Cause Of Diabetic Foot Ulcers Research Articles

Network pharmacology-based approach for exploring the biotargets and mechanisms of vitamin A for the treatment of diabetic foot ulcers

Abstract Background In some developing countries, people have little knowledge about the causes of diabetic foot ulcers. Therefore, public health education for patients on these conditions is a prerequisite for effective pharmacological treatment. Diabetic foot ulcers are a complex symptom of diabetes and are hard to cure due to the lack of efficacious medicine and alternative treatment approaches. Vitamin A (VA) is known to have potent biological functions, including skin repair and immunoregulation. However, the potential pharmacological effects and molecular mechanisms of VA on foot ulcers are still to be discovered. Methods By using bioinformatic/computational analyses, including network pharmacology, gene ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we aimed to identify and reveal the pharmacological targets, molecular mechanisms, biological functions, and signaling pathways of VA in the treatment of diabetic foot ulcers. Results A total of 66 intersection genes were identified as candidate targets of VA, which are related to diabetic foot ulcers. Therein, 18 core genes/targets, namely JUN, MAPK1, THRB, MAPK14, MTNR1B, CXCR3, ESR1, AR, HDAC1, IL-10, CNR1, DRD2, EGFR, ADRA2A, CCND1, RXRB, RARA, and RXRA, were further identified. Furthermore, the biological processes, cell components, and molecular functions which may underlie the effects of VA against diabetic foot ulcers were characterized. Conclusion Based on our findings, we concluded that the pharmacological effects of VA on diabetic foot ulcers primarily involve the promotion of cellular regeneration and proliferation and the inhibition of inflammatory response. The core genes/targets may potentially serve as promising biomarkers for the diagnosis of diabetic foot ulcers.

Analysis of patient characteristics and clinical outcome in wound grades of diabetic foot ulcer in Peshawar Khyber Pakhtunkhwa

Introduction: Diabetic foot is utmost severe factor of diabetes which has negative consequences on the sufferance’s life. Among diabetes serious and life threatening complications, diabetic foot ulcer (DFU) is very serious problem. Macro and micro vascular complications, time period of diabetes mellitus and bordering neuropathy govern the chance of foot ulcer. Staphylococcus aureus (a Bacterium) is the main cause of diabetic foot ulcer it has antibiotic resistance genes which makes it resistant to antibiotics. Diabetic fool ulcer is spread by harmful and lytic way on the host cell. Objective: To analyze the patient characteristics and clinical outcome in wound grades of diabetic foot ulcer. Material and Method: First sample is collected from 150 patients suffering from DFU. Bacterial colonies were obtained from culture. Kirby Bauer disc diffusion method was used to check the antibiotic susceptibility. DNA was extracted and PCR was run to amplify Pantone Valentine Leukocidin gene using primers. Results were analyzed through SPSS version. Results: Total patients were 150. More than 50yrs was the mean age. 51.3% were female and on the other hand, 48.7% were male.

LncRNA SNHG16 Knockdown Promotes Diabetic Foot Ulcer Wound Healing via Sponging MiR-31-5p.

Diabetic foot ulcers are caused by nerve abnormalities and vascular lesions in the distal lower limbs of diabetic patients. However, the causes of diabetic foot ulcers are diverse and the treatment process is complex. Therefore, understanding the pathogenesis of diabetic foot ulcers through lncRNA and formulating effective means are the key to the cure of patients. Tissues were collected from 76 diabetic foot ulcer patients and 50 non-diabetic patients undergoing traumatic amputation. Human dermal fibroblasts (HDFs) were induced by high glucose to obtain diabetic foot ulcer cell model. The lncRNA SNHG16 (SNHG16) and miR-31-5p expression in tissues and cells was detected by real-time quantitative reverse transcription PCR (RT-qPCR). Cell Counting Kit-8 (CCK-8) and Transwell assays were used to evaluate the biological behavior of the cells, and the association between SNHG16 and miR-31-5p was explored by luciferase reporting assay. SNHG16 was distinctly expressed in diabetic foot ulcer tissue samples, while miR-31-5p was decreased. In vitro cell function assays confirmed that the proliferation level was inhibited in the constructed diabetic foot ulcer cell model (HG group), as was the migration and invasion ability. After transfection with silencing SNHG16, the biological behavior of the cells was promoted. Mechanistically, SNHG16 sponge miR-31-5p regulated disease progression. Recovery experiments revealed that miR-31-5p inhibitor counteracted the effect of silencing SNHG16 on cell viability. SNHG16 knockdown may regulate the biological function of cells by targeting miR-31-5p to promote wound healing and ameliorate the condition of diabetic foot ulcer patients.

Longitudinal physiological remoulding of lower limb skin as a cause of diabetic foot ulcer: a histopathological examination.

Diabetic foot ulcer (DFU) is recognised as a severe complication in patients with type 2 diabetes. With the increasing incidence of diabetes, it represents a major medical challenge. Several models have been proposed to explain its aetiology; however, they have never been assessed by longitudinal histopathological examination, which this study aims to address. Multiplex-immunofluorescence analysis was carried out with lengthwise serial skin specimens obtained from the medial thigh, lower leg, ankle, dorsum of foot and acrotarsium close to the DFU region of a patient with type 2 diabetes receiving above the knee amputation. Proximal-to-distal gradual loss of peripheral nerve was demonstrated, accompanied by compromised capillaries in the superficial papillary plexus and distended CD31-positive capillaries in the dorsum of foot. Neural fibres and capillaries were also significantly compromised in the sweat gland acinus in the ankle and dorsum of foot. Injuries in the superficial papillary plexus, sweat gland acinus, and sweat gland-associated adipose tissues were accompanied by significant infiltration of macrophages. These results indicated that longitudinal impairment of local blood circulation could be the cause of peripheral neuropathy, which initiated ulcer formation. Resultant chronic inflammation, involving sweat gland-associated adipose tissue, gave rise to impairment of wound healing, and thus DFU formation. Longitudinal histopathological examination demonstrated that impairment of local microvascular circulation (rather than the systemic complication caused by type 2 diabetes) was considered the primary cause of peripheral neuropathy, which initiated ulceration. Together with chronic inflammation in the superficial papillary plexus and sweat gland-associated adipose tissue, it resulted in the development of a DFU. Although this is a study of just one individual's limb, our study provided a unique observation, contributing mechanistic insights into developing novel intervening strategies to prevent and treat DFUs.

Accuracy and Cost-effectiveness of the Diabetic Foot Screen Proforma in Detection of Diabetic Peripheral Neuropathy in Myanmar.

ObjectiveProper foot assessment is important for early detection and treatment of diabetic peripheral neuropathy (DPN), the main cause of diabetic foot ulcers (DFUs). This study aimed to determine the accuracy and cost-effectiveness of the locally developed Diabetic Foot Screen (DFS) proforma in detecting DPN among diabetic patients at 10 selected clinics in Yangon, Myanmar.MethodologyThe study included 625 type 2 diabetics from 10 primary care clinics who participated in the diagnostic accuracy and cost-effectiveness analysis. They were assessed with DFS proforma and biothesiometry by two examiners independently. The cost-effectiveness analysis was conducted based on available data in the local primary care setting.ResultsThe overall accuracy of the DFS proforma assessment was 74.76% (95% CI: 70.46%- 79.06%). The optimal cut-off DFS score was ≥1.5 (sensitivity 62%; specificity 76%) in detecting DPN. Compared to biothesiometry, the cost-effectiveness of DFS proforma assessment in DPN detection was 41.79 USD per DPN case detected.ConclusionThis study supported the use of DFS proforma for DPN detection in primary care clinics. It also provided new information on the estimated costs per patient with DPN detected in Myanmar.

Prevalence of DFU among diabetic patients and its management

: To study the prevalence of DFU among diabetic patients and the management of DFU among diabetic patients.: Prospective observational study. : The study was conducted in inpatients with diabetes of all departments and inpatients with diabetic foot ulcer (DFU) of surgical department of age 20 to 80 of both genders with sample size 150 were included from September 2019 to march 2020. The prevalence of DFU among diabetic patients was 16%. Among them more diabetic cases were seen in age group of 50-59 and DFU in 40-49 and More diabetic cases are observed in male compared to female. DFU observed equally and the most common causative organism for DFU was staphylococcus aureus followed by proteus species, klebsiella and pseudomonas aeruginosa and more cases of DFU were noticed in diabetic patients with duration of 6-10 years. As the main cause of DFU is infection the primary treatment is anti microbial therapy and the most prescribed class of antibiotics is cephalosporins followed by nitroimidazoles, penicillins, oxazolidinones, lincosamides etc. surgical procedures like debridement, amputation and sometimes both were done in 9,14,1 patients respectively. : Our study revealed the information regarding the prevalence of DFU among diabetic patients is due to lack of knowledge and uncontrolled diabetes may develop poor circulation which leads to wound that may heal slowly which leads to DFU.

The Role of Cutaneous Microcirculatory Responses in Tissue Injury, Inflammation and Repair at the Foot in Diabetes.

Diabetic foot syndrome is one of the most costly complications of diabetes. Damage to the soft tissue structure is one of the primary causes of diabetic foot ulcers and most of the current literature focuses on factors such as neuropathy and excessive load. Although the role of blood supply has been reported in the context of macro-circulation, soft tissue damage and its healing in the context of skin microcirculation have not been adequately investigated. Previous research suggested that certain microcirculatory responses protect the skin and their impairment may contribute to increased risk for occlusive and ischemic injuries to the foot. The purpose of this narrative review was to explore and establish the possible link between impairment in skin perfusion and the chain of events that leads to ulceration, considering the interaction with other more established ulceration factors. This review highlights some of the key skin microcirculatory functions in response to various stimuli. The microcirculatory responses observed in the form of altered skin blood flow are divided into three categories based on the type of stimuli including occlusion, pressure and temperature. Studies on the three categories were reviewed including: the microcirculatory response to occlusive ischemia or Post-Occlusive Reactive Hyperaemia (PORH); the microcirculatory response to locally applied pressure such as Pressure-Induced Vasodilation (PIV); and the interplay between microcirculation and skin temperature and the microcirculatory responses to thermal stimuli such as reduced/increased blood flow due to cooling/heating. This review highlights how microcirculatory responses protect the skin and the plantar soft tissues and their plausible dysfunction in people with diabetes. Whilst discussing the link between impairment in skin perfusion as a result of altered microcirculatory response, the review describes the chain of events that leads to ulceration. A thorough understanding of the microcirculatory function and its impaired reactive mechanisms is provided, which allows an understanding of the interaction between functional disturbances of microcirculation and other more established factors for foot ulceration.

Diabetes and peripheral artery disease: A review.

Peripheral arterial disease (PAD) refers to partial or complete occlusion of the peripheral vessels of the upper and lower limbs. It usually occurs as part of systemic atherosclerosis in the coronary and cerebral arteries. The prevalence of PAD is expected to continue to increase in the foreseeable future owing to the rise in the occurrence of its major risk factors. Nonhealing ulcers, limb amputation and physical disability are some of its major complications. Diabetes mellitus (DM) remains a major risk for PAD, with DM patients having more than two-fold increased prevalence of PAD compared with the general population. The clinical presentation in people with DM also differs slightly from that in the general population. In addition, PAD in DM may lead to diabetic foot ulcers (DFUs), which precipitate hyperglycaemic emergencies and result in increased hospital admissions, reduced quality of life, and mortality. Despite the epidemiological and clinical importance of PAD, it remains largely under diagnosed and hence undertreated, possibly because it is largely asymptomatic. Emphasis has been placed on neuropathy as a cause of DFUs, however PAD is equally important. This review examines the epidemiology, pathophysiology and diagnosis of lower limb PAD in people with diabetes and relates these to the general population. It also highlights recent innovations in the management of PAD.

Is Toe Brachial Index a Better Tool than Ankle Brachial Index for Predicting Outcomes in Diabetic Foot Patients?

Introduction: Diabetes accounts for more than 50% of lower extremity amputation, of which 85% of lower limb amputation in diabetic patients are preceded by foot ulcers. The increasing prevalence of ischaemic ulcers has made ischaemia probably the most important cause of Diabetic Foot Ulcers (DFUs) today. Modalities for assessment of vasculopathy include clinical examination of pulses, Ankle Brachial Pressure Index (ABI), Toe Brachial Pressure Index (TBI), Transcutaneous partial pressure of Oxygen (TCpO2), Duplex imaging, Magnetic Resonance (MR) and Computed Tomography Angiography (CTA). Aim: This study was aimed at evaluation of ABI and TBI in assessment of vasculopathy in DFUs and their association with the various surgical outcomes. Materials and Methods: This study was done as a cross-sectional study on 100 patients with diabetic foot, from December 2016 to April 2018, with prospective follow-up till the outcome of “ulcer healed”, “minor/major amputation” with healing of the amputation stump, was achieved. The multimodality approach for treatment of DFU was taken. Variables like age, gender, duration of present ulcer, previous history of ulcers and interventions, comorbidities, history of smoking and duration of diabetes were recorded and assessed. The examination included examination of peripheral pulses, presence of neuropathy, measurement of ABI and TBI. Investigations included HbA1c levels, swab or pus cultures from the ulcers, objective evaluation of Peripheral Arterial Disease (PAD) by Duplex Ultrasonography and CT Angiography where an intervention was contemplated. The data was entered in MS Excel spreadsheet and analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. Results: The mean age was 62.55±9.21 years, with maximum patients belonging to the age group 61-70 years (38%) followed by 51-60 years age group (33%). Smoking as a risk factor was present in 59% of all the patients. A total of 53 patients underwent amputation among which 28 were smokers (52.8%). Neuropathy was present in 47.22% (n=51), with 60.87% of all patients with neuropathy undergoing amputation which was significant (p-value=0.005). When defined by ABI alone (ABI <0.9), 46.3% patients had PAD, however, using TBI <0.7 for defining PAD, incidence of PAD increased to 68.31% patients. Thus identifying 21 more patients with PAD as compared to ABI. Poor glycaemic control was significantly associated with poor outcome in the form of amputation (p<0.001). Patients who underwent major amputation had a mean ABI of 0.54±0.22, for minor amputation the mean ABI was 0.85±0.19 and for those who had healed ulcers, had a mean ABI of 0.61±0.27. The cut-off value for ABI to predict amputation was >0.51 with a sensitivity of 77.14 and a specificity of 56.1, which was not found to be significant (p-value=0.0796). The mean TBI for the diabetic feet was 0.25±0.12 for major amputation, 0.42±0.26 for minor amputation and 0.61±0.19 for ulcer healed. With a cut-off value of ≤0.3, the sensitivity and specificity for predicting amputation were 68.75 and 88.68 respectively which was found to be significant (p<0.001). Conclusion: The ABI has been found to under-report ischemia as compared to TBI in diabetic patients. TBI also correlates better with the outcome of a DFU. Thus, making TBI a part of assessment of vasculopathy in DFU patients who have not undergone toe amputations, would help in correctly identifying ischemia and early institution of possible intervention in such patients.

Measuring Plantar Tissue Stress in People With Diabetic Peripheral Neuropathy: A Critical Concept in Diabetic Foot Management.

Excessive stress on plantar tissue over time is one of the leading causes of diabetic foot ulcers among people with diabetic peripheral neuropathy. Plantar tissue stress (PTS) is a concept that attempts to integrate several well-known mechanical factors into one measure, including plantar pressure, shear stress, daily weight-bearing activity, and time spent in prescribed offloading interventions (adherence). Despite international diabetic foot guidelines recommending the measure of each of these individual mechanical factors in people with neuropathy, only recently has technology enabled their combined measurement to determine PTS. In this article we review the concept of PTS, the mechanical factors involved, and the findings of pivotal articles reporting measures of PTS in people with neuropathy. We also discuss key existing gaps in this field, including the lack of standards to measure and report PTS, a lack of practical solutions to measure shear stress, and the lack of PTS thresholds that may indicate benefit or detriment to people with neuropathy. To address some of these gaps, we propose recommended clinical and research standards for measuring and reporting PTS in people with neuropathy. Last, we forecast future clinical, research, and technological advancements that may use PTS to highlight the importance of this critical concept in the prevention and management of diabetic foot ulcers.

Hubungan Profil Lipid dengan Kejadian Ulkus Kaki Diabetik pada Pasien Diabetes Melitus Tipe 2 RSUP dr. Mohammad Hoesin Palembang

Diabetic foot ulcersare long-term complications of diabetes mellitus that may increase morbidity and mortality, also reduce the quality of life of the patients. One of the causes of diabetic foot ulcers is peripheral arterial disease due to dyslipidemia. This study was conducted to determine the relationships of lipid profile with diabetic foot ulcers in patients with type 2 diabetes mellitus. Analytical observational study with cross-sectional design was conducted in 69 diabetic patients. Data was retrieved secondarily by observing the medical records. Total cholesterol, triglycerides, LDL, HDL, and consumption of lipid-lowering drugs of the patients were all recorded. Documented variables were analyzed using Fisher Exact test if Chi-square test criterias were not fulfilled. There was a significant association between diabetic foot ulcers with total cholesterol (p=0,001) and HDL (p=0,015), while triglycerides (p=0,393) and LDL (p=0,176) did not have a significant association with diabetic foot ulcers.Multivariable logistic regression identified HDL (B=2,221, S.E.=1,131, Wald=3,855, p=0,050, exp(B)=9,220 IK95% 1,004–84,691)as the most influential lipid profile fraction to the incident diabetic foot ulcers. Total cholesterol and HDL had a significant association with diabetic foot ulcers. The most influential lipid profile fraction to the incident diabetic foot ulcers is HDL.

Toe ulcers and early diagnosis of osteomyelitis in diabetic patients

Category: Diabetes Introduction/Purpose: Neuropathy and Peripheral arterial disease are the main causes of diabetic foot ulcers. Toes are the most frequent location. Osteomyelitis diagnosis of foot ulcers is still controversial, mainly in ulcers without bone exposure. Although MRI has 90% sensitivity and 85% specificity for osteomyelitis diagnosis, it is not usually used for early detection of bone changes, due to lack of availability and high cost. Bone biopsy puncture is considered the gold standard methodology together with microbiological and histological examinations, but it is not always available in all practices. The purpose of this study was to describe the diagnosis in forefoot ulcers found in diabetic patients using MRI and bone biopsy puncture. Methods: This is a retrospective study, a case series. Clinical records of patients with injuries limited to toes between January 2013 and December 2015 were analyzed. The inclusion criteria were: patients with Diabetes Mellitus (DM) diagnosis and with a grade 1 or 2 digital ulcer according to Wagner’s classification for at least 3 weeks, with visible bone edema in the magnetic resonance (MRI) and those with a bone biopsy performed, and with a minimum follow–up of a year. Patients with diabetic foot ulcers were evaluated by an interdisciplinary team. Laboratory standards were evaluated preoperative and during antibiotic therapy. The surgical bone biopsy was performed by a foot and ankle surgeon with experience in Diabetic foot pathologies. Microbiological and histological study was analyzed. We also recorded the demographic data and identified the patients who had received previous empiric antibiotic therapy. Statistical analysis was performed. Results: Thirty patients out of 93 patients fulfilled inclusion criteria between January 2013 and December 2015. Eleven patients had grade 1 ulcers and 19 grade 2. Twenty-two patients (73.3%) got bone biopsies with positive cultures and 14 (63,3%) had a positive pathological anatomy. Eight patients got negative cultures and pathology. Six patients that did not received empiric antibiotic therapy and 19 patients out of 24 who had received empiric antibiotics had positive cultures. Mean healing time for patients who did not had antibiotics was 4 weeks (3-12) and for the group who received empiric antibiotics was 6 weeks (4-10/) Only 4 patients out of 19 patients with Wagner II ulcers had the toe amputated. Conclusion: A precise diagnosis of the germ was obtained in 73.3% of the patients and a specific antibiotic treatment was completed. Although empiric antibiotic therapy 19 out of 24 patients had positive bone cultures and healing time was longer. Amputation index was 13%, all of them were grade 2 ulcers. There were no major amputations. We consider that in these kind of ulcers that had more than 3 weeks without healing and had no radiographic changes, MRI can show bone edema. Surgical bone biopsy should be done to begin specific antibiotic therapy and improve healing time.

Peripheral Neuropathy and Vasculopathy; Frequency and Associated Risk Factors in Newly Diagnosed Treatment Naive Type 2 Diabetes

Background: The prevalence of diabetes in Pakistan is 11.45%. The reported prevalence of diabetic foot ulceration in Pakistan is between 4% and 10%, with the amputation rate of 8% - 21%. Peripheral neuropathy and vasculopathy are main underlying cause of diabetic foot ulcers. Methodology: It was a cross-sectional non-interventional cohort study where all newly diagnosed treatment naïve type 2 diabetic patients were enrolled. Peripheral neuropathy and vasculopathy were detected by Michigan neuropathy screening instrument (MNSI) and ankle brachial index (ABI) respectively. Risk factors for peripheral neuropathy and vasculopathy were determined by univariate and multivariate logistic regression analysis. Statistical significance was considered with P value of ïve patients of type 2 DM. Age, duration of symptoms prior to diagnosis, metabolic parameters like raised HbA1C, hyperlipidemia and spot random albumin creatinine ratio are found to be risk factors for both peripheral neuropathy and vasculopathy.

The external force associated with callus formation under the first metatarsal head is reduced by wearing rocker sole shoes.

Callus is one of the main causes of diabetic foot ulcers. Therefore, preventing callus formation is very important. In a previous study, it was clarified that callus formation under the first metatarsal head (MTH) is associated with high shear stress time integral/pressure time integral (SPR-i). another study, it was clarified that rocker sole shoes are effective in reducing peak pressure under the first MTH. Therefore, we hypothesized that rocker sole shoes reduce SPR-i under the first MTH. This study aimed to clarify the effect of rocker sole shoes for external forces and leg motions in comparison with that of the normal sole shoes. In-shoe external forces and leg motions were measured during walking wearing the normal sole shoes or the rocker sole shoes in healthy participants. As the external forces, the peak plantar pressure (PP), pressure time integral (PI), peak shear stress (PSS), and shear stress integral (SSI) of each gait cycle were calculated. Additionally, shear stress-pressure ratios (SPR) were calculated by dividing shear stress by pressure; concretely, peak values (SPR-p) and time integral values (SPR-i). As the leg motion, hip and knee joint motions were analyzed for the axis of flexion- extension. Three axes of ankle joint motion (inversion-eversion, plantar flexion-dorsiflexion, and adduction-abduction) were analyzed. Six participants attended, and twelve feet were analyzed. When wearing the rocker sole shoes, the SPR-i under the first MTH was significantly smaller than when wearing the normal sole shoes. The SPR-i higher than 0.60 is associated with callus formation under the first MTH. In three of five feet with callus, SPR-i exceeded 0.60 in the normal sole shoes. The SPR-i of all three feet became smaller than 0.60 when wearing the rocker sole shoes. Although the knee (flexion-extension) and ankle (plantar flexion-dorsiflexion) joint motion became smaller when wearing the rocker sole shoes, there was no significant difference in walking speed. It is considered that propulsion was maintained by the push-off support provided by rocker sole shoes. It was suggested that rocker sole shoes are effective preventing callus formation under the first MTH.

ASSESSMENT OF PREVALENCE AND RISK FACTORS OF PERIPHERAL ARTERIAL DISEASE IN DIABETIC FOOT ULCER

INTRODUCTION: Diabetic foot ulcer(DFU) is very common yet challenging complication of diabetes worldwide. These ulcers are biologically compromised majorly by ischemia and neuropathy. Ischemia has gained recognition as a significant cause of DFU. The association of peripheral arterial disease(PAD) largely impacts the treatment outcomes of DFU in terms of ulcer healing, lower limb amputations and mortality. The burden of PAD in DFU in South Indian population has not been assessed adequately in the recent years. A multidisciplinary approach to DFU and prompt diagnosis of ischemia will decrease the loss of limb and life. OBJECTIVE: The objective of the study was to assess the peripheral arterial disease and associated risk factors in patients with diabetic foot ulcer. METHODS: A total of 100 patients were evaluated in this study. The patients were subjected to detailed history and clinical examination which included distal pulse assessment, ankle-brachial index(ABI) and duplex scan to evaluate PAD. The data was subjected to statistical analysis to find out association between parameters of interest. RESULTS: The prevalence of PAD in DFU was found to be 36%. It was more prevalent in males and in age>40 years and higher with increasing age. PAD was associated almost equally with plantar and dorsal ulcers, more often whole of foot was involved. There is significant association of PAD with longer diabetic duration(p

Identification, antifungal resistance profile, in vitro biofilm formation and ultrastructural characteristics of Candida species isolated from diabetic foot patients in Northern India

Purpose: Diabetic foot ulcers are a serious cause of diagnostic and therapeutic concern. The following study was undertaken to determine the fungal causes of diabetic foot ulcers, with their phenotypic and genotypic characterisation. Materials and Methods: A total of 155 diabetic foot ulcers were studied for 1 year. Deep tissue specimen was collected from the wounds, and crushed samples were plated on Sabouraud dextrose agar with chloramphenicol (0.05 g). Identification was done by growth on cornmeal agar, germ tube formation and urease test. For molecular identification, conserved portion of the 18S rDNA region, the adjacent internal transcribed spacer 1 (ITS1) and a portion of the 28S rDNA region were amplified, using the ITS1 and ITS2 primers. Antifungal susceptibility against voriconazole, fluconazole and amphotericin B was determined by standard broth microdilution method. Biofilm formation was studied in three steps. First, on the surface of wells of microtiter plates followed by quantification of growth by fungal metabolism measurement. Finally, biofilms were analysed by scanning electron microscopy (SEM). Results: Fungal aetiology was found in 75 patients (48.38%). All were identified as Candida species (100%). The prevalence of different species was Candida tropicalis (34.6%), Candida albicans (29.3%), Candida krusei (16.0%), Candida parapsilosis (10.6%), Candida glabrata (9.33%). All were susceptible to amphotericin B (100%). On microtiter plate, all the isolates were viable within 48 h showing biofilms. The metabolic activity of cells in the biofilm increased with cellular mass, especially in the first 24 h. On SEM, majority showed budding yeast form. Conclusion: Non-albicans Candida spp. with potential biofilm forming ability are emerging as a predominant cause of diabetic foot ulcers.

Recognizing the Prevalence of Changing Adult Foot Size

Ill-fitting shoes may precipitate up to half of all diabetes-related amputations and are often cited as a leading cause of diabetic foot ulcers (DFU), with those patients being 5 to 10 times more likely to present wearing improperly fitting shoes. Among patients with prior DFU, those who self-select their shoe wear are at a three-fold risk for reulceration at 3 years versus those patients wearing prescribed shoes. Properly designed and fitted shoes should then address much of this problem, but evidence supporting the benefit of therapeutic shoe programs is inconclusive. The current study, performed in a male veteran population, is the first such effort to examine the prevalence and extent of change in foot length affecting individuals following skeletal maturity. Nearly half of all participants in our study experienced a ≥1 shoe size change in foot length during adulthood. We suggest that these often unrecognized changes may explain the broad use of improperly sized shoe wear, and its associated sequelae such as DFU and amputation. Regular clinical assessment of shoe fit in at-risk populations is therefore also strongly recommended as part of a comprehensive amputation prevention program.

Robert Tattersall, Diabetes: The Biography, Biographies of Disease Series (Oxford: Oxford University Press, 2009), pp. 223, £12.99/$24.95, hardback, ISBN: 978-0-19-954136-2.

Although diabetes is a disease marked mostly by excess—elevated blood glucose, superabundant calories, increasing prevalence in sedentary societies—the historical literature about diabetes is notably lean. Most welcome, then, is the addition of Robert Tattersall’s Diabetes: The Biography, which does a great job of compiling a formidable amount of information, clearly organised in mostly chronological order and written in an engaging manner, within the span of 200 pages. And unlike the few other historical books on diabetes, which tend to focus on one particular episode in the overall story line with the remainder sketched in only briefly, here attention is divided equally across the various plots and themes that make the history of diabetes so redolent of the modern medical enterprise. The book is perhaps best appreciated as a blended biography of diabetes-the-disease and of the diabetologist-author, wherein the perspectives of past physicians and scientists are merged, sometimes in the compass of a single sentence, with the perspective of an adroit present day doctor who has devoted his career to the study of aspects of the disease and to the care of persons afflicted by it. The result is a narrative that is likely quite congenial to both thoughtful physicians who seek to historicise their clinical practice, and inquisitive patients who seek to augment their lived experience, searching for the origins of contemporary concepts and practices, and to deepen their understanding of the predicaments created by human disease and medical care. In Tattersall’s account, particulars dominate: the book is crammed full of historical figures—mostly consisting of physicians and scientists, but also including occasional patients and fleeting mention of diabetes specialist nurses—and what they discovered or did. The result is a diabeto-copia of facts about the journey of discovery and diabetes disease transformation from initial descriptions in antiquity and the dietary treatments of the eighteenth and nineteenth centuries, across the drastic changes wrought by the introduction of insulin into clinical practice in the 1920s, through the era of reckoning with late onset diabetes complications, and into the present day with diabetes perceived as a looming epidemic. One learns, for instance, that a serendipitous observation in 1942 of patients with typhoid who were treated with a sulfa-based antimicrobial drug and suffered fits of hypoglycemia led to the development of oral drugs for Type II diabetes. And that a young girl whose life was saved first from diabetic ketoacidosis (DKA) by insulin and soon thereafter by an iron lung breathing machine, which supported her through a period of respiratory failure due to a mysterious muscle weakness that so often was the cause of death following apparent recovery from DKA, was the first to be diagnosed with DKA associated hypokalemia and successfully treated with a dose of potassium. And even, spanning decades, how knowledge of diabetic nerve damage resulting in feet that could no longer feel pain was only gradually attributed as a primary cause of diabetic foot ulcers—and done so by a physician who took care of patients with leprosy, and who had come to understand that the ‘problem is really one of mechanics not medicine’ (p. 120). While no particular historical argument or approach dominates the book, other than a broad sense of progress, Tattersall does put forward the notion of that diabetes care currently is aptly characterised as the ‘pharmaceutical era, because after 1980 treatment of diabetes came to be dominated by increasingly powerful drug companies’(p. 159) and he speaks against the clinical practices that dominated the diabetes landscape of the 1970s, when ‘patients’ views were not solicited, and the idea that they might have any input in designing their regimen was unthinkable’(p. 197). In a survey such as is offered in this book, though, which is not so much ‘the’ biography as ‘a’ biography, these and many other possible arguments and insights remain for future students of this protean disease to develop to full fruition.

Comment on: Kalra B, Kalra S, Chatley G, Singh H (2006) Rat bite as a cause of diabetic foot ulcer—a series of eight cases. Diabetologia 49:1452–1453

To the Editor: We read with interest the report by Kalra et al. describing rat bites in rural patients presenting to their hospital in India [1]. Although we welcome their highlighting the role of rat bites as an important cause of diabetic foot ulcers in less developed countries, and their addition to the sparse body of literature on the subject, we have some concerns regarding their report. First, the authors did not carry out a relevant, comprehensive literature search—an indispensable prerequisite for writing on any topic. Indeed, a thorough review of the literature would have identified our series of 34 diabetic patients in Tanzania, who developed foot ulcers through rat bites [2]. Our paper was published in 2005 and remains the largest published series to date. In addition, there have been two previous reports from India and one from the West Indies in which rat bites were recognised as the underlying precipitators of diabetic foot ulcers [3–5]. In all these reports, high rat populations, poor housing, and crowding were identified as the major underlying risk factors for rat bite injuries among diabetic patients. However, none of these reports, including our series, were cited by Kalra et al. The 34 patients in our series all had peripheral neuropathy and, similar to the eight patients described by Kalra et al., peripheral vascular disease was not an underlying risk factor. In addition, patients in our series had rat bite-associated foot ulcers of varying degrees of severity, which dictated how they were managed. For example, for rat bite ulcers that were complicated by localised infection, we prescribed oral flucloxacillin, ampicillin and metronidazole; patients with severely infected ulcers or who had progressed to systemic infection required intravenous therapy with third-generation cephalosporins and adjunct surgery. In fact, adjunct amputation was required for 17 of our patients, four of them major and 13 minor. Thus, the statement by Kalra et al. that ‘treatment is fairly simple and does not require third-generation antibiotics’ is misleading and ignores the fact that affected patients could easily develop progressive infection. Four of the patients in our series died from overwhelming sepsis after developing synergistic gangrene of the affected limb [6]; all four had been treated with intravenous antimicrobials and undergone surgical debridement and amputation. We found that diabetic patients who delayed seeking medical attention after recognising a rat bite injury to the foot were significantly more likely to develop gangrene than those who did not delay. In fact, all four deaths described above were of patients who had delayed seeking medical attention for more than 1 week after recognising the injury. Of note, we found that patients with cataracts were more likely to delay seeing a doctor than patients without cataracts—a reflection of the fact that patients with reduced visual acuity and severe peripheral neuropathy are less likely to be aware that they have sustained a rat bite injury. We do not agree with Kalra et al. that rat bites are especially restricted to patients from rural areas. The Diabetologia (2006) 49:2811–2812 DOI 10.1007/s00125-006-0424-z

Rat bite as a cause of diabetic foot ulcer—a series of eight cases

Rat bite as a cause of diabetic foot ulcer—a series of eight cases