IJCRR - 4(6), March, 2012
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RISK FACTORS FOR LOWER EXTREMITY AMPUTATION IN PATIENTS WITH DIABETIC FOOT ULCERS
Author: B A Nikhil Nanjappa, Karthik P, T Tirou Aroul, S. Robinson Smile
Abstract:Background: The number patients with diabetic foot ulcers presenting to surgery clinics has been increasing at an alarming rate. Diabetic foot ulcers are the most common cause for nontraumatic foot amputation. This study was undertaken to analyze both the risk factors for development of foot ulcers in diabetics and for lower extremity amputation (LEA) in patients with diabetic foot ulcers. Methods: A prospective analytical study that assessed the various risk factors associated with the development of foot ulcers in diabetics and that eventually lead to LEA in these patients. Univariate analysis and multivariate logistic regression (WALD's TEST) were used to assess statistical significance. Results: A total of 120 patients were included in the study, of which 53 underwent LEA. The incidence of foot ulcers was found to be higher in the following categories: males, 5th decade, associated hypertension, hyperlipidemia, and duration of diabetes more than 5 years. The significant risk factors for LEA are male gender, smoking, alcohol consumption, duration of DM more than 5 years, ABPI< 0.9. Conclusion: Smoking, alcohol consumption, duration of diabetes> 5 years, male gender and peripheral vascular diseases (ABPI< 0.9) are statistically significant risk factors for amputation of diabetic foot ulcer.
Keywords: lower limb amputation, diabetic foot ulcers, risk factors for amputation.
Diabetic foot ulcer is a rising health problem with the surge in prevalence of diabetes. Foot ulcers have become the leading cause for hospitalization (20-30%) and the most important cause for prolonged hospitalization in diabetics. The prevalence of foot ulcers in diabetics is between 5- 10%. Upto 85% of all diabetic foot and its related problems are preventable through a combination of good foot care and health education for both patients and their healthcare providers. The holistic care of a diabetic foot ulcer needs a multidisciplinary approach: apart from glycemic control; the treatment includes meticulous debridement, sterile dressing, off-loading and appropriate antibiotics. Lower extremity amputation is one of the most feared outcomes of diabetes. About half of non-traumatic lower limb amputations are performed in diabetics and the post amputation mortality in 5 years is 39-80%. The number of diabetics in India is predicted to reach 57 million by 2025. In lines with these concerns, the slogan for World Diabetes Day 2005 was ?PUT FOOT FIRST: PREVENT AMPUTATION?. This study was undertaken to assess the risk factors that would lead to the development of foot ulcers in diabetics and lower extremity amputation (LEA) in these patients.
Aims and Objectives of the study
To identify the risk factors for lower extremity amputation (LEA) in patients with diabetic foot ulcers and also to analyze the risk factors for development of foot ulcers in patients with diabetes.
A prospective study was conducted at Mahatma Gandhi Medical College and Research Institute, Pondicherry from June 2007 to August 2009. A total 120 patients were studied. 53 of the 120 patients underwent amputation, which was around (44.16%). The study involved risk factors such as gender, smoking, alcohol consumption, duration of diabetes, ankle-brachial index (ABPI), complications like osteomyelitis and associated complications of diabetes such as neuropathy, retinopathy and nephropathy. Univariate analysis and multivariate logistic regression (WALD‘s TEST) were done to find out statistical significance. P value of less than 0.05 is considered significant. RESULTS This was a prospective study to identify the risk factors leading to lower extremity amputation (LEA) in known diabetic patients presenting with foot ulcers. The patients were between 32 and 78 years of age with a peak incidence in the 5thdecade. The following data has been observed: 41 patients (36.7%) were in the age group of 41-50 years, 30 patients (25%) in 6th decade, 22 patients (18.3%) in the 4th decade, 19 patients (15.8%) in the 7th decade and 5 patients (4.2%) in the 8th decade. Of the 120 patients studied, 73 patients (60.8%) were male and 47 patients (39.2%) were female (Table1).The incidence of foot ulcers increases with the duration of diabetes. Of the 120 patients who presented with foot ulcers, 78 patients (65%) had diabetes for over 5 years, 86 patients (71.7%) had associated hypertension, and 98 patients (81.7%) had hyperlipidemia. The P values were 0.0000 for both and are statistically significant risk factors for the development of foot ulcers in diabetics. The site of the ulcers was most commonly in the forefoot region, seen in 87 of 120 patients (72.5%), followed by mid foot ulcers in 24 patients (20%) and hind foot ulcers in 9 patients (7.5%). The microorganisms which grew on the culture and sensitivity were predominantly Proteus in 32 patients (26.7%), followed by E.Coli in 25 patients (20.8%), Polymicrobial flora in 23 patient (19.2%), Pseudomonasin 14 patients (11.7%), Klebsiella in 14 patients (11.7%), Alpha hemolytic streptococci in 9 patients (7.5%), and MRSA (methicillin resistant Staphylococcus aureus)in 3 patients (2.4%). Of the 120 patients, 53 (44.16%) underwent amputation. 38 (71.7%) of the 53 patients were male and 15 patients (28.3%) were females. The P value was 0.0301; which is statistically significant and shows that males are more prone for LEA. Of the 53 patients who underwent LEA, 11 patients (20.7%) underwent below knee amputations and 1 patient (2%) underwent above knee amputation and minor amputation (removal of toes) was done in 41 patients (77.3%). Thirty three (62.2%) of 53 patients who underwent LEA consumed alcohol and 37 patients (69.8%) were smokers. The P values were 0.0014 for both and are statistically significant risk factors for amputation. Peripheral vascular disease or vasculopathy was studied as a risk factor for LEA. Ankle-brachial pressure index (ABPI) was calculated for all patients, ABPI 0.9 and 51 patients (96.2%) had ABPI < 0.9. The P value was 0.00035 and is statistically significant for LEA (Table 2).The duration of diabetes has always played an important role in amputation. Eight of 12 patients (66.6%) who underwent major amputation and 36 of 41 patients (87.8%) who underwent minor amputation had diabetes for more than 5 years. P value was 0.00049 and is statistically significant for LEA. Out of the 12 major amputations, 6 patients (50%) had forefoot ulcers, 4 patients (33.3%) had mid foot ulcers and 2 patients (16.7%) had hind foot ulcers. Associated complications of diabetes such as neuropathy, retinopathy and nephropathy was present in 33 (62.2%), 33 (62.2%) and 26 (49.0%) of the 53 patients who underwent amputation. Since the three parameters could not be studied in all patients of the non-amputation group, the statistical significance was not determined. Osteomyelitis was present in 27 patients (50.9%) of the 53 that underwent amputation, but the statistical significance could not be determined as all the patients of the non-amputated were not assessed for osteomyelitis. Table 3 shows the Univariate analysis of risk factors for amputation. Smoking, alcohol consumption, male gender, duration of diabetes more than 5 years and PVD (ABPI)<0.9 were found to be statistically significant.The risk factors had significant P values on Univariate analysis when amputation group was compared with non-amputation group. But there was no significance when Univariate analysis was done on each factor while comparing major and minor amputation groups. Significant factors in multiple logistic regression test (WALD‘S test) were male gender and PVD (ABPI<0.9).
Foot infection in diabetes patients is a common (20% of all hospital admissions of diabetic patients), complex, and expensive issue . In addition to causing severe morbidity they now account for the largest number of diabetes-related hospital bed days (as long as 26 weeks for full recovery)  and are also the most common non traumatic cause for amputation (6 per 1000) . Observational studies suggest that 6-43% patients of diabetic foot ulcers will eventually progress to amputation [13, 14] . Ramsey et al.  reported amputation rates of 11.2% in patients with new onset foot ulcers over a 4-year period. In our study, 53 of the 120 patients (44.17 %) studied underwent amputation and is in accordance with the reported rates in literature. The incidence of diabetic foot ulcers increases with progression of age. Many studies revealed that the mean age group was in the 6th and 7thdecade [4, 5, 6] . Mehamud et al. of Pakistan in his paper, ?clinical profile, management and outcome of diabetic foot ulcers in tertiary care hospital‘, determined that out of 120 patients, majority of patients who underwent amputation had type 2 diabetes (95.7%), males (66%), with duration of diabetes more than 10 years (p<0.05). The mean age was 54.29 +/- 7.71 years. Male gender is a significant risk factor for amputation [4, 5, 6]. In our study we found that the highest incidence was in the 5th decade (36.7%) and 60.8% were males. Many observational studies have claimed that associated co-morbidities of diabetes like hypertension and hyperlipidemia, contribute to development of foot ulcers, via their effects on micro-circulation (7, 8, 10, 21). We found that associated hypertension and hyperlipidemia were significant factors that lead to diabetic foot ulcers.
Duration of diabetes also plays an important role leading to ulcer formation. The incidence of lower extremity amputation is more in patients who have had diabetes for more than 5 years .Duration of diabetes and glycemic control is directly related to micro vascular damage and is considered a significant factor for amputation. In our study 83% of patients who underwent amputation had diabetes for more than 5 years. It was found to be a statistically significant risk factor for LEA. Winkley et al. of UK in, ?Risk factors associated with adverse outcomes in a population based prospective cohort study of people with their first diabetic foot ulcer‘, explained that the significant risk factors were age, male gender, smoking, ulcer site, size, severity of neuropathy, ischemia, Hba1c levels, and presence of vascular complications. Micro vascular complications were the only explanation for recurrent ulceration .Chaturvedi in his article, ?risk of diabetes related amputation in South Asians and Europeans in UK‘, observed a decrease by quarter in the risk of amputation in South Asians compared to Europeans. This was explained by the low rate of peripheral vascular disease (PVD), neuropathy, and smoking in South Asians compared to the Europeans .In our study we found that smoking and alcohol consumption were statistically significant risk factors for LEA in patients with diabetic foot ulcers. The absence of peripheral pulses (dorsalis pedis andposterior tibial) and ABPI<0.9, indicates Peripheral vascular disease (PVD). PVD favors the occurrence of diabetic foot ulcers and eventually lead to amputation. ABPI less than 0.9; which is an outcome of PVD precede amputation [9, 10]. Dalla et al. claimed that PVD is the only major risk factor leading to amputation  . Neuropathy is considered if three of the following four sensations were absent: light touch, pain, vibration, and tendon reflexes. The risk for amputation is higher with PVD than that for neuropathy . Distinction between neuropathic and vascular ulcers is not clear cut, because neuropathy may contribute to foot ulceration via effects on the microcirculation. Lavery et al.  claimed that neuropathy, but not vasculopathy, in the patients with diabetes was a risk factor for ulcers . It is plausible that neuropathy may precipitate an ulcer and vasculopathy may prevent its healing. In our study 51 out of 53 patients who underwent amputation had PVD (ABPI less than 0.9). This finding emphasizes the importance of PVD and its significance to LEA. Faglia et al.  in, ?Peripheralangioplasty, as the first choice revascularization procedure in diabetic patients with critical limb ischemia‘, evaluated 993 patients who underwent peripheral angioplasty. The 5 year primary patency was 88%. He proved that peripheral angioplasty is the first choice revascularization procedure that it is feasible, safe, and effective for limb salvage in a high percentage of diabetic patients. Wijeyaratnae  et al. in his publication, ?Revascularization in diabetic small vessel disease of lower limbs: is it worthwhile?‘ used saphenous vein to bypass occluded infra-popliteal arteries in diabetics with critical limb ischemia over a 5-year period. He noted patency in 65% of patients at a mean follow up of 30 months. He concluded that bypass of diabetic small vessel disease of lower limb is feasible and effective in preventing major amputation and independent mobility. Both these authors concluded that, revascularization helps in salvaging the limb. However, stenosis in diabetes is commonly located peripheral to the popliteal artery, which is factor reducing the patency of bypass or other surgery  . Mehmood K  et al. in their paper, ?Clinical profile and management outcome of diabetic foot ulcers in Pakistan‘ and Carlson T  proved that males were at higher risk for amputation. The above mentioned studies were carried out in diverse populations. The probable cause is the higher incidence of alcohol consumption, smoking, hypertension among other genetic predisposing factors. In our study, male gender, smoking, alcohol consumption were significant risk factors for amputation.
The incidence of diabetic foot ulcers is higher in males of that in the 5th decade of life; Males are more prone for amputation. Associated Hypertension and Hyperlipidemia are statistically significant risk factors leading to foot ulcers in diabetics. Smoking and Alcohol consumption and PVD (ABPI<0.9), and duration of diabetes more than 5 years are statistically significant risk factors for LEA. Statistical significance of associated complications such as neuropathy, nephropathy, retinopathy, and osteomyelitis could not be determined. This study provides information for primary care and specialist practitioners to identify diabetic patients at high risk for lower extremity amputation. Of the significant risk factors for LEA mentioned in our study; smoking, alcohol intake, and PVD are preventable. It underlines the importance of health education and health promotion among the public. Diabetics have to be urged to quit smoking and alcohol consumption at the time of diagnosis of diabetes. The value of early diagnosis and management of diabetes cannot to be overemphasized as it may significantly reduce or delay the incidence of PVD.
Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed
An informed consent was sought from all the patients who were included in the study. The methodology of the study was explained to the patients individually in a language of their understanding. The patients were allowed to withdraw from the study at any point. The patients were also informed that the data collected from this study would be used for medical research and the material could be published, and they authors would take responsibility to protect the privacy of the patients. The format of the informed consent was approved by the institutional human ethics committee.
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List of Abbreavations LEA: Lower extremity amputation. ABPI: Ankle-brachial pressure index. PVD: Peripheral vascular disease. mmHg : millimeters of mercury