3, has a wide range of patients. This situation reduces the power of the study.
As a result; the criteria for amputation in patients with diabetic foot syndrome are still unclear. However, male sex, presence of coronary artery disease, peripheral arterial disease, hypertension, proteinuria, ulcer with wagner stage 4–5, smoking, previous diabetic ulcer history and previous amputation history seem to be effective factors in predicting amputation. The specificity of the model with these variables was determined as 86% in the patients who did not need amputation. Significant determinants were peripheral artery disease presence and diabetic foot ulcer history. It is clear that there is a need for more extensive work with higher numbers of patients to be able to make the amputation decision more eloquently.
Conflict of Interest None.
Funding There is no funding in this study.
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