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1.  Sudeck's disease stage 1, or diabetic Charcot's foot stage 0? Case report and assessment of the diagnostic value of MRI 
Background
The diagnosis of Sudeck's syndrome stage 1 (nowadays termed complex regional pain syndrome I, abbreviated CRPS I) is based on clinical features, namely swelling and pain in a limb. Plain X-ray may be normal. In the absence of pain sensitivity, e.g. in diabetic neuropathy, CRPS I of the foot can be mistaken for Charcot's foot stage 0 (so-called neuro-osteoarthropathy).
Case presentation
The case of a type-1 diabetic woman is reported, in whom CRPS I following a calcaneal fracture was mistaken for Charcot's osteoarthropathy (because of bone marrow edema displayed by conventional MR imaging). In addition, a review is presented on 6 consecutive cases with CRPS I of the foot, and on 20 cases with Charcot's foot stage 0, with particular emphasis on MR imaging findings. The number of bones per foot affected with marrow edema was similar in either condition, with a tendency towards a more patchy, diffuse distribution of bone marrow edema in CRPS I. Bone marrow edema apparently regressed more promptly in response to treatment in Charcot's foot stage 0.
Conclusion
Differentiation of CRPS I from Charcot's foot stage 0 remains a diagnostic dilemma in patients with pain insensitivity. Conventional MRI may be helpful, when repeated for monitoring the treatment response.
doi:10.1186/1758-5996-2-60
PMCID: PMC2958966  PMID: 20923545
2.  Etiology, pathophysiology and classifications of the diabetic Charcot foot 
Diabetic Foot & Ankle  2013;4:10.3402/dfa.v4i0.20872.
In people with diabetes mellitus, the Charcot foot is a specific manifestation of peripheral neuropathy that may involve autonomic neuropathy with high blood flow to the foot, leading to increased bone resorption. It may also involve peripheral somatic polyneuropathy with loss of protective sensation and high risk of unrecognized acute or chronic minor trauma. In both cases, there is excess local inflammatory response to foot injury, resulting in local osteoporosis. In the Charcot foot, the acute and chronic phases have been described. The former is characterized by local erythema, edema, and marked temperature elevation, while pain is not a prominent symptom. In the latter, signs of inflammation gradually recede and deformities may develop, increasing the risk of foot ulceration. The most common anatomical classification describes five patterns, according to the localization of bone and joint pathology. This review article aims to provide a brief overview of the diabetic Charcot foot in terms of etiology, pathophysiology, and classification.
doi:10.3402/dfa.v4i0.20872
PMCID: PMC3661901  PMID: 23705058
Charcot foot; classification; diabetes mellitus; diabetic foot; neuropathy; osteoarthropathy
3.  Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma 
Diabetic Foot & Ankle  2014;5:10.3402/dfa.v5.24926.
Introduction and objective
Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy).
Design and methods
A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture). Cases were 12 patients (11 diabetic subjects) with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT) and deep pressure pain perception threshold (DPPPT) were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®).
Results
In the control group, post-traumatic DPPPT (but not CPPPT) at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal) versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group); CPPPT did not decrease post-operatively.
Conclusion
Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic) neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking.
doi:10.3402/dfa.v5.24926
PMCID: PMC4224703  PMID: 25397867
quantitative sensory testing; allodynia; neuropathy; neuropathic ulcer; neuropathic arthropathy; nociception
4.  Midfoot and hindfoot arthrodeses in diabetic Charcot arthropathy 
Canadian Journal of Surgery  2000;43(6):449-455.
Objectives
To review the clinical outcome of arthrodesis of the foot in patients with diabetic Charcot arthropathy and to review the pathophysiology, clinical and radiographic features of Charcot arthropathy.
Design
A retrospective review and clinical follow-up of a series of patients.
Setting
St. Michael’s Hospital, Toronto, a tertiary care teaching hospital.
Patients
Ten diabetic patients treated between 1996 and 1998 who required an arthrodesis of the midfoot or hindfoot secondary to deformity of diabetic neuropathic joints.
Interventions
Three midfoot (Lisfranc) and 7 hindfoot arthrodeses with autogenous iliac-crest bone grafting and internal fixation.
Outcome measures
Patient satisfaction, maintenance of the correction of the deformity and avoidance of amputation. Western Ontario/McMaster University score and midfoot/hindfoot American Orthopaedic Foot and Ankle Society foot ratios. Clinical examination including E-MED pedographic examination. Correction and evidence of bony or fibrous union assessed radiologically.
Results
The postoperative correction was maintained, no further skin ulceration occurred and amputation was avoided in 9 of 10 patients. Because this is a salvage procedure and there was often significant concomitant illness, the results of clinical rating systems were poor. Five of 9 patients had clinical and radiographic evidence of a solid bony arthrodesis; 4 had a stable fibrous union.
Conclusions
With careful surgical technique, a reasonable number of feet can be salvaged by an arthrodesis of a diabetic neuropathic joint when nonoperative measures fail. Patient selection is important because there is a significant complication rate.
PMCID: PMC3695201  PMID: 11129834
5.  Osteomyelitis or Charcot neuro-osteoarthropathy? Differentiating these disorders in diabetic patients with a foot problem 
Diabetic Foot & Ankle  2013;4:10.3402/dfa.v4i0.21855.
Both osteomyelitis and Charcot neuro-osteoarthropathy (CN) are potentially limb-threatening complications of diabetic neuropathy, but they require quite different treatments. Almost all bone infections in the diabetic foot originate from an infected foot ulcer while diabetic osteoarthropathy is a non-infectious process in which peripheral neuropathy plays the critical role. Differentiating between diabetic foot osteomyelitis and CN requires careful evaluation of the patient, including the medical history, physical examination, selected laboratory findings, and imaging studies. Based on available studies, we review the approaches to the diagnostic differentiation of osteomyelitis from CN of the foot in diabetic patients.
doi:10.3402/dfa.v4i0.21855
PMCID: PMC3819473  PMID: 24205433
diabetic foot; osteomyelitis; Charcot neuro-osteoarthropathy
6.  Comparative analysis of uniplanar external fixator and retrograde intramedullary nailing for ankle arthrodesis in diabetic Charcot's neuroarthropathy 
Indian Journal of Orthopaedics  2011;45(4):359-364.
Background:
Charcot's neuroarthropathy of ankle leads to instability, destruction of the joint with significant morbidity that may require an amputation. Aim of surgical treatment is to achieve painless stable plantigrade foot through arthrodesis. Achieving surgical arthrodesis in Charcot's neuroarthropathy has a high failure rate. This is a retrospective nonrandomized comparative study assessing the outcomes of tibio-talar arthrodesis for Charcot's neuroarthropathy treated by uniplanar external fixation assisted by external immobilization or retrograde intramedullary interlocked nailing.
Materials and Methods:
Records of the authors′ institution were reviewed to identify those patients who had undergone ankle fusion for diabetic neuroarthropathy from January 1998 to December 2008. A total of11 patients (six males and five females) with a mean age of 56 year and diabetes of a mean duration of 15.4 years with ankle tibio-talar arthrodesis using retrograde nailing or external fixator for Charcot's neuroarthropathy were enrolled for the analysis. Neuropathy was clinically diagnosed, documented and substantiated using the monofilament test. All procedures were performed in Eichenholz stage II/III.Six patients were treated with uniplanar external fixator, while the remaining five underwent retrograde intramedullary interlocking nail. The outcomes were measured for union radiologically, development of complications and clinical follow-up, according to digital archiving systems and old case notes.
Results:
All five (100%) patients treated by intramedullary nailing achieved radiological union on an average follow-up of 16 weeks. The external fixation group had significantly higher rate of complications with one amputation, four non unions (66.7%) and a delayed union which went on to full osseous union.
Conclusion:
The retrograde intramedullary nailing for tibio-talar arthrodesis in Charcot's neuroarthropathy yielded significantly better outcomes as compared to the use of uniplanar external fixator.
doi:10.4103/0019-5413.82343
PMCID: PMC3134023  PMID: 21772631
Charcot's diabetic neuropathy; retrograde intramedullary nailing; tibio-talar arthrodesis; uniplanar external fixator
7.  The foot-health of people with diabetes in a regional Australian population: a prospective clinical audit 
Background
There is limited understanding of the foot-health of people with diabetes in Australian regional areas. The aim of this study was to document the foot-health of people with diabetes who attend publically funded podiatric services in a regional Australian population.
Methods
A three month prospective clinical audit was undertaken by the publically-funded podiatric services of a large regional area of Victoria, Australia. The primary variables of interest were the University of Texas (UT) diabetic foot risk classification of each patient and the incidence of new foot ulceration during the study period. Age, gender, diabetes type, duration of diabetes and the podiatric service the patients attended were the other variables of interest.
Results
Five hundred and seventy six patients were seen during the three month period. Over 49% had a UT risk classification at a level at least peripheral neuropathy or more serious diabetes-related foot morbidity. Higher risk at baseline was associated with longer duration of diabetes (F = 31.7, p < 0.001), male gender (χ2 = 40.3, p <0.001) and type 1 diabetes (χ2 = 37.3, p <0.001). A prior history of foot pathology was the overwhelming predictor for incident ulceration during the time period (OR 8.1 (95% CI 3.6 to 18.2), p < 0.001).
Conclusions
The publically funded podiatric services of this large regional area of Australia deal with a disproportionally large number of people with diabetes at high risk of future diabetes-related foot complications. These findings may be useful in ensuring appropriate allocation of resources for future public health services involved in diabetic foot health service delivery in regional areas.
doi:10.1186/1757-1146-5-6
PMCID: PMC3353842  PMID: 22400802
Podiatry; Diabetic Foot; Epidemiology; Rural Health
8.  An overview of the Charcot foot pathophysiology 
Diabetic Foot & Ankle  2013;4:10.3402/dfa.v4i0.21117.
Charcot arthropathy of the foot is a rare but devastating complication of diabetes that remains to be a challenging issue for the foot and ankle surgeons. Charcot foot fails to be an obvious diagnostic option that comes to mind, even in a pathognomonic clinical appearance. The rarity of the disorder, more common pathologies that mimic the condition, and the self-limiting prognosis deviate the clinician from the right diagnosis. The clinical challenges in the diagnosis of Charcot foot require in-depth investigations of its enigmatic nature to establish useful guidelines. Yet, this goal seems to be beyond reach, without a holistic view of the immense literature concerning the pathophysiology of the disorder. The primary objective of this article is to put together and review the recent advancements about the etiology and intrinsic mechanisms of diabetic Charcot foot.
doi:10.3402/dfa.v4i0.21117
PMCID: PMC3733015  PMID: 23919113
Charcot foot; pathophysiology; diabetes mellitus; neuropathy; neuropeptides
9.  High levels of anxiety and depression in diabetic patients with Charcot foot 
Background/aims
Charcot foot is a rare but devastating complication of diabetes. Little research is available on the mental health impact of Charcot foot. Aim of the study is to assess mental health in diabetes patients with Charcot foot and to investigate the moderating effects of socio-demographic factors. The severity of the problem will be statistically evaluated with the help of a reference data set.
Methods
Cross-sectional questionnaire data using the Hospital Anxiety and Depression Scale (HADS) and demographic background were collected from 50 patients with diabetes and Charcot complications (males 62%; mean age 62.2 ± 8.5 years). Statistical comparisons with a large data set of general diabetes patients acting as a point of reference were carried out.
Results
Anxiety and depression levels were high, (anxiety and depression scores 6.4 ± 4 and 6.3 ± 3.6 respectively). Females reported more severe anxiety and depression. Ethnic minorities and patients out of work reported more severe anxiety. Comparisons with published HADS data indicate that diabetes patients with Charcot foot experience more serious levels of anxiety and depression.
Conclusions
The high levels of mental health problems which were found in this study in diabetes patients with Charcot foot require recognition by researchers and clinicians. The findings imply the need to screen for mental health problems in diabetes patients with Charcot foot.
doi:10.1186/1757-1146-7-22
PMCID: PMC3999891  PMID: 24650435
Charcot foot; Diabetic foot; Diabetes; Depression; Anxiety
10.  The role of an extended medial column arthrodesis for Charcot midfoot neuroarthropathy 
Diabetic Foot & Ankle  2010;1:10.3402/dfa.v1i0.5282.
The etiology of diabetic Charcot neuroarthropathy involving the midfoot often includes an inciting traumatic event or repetitive micro-trauma from an uncompensated biomechanical imbalance that potentiates an incompletely understood pathway leading to a rocker-bottom foot deformity and ulceration. In the setting of a severe Charcot foot fracture and/or dislocation with obvious osseous instability, diagnostic delay can potentiate the limb-threatening sequelae of infected midfoot ulcerations in this patient population. In this article, the authors discuss the thought process as well as the advantages of performing an extended medial column arthrodesis for selected Charcot midfoot deformities.
doi:10.3402/dfa.v1i0.5282
PMCID: PMC3284288  PMID: 22396811
diabetes mellitus; Charcot foot; midfoot arthrodesis; locking plate technology; external fixation
11.  Evaluation of foot problems among diabetics in rural population 
The Indian Journal of Surgery  2008;70(4):175-180.
Introduction
Diabetes is the most common metabolic disease encountered by a surgeon. A sound knowledge of symptomatology, clinical signs and etiology can prevent most of the disease burden and complications and thus reduce social burden. The study tells about common foot problems among diabetes and correlates it with the awareness among people.
Aim and objectives
The study aims to obtain an initial and representative data sample to identify the common pedal complications of diabetes mellitus and to provide an initial projection for the development of a podiatric foot health education program within the Hospital-Medical Centre Complex.
Materials and methods
500 diabetic patients were examined of whom 52 had diabetic foot lesions. The symptoms, signs and grade of foot lesion were cross studied with duration, type and occupation of patient. Chi square test was performed and a probability value of p <0.05 was considered significant.
Conclusion
The prevalence of diabetic foot in a hospital based rural diabetic population was observed to be 10.4%. Foot lesion were common in the age group 41–60 years. The most common symptom was numbness in foot ( 40.6%) and was more common in long duration diabetes, Type II diabetes and outdoor workers. Common foot deformity observed were callosities (54.6%) and Hallux valgus/ varus (28%). The least common was Charcot’s deformity (3.6%). Ulceration (23%) and amputation (5.7%) were higher in outdoor workers. Wagner’s grade 2 lesions were the most common foot lesion with diabetic foot. The questionare regarding knowledge, awareness and foot care showed. 99.8% did not inspect the feet properly and 74% washed their feet properly.
doi:10.1007/s12262-008-0048-2
PMCID: PMC3452766  PMID: 23133052
Diabetes; Foot deformities; Wagner’s grade; Lesions
12.  A Prospective Study of Calcaneal Bone Mineral Density in Acute Charcot Osteoarthropathy 
Diabetes Care  2010;33(10):2254-2256.
OBJECTIVE
To measure prospectively bone mineral density (BMD) of the Charcot and non-Charcot foot in 36 diabetic patients presenting with acute Charcot osteoarthropathy.
RESEARCH DESIGN AND METHODS
Calcaneal BMD was measured with quantitative ultrasound at presentation, at 3 months of casting, and at the time of the clinical resolution.
RESULTS
BMD of the Charcot foot was significantly reduced compared with BMD of the non-Charcot foot at presentation (P = 0.001), at 3 months of casting (P < 0.001), and at the time of clinical resolution (P < 0.001). Overall, from the time of presentation to the time of resolution there was a significant fall of BMD of the Charcot foot (P < 0.001) but not of the non-Charcot foot (P = 0.439).
CONCLUSIONS
Although the Charcot foot was treated with casting until clinical resolution, there was a significant fall of BMD only from presentation up until 3 months of casting.
doi:10.2337/dc10-0636
PMCID: PMC2945169  PMID: 20628091
13.  Plantar Temperature Response to Walking in Diabetes with and without Acute Charcot: The Charcot Activity Response Test 
Journal of Aging Research  2012;2012:140968.
Objective. Asymmetric plantar temperature differences secondary to inflammation is a hallmark for the diagnosis and treatment response of Charcot foot syndrome. However, little attention has been given to temperature response to activity. We examined dynamic changes in plantar temperature (PT) as a function of graduated walking activity to quantify thermal responses during the first 200 steps. Methods. Fifteen individuals with Acute Charcot neuroarthropathy (CN) and 17 non-CN participants with type 2 diabetes and peripheral neuropathy were recruited. All participants walked for two predefined paths of 50 and 150 steps. A thermal image was acquired at baseline after acclimatization and immediately after each walking trial. The PT response as a function of number of steps was examined using a validated wearable sensor technology. The hot spot temperature was identified by the 95th percentile of measured temperature at each anatomical region (hind/mid/forefoot). Results. During initial activity, the PT was reduced in all participants, but the temperature drop for the nonaffected foot was 1.9 times greater than the affected side in CN group (P = 0.04). Interestingly, the PT in CN was sharply increased after 50 steps for both feet, while no difference was observed in non-CN between 50 and 200 steps. Conclusions. The variability in thermal response to the graduated walking activity between Charcot and non-Charcot feet warrants future investigation to provide further insight into the correlation between thermal response and ulcer/Charcot development. This stress test may be helpful to differentiate CN and its response to treatment earlier in its course.
doi:10.1155/2012/140968
PMCID: PMC3413979  PMID: 22900177
14.  Volumetric Quantitative Computed Tomography Measurement Precision for Volumes and Densities of Tarsal and Metatarsal Bones 
Diabetic foot diseases, such as ulcerations, infections, and neuropathic (Charcot’s) arthropathy are major complications of diabetes mellitus and peripheral neuropathy and may cause osteolysis (bone loss) in foot bones. The purposes of our study were to make computed tomography (CT) measurements of foot-bone volumes and densities and to determine measurement precision (percent coefficients of variation for root mean square-standard deviations) and least significant changes in these percentages that could be considered biologically real with 95% confidence. Volumetric quantitative CT scans were performed and repeated on 10 young, healthy subjects and 13 subjects with diabetes mellitus and peripheral neuropathy. Two raters used the original- and repeat-scan data sets to make measurements of volumes and bone mineral densities (BMDs) of the tarsal and metatarsal bones of the two feet (24 bones). Precisions for the bones ranged from 0.1% to 0.9% for volume measurements and from 0.6% to 1.9% for BMD measurements. The least significant changes ranged from 0.4% to 2.5% for volume measurements and from 1.5% to 5.4% for BMD measurements. Volumetric quantitative CT provides precise measurements of volume and BMD for metatarsal bones and tarsal bones where diabetic foot diseases commonly occur.
doi:10.1016/j.jocd.2011.05.006
PMCID: PMC3201781  PMID: 21723764
Precision; Whole Bone Volume; Bone Mineral Density; Foot; Diabetes Mellitus; Peripheral Neuropathy
15.  Mortality Risk of Charcot Arthropathy Compared With That of Diabetic Foot Ulcer and Diabetes Alone 
Diabetes Care  2009;32(5):816-821.
OBJECTIVE
The purpose of this study was to compare mortality risks of patients with Charcot arthropathy with those of patients with diabetic foot ulcer and those of patients with diabetes alone (no ulcer or Charcot arthropathy).
RESEARCH DESIGN AND METHODS
A retrospective cohort of 1,050 patients with incident Charcot arthropathy in 2003 in a large health care system was compared with patients with foot ulcer and those with diabetes alone. Mortality was determined during a 5-year follow-up period. Patients with Charcot arthropathy were matched to individuals in the other two groups using propensity score matching based on patient age, sex, race, marital status, diabetes duration, and diabetes control.
RESULTS
During follow-up, 28.0% of the sample died; 18.8% with diabetes alone and 37.0% with foot ulcer died compared with 28.3% with Charcot arthropathy. Multivariable Cox regression shows that, compared with Charcot arthropathy, foot ulcer was associated with 35% higher mortality risk (hazard ratio 1.35 [95% CI 1.18–1.54]) and diabetes alone with 23% lower risk (0.77 [0.66–0.90]). Of the patients with Charcot arthropathy, 63% experienced foot ulceration before or after the onset of the Charcot arthropathy. Stratified analyses suggest that Charcot arthropathy is associated with a significantly increased mortality risk independent of foot ulcer and other comorbidities.
CONCLUSIONS
Charcot arthropathy was significantly associated with higher mortality risk than diabetes alone and with lower risk than foot ulcer. Patients with foot ulcers tended to have a higher prevalence of peripheral vascular disease and macrovascular diseases than patients with Charcot arthropathy. This finding may explain the difference in mortality risks between the two groups.
doi:10.2337/dc08-1695
PMCID: PMC2671113  PMID: 19196882
16.  Pressure pain perception in the diabetic Charcot foot: facts and hypotheses 
Diabetic Foot & Ankle  2013;4:10.3402/dfa.v4i0.20981.
Background
Reduced traumatic and posttraumatic (nociceptive) pain is a key feature of diabetic neuropathy. Underlying condition is a gradual degeneration of endings of pain nerves (A-delta fibers and C-fibers), which operate as receivers of noxious stimuli (nociceptors). Hence, the absence of A-delta fiber mediated sharp pain (“first” pain), and of C-fiber mediated dull pain (“second” pain). However, patients with diabetic neuropathy and acute Charcot foot often experience deep dull aching in the Charcot foot while walking on it.
Aim
To create a unifying hypothesis on the kind of pain in an acute Charcot foot.
Result
Absence of punctuate (pinprick) pain perception at the sole of a Charcot foot, as was shown recently, likely corresponds to vanished intraepidermal A-delta fiber endings. C-fiber nociceptors are reduced, according to histopathology studies. Both types of fibers contribute to posttraumatic hyperalgesia at the skin level, as studies show. Their deficiencies likely impact on posttraumatic hyperalgesia at the skin level and, probably, also at the skeletal level.
Conclusion
It is hypothesised that deep dull aching in an acute diabetic Charcot foot may represent faulty posttraumatic hyperalgesia involving cutaneous and skeletal tissues.
doi:10.3402/dfa.v4i0.20981
PMCID: PMC3661900  PMID: 23705057
pain perception; diabetic neuropathy; Charcot neuroarthropathy
17.  Diabetic foot syndrome: Immune-inflammatory features as possible cardiovascular markers in diabetes 
World Journal of Orthopedics  2015;6(1):62-76.
Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality. Diabetic foot syndrome (DFS), as defined by the World Health Organization, is an “ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection”. Pathogenic events able to cause diabetic foot ulcers are multifactorial. Among the commonest causes of this pathogenic pathway it’s possible to consider peripheral neuropathy, foot deformity, abnormal foot pressures, abnormal joint mobility, trauma, peripheral artery disease. Several studies reported how diabetic patients show a higher mortality rate compared to patients without diabetes and in particular these studies under filled how cardiovascular mortality and morbidity is 2-4 times higher among patients affected by type 2 diabetes mellitus. This higher degree of cardiovascular morbidity has been explained as due to the observed higher prevalence of major cardiovascular risk factor, of asymptomatic findings of cardiovascular diseases, and of prevalence and incidence of cardiovascular and cerebrovascular events in diabetic patients with foot complications. In diabetes a fundamental pathogenic pathway of most of vascular complications has been reported as linked to a complex interplay of inflammatory, metabolic and procoagulant variables. These pathogenetic aspects have a direct interplay with an insulin resistance, subsequent obesity, diabetes, hypertension, prothrombotic state and blood lipid disorder. Involvement of inflammatory markers such as IL-6 plasma levels and resistin in diabetic subjects as reported by Tuttolomondo et al confirmed the pathogenetic issue of the a “adipo-vascular” axis that may contribute to cardiovascular risk in patients with type 2 diabetes. This “adipo-vascular axis” in patients with type 2 diabetes has been reported as characterized by lower plasma levels of adiponectin and higher plasma levels of interleukin-6 thus linking foot ulcers pathogenesis to microvascular and inflammatory events. The purpose of this review is to highlight the immune inflammatory features of DFS and its possible role as a marker of cardiovascular risk in diabetes patients and to focus the management of major complications related to diabetes such as infections and peripheral arteriopathy.
doi:10.5312/wjo.v6.i1.62
PMCID: PMC4303791  PMID: 25621212
Diabetic foot syndrome; Inflammation; Cytokines; Cardiovascular risk; Marker
18.  Management of diabetic neuropathic foot and ankle malunions and nonunions  
Diabetic Foot & Ankle  2011;2:10.3402/dfa.v2i0.6287.
The management of diabetic neuropathic foot and ankle malunions and/or nonunions is often complicated by the presence of broken or loosened hardware, Charcot joints, infection, osteomyelitis, avascular bone necrosis, unstable deformities, bone loss, disuse and pathologic osteopenia, and ulcerations. The author discusses a rational approach to functional limb salvage with various surgical techniques that are aimed at achieving anatomic alignment, long-term osseous stability, and adequate soft tissue coverage. Emphasis is placed on techniques to overcome the inherent challenges that are encountered when surgically managing a diabetic nonunion and/or malunion. Particular attention is directed to the management of deep infection and Charcot neuroarthropathy in the majority of the cases presented.
doi:10.3402/dfa.v2i0.6287
PMCID: PMC3284265  PMID: 22396816
charcot foot; external fixation; malunions; nonunions; diabetic foot
19.  Socioeconomic profile of diabetic patients with and without foot problems 
Diabetic Foot & Ankle  2010;1:10.3402/dfa.v1i0.5523.
Introduction
To identify the differences in a socioeconomic profile between two cohorts of diabetic patients – one with diabetic foot problems and another without diabetic foot problems.
Materials and methods
The cohort with diabetic foot problems (including cellulitis, abscess, osteomyelitis, septic arthritis, gangrene, ulcers, or Charcot joint disease) consisted of 122 diabetic patients, while the other cohort without foot problems consisted of 112 diabetic patients. Both were seen at the National University Hospital from January to April 2007. A detailed protocol was designed and the factors studied included patient profile, average monthly household income, education, compliance to diabetic medication, attendance at clinics for diabetic treatment, exercise, smoking, alcohol consumption, gender, and glycosylated haemoglobin (HbA1C) level. These were studied for significant differences using univariate and stepwise multivariate logistic regression analysis.
Results
With multivariate analysis, Malay ethnicity (p<0.001), education of up to secondary school only (p=0.021), low average monthly household income of less than SGD $2,000 (p=0.030), lack of exercise (at least once a week, p=0.04), and elevated HbA1C level (>7.0%; p=0.015) were found to be significantly higher in the cohort with diabetic foot problems than the cohort without.
Conclusions
There are significant differences in the socioeconomic factors between diabetic patients with diabetic foot problems and those without.
doi:10.3402/dfa.v1i0.5523
PMCID: PMC3284310  PMID: 22396814
diabetic foot; social conditions; patient compliance; income; HbA1c
20.  Lower-Extremity Amputation Risk After Charcot Arthropathy and Diabetic Foot Ulcer 
Diabetes Care  2009;33(1):98-100.
OBJECTIVE
To compare risks of lower-extremity amputation between patients with Charcot arthropathy and those with diabetic foot ulcers.
RESEARCH DESIGN AND METHODS
A retrospective cohort of patients with incident Charcot arthropathy or diabetic foot ulcers in 2003 was followed for 5 years for any major and minor amputations in the lower extremities.
RESULTS
After a mean follow-up of 37 ± 20 and 43 ± 18 months, the Charcot and ulcer groups had 4.1 and 4.7 amputations per 100 person-years, respectively. Among patients <65 years old at the end of follow-up, amputation risk relative to patients with Charcot alone was 7 times higher for patients with ulcer alone and 12 times higher for patients with Charcot and ulcer.
CONCLUSIONS
Charcot arthropathy by itself does not pose a serious amputation risk, but ulcer complication multiplicatively increases the risk. Early surgical intervention for Charcot patients in the absence of deformity or ulceration may not be advisable.
doi:10.2337/dc09-1497
PMCID: PMC2797995  PMID: 19825822
21.  Clinical Implications of Diabetes on the Foot 
Journal of Athletic Training  1997;32(1):55-58.
Objective:
Athletic trainers must understand the clinical implications of diabetes on the athletic foot in order to promote proper foot care and footwear and to adapt protocols for treatment and exercise of the affected athlete.
Data Sources:
The MEDLINE and CINAHL databases were searched for the years 1984 to 1996 with the terms “diabetes and foot,” “neuropathy,” and “Charcot joint.”
Data Synthesis:
As more athletes with diabetes participate in sports, athletic trainers must develop the skills and knowledge necessary to manage this metabolic illness. Although the need to keep blood glucose levels carefully controlled is well known, the impact of diabetes on the foot is not as well recognized. Peripheral vascular disease, soft tissue neuropathy, and neuropathic arthropathy are the most common complications of diabetes affecting the foot. However, with proper management, these complications can be minimized, allowing diabetic athletes and nonathletes to lead more normal and functional lives.
Conclusions/Recommendations:
The athletic trainer can assist the diabetic athlete by promoting proper foot care and footwear and adapting protocols for treatment and exercise.
PMCID: PMC1319237  PMID: 16558434
peripheral vascular disease; neuropathy; neuropathic arthropathy
22.  Conservative and surgical treatment of the chronic Charcot foot and ankle 
Diabetic Foot & Ankle  2013;4:10.3402/dfa.v4i0.21177.
Charcot neuroarthropathy (CN) is a severe joint disease in the foot and ankle that can result in fracture, permanent deformity, and limb loss. It is a serious and potentially limb-threatening lower-extremity late complication of diabetes mellitus. The aim of this manuscript was to evaluate modern concepts of chronic CN through a review of the available literature and to integrate a perspective of management from the authors’ extensive experience.
doi:10.3402/dfa.v4i0.21177
PMCID: PMC3733018  PMID: 23919114
Charcot foot; diabetes mellitus; total contact cast; arthrodesis; diabetic neuropathy
23.  Painless stress fractures in diabetic neuropathic feet. 
Postgraduate Medical Journal  1997;73(858):241-242.
We describe two patients with diabetes mellitus and associated neuropathy, who presented with painless foot swelling and no history of trauma. X-Rays revealed recent underlying fractures-in one of a metatarsus, and the other of a proximal phalanx. These were assumed to be 'stress' fractures unassociated with pain because of the severe sensory neuropathy. Though spontaneous fractures in neuropathic feet have been previously described, they almost always occur in association with Charcot joints, and are usually painful. The differential diagnosis of acute swelling in the foot of a diabetic patient with sensory neuropathy should include stress fracture.
Images
PMCID: PMC2431288  PMID: 9156130
24.  Functional Reconstruction of the Diabetic Foot 
Seminars in Plastic Surgery  2010;24(1):43-56.
ABSTRACT
The diabetic triad of neuropathy, vasculopathy, and foot deformity can be surgically challenging to the reconstructive surgeon. Soft tissue deficits must be closed to protect underlying structures from infection and to provide a stable environment for healing. It is critical to have adequate blood flow and to debride the wound to clean healthy tissue before considering reconstruction. Surgical options commonly used include healing by secondary intention, local flap closure, skin grafts, pedicled flaps, and free tissue transfer. Despite a surgeon's best operative efforts, these strategies may fail perioperatively due to postoperative shear forces created by premature joint motion and/or pressure (either weight bearing or decubitus). In the properly selected patient population, external fixators serve as an indispensable adjunct to wound healing in the Charcot foot by providing temporary but reliable offloading and/or immobilization of joints. Using a team approach is critical to the success of diabetic limb reconstruction.
doi:10.1055/s-0030-1253239
PMCID: PMC2886999  PMID: 21286304
Diabetes; reconstructive surgery; neuropathy; lower-extremity flaps
25.  Association Between Osteoprotegerin G1181C and T245G Polymorphisms and Diabetic Charcot Neuroarthropathy 
Diabetes Care  2009;32(9):1694-1697.
OBJECTIVE
Charcot neuroarthropathy is a disabling complication of diabetes. Although its pathogenesis remains unknown, we suppose that genetics may play a relevant role.
RESEARCH DESIGN AND METHODS
We performed a case-control study with 59 subjects with diabetic Charcot neuroarthropathy (Ch group), 41 with diabetic neuropathy without Charcot neuroarthropathy (ND group), and 103 healthy control subjects (H group) to evaluate the impact of two single nucleotide polymorphisms (SNPs) of the osteoprotegerin gene (G1181C and T245G) on the risk of Charcot neuroarthropathy.
RESULTS
Regarding the SNPs of G1181C, we found a significant linkage between the G allele and Charcot neuroarthropathy (Ch vs. ND, odds ratio [OR] 2.32 [95% CI 1.3–4.1], P = 0.006; Ch vs. H, 2.10 [1.3–3.3], P = 0.002; and ND vs. H, 0.90 [0.7–1.9], P = 0.452); similarly, we found a linkage with the G allele of T245G (Ch vs. ND, 6.25 [2.2–19.7], P < 0.001; Ch vs. H, 3.56 [1.9–6.7], P = 0.001; and ND vs. H, 0.54 [0.6–5.7], P = 0.304), supporting a protective role for the allele C and T, respectively. For this reason we investigated the frequency of the protective double homozygosis CC + TT (7% in Ch) that was significantly lower in Ch compared with H (0.18 [0.06–0.5], P = 0.002) and with ND (0.17 [0.05–0.58], P = 0.006), whereas there was no difference between H and ND (1.05 [0.43–2.0], P = 0.468). In a multivariate logistic backward regression model, only weight and the lack of CC and TT genotypes were independently associated with the presence of Charcot neuroarthropathy.
CONCLUSIONS
This is the first study that shows an association between genetic regulation of bone remodeling and Charcot neuroarthropathy.
doi:10.2337/dc09-0243
PMCID: PMC2732132  PMID: 19502537

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