This study aimed at identifying factors that worsen the prognosis of diabetic foot, one of the most common complications seen in patients with diabetes.

Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality; in fact, some authors showed a higher prevalence of major, previous and new-onset, cardiovascular, and cerebrovascular events in diabetic patients with foot ulcers than in those without these complications. This is consistent with the fact that in diabetes there is a complex interplay of several variables with inflammatory metabolic disorders and their effect on the cardiovascular system that could explain previous reports of high morbidity and mortality rates in diabetic patients with amputations. Involvement of inflammatory markers such as IL-6 plasma levels and resistin in diabetic subjects confirmed the pathogenetic issue of the "adipovascular" axis that may contribute to cardiovascular risk in patients with type 2 diabetes. In patients with diabetic foot, this "adipovascular axis" expression in lower plasma levels of adiponectin and higher plasma levels of IL-6 could be linked to foot ulcers pathogenesis by microvascular and inflammatory mechanisms. The purpose of this review is to focus on the immune inflammatory features of DFS and its possible role as a marker of cardiovascular risk in diabetes patients.

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.

We aimed to identify which individual risk factors best predict foot ulceration in routine clinical practice and whether an integrated clinical tool is a better screening tool for future foot ulceration.

Routinely collected clinical information on foot and general diabetes indicators were recorded on the regional diabetes electronic register. Follow-up data on foot ulceration were collected from the same electronic record, the local multidisciplinary foot clinic and community and hospital podiatry paper records. Data were electronically linked to see which criteria best predicted future foot ulceration.

Foot risk scores were recorded on 3719 patients (44% female, mean age 59±15years) across community and hospital clinics. Overall, 851 (22.9%) had insensitivity to monofilaments, in 629 (17.2%) both pulses were absent and 184 (4.9%) had a prior ulcer. In multivariate analysis, the strongest predictors of foot ulceration were prior ulcer, insulin treatment, absent monofilaments, structural abnormality and proteinuria and retinopathy. The sensitivity of predicting foot ulceration was 52% for prior ulcer, 61% for absent monofilaments, 75% for 'high risk' on an integrated risk score and 91% for high and moderate risk combined. The corresponding specificities were 99, 81, 89 and 61%. Positive likelihood ratio was 52 for prior ulcer and 6.8 for foot risk, with negative likelihood ratios of 0.48 and 0.15, respectively.

Integrated foot risk scores are more sensitive than individual clinical criteria in predicting future foot ulceration and are likely to be better screening tools, where excluding false negative results is of paramount importance.

The incidence of minor amputation may vary significantly, and determinants of minor amputation have not been studied systematically. We evaluated minor amputation rate, the determinants of minor amputation and differences in amputation rate between European centres.

In the Eurodiale study, a prospective cohort study of 1232 patients (1088 followed until end-point) with a new diabetic foot ulcer were followed on a monthly basis until healing, death, major amputation or up to a maximum of 1 year. Ulcers were treated according to international guidelines. Baseline characteristics independently associated with minor amputation were examined using multiple logistic regression modelling. Based on the results of the multivariable analysis, a disease severity score was calculated for each patient.

One hundred and ninety-four (18%) patients underwent a minor amputation. Predictors of minor amputation were depth of the ulcer (odds ratio 6.08, confidence interval 4.10-9.03), peripheral arterial disease (odds ratio 1.84, confidence interval 1.30-2.60), infection (odds ratio 1.56, confidence interval 1.05-2.30) and male sex (odds ratio 1.42, confidence interval 0.99-2.04). Minor amputation rate varied between 2.4 and 34% in the centres. Minor amputation rate in centres correlated strongly with disease severity score at the moment of presentation to the foot clinic (r=0.75).

Minor amputation is performed frequently in diabetic foot centres throughout Europe and is determined by depth of the ulcer, peripheral arterial disease, infection and male sex. There are important differences in amputation rate between the European centres, which can be explained in part by severity of disease at presentation. This may suggest that early referral to foot clinics can prevent minor amputations.

This study was performed to evaluate the effectiveness of hyperbaric oxygen therapy (HBOT) in the treatment of the infected diabetic foot.

Forty-two patients with 44 infected diabetic feet receiving HBOT were divided into two groups. One group of 21 patients with 21 feet received <10 sessions of HBOT. The other 21 patients with 23 feet received >10 sessions of HBOT.

In patients who received <10 sessions of HBOT, seven patients achieved satisfactory wound healing. Feet were preserved in 33.3%. In patients with >10 sessions of HBOT, 16 patients with 18 feet achieved good wound healing. Of these patients, 78.3% preserved their feet. This group of patients received an average of 22.8 HBOT treatments.

Adjunctive HBOT has a positive effect on wound healing in diabetic foot with infection. The effect of HBOT seems dose dependent because the amputation rate is decreased in patients who receive adequate HBOT.

Despite an improvement in our understanding of the aetiopathogenesis of diabetic foot problems in the last 2 decades, the 21st Century epidemic of type 2 diabetes will ensure that the incidence of foot problems will continue to increase in the diabetic population. In the aetiopathogenesis it is important to understand that a number of factors working together usually result in foot ulceration: the commonest trio is neuropathy, deformity and trauma. In Western countries, the incidence of neuroischaemic ulcers is now increasing making early detection of those at risk even more important. In the pathogenesis of Charcot neuroarthropathy, recent advances in our understanding of the mechanisms underlying the development of osteopenia and osteoporosis include the central role of the RANK-L OPG signalling system. Finally, in terms of wound healing, the most frequently neglected aspect of care is appropriate offloading of neuropathic or neuroischaemic foot ulcers. The next decades will undoubtedly see the application of stem cell therapy in the management of diabetic foot ulceration.

Since diabetes mellitus is growing at epidemic proportions worldwide, the prevalence of diabetes-related complications is bound to increase. Diabetic foot disorders, a major source of disability and morbidity, are a significant burden for the community and a true public health problem. Many epidemiological data have been published on the diabetic foot but they are difficult to interpret because of variability in the methodology and in the definitions used in these studies. Moreover, there is a lack of consistency in population characteristics (ethnicity, social level, accessibility to care) and how results are expressed. In westernized countries, two of 100 diabetic patients are estimated to suffer from a foot ulcer every year. Amputation rates vary considerably: incidence ranges from 1 per thousand in the Madrid area and in Japan to up to 20 per thousand in some Indian tribes in North America. In metropolitan France, the incidence of lower-limb amputation is approximately 2 per thousand but with marked regional differences, and in French overseas territories, the incidence rate is much higher. Nevertheless, the risk for ulceration and amputation is much higher in diabetics compared to the nondiabetic population: the lifetime risk of a diabetic individual developing an ulcer is as high as 25% and it is estimated that every 30s an amputation is performed for a diabetic somewhere in the world. As reviewed in this paper, peripheral neuropathy, arterial disease, and foot deformities are the main factors accounting for this increased risk. Age and sex as well as social and cultural status are contributing factors. Knowing these factors is essential to classify every diabetic using a risk grading system and to take preventive measures accordingly.

The purpose of this study was to estimate the risks of nontraumatic lower-extremity amputations (LEAs) in patients with type 1 diabetes.

We identified 31,354 patients with type 1 diabetes (15,001 women and 16,353 men) in the Swedish Inpatient Register between 1975 and 2004. The incidence of nontraumatic LEAs was followed up until 31 December 2004 by cross-linkage in the Inpatient Register and linkage to the Death and Migration registers. Poisson regression modeling was used to compare the risks of nontraumatic LEAs during different calendar periods of follow-up, with adjustment for both sex and attained age at follow-up. Standardized incidence ratios (SIRs) were used to estimate the relative risks (RRs) with the age-, sex-, and calendar period-matched general Swedish population as reference. The cumulative probability of nontraumatic LEAs was calculated by the Kaplan-Meier method.

In total, 465 patients with type 1 diabetes underwent nontraumatic LEAs. The risk was lower during the most recent calendar period (2000-2004) than during the period before 2000 (RR 0.6 [95% CI 0.5-0.8]). However, even in this most recent period, the risk for nontraumatic LEAs among these relatively young patients was 86-fold higher than that in the matched general population (SIR 85.8 [72.9-100.3]). By age 65 years, the cumulative probability of having a nontraumatic LEA was 11.0% for women with type 1 diabetes and 20.7% for men with type 1 diabetes.

Although the risks appeared to have declined in recent years, patients with type 1 diabetes still have a very high risk for nontraumatic LEAs.

Management of the septic foot is a challenge in diabetic patients, and this condition often progresses to amputation in an effort to alleviate otherwise incurable infection. We designed and followed a protocol for the management of the septic diabetic foot and, after 2 years (May 2004 through June 2006), we analyzed the data related to 31 septic feet of 139 patients. The treatment protocol consisted of blood glucose control, intravenous antibiotic therapy, controlling comorbidities, revascularization, ulcer drainage and irrigation, systematic debridement, dressing changes and wound care, and amputation if necessary. The outcomes of interest were amputation and limb salvage. The analyses showed that frequent drainage and debridement, along with revascularization when indicated and possible, resulted in 4 (12.9%) major (below-the-knee) amputations and 3 transmetatarsal amputations. Of the 7 amputations, 3 were associated with ischemia, 4 with neuropathy, and 1 with neuropathy and ischemia. In follow-up, 1 patient with a prior history of septic diabetic foot required major amputation. Based on these findings, it is concluded that the septic diabetic foot is not necessarily an indication for amputation, and aggressive management by means of metabolic and surgical care can lead to a favorable outcome.

2.

Diabetes pedal infections are too prevalent and will become more so as the numbers of diabetic patients increase. The goal is to prevent amputations or at least to remove as little of the foot as possible. Prompt surgical intervention and better diabetic pedal education will go a long way to achieving that goal.

The aim was to evaluate over 18 months whether depression was associated with mortality in people with their first foot ulcer.

A prospective cohort design was used. Adults with their first diabetic foot ulcer were recruited from foot clinics in southeast London, U.K. At baseline, the Schedules for Clinical Assessment in Neuropsychiatry 2.1 was used to define those who met DSM (Diagnostic and Statistical Manual of Mental Disorders)-IV criteria for minor and major depressive disorders. Potential covariates were age, sex, marital status, socioeconomic status, smoking, antidepressant use, A1C, macro- and microvascular complications, and University of Texas classification-based severity and size of ulcer. The main outcome was mortality 18 months later, and A1C was the secondary outcome. The proportion who had an amputation, had recurrence, and whose ulcer had healed was recorded.

A total of 253 people with their first diabetic foot ulcer were recruited. The prevalence of minor and major depressive disorder was 8.1% (n = 21) and 24.1% (n = 61), respectively. There were 40 (15.8%) deaths, 36 (15.5%) amputations, and 99 (43.2%) recurrences. In the adjusted Cox regression analysis, minor and major depressive disorders were associated with an approximately threefold hazard risk for mortality compared with no depression (3.23 [95% CI 1.39-7.51] and 2.73 [1.38-5.40], respectively). There was no association between minor and major depression compared with no depression and A1C (P = 0.86 and P = 0.43, respectively).

One-third of people with their first diabetic foot ulcer suffer from clinical depression, and this is associated with increased mortality.

Diabetes is an increasing health problem, but efforts to handle this pandemic by disease management programs (DMP) have shown conflicting results. Our hypothesis is that, in addition to a program's content and setting, the choice of the right patients is crucial to a program's efficacy and effectiveness. We used individualized predictive disease modeling (IPDM) on a cohort of 918 patients with type 2 diabetes to identify those patients with the greatest potential to benefit from inclusion in a DMP. A portion of the patients (4.7%) did not have even a theoretical potential for an increase in life expectancy and would therefore be unlikely to benefit from a DMP. Approximately 16.1% had an increase in life expectancy of less than half a year. Stratification of the entire cohort by surrogate parameters like preventable 10-year costs or gain in life expectancy was much more effective than stratification by classical clinical parameters such as high HbA1c level. Preventable costs increased up to 50.6% (or 1,010 per patient (1 = US dollars 1.28), p < 0.01) and life expectancy increased up to 54.8% (or 2.3 years, p < 0.01). IPDM is a valuable strategy to identify those patients with the greatest potential to avoid diabetes-related complications and thus can improve the overall effectiveness and efficacy of DMPs for diabetes mellitus.

Diabetic foot ulcers are among the most common severe complications of diabetes, affecting up to 68 per 1,000 persons with diabetes per year in the United States. Over half of these patients develop an infection and 20% require some form of amputation during the course of their malady. The key risk factors of diabetic foot ulceration include neuropathy, deformity and repetitive stress (trauma). The key factors associated with non healing of diabetic foot wounds (and therefore amputation) include wound depth, presence of infection and presence of ischaemia. This manuscript will discuss these key risk factors and briefly outline steps for simple, evidence-based assessment of risk in this population.

The Economic Assessment of Glycemic control and Long-term Effects of diabetes (EAGLE) model was developed to provide a flexible and comprehensive tool for the simulation of the long-term effects of diabetes treatment and related costs in type 1 and type 2 diabetes.

EAGLE simulations are based on risk equations, which were developed using published data from several large studies including the Diabetes Control and Complications Trial, the United Kingdom Prospective Diabetes Study, and the Wisconsin Epidemiological Study of Diabetic Retinopathy. Risk equations for the probability of complications (including hypoglycemia, retinopathy, macular edema, end-stage renal disease, neuropathy, diabetic foot syndrome, myocardial infarction, and stroke) were based on regression analyses, using linear, exponential, and quadratic regression formulae. Subsequent cost calculations are made from the simulated event rates. Internal validation of the EAGLE model was completed by comparing simulated event rates with the published event rates used as the basis for the model.

EAGLE provides microsimulations of virtual patient cohorts for type 1 and type 2 diabetes over n years in 1-year cycles. Complications include microvascular and macrovascular events and death, which are calculated over time as cumulative incidences. Glycosylated hemoglobin levels over time are simulated in relation to treatment regimen. Internal validation demonstrated that each mean event rate simulated by EAGLE overlapped with the published mean event (within a range of +/-10%).

The EAGLE model is an evidence-based, internally valid tool for the assessment of the long-term effects of diabetes treatment and related costs.

Our aim was to see the levels of lipoprotein (a) (Lp (a)) in patients with gangrenous or non-gangrenous diabetic foot lesions. Twenty-two patients with gangrenous foot lesions, 11 with non-gangrenous foot lesions and 10 healthy subjects were included in the study. All the patients had similar glycemic control and duration of diabetes. The main outcome measure was serum Lp (a) levels in both group of patients with diabetes and healthy subjects. Diabetic patients with gangrenous foot lesions had significantly higher Lp (a) levels (83.8+/-8.3 mg/dl) than the patients with non-gangrenous foot lesions (38.3+/-5.8 mg/dl) and healthy subjects (35.6+/-4.2 mg/dl). Lp (a) levels were not significantly different in healthy subjects and in patients with non-gangrenous foot lesions. Lp (a) levels may have a pathogenetic role in the development of gangrenous foot lesions in patients with diabetes mellitus.

To compare the Health Related Quality of Life (HRQL) of French diabetic patients with and without foot ulcers and to determine the factors influencing disease-specific HRQL for those with foot ulcers.

355 diabetic patients, including 239 with foot ulcers (group 1) and 116 without foot ulcers (group 2) were studied in a cross-sectional setting. Socio-demographic and clinical variables were recorded and HRQL was evaluated using a generic HRQL questionnaire (SF-36) for all subjects. For group 1, the severity of foot ulcers was assessed according to Wagner's classification, and disease-specific HRQL assessed using the Diabetes Foot Ulcer Scale (DFS).

HRQL was found to be significantly lower (P = 0.0001) in group 1 than in group 2 for all domains of the SF-36. Independent inverse relationships were found between good HRQL in the DFS domain of Leisure and Wagner grade (OR = 0.136 [0.029-0.467]) as well as the number of foot ulcers (OR = 0.365 [0.191-0.678]). Age was significantly associated with several DFS domains including Daily Activities, Physical Health and Dependence.

Our findings suggest that the number and severity of foot ulcers are associated with patient HRQL, especially in terms of leisure activity disruption and constraints due to treatment. These findings have implications for the evaluation, planning and management of patient care in diabetic foot disease.

Although literature is scarce, it is a common belief that patients with lower social background are more prone to diabetic complications. The purpose of this study was to identify local, systemic, and psychosocial risk factors that can lead to severe foot infections and subsequent amputations.

This study was set up as a case-control study. We enrolled 112 persons with diabetes, in an approximately 1:1 case to control ratio. Cases were defined as patients admitted to the hospital with a severe foot infection, possibly necessitating a lower extremity amputation; controls were patients admitted for nonemergent medical or surgical cause. Study participants received a physical examination and interview to evaluate exposure variables, including demographic data, general medical, surgical, diabetes, and diabetes-related complication history. Socioeconomic status was quantified with the Duncan socioeconomic impact and Siegel prestige score. The patient's knowledge of foot care was evaluated as well. The risks for severe foot infection of social, economical, and physical risk factors were compared in a stepwise logistic regression analysis.

The following variables were significant factors for severe foot infection: history of previous amputation [odds ratio (OR)=19.9, P=.01], peripheral vascular disease (OR=5.5, P=.007), and peripheral neuropathy, as measured with vibratory perception threshold (OR 3.4, P=.044). Social and economic factors were not significant in this model.

These data suggest that physical risk factors are important in foot infection and that the additional risk of socioeconomic status or knowledge of foot care is limited in this population.

The purposes of this study were to determine the effects of tendon Achilles lengthening (TAL) on ambulatory plantar pressures and ankle range of motion, moment, and power, and to determine whether changes in forefoot pressure after treatment of a neuropathic ulcer are related to changes in ankle dorsiflexion range of motion (DFROM) or plantar flexor (PF) power during gait. Pressure and gait tests were performed before treatment, and at 3 weeks and 8 months after treatment in two randomly assigned groups of subjects with diabetes, equinus deformity, and a neuropathic forefoot ulcer treated with TAL and total contact casting (TAL group, n=14), or total contact casting alone (TCC group, n=14). The TAL group had an initial decrease in forefoot peak pressure (PP) (27%), forefoot pressure-time integral (PTI) (42%), PF moment (53%), and PF power (65%), along with an initial increase in rear foot PP (34%), rear foot PTI (48%), and DFROM (74%). Post-surgical changes in rear foot pressure and DFROM were maintained up to 8 months after treatment with TAL, whereas forefoot pressure and PF moment and power increased significantly. Changes in forefoot pressure after treatment in either group were correlated with changes in PF power (r=0.45-0.60), but not with changes in DFROM during gait (r=-0.02-0.08). Results suggest TAL causes a temporary reduction in forefoot pressure primarily by reducing PF power during gait. The initial decrease in forefoot pressure, followed by progressive reloading of forefoot tissues as PF muscles regain strength after TAL, may help reduce the risk of ulcer recurrence in patients with diabetes.

To assess the impact of an educational training program we initiated in 1994 for GPs about diabetic foot ulcer (DFU) management, we compared the rate and level of lower limb amputation (LLA) in diabetic patients performed in our unit between two consecutive five-year periods, 1989-1993 and 1994-1998.

During the first period, 132 patients with 163 lesions (9.2% of the total admissions for diabetes) were compared with 176 with 183 lesions (10.5%) during the second period. Patients' mean age was the same in both periods: 59.6 +/- 11.7 in 1989-1993 and 58.3 +/- 13.1 in 1994-1998 [Not statistically significant, NS].

Patients age, sex ratio, type of diabetes and severity of the lesion (as assessed according to Wagner classification) were essentially the same during the two periods. Most of the foot lesions ( approximately 90%) were purely neuropathic or neuro-ischaemic, with no change in repartition between the two periods. Primary healing was 59.1% in the 1st period and 56.8% in the second. No change in minor and major amputation rate was observed between the 1st period (14.4 and 15.9%, respectively) and the second (11.4 and 16.5%, respectively). The in-hospital mortality rate was unchanged (9.1 vs 8.5%, NS), while the percentage of patients who left hospital against medical advice and dropped out of follow up increased from 1.5 to 6.8% (p<0.04). Mean length of hospitalisation was identical, about 43 days.

In spite of implementing educational program for GPs, no improvement in the DFU management was noted as emphasised by absence of any significant change in amputation rate before (1st period) and after initiating the program (2nd period). These disappointing results can be explained by several factors: weakness of our educational program, lack of motivation from GPs, absence of a structured multidisciplinary prevention approach. The main problem, common to developing countries, remains the insufficiency of financial resources. Moreover, civil disturbances can make the problem more difficult to manage, as in Algeria since 1991.

To determine health care costs associated with pressure ulcers, ulcers of the lower limbs, other chronic ulcers, and venous leg ulcers from the New Mexico Medicaid fee-for-service program perspective.

Retrospective analysis of claims database

Physician visit, hospital, and prescription costs were determined for New Mexico Medicaid patients with a primary and/or secondary diagnosis of 1 of 4 identified categories of skin ulcers from January 1, 1994, through December 31, 1998. Costs were determined in terms of mean and median annual cost per patient and total costs per year. Zero dollar claims were included within the cost calculations. All costs are expressed in 2000-dollar values.

Mean annual physician visit costs per patient ranged from $71 (standard deviation [SD] = $60) for venous leg ulcers in 1998 to $520 (SD = $1228) for pressure ulcers in 1996. Mean annual hospital costs per patient ranged from $266 (SD = $348) for other chronic ulcers in 1998 to $15,760 (SD = $30,706) for pressure ulcers in 1998. Mean annual prescription costs per patient ranged from $145 (SD = $282) for other chronic ulcers in 1998 to $654 (SD = $1488) for pressure ulcers in 1994.

The New Mexico Medicaid fee-for-service system incurred a total cost of approximately $11.6 million (in 2000 dollars) from 1994 through 1998 for the treatment of the 4 categories of skin ulcers studied. The data showed that the majority of wounds were coded as pressure ulcers, which had the highest associated costs.

Our study allowed us to exhaustively list up all the cases of lower limb amputation carried out in the hospitals of the island from May 1st, 2000 to April 30, 2001.

We studied the medical files of all the diabetic patients having undergone a non traumatic amputation and they all had an interview with an inquiring doctor.

406 amputations (including 11 traumatic ones) have been carried out over the 12 months of our study. On a total of 395 non traumatic amputations, 70% were made among diabetics and concerned 278 patients among whom 179 are type 2 diabetics. Men are more concerned than women. If the distribution of amputation levels does not differ between diabetics and non-diabetics, the former more often undergo multiple interventions. 72% of the patients have a level of primary education, 59% have difficulties reading, and most of them have a very limited knowledge on their disease and do not practise any prevention for podologic traumatism.

In a region where 718 220 inhabitants live and where the rate of diabetes prevalence is high (17.7% for 30-69 years), we could be afraid for the years to come of an important increase of the prevalence and diabetes chronic complications incidence rates. Authorities have to become aware of the current risks and of increasing equipments and personnel for the prevention and the follow-up of this insidious pathology. Programmes for the prevention of podologic complications should be supported by taking into account local specificities.

The ability to perceive vibration (vibration detection) has been shown to be a good predictor of the long-term complications of diabetic peripheral neuropathy (DPN). We aimed to estimate the predicted complications and costs for the U.S. health care system associated with reduced vibration detection (vibration perception threshold >or=25 V), estimated using a quantitative sensory testing device.

A Markov model was constructed for a hypothetical cohort of people with DPN. The model was run over a 10-year period using Monte Carlo simulations to estimate disease progression, predicted costs, and complications according to vibration detection levels.

The average individual with reduced vibration detection incurs approximately five times more direct medical costs for foot ulcer and amputations, yields 0.18 fewer quality-adjusted life-years, and lives for approximately 2 months less than an average individual with normal vibration detection.

The treatment of foot ulceration and amputation is time-consuming and expensive. If individuals with reduced vibration detection could be identified, then preventative care could be concentrated on those patients, potentially saving valuable resources and improving health outcomes.

To evaluate the influence of regular chiropodist care on the recurrence rate of diabetic foot ulcers within 1 year.

Ninety-one diabetic outpatients with healed foot ulcers (age 65 +/- 11 years, 40 women and 51 men, diabetes type 1 (n = 6) or 2 (n = 85), BMI 28.5 +/- 4.4, diabetes duration 16 +/- 11 years, HbA(1c) 8.4 +/- 1.6%) were randomized to a group that received monthly remunerated routine chiropodist care (n = 47) or a control group (n = 44).

Within a median follow-up of 386 days, ulceration recurred in 18 patients in the chiropodist group and 25 patients in the control group (hazard ratio [HR] 0.60; 95% CI, 0.32, 1.08; P = 0.09). Analysis of ulceration per foot demonstrated a significant reduction (20 vs. 32 ulcerations; Cox relative risk [Cox RR] 0.52; 95% CI, 0.30, 0.93; P = 0.03) in favor of chiropodist care. Per protocol, analysis of patients who actually underwent chiropodist foot care on a regular basis also indicates the beneficial influence of chiropodist care with ulceration in 13 vs. 30 patients (HR, 0.53; 95% CI, 0.30-1.01; P = 0.05) and in 15 vs. 37 feet (Cox RR, 0.46; 95% CI, 0.24-0.90; P = 0.02) for the intervention and control groups, respectively. Minor amputation was required in two patients in the intervention group and one patient in the control group. Four patients in the control group and two patients in the intervention group died during the trial.

These data suggest that secondary preventive measures by a chiropodist may reduce recurrence of foot ulcers in diabetic patients.

This study was designed to determine the incidence and prevalence of amputations in diabetic Mexican American elders and to identify correlates of lower extremity amputations. Data for this study came from baseline and two follow-up interviews of the Hispanic Established Population for the Epidemiological Study of the Elderly (EPESE) conducted in five southwestern states (Texas, California, New Mexico, Colorado and Arizona) in 1993-1994. Of the 3050 subjects aged 65 and older, 690 reported diabetes, and from these, 60 (8%) reported having at least one lower extremity amputation. Losing a leg was the most common type of amputation (53%). Twelve percent of respondents reported a new amputation and 40% of amputees reported a second amputation during follow-up. Mortality among amputees was 46% during a 5-year follow-up. Multiple logistic regression analysis showed that being male and having eye problems, hip fracture and diabetes for 10 or more years were significantly associated with lower extremity amputations at baseline, whereas obesity, stroke and 10 or more years with diabetes were significantly associated with new amputations at 5-year follow-up. Gender and disease history were associated with lower extremity amputations at baseline and follow-up. These variables may be useful in developing patient education and intervention programs.

Diabetes mellitus is a chronic condition that affects the health of Americans and the US health care system on many levels. According to the American Diabetes Association, approximately 16 million Americans have diabetes mellitus. The onset of type 2 diabetes mellitus, which accounts for the vast majority (90%-95%) of cases, precedes diagnosis by a mean 7 years, with the disease typically manifesting during adulthood. It is not uncommon for people to first realize they have diabetes mellitus due to the appearance of a related complication.

The goal of this analysis was to estimate the direct medical costs of managing microvascular and macrovascular complications of type 2 diabetes mellitus in the United States in the year 2000.

Complication costs were estimated by applying unit costs to typical resource-use profiles. A combination of direct data analysis and cost modeling was used. For each complication, the event costs referred to those associated with the acute episode and subsequent care in the first year. State costs were the annual costs of continued management. Data were obtained from many sources, including inpatient, ambulatory, and emergency department care databases from several states; national physician and laboratory fee schedules; government reports; and literature. All costs were expressed in 2000 US dollars.

Major events (eg, acute myocardial infarction--30,364 dollars event cost, 1678 dollars state cost) generated a greater financial burden than early-stage complica- tions (eg, microalbuminuria--63 dollars event cost, 15 dollars state cost). However, complications that were initially relatively low in cost (eg, microalbuminuria) can progress to more costly advanced stages (eg, end-stage renal disease--37,022 dollars state cost).

Given the scope of diabetes mellitus in the United States and its impact on health care and budgets, it is important for policy makers to have up-to-date information about treatment outcomes and costs. The costs presented here provide essential components for any analysis examining the economic burden of the complications of diabetes mellitus.

To describe ethnic differences in the risk of amputation in diabetic patients with diabetic nephropathy.

A retrospective cohort study was conducted on a national cohort of diabetic patients who received primary care within the Veterans Affairs (VA) Health Care System. Hospitalizations for lower-limb amputations were established by ICD-9-CM procedure codes. Relative risk of amputation in diabetic patients with and without diabetic nephropathy was determined using Cox proportional hazard modeling for unadjusted and adjusted models.

Of the 429,918 subjects identified with diabetes (mean age 64 +/- 11 years, 97.4% male), 3,289 individuals were determined to have had a lower-limb amputation during the study period. Compared with diabetic patients without amputations, amputees were on average older, more likely to belong to a minority group, and were more likely to have received treatment for more comorbid conditions. Asians were more likely to have toe amputations compared with whites or other ethnicities, while Native Americans were more likely to have below-the-knee amputations. Native Americans had the highest risk of amputation (RR 1.74, 95% CI 1.39-2.18), followed by African Americans (RR 1.41, 95% CI 1.34-1.48) and Hispanics (RR 1.28, 95% CI 1.20-1.38) compared with whites. The presence of diabetic nephropathy increased the risk of amputation threefold in all groups. Asian subjects with diabetes had the lowest adjusted relative risk of amputation (RR 0.31, 95% CI 0.19-0.50).

Among diabetic patients, certain ethnic minority individuals have an increased risk of lower-extremity amputation compared with whites. Presence of diabetic nephropathy further increases this risk.

To assess the efficacy of maggot therapy for treating foot and leg ulcers in diabetic patients failing conventional therapy.

Retrospective comparison of changes in necrotic and total surface area of chronic wounds treated with either maggot therapy or standard (control) surgical or nonsurgical therapy.

In this cohort of 18 patients with 20 nonhealing ulcers, six wounds were treated with conventional therapy, six with maggot therapy, and eight with conventional therapy first, then maggot therapy. Repeated measures ANOVA indicated no significant change in necrotic tissue, except when factoring for treatment (F [1.7, 34] = 5.27, P = 0.013). During the first 14 days of conventional therapy, there was no significant debridement of necrotic tissue; during the same period with maggot therapy, necrotic tissue decreased by an average of 4.1 cm(2) (P = 0.02). After 5 weeks of therapy, conventionally treated wounds were still covered with necrotic tissue over 33% of their surface, whereas after only 4 weeks of therapy maggot-treated wounds were completely debrided (P = 0.001). Maggot therapy was also associated with hastened growth of granulation tissue and greater wound healing rates.

Maggot therapy was more effective and efficient in debriding nonhealing foot and leg ulcers in male diabetic veterans than was continued conventional care.

The aim of this study was to assess the efficacy of a preventative foot care programme, applied in a normal outpatient setting to decrease the incidence of foot ulcers in people with diabetes diagnosed as having neuropathy by neuropathy disability score (NDS), in relation to the severity of neuropathy based on the vibration perception threshold (VPT). A structured continuous preventative foot care programme was designed to ensure proper footwear, walking foot hygiene, callus care, nailcutting, water temperature checks, use of warming devices, bathroom surgery, foot care products and self-inspection. Continual foot-care education and treatment, including podiatry, were available. Evaluation was at least every 6 months. Diabetic patients (n=308) with neuropathy (NDS > or =6), 72.3+/-10.7 years old, 45% men, 10.9+/-8.8 years duration of diabetes, and HbA(1c) 6.5+/-1.3%, without a history of foot lesions were recruited over 3 years and followed-up for 4.6 (3-6) years. A low risk group (n=124) had a VPT<25 V while 184 had a VPT > or =25 V (high risk). In all 220 patients (71%) complied with the programme, compliance being 76 and 68% in low and high risk groups. The low risk group developed nine ulcers in nine patients, and the high risk group 24 ulcers in 19 patients. Of these eight and 19 ulcers, respectively, were in the non-compliant patient group, giving relative risk of 22 and eight compared with people attending the programme. Thus compliance with a preventative foot programme reduces the incidence of foot ulceration in people with diabetes with neuropathy. This decrease is relatively greater in patients with less severity of neuropathy. The simple design should be widely generalisable.

To test the applicability of a bedside scoring method for screening for diabetic peripheral neuropathy (DPN) in patients with type 1 diabetes mellitus (DM) in an ambulatory clinic. The prevalence of DPN was estimated and its risk factors identified.

A total of 217 patients (102 males) with type 1 DM, median age 23.4 years (7.5-49 years) and median duration of DM 13.2 years (1-34 years) were evaluated for DPN using the bedside Neuropathy Disability Score (NDS). A score of 3-5 indicated mild DPN, 6-8 moderate DPN and 9-10 severe DPN. The presence of DPN was correlated with possible predictive factors.

The NDS was reliable and highly reproducible. The overall prevalence of DPN was 17.1%: mild in 14.3%, moderate in 2.3%, and severe in 0.5% of patients. The prevalence and severity of DPN were significantly related to long-term glycemic control (p < 0.001), DM duration (p < 0.005), age (p = 0.005), and duration of pubertal DM duration (p = 0.03). The prevalence of DPN was significantly associated with the presence of retinopathy (p < 0.002) and overt proteinuria (p < 0.005).

The NDS is a simple, reliable and reproducible screening method for use in the ambulatory clinic to identify the early signs of DPN, leading to early institution of intensive diabetes control measures and preventive foot care.

Proteases play a critical role in many of the physiologic processes of wound repair. However, if their activity becomes uncontrolled proteases can mediate devastating tissue damage and consequently they have been implicated in chronic wound pathophysiology. Previous studies have shown that chronic wound fluid contains elevated protease levels that have deleterious effects, degrading de novo granulation tissue and endogenous biologically active proteins such as growth factors and cytokines. Therefore, we have proposed that an effective therapeutic approach for chronic wounds would be to modify this hostile environment and redress this proteolytic imbalance. Using an ex vivo wound fluid model, we show the ability of a proprietary new wound treatment to bind and inactivate proteases. We have shown that the addition of this test material to human chronic wound fluid obtained from diabetic foot ulcer patients resulted in a significant reduction in the activities of neutrophil-derived elastase, plasmin, and matrix metalloproteinase when compared to wet gauze. This study provides mechanistic evidence to support the hypothesis that this novel treatment modality for chronic wounds physically modifies the wound microenvironment, and thereby promotes granulation tissue formation and stimulates wound repair.

The Objective of this study was to determine whether peak expiratory flow rate is a predictor of complications of diabetes. Peak expiratory flow rate was measured at the 10-year follow-up (third examination) of a cohort of persons with younger-onset diabetes. The relationships of progression of diabetic retinopathy by two steps, progression to proliferative retinopathy and of incidences of macular edema, sore or ulcers on feet or ankles, lower extremity amputation, proteinuria, and cardiovascular disease 4 years after this examination with respect to peak expiratory flow rate were evaluated. Study procedures including measurements of blood pressure, height and weight, grading of fundus photographs, peak expiratory flow rate, urinalysis, and medical history were performed according to standard protocols. Peak expiratory flow rate was not associated in univariate analyses with progression of retinopathy, incidences of proliferative retinopathy, macular edema or lower extremity amputation, sores or ulcers on feet or ankles, gross proteinuria, or self-reported cardiovascular disease. However, when using multivariable models to include the effects of other risk factors, peak expiratory flow rate was significantly associated with the combined incidences of sores or ulcers on feet and ankles, or lower extremity amputations (OR=0.61, 95% CI 0.42-0.88). These data suggest that peak expiratory flow rate is a predictor of subsequent complications in the lower extremities in those with long duration of younger-onset diabetes. Evaluating this association in an incipient cohort would illuminate whether the relationship we found is likely to be causal.

Starting from identical patients with type 2 diabetes, we compared the 20-year predictions of two computer simulation models, a 1998 version of the IMIB model and version 2.17 of the Global Diabetes Model (GDM). Primary measures of outcome were 20-year cumulative rates of: survival, first (incident) acute myocardial infarction (AMI), first stroke, proliferative diabetic retinopathy (PDR), macro-albuminuria (gross proteinuria, or GPR), and amputation. Standardized test patients were newly diagnosed males aged 45 or 75, with high and low levels of glycated hemoglobin (HbA(1c)), systolic blood pressure (SBP), and serum lipids. Both models generated realistic results and appropriate responses to changes in risk factors. Compared with the GDM, the IMIB model predicted much higher rates of mortality and AMI, and fewer strokes. These differences can be explained by differences in model architecture (Markov vs. microsimulation), different evidence bases for cardiovascular prediction (Framingham Heart Study cohort vs. Kaiser Permanente patients), and isolated versus interdependent prediction of cardiovascular events. Compared with IMIB, GDM predicted much higher lifetime costs, because of lower mortality and the use of a different costing method. It is feasible to cross-validate and explicate dissimilar diabetes simulation models using standardized patients. The wide differences in the model results that we observed demonstrate the need for cross-validation. We propose to hold a second 'Mt Hood Challenge' in 2001 and invite all diabetes modelers to attend.

The aim of the study was to find factors predicting lower extremity amputation in patients with type 1 or type 2 diabetes mellitus through a 7-year follow-up period.

Follow-up study.

Altogether 733 diabetic patients. aged 10-79 years, were drawn from the national drug reimbursement register.

At baseline, the patients underwent a podiatric, circulatory and neurophysiological examination. Seven years later a follow-up study was performed based on clinical and register data. Patient data for those who died during the follow-up were collected from hospital records and death certificates. All amputations were recorded. The patients with amputation were compared with the other patients and also, in a case-control manner, by taking three nonamputated patients matched by sex, type of diabetes, and age for each patient with amputation.

The number of amputations was 25 in the sample. Compared with all patients without amputation, patients with amputation differed in altogether 24 variables concerning diabetes and its complications. Compared with the matched non-amputated patients, the amputated patients had longer duration of diabetes, lower ankle/brachial pressure index (ABI), more often history of retinopathy, nephropathy, and hypertension, more often visual handicap, elevated serum creatinine level, abnormal neurophysiological indices and electrophysiological findings. In the logistic regression analysis, vibration perception threshold, low ABI, history of retinopathy, visual handicap, and male sex were independently associated with lower extremity amputation.

Lower extremity amputations were strongly associated with retinopathy, nephropathy, and neuropathy. The presence of any of these complications should lead to intensified actions in order to prevent amputations. As far as arterial circulation is concerned, claudication or absent peripheral pulses were not good predictors of amputation, whereas low ABI, despite its known weaknesses, was a reliable indicator of future amputation.

To investigate factors predisposing to recurrent foot ulceration in patients with diabetes mellitus.

Two groups of patients who had attended a specialist Diabetes Foot Centre were assessed: relapsers (n = 26), whose foot ulceration had recurred at least twice, and nonrelapsers (n = 25), whose initial ulcer had not recurred for at least 2 years.

In the relapser group 10/26 patients waited at least 24 h before reporting symptoms compared with only 2/25 in the nonrelapser group (P < 0.05). Vibration perception threshold (volts) was 38 +/- 12 (mean +/- SD) in relapsers compared with 25 +/- 13 in nonrelapsers (P < 0.005). Cold perception threshold (degrees C) was 9.1 +/- 4.6 in relapsers compared with 5.1 +/- 3.5 in nonrelapsers (P<0.005). HbA1c (%) was significantly raised at 8.5 +/- 1.7 in relapsers compared with 7.6 +/- 1.2 in nonrelapsers (P = 0.03). Alcohol intake was 0.5 (median, interquartile range 0-2) units per day in relapsers compared with 0.0 (median, interquartile range 0-0.25) units in nonrelapsers (P = 0.04). Smoking habits, housing conditions, visual acuity, threshold for warm perception and the Doppler pressure index were not significantly different in the two groups.

Patients who develop recurrent foot ulceration delay in reporting symptoms, when compared with diabetic patients whose foot ulceration does not recur. The relapsers also have evidence of poorer glycaemic control, more neuropathy and increased alcohol intake.

Prevention and care of diabetic foot complications continue to represent a major challenge to the treating clinician. Neuropathy, infection, deformity, and vascular insufficiency threaten the diabetic foot and the overall functional well being of the diabetic patient. Although foot problems in diabetes cannot be eradicated completely, the opportunity exists to diagnose and manage diabetic foot conditions effectively, to educate and motivate patients to care for their feet, to minimize complications, and to decrease health care costs.

Medical and pharmaceutical insurance claims associated with lower extremity diabetic ulcers were examined retrospectively to better understand the costs and duration of treatment in clinical practice. The study population consisted of working-age individuals (18 to 64 years old) with health care benefits provided through private employer-sponsored insurance plans. Diagnostic information contained in the claims database was used to identify the severity of the ulcers, and the charges associated with treatment were based on claims data. Claims for lower extremity ulcers were found in 5.1% of individuals with diabetes. Although many lower extremity ulcers heal with standard treatment, some are more resistant to treatment and require costly ongoing medical care. Almost half of these cases were associated with deep infection, osteomyelitis, or amputation. Total payments for treatment of lower extremity ulcers in this population averaged $2687 per patient per year, or $4595 per ulcer episode, with inpatient expenditures accounting for more than 80% of these costs. Costs were significantly higher for patients with more severe ulcers or with inadequate vascular status in the affected limb. We concluded that lower extremity ulcers occur in a large number of working-age people with diabetes and contribute significantly to the morbidity associated with this disease. The high cost of treating diabetic foot ulcers suggested by this analysis argues for the development of better treatment strategies and outcomes assessments for these patients.

The purpose of the study was to assess the prevalence of foot (pre-)ulcers and their determinants in type II diabetic patients in a primary health care setting. Six hundred and nine patients (246 men, mean age 64.8 (range, 40-94) years, diabetes duration, 4.3 (0-44.9) years) from 22 general practices attended a regional shared care project in Amsterdam. At first visit all patients were examined by a podiatrist. Amputations, active fool ulcers (Wagner stage 1 or 2) and pre-ulcers (Wagner stage 0, hard skin with or without macerating changes) were recorded in 0 (0%), 11 (1.8%) and 79 (12.9%) patients, respectively. In multivariate logistic regression analysis, after adjustment for age and gender, diabetes duration, cigarette smoking, peripheral vascular disease (assessed by calculating ankle/brachial index), sensory neuropathy (by Semmes-Weinstein monofilament 5.07), dry feet and severe hammer toes were independently and significantly associated (pre-)ulceration. In conclusion, one of every seven type II diabetic patients in primary health care has a foot (pre-)ulcer. Patients at risk for foot ulceration can be identified by inspection and the use of simple instruments.

Between 1993 and 1995, 93 neuropathic diabetes mellitus patients with foot ulcers underwent a total contact cast (TCC) protocol. A randomly chosen group of 21 patients (Group I) demonstrated ulcer healing in a mean time of 43.5 days. Despite 9 weeks of TCC, 15 patients (Group II) with forefoot ulcers failed to heal. Physical examination of Group I revealed plantarflexion/dorsiflexion range of motion of the ankle of 33.8 degrees / 1.9 degrees compared to 32.3 degrees / -10.5 degrees of Group II, demonstrating an ankle equinus deformity and limited joint motion. Group II patients underwent a correction of the equinus deformity with percutaneous tendo-Achilles lengthening (TAL), followed by a TCC. All but one ulcer (93.3%) healed within 39.4 days. Four (19.0%) ulcers recurred (at the same site) in Group I, compared to none in Group II at the latest follow up of 17.3 months. Surgical correction with percutaneous TAL and TCC results in healing of forefoot ulcer and helps prevent ulcer recurrence.

The prevalence of peripheral vascular disease (PVD) was assessed in terms of ankle/brachial index by doppler studies in a large cohort of non-insulin-dependent diabetes mellitus (NIDDM) patients in South India. One hundred and ninety-two out of 4941 patients (3.9%) had evidence of PVD. There was a slight female excess in PVD patients. There was a linear increase in prevalence of PVD with increasing duration of diabetes. Multiple logistic regression analyses showed that serum cholesterol, serum creatinine, systolic BP, duration of diabetes and ishaemic heart disease are strong predictive factors for PVD. The prevalence of PVD in South Indians is lower than that reported in European populations.