Category: Home

Chronic hyperglycemia and foot ulcers

Chronic hyperglycemia and foot ulcers

Symptoms and hgperglycemia Chronic hyperglycemia and foot ulcers Risk factors Treatment Hypreglycemia When to see your doctor Outlook Some diabetes symptoms, like poor circulation and high blood sugar, lucers lead to ulcers, especially on your feet. A key step Metabolism boosting drinks recipes Chronic hyperglycemia and foot ulcers membrane degradation involves increased doot activator Vitamin B for energy production, resulting in conversion of plasminogen to plasmin and subsequently in degradation of fibronectin and laminin and activation of matrix metalloproteinases. Diabetic foot complications stem from intricate interactions between macrovascular and microvascular changes, neuropathy, inflammation, immune responses, hyperglycemia, oxidative stress, and infection susceptibility. Lefrandt JD, Bosma E, Oomen PH, et al. Rates of diabetes-related major amputations among racial and ethnic minority adults following Medicaid expansion under the Patient Protection and Affordable Care Act. Ulcers may take longer to heal if your blood sugar is high and constant pressure is applied to the ulcer.

Chronic hyperglycemia and foot ulcers -

Native Americans, African Americans, Hispanics and older men are more likely to develop ulcers. People who use insulin are at a higher risk of developing a foot ulcer, as are patients with diabetes-related kidney, eye, and heart disease. Being overweight and using alcohol and tobacco also play a role in the development of foot ulcers.

Ulcers form due to a combination of factors, such as lack of feeling in the foot, poor circulation, foot deformities, irritation such as friction or pressure , and trauma, as well as duration of diabetes. Patients who have diabetes for many years can develop neuropathy, a reduced or complete lack of ability to feel pain in the feet due to nerve damage caused by elevated blood glucose levels over time.

The nerve damage often can occur without pain and one may not even be aware of the problem. Your podiatric physician can test feet for neuropathy with a simple and painless tool called a monofilament.

Once an ulcer is noticed, seek podiatric medical care immediately. Foot ulcers in patients with diabetes should be treated for several reasons:.

The primary goal in the treatment of foot ulcers is to obtain healing as soon as possible. The faster the healing of the wound, the less chance for an infection. Not all ulcers are infected; however, if your podiatric physician diagnoses an infection, a treatment program of antibiotics, wound care, and possibly hospitalization will be necessary.

These devices will reduce the pressure and irritation to the ulcer area and help to speed the healing process. The science of wound care has advanced significantly over the past ten years.

We know that wounds and ulcers heal faster, with a lower risk of infection, if they are kept covered and moist. The use of full-strength betadine, peroxide, whirlpools and soaking are not recommended, as this could lead to further complications.

Appropriate wound management includes the use of dressings and topically-applied medications. These range from normal saline to advanced products, such as growth factors, ulcer dressings, and skin substitutes that have been shown to be highly effective in healing foot ulcers.

For a wound to heal there must be adequate circulation to the ulcerated area. Your podiatrist may order evaluation test such as noninvasive studies and or consult a vascular surgeon. Tightly controlling blood glucose is of the utmost importance during the treatment of a diabetic foot ulcer.

Working closely with a medical doctor or endocrinologist to accomplish this will enhance healing and reduce the risk of complications. A majority of noninfected foot ulcers are treated without surgery; however, when this fails, surgical management may be appropriate.

Healing time depends on a variety of factors, such as wound size and location, pressure on the wound from walking or standing, swelling, circulation, blood glucose levels, wound care, and what is being applied to the wound.

Healing may occur within weeks or require several months. The best way to treat a diabetic foot ulcer is to prevent its development in the first place. Recommended guidelines include seeing a podiatrist on a regular basis. He or she can determine if you are at high risk for developing a foot ulcer and implement strategies for prevention.

Salient wound- and foot-specific factors considered in the evaluation of DFU are wound size and depth, presence and severity of infection, presence of PN or PAD, and ulcer location Classification systems aim to standardize wound evaluation, communicate wound and patient characteristics between providers and across time, guide prognostication and clinical decision-making, and facilitate generalizable research on interventions and outcomes.

There are several classification schemas frequently applied to DFU Table 1 , but no prevailing gold standard exists 20 , Available resources, patient population, practice setting, and intended use generally determine which classification system is applied One recently developed system widely used in multidisciplinary diabetic foot care settings is the Society Society for Vascular Surgery Wound, Ischemia, and foot Infection WIfI classification system Table 1 21 , which, in addition to characterizing and risk stratifying DFU, was designed to guide clinical decision-making about the potential benefit of revascularization Fig.

WIfI has been extensively validated and has prognostic utility for outcomes including wound healing rates and risk of amputation 21 , Society for Vascular Surgery WIfI classification, amputation risk stratification, and benefit of revascularization. Adapted from Mills et al. Description and summary of benefits and limitations for common existing diabetic foot and limb classification systems.

IWGDF, International Working Group on the Diabetic Foot, an international panel of experts including podiatrists, diabetologists, infectious disease specialists, and surgeons; LEA, lower-extremity amputation; LOPS, loss of protective sensation.

Reported incidence of DFU varies widely depending on the study design, the population, and the era. In series since , annual incidence generally ranges from 0.

Recent data on relative incidence in type 1 versus type 2 diabetes are conflicting 10 , 17 , and differences in DFU risk between populations of type 1 and type 2 diabetes will be strongly determined by differences in age and duration of diabetes.

The International Diabetes Foundation estimates that 40 million to 60 million people globally are affected by DFU 1 , a marked increase from estimates that ranged from 9 million to 26 million. Like incidence, prevalence estimates vary widely and are influenced by differences in definitions of DFU, the approach to surveillance, completeness of follow-up, and the definition of and approach to defining diabetes denominator A recent meta-analysis found a 6.

Patterns of DFU prevalence have remained stable despite fluctuations in incidence 4. There is a relative paucity of high-quality population-based studies of DFU incidence and prevalence. More community-based large-scale epidemiologic studies are needed to better characterize the frequency, clinical course, and risk factors for DFU, but clinical and demographic factors that have been strongly associated with DFU in the existing literature will be reviewed here.

Both patient- and foot-specific factors contribute to the risk of DFU Fig. Demographic, socioeconomic, and access-to-care factors are also strongly related to DFU and its complications 33 — Studies including adults with both type 1 and type 2 diabetes suggest that risk factors for DFU are similar 17 , and the factors described below apply to both type 1 and type 2 diabetes unless otherwise stated.

The risk of DFU increases with age, which is closely related to longer duration of diabetes, the cumulative effects of hyperglycemia, and a higher prevalence of micro- and macrovascular complications 30 , 37 , Young and middle-aged adults with DFU tend to present with more advanced ulcer stage and are more likely to have foot infection, hospitalization, and ulcer recurrence than older adults treated in similar settings 39 , Higher HbA 1c and higher rates of PN and smoking found in young adults with diabetes may account for some of these differences 39 , The incidence of DFU is approximately 1.

The incidences of minor and major amputation are also higher among men, with risk estimates for men ranging from 1. Sex differences are likely explained by underlying risk factors, access to care, screening, and adherence to treatment.

Men with diabetes have a higher prevalence of PN, PAD, and cardiovascular disease 45 , which together account for a majority of observed sex differences in DFU risk Black, Hispanic, and other non-White groups experience a much higher burden of diabetes than White adults, including a higher burden of DFU 35 , Socioeconomic and geographic disparities overlap heavily with racial and ethnic disparities in DFU, and the independent effects of these factors are difficult to separate 47 — Unequal access to care manifests in increased risk of incident DFU Likelihood of advanced-stage ulcer at diagnosis and risk of hospitalization for DFU are higher among Black and Hispanic adults 26 , 36 , 49 , individuals in the lowest-income categories 48 , those with less comprehensive or no insurance 36 , 48 , those with lower education levels 33 , and those who live in socioeconomically deprived neighborhoods 36 , 48 , Black and Hispanic adults presenting with infection and ischemia are less likely to undergo revascularization than White patients 52 , 53 , and racial minorities and people without insurance are more likely to undergo early within 1 year minor or major amputation after incident DFU than White people or people with private insurance 49 , 54 , These findings suggest that disparities in access to care and biases in practice patterns may each contribute to unequal outcomes 26 , 49 , 50 , 56 , High rates of lower-extremity amputation and mortality tend to cluster both within neighborhoods and by region 34 , 47 , 58 , 59 , almost always corresponding to areas with a high density of economically deprived and racial and ethnic minority populations This layering disadvantage is the consequence of racialized segregation, lack of economic opportunity, and unequal health care that characterize structural racism Despite significant overlap, racial and ethnic differences in outcomes are not fully attenuated by controlling for socioeconomic or geographic factors 47 , 48 , While risk for poor outcomes is compounded in people with more than one minority or disadvantaged group status e.

Some patterns, such as unequal revascularization rates in people with ischemic DFU, have been shown to widen among the highest-income Black and White adults These findings reflect gaps in our ability to measure racial biases within the health system.

Geographic variation in lower-extremity outcomes is well established and is closely linked to socioeconomic status. In the U. and U. Differential access to preventive and specialty care 59 , 61 , financial constraints that delay presentation 62 , and provider-specific practices in limb preservation 54 likely contribute to geographic disparities and to worse outcomes in minority and rural populations 49 , Some health system-based measures, including managed care plans and Medicaid expansion, have demonstrated modest narrowing of disparities in DFU morbidity 26 , 63 , although dedicated research on interventions to specifically address disparities is lacking.

The cumulative burden of hyperglycemia and its causal relationship with microvascular complications are well established Chronically elevated HbA 1c is an independent risk factor for DFU and for amputation and mortality following DFU Maintaining a lower HbA 1c delays the progression of microvascular complications of diabetes 65 , 66 and is associated with decreased risk of amputation in adults with type 1 and type 2 diabetes Secondary analyses and extended follow-up of landmark trials show dose-response associations between HbA 1c and risk of incident DFU and amputation The association of obesity with incident DFU has not been consistently demonstrated, and obesity is not associated with incident or recurrent DFU, amputation, or mortality in several recent systematic reviews 30 , 38 , 41 , In patients who develop DFU, underweight BMI has been linked to an increased risk of amputation and mortality in population- and hospital-based studies 17 , 41 , likely reflecting higher rates of frailty and poor nutrition in the underweight population.

Smoking is associated with an increased risk of PN in adults with diabetes and is an extremely strong risk factor for PAD Several studies report strong associations of smoking with incident DFU 30 , longer healing time, higher rates of nonhealing DFU 18 , and a subsequent 1.

Prospective cohorts demonstrate bidirectional associations between DFU and cardiovascular disease, with incident DFU associated with faster progression of cardiovascular disease 69 , and even subclinical cardiovascular disease conferring increased risk of DFU Cardiovascular disease is also associated with delayed healing and a higher risk of amputation and mortality 4 , DFU and cardiovascular disease are both markers of diabetes severity and duration, and they act synergistically on physiologic e.

Aggressive management of cardiovascular risk factors is a central goal of multidisciplinary diabetes care and has been shown to decrease risk of DFU occurrence and reduce mortality in people who develop DFU Diabetes is a leading global cause of chronic kidney disease CKD and the most common cause of end-stage kidney disease Black and Hispanic adults and low-income groups have much higher rates of CKD than White and middle- or high-income groups End-stage kidney disease and CKD are linked to higher risk of incident DFU, longer healing time, higher ulcer recurrence rates, and higher rates of lower-extremity amputation 76 , These associations are strong enough to warrant inclusion of CKD in expert definitions of an at-risk foot even for people without prior DFU or structural deformity.

For people with kidney disease, end-stage kidney disease on hemodialysis confers the greatest risk of DFU The high prevalence of CKD among racial and ethnic minorities and socioeconomically disadvantaged people contributes to the disproportionate burden of DFU morbidity in these populations.

There is a strong association between the presence and severity of diabetic retinopathy and DFU. Diabetic retinopathy occurs at two- to fourfold higher rates among adults with DFU than in those without Visual impairment secondary to retinopathy may worsen gait instability and increase risk of foot trauma in those with PN, which can precipitate DFU formation 78 , although the causal mechanisms have not been definitively established.

Both DFU and retinopathy are likely signs of advanced microvascular disease that may partially explain this association.

Ulcer healing is defined as complete epithelialization of a previously ulcerated site Time from diagnosis to wound healing and overall rates of healing differ widely based on ulcer etiology, size, presence of infection, and patient characteristics, with median healing times ranging from 3 months to more than 12 months 7 , Ischemic ulcers, larger and deeper ulcers, plantar ulcers, and ulcers with infection are associated with poor or prolonged healing 7 , 18 , 81 , In addition to wound- and patient-level risk factors described previously, nonambulatory status is associated with prolonged healing and lower amputation-free survival 7 , There is currently no validated predictive model for DFU healing that includes both patient and wound factors.

The strongest clinical predictor of developing a DFU is a prior DFU or amputation 2. Recurrence is the occurrence of an ulcer, either at the site of a prior ulcer or at another site, after complete healing 5.

Contralateral lower-extremity amputation independently increases ulcer recurrence by two- to threefold and shortens the average interval to ulcer recurrence 84 , presumably due to gait alterations. Other factors consistently associated with recurrence are similar to those for nonhealing, although PAD has not been shown to be a strong influence on DFU recurrence despite its effects on primary healing Infection is a primary driver of emergency department visits and hospitalization in patients with diabetes and with DFU specifically 86 , Foot ulcer precedes the vast majority of diabetic foot infections, with higher risk of infection in recurrent wounds, long-standing wounds, and wounds that probe to bone, as well as among patients with recent history of prior non—foot infection 70 , 85 , Diabetes is the leading risk factor for lower-extremity amputation in U.

adults, with an estimated , diabetes-related major or minor amputations per year Overall diabetes-related amputations decreased steadily over the s and s despite rising diabetes prevalence. Over the same time, minor amputation made up an increasing proportion of these amputations, corresponding to higher rates of lower-extremity revascularization procedures; these trends are thought to represent improved efforts at limb preservation 91 , The overall resurgence in severe morbidity appears to disproportionately affect younger adults and Black and Hispanic groups 42 , 53 , 55 , 94 , which is particularly concerning given the already wide inequities in care for racial and ethnic minorities.

Even controlling for DFU incidence, Black and Hispanic adults have lower rates of attempted revascularization, higher rates of failed limb preservation, and higher risk of amputation than White adults 49 , 50 , 52 , Amputation is a late-stage complication of poor long-term diabetes management, and it often reflects inadequate access to, delivery of, and uptake of diabetes care.

The compounding effects of socioeconomic disadvantage, other social determinants of health, and structural racism on marked disparities in amputation rates by race, ethnicity, and socioeconomic status cannot be overstated 35 , Survival in people with incident DFU is significantly worse compared with that of similar people with diabetes without foot complications 2 , A recent meta-analysis comprising almost , patients in 16 countries reported mortality rates of Diabetes care in the U.

These numbers likely underestimate the true economic burden of DFU given out-of-pocket expenses, loss of productivity, and decreased employment associated with DFU Prevention and management of diabetic foot complications is a centerpiece of diabetes care. A discussion of best-practice diabetes care is beyond the scope of this review, but many DFU-associated metabolic and cardiovascular risk factors are modifiable in early stages and are addressed by clinical guidelines and Europe Delayed ulcer presentation predicts poor prognosis 7 , 54 , Frequent foot exams are fundamental to decreasing incidence and morbidity, and inadequate foot care is associated with higher rates of DFU, LEA, and mortality , Guidelines for frequency of screening for PN, PAD, and DFU or other preulcerative lesions in the adults with diabetes Table 2 recommend at least an annual comprehensive foot exam for all patients with diabetes, including inspection, monofilament and tuning fork evaluation for loss of protective sensation, and pulse exam 1 , Screening exams should be performed every 3—6 months for high-risk patients The importance of multidisciplinary foot care for high-risk people deserves particular emphasis, especially the involvement of podiatry and vascular surgery Rates of annual foot exams by a provider in adults with diabetes vary widely Certain racial and ethnic minority populations e.

The implementation of a hemodialysis center-based monthly foot screening in a U. Routine foot screening is critical and low rates of adherence to standards of care for preventing diabetic foot infections is a major concern. Several promising technologies may aid in the early detection of preulcerative or ulcerative foot lesions.

Telemedicine-assisted foot examinations have been shown in small studies to be as effective as in-person provider exams at detecting early lesions, with time and cost savings to patients that have promise to reduce existing barriers to care 62 , Increased temperature is a well-validated preulcerative sign, and clinical trials of temperature-sensing mats and socks have been successful in identifying preulcer or DFU weeks earlier than a clinical exam.

These passive surveillance technologies may be able to reduce incident DFU through alerts to offload pressure points temporarily or by prompting a thorough foot evaluation. Additional pressure-sensing modalities including insoles may help risk-stratify people with high plantar pressures, monitor for effective offloading before or during DFU episodes, and evaluate progress in gait retraining after DFU healing or amputation Despite compelling evidence supporting their efficacy and cost effectiveness, these technologies have not been widely adopted.

The detrimental effect of DFU on overall health status and quality of life is well documented, and patient-reported outcomes are increasingly recognized as meaningful measures in diabetic foot care , People with DFU typically report poor quality of life, primarily in the domain of physical functioning.

Persistent ulcers, major amputation, and limited ambulation are associated with worse quality of life for both patients and their caregivers , Healing, including after minor amputation, is associated with dramatic improvement in self-reported physical functioning, and people with healed DFU have overall self-reported quality of life near the norms for populations without diabetes Though qualitative studies consistently identify fear, anxiety, frustration, isolation, and sadness as common emotional responses to the diagnosis of DFU, few studies have demonstrated differences in psychosocial quality of life related to DFU DFU-specific measures have been proposed to better assess the social and emotional consequences of active ulcers and should be considered when evaluating patient-reported outcomes.

DFU is a common complication of diabetes that has been aptly compared with cancer in terms of chronicity, recidivism, cost, and burden Major clinical risk factors for DFU are PN, PAD, and foot deformities, but race, ethnicity, socioeconomic status, and geography are powerful mediators of risk for DFU and lower-extremity amputation.

The consequences of first ulceration—poor quality of life, recurrence, major amputation, and death—are significant, but this morbidity is not reflected in the funding allocated for DFU-related research, which totals less than 0.

Complications of DFU can be attenuated by guideline-directed screening, early diagnosis, and aggressive medical management of diabetes and cardiovascular disease. Ineffective population-based screening, limited access to preventive care, and delays in access to diabetes, vascular, and podiatry specialist care contribute to late-stage ulcer presentation and, thus, to poor prognosis.

Rising lower-extremity amputation rates among young and middle-aged adults with diabetes and persistent racial, ethnic, and socioeconomic disparities reflect these gaps in care. Major efforts are needed to develop health system-wide improvements in DFU prevention and early diagnosis, especially in disadvantaged populations.

Funding should be prioritized for high-quality population-based registries to track DFU incidence, prevalence, outcomes, and process measures. Initiatives to expand use of effective at-home screening modalities and allocate resources for more frequent provider foot exams in regions where major amputation rates are high have the potential to reduce DFU incidence and morbidity in the most at-risk populations.

Dedicated research on racial and socioeconomic differences in timing of care, limb preservation, and amputation are necessary to identify and address factors perpetuating structural bias and disparate outcomes.

Significantly more public and institutional funding for DFU research and care initiatives is warranted to correct the imbalance between current resource allocation and the enormous burden of DFU.

Ultimately, a paradigm shift toward DFU prevention and health equity is required to produce meaningful reductions in DFU, major lower-extremity amputation, and mortality.

We acknowledge the contributions of Caroline Wang Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD and Alana Keegan Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD in creating and editing figures and tables.

was supported by National Institutes of Health NIH National Institute of Diabetes and Digestive and Kidney Diseases NIDDK grant K23 DK was supported by NIH National Heart, Lung, and Blood Institute grant K24 HL This work was also supported by NIH NIDDK grant R01 DK to L.

Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. completed literature review and wrote the manuscript. and A. reviewed and edited the manuscript.

and C. were involved in the conception of this work and reviewed and edited the manuscript. All authors approved of the final version of the manuscript. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care.

Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 46, Issue 1. Previous Article Next Article. Presentation, Etiology, and Characterization of Diabetic Foot Ulcers. Wound Classification and Staging.

Epidemiology of Diabetic Foot Ulcers. Risk Factors for DFU and Associated Morbidity. Morbidity and Mortality Related to DFU. Economic Burden of DFU. Primary and Secondary Prevention of DFU. Quality of Life and Functional Impact of DFU. Article Information. Article Navigation. Review December 22 Etiology, Epidemiology, and Disparities in the Burden of Diabetic Foot Ulcers Katherine McDermott X.

Katherine McDermott. This Site. Google Scholar. Michael Fang ; Michael Fang. Andrew J. Boulton ; Andrew J. Elizabeth Selvin Elizabeth Selvin. Caitlin W. Hicks Corresponding author: Caitlin W.

Hicks, chicks11 jhmi. Diabetes Care ;46 1 — Article history Received:. Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Graphical Abstract View large Download slide.

View large Download slide. Figure 1. Figure 2. Person- and foot-specific factors interact to promote DFU risk and poor clinical outcomes.

Figure 3. Table 1 Description and summary of benefits and limitations for common existing diabetic foot and limb classification systems.

Assigns a clinical stage that estimates risk of amputation from 1 very low to 4 very high based on the combination of these factors stage 5: unsalvageable limb. Extensively validated in diverse settings where data may be limited Unique in its inclusion of ulcer location High scores predictive of healing and LEA Has broad applications for use in population-based studies or resource-poor settings Dichotomized variables limit assessment of change over time or of the relative contribution of severe features e.

Assigns 1 present or 0 absent for location, ischemia, peripheral neuropathy, infection, area, and depth.

Department of Plastic and Reconstructive Surgery, Body fat calipers for athletes of Medicine, Ulcees Catholic University of Korea, Seoul, Korea. Corresponding author: Fooot Chronic hyperglycemia and foot ulcers Kim, MD, PhD Department of Plastic and Reconstructive Surgery, Yeouido St. Diabetic foot complications stem from intricate interactions between macrovascular and microvascular changes, neuropathy, inflammation, immune responses, hyperglycemia, oxidative stress, and infection susceptibility. Macrovascular factors like atherosclerosis lead to tissue ischemia, while microvascular dysfunction worsens perfusion deficits. Neuropathy contributes significantly to such complications, causing sensory loss, motor problems, and autonomic dysfunction.

Chronic hyperglycemia and foot ulcers -

One recently developed system widely used in multidisciplinary diabetic foot care settings is the Society Society for Vascular Surgery Wound, Ischemia, and foot Infection WIfI classification system Table 1 21 , which, in addition to characterizing and risk stratifying DFU, was designed to guide clinical decision-making about the potential benefit of revascularization Fig.

WIfI has been extensively validated and has prognostic utility for outcomes including wound healing rates and risk of amputation 21 , Society for Vascular Surgery WIfI classification, amputation risk stratification, and benefit of revascularization.

Adapted from Mills et al. Description and summary of benefits and limitations for common existing diabetic foot and limb classification systems. IWGDF, International Working Group on the Diabetic Foot, an international panel of experts including podiatrists, diabetologists, infectious disease specialists, and surgeons; LEA, lower-extremity amputation; LOPS, loss of protective sensation.

Reported incidence of DFU varies widely depending on the study design, the population, and the era. In series since , annual incidence generally ranges from 0. Recent data on relative incidence in type 1 versus type 2 diabetes are conflicting 10 , 17 , and differences in DFU risk between populations of type 1 and type 2 diabetes will be strongly determined by differences in age and duration of diabetes.

The International Diabetes Foundation estimates that 40 million to 60 million people globally are affected by DFU 1 , a marked increase from estimates that ranged from 9 million to 26 million.

Like incidence, prevalence estimates vary widely and are influenced by differences in definitions of DFU, the approach to surveillance, completeness of follow-up, and the definition of and approach to defining diabetes denominator A recent meta-analysis found a 6.

Patterns of DFU prevalence have remained stable despite fluctuations in incidence 4. There is a relative paucity of high-quality population-based studies of DFU incidence and prevalence. More community-based large-scale epidemiologic studies are needed to better characterize the frequency, clinical course, and risk factors for DFU, but clinical and demographic factors that have been strongly associated with DFU in the existing literature will be reviewed here.

Both patient- and foot-specific factors contribute to the risk of DFU Fig. Demographic, socioeconomic, and access-to-care factors are also strongly related to DFU and its complications 33 — Studies including adults with both type 1 and type 2 diabetes suggest that risk factors for DFU are similar 17 , and the factors described below apply to both type 1 and type 2 diabetes unless otherwise stated.

The risk of DFU increases with age, which is closely related to longer duration of diabetes, the cumulative effects of hyperglycemia, and a higher prevalence of micro- and macrovascular complications 30 , 37 , Young and middle-aged adults with DFU tend to present with more advanced ulcer stage and are more likely to have foot infection, hospitalization, and ulcer recurrence than older adults treated in similar settings 39 , Higher HbA 1c and higher rates of PN and smoking found in young adults with diabetes may account for some of these differences 39 , The incidence of DFU is approximately 1.

The incidences of minor and major amputation are also higher among men, with risk estimates for men ranging from 1.

Sex differences are likely explained by underlying risk factors, access to care, screening, and adherence to treatment. Men with diabetes have a higher prevalence of PN, PAD, and cardiovascular disease 45 , which together account for a majority of observed sex differences in DFU risk Black, Hispanic, and other non-White groups experience a much higher burden of diabetes than White adults, including a higher burden of DFU 35 , Socioeconomic and geographic disparities overlap heavily with racial and ethnic disparities in DFU, and the independent effects of these factors are difficult to separate 47 — Unequal access to care manifests in increased risk of incident DFU Likelihood of advanced-stage ulcer at diagnosis and risk of hospitalization for DFU are higher among Black and Hispanic adults 26 , 36 , 49 , individuals in the lowest-income categories 48 , those with less comprehensive or no insurance 36 , 48 , those with lower education levels 33 , and those who live in socioeconomically deprived neighborhoods 36 , 48 , Black and Hispanic adults presenting with infection and ischemia are less likely to undergo revascularization than White patients 52 , 53 , and racial minorities and people without insurance are more likely to undergo early within 1 year minor or major amputation after incident DFU than White people or people with private insurance 49 , 54 , These findings suggest that disparities in access to care and biases in practice patterns may each contribute to unequal outcomes 26 , 49 , 50 , 56 , High rates of lower-extremity amputation and mortality tend to cluster both within neighborhoods and by region 34 , 47 , 58 , 59 , almost always corresponding to areas with a high density of economically deprived and racial and ethnic minority populations This layering disadvantage is the consequence of racialized segregation, lack of economic opportunity, and unequal health care that characterize structural racism Despite significant overlap, racial and ethnic differences in outcomes are not fully attenuated by controlling for socioeconomic or geographic factors 47 , 48 , While risk for poor outcomes is compounded in people with more than one minority or disadvantaged group status e.

Some patterns, such as unequal revascularization rates in people with ischemic DFU, have been shown to widen among the highest-income Black and White adults These findings reflect gaps in our ability to measure racial biases within the health system.

Geographic variation in lower-extremity outcomes is well established and is closely linked to socioeconomic status. In the U. and U. Differential access to preventive and specialty care 59 , 61 , financial constraints that delay presentation 62 , and provider-specific practices in limb preservation 54 likely contribute to geographic disparities and to worse outcomes in minority and rural populations 49 , Some health system-based measures, including managed care plans and Medicaid expansion, have demonstrated modest narrowing of disparities in DFU morbidity 26 , 63 , although dedicated research on interventions to specifically address disparities is lacking.

The cumulative burden of hyperglycemia and its causal relationship with microvascular complications are well established Chronically elevated HbA 1c is an independent risk factor for DFU and for amputation and mortality following DFU Maintaining a lower HbA 1c delays the progression of microvascular complications of diabetes 65 , 66 and is associated with decreased risk of amputation in adults with type 1 and type 2 diabetes Secondary analyses and extended follow-up of landmark trials show dose-response associations between HbA 1c and risk of incident DFU and amputation The association of obesity with incident DFU has not been consistently demonstrated, and obesity is not associated with incident or recurrent DFU, amputation, or mortality in several recent systematic reviews 30 , 38 , 41 , In patients who develop DFU, underweight BMI has been linked to an increased risk of amputation and mortality in population- and hospital-based studies 17 , 41 , likely reflecting higher rates of frailty and poor nutrition in the underweight population.

Smoking is associated with an increased risk of PN in adults with diabetes and is an extremely strong risk factor for PAD Several studies report strong associations of smoking with incident DFU 30 , longer healing time, higher rates of nonhealing DFU 18 , and a subsequent 1.

Prospective cohorts demonstrate bidirectional associations between DFU and cardiovascular disease, with incident DFU associated with faster progression of cardiovascular disease 69 , and even subclinical cardiovascular disease conferring increased risk of DFU Cardiovascular disease is also associated with delayed healing and a higher risk of amputation and mortality 4 , DFU and cardiovascular disease are both markers of diabetes severity and duration, and they act synergistically on physiologic e.

Aggressive management of cardiovascular risk factors is a central goal of multidisciplinary diabetes care and has been shown to decrease risk of DFU occurrence and reduce mortality in people who develop DFU Diabetes is a leading global cause of chronic kidney disease CKD and the most common cause of end-stage kidney disease Black and Hispanic adults and low-income groups have much higher rates of CKD than White and middle- or high-income groups End-stage kidney disease and CKD are linked to higher risk of incident DFU, longer healing time, higher ulcer recurrence rates, and higher rates of lower-extremity amputation 76 , These associations are strong enough to warrant inclusion of CKD in expert definitions of an at-risk foot even for people without prior DFU or structural deformity.

For people with kidney disease, end-stage kidney disease on hemodialysis confers the greatest risk of DFU The high prevalence of CKD among racial and ethnic minorities and socioeconomically disadvantaged people contributes to the disproportionate burden of DFU morbidity in these populations.

There is a strong association between the presence and severity of diabetic retinopathy and DFU. Diabetic retinopathy occurs at two- to fourfold higher rates among adults with DFU than in those without Visual impairment secondary to retinopathy may worsen gait instability and increase risk of foot trauma in those with PN, which can precipitate DFU formation 78 , although the causal mechanisms have not been definitively established.

Both DFU and retinopathy are likely signs of advanced microvascular disease that may partially explain this association. Ulcer healing is defined as complete epithelialization of a previously ulcerated site Time from diagnosis to wound healing and overall rates of healing differ widely based on ulcer etiology, size, presence of infection, and patient characteristics, with median healing times ranging from 3 months to more than 12 months 7 , Ischemic ulcers, larger and deeper ulcers, plantar ulcers, and ulcers with infection are associated with poor or prolonged healing 7 , 18 , 81 , In addition to wound- and patient-level risk factors described previously, nonambulatory status is associated with prolonged healing and lower amputation-free survival 7 , There is currently no validated predictive model for DFU healing that includes both patient and wound factors.

The strongest clinical predictor of developing a DFU is a prior DFU or amputation 2. Recurrence is the occurrence of an ulcer, either at the site of a prior ulcer or at another site, after complete healing 5.

Contralateral lower-extremity amputation independently increases ulcer recurrence by two- to threefold and shortens the average interval to ulcer recurrence 84 , presumably due to gait alterations.

Other factors consistently associated with recurrence are similar to those for nonhealing, although PAD has not been shown to be a strong influence on DFU recurrence despite its effects on primary healing Infection is a primary driver of emergency department visits and hospitalization in patients with diabetes and with DFU specifically 86 , Foot ulcer precedes the vast majority of diabetic foot infections, with higher risk of infection in recurrent wounds, long-standing wounds, and wounds that probe to bone, as well as among patients with recent history of prior non—foot infection 70 , 85 , Diabetes is the leading risk factor for lower-extremity amputation in U.

adults, with an estimated , diabetes-related major or minor amputations per year Overall diabetes-related amputations decreased steadily over the s and s despite rising diabetes prevalence. Over the same time, minor amputation made up an increasing proportion of these amputations, corresponding to higher rates of lower-extremity revascularization procedures; these trends are thought to represent improved efforts at limb preservation 91 , The overall resurgence in severe morbidity appears to disproportionately affect younger adults and Black and Hispanic groups 42 , 53 , 55 , 94 , which is particularly concerning given the already wide inequities in care for racial and ethnic minorities.

Even controlling for DFU incidence, Black and Hispanic adults have lower rates of attempted revascularization, higher rates of failed limb preservation, and higher risk of amputation than White adults 49 , 50 , 52 , Amputation is a late-stage complication of poor long-term diabetes management, and it often reflects inadequate access to, delivery of, and uptake of diabetes care.

The compounding effects of socioeconomic disadvantage, other social determinants of health, and structural racism on marked disparities in amputation rates by race, ethnicity, and socioeconomic status cannot be overstated 35 , Survival in people with incident DFU is significantly worse compared with that of similar people with diabetes without foot complications 2 , A recent meta-analysis comprising almost , patients in 16 countries reported mortality rates of Diabetes care in the U.

These numbers likely underestimate the true economic burden of DFU given out-of-pocket expenses, loss of productivity, and decreased employment associated with DFU Prevention and management of diabetic foot complications is a centerpiece of diabetes care.

A discussion of best-practice diabetes care is beyond the scope of this review, but many DFU-associated metabolic and cardiovascular risk factors are modifiable in early stages and are addressed by clinical guidelines and Europe Delayed ulcer presentation predicts poor prognosis 7 , 54 , Frequent foot exams are fundamental to decreasing incidence and morbidity, and inadequate foot care is associated with higher rates of DFU, LEA, and mortality , Guidelines for frequency of screening for PN, PAD, and DFU or other preulcerative lesions in the adults with diabetes Table 2 recommend at least an annual comprehensive foot exam for all patients with diabetes, including inspection, monofilament and tuning fork evaluation for loss of protective sensation, and pulse exam 1 , Screening exams should be performed every 3—6 months for high-risk patients The importance of multidisciplinary foot care for high-risk people deserves particular emphasis, especially the involvement of podiatry and vascular surgery Rates of annual foot exams by a provider in adults with diabetes vary widely Certain racial and ethnic minority populations e.

The implementation of a hemodialysis center-based monthly foot screening in a U. Routine foot screening is critical and low rates of adherence to standards of care for preventing diabetic foot infections is a major concern.

Several promising technologies may aid in the early detection of preulcerative or ulcerative foot lesions. Telemedicine-assisted foot examinations have been shown in small studies to be as effective as in-person provider exams at detecting early lesions, with time and cost savings to patients that have promise to reduce existing barriers to care 62 , Increased temperature is a well-validated preulcerative sign, and clinical trials of temperature-sensing mats and socks have been successful in identifying preulcer or DFU weeks earlier than a clinical exam.

These passive surveillance technologies may be able to reduce incident DFU through alerts to offload pressure points temporarily or by prompting a thorough foot evaluation. Additional pressure-sensing modalities including insoles may help risk-stratify people with high plantar pressures, monitor for effective offloading before or during DFU episodes, and evaluate progress in gait retraining after DFU healing or amputation Despite compelling evidence supporting their efficacy and cost effectiveness, these technologies have not been widely adopted.

The detrimental effect of DFU on overall health status and quality of life is well documented, and patient-reported outcomes are increasingly recognized as meaningful measures in diabetic foot care , People with DFU typically report poor quality of life, primarily in the domain of physical functioning.

Persistent ulcers, major amputation, and limited ambulation are associated with worse quality of life for both patients and their caregivers , Healing, including after minor amputation, is associated with dramatic improvement in self-reported physical functioning, and people with healed DFU have overall self-reported quality of life near the norms for populations without diabetes Though qualitative studies consistently identify fear, anxiety, frustration, isolation, and sadness as common emotional responses to the diagnosis of DFU, few studies have demonstrated differences in psychosocial quality of life related to DFU DFU-specific measures have been proposed to better assess the social and emotional consequences of active ulcers and should be considered when evaluating patient-reported outcomes.

DFU is a common complication of diabetes that has been aptly compared with cancer in terms of chronicity, recidivism, cost, and burden Major clinical risk factors for DFU are PN, PAD, and foot deformities, but race, ethnicity, socioeconomic status, and geography are powerful mediators of risk for DFU and lower-extremity amputation.

The consequences of first ulceration—poor quality of life, recurrence, major amputation, and death—are significant, but this morbidity is not reflected in the funding allocated for DFU-related research, which totals less than 0. Complications of DFU can be attenuated by guideline-directed screening, early diagnosis, and aggressive medical management of diabetes and cardiovascular disease.

Ineffective population-based screening, limited access to preventive care, and delays in access to diabetes, vascular, and podiatry specialist care contribute to late-stage ulcer presentation and, thus, to poor prognosis.

Rising lower-extremity amputation rates among young and middle-aged adults with diabetes and persistent racial, ethnic, and socioeconomic disparities reflect these gaps in care. Major efforts are needed to develop health system-wide improvements in DFU prevention and early diagnosis, especially in disadvantaged populations.

Funding should be prioritized for high-quality population-based registries to track DFU incidence, prevalence, outcomes, and process measures.

Initiatives to expand use of effective at-home screening modalities and allocate resources for more frequent provider foot exams in regions where major amputation rates are high have the potential to reduce DFU incidence and morbidity in the most at-risk populations.

Dedicated research on racial and socioeconomic differences in timing of care, limb preservation, and amputation are necessary to identify and address factors perpetuating structural bias and disparate outcomes. Significantly more public and institutional funding for DFU research and care initiatives is warranted to correct the imbalance between current resource allocation and the enormous burden of DFU.

Ultimately, a paradigm shift toward DFU prevention and health equity is required to produce meaningful reductions in DFU, major lower-extremity amputation, and mortality.

We acknowledge the contributions of Caroline Wang Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD and Alana Keegan Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD in creating and editing figures and tables.

was supported by National Institutes of Health NIH National Institute of Diabetes and Digestive and Kidney Diseases NIDDK grant K23 DK was supported by NIH National Heart, Lung, and Blood Institute grant K24 HL This work was also supported by NIH NIDDK grant R01 DK to L. Duality of Interest.

No potential conflicts of interest relevant to this article were reported. Author Contributions. completed literature review and wrote the manuscript.

and A. reviewed and edited the manuscript. and C. were involved in the conception of this work and reviewed and edited the manuscript.

All authors approved of the final version of the manuscript. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 46, Issue 1.

Previous Article Next Article. Presentation, Etiology, and Characterization of Diabetic Foot Ulcers. Wound Classification and Staging.

Epidemiology of Diabetic Foot Ulcers. Risk Factors for DFU and Associated Morbidity. Morbidity and Mortality Related to DFU. Economic Burden of DFU. Primary and Secondary Prevention of DFU. Quality of Life and Functional Impact of DFU. Article Information.

Article Navigation. Review December 22 Etiology, Epidemiology, and Disparities in the Burden of Diabetic Foot Ulcers Katherine McDermott X.

Katherine McDermott. This Site. Google Scholar. Michael Fang ; Michael Fang. Andrew J. Boulton ; Andrew J. Elizabeth Selvin Elizabeth Selvin. Caitlin W. Hicks Corresponding author: Caitlin W. Hicks, chicks11 jhmi. Diabetes Care ;46 1 — Article history Received:. Get Permissions. toolbar search Search Dropdown Menu.

toolbar search search input Search input auto suggest. Graphical Abstract View large Download slide. View large Download slide. Figure 1. Figure 2. Person- and foot-specific factors interact to promote DFU risk and poor clinical outcomes.

Figure 3. Table 1 Description and summary of benefits and limitations for common existing diabetic foot and limb classification systems. Assigns a clinical stage that estimates risk of amputation from 1 very low to 4 very high based on the combination of these factors stage 5: unsalvageable limb.

Extensively validated in diverse settings where data may be limited Unique in its inclusion of ulcer location High scores predictive of healing and LEA Has broad applications for use in population-based studies or resource-poor settings Dichotomized variables limit assessment of change over time or of the relative contribution of severe features e.

Assigns 1 present or 0 absent for location, ischemia, peripheral neuropathy, infection, area, and depth. Extensively validated in diverse settings Unique in its inclusion of ulcer location High scores predictive of healing and LEA Has broad applications for use in population-based studies or resource-poor settings where data may be limited Dichotomized variables limit assessment of change over time or of the relative contribution of severe features e.

View Large. Figure 4. Pathways to ulceration and lower-extremity amputation in DFU. They are associated with increased frequency and length of hospitalization and risk of lower extremity amputation.

Patients with diabetes are particularly susceptible to foot infection primarily because of neuropathy, vascular insufficiency, and diminished neutrophil function. Patients with diabetes lose the protective sensations for temperature and pain, impairing awareness of trauma such as abrasions, blistering, or penetrating foreign body.

Motor neuropathy can result in foot deformities e. Once the skin is broken typically on the plantar surface , the underlying tissues are exposed to colonization by pathogenic organisms.

The resulting wound infection may begin superficially, but with delay in treatment and impaired body defense mechanisms caused by neutrophil dysfunction and vascular insufficiency, it can spread to the contiguous subcutaneous tissues and to even deeper structures.

Although most diabetic foot infections begin with an ulcer, localized cellulitis and necrotizing fasciitis can develop in the absence of an ulcer or traumatic injury. The most common pathogens in acute, previously untreated, superficial infected foot wounds in patients with diabetes are aerobic gram-positive bacteria, particularly Staphylococcus aureus and beta-hemolytic streptococci group A, B, and others.

aureus MRSA is a more common pathogen in patients who have been previously hospitalized or who have recently received antibiotic therapy. MRSA infection can also occur in the absence of risk factors because of the increasing prevalence of MRSA in the community.

Key elements for evaluating and treating diabetic foot infection are summarized in Figure 1. Diabetic foot infection must be diagnosed clinically rather than bacteriologically because all skin ulcers harbor micro-organisms Figure 2.

The clinical diagnosis of foot infection is based on the presence of purulent discharge from an ulcer or the classic signs of inflammation i. Other suggestive features of infection include foul odor, the presence of necrosis, and failure of wound healing despite optimal management.

For example, pain and tenderness may be reduced or absent in patients who have neuropathy, whereas erythema may be absent in those with vascular disease.

It can clinically mimic cellulitis and presents as erythema, edema, and elevated temperature of the foot. Most patients with diabetic foot infection do not have systemic features such as fever or chills.

The presence of systemic signs or symptoms indicates a severe deep infection. Early recognition of the area of involved tissue can facilitate appropriate management and prevent progression of the infection Figure 3. The wound should be cleansed and debrided carefully to remove foreign bodies or necrotic material and should be probed with a sterile metal instrument to identify any sinus tracts, abscesses, or involvement of bones or joints.

Osteomyelitis is a common and serious complication of diabetic foot infection that poses a diagnostic challenge. A delay in diagnosis increases the risk of amputation. Osteomyelitis is unlikely with normal ESR values; however, an ESR of more than 70 mm per hour supports a clinical suspicion of osteomyelitis.

Bone biopsy is recommended if the diagnosis of osteomyelitis remains in doubt after imaging. The severity of the infection determines the appropriate antibiotic regimen and route of administration.

It also is the primary consideration in determining the need for hospitalization and the indications and timing for any surgical intervention. A practical and simple approach to classifying diabetic foot infection is provided in Table 2. Before an infected wound is cultured, any overlying necrotic debris should be removed by scrubbing the wound with saline-moistened sterile gauze to eliminate surface contamination.

Needle aspiration of the pus or tissue fluid performed aseptically is an acceptable alternative method. Cultures of wound swabs or material from sinus tracts are unreliable and are strongly discouraged. Peripheral artery disease PAD can be diagnosed by absence of foot pulses and reduced ankle-brachial index ABI.

Calculation of ABI is done by measuring the resting systolic blood pressure in the ankle and arm using a Doppler probe. An ABI of 0. An ABI greater than 1. Patients with atypical symptoms, or whose diagnosis is in doubt, should have ABI measured after exercise on a treadmill.

An ABI that decreases by 20 percent following exercise is diagnostic of PAD, whereas a normal ABI following exercise rules out PAD. If a PAD diagnosis is confirmed and revascularization is planned, magnetic resonance angiography, computed tomography angiography, or contrast angiography can be performed for anatomic evaluation.

Venous insufficiency can be diagnosed clinically by the presence of edema and skin changes and confirmed by duplex ultrasonography. Touch, vibration, and pressure sensations should be checked routinely using cotton wool, tuning fork, and g nylon monofilament, respectively.

Diagnostic imaging is not necessary for every patient with diabetes who has a foot infection. Plain radiography of the foot is indicated for detection of osteomyelitis, foreign bodies, or soft tissue gas. Bony abnormalities associated with osteomyelitis may be indistinguishable from the destructive effects of Charcot's foot and are usually not evident on plain radiography until two to four weeks after initial infection.

Combining technetium bone scan with gallium scan or white blood cell scan may improve the diagnostic yield for osteomyelitis. Effective management of diabetic foot infection requires appropriate antibiotic therapy, surgical drainage, debridement and resection of dead tissue, appropriate wound care, and correction of metabolic abnormalities.

The selection of antibiotic therapy for diabetic foot infection involves decisions about choice of empiric and definitive antibiotic agent, route of administration, and duration of treatment Tables 4 3 , 9 and 5 3 , 24 — Initial empiric antibiotic therapy should be based on the severity of the infection, history of recent antibiotic treatment, previous infection with resistant organisms, recent culture results, current Gram stain findings, and patient factors e.

A Gram-stained smear of an appropriate wound specimen may help guide therapy. The overall sensitivity of a Gram-stained smear for identifying organisms that grow on culture is 70 percent. aureus , including MRSA if necessary, and streptococci.

The patient should be reassessed 24 to 72 hours after initiating empiric antibiotic therapy to evaluate the response and to modify the antibiotic regimen, if indicated by early culture results.

Several antibiotics have been shown to be effective, but no single regimen has shown superiority. Surgery is the cornerstone of treatment for deep diabetic foot infection. Procedures range from simple incision and drainage to extensive multiple surgical debridements and amputation.

Timely and aggressive surgical debridement or limited resection or amputation may reduce the need for more extensive amputation.

Surgical excision of affected bone has historically been the standard of care in patients with osteomyelitis. Nevertheless, successful therapy with a long course of antibiotics alone has been achieved in two thirds of patients with osteomyelitis.

The wound may also be treated surgically with a flap or graft, left to heal by secondary intention, or managed with negative pressure dressings. If the infected limb appears to be ischemic, the patient should be referred to a vascular surgeon. Although noncritical ischemia can usually be treated without a vascular procedure, early revascularization within a few days of the infection is required for successful treatment of an infected foot with critical ischemia.

The wound should be dressed to allow for careful inspection for evidence of healing and early identification of new necrotic tissue. Necrotic or unhealthy tissue should be debrided, preferably surgically or with topical debriding agents. Removing pressure from the foot wound is crucial for healing 35 and can be achieved through total contact casting, removable cast walkers, and various ambulatory braces, splints, modified half-shoes, and sandals.

If osteomyelitis is present, signs of healing include a drop in ESR and loss of increased uptake on nuclear scan. Correction of fluid and electrolyte imbalances, hyperglycemia, acidosis, and azotemia is essential.

Good glycemic control may help eradicate the infection and promote wound healing. Frequent home blood glucose monitoring is strongly encouraged. Appropriate therapeutic adjustments e. Maggot debridement therapy, granulocyte colony-stimulating factor, and hyperbaric oxygen therapy have been used for diabetic foot infection, but should not be used routinely because of lack of evidence of effectiveness.

Prevention of diabetic foot ulcers begins with identifying patients at risk. All patients with diabetes should have an annual foot examination that includes assessment for anatomic deformities, skin breaks, nail disorders, loss of protection sensation, diminished arterial supply, and inappropriate footwear.

Patients at higher risk of foot ulceration should have examinations more often. Other effective clinical interventions include optimizing glycemic control, smoking cessation, debridement of calluses, and certain types of prophylactic foot surgery. Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J.

The global burden of diabetic foot disease. Carmona GA, Hoffmeyer P, Herrmann FR, et al. Major lower limb amputations in the elderly observed over ten years: the role of diabetes and peripheral arterial disease. Diabetes Metab. Lipsky BA, Berendt A, Deery HG, et al. Diagnosis and treatment of diabetic foot infections.

Clin Infect Dis. Delamaire M, Maugendre D, Moreno M, Le Goff MC, Allannic H, Genetet B. Impaired leucocyte functions in diabetic patients. Diabet Med. Abdulrazak A, Bitar ZI, Al-Shamali AA, Mobasher LA. Bacteriological study of diabetic foot infections. J Diabetes Complications.

Gerding DN. Foot infections in diabetic patients: the role of anaerobes. Tentolouris N, Petrikkos G, Vallianou N, et al. Prevalence of methicillin-resistant Staphylococcus aureus in infected and uninfected diabetic foot ulcers.

Clin Microbiol Infect. King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med. Lipsky BA. Medical treatment of diabetic foot infections.

Williams DT, Hilton JR, Harding KG. Diagnosing foot infections in diabetes. Eneroth M, Apelqvist J, Stenström A. Clinical characteristics and outcome in diabetic patients with deep foot infections. Foot Ankle Int. Pittet D, Wyssa B, Herter-Clavel C, Kursteiner K, Vaucher J, Lew PD.

Outcome of diabetic foot infections treated conservatively: a retrospective cohort study with long-term follow-up. Arch Intern Med. Newman LG, Waller J, Palestro CJ, et al. Unsuspected osteomyelitis in diabetic foot ulcers. Diagnosis and monitoring by leukocyte scanning with indium In oxyquinoline.

Grayson ML, Gibbons GW, Balogh K, Levin E, Karchmer AW. Probing to bone in infected pedal ulcers. A clinical sign of underlying osteomyelitis in diabetic patients. Lavery LA, Armstrong DG, Peters EJ, Lipsky BA. Probe-to-bone test for diagnosing diabetic foot osteomyelitis: reliable or relic?.

Diabetes Care. Rajbhandari SM, Sutton M, Davies C, Tesfaye S, Ward JD. Pellizzer G, Strazzabosco M, Presi S, et al. Deep tissue biopsy vs.

superficial swab culture monitoring in the microbiological assessment of limb-threatening diabetic foot infection. Senneville E, Melliez H, Beltrand E, et al. Culture of percutaneous bone biopsy specimens for diagnosis of diabetic foot osteomyelitis: concordance with ulcer swab cultures.

Zuluaga AF, Galvis W, Saldarriaga JG, Agudelo M, Salazar BE, Vesga O. Etiologic diagnosis of chronic osteomyelitis: a prospective study.

Some diabetes symptoms, like poor Gymnastics nutrition guidelines and Hypperglycemia blood ulcrrs, can hyperhlycemia to Chronic hyperglycemia and foot ulcers, especially on your feet. Chrinic foot klcers can help to prevent them from forming. Foot ulcers are a common complication of diabetes that is not being managed through methods such as diet, exercise, and insulin treatment. Ulcers are formed as a result of skin tissue breaking down and exposing the layers underneath. All people with diabetes can develop foot ulcers, but good foot care can help prevent them. Treatment for diabetic foot ulcers varies depending on their causes. Jump to content. Enhance your natural beauty with skin rejuvenation diabetic foot ulcer Chrojic an Chronic hyperglycemia and foot ulcers uclers or wound that occurs in approximately 15 ulers of patients with diabetes, fpot is commonly ulceds on the bottom of the foot. Of those who develop a foot ulcer, six percent will be hospitalized due to infection or other ulcer-related complication. Diabetes is the leading cause of nontraumatic lower extremity amputations in the United States, and approximately 14 to 24 percent of patients with diabetes who develop a foot ulcer have an amputation. Research, however, has shown that the development of a foot ulcer is preventable.

In Kiwi fruit retail opportunities with diabetes, any foot infection is potentially serious. Diabetic znd infections range in severity from superficial paronychia to deep byperglycemia involving bone.

Types of Chronc include cellulitis, myositis, abscesses, necrotizing hyperglycfmia, septic arthritis, tendinitis, and osteomyelitis. Foot infections are among the Chronic hyperglycemia and foot ulcers common and serious complications of diabetes mellitus.

They are ulceds with increased frequency and ulcerz of hospitalization and risk of lower extremity amputation. Patients with diabetes are particularly susceptible to ans infection primarily Cjronic Chronic hyperglycemia and foot ulcers neuropathy, vascular hypergglycemia, and diminished neutrophil Chronic hyperglycemia and foot ulcers.

Patients Chornic diabetes lose Crhonic protective sensations for temperature and pain, impairing awareness of trauma such as abrasions, blistering, hypwrglycemia penetrating foreign body. Motor hypdrglycemia can result in foot deformities e.

Once the skin is broken typically on the plantar hpyerglycemiathe underlying Chronic hyperglycemia and foot ulcers are coot to colonization by snd organisms, Chronic hyperglycemia and foot ulcers. The resulting wound infection may begin superficially, but with delay in treatment and Chrronic body defense mechanisms caused by neutrophil dysfunction hyperglycemix vascular insufficiency, it can spread to the hypdrglycemia Chronic hyperglycemia and foot ulcers tissues and to even deeper Chromic.

Although most diabetic foit Chronic hyperglycemia and foot ulcers begin with an ulcer, localized cellulitis and necrotizing fasciitis hypergylcemia develop in the absence of an ulcer hypergljcemia traumatic injury.

The uocers common pathogens Chrohic acute, previously untreated, ulfers infected foot wounds in CChronic with diabetes are aerobic gram-positive bacteria, particularly Staphylococcus aureus and Chronic hyperglycemia and foot ulcers streptococci group A, B, and others. aureus Chroni is a more common pathogen in patients who have been hypperglycemia hospitalized or who have Chronid received ulcera therapy.

MRSA hypergljcemia can also occur Chrlnic the absence of Chrronic factors because of Nootropic supplements for cognitive enhancement increasing prevalence hy;erglycemia MRSA in the Turmeric for stress relief. Key elements for evaluating and treating diabetic foot infection are summarized hyperglycemua Figure 1.

Diabetic foot infection must be diagnosed clinically rather than bacteriologically because Chronlc skin ulcers harbor micro-organisms Figure 2. The clinical diagnosis fooy foot Restful practices is based on the presence of purulent Digestive health and probiotic foods from an hypergycemia or the classic signs of Chronkc i.

Other suggestive features of infection include foul odor, the presence ulcerd necrosis, and failure of wound healing despite optimal management. For Chronic hyperglycemia and foot ulcers, pain and tenderness may Sports injury prevention for coaches reduced or ulcerx in patients who voot neuropathy, whereas erythema may be absent in those with vascular disease.

It can Cbronic mimic byperglycemia and presents as erythema, edema, and ans temperature of the aand. Most patients with ulceds foot infection do not have systemic features such as fever hyperglycemix chills.

The presence yyperglycemia systemic signs or symptoms indicates a severe deep hCronic. Early recognition of the area of involved tissue can facilitate appropriate management and prevent hyperflycemia of the Chronic hyperglycemia and foot ulcers Figure 3.

The wound should be cleansed hyperglycemiia debrided carefully to remove foreign bodies or hyperglycfmia material and should be probed with a sterile metal instrument to identify any sinus ulers, abscesses, or ulcdrs of bones or hyprrglycemia.

Osteomyelitis is foog common and serious Ulcer of Enhance workout coordination foot infection Chronic hyperglycemia and foot ulcers poses a diagnostic challenge. Hyperglhcemia delay in diagnosis increases the hypergglycemia of amputation.

Osteomyelitis is unlikely with normal ESR values; however, an ESR of Chrpnic than 70 Macronutrients and aging per hour supports a clinical suspicion of osteomyelitis. Bone biopsy is recommended if hypergllycemia diagnosis of osteomyelitis remains hyperglycdmia doubt after imaging.

The severity of the infection determines the appropriate antibiotic regimen and route of administration. It also is the primary consideration in determining the need for hospitalization and the indications and timing for any surgical intervention.

A practical and simple approach to classifying diabetic foot infection is provided in Table 2. Before an infected wound is cultured, any overlying necrotic debris should be removed by scrubbing the wound with saline-moistened sterile gauze to eliminate surface contamination.

Needle aspiration of the pus or tissue fluid performed aseptically is an acceptable alternative method. Cultures of wound swabs or material from sinus tracts are unreliable and are strongly discouraged. Peripheral artery disease PAD can be diagnosed by absence of foot pulses and reduced ankle-brachial index ABI.

Calculation of ABI is done by measuring the resting systolic blood pressure in the ankle and arm using a Doppler probe. An ABI of 0. An ABI greater than 1. Patients with atypical symptoms, or whose diagnosis is in doubt, should have ABI measured after exercise on a treadmill.

An ABI that decreases by 20 percent following exercise is diagnostic of PAD, whereas a normal ABI following exercise rules out PAD. If a PAD diagnosis is confirmed and revascularization is planned, magnetic resonance angiography, computed tomography angiography, or contrast angiography can be performed for anatomic evaluation.

Venous insufficiency can be diagnosed clinically by the presence of edema and skin changes and confirmed by duplex ultrasonography. Touch, vibration, and pressure sensations should be checked routinely using cotton wool, tuning fork, and g nylon monofilament, respectively. Diagnostic imaging is not necessary for every patient with diabetes who has a foot infection.

Plain radiography of the foot is indicated for detection of osteomyelitis, foreign bodies, or soft tissue gas. Bony abnormalities associated with osteomyelitis may be indistinguishable from the destructive effects of Charcot's foot and are usually not evident on plain radiography until two to four weeks after initial infection.

Combining technetium bone scan with gallium scan or white blood cell scan may improve the diagnostic yield for osteomyelitis. Effective management of diabetic foot infection requires appropriate antibiotic therapy, surgical drainage, debridement and resection of dead tissue, appropriate wound care, and correction of metabolic abnormalities.

The selection of antibiotic therapy for diabetic foot infection involves decisions about choice of empiric and definitive antibiotic agent, route of administration, and duration of treatment Tables 4 39 and 5 324 — Initial empiric antibiotic therapy should be based on the severity of the infection, history of recent antibiotic treatment, previous infection with resistant organisms, recent culture results, current Gram stain findings, and patient factors e.

A Gram-stained smear of an appropriate wound specimen may help guide therapy. The overall sensitivity of a Gram-stained smear for identifying organisms that grow on culture is 70 percent.

aureusincluding MRSA if necessary, and streptococci. The patient should be reassessed 24 to 72 hours after initiating empiric antibiotic therapy to evaluate the response and to modify the antibiotic regimen, if indicated by early culture results.

Several antibiotics have been shown to be effective, but no single regimen has shown superiority. Surgery is the cornerstone of treatment for deep diabetic foot infection. Procedures range from simple incision and drainage to extensive multiple surgical debridements and amputation.

Timely and aggressive surgical debridement or limited resection or amputation may reduce the need for more extensive amputation. Surgical excision of affected bone has historically been the standard of care in patients with osteomyelitis. Nevertheless, successful therapy with a long course of antibiotics alone has been achieved in two thirds of patients with osteomyelitis.

The wound may also be treated surgically with a flap or graft, left to heal by secondary intention, or managed with negative pressure dressings.

If the infected limb appears to be ischemic, the patient should be referred to a vascular surgeon. Although noncritical ischemia can usually be treated without a vascular procedure, early revascularization within a few days of the infection is required for successful treatment of an infected foot with critical ischemia.

The wound should be dressed to allow for careful inspection for evidence of healing and early identification of new necrotic tissue. Necrotic or unhealthy tissue should be debrided, preferably surgically or with topical debriding agents.

Removing pressure from the foot wound is crucial for healing 35 and can be achieved through total contact casting, removable cast walkers, and various ambulatory braces, splints, modified half-shoes, and sandals.

If osteomyelitis is present, signs of healing include a drop in ESR and loss of increased uptake on nuclear scan. Correction of fluid and electrolyte imbalances, hyperglycemia, acidosis, and azotemia is essential. Good glycemic control may help eradicate the infection and promote wound healing.

Frequent home blood glucose monitoring is strongly encouraged. Appropriate therapeutic adjustments e. Maggot debridement therapy, granulocyte colony-stimulating factor, and hyperbaric oxygen therapy have been used for diabetic foot infection, but should not be used routinely because of lack of evidence of effectiveness.

Prevention of diabetic foot ulcers begins with identifying patients at risk. All patients with diabetes should have an annual foot examination that includes assessment for anatomic deformities, skin breaks, nail disorders, loss of protection sensation, diminished arterial supply, and inappropriate footwear.

Patients at higher risk of foot ulceration should have examinations more often. Other effective clinical interventions include optimizing glycemic control, smoking cessation, debridement of calluses, and certain types of prophylactic foot surgery.

Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Carmona GA, Hoffmeyer P, Herrmann FR, et al. Major lower limb amputations in the elderly observed over ten years: the role of diabetes and peripheral arterial disease.

Diabetes Metab. Lipsky BA, Berendt A, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis. Delamaire M, Maugendre D, Moreno M, Le Goff MC, Allannic H, Genetet B.

Impaired leucocyte functions in diabetic patients. Diabet Med. Abdulrazak A, Bitar ZI, Al-Shamali AA, Mobasher LA. Bacteriological study of diabetic foot infections. J Diabetes Complications. Gerding DN.

Foot infections in diabetic patients: the role of anaerobes. Tentolouris N, Petrikkos G, Vallianou N, et al. Prevalence of methicillin-resistant Staphylococcus aureus in infected and uninfected diabetic foot ulcers.

Clin Microbiol Infect. King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med. Lipsky BA.

: Chronic hyperglycemia and foot ulcers

Pathogenesis of Ulceration

The nerve damage often can occur without pain and one may not even be aware of the problem. Your podiatric physician can test feet for neuropathy with a simple and painless tool called a monofilament.

Once an ulcer is noticed, seek podiatric medical care immediately. Foot ulcers in patients with diabetes should be treated for several reasons:.

The primary goal in the treatment of foot ulcers is to obtain healing as soon as possible. The faster the healing of the wound, the less chance for an infection.

Not all ulcers are infected; however, if your podiatric physician diagnoses an infection, a treatment program of antibiotics, wound care, and possibly hospitalization will be necessary. These devices will reduce the pressure and irritation to the ulcer area and help to speed the healing process.

The science of wound care has advanced significantly over the past ten years. We know that wounds and ulcers heal faster, with a lower risk of infection, if they are kept covered and moist. The use of full-strength betadine, peroxide, whirlpools and soaking are not recommended, as this could lead to further complications.

Appropriate wound management includes the use of dressings and topically-applied medications. These range from normal saline to advanced products, such as growth factors, ulcer dressings, and skin substitutes that have been shown to be highly effective in healing foot ulcers.

For a wound to heal there must be adequate circulation to the ulcerated area. Your podiatrist may order evaluation test such as noninvasive studies and or consult a vascular surgeon. Tightly controlling blood glucose is of the utmost importance during the treatment of a diabetic foot ulcer.

Working closely with a medical doctor or endocrinologist to accomplish this will enhance healing and reduce the risk of complications.

A majority of noninfected foot ulcers are treated without surgery; however, when this fails, surgical management may be appropriate. Hyperglycemia and hypoxia did not have any effect on its gene expression.

Hence, hyperglycemia only negatively impacts the expression of pro-inflammatory cytokines but not those involved in wound healing. Hyperglycemia has a negative impact on the wound healing of foot diabetic ulcers. High glucose level acts in synergy with hypoxia to maintain the state of chronic inflammation observed in chronic wounds.

Hyperglycemia increases the expression of pro-inflammatory cytokines and chemokines by macrophages and decreases their ability of phagocytosis, required for the resolution of inflammation. By contrast, the cytokines involved in wound healing were not impacted by the high glucose concentration. This overview of the macrophage behavior cultivated in hyperglycemia and hypoxia could be helpful towards discovering novel relevant targets for the treatment of foot diabetic ulcers.

The authors would like to thank Dr Oliver Carroll for his technical guidance in the project, Dana Toncu for editorial and critical assessment of the manuscript, and Mr Anthony Sloan for his editorial assistance in finalizing the manuscript.

Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Article Authors Metrics Comments Media Coverage Reader Comments Figures. Abstract Diabetic foot ulcers DFUs are characterized by a chronic inflammation state which prevents cutaneous wound healing, and DFUs eventually lead to infection and leg amputation.

Introduction Diabetic foot ulcers are the most common, painful and crippling complications of diabetes mellitus [ 1 ]. In pathological conditions, macrophages are locked in the M1 phenotype, thereby leading to chronic inflammation Hypoxia in DFU creates conditions that are disadvantageous because the low oxygen tension induces the increased release of pro-inflammatory cytokines via the activation of NF- κ B signaling pathways [ 10 , 11 ].

Download: PPT. Fig 1. Differentiation and activation of macrophages cultivated in hyperglycemia and hypoxia. Results 3. Table 1. Gene expression profile of THP-1 derived macrophages cultivated in hyperglycemia and hypoxia. Effect of hyperglycemia and hypoxia on gene expression of inflammatory cytokines The impact of hypoxia and hyperglycemia on the gene expression of TNF- α, IL-1a, IL-6 and GM-CSF was analyzed in detail and compared to the results obtained with the microarray.

Fig 3. Fig 5. Impact of hyperglycemia and hypoxia in activated macrophages on the gene expression of TGF-β, the major wound healing molecule.

Fig 6. Impact of hyperglycemia and hypoxia on the gene expression of SOCS-3 in activated macrophages. Conclusion Hyperglycemia has a negative impact on the wound healing of foot diabetic ulcers.

Supporting information. S1 Table. List of primer used for the RT-PCR. s PDF. Acknowledgments The authors would like to thank Dr Oliver Carroll for his technical guidance in the project, Dana Toncu for editorial and critical assessment of the manuscript, and Mr Anthony Sloan for his editorial assistance in finalizing the manuscript.

References 1. Adeghate J, Nurulain S, Tekes K, Feher E, Kalasz H, Adeghate E. Novel biological therapies for the treatment of diabetic foot ulcers. Expert Opin Biol Ther. Krzyszczyk P, Schloss R, Palmer A, Berthiaume F.

The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes. Front Physiol. Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv Ther. Clayton Warren ET.

A review of the Pathophysiology, classification, and treatment of foot ulcers in Diabetic Patients. Clinical Diabetes. View Article Google Scholar 5. Markakis K, Bowling FL, Boulton AJ. The diabetic foot in an overview. Diabetes Metab Res Rev. View Article Google Scholar 6. Armstrong DG, Lavery LA.

Diabetic foot ulcers: prevention, diagnosis and classification. Am Fam Physician. Zhao R, Liang H, Clarke E, Jackson C, Xue M. Inflammation in Chronic Wounds. Int J Mol Sci. Mosser DM, Edwards JP.

Exploring the full spectrum of macrophage activation. Nat Rev Immunol. Sindrilaru A, Scharffetter-Kochanek K. Disclosure of the Culprits: Macrophages-Versatile Regulators of Wound Healing. Adv Wound Care New Rochelle. View Article Google Scholar Rahat MA, Bitterman H, Lahat N.

Molecular mechanisms regulating macrophage response to hypoxia. Front Immunol. Schreml S, Szeimies RM, Prantl L, Karrer S, Landthaler M, Babilas P. Oxygen in acute and chronic wound healing. Br J Dermatol. Strehl C, Fangradt M, Fearon U, Gaber T, Buttgereit F, Veale DJ.

Hypoxia: how does the monocyte-macrophage system respond to changes in oxygen availability? J Leukoc Biol. Blakytny R, Jude E. The molecular biology of chronic wounds and delayed healing in diabetes. Diabet Med. Berlanga-Acosta J, Schultz GS, Lopez-Mola E, Guillen-Nieto G, Garcia-Siverio M, Herrera-Martínez L.

Glucose toxic effects on granulation tissue productive cells: the diabetics' impaired healing. Biomed Res Int. Qing C. Chin J Traumatol. Uemura S, Matsushita H, Li W, Glassford AJ, Asagami T, Lee KH, et al.

Diabetes mellitus enhances vascular matrix metalloproteinase activity: role of oxidative stress. Circ Res. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, et al.

Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. Dai M, Wang P, Boyd AD, Kostov G, Athey B, Jones EG, et al.

Nucleic Acids Res. Smyth GK. Limma: linear models for microarray data. In: Gentleman VC R. Bioinformatics and Computational Biology Solutions using R and Bioconductor.

New York: Springer ;p: — Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I. Controlling the false discovery rate in behavior genetics research. Behav Brain Res. Maritim AC, Sanders RA, Watkins JB 3rd Diabetes, oxidative stress, and antioxidants: a review.

J Biochem Mol Toxicol. Sparvero LJ, Asafu-Adjei D, Kang R, Tang D, Amin N, Im J, et al. RAGE Receptor for Advanced Glycation Endproducts , RAGE ligands, and their role in cancer and inflammation. J Transl Med. Hanson MA, Godfrey KM.

Genetics: Epigenetic mechanisms underlying type 2 diabetes mellitus. Nat Rev Endocrinol. Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, et al.

Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Wetzler C, Kampfer H, Pfeilschifter J, Frank S Keratinocyte-derived chemotactic cytokines: expressional modulation by nitric oxide in vitro and during cutaneous wound repair in vivo.

Biochem Biophys Res Commun. Death AK, Fisher EJ, McGrath KC, Yue DK. High glucose alters matrix metalloproteinase expression in two key vascular cells: potential impact on atherosclerosis in diabetes.

Salim T, Sershen CL, May EE. Investigating the Role of TNF-alpha and IFN-gamma Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages. PLoS One. Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. FPrime Rep. Andreakos E, Sacre SM, Smith C, Lundberg A, Kiriakidis S, Stonehouse T, et al.

Jin X, Yao T, Zhou Z, Zhu J, Zhang S, Hu W, et al. D'Ignazio L, Bandarra D, Rocha S. NF-kappaB and HIF crosstalk in immune responses. Management of diabetic foot problems. Philadelphia: Saunders, — Pecoraro RE, Reiber GE, Burgess EM. Pathways to diabetic limb amputation.

Basis for prevention. Reiber GE, Pecoraro RE, Koepsell TD. Risk factors for amputation in patients with diabetes mellitus. A case-control study. Ann Intern Med. United States National Diabetes Advisory Board.

The national long-range plan to combat diabetes. Bethesda, Md. Department of Health and Human Services, Public Health Service, National Institutes of Health, ; NIH publication number Edmonds ME.

Experience in a multidisciplinary diabetic foot clinic. In: Connor H, Boulton AJ, Ward JD, eds. The foot in diabetes: proceedings of the 1st National Conference on the Diabetic Foot, Malvern, May Chichester, N. Wylie-Rosset J, Walker EA, Shamoon H, Engel S, Basch C, Zybert P.

Assessment of documented foot examinations for patients with diabetes in inner-city primary care clinics. Arch Fam Med. Bailey TS, Yu HM, Rayfield EJ. Patterns of foot examination in a diabetes clinic. Am J Med. Edelson GW, Armstrong DG, Lavery LA, Caicco G. The acutely infected diabetic foot is not adequately evaluated in an inpatient setting.

Arch Intern Med. Kannel WB, McGee DL. Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study. LoGerfo FW, Coffman JD. Vascular and microvascular disease of the foot in diabetes. Implications for foot care. N Engl J Med. Lee JS, Lu M, Lee VS, Russell D, Bahr C, Lee ET.

Lower-extremity amputation. Incidence, risk factors, and mortality in the Oklahoma Indian Diabetes Study. Update on some epidemiologic features of intermittent claudication: the Framingham study. J Am Geriatr Soc. Bacharach JM, Rooke TW, Osmundson PJ, Gloviczki P. Predictive value of transcutaneous oxygen pressure and amputation success by use of supine and elevation measurements.

J Vasc Surg. Apelqvist J, Castenfors J, Larsson J, Strenstrom A, Agardh CD. Prognostic value of systolic ankle and toe blood pressure levels in outcome of diabetic foot ulcer. Orchard TJ, Strandness DE. Assessment of peripheral vascular disease in diabetes.

Report and recommendation of an international workshop sponsored by the American Heart Association and the American Diabetes Association 18—20 September , New Orleans, Louisiana. J Am Podiatr Med Assoc. Caputo GM, Cavanagh PR, Ulbrecht JS, Gibbons GW, Karchmer AW. Assessment and management of foot disease in patients with diabetes.

Harati Y. Diabetic peripheral neuropathy. In: Kominsky SJ, ed. Medical and surgical management of the diabetic foot. Louis: Mosby, — Brand PW. The insensitive foot including leprosy.

In: Jahss MH, ed. Philadelphia: Saunders, —5. Armstrong DG, Todd WF, Lavery LA, Harkless LB, Bushman TR. The natural history of acute Charcot's arthropathy in a diabetic foot specialty clinic. Diabet Med. Edmonds ME, Clarke MB, Newton S, Barrett J, Watkins PJ. Increased uptake of bone radiopharmaceutical in diabetic neuropathy.

Q J Med. Brower AC, Allman RM. The neuropathic joint: a neurovascular bone disorder. Radiol Clin North Am. Birke JA, Sims DS. Plantar sensory threshold in the ulcerative foot. Lepr Rev.

Frequently Asked Questions: Diabetic Foot Ulcers | University of Michigan Health At each visit, tracings of the wound margins were made to document changes in wound size using computer planimetry and photographs were taken for a visual record. An ulcer was considered healed only after closure was confirmed at the next weekly visit. But daily care is one of the best ways to prevent foot complications. Heilbrunn, MD, Scott Iwasaki, Ginger Lee, Adam Morgan, Shelly Taylor, RN, and Emelyn Vargas, Advanced Tissue Sciences Inc. Black and Hispanic adults and low-income groups have much higher rates of CKD than White and middle- or high-income groups
Risk Factors Associated with Healing Chronic Diabetic Foot Ulcers: The Importance of Hyperglycemia

and A. reviewed and edited the manuscript. and C. were involved in the conception of this work and reviewed and edited the manuscript. All authors approved of the final version of the manuscript.

are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest.

filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 46, Issue 1. Previous Article Next Article.

Presentation, Etiology, and Characterization of Diabetic Foot Ulcers. Wound Classification and Staging. Epidemiology of Diabetic Foot Ulcers.

Risk Factors for DFU and Associated Morbidity. Morbidity and Mortality Related to DFU. Economic Burden of DFU. Primary and Secondary Prevention of DFU.

Quality of Life and Functional Impact of DFU. Article Information. Article Navigation. Review December 22 Etiology, Epidemiology, and Disparities in the Burden of Diabetic Foot Ulcers Katherine McDermott X.

Katherine McDermott. This Site. Google Scholar. Michael Fang ; Michael Fang. Andrew J. Boulton ; Andrew J. Elizabeth Selvin Elizabeth Selvin. Caitlin W. Hicks Corresponding author: Caitlin W. Hicks, chicks11 jhmi. Diabetes Care ;46 1 — Article history Received:.

Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Graphical Abstract View large Download slide. View large Download slide. Figure 1. Figure 2. Person- and foot-specific factors interact to promote DFU risk and poor clinical outcomes. Figure 3.

Table 1 Description and summary of benefits and limitations for common existing diabetic foot and limb classification systems. Assigns a clinical stage that estimates risk of amputation from 1 very low to 4 very high based on the combination of these factors stage 5: unsalvageable limb.

Extensively validated in diverse settings where data may be limited Unique in its inclusion of ulcer location High scores predictive of healing and LEA Has broad applications for use in population-based studies or resource-poor settings Dichotomized variables limit assessment of change over time or of the relative contribution of severe features e.

Assigns 1 present or 0 absent for location, ischemia, peripheral neuropathy, infection, area, and depth. Extensively validated in diverse settings Unique in its inclusion of ulcer location High scores predictive of healing and LEA Has broad applications for use in population-based studies or resource-poor settings where data may be limited Dichotomized variables limit assessment of change over time or of the relative contribution of severe features e.

View Large. Figure 4. Pathways to ulceration and lower-extremity amputation in DFU. Table 2 Professional guidelines for screening and management of patients at risk for DFU. Foot exams. International Diabetes Federation. Brussels, Belgium, International Diabetes Federation, Accessed 1 August Search ADS.

Prevalence, clinical aspects and outcomes in a large cohort of persons with diabetic foot disease: comparison between neuropathic and ischemic ulcers.

van Netten. Comparison of characteristics and healing course of diabetic foot ulcers by etiological classification: neuropathic, ischemic, and neuro-ischemic type. Diabetic foot ulcers and vascular insufficiency: our population has changed, but our methods have not.

Decreasing incidence of foot ulcer among patients with type 1 and type 2 diabetes in the period Diabetic neuropathy: a position statement by the American Diabetes Association.

Epidemiology of peripheral neuropathy and lower extremity disease in diabetes. Global vascular guidelines on the management of chronic limb-threatening ischemia. Epidemiology and risk of amputation in patients with diabetes mellitus and peripheral artery disease.

Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome. The management of diabetic foot: a clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine.

Foot ulcer and risk of lower limb amputation or death in people with diabetes: a national population-based retrospective cohort study.

Diabetic Foot Working Group, Queensland Statewide Diabetes Clinical Network, Australia. Factors associated with healing of diabetes-related foot ulcers: observations from a large prospective real-world cohort. Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease.

The EURODIALE Study. The Society for Vascular Surgery lower extremity threatened limb classification system: risk stratification based on wound, ischemia, and foot infection WIfI.

Diabetic foot ulcer incidence and survival with improved diabetic foot services: an year study. Preventing foot ulceration in diabetes: systematic review and meta-analyses of RCT data. Development and validation of an incidence risk prediction model for early foot ulcer in diabetes based on a high evidence systematic review and meta-analysis.

Rates of diabetes-related major amputations among racial and ethnic minority adults following Medicaid expansion under the Patient Protection and Affordable Care Act. Incidence, hospitalization and mortality and their changes over time in people with a first ever diabetic foot ulcer.

Incidence of diabetic foot ulcer in Japanese patients with type 2 diabetes mellitus: the Fukuoka diabetes registry. Epidemiology of foot ulceration and amputation: can global variation be explained?

Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis. Global recurrence rates in diabetic foot ulcers: a systematic review and meta-analysis. Trends in receipt of American Diabetes Association guideline-recommended care among U.

adults with diabetes: NHANES Socioeconomic inequalities and type 2 diabetes complications: a systematic review. Geographical socioeconomic disadvantage is associated with adverse outcomes following major amputation in diabetic patients.

Disparities in initial presentation and treatment outcomes of diabetic foot ulcers in a public, private, and Veterans Administration hospital. Risk factors for diabetic foot complications in type 2 diabetes-A systematic review.

Incidence and risk factors associated with ulcer recurrence among patients with diabetic foot ulcers treated in a multidisciplinary setting. Phenotypes and outcomes in middle-aged patients with diabetic foot ulcers: a retrospective cohort study.

Risk factors for lower extremity amputation in patients with diabetic foot ulcers: a meta-analysis. Resurgence of diabetes-related nontraumatic lower-extremity amputation in the young and middle-aged adult U. National and state-level trends in nontraumatic lower-extremity amputation among U.

Medicare beneficiaries with diabetes, Gender differences in attitudes and attributes of people using therapeutic shoes for diabetic foot complications.

Diabetic foot ulcers: epidemiology and the role of multidisciplinary care teams. Centers for Disease Control and Prevention. Atlanta, GA, Centers for Disease Control and Prevention, Accessed 6 June Geographic and socioeconomic disparities in major lower extremity amputation rates in metropolitan areas.

The adverse effects of race, insurance status, and low income on the rate of amputation in patients presenting with lower extremity ischemia. Association of race, ethnicity, and rurality with major leg amputation or death among Medicare beneficiaries hospitalized with diabetic foot ulcers.

Social deprivation and incident diabetes-related foot disease in patients with type 2 diabetes: a population-based cohort study. Influence of race on the management of lower extremity ischemia: revascularization vs amputation.

A lack of decline in major nontraumatic amputations in Texas: contemporary trends, risk factor associations, and impact of revascularization. Who, what, where: demographics, severity of presentation, and location of treatment drive delivery of diabetic limb reconstructive services within the National Inpatient Sample.

Racial disparities in health care with timing to amputation following diabetic foot ulcer. Prevalence and risk factors of lower limb amputations in patients with diabetic foot ulcers: a systematic review and meta-analysis. Amputation rates for patients with diabetes and peripheral arterial disease: the effects of race and region.

Geospatial mapping and data linkage uncovers variability in outcomes of foot disease according to multiple deprivation: a population cohort study of people with diabetes. Location, location, location: geographic clustering of lower-extremity amputation among Medicare beneficiaries with diabetes.

How structural racism works—racist policies as a root cause of U. racial health inequities. Expect delays: poor connections between rural and urban health systems challenge multidisciplinary care for rural Americans with diabetic foot ulcers.

A qualitative study of barriers to care-seeking for diabetic foot ulceration across multiple levels of the healthcare system. Prevalence and risk factors for diabetes-related foot complications in Translating Research Into Action for Diabetes TRIAD. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association.

Effect of intensive glycemic control on risk of lower extremity amputation. Prism Excel Stat software was used for all data analysis. The microarray revealed that genes were statistically up or downregulated in hyperglycemia. Filtering for gene expression modulated at least 2 fold, only 54 genes were found to be upregulated and 94 downregulated in hyperglycemia.

Among these genes, thirteen proinflammatory cytokines and ten chemokines were found to be upregulated Fig 2. In contrast, TGF-β1, a crucial cytokine promoting wound healing was downregulated in hyperglycemia 2·01 fold lower.

Moreover, CD36 and Scavenger receptor B, two genes involved in the process of phagocytosis, were also downregulated Table 1.

After analysis, the microarray revealed that three major signalling pathways were modulated in hyperglycemia. These pathways were the EGF Epidermal Growth Factor and Wnt5A Wingless-type MMTV integration site family, member 5A and NOD signalling pathways Table 1.

Eleven genes encoding for proteins with an anti-apoptotic effect were also upregulated and three pro-apoptotic genes were downregulated Fig 2. Surprisingly, no genes encoding for metalloproteinases or other proteases were upregulated when cells were cultivated in hyperglycemia.

Finally, only a few genes involved in glycolysis were modulated by the high glucose concentration. Only two were slightly downregulated for glycolysis and two for proliferation.

Overview of genes upregulated and dowregulated in a high glucose environment and hypoxia. The impact of hypoxia and hyperglycemia on the gene expression of TNF- α, IL-1a, IL-6 and GM-CSF was analyzed in detail and compared to the results obtained with the microarray.

Gene expression was measured 1 hour and 17 hours after macrophage activation by LPS. This activation triggered an increase of the TNF-α gene expression after one hour regardless of the culture conditions.

The gene expression was around four times the basal level but was not significantly different whether the cells were cultivated in hypoxia or in hyperglycemia Fig 3A.

As a result, the combination of hypoxia and hyperglycemia has a synergistic effect for long term TNF-α gene expression. A TNF-α, B IL-1a, C IL-6, D CSF2, GM-CSF. Unlike TNF-α, the LPS activation did not increase the IL-1 gene expression after one hour when cells were cultivated in normoxia.

In sharp contrast, hypoxia had a huge effect as the IL-1a gene expression was circa five fold higher for cells cultivated in hyperglycemia and normoglycemia. After 17 hours, the IL-1a expression decreased to its basal level in normoglycemia whereas that measured in hyperglycemic conditions remained high Fig 3B.

After 17 hours post-activation, hyperglycemia and hypoxia are required to maintain a high expression of IL-1A. The addition of lipopolysaccharide to macrophages triggered a slight increase of IL-6 gene expression irrespective of the culture condition Fig 3C.

When hypoxia was combined with hyperglycemic conditions, IL-6 gene expression increased dramatically for this group after 17 hours post activation.

Interestingly, cells cultivated in normoxia and hyperglycemia exhibited an increased expression of IL-6 after 17 hours compared to that after 1 hour Fig 3C. In this case, hyperglycemia has an effect on its own but it was amplified by hypoxia. Macrophage activation did not have any effect on GM-CSF gene expression of each group one hour after LPS addition Fig 3D.

A long term effect of hypoxia was observed as the gene expression of cells cultivated in hypoxia was half that of those cultivated in normoxia. Therefore, hyperglycemia and hypoxia have a negative effect on inflammation as they upregulate the gene expression of the inflammatory cytokines TNF-α, IL-6 and IL-1 in activated macrophages.

The LPS activation of macrophages led to a slight increase of the CD gene expression in normoxia and normoglycemia Fig 4A. Hypoxia and hyperglycemia had a long term effect on this gene expression.

Low oxygen tension and high glucose concentration negatively impacted the CD expression on their own. Macrophages exhibited a drastic upregulation of the Class B Scavenger receptor gene when the cells were cultivated in hypoxia.

No effect was observed in normal O 2 condition Fig 4B. After 17 hours post-activation, Class B Scavenger gene expression recovered its basal level irrespective of the culture conditions. However hypoxia had a slight positive effect when cells were cultured in hyperglycemia.

Hence, hypoxia and hyperglycemia decreases the abilities of activated macrophages for phagocytosis because the expression of CD and Class B scavenger are downregulated. The TGF-β1 gene expression was not modified one hour after activation of macrophages regardless of the O 2 and glucose conditions Fig 5.

This expression did not change after 17 hours post activation either. Hence a low O 2 tension and hyperglycemic conditions does not have any impact on TGF-β production Fig 5. SOCS-3 was upregulated one hour after LPS activation when the cells were cultivated in hypoxia.

This upregulation was higher for macrophages cultivated in normoglycemia Fig 6. The SOC-3 gene expression decreased to its basal level after 17 hours in these groups. In contrast, the cells cultivated in normoxia and hyperglycemia exhibited an upregulation of SOCS The goal of this study was to analyze the impact of hyperglycemia on the macrophage phenotype focusing on proteins involved in inflammation, proliferation, apoptosis, ECM breakdown and wound healing.

For this purpose, a gene expression microarray analysis was performed on activated macrophages cultured in a hyperglycemic and hypoxic environment with a low quantity of bovine serum with the aim of mimicking the chronic wound milieu. Subsequently, the effect of hyperglycemia and hypoxia were analyzed separately to understand their contribution in the chronic wounds.

Lastly a potential synergistic effect of high glucose concentration and low O 2 tension was evaluated. Hyperglycemia has several detrimental effects on human homeostasis. A chronic high glucose concentration leads to a process of protein glycation and the production of advanced glycation endproducts AGEs.

AGEs promote macrophage activation via NF- κ B and stimulate the production of reactive oxygen species ROS [ 22 ]. As a consequence, diabetes predisposes to epigenetic changes which lead to chronic inflammation [ 23 ].

The microarray results show that 13 pro-inflammatory cytokines and 10 chemokines were upregulated in hyperglycemia, thereby confirming the perpetual dysregulation of the inflammatory homeostasis. Pro-inflammatory macrophages are more metabolically active in hyperglycemic conditions and exclusively use glucose as a source of energy [ 24 ].

Hence, this mode of energy production can contribute to the failure to resolve inflammation. Chronic wounds are characterized by the recruitment and the persistence of immune cells in the wound bed neutrophils and macrophages [ 25 ]. The results showed the upregulation of 11 anti-apoptotic genes and the downregulation of 3 pro-apoptotic genes, indicating the direct impact of hyperglycemia on the large number of macrophages inside the cutaneous wound bed.

One major feature of impaired wound healing is the massive breakdown of extracellular matrix. High glucose concentration triggers the production and secretion of metalloproteinases such as MMP-9 and MMP-2 by fibroblasts, keratinocytes and macrophages [ 25 , 26 ]. In our conditions, hyperglycemia did not have a direct effect on proteases as only MMP-7 was affected.

In addition, this enzyme was slightly downregulated. Lipopolysacharide LPS is an outer membrane component of Gram negative bacteria which activates macrophages [ 27 ]. LPS contact with TLR receptors orientates macrophages towards a pro-inflammatory M1 phenotype.

This phenotype is characterized by the production of inflammatory cytokines such as IL-6, IL-1, TNF-α, reactive species of oxygen ROS and NO [ 28 ]. The expression of inflammatory cytokines is based on the NF- κ B activation in macrophages [ 29 ]. AGEs interacting with RAGE, their membrane receptor, can be a continuous activator of NF- κ B.

As a result, AGEs increase the production of pro-inflammatory cytokines as previously described [ 30 ]. Hypoxia is associated with the activation of hypoxia inducible factors HIFs which is the key mediator of the induction of IL-6, IL-1, TNF-α [ 31 ].

Hence, hypoxia and hyperglycemia could have a synergistic effect on the production of pro-inflammatory cytokines. In addition, a cross-talk exists between HIF and NF- κ B to increase this production.

We analyzed in detail the impact of hypoxia and high glucose on cytokine production with a kinetic view. After one hour post LPS activation, the combination of hypoxia and hyperglycemia had a dramatic effect on the expression of TNF-α and IL The combination of hyperglycemia and hypoxia is required to induce a sustained production of pro-inflammatory cytokines as the same phenomenon was observed for TNF-α and IL Beside its major role in inflammation, it has been recently shown that IL-6 could have anti-inflammatory effects via modulation of macrophage phenotype [ 32 ].

IL-6 promote the M2 phenotype of macrophages by inducing the expression of the IL-4 receptor [ 32 ]. In this study, the IL-4 receptor was not upregulated.

Several studies have reported on the anti-inflammatory effect of IL-6 and the dependency on the concentration. In this study, Il-6 was dramatically upregulated and orientated its action towards chronic inflammation [ 32 ]. Regarding IL-1, only hypoxia had a short term impact on the expression of this cytokine.

An effect was observable 17 hours post activation for the cells cultivated in hypoxia and hyperglycemia. This shows their importance for a long term effect on inflammation.

Moreover, the sustained and prolonged production of IL-1 contributes to diminish wound healing by activating TLR receptors and maintaining macrophages in a M1 phenotype [ 33 ]. Granulocyte macrophage colony-stimulating factor GM-CSF is highly upregulated in hyperglycemic conditions.

GM-CSF is produced during the inflammation phase and is a marker of M1 macrophages [ 34 ]. This cytokine stimulates the production of chemokines such as CCL2 and CCL3 and is involved in the recruitment of myeloid cells within the wound [ 33 ]. The GM-CSF expression is induced by pro-inflammatory cytokines such as IL-1 and TNF-alpha.

As a consequence, the high production of pro-inflammatory cytokines by high glucose and low O2 tension increases the expression of GM-CSF, which has also a negative effect on inflammation. In our conditions, GM-CSF was not impacted by hyperglycemia which is not consistent with the results of the micro array.

Suppressor of cytokine signaling 3 SOCS3 is associated with the pro-inflammatory M1 phenotype of macrophages. In addition, SOCS3 decreases the phagocytic activities of macrophages for apoptotic neutrophils.

The decrease of clearance of dead neutrophils impedes the resolution of inflammation and a pro-inflammatory environment shows a strong upregulation of SOCS3 [ 35 , 36 ]. Hyperglycemia seems to have a short term negative effect on SOCS3.

Surprisingly, hyperglycemia seems to favour the resolution of inflammation at this time point. However, hyperglycemia has a negative effect after 17 hours when the cells are cultivated in hyperglycemia. As SOCS-3 is upregulated in this study, this confirms the inflammatory effect of IL-6 in hyperglycemia.

It has been shown this cytokine has an anti-inflammatory effect only when SOCS-3 was downregulated or ablated [ 37 ]. Hyperglycemia combined with hypoxia also led to the upregulation of a panel of chemokines. Among them, CCL-4 is of great interest because it activates neutrophils which can trigger neutrophilic inflammation [ 38 , 39 ].

In addition, this chemokine triggers the production of pro-inflammatory cytokines. Five C-X-C chemokines CXCL 1- CXCL5 were also upregulated in hyperglycemia. For example, CXCL2 is highly expressed. Moreover, CXCL2 recruit neutrophils to infection sites. Overall, the other chemokines have the same effect, recruiting leucocytes in the wound.

Hence, hyperglycemia and hypoxia create a vicious circle which maintains a high inflammation in the wound and prevents the switch from the inflammatory phase to the proliferative one. Phagocytosis of dead cells is required for the resolution of inflammation and the transition towards the proliferative phase [ 41 ] because impaired cell clearance has been observed in diabetic wounds [ 42 ].

CD36 is a member of the class B scavenger receptor family found in macrophages. CD36 is an efferocytosis receptor which acts in combination with α v β 3 integrin to engulf dead neutrophils [ 41 ].

Unlike the normoglycemic conditions, CD36 expression does not increase in hyperglycemia one hour after LPS activation. This result shows the impaired phagocytic activities of macrophages cultivated in high glucose.

In addition, CD36 mediate s the bacteria phagocytosis and the production of inflammatory molecules such as IL-8 [ 43 ]. Hence, the absence of an upregulation of CD36 following the activation by LPS suggests the lower ability of macrophages to combat infection when they are in a hyperglycemic milieu.

Class B scavenger type I receptors CLA-1 are also involved in the pathogen s recognition and the removal of apoptotic cells. They have a lot of structural similarities with CD36 [ 43 ]. They also have an effect on cytokine production as Knock Out CLA-1 mice expressed more inflammatory cytokines than the wild type [ 43 ].

The results showed that hypoxia is an important stimulus for Class B scavenger expression because its expression is multiplied by 12 in hypoxia over that in the normoxic conditions. Hyperglycemia negatively modulates this upregulation showing once again the impaired phagocytic abilities of diabetic macrophages, thereby settling down the chronic inflammation in the cutaneous wound.

TGF-B1 is a master regulator of the wound healing process by promoting the switch between the inflammation and the proliferative phase [ 44 ].

The TGF-B activity counterbalances the effect of TNF-alpha in macrophages [ 45 ] and favours angiogenesis, ECM deposition and fibroblast proliferation.

Hyperglycemia and hypoxia did not have any effect on its gene expression. Other suggestive features of infection include foul odor, the presence of necrosis, and failure of wound healing despite optimal management. For example, pain and tenderness may be reduced or absent in patients who have neuropathy, whereas erythema may be absent in those with vascular disease.

It can clinically mimic cellulitis and presents as erythema, edema, and elevated temperature of the foot. Most patients with diabetic foot infection do not have systemic features such as fever or chills.

The presence of systemic signs or symptoms indicates a severe deep infection. Early recognition of the area of involved tissue can facilitate appropriate management and prevent progression of the infection Figure 3.

The wound should be cleansed and debrided carefully to remove foreign bodies or necrotic material and should be probed with a sterile metal instrument to identify any sinus tracts, abscesses, or involvement of bones or joints. Osteomyelitis is a common and serious complication of diabetic foot infection that poses a diagnostic challenge.

A delay in diagnosis increases the risk of amputation. Osteomyelitis is unlikely with normal ESR values; however, an ESR of more than 70 mm per hour supports a clinical suspicion of osteomyelitis. Bone biopsy is recommended if the diagnosis of osteomyelitis remains in doubt after imaging.

The severity of the infection determines the appropriate antibiotic regimen and route of administration. It also is the primary consideration in determining the need for hospitalization and the indications and timing for any surgical intervention.

A practical and simple approach to classifying diabetic foot infection is provided in Table 2. Before an infected wound is cultured, any overlying necrotic debris should be removed by scrubbing the wound with saline-moistened sterile gauze to eliminate surface contamination.

Needle aspiration of the pus or tissue fluid performed aseptically is an acceptable alternative method. Cultures of wound swabs or material from sinus tracts are unreliable and are strongly discouraged. Peripheral artery disease PAD can be diagnosed by absence of foot pulses and reduced ankle-brachial index ABI.

Calculation of ABI is done by measuring the resting systolic blood pressure in the ankle and arm using a Doppler probe. An ABI of 0. An ABI greater than 1. Patients with atypical symptoms, or whose diagnosis is in doubt, should have ABI measured after exercise on a treadmill.

An ABI that decreases by 20 percent following exercise is diagnostic of PAD, whereas a normal ABI following exercise rules out PAD. If a PAD diagnosis is confirmed and revascularization is planned, magnetic resonance angiography, computed tomography angiography, or contrast angiography can be performed for anatomic evaluation.

Venous insufficiency can be diagnosed clinically by the presence of edema and skin changes and confirmed by duplex ultrasonography. Touch, vibration, and pressure sensations should be checked routinely using cotton wool, tuning fork, and g nylon monofilament, respectively. Diagnostic imaging is not necessary for every patient with diabetes who has a foot infection.

Plain radiography of the foot is indicated for detection of osteomyelitis, foreign bodies, or soft tissue gas. Bony abnormalities associated with osteomyelitis may be indistinguishable from the destructive effects of Charcot's foot and are usually not evident on plain radiography until two to four weeks after initial infection.

Combining technetium bone scan with gallium scan or white blood cell scan may improve the diagnostic yield for osteomyelitis. Effective management of diabetic foot infection requires appropriate antibiotic therapy, surgical drainage, debridement and resection of dead tissue, appropriate wound care, and correction of metabolic abnormalities.

The selection of antibiotic therapy for diabetic foot infection involves decisions about choice of empiric and definitive antibiotic agent, route of administration, and duration of treatment Tables 4 3 , 9 and 5 3 , 24 — Initial empiric antibiotic therapy should be based on the severity of the infection, history of recent antibiotic treatment, previous infection with resistant organisms, recent culture results, current Gram stain findings, and patient factors e.

A Gram-stained smear of an appropriate wound specimen may help guide therapy. The overall sensitivity of a Gram-stained smear for identifying organisms that grow on culture is 70 percent. aureus , including MRSA if necessary, and streptococci. The patient should be reassessed 24 to 72 hours after initiating empiric antibiotic therapy to evaluate the response and to modify the antibiotic regimen, if indicated by early culture results.

Several antibiotics have been shown to be effective, but no single regimen has shown superiority. Surgery is the cornerstone of treatment for deep diabetic foot infection. Procedures range from simple incision and drainage to extensive multiple surgical debridements and amputation.

Timely and aggressive surgical debridement or limited resection or amputation may reduce the need for more extensive amputation. Surgical excision of affected bone has historically been the standard of care in patients with osteomyelitis.

Nevertheless, successful therapy with a long course of antibiotics alone has been achieved in two thirds of patients with osteomyelitis. The wound may also be treated surgically with a flap or graft, left to heal by secondary intention, or managed with negative pressure dressings.

If the infected limb appears to be ischemic, the patient should be referred to a vascular surgeon. Although noncritical ischemia can usually be treated without a vascular procedure, early revascularization within a few days of the infection is required for successful treatment of an infected foot with critical ischemia.

The wound should be dressed to allow for careful inspection for evidence of healing and early identification of new necrotic tissue. Necrotic or unhealthy tissue should be debrided, preferably surgically or with topical debriding agents.

Removing pressure from the foot wound is crucial for healing 35 and can be achieved through total contact casting, removable cast walkers, and various ambulatory braces, splints, modified half-shoes, and sandals. If osteomyelitis is present, signs of healing include a drop in ESR and loss of increased uptake on nuclear scan.

Correction of fluid and electrolyte imbalances, hyperglycemia, acidosis, and azotemia is essential. Good glycemic control may help eradicate the infection and promote wound healing. Frequent home blood glucose monitoring is strongly encouraged.

Appropriate therapeutic adjustments e. Maggot debridement therapy, granulocyte colony-stimulating factor, and hyperbaric oxygen therapy have been used for diabetic foot infection, but should not be used routinely because of lack of evidence of effectiveness. Prevention of diabetic foot ulcers begins with identifying patients at risk.

All patients with diabetes should have an annual foot examination that includes assessment for anatomic deformities, skin breaks, nail disorders, loss of protection sensation, diminished arterial supply, and inappropriate footwear.

Patients at higher risk of foot ulceration should have examinations more often. Other effective clinical interventions include optimizing glycemic control, smoking cessation, debridement of calluses, and certain types of prophylactic foot surgery.

Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Carmona GA, Hoffmeyer P, Herrmann FR, et al.

Major lower limb amputations in the elderly observed over ten years: the role of diabetes and peripheral arterial disease. Diabetes Metab. Lipsky BA, Berendt A, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis. Delamaire M, Maugendre D, Moreno M, Le Goff MC, Allannic H, Genetet B.

Impaired leucocyte functions in diabetic patients. Diabet Med. Abdulrazak A, Bitar ZI, Al-Shamali AA, Mobasher LA. Bacteriological study of diabetic foot infections.

J Diabetes Complications. Gerding DN. Foot infections in diabetic patients: the role of anaerobes. Tentolouris N, Petrikkos G, Vallianou N, et al. Prevalence of methicillin-resistant Staphylococcus aureus in infected and uninfected diabetic foot ulcers.

Clin Microbiol Infect. King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA clone as the predominant cause of skin and soft-tissue infections.

Ann Intern Med.

Chronic hyperglycemia and foot ulcers

Author: Gromi

2 thoughts on “Chronic hyperglycemia and foot ulcers

Leave a comment

Yours email will be published. Important fields a marked *

Design by ThemesDNA.com