Comparison of characteristics and healing course of diabetic foot ulcers by etiological classification: Neuropathic, ischemic, and neuro-ischemic type

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Abstract

Aims

To identify differences in the characteristics of patients with diabetic foot ulcers (DFUs) according to their etiological classification and to compare their healing time.

Methods

Over a 4.5-year period, 73 patients with DFUs were recruited. DFUs were etiologically classified as being of neuropathic, ischemic, or neuro-ischemic origin. Descriptive analyses were performed to characterize study subjects, foot-related factors, and healing outcome and time. Duration of healing was assessed using the Kaplan–Meier method. Healing time among the three types was compared using the log rank test.

Results

The number of patients manifesting neuropathic, ischemic, and neuro-ischemic ulcers was 30, 20, and 14, respectively. Differences were identified for age, diabetes duration, body mass index, hypertension, and estimated glomerular filtration rate. Patients with neuro-ischemic ulcers had better ankle–brachial index, skin perfusion pressure (SPP), and transcutaneous oxygen pressure values compared to those with ischemic ulcers. The average time in which 50% of patients had healed wounds was 70, 113, and 233 days for neuropathic, neuro-ischemic, and ischemic ulcers, respectively. Main factors associated with healing were age and SPP values.

Conclusions

Based on the etiological ulcer type, DFU healing course and several patient factors differed. Failure to consider the differences in DFU etiology may have led to heterogeneity of results in previous studies on DFUs.

Introduction

Diabetic foot ulcers (DFUs) are one of the most serious and disabling complications of diabetes. Prevalence of DFUs among diabetic patients is reported to be between 4% and 10%, with an estimated lifetime incidence of almost 25% (Singh, Armstrong, & Lipsky, 2005). Due to delayed wound healing, DFUs may lead to lower limb amputations, which deteriorate patients’ quality of life and increase morbidity (Nabuurs-Franssen, Huijberts, Nieuwenhuijzen Kruseman, Willems, & Schaper, 2005). DFUs often require prolonged hospital care, and impose a major burden not only on patients, but also on society with considerable medical cost (Prompers, Huijberts, et al., 2008, Stockl et al., 2004). Given these various negative impacts, determination of the factors related to ulcerations and wound healing delay is of major importance.

Previous studies have reported multiple risk factors associated with DFU development (Crawford et al., 2007, Monteiro-Soares et al., 2012). These include, but are not limited to: age, gender, duration of diabetes, body mass index (BMI), co-morbidities including retinopathy and nephropathy, glycated hemoglobin level, macro-vascular complications, foot deformity, edema, and foot self-care habits. However, there is inconsistent evidence regarding the association between these factors and DFUs (Monteiro-Soares et al., 2012). Some studies have demonstrated that younger patients were at higher risk for DFU development than older counterparts (Armstrong et al., 2007), while other studies observed opposite results (Abbott et al., 2002, Monami et al., 2009). Only a few studies have shown an association between BMI and DFUs (Carrington et al., 2002, McNeely et al., 1995, Tentolouris et al., 2009), or between hypertension and DFUs (Guerrero-Romero and Rodriguez-Moran, 1998, Margolis et al., 2008).

To unfold the complexity of DFUs, they can be classified by their underlying etiology — by the presence of peripheral neuropathy, and/or peripheral arterial disease (PAD), i.e., neuropathic, ischemic, and neuro-ischemic type (Caputo et al., 1994, Frykberg et al., 2000, McNeely et al., 1995). Peripheral neuropathy is one form of micro-vascular complications of diabetes, together with nephropathy and retinopathy. On the other hand, PAD is one form of macro-vascular complications and is known to be positively associated with age and other forms of macro-vascular complications, including hypertension and myocardial infarction (Savji et al., 2013). Therefore, there may be differences in patient characteristics when DFUs are grouped using this etiological classification. Previously, Zimny et al. categorized individuals with DFUs into these three ulcer types, and observed discrepancies in diabetes duration, peripheral circulation measurements, and ulcer size in relation to healing (Zimny, Schatz, & Pfohl, 2002). Thus, it is important to compare these three ulcer types and understand the differences in their characteristics and healing process. This may aid development of effective screening and management tools for DFUs. Notably, the study by Zimny et al. was limited by its small sample size and associated factors. Furthermore, to our knowledge no study has compared the healing time of these three ulcer types.

The aim of this study was to identify differences in characteristics of DFU patients according to etiological classification, namely neuropathic, ischemic, and neuro-ischemic ulcer type, and to compare the DFU healing time. The findings of this study may serve as a guide to clinical decision-making in both prevention and management of DFUs.

Section snippets

Patients

Between October 2009 and March 2013, we prospectively recruited a total of 84 type 2 diabetic patients with DFUs, aged between 35 and 87 years (average age 65.2 ± 12.1 years), who were treated in a tertiary hospital in Japan. All patients received standardized treatment. The end-points of follow-up were healing, lower limb amputation, or death, or the end of the study period. We defined DFUs as ulcers located below the ankle that needed more than 14 days to heal, and we defined healing as complete

Results

In this study, there were 39 patients (30 males, 9 females) with neuropathic ulcers, 20 patients (16 males, 4 females) with ischemic ulcers, and 14 patients (11 males, 3 females) with neuro-ischemic ulcers.

Table 1 summarizes the characteristics of patients with DFUs according to ulcer types. Regarding mean patient age, patients with neuropathic ulcers were the youngest, with 10 years’ age difference between neuropathic and neuro-ischemic groups, and 20 years’ difference between neuropathic and

Discussion

This clinical study identified some differences in factors potentially associated with foot ulceration among three types of DFUs classified by their etiology (neuropathic, ischemic, and neuro-ischemic type). There was significant variation between the three groups regarding patient age, duration of diabetes, BMI, and hypertension. Notably, previous studies have neglected to classify DFUs into the etiological ulcer types when investigating these factors, which may have precluded the

Acknowledgments

We thank Deirdre Walshe and Kumail Versi for editing assistance. This study was funded through the National Center for Global Health and Medicine (22-120) and St. Luke’s Life Science Institute.

References (54)

  • J.H. Sun et al.

    Risk factors for lower extremity amputation in diabetic foot disease categorized by Wagner classification

    Diabetes Research and Clinical Practice

    (2012)
  • F.W. Tsai et al.

    Skin perfusion pressure of the foot is a good substitute for toe pressure in the assessment of limb ischemia

    Journal of Vascular Surgery

    (2000)
  • C. Voulgari et al.

    The association between cardiac autonomic neuropathy with metabolic and other factors in subjects with type 1 and type 2 diabetes

    Journal of Diabetes and its Complications

    (2011)
  • S. Zimny et al.

    Determinants and estimation of healing times in diabetic foot ulcers

    Journal of Diabetes and its Complications

    (2002)
  • C.A. Abbott et al.

    The North-West Diabetes Foot Care Study: Incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort

    Diabetic Medicine

    (2002)
  • J. Apelqvist et al.

    Wound classification is more important than site of ulceration in the outcome of diabetic foot ulcers

    Diabetic Medicine

    (1989)
  • D.G. Armstrong et al.

    Choosing a practical screening instrument to identify patients at risk for diabetic foot ulceration

    Archives of Internal Medicine

    (1998)
  • E.J. Boyko et al.

    Prediction of diabetic foot ulcer occurrence using commonly available clinical information: The Seattle Diabetic Foot Study

    Diabetes Care

    (2006)
  • G.M. Caputo et al.

    Assessment and management of foot disease in patients with diabetes

    New England Journal of Medicine

    (1994)
  • A.L. Carrington et al.

    Can motor nerve conduction velocity predict foot problems in diabetic subjects over a 6-year outcome period?

    Diabetes Care

    (2002)
  • F. Crawford et al.

    Predicting foot ulcers in patients with diabetes: A systematic review and meta-analysis

    QJM

    (2007)
  • M.H. Criqui et al.

    Ethnicity and peripheral arterial disease: The San Diego Population Study

    Circulation

    (2005)
  • R.G. Frykberg et al.

    Diabetic foot disorders. A clinical practice guideline. For the American College of Foot and Ankle Surgeons and the American College of Foot and Ankle Orthopedics and Medicine

    The Journal of Foot and Ankle Surgery

    (2000)
  • E. Ghanassia et al.

    Long-term outcome and disability of diabetic patients hospitalized for diabetic foot ulcers: A 6.5-year follow-up study

    Diabetes Care

    (2008)
  • A. Gul et al.

    Role of wound classification in predicting the outcome of diabetic foot ulcer

    The Journal of the Pakistan Medical Association

    (2006)
  • L. Hurley et al.

    A prospective study of risk factors for foot ulceration: The West of Ireland Diabetes Foot Study

    QJM

    (2013)
  • J.H. Ix et al.

    Association of body mass index with peripheral arterial disease in older adults: The Cardiovascular Health Study

    American Journal of Epidemiology

    (2011)
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    Conflict of interest: The authors declare that there are no known conflicts of interest.

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