Long-Term Changes in Sarcopenia and Body Composition in Diabetes Patients with and without Charcot Osteoarthropathy.

BACKGROUND: Charcot osteoarthropathy of the foot (COA) can currently only be treated using prolonged periods of immobilization of the affected extremity. Therefore, the hypothesis is that COA leads to altered body composition and increased sarcopenia. OBJECTIVE: To investigate the changes over several years in sarcopenia, body composition, and fat distribution in diabetes patients with previous COA compared to diabetes patients without previous COA. METHODS: Prospective observational clinical study. Twenty-one subjects were included and had two DXA scans done with mean 8.6-year intervals to compare changes in lean mass and fat distribution. The lean mass of limbs was used as an estimate of appendicular lean mass (aLM). Fat mass and aLM were then used to detect sarcopenic individuals using different methods. Results and Conclusions. As compared to baseline, both groups had significant loss of lean mass, and diabetics without COA had significant gain of total fat percentage. No statistically different prevalence of sarcopenia between the groups could be established. Likewise, no difference was found in total lean and fat mass changes. None of the groups had statistically significant changes of android fat distribution. As compared with published data on sarcopenia, people with diabetes might be more prone to sarcopenia than healthy individuals.

Risk factors for development of nephropathy in patients with a diabetic Charcot foot.

OBJECTIVE: Charcot foot is a rare complication to neuropathy and can cause severe foot deformities and ulcerations, which often require prolonged antibiotical treatment. The objective of this retrospective study was to investigate whether this treatment is associated to impaired renal function. RESULTS: In total, 163 patients were included, of whom 105 (64%) had received ß-lactam antibiotics for a mean total duration of 13.0 months. There was a significant increase in the urine albumin/creatinine ratio in the group that received antibiotics (p = 0.017), and the use of antibiotics was associated to a subsequent diagnosis of nephropathy (p = 0.01). Patients treated with antibiotics had a 21.9% risk of developing subsequent nephropathy versus 5.2% for patients not treated with antibiotics. We suggest increased awareness on signs of nephropathy in patients with severe Charcot foot.

Mortality and complications after treatment of acute diabetic Charcot foot.

AIMS: Charcot foot is a rare but disabling complication to diabetic neuropathy, and can cause permanent, limb-threatening deformities. The aim of this study was to investigate a population of patients a Charcot foot on a case-by-case basis, in order to assess the consequences of an acute Charcot foot and its complications. METHODS: The study was conducted a retrospective study of patients admitted to the Copenhagen Wound Healing Center between 1996 and 2015 with the diagnosis of Charcot foot (DM14.6) and diabetes mellitus type 1 or 2 (DE10.X and DE11.X). Physical and electronic records were used, and compared to data from the Danish Diabetes Registry. RESULTS: In total 392 patients were identified of which 173 were included. There were 26% with type 1 diabetes (initial HbA1c 81.7 ±â€¯21.4 mmol/mol) and 74% with type 2 diabetes (initial HbA1c 66.5 ±â€¯20.3 mmol/mol). Primary off-loading was with a removable walker in 95% of the cases (average off-loading time 8.3 months). The 5-year mortality was 14% with a mean survival time of 12.7 years. There was an association between lack of compliance and occurrence of foot complications, as well as between having a Charcot foot and leaving the workforce. CONCLUSION: More patients had type 1 diabetes compared to the background population, and they had a higher HbA1c than the general population of diabetes patients. A total of 67% developed complications such as ulcers, while patients non-compliant to treatment did significantly worse than those being compliant. The 5-year mortality was low, 14%, and comparable to diabetes patients without Charcot foot.

Long-term effects on the progress of neuropathy after diabetic Charcot foot: an 8.5-year prospective case-control study.

OBJECTIVE: Charcot foot is a severe complication to diabetes mellitus, associated with diabetic neuropathy. Any long-term effects of a Charcot foot on the progress of neuropathy are still largely unexplored. The objective was to investigate whether a previous Charcot foot had any long-term effects on the progress of neuropathy. RESULTS: An 8.5-year follow-up case-control study of 49 individuals with diabetes mellitus, 24 of whom also had Charcot foot at baseline visit in 2005-2007. Neuropathy was assessed with a questionnaire, biothesiometry, heart rate variability and venous occlusion plethysmography. Of the 49 baseline participants, 22 were able to participate in the follow-up. Twelve had passed away in the meantime. Heart rate variability was unchanged in both groups; from 9.7 to 7.2 beats/min (p = 0.053) in the Charcot group, and 14.3 to 12.6 beats/min (p = 0.762) in the control group. Somato-sensoric neuropathy showed no difference between baseline and follow-up in the Charcot group (from 39.1 to 38.5 V) (p = 0.946), but a significantly worsened sensitivity in the control group (from 25.1 to 38.9 V) (p = 0.002). In conclusion, we found that any differences in somatic or cardial autonomic neuropathy present at baseline had disappeared at follow-up after 8.5 years.

Bone mineral density and markers of bone turnover and inflammation in diabetes patients with or without a Charcot foot: An 8.5-year prospective case-control study.

BACKGROUND AND AIMS: Charcot foot is a rare but severe complication to diabetes and peripheral neuropathy. It is still unclear if an acute Charcot foot has long-term effects on the bone metabolism. To investigate this, we conducted a follow-up study to examine if a previously acute Charcot foot has any long-term effects on bone mineral density (BMD) or local or systemic bone metabolism. METHODS: An 8.5-year follow-up case-control study of 44 individuals with diabetes mellitus, 24 of whom also had acute or chronic Charcot foot at the baseline visit in 2005-2007, who were followed up in 2015 with DXA scans and blood samples. RESULTS: 21 of the 44 baseline participants participated in the follow-up. There were no difference in the change in total hip BMD from baseline to follow-up in either the Charcot or the control group (p = 0.402 and 0.517), and no increased risk of osteoporosis in the previous Charcot feet either. From baseline to follow-up, there was a significant difference in the change in levels of fsRANK-L in the Charcot group, but not in the control group (p = 0.002 and 0.232, respectively). At follow-up, there were no differences in fsRANK-L between the groups. The fsRANK-L/OPG ratio also significantly decreased from baseline to follow-up in the Charcot group (3.4 versus 0.5) (p = 0.009), but not in the control group (1.3 versus 1.1) (p = 0.302). CONCLUSION: We found that diabetes patients with an acute Charcot foot have an elevated fsRANK-L/OPG ratio, and that the level decreased from baseline to follow-up to be comparable to the level in diabetes patients without previous or current Charcot foot. We found no permanent effect of an acute Charcot foot on hip or foot BMD.

Diabetic complications do not hamper improvement of health-related quality of life over the course of treatment of diabetic foot ulcers - the Eurodiale study.

AIMS: Diabetic complications, and in particular diabetic foot ulcers (DFUs), are associated with low health-related quality of life (HRQoL). We evaluated whether the presence of diabetic complications also influenced the improvement of HRQoL during DFU treatment. METHODS: 1088 patients presenting for DFU treatment at the centers participating in the Eurodiale study were followed prospectively up to one year. HRQoL was measured both at presentation and after healing or at end of follow up, using EQ-5D: a standardized instrument consisting of five domains and a summary index. The influence of diabetic comorbidity on the course of HRQoL was evaluated for each of the EQ-5D outcomes in multi-level linear regression analyses, adjusting for baseline characteristics. RESULTS: HRQoL improved in all EQ-5D outcomes over the course of treatment for those DFUs that healed. The few significant differences in the development of HRQoL between patients with and without comorbidity showed a more beneficial development for patients with comorbidity in DFUs that did not heal or healed slowly. CONCLUSIONS: Comorbidity does not hamper improvement of HRQoL in DFU treatment. On the contrary, HRQoL improved sometimes more in patients with certain comorbidity with hard-to-heal ulcers.

Sarcopenia and body composition in diabetic Charcot osteoarthropathy.

BACKGROUND: Treatment of Charcot osteoarthropathy (COA) requires restricted walking and offloading for several months, which lead to fat re-distribution and increased sarcopenia. OBJECTIVES/AIM: To investigate whether subjects with COA have an altered body composition compared to controls. METHODS: Cross-sectional case-control study of people with diabetes with acute or chronic Charcot osteoarthropathy, matched with otherwise healthy people with diabetes. A total of 49 subjects (distribution ~1:1) had a total body DXA-scanning, measuring appendicular lean mass, android/gynoid and truncal/total body fat distribution ratios. RESULTS: Sarcopenia frequency was higher in the total population with diabetes overall (9-40%), compared to normal materials. Using two different models for correlating appendicular lean mass to sarcopenia, there were no differences in sarcopenia-rates between the groups (P=0.413 and 0.948 respectively). There was no significant difference in lean tissue mass between the affected and the unaffected leg in the immobilised subject group (P=0.830). The average fat percentage was (29.4-37.7%) in the population with diabetes, compared to a matching background population (24.5-31.9%), whereas there were no significant differences found between the groups (P=0.065). Neither truncal/total fat percent nor android/gynoid fat percent ratios showed differences between the groups. CONCLUSION: To our knowledge, this is the first published dataset investigating body composition in subjects with Charcot osteoarthropathy. The study population of diabetics were more fat and sarcopenic than normal subjects, whereas no statistically significant impact of Charcot osteoarthropathy was found.

Health-related quality of life predicts major amputation and death, but not healing, in people with diabetes presenting with foot ulcers: the Eurodiale study.

OBJECTIVE: Low health-related quality of life (HRQoL) has been consistently reported to be associated with poor prognosis for a variety of health outcomes in various settings. We aimed to evaluate whether HRQoL in patients presenting with new diabetic foot ulcers (DFUs) has prognostic significance for ulcer healing, major amputation, and death. RESEARCH DESIGN AND METHODS: We followed 1,088 patients with new DFUs presenting for treatment at one of the 14 centers in 10 European countries participating in the Eurodiale (European Study Group on Diabetes and the Lower Extremity) study, prospectively until healing (76.9%), major amputation (4.6%), or death (6.4%) up to a maximum of 1 year. At baseline, patient and ulcer characteristics were recorded as well as EQ-5D, a standardized instrument consisting of five domains and a visual analog scale for use as a measure of HRQoL. The prognostic influence of the EQ-5D domains was evaluated in multivariable Cox regression analyses on the time-to-event data, adjusting for baseline clinical characteristics of the ulcer and comorbidities. RESULTS: While predictive effects of HRQoL, adjusted for possible confounders, were absent for healing, decreased HRQoL, especially in the physical domains, was statistically significant for major amputation (mobility, self-care, usual activities) and death (self-care, usual activities, pain/discomfort). CONCLUSIONS: Low HRQoL appears to be predictive for major amputation and death, but high HRQoL does not increase healing. Future studies into the influence of HRQoL on ulcer outcome are important in attempts to decrease treatment failure and mortality.

Diabetic foot disease: impact of ulcer location on ulcer healing.

BACKGROUND: Healing of heel ulcers in patients with diabetes is considered to be poor, but there is relatively little information on the influence of ulcer location on ulcer healing. METHODS: The influence of ulcer location on time to healing of diabetic foot ulcers was analysed by multivariate Cox regression analysis for 1000 patients included in the Eurodiale study, a prospective cohort study of patients with diabetic foot disease. RESULTS: Median time to healing was 147 days for toe ulcers [(95% confidence interval (CI) 135-159 days)], 188 days for midfoot ulcers (95% CI 158-218 days) and 237 days for heel ulcers (95% CI 205-269 days) (p < 0.01). The median time to healing for plantar ulcers was 172 days (95% CI 157-187 days) and 155 days (95% CI 138-172 days) for nonplantar ulcers (p = 0.71). In multivariate Cox regression analysis, the hazard ratio for ulcer healing for midfoot and heel ulcers compared with toe ulcers was 0.77 (95% CI 0.64-0.92) and 0.62 (95% CI 0.47-0.83), respectively; the hazard ratio for ulcer healing for plantar versus nonplantar ulcers was 1 (95% CI 0.84-1.19). Other factors significantly influencing time to healing were the duration of diabetes, ulcer duration, the presence of heart failure and the presence of peripheral arterial disease. CONCLUSIONS: Time to ulcer healing increased progressively from toe to midfoot to heel, but did not differ between plantar and nonplantar ulcers. Our data also indicate that risk factors for longer time to healing differ from factors that affect the ultimate number of ulcers that heal (healing rate).

Duration of off-loading and recurrence rate in Charcot osteo-arthropathy treated with less restrictive regimen with removable walker.

OBJECTIVE: Recent literature on acute diabetic Charcot osteoarthropathy (CA) reports unusually long periods of off-loading. Data suggest that this might increase the re-currence rate. Subsequently we evaluated the influence of duration of off-loading on the risk of required re-casting. RESEARCH DESIGN AND METHODS: In this retrospective consecutive series from 2000 to 2005, 56 people with diabetes and an acute Charcot foot were included. The inclusion criteria were an initial persistent temperature difference more than 2°C between the two feet, oedema, and typical hot spots on a bone scintigram, radiology, and a typical clinical course. Treatment was off-loading in a removable cast and 2 crutches. In-door walking was allowed. Gradually augmented weight bearing was prescribed when the skin temperature difference had decreased to a level less than 2°C and edema had subsided. Re-casting was required for immediate exacerbation during re-load as well as for recurrence - defined as new swelling and skin temperature difference of more than 2°C in the same foot occurring after a stable interval of at least one month after full weight bearing. RESULTS: The duration of off-loading for all patients was 141±21 days (mean±SD). Three patients (5%) were re-casted immediately for exacerbation after re-load and 7 patients (12 %) after recurrence of the CA. Duration of re-casting was 79±44 days. The primary period of off-loading was not statistically significantly different for those not requiring versus those requiring re-casting: 142±24 days compared to 134±41 days. Neither were the differences in demographic data, metabolic regulation, BMI or localization of CA. CONCLUSIONS: Patients with risk of exacerbation or recurrence of CA could not be identified in the present study and there was no relation to the duration of off-loading. Nevertheless off-loading periods with immobilisation should be kept as short as possible, due to other side effects. This can be obtained by early gradual augmented re-loading.

Sympathetic neuropathy in diabetes mellitus patients does not elicit Charcot osteoarthropathy.

AIM: The aim of the study was to determine the degree of neuropathy (autonomic and somatic) in patients with diabetes mellitus with or without Charcot osteoarthropathy (CA). METHODS: Forty-nine patients with diabetes mellitus type 1 or 2 were investigated. The patient population of interest was the patients with acute Charcot foot (n=17) or chronic Charcot foot (n=7). The inclusion criterion for an acute Charcot foot was a temperature difference of more than 2° between the two feet, oedema of the affected foot, typical hotspots in a bone scintigram and a typical clinical course. In addition, patients with first toe amputation (n=5), a high-risk group for development of CA, and two control groups consisting of diabetes patients with (n=9) or without somatic neuropathy (n=11) were investigated. Regional blood flow in the feet was measured by venous occlusion plethysmography. Quantitation of somatic neuropathy was done by the Neuropathy Disability Score and modified Neuropathy Symptom Score. Quantitation of autonomic neuropathy was done by measurements of local venoarteriolar sympathetic axon reflex in the feet and of heart rate variability during deep breathing and orthostatic challenge. RESULTS: The patients with acute Charcot foot and first toe amputation had an increased blood flow in the affected foot and weakened but not absent venoarteriolar sympathetic axon reflex. In the other patient groups, a normal venoarteriolar sympathetic axon reflex in the feet was found. CONCLUSIONS: Peripheral sympathetic neuropathy is not likely to be the pathophysiologic mechanism behind the hyperemia in the foot during an acute attack of CA. The hyperemia is more likely secondary to local inflammatory events.

Bone mineral density in diabetes mellitus patients with and without a Charcot foot.

OBJECTIVE: To measure bone mineral density in patients with diabetes mellitus and the complication Charcot osteoarthropathy (CA). RESEARCH DESIGN AND METHODS: A total of 49 patients with diabetes were investigated. The population consisted of patients with an acute CA (n = 17) or chronic CA (n = 7). Control groups consisted of diabetes patients with (n = 9) and without neuropathy (n = 11) and who had an amputation of the first toe (n = 5). Values measured were bone mineral density (BMD) in lumbar spine, hip and calcaneus, using lunar DEXA scanner. The bone turnover markers CTX-1 and N-MID were measured. RESULTS: There were no differences in BMD measured in the spine and hip. There was an increase in the markers of bone turnover in the patients with acute CA. The BMD of the calcaneus was statistically lower in the affected foot in patients with chronic Charcot (P < 0.01), than in the unaffected foot, but there were no statistically significant differences between the BMD of the calcaneus in the feet in the other groups. CONCLUSIONS: From this study, we can conclude that there were no differences in BMD values in the spine and hip between groups. There were no differences between BMD of the calcaneus between groups, except that patients with chronic Charcot had a significantly lower calcaneal BMD in the affected foot than in the healthy foot. Furthermore, there was an increased bone turnover in the group with acute CA, which was not found in the other patients groups. This suggests that the Charcot foot is a rather local phenomenon, with little effect on the skeleton in general.

Epidemiology of chronic wound patients and relation to serum levels of mannan-binding lectin.

The aim of this study was to describe the epidemiology of chronic wounds in a large cohort of patients from a tertiary hospital out-patient clinic, and examine the significance of serum mannan-binding lectin for the occurrence and clinical presentation of such wounds. The study comprised 489 consecutive patients with chronic foot and leg ulcers. A clinical classification of wound- aetiology was performed, and mannan-binding lectin was measured in the sera of patients and healthy controls. The patients presented with 639 wounds altogether; diabetic foot ulcers (309), venous leg ulcers (188), arterial ulcers (109), and vasculitis (33). The mannan-binding lectin levels of patients with venous leg ulcer, alone or in combination with other types of wounds, differed significantly from the control group, and the frequency of values < 100 ng/ml was significantly higher. In diabetic and arterial ulcer patients the frequency of values >or= 3000 ng/ml was significantly higher than that of the control group. This suggests a role for the innate immunity in the pathology of venous leg ulcers, and indicates different roles for mannan-binding lectin in the development of ulcers with different aetiologies; it further suggests that mannan-binding lectin substitution should be tested in a controlled clinical trial.

Incidence of bullosis diabeticorum--a controversial cause of chronic foot ulceration.

Bullosis diabeticorum (BD) is considered a rare and relatively harmless skin manifestation with tense blisters appearing rapidly and mostly on the feet. Most papers report only a few cases and the cause of the blisters is not known. We have experienced that the lesions are not so rare and may turn into chronic foot ulcers with complications. Retrospective study of 25 consecutive patients with 35 outbreaks and 93 bullae in a population of 5000 people with diabetes treated during a 3-year period. The bullae were deroofed in order to examine the bulla base and treated as foot ulcers including debridement, antibiotics, bandage and protective footwear. The incidence of BD per year in the present diabetic population is 0.16%. In 29 outbreaks, there were hypoglycaemic episodes or highly varying blood glucose. Antibiotics were given in 17 of 35 episodes. Time to healing was as much as median 2.5 months (range 0.5-23 months). Two patients had minor amputations. BD should be well known to all members of diabetic foot care teams. Blood glucose control with special attention to hypoglycaemia at the time of eruption, deroofing of the bullae and foot ulcer care are recommended.

Arthrodesis with external fixation in the unstable or misaligned Charcot ankle in patients with diabetes mellitus.

The unstable or misaligned Charcot ankle with or without chronic foot ulceration is a major clinical challenge. When it cannot be accommodated with an ankle foot orthosis, surgical treatment is indicated in order to avoid leg amputation. This requires extensive soft tissue release and bony resection to realign the foot and arthrodesis with internal or external fixation. The guidance in the literature favors internal fixation. This article reports results with external fixation in 11 patients (12 feet) over a period of 12 years. External fixation was chosen as the surgical option because of the presence of foot ulcers with the attendent risk of infection. There were 7 tibio-talar and 5 tibio-calcaneal fusions. Compression was applied for 6 weeks with an external frame according to Charnley, followed by 6 weeks with total-contact cast. Weight bearing with a rigid leather brace was allowed after 12 weeks. In one case, transtibial amputation was required due to loosening of the distal pins from osteopenic disintegrating bone. In 11 cases (92%), the foot was successfully realigned and independent walking with a brace retained during the follow-up of median 48 months (10-102 months). Bony union took place in 5 out of 7 cases with tibio-talar fusion and in 1 out of 5 with tibio-calcaneal fusion. The functional result in cases with fibrous union was, however, satisfactory. Although meaningful comparisons of series are difficult to conduct and interpret from, the limb salvage rate was similar to results with internal fixation. The authors consider the results to be encouraging and to be used to develop a higher level of evidence.

Standardised method of surgical treatment of chronic leg ulcers.

Healing and recurrence rates were compared in leg ulcers of different aetiology in 385 patients with 406 chronic leg ulcers. Standard treatment was excision of the ulcer followed by meshed split-skin grafting and correction of superficial venous insufficiency in the area. The median age of the patients was 75 years (range 16-95). After one year 345 patients with 357 leg ulcers were alive. Overall healing rate was 64% (227 in 357 legs) after one year. The best results were achieved in traumatic ulcers (31 in 36 ulcers) and worst for the arterial ulcers (4 in 20 ulcers). Recurrence rate in venous and venous/ischaemic ulcers was 14% (33 in 235 legs) and 8% (n=3) in the traumatic ulcers. Vasculitic ulcers tend to recur 59% (n=10), but the graft does relieve pain.

Decrease of collagen deposition in wound repair in type 1 diabetes independent of glycemic control.

HYPOTHESIS: Type 1 and type 2 diabetes mellitus and glycemic control influence wound healing in humans. DESIGN: Experimental study using a human wound-healing model. SETTING: Collaboration among a multidisciplinary wound-healing department, department of medicine, and research laboratories. PATIENTS, CONTROL SUBJECTS, AND METHODS: In 34 patients with type 1 (insulin-dependent) and 25 with type 2 (non-insulin-dependent) diabetes and 5 nondiabetic control subjects matched with the type 2 diabetic patients, wound-healing capacity was determined as subcutaneous accumulation of collagen measured as hydroxyproline. Two expanded polytetrafluoroethylene tubes were implanted and removed 10 days later. The hydroxyproline level was determined by means of high-performance liquid chromatography; the collagenase activity, by using a radiolabeled collagen substrate. Proliferation of fibroblasts cultured from the wounds was studied in patient groups. RESULTS: The deposition of hydroxyproline decreased by 40% (P =.03) in type 1 compared with type 2 diabetes (median, 0.70 vs 1.16 nmol/mg; interquartile range, 0.48-1.04 vs 0.56-1.63 nmol/mg), which in turn did not differ significantly from that of controls (median, 1.35 nmol/mg; interquartile range, 0.72-1.88 nmol/mg). The decreased collagen deposition in type 1 diabetes was not caused by increased collagenase activity. The deposition of hydroxyproline did not correlate significantly (r(s) = 0.07; P =.63) with glycosylated hemoglobin levels in either diabetic group. Fibroblast growth was also decreased in type 1 compared with type 2 diabetic patients and controls. CONCLUSIONS: Collagen deposition in acute wounds is impaired in type 1 diabetes, possibly due to a decreased fibroblast proliferation. In type 2 diabetes, collagen deposition is normal. Glycemic control does not influence collagen deposition in acute wound repair in type 1 or in type 2 diabetes mellitus.