Assessment of Ulcer Related Outcomes in Type 2 Diabetic Patients with Foot Ulceration in India

Assessment of Ulcer Related Outcomes in Type 2 Diabetic Patients with Foot Ulceration in India Authors: Vijay Viswanathan, MD, PhD 1, Satyavanij Kumpatla, MSc, MTech, PhD 2, Saraswathy Gnanasundaram, ME, PhD 3, Gautham Gopalakrishna, ME 4, Bhadendranath Das, MTech, PhD 5 The Journal of Diabetic Foot Complications, Volume 1, Issue 2, No. 3, All rights reserved. Abstract: Aim: The aim of this study was to assess the ulcer related and patient related outcomes in type 2 diabetic with foot ulceration in India. Research design and methods: A total of 1143 (M:F, 756:387) consecutive type 2 diabetic neuropathic subjects with foot ulceration seen during a period of 48 months were selected from a well established foot clinic of a tertiary care centre in India. Ulcer related outcomes were assessed. Details about smoking habits and presence of micro and macro vascular complications of diabetes were recorded. HbA 1 c% was estimated by immunoturbidimetric method. Neuropathy was diagnosed by vibration perception threshold. Education on foot examination had been carried out for all the and they had been provided with customized orthoses to reduce foot pressures. Results: Approximately 60% of ulcers healed and remained ulcer free over a mean of 34.2 months period of observation. In contrast, 23.4% of ulcers never healed and recurrence was seen in 15.1% of the ulcers. Fifteen required an amputation and 5 of the died. The median number of days for the ulcer to heal was 241 days and a recurrent or a new ulcer developed after a median of 205 days. The median time for the to be free from ulcer was 6 months. Mean HbA 1 C % and prevalence of smoking were higher in recurrent ulcer and never healed, while usage of therapeutic foot wear was lower among them when compared with ulcer free. Conclusions: The present study showed that about 60% of ulcers healed and remained ulcer free over a 34.2 months period of observation. Recurrence of healed ulcers occurred in only one sixth of and amputation in this large series was necessary in just over 1% of subjects.. It is possible to reduce the burden of foot problems by educating on foot care and by providing appropriate foot wear. Key words: Foot ulcer, ulceration related outcomes, Type 2 diabetes, Asian Indians. Address for Correspondence: Dr. Vijay Viswanathan,M.D., Ph.D., MNAMS, Diabetes Research Centre, WHO collaborating centre for Research, Education and Training in Diabetes. 4, Main Road, Royapuram, Chennai 600 013, India. Tel No. 91-44-2595 4913-15 Fax No. 91-44-2595 4919 Email: dr_vijay @vsnl.com 1,2 M. V Hospital for Diabetes and Diabetes Research Centre, Royapuram, Chennai 600013 [WHO collaborating centre for Research, Education and Training in Diabetes] 3,4,5 Central Leather Research Institute, Adyar, Chennai 600020 40

I ntroduction The high rates of type 2 diabetes and its complications are among the most serious of public health concerns around the world. Developing countries, especially India, face a major problem due to high prevalence of diabetes. 1 Considering the large population and the high prevalence of diabetes, the burden of diabetes in India will become enormous. Foot infection is a common complication of diabetes and is a leading cause for hospital admission among diabetic in India. 2 Recurrence of foot infection is commonly seen and is mainly due to the presence of neuropathy and peripheral vascular disease. 3,4 Diabetic foot ulcer management in India is similar to that practiced in other parts of the world.. Nonetheless, the outcome of clinical management is different due to patient related and ulcer related measures. Therefore a common entity to measure the outcome will be useful to compare performance between different specialty centres. Assessment of ulcer free survival of diabetic has been used as a measure of effectiveness of management of diabetic foot ulcers in the past few years. Careful management of diabetic foot complications are essential to ensure the best outcome. Pound et al 5 in a prospective study determined ulcer-free survival and examined the differences between healed and unhealed, as well as recurrent and non recurrent ulcers among diabetic from United Kingdom. They recommended ulcer free survival as a measure of the effectiveness of management of with foot ulceration. A prospective study was conducted by Jeffcoate et al 6 in a single specialist centre for the management of diabetic foot lesions over a 4 year period that assessed the outcome of foot ulcers using ulcer related and person related measures. The authors strongly suggested that when attempts are made to compare the effectiveness of management in different centres, greater emphasis should be placed on patient related outcome measures than ulcer related outcomes because ulcer related outcomes may underestimate the true morbidity and mortality associated with diabetic foot disease. It is necessary 41 to consider patient related measures such as survival with or without amputation, survival with healed or unhealed ulcer, ulcer free status and duration of ulcer free survival to ensure the best management of diabetic ulcers. Another report from the UK examined the association between ulcer characteristics at baseline and clinical outcome. 7 The report confirmed the close relationship between ulcer duration and ulcer area and outcome and emphasized the importance of early assessment of newly occurring neuropathic ulcers. There are many reports published on the survival of diabetic amputees 8,9 but only a few reports are available on the survival of diabetic with foot ulceration. 5,10 Most of the studies on diabetic foot ulcer outcome were short-term 11,12 whereas one recent study evaluated long term outcome (6.5 years) including disability as an end point. 13 The aim of this study was to assess the ulcer related and patient related outcomes in Indian type 2 diabetic with foot ulceration in a single multidisciplinary clinic for management of diabetic foot ulcers. Research and Design Methods The study were selected from a well established foot clinic of a tertiary care centre for diabetes in India. Diabetic of all socio-economic strata attend the centre for routine management of diabetes. Consecutive type 2 diabetic neuropathic subjects with foot ulceration visits during a period of 48 months were selected for this analysis. High risk subjects according to International consensus on diabetic foot 14 with foot ulcers (n=1143, M: F- 756:387) were used to assess the ulcer related outcomes. A foot ulcer was defined as any break in the epithelium below the level of ankle or discontinuity of epithelium where the deeper structures are exposed. Each patient was found to have a single ulcer on either plantar or dorsal side of the foot. Patients who had ulcers with intact skin were excluded from the study. Outcomes were determined after a minimum follow up of 3 months. Written informed consent was obtained from all the subjects and the ethics committee of the institution approved the study.

Demographic details and duration of diabetes was recorded for all the. HbA1c% was estimated by immunoturbidimetric method. Urea, creatinine and lipid profile was measured by using standard enzymatic procedures. Patients details about smoking habits and alcohol intake were recorded. Presence of micro and macro vascular complications of diabetes was also measured. Neuropathy was diagnosed by vibration perception threshold 15 and a value of >25 V was considered as abnormal. Patients with some loss of protective sensation to marked loss of protective sensation were included in this study. Peripheral vascular disease (PVD) was diagnosed if the ankle brachial pressure index (ABI) was <0.8. Ulcer outcomes were defined as healed, unhealed, major or minor amputation, and death. Healing was defined as complete epithelialization without discharge. Recurrence was defined as a further ulceration on either foot at the same or different location. Ulcers were managed by following standard outpatient care which included pressure offloading, treatment of infection and podiatric care. Patients were admitted to the hospital only for amputation and for management of intercurrent illness. All the subjects were educated regarding diabetic foot disease and its complications and the need for regular foot examination. Education on diabetic foot care is given to all and their attendants during their first visit by a qualified foot specialist. They were individually shown how to check for any minor foot injuries using a mirror. Handouts in the regional language emphasizing the need for foot care were also provided. Patients with neuropathic feet and deformities were provided with therapeutic footwear to prevent ulceration. Tovey s suggestions for correct selection of shoes and insoles are used as guideline for therapeutic footwear. 16 Patients were also provided with customized orthoses to reduce foot pressure. Different kinds of insoles such as molded EVA (Ethylene vinyl acetate), MCR (Microcellular rubber) or PU (polyurethane) foam were used to develop therapeutic foot wear for the with foot ulcers. Some were 42 provided footwear with rocker bottom soles while a few refused to buy therapeutic footwear and used their own normal footwear. Statistical Analysis Statistical analysis was carried out using SPSS for Windows version 10.0 package. Descriptive statistics were computed with means and standard deviation (sd) for continuous measurements. Median and range are reported and group comparisons were done by chi-square test and ANOVA as relevant. Kaplan-Meier techniques were used for survival analysis. Gender differences in survival analysis was done by Taron-Wale statistics. For all comparisons P<0.05 was considered as statistically significant. Results Mean (±sd) age of the study subjects was 57.6 ± 9.0 years and duration of diabetes was 12 ± 7.6 years. Twenty-eight subjects had presence of foot deformities at presentation and 112 subjects had a previous history of ulceration. Outcome was known in all the study subjects. Ulcer related outcomes among the study subjects are shown in Table 1. Out of 1143 subjects, a total of 876 (76.6%) ulcers healed, but only 704 (61.6%) of ulcers healed and remained ulcer free over a mean follow up period of 34.2 months. About 267 (23.4%) ulcers never healed and in 172 (15.1%) ulcers healed and recurrence of ulcer was seen. A total of 15 ulcers required an amputation while 5 of the died. Table 2 shows the time to outcome of neuropathic ulcers. The median (range) number of days for the ulcer to heal was 241 (95 313) days while a recurrent or a new ulcer developed in a median of 205 (142 383) days after healing of the initial ulcer which was present on enrollment. The median time for the to be free from ulcer was 6 months over a mean follow up period of 34.2 months. No gender wise difference (p > 0.05) was noted in the survival analysis (not shown).

n (M:F) 1143 (756:387) Values are n (%) Healed 876 (76.6) Unhealed 267 (23.4) Healed and remained ulcer free Healed and recurrence of ulcer No. of amputations (minor) 15 No. of deaths 5 704 (61.6) 172 (15.1) Table 1 Ulcer related outcomes among the study subjects. Ulcer to heal 241 (95-313) Recurrent or new ulcer after healing of initial ulcer present on enrollment 205 (142-383) Table 2 The time (in days) to outcome of neuropathic ulcer. Table 3 shows the comparison between healed ulcer, recurrent ulcer and ulcer never healed. Intergroup differences are not seen for mean age and duration of diabetes. Mean HbA 1 c% was significantly higher among with recurrent ulcer and ulcer never healed compared to healed ulcer (P <0.0001). Urea and triglycerides levels were higher in with recurrent ulcers. Prevalence of smoking (20.3 vs 5.8%, p<0.0001) was higher and usage of therapeutic footwear (24.4 vs 63.4% p<0.0001) was lower among with recurrent ulcers when compared with healed ulcer. A similar result was seen in never healed ulcer also when compared with healed ulcer 43 (smoking: 27.7 vs 5.8%, p<0.0001, therapeutic foot wear: 8.9 vs 63.4%, p<0.0001) Table 4 shows the details of presence of diabetic complications in healed, recurrent ulcer and never healed ulcer. Patients who never became ulcer free had a high prevalence of nephropathy and peripheral vascular disease compared to healed ulcer. Prevalence of retinopathy and peripheral vascular disease was higher in recurrent ulcer than ulcer free. Discussion To our knowledge this is the first study in India to assess ulcer related outcomes over a period of almost three years. The study showed that approximately 77% of ulcers healed during a median period of 241 days. About 60% of ulcers healed and remained ulcer free over a mean of 34.2 months period of observation. The rate of healing was similar to that reported in other cohorts. 6,17,18 The time period taken for the ulcer to heal might be longer but more than 60% of the ulcers remained ulcer free at the end of the follow up and the number of amputations were less than in other studies. This observation was similar to that reported from UK. 5 Median time to healing was 78 days in another prospective study. 6 Our results showed that 23% of ulcers never healed during the follow up period whereas in the UK study it was 33% who never became ulcer free during the follow up period. 5 These differences emphasize the need to look at population studies, characteristics and treatment options. Fifteen ulcers were amputated in our study; each of them had ABI < 0.6 and could not be revascularized. Only five died during the period of follow up. Pound et al reported a median of 126 days for the development of a recurrent or new ulcer. 5 In our study, recurrence or new ulceration was seen in 15 % of ulcers with a median time of 205 days. The total number of whose ulcer persisted throughout the entire study period along with the number of who developed a new foot ulcer is 439 out of 1143 or 38.4%. Recurrence or development of new ulceration was associated with

Healed ulcer Recurrent ulcer Ulcer never healed Number 704 172 267 M/F 442/262 102/71 182/85 P value Age (in years) 57.5 (9.0) 57.8 (8.9) 57.9 (8.9) 0.79 Duration of diabetes (in years) 11.9 (7.4) 12.5 (8.2) 12.53 (8.2) 0.44 HbA1C % 8.9 (3.3) 10.6 (4.2) 9.9 (3.9) <0.0001 Urea (mg/dl) 29.8 (22.2) 34.2 (18.2) 30.8 (28.0) 0.08 Creatinine (mg/dl) 1.0 (1.0) 1.1 (1.0) 1.15 (1.1) 0.1 Triglycerides (mg/dl) 166 (90) 184 (120) 164 (82.9) 0.05 Total Cholesterol (mg/dl) 190 (51.6) 182 (53.5) 188.9 (50.5) 0.18 Smoking n, (%) 41 (5.8) 35 (20.3)* 74 (27.7)** <0.0001 Therapeutic foot wear n,(%) 446 (63.4) 42 (24.4)* 24 (8.9)**, # <0.0001 Table 3 Comparison of characteristics among healed ulcer, recurrent ulcer and ulcer never healed. Values are mean (sd) * Healed ulcer vs. Recurrent ulcer, ** Healed ulcer vs. Ulcer never healed, # Recurrent ulcer vs. ulcer never healed. Chi square test: Smoking: * χ 2 = 34.9, p<0.0001 Therapeutic foot wear: * χ 2 = 83.34, p<0.0001 ** χ 2 = 86.7, p<0.0001 ** χ 2 = 227, p<0.0001 # χ 2 = 18.3, p<0.0001 poorer glycemic control, smoking, less usage of therapeutic foot wear, high rates of retinopathy and peripheral vascular disease. Mantey et al showed that recurrence was associated with smoking, poorer glycemic control, increased alcohol intake and greater degrees of neuropathy. 19 In another study which included only neuropathic ulcers, it was found that recurrence was associated with poor glycemic control, alcohol use in men and less favorable markers of self care. 20 We have excluded alcohol use because consumption of alcohol was much less in our. Appropriate education for, the provision of proper foot wear and regular foot care can reduce rates of reulceration. This study clearly showed that management of diabetic foot ulcer involves maintenance of good 44 glycemic control and lipid levels and management of other complications of diabetes. Several studies have shown that high ulcer recurrence rates are associated with higher amputation rates and that approximately 27% of ulcers are associated with amputations. 21,22 In a long term study, outcome of hospitalized for diabetic foot ulcers was poor. About 77.5% experienced primary healing without major amputation and those who experienced primary healing about 60.9% had recurrence of ulcer. In that study 43.8 % underwent amputation and 51.7% died due to all cause mortality. 13 A recent study examined the outcome of neuropathic foot ulcers based on the duration and area of ulcers at baseline. 7

Healed ulcer Recurrent ulcer Ulcer never healed Number of 704 172 267 Trend χ 2, p value Hypertension 284 (40.3) 81 (47.1) 107 (40.1) 2.8, 0.25 Retinopathy 72 ((10.2) 29 (16.9) 23 (8.6) 8.1, 0.018 Nephropathy 43 (6.1) 14 (8.1) 43 (16.1) 24.3, <0.0001 PVD 18 (2.6) 27 (15.7) 37 (13.9) 59.2, <0.0001 Table 4 Details of presence of diabetic complications in healed ulcer, recurrent ulcer and ulcer never healed. Values are n (%). We did not look into such associations in the present study. Ulcer free survival is a new concept in the management of foot ulcers. Median time for our to be free from ulcer was 6 months over a mean period of 34.2 months. There was no significant difference between genders in this regard. Earlier reports showed the importance of documenting ulcer-free survival and to use it as a measure of the overall effectiveness of management of foot ulcers. 5 Preventive measures are known to lower the risk of amputation by 50%. 23 Careful observation and assessment of ulcers and monitoring of foot pulses, peripheral vascular disease and/or neuropathy is essential to ensure that the integrity of the limb is not threatened. A multidisciplinary team approach is the key to successful management of diabetic foot ulceration. Strategies such as intensive diabetes management and foot care education have been shown successful in preventing foot complications and surgery. 24 In summary, our study showed that about 60% of ulcers healed and remained ulcer-free over a 34.2 months period of observation. Recurrence of ulceration and number of amputations were low. This was achieved by providing education on foot care and appropriate protective foot wear to the. The growing burden of foot problems may be reduced by initiating simple preventive measures such as these in developing countries. Ulcer free survival is a fairly new concept and can be used as a measure of success in the overall management of foot ulcers. Conflict of interest: None declared. Acknowledgement: We acknowledge the help rendered by Ms. M. Sivagami for data collection, Ms. Lavanya Senthil and Ms. Priyanka Tilak in the preparation of manuscript. 45

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