PROFILE OF DIABETIC FOOT ULCER PATIENTS AT TERTIARY CARE HOSPITAL IN SURABAYA, INDONESIA

1 Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia, arisviasukma@gmail.com 2 Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga – Dr. Soetomo General Hospital, Surabaya, Indonesia, hermina-n@fk.unair.ac.id 3 Department of Orthopaedic and Traumatology, Faculty of Medicine, Universitas Airlangga – Dr. Soetomo General Hospital, Surabaya, Indonesia, mouli-edward@fk.unair.ac.id Correspondence Author: Hermina Novida, hermina-n@fk.unair.ac.id, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, 60132, Indonesia


INTRODUCTION
Diabetes Mellitus (DM) is a noncommunicable disease that has been a burden on many countries, including Indonesia. Indonesia was ranked sixth worldwide in 2017 in terms of DM prevalence, with a total of 10.3 million DM patients aged 20-79 years old; this number is expected to rise to 16.70 million in 2045 (International Diabetes Federation, 2019). Six per cent of deaths at all ages in Indonesia (approximately 100,000) were caused by DM (World Health Organization, 2016). This high mortality rate is associated with DM complications, including Diabetic Foot Ulcer (DFU) (International Diabetes Federation, 2019).
DFUs are multifactorial complications initiated by DM-related complications, specifically Peripheral Vascular Disease (PVD) and neuropathy. Predisposing factors of DFU include both intrinsic factors (e.g., foot deformity) and extrinsic factors (e.g., trauma and bad footcare behavior). Infection is a secondary phenomenon of DFU preceding sepsis, which represents the endstage of DFU and often leads to amputation or death (Boulton, 2019;Forsyth, 2016). DM patients have a 15-25% risk of developing foot ulcers (Yazdanpanah et al., 2018). Lower Extremity Amputation (LEA) occurs every 30 seconds worldwide (International Diabetes Federation, 2019). Additionally, the mortality rate of DFU patients was found to be approximately 40% (Jupiter, Thorud, Buckley, & Shibuya, 2016). This research describes the profile of hospitalized DFU patients at a tertiary care hospital in Surabaya, with specific focus on the characteristics and outcomes of the patients. The results demonstrate how devastating DFU is.

METHODS
This research was a retrospective descriptive study employing the medical records of hospitalized Type 2 DM (T2DM) patients with DFU in Dr. Soetomo General Hospital, Surabaya, Indonesia. A total of 397 samples were included. The samples were patients ≥ 21 years old between 2016-2018. A total sampling technique was employed in this research using available medical records. A diagnosis of T2DM patients with ulcers was defined by ICD-10 code E11.5. Finally, DFU was confirmed by the doctors' handwritten diagnosis in the medical record. Ethical clearance was obtained from the Medical Ethics Committee of Dr. Soetomo General Hospital (1379/KEPK/VIII/2019).
The data collected were as follows: demographic data (age, gender, occupation); anamnesis (duration of DM, history of insulin admission, duration of DFU, history of foot ulceration, previous amputation, precipitating factors of DFU); physical examination (systole, diastole, diagnosis of the diseases, Wagner severity grade of ulcer); therapy records (daily foot ulcer treatment, debridement, necrotomy, underwent amputation); laboratory results (serum creatinine, Random Blood Glucose (RBG), glycated hemoglobin (HbA1C), albumin serum, hemoglobin, leukocytes, C-Reactive Protein (CRP), platelets); radiology findings (previous amputation, Wagner severity grade of ulcer); microorganism culture results; summary (diagnosis of the diseases, causes of death, length of hospital stay). Some data were obtained from more than one source. Data that was obtained from demographic data, anamnesis, physical examination, and laboratory results were collected when the patients were admitted to the hospital. eGFR was calculated by employing the Modification of Diet in Renal Disease (MDRD) formula, which required age, gender, and serum creatinine level. Systole and diastole were used to diagnose hypertension using Joint National Committee (JNC) VII classification.
The characteristics of all patients with medical records were included. Descriptive analysis was presented in the form of narrative, tables, and diagrams. Mean, Standard Deviation (SD), Median, Maximum, and Minimum were statistically employed to analyze the numerical data. If the value of SD was higher than the Mean, the Median with Maximum and Minimum data was utilized for fit data. The characteristics and therapy were also illustrated in the tables based on the Wagner severity grade of ulcers.

RESULTS
This research employed 397 hospitalized T2DM patients with foot ulcers from 2016-2018 (Table 1). The average duration of the patients' hospital stay was 6.75 ± 5.60 days. The prevalence of DFU among T2DM hospitalized patients was 9.08%. In total, 10.58% of patients with apparent foot ulcers during their hospital admission were newly diagnosed with T2DM. Patients who had previous and first-time foot ulcers amounted to 13.85% and 86.15%, respectively, while amputation had previously been performed on 12.59% of the patients. The average patient age was 57.00 ± 9.83 years. There was no significant difference in the number of male patients (47.36%) and female patients (52.64%). Most patients worked as salarymen (35.26%) or were housewives (27.71%).
Ulcers of Wagner grades 4 and 5 (representing gangrene) occurred frequently (41.31%) ( Figure 1). Overall, 40.05% of patients came to the hospital with less than a month's duration of DFU, while only 3.02% had old ulcers that had been present for more than a year.
The main precipitating factors of DFU ( Figure 2) were trauma (12.59%) due to falling from a height, followed by blister (10.33%), and swelling (9.82%). Microorganisms were found in 98 out of 112 patients when microorganism cultures were performed. Thirty-four patients (34.69%) had polymicrobial results. Gramnegative (70.41%) microorganisms were more prevalent than Gram-positive (61.22%) microorganisms. The culture showed various results, with Escherichia coli (20.41%), Enterococcus faecalis (13.27%), Staphylococcus aureus (12.24%), Acinetobacter baumanni (12.24%), Proteus mirabilis (11.22%), Klebsiella pneumoniae (7.14%), Pseudomonas aeruginosa (6.12%), and Streptococcus agalactiae (6.12%) as the main microorganisms that infected DFU patients. Table 2 presents the characteristics of DFU patients based on the Wagner grade of their ulcers. The average age of patients with Wagner grade 2 ulcers was the highest (57.79 ± 8.33 years). The median of both duration of DM and DFU showed no significant difference in number between Wagner grades. The average length of hospital stay was higher in patients with severe ulcers without gangrene. On the other hand, patients with gangrene in their feet had shorter hospital stay durations than patients with Wagner grade 3 ulcers. The lower the Wagner grade of the ulcer, the higher the Mean of RBG. Furthermore, the higher the Wagner grade of the ulcer, the higher the Mean of HbA1c, except for Wagner grade 2. The highest percentage of sepsis (80.49%) and the average leukocyte levels were found in gangrenous feet (22.60 ± 11.95 x 10 9 /L), confirming that the infection was severe in that grade of ulcer. Anemia was also more predominant and severe in the higher Wagner grade of ulcers (Table 2). Table 3 shows that 72.29%, 30.73%, and 17.88% of DFU patients had daily foot ulcer treatment, debridement, and necrotomy, respectively. Those treatments were most frequent in ulcers of Wagner grade 3. A total of 57 patients (14.11%) underwent amputation while hospitalized.  There were 21 major amputations (above and below the knee), 35 minor amputations (digiti site), and one unknown site amputation. Patients with ulcers of Wagner grade 1 received no amputation. A major (above-knee) amputation was performed on a patient with a Wagner grade 2 ulcer that progressed to grade 4. Moreover, only 17.54% of amputations were performed on patients who were admitted to the hospital with a non-gangrenous foot; the remainder (82.36%) were performed on patients with gangrenous feet (Table 3).

DISCUSSION
The prevalence of foot ulcers among T2DM hospitalized patients in the hospital under investigation was 9%; in terms of other tertiary hospitals, this figure was lower in Semarang (4%) (T. G. D. Pemayun & Naibaho, 2017) and higher in Makassar (12%) (Yusuf et al., 2016). Length of hospital stay in our study was 6.75 days on average, which is somewhat shorter than in other studies (T. G. D. Pemayun & Naibaho, 2017;Rigato et al., 2018). Our population was characterized by either early death or discharge from the hospital due to a good prognosis, resulting in relatively short durations of hospitalization. Hospital stay duration could be predicted by the Wagner severity grade of the ulcers, as was determined in a previous study (Tabur et al., 2015). The results in Table 2 indicate that more severe DFU without gangrene resulted in more extended hospital stays. Moreover, and surprisingly, gangrene patients had shorter durations of hospital stay than those with Wagner grade 3 ulcers; however, this was due to severe prognosis leading to early in-hospital mortality.
Our study reported that elderly patients dominated the population, with 71.79% aged between 45-65, while 16.12% were above 65 years old. Moreover, previous research Al- Rubeaan et al (2015) has found that older patients were at higher risk than younger ones for more complications, including DFU, which explains the older study population in our research. The percentage of females (52.64%) was slightly higher than males (47.36%). Only 16.12% of the patients were classified as being in retirement or old age (> 65 years old), with an average age of 57     Anemia and hypoalbuminemia were signs of chronic diseases and malnutrition that could be initiated by DFU (Jeyaraman, Berhane, Hamilton, Chandra, & Falhammar, 2019). The majority of patients had hypoalbuminemia (89.97%), with an average level of 2.63 ± 0.60 mg/dL. Secondly, there is a compensatory response impairment to decreased hemoglobin levels in DM patients; this leads to reduced oxygen delivery to tissues, causing poor healing and infection control (Khanbhai, Loukogeorgakis, Wright, Hurel, & Richards, 2012). Most of the patients in the current study had anemia. Moreover, an increased Wagner grade of ulcers was associated with increased anemia rate and decreased Hb on average. Furthermore, amputees (76.36%) and patients who died (73.81%) were predominantly anemic.
Patients with renal disease who were undergoing dialysis had a higher risk of developing ulcers and of amputation (Al-Rubeaan et al., 2015;Dòria et al., 2016). Furthermore, a correlation was found between serum creatinine and the number of microbiological agents growing in diabetic foot infections (Zubair, Malik, & Ahmad, 2019). Moreover, the majority (62.72%) of our DFU patients' renal function was impaired. Hypertension and macro-vascular disease (i.e., coronary artery disease, cerebrovascular disease, PVD) were risk factors for DFU, reported in 27.20% and 19.40% of our study patients, respectively. Therefore patients with DM-related chronic complications were at risk of foot ulcers because the same mechanism preceded chronic DM complications among most of the patients (Singh, Bali, Singh, & Jaggi, 2014).
Gangrene in the foot and respiratory complications preceded sepsis at rates of 41.31% and 32.24%, respectively, in our research (Chen et al., 2018;Forsyth, 2016). Sepsis developed among patients with both DFU and respiratory disease tended to be worse; thus, 2.24% of patients had a poor prognosis. Diabetic foot sepsis diminished both the blood supply and the delivery of antibiotics to the infected site, thus decreasing the natural healing (Forsyth, 2016).
The median duration of ulcers of Wagner grades 2, 3, and 4-5 among DFU patients with DM was five years; this is the same as the median of DM duration in general, indicating that the severity of the ulcers was not affected. Nevertheless, pre-diabetes patients suffer neuropathy, which is one of the main etiologies of DFU (Dimova et al., 2017). More than half of gangrene patients had DFU for more than four weeks; meanwhile, only 10.36% of gangrene patients had been newly diagnosed with DM. Furthermore, 3.02% of the patients had had ulcers for more than a year. These findings show that foot ulcers that remain untreated in DM patients (who tend to have angiopathy and neuropathy complications) lead to DFU (Boulton, 2019).
Minor trauma was found to be the most common precipitating factor of DFU (12.59%), supporting the findings of T. G. D. Pemayun & Naibaho (2017). It is crucial to immediately seek medical care for DFU, since it can proceed to sepsis and end in amputation or death; this is true even if the appearance of the patient's ulcer is initially mild. A total of 47.86% of patients found the ulcers in their feet spontaneously at home or in hospital (Forsyth, 2016). Some of these patients had risk factors for DFU, such as previous foot ulcers, previous amputation, impairment of sight, and poor social circumstances (Boulton, 2019;Lim, Ng, & Thomas, 2017). Among the 397 DFU patients in this study, nine patients had retinopathy that impaired their sight, 55 had previous ulcers, 50 had previous amputations, 64 were above 65 years of age and nine were retired, which suggested the possibility of being in poor social circumstances. Impaired renal function tends to lead to End-Stage Renal Disease (ESRD) if not treated immediately, while ESRD patients also have a higher risk of developing DFU. Foot deformity in one patient was also a risk factor for ulceration (Boulton, 2019).
Recurrence of ulcers was reported in 13.85% of patients, similar to the study conducted by Bondor et al (2016). Our study determined postamputation to be one of the predisposing factors of ulcer recurrence in 15 patients. Unsolved etiologies of previous healed DFUs were among the reasons for ulcer recurrence, as well as bad patient behavior (Armstrong, Boulton, & Bus, 2017).
The amputation rate among patients in the present study (14%) was comparatively lower than that in other research in Indonesia, which reported 36% (T. G. D. Pemayun & Naibaho, 2017). In addition, the amputation rate was higher in cases of severe DFU (24.82% and 44.44%). Tabur et al (2015) and Ugwu et al (2019) demonstrated that the severity of ulcers based on Wagner classification was useful in predicting amputation. Daily foot ulcer treatment while hospitalized was performed for 72% of patients. The remainder (28%) were either discharged from the hospital due to good prognosis or died before the ulcer could be treated. Good prognosis patients would receive daily foot ulcer treatment after being discharged from the hospital. Finally, the mortality rate of DFU in this population was 40.93%, similar to the findings of the systematic review conducted by Jupiter, Thorud, Buckley, & Shibuya (2016).

CONCLUSION
The prevalence of DFU among T2DM patients in the tertiary care hospital under investigation was relatively high. Most of the patients had poor glycemic control, a high Wagner's grade of ulcer, anemia, sepsis, and renal complications when admitted to the hospital. DFU must never be neglected due to its high mortality rate; early and aggressive treatment is a necessity.

CONFLICT OF INTEREST
The authors declare that no conflict of interest in this study.