Diabetes and Peripheral Vascular Disease: Diagnosis and Management

By Gautam V. Shrikhande

In Diabetes and Peripheral Vascular Disease, a panel of distinguished leaders in the field of medicine, podiatry, and vascular and endovascular therapy assimilate the latest literature on these issues and others for an in-depth review of the management of peripheral vascular disease. Providing an overview of the management of diabetes and diabetic foot changes as well as providing a view of cutting-edge and emerging topics in optimization of arterial status, this important title addresses pathophysiology, anatomy, diagnosis and management of diabetic peripheral vascular disease, emphasizing a multi-disciplinary approach. The first chapter of the book provides an overview of this complex disease process and discusses the teamwork required for optimal management. The chapters continue with the basic pathophysiology of diabetic atherosclerosis and a contemporary review of the management of diabetes. The genesis of diabetic foot ulceration and prevention and management strategies is covered, as is the effects of neuropathy and microvascular changes in the diabetic foot. In addition, Diabetes and Peripheral Vascular Disease covers the microbiology of diabetic foot infections, the role of endovascular interventions and vascular surgery as well as the management of the complications of these procedures, the process of amputation for those patients who have progressed beyond a limb salvage situation, and the effects of diabetes on the cerebrovascular system as well as its implications in patients with aortoiliac disease. An invaluable addition to the literature on diabetes and peripheral vascular disease, the book will be of great interest internists, family practitioners, surgeons, podiatrists, wound care specialists, and vascular specialists. Students, residents, and fellows in surgical and medical specialties should also find this book of significant value and interest.

• Language: English
• Publisher: Humana Press
• Release date: Oct 19, 2012
• ISBN: 9781627031585

Book preview

Gautam V. Shrikhande and James F. McKinsey (eds.)Contemporary DiabetesDiabetes and Peripheral Vascular Disease2012Diagnosis and Management10.1007/978-1-62703-158-5_1© Springer Science+Business Media New York 2012

1. General Considerations in the Diabetic Patient with Peripheral Vascular Disease

Rishi Kundi¹  , Andrew J. Meltzer²   and Danielle Bajakian³

(1)

Department of Vascular Surgery, Columbia University Medical Center, New York Presbyterian Medical Center, 353 East 17th Street Apt. 22B, New York, NY 10032, USA

(2)

Division of Vascular Surgery and Endovascular Interventions, New York Presbyterian Hospital, Presbyterian Hospital, 526 East 68th Street, P706, New York, NY 10021, USA

(3)

Critical Limb Ischemia Program, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY, USA

Rishi Kundi (Corresponding author)

Email: [e-mail]

Andrew J. Meltzer

Email: [e-mail]

Abstract

The confluence of diabetes and peripheral vascular disease results in a complex relationship in which each contributes to and encourages progression of the other. As the prevalence of each disease increases, the clinician caring for the diabetic patient must be prepared to take several factors into account when assessing and treating vascular disease. The evaluation and diagnosis of peripheral vascular disease is reviewed, as are nonsurgical treatment options. The indications, efficacy, and morbidity of surgical and endovascular revascularization are also discussed, as are the merits of each relative to the other. The benefits of amputation, minor and major, are considered. The frequent phenomenon of the diabetic ulcer with concurrent infection is assessed. Finally, the organization, composition, and benefits of the multidisciplinary care team are considered.

Keywords

DiabeticVasculopathyIschemicFootNeuropathicUlcerAmputation

Introduction

The prevalence of peripheral arterial disease (PAD) among American adults is estimated at 4% [1]. Among the elderly, the prevalence exceeds 20%, affecting over four million individuals, and accounting for over $20 billion in annual healthcare costs [1, 2]. Its most advanced form, critical limb ischemia (CLI), is a highly morbid condition with 1-year mortality and major amputation rates estimated at 20% and 35%, respectively.

The frequent coexistence of diabetes mellitus (DM) and PAD is readily apparent to healthcare providers involved in the care of patients with either condition [3]. The co-prevalence of these conditions is not simply an association due to shared risk factors; DM plays a fundamental role in the pathophysiology of PAD.

The relationship between diabetes and vasculopathy is complex, and despite a significant research effort in molecular, animal, and translational models, the details of this relationship have yet to be completely elucidated. At present, the end result of peripheral ischemia is thought to result from the interplay between hemodynamic, neurohumoral, and metabolic factors, culminating in endothelial dysfunction [4]. This, in turn, leads to medial smooth muscle cell dysfunction, platelet hyperactivity, and impaired fibrinolysis coupled with hypercoagulability [5]. Fundamental concerns remain unanswered. An example is the phenomenon that the regression in microvascular disease following strict blood glucose control is not observed in the larger vessels encountered by the vascular specialist [6].

Despite a considerable research effort, as well as improvements in patient education, attention to risk factor modification, and aggressive medical management, the natural history of DM is progressive and frequently includes renal disease, cardiac disease, retinopathy, and PAD [7]. Even more concerning are current statistics that identify significant geographic and socioeconomic variation in lower extremity amputation in this patient population [8, 9].

These findings highlight the need for an aggressive, multidisciplinary approach to limb salvage in the diabetic population. As an introduction to this multidisciplinary textbook, the objective of this chapter is to describe the epidemiology, pathophysiology, and management of coexistent DM and PAD. The development of a multidisciplinary team is paramount to achieving limb salvage in patients with DM and CLI. Collaboration between vascular specialists, podiatrists, medical physicians, wound care specialists, and allied health professionals has proven beneficial to the management of patients with coexisting DM and PAD; it is our hope that this introductory chapter and those that follow will provide a framework for the development of multidisciplinary efforts, resulting in improved limb salvage rates among diabetic patients and elimination of geographic disparities in care.

Epidemiology of Diabetes and Peripheral Arterial Disease

The prevalence of DM among the US elderly population approaches 20% by self-report; these CDC estimates are thought to underestimate the true prevalence by as much as 33% [10]. The dreaded complication of diabetic foot ulceration may result from acute or chronic cutaneous injury, diabetic neuropathy, or arterial insufficiency; however, it is frequently multifactorial [11]. Despite advances in diabetes management and increased awareness of PAD, the majority of diabetic foot ulcerations are now attributable to PAD alone or in combination with neuropathy (neuroischemic) [12]. The significance of neuroischemic ulceration in diabetics has been well demonstrated; it is the precipitating event for the vast majority of non-traumatic lower extremity amputations performed worldwide [13]. While primary prevention of neuroischemic ulceration may therefore appear to be an effective means of amputation prevention, there is dramatic variation in amputation rates in the US population, with clustering of high amputation rates among diabetic Medicare recipients by hospital referral region [14]. These discrepancies are not unique to the USA; in Sweden amputation rates at specialized centers can be as low as 10%, whereas rates in centers without specialization may be twice as high [13].

The tremendous variation in amputation rates among diabetics with neuroischemic ulceration suggests significant room for improvement, not only with primary prevention of neuroischemic ulceration, but with the response of healthcare providers. Through aggressive revascularization and wound care, the impressive limb salvage rates at specialized centers should be attainable irrespective of geography.

In the US population, lower socioeconomic status is itself associated with diabetes. The Boston Community Health Survey was an NIH-supported community health survey of more than 5,500 residents equally distributed amongst racial/ethnic and socioeconomic categories conducted between 2002 and 2005. The results of the survey demonstrated that lower socioeconomic class was correlated with a higher likelihood of both diagnosed and undiagnosed diabetes [15]. Moreover, ethnic differences in the prevalence of diabetes have been well documented, with nonwhite Americans being at higher risk for the disease [16]. CDC data indicate that the prevalence of diabetes among Hispanics was almost double that among whites [17]. Racial differences in the metabolic syndrome have also been demonstrated, with a resultant unequal distribution of the cardiovascular risk increase attendant to the syndrome [18].

Compounding the discrepant effects of diabetes in the USA is the well-established discrepancy in healthcare delivery that exists, particularly that regarding diabetes. 2004 CDC data indicate that Hispanics with diabetes are significantly less likely to have had their HbA1c or their feet checked for either neuropathy or ulcer within the previous year compared to white diabetics. This reduction in healthcare provision persisted even when adjustments were made for socioeconomic status and availability of care [19]. A similar examination of CDC data from 1994 to 2002 showed a similar decrease in glycemic control monitoring among blacks in Missouri [20]. Veterans’ Administration data confirm that minority patients were less likely to achieve sufficient glucose control or receive adequate monitoring than whites [21].

The combination of an increased risk of diabetes and a disparity in provision of diabetic care in those patients at highest risk has resulted in an increased risk of diabetic complications in minority patients, particularly among the vascular diseases. Community-based studies have shown that Hispanics and blacks are at significantly greater risk for neuropathy than whites and less likely to receive professional foot care [22]. African Americans and Hispanic Americans are similarly more likely to suffer from dialysis-dependent, diabetes-related end-stage renal disease and yet are less likely to have been cared for by a nephrologist before the initiation of hemodialysis [23].

Perhaps most alarming is the relatively high rate of lower extremity amputation amongst minority populations. Race was an independent risk factor for amputation among patients in a multi-institutional, 8 year study of patients in Chicago hospitals, with black patients being 1.7 times likely to undergo primary amputation than whites [24]. Among patients in Texas, the age-adjusted incidence of diabetic amputation among blacks was more than twice that of whites with Hispanic patients being between the two. Exacerbating this difference is evidence showing that the mortality of diabetes-related amputation is further increased amongst minorities [25]. There is also a disparity in overall vascular care. Using inpatient Medicare data, Holman et al. examined vascular care delivered in the 2 years prior to amputation. They found that blacks were significantly less likely to have undergone any wound debridement, toe amputation, attempted revascularization, or any limb-related admission at all prior to their major amputation [26].

The population at increased risk for diabetes and its vascular complications is also the population at increased risk for insufficient treatment for diabetes and its vascular manifestations, whether that care concerns glycemic control, kidney disease, foot care, wound care, or vascular disease. From the perspective of the vascular surgeon, the multifactorial nature of diabetic vasculopathy contributes to the problem, since without the care provided by several different specialties, the prevention of vascular disease and the success of any vascular intervention are improbable.

Pathophysiology of Diabetes and Peripheral Arterial Disease

As is detailed in Chap. 2, diabetes affects the vasculature in its entirety. Altered metabolism associated with the hyperglycemic state leads to altered arterial structure and function at the tissue, cellular, and molecular levels. Specifically, DM is a pro-inflammatory condition, as evidenced by elevations in C-reactive protein (CRP), which is associated with both DM and PAD [27, 28]. More than a mere inflammatory marker, CRP binds to endothelial cell receptors and has numerous molecular effects, including inhibition of endothelial nitric oxide synthase (eNOS), stimulates tissue factor production, and increases production of anti-fibrinolytic factors including plasminogen activator inhibitor (PAI)-1 [29].

While a comprehensive discussion of nitric oxide (NO) metabolism and its vascular smooth muscle and endothelial cell effects is beyond the scope of this text, it is important to note that alterations in NO metabolism are prevalent among patients with PAD, and these alterations are thought to play an important role in atherogenesis [30]

In diabetics, alterations in NO metabolism result from hyperglycemia and insulin resistance. The immediate result is the development of a pro-inflammatory state that eventually leads to atheroma formation via well-established molecular and cellular pathways.

Additional effects of diabetes on the peripheral vasculature, as previously mentioned, include vascular smooth muscle cell dysfunction and alterations in platelet function and fibrinolysis that lead to a hypercoagulable state, further potentiating atherogenesis and potentially contributing to the adverse outcomes after revascularization discussed later [31].

Diagnosis of PAD in the Diabetic Patient

Patients with diabetes should undergo a comprehensive history and physical examination with specific attention to symptoms suggestive of PAD, including claudication, rest pain, or known ulceration. It is important to consider that the spectrum of PAD ranges from asymptomatic patients to those with advanced tissue loss and gangrene. The physical examination must include a complete vascular examination and specific evaluation of the feet, with attention not only to evident ulceration but also temperature, dependent rubor, pallor on elevation, hairlessness, and dystrophic nails. If there is evidence of any of these stigmata of peripheral vascular disease, particularly in the setting of non-palpable pedal pulses, assessment of the ankle-brachial index is warranted. The ratio of the systolic blood pressure in the ankle divided by the systolic blood pressure at the arm is easily determined with a blood pressure cuff and handheld Doppler at the bedside. In practice, this is generally performed in the vascular laboratory, although the technique and principle should be known to all practitioners caring for diabetic patients. The ABI is considered normal if >0.91. Mild obstruction manifests as an ABI as 0.7–0.9; moderate obstruction 0.4–0.69, and severe obstruction consistent with CLI generally results in an ABI < 0.4. In patients with noncompressible arteries (such as may be found in the setting of diabetes and renal insufficiency), the ABI may be noncompressible (>1.0).

Screening ABI’s are recommended by the American Diabetes Association (ADA) in asymptomatic patients over the age of 50, or younger in the presence of other risk factors for PAD. Diagnostic testing is warranted in symptomatic patients. Referral to the vascular laboratory permits formal measurement of ABI as well as pulse volume recordings (PVRs) that permit localization of the anatomic distribution of disease. Additional studies that may be performed in the vascular laboratory, and are discussed in detail later in this text, include exercise (treadmill) testing, toe pressure measurement, and duplex ultrasound.

Medical Management and Lifestyle Modification

Although medical management of patients with PAD and DM will be discussed in detail in Chap. 3, there are several fundamental points that warrant discussion in this introductory section. Diabetes and smoking are the two most significant risk factors for eventual amputation among patients with PAD. Therefore, smoking cessation must be achieved in the diabetic smoker. It is the single most significant modifiable risk factor for amputation, PAD progression, and adverse cardiovascular events.

As previously discussed, tight glucose control does not appear to inhibit PAD to the extent that it permits avoidance of microvascular complications. Nonetheless, general guidelines advise that Hgb A1C <7.0% is a good target, provided it can be achieved without complications related to hypoglycemic events.

Hypertension is associated with atherosclerosis and the development of symptomatic PAD. The hemodynamic consequences of diabetes are irrevocably tied to hypertension, from which over 70% of type II diabetics suffer [32]. Several studies have demonstrated that inhibition of the renin–angiotensin axis with ACE modifiers can result in a decrease in vascular morbidity, most notably the MICRO-HOPE trial which demonstrated a 17% reduction in the risk of vascular disease requiring revascularization among patients who were treated with ramipril [33]. Not only was this reduction too great to attribute to the blood pressure effects alone, but animal studies employing doses of ACE inhibitors subtherapeutic for hypertension control have demonstrated decreases in vascular remodeling [34]. Treatment recommendations, however, are based primarily on the generalized cardiovascular benefit [35]. Recommendations include blood pressure control with lifestyle modifications and medications to achieve blood pressure <130/80 mmHg in patients with PAD and diabetes.

Similarly, dyslipidemia should be addressed; although studies evaluating specific effects of LDL cholesterol levels on PAD progression in diabetic patients are lacking, guidelines recommend a target LDL cholesterol level <100 mg/dl to avoid adverse cardiovascular events. Antiplatelet therapy is recommended in DM; the role of dual antiplatelet therapy remains controversial. Current guidelines suggest aspirin is sufficient for asymptomatic patients with DM and PAD, although ADA documents suggest that clopidogrel may have greater benefit in diabetics [7, 30, 31, 35].

For symptomatic patients with claudication, therapy may include exercise therapy, medical treatment, and revascularization. Diabetic patients presenting with evidence of chronic CLI necessitate an aggressive approach to revascularization and wound care in order to avoid amputation.

In claudicants, supervised exercise therapy has proven an effective and cost-sensitive alternative to immediate revascularization. While non-supervised exercise therapy is insufficient, the results from the recently published Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) trial suggested that supervised exercise therapy was as effective as endovascular revascularization [36]. With respect to the diabetic population, however, these results should be applied cautiously, as only 23% of patients in CLEVER were diabetic. Given the aforementioned effects of the hyperglycemic state on the vascular endothelium, smooth muscle cells, and angiogenesis, it is reasonable to hypothesize that the mechanism of improvement (i.e., collateral development secondary to neovascularization) may be impaired in diabetic patients, although to our knowledge this has not been specifically addressed.

Proven medical treatment for claudication is limited to cilostazol, an oral phosphodiesterase inhibitor. Although cilostazol was approved after pentoxifylline, it is the only drug that reproducibly improves walking distance in the setting of claudication. It is recommended as medical therapy for patients with DM and intermittent claudication, provided there is no evidence of congestive heart failure, which is a contraindication to its use.

Peripheral Bypass Surgery and Endovascular Therapy

While medical management and supervised exercise therapy are reasonable alternatives to patients with DM and symptomatic PAD manifest as claudication, for those patients with CLI (rest pain or ulceration with evidence of vascular insufficiency), an aggressive approach is warranted.

Current treatment options include surgical bypass and endovascular therapy (ET). Although these approaches will be discussed in detail in Chaps. 9 and Chaps. 10, some general principles warrant discussion.

Although diabetes is highly prevalent among patients with CLI, the observation that DM is associated with a poor outcome following any revascularization has been reported [37]. The pervasiveness of this opinion, even among vascular specialists, may partially explain the high amputation rates in some geographic regions in the USA.

The association between DM and poor outcomes with revascularization is perhaps secondary to the typical pattern of arterial disease seen in DM, in which infrapopliteal disease with relative sparing of the pedal vessels predominates, and multilevel disease is commonplace [37]. Moreover, the comorbidities often associated with CLI include coronary artery disease, heart failure, and renal insufficiency. In the pre-endovascular era, these associated comorbidities rendered many patients with DM and CLI unsuitable for open revascularization, thus propagating a tendency towards primary amputation.

Although some early reports suggested the futility of distal bypass surgery in these patients, 5-year patency rates for autogenous vein bypass grafts to infrapopliteal targets range from 50 to 70% in retrospective series; limb salvage rates exceed 80% [38]. The preconception that DM is associated with poor outcomes after surgical bypass appears to be misguided, as it is not DM per se, but rather associated comorbidities and the anatomic pattern of disease in these patients that results in poor outcome [39]. With appropriate patient selection, adequate conduit, and attention to the technical details of the procedure, surgical bypass remains the gold standard approach to achieve limb salvage in the patient with DM and CLI [39].

For patients without suitable venous conduit, or in whom medical comorbidities are believed to prohibit surgical bypass, endovascular therapy has assumed an integral role in the management of patients with DM and PAD. Although the durability of peripheral bypass surgery is proven, it is associated with significant perioperative morbidity and mortality [40]. Conversely, endovascular interventions are associated with reduced durability and may require serial interventions to achieve limb salvage [41–43]. However, due to the minimally invasive nature of these procedures, they are associated with reduced perioperative risk.

Given the high prevalence of medical comorbidities among patients with PAD, many vascular specialists advocate aggressive use of endovascular therapy as first-line treatment for PAD. We recently reported a series of 1,220 patients undergoing intervention for claudication (22.5%) or CLI (77.5%) [42]. By multivariate analysis, predictors of primary patency loss included TASC C/D disease (HR: 1.375 [1.164–1.624]; P < 0.001), chronic total occlusion (1.225 [1.041–1.443]; P = 0.015); DM (1.243 [1.056–1.463]; P = 0.009), congestive heart failure (1.204 [1.011–1.434]; P = 0.038), and current smoking (1.529 [1.223–1.913]; P = 0.001).

The reduced durability associated with endovascular therapy is well established; however, it is expected that serial interventions to maintain patency may permit durable limb salvage. It is therefore essential to examine those factors associated with reduced secondary patency. In the aforementioned series, these included: TASC C/D disease (1.400 [1.111–1.764]; P = 0.004), DM (1.279 [1.017–1.608]; P = 0.036), congestive heart failure (1.463 [1.168–1.833]; P = 0.001), current smoking (1.789 [1.338–2.392]; P < 0.001), and CLI (4.007 [3.106–5.169]; P = 0.001). By multivariate analysis, the only independent risk factors for limb loss were current smoking (2.3 [1.24–4.01]; P = 0.007), end-stage renal disease (1.9 [1.018–3.587]; P = 0.044), and diabetes (2.13 [1.21–3.76]; P = 0.008).

The significance of diabetes as an independent predictor of poor outcome after endovascular therapy in our series is supported by prior reports. Abularrage and colleagues at the Massachusetts General Hospital performed a retrospective analysis of over 1,000 limbs to assess the importance of diabetes on outcome after endovascular intervention. In this series, which compared 533 diabetic to 542 nondiabetic limbs, actuarial primary patency at 5 years was 42% ± 2.4%, assisted patency was 81% ± 2.0%, and limb salvage was 89% ± 1.6%. By univariate analysis, diabetes was associated with inferior 5-year primary patency (37% ± 3.4% vs. 46% ± 3.3%; P = 0.009), reduced limb salvage (84% ± 2.6% vs. 93% ± 1.8%, P < 0.0001), and survival (52% ± 3.5% vs. 68% ± 3.1%; P = 0.0001). There was no difference between diabetic and nondiabetic patients with respect to assisted patency. By multivariate analysis, diabetes was associated with reduced primary patency (1.25 [1.01–1.54]; P = 0.04), along with single-vessel peroneal runoff (HR, 1.54; 95% CI, 1.16–2.08; P < 0.003), and dialysis dependence (HR, 1.59; 95% CI, 1.10–2.33; P < 0.02). Multivariate analysis to identify those factors predicting limb loss included CLI (HR, 9.09; 95% CI, 4.17–20.00; P < 0.0001) and dialysis dependence (HR, 2.94; 95% CI, 1.39–5.00; P = 0.003; HR, 4.24; 95% CI, 2.80–6.45; P < 0.0001) [37].

Guidelines and Outcome Metrics

Understanding the success of various treatment options for PAD and diabetes requires familiarity with the language of outcomes assessment as it pertains to this group of patients. It is imperative that vascular specialists treating PAD are familiar with treatment guidelines, reporting standards, and outcome definitions.

A general overview of the management of patients with DM and PAD has been released by the ADA. This document summarizes the global approach to these patients, and includes recommendations ranging from routine preventive care to medical management and revascularization [29]. With regard to surgical revascularization, formal reporting standards have been endorsed by the Society for Vascular Surgery. This document, also known as the Rutherford Reporting Guidelines, contains an overview of the classification and surgical treatment for PAD [44]. As will be discussed in later chapters, decision-making with respect to appropriateness of endovascular (versus surgical) revascularization may be guided by the Inter-Society Consensus Guidelines for the Management of Peripheral Arterial Disease TASC-II (revised) document [45]. Recently, the Society for Vascular Surgery published Objective Performance Goals for the management of CLI, in an effort to standardize clinical studies involving the application of new technology to the management of patients with chronic CLI [46].

With respect to the outcomes of revascularization, commonly reported outcome metrics include, clinical response, primary patency, assisted primary patency, secondary patency, target lesion (or limb) revascularization, and limb salvage. Additional measures include freedom from bypass surgery, and composite endpoints (such as amputation-free survival). The following definitions of accepted outcome measures represent a summary of pertinent points from these documents.

Technical success after revascularization may be claimed in the setting of (1) antegrade flow through the treated lesion; (2) less than 25–30% residual stenosis; (3) in-line flow to the pedal arch. Post-intervention vascular laboratory studies should reveal a peak systolic velocity ratio of 2.5 or less at the treatment site and/or an ABI improvement of 0.15 or greater. Ongoing hemodynamic success relies on vascular laboratory evaluation, with a maintained ABI increase greater than 0.15 from the early post-procedural level, biphasic or triphasic waveforms. For clinical success to be claimed, these hemodynamic and technical measures must be attained in the setting of clinical improvement [44]. Clinical success is perhaps the most ambiguous outcome measure, yet at the same time the most important from a patient-centered standpoint. Clinical improvement requires improvement by at least one Rutherford–Becker clinical category, with the exception of patients with tissue loss (Rutherford–Becker 5/6) who must advance two categories, to claudication or rest pain, respectively. In each case, wound healing must occur. Moreover, improvement must be clearly attributable to the intervention, and requires hemodynamic confirmation of success: a minimum change in ABI of 0.1 is recommended [44]. Primary patency implies freedom from thrombosis and restenosis. It is generally reported using life-table analysis or Kaplan–Meier survival function. Generally some degree of restenosis is allowable (30–50%), which correlates with noninvasive vascular studies indicating a systolic velocity ratio greater than 2–2.5 or ABI decrease greater than 0.15 results in loss of primary patency. Assisted patency, also referred to as primary-assisted patency or assisted primary patency, refers to interventions necessitating a subsequent interventional procedure to maintain patency. Secondary patency refers to restoration of patency after re-occlusion. As duplex ultrasound surveillance is generally recommended after peripheral endovascular interventions, these outcome measures are generally comparable, with secondary patency calculations including those in which patency is maintained in the setting of restenosis detected by ultrasound (assisted patency) as well as re-­interventions for occlusion. Assisted patency and secondary patency are reported with Kaplan–Meier function estimation or life-table analysis.

The most relevant outcome measure for patients with CLI is limb salvage. Minor amputations (at the toe or trans-metatarsal level) are not considered limb loss. When evaluating long-term limb salvage data, it is important to note that due to the high prevalence of significant comorbidities among these patients, survival is generally poor and therefore many patients are censored due to death throughout follow-up. This fact, combined with an unclear yet significant success rate with medical therapy and wound care alone, may artificially inflate limb salvage estimates after any revascularization procedure.

It is noteworthy that, in addition to these generally accepted outcome metrics, there has been a recent paradigm shift towards the study of patient-centered outcomes that attempt to measure quality of life, permitting comparisons of the efficacy of interventions from a patient-centered perspective.

Some progressive outcomes investigators have applied various objective quality of life assessment tools to patients with CLI undergoing revascularization. These utilities range from simple postoperative functional status assessments to generalized quality of life metrics (e.g., Short Form-36, EuroQol, Nottingham Health Profile) to disease-specific (e.g., VascuQol and Walking Impairment Questionnaire) tools that account for social functioning, emotional well-being, pain, symptomatology, and overall quality of life [47–49]. It is anticipated that, given current trends in healthcare, increasing importance will be placed on these instruments in an effort to individualize clinical decision-making and outcomes reporting.

Wound Care, Debridement, Minor Amputation, and Pedal Sepsis

While neuropathic ulceration is frequently found on the plantar surface, ischemic ulceration tends to occur around the edges of the foot, in the toe or heel, at the most distal sites of perfusion. Frequently ulceration follows minor trauma, such as may occur from the use of inappropriate footwear. This phenomenon emphasizes the importance of routine preventive foot care for the diabetic patient.

Once the diabetic patient has developed ischemic or neuroischemic ulceration, timely involvement of all members of the multidisciplinary team is essential. The prior sections in this introduction, and following chapters, highlight the importance of aggressive medical management, evaluation for ischemia, and revascularization by either open or endovascular therapy, as appropriate. This involves the work of medical physicians, endocrinologists, vascular specialists specializing in limb salvage, podiatrists, and wound care specialists.

In addition to aggressive medical management, PAD evaluation, and treatment, it is imperative to address the visible manifestation of PAD and diabetes: the pedal ulcer or wound itself. Techniques include surgical debridement, the application of bioactive dressings, and minor amputation. Although a fundamental goal of the multidisciplinary approach to limb salvage is avoiding amputation, there is still a role for primary major amputation, particularly among patients presenting with pedal sepsis in whom less aggressive options pose a threat to life.

When debridement is warranted, frequent sharp debridement is the preferred method of treatment when necrotic tissue is present. Localized fluctuance, suggesting underlying purulence, must be drained. The presence of air in the soft tissues on radiography, or crepitance on examination, should alert providers to significant underlying infection and prompt plans for immediate surgical management in addition to administration of intravenous antibiotics. These findings suggest wet gangrene; such a diabetic foot infection must be regarded as a surgical emergency.

Incision and drainage must be sufficiently wide as to allow for egress of purulence and facilitate subsequent dressing changes. One must balance this need with the desire to spare tissue; as a result the use of counter incisions remains somewhat controversial. In cases of localized sepsis, toe amputation may be necessary for drainage and removal of necrosis. Review of results with minor amputation (at the toe or forefoot level) suggests that these techniques, followed by revascularization efforts and local wound care, may permit control of infection and long-term limb salvage, although wound healing may be slow [49].

Major Amputation

While the ultimate goal of care in the management of PAD and diabetes is avoidance of amputation, in some cases major amputation is inevitable (discussed further in Chap. 12). In the setting of sepsis and extensive gangrene, for example, emergent guillotine amputation may be necessary as a lifesaving measure. Although there remains a role for primary amputation (i.e., amputation without efforts at revascularization), this probably applies to a smaller subgroup of patients than previously recognized. While extensive tissue loss, non-ambulatory status, the presence of significant contractures, and the absence of target vessels are indications to consider primary amputation, the role of systemic comorbidities in clinical decision-making remains ill defined. Using propensity score matched National Surgical Quality Improvement Program data, Barshes and colleagues at the Brigham and Women’s Hospital recently reported that, in the most systemically ill patients with CLI, amputation was no less morbid than surgical revascularization [50]. This study does not even take into consideration the possibility of endovascular revascularization, which is associated with reduced perioperative morbidity and mortality. Given these findings, considered in the context of the endovascular era, it would appear that comorbidities should not preclude efforts at revascularization.

A Multidisciplinary Approach to Limb Salvage

This introduction provides an overview of general considerations in the management of coexistent DM and PAD. These topics, from risk factor modification to revascularization and amputation will be individually emphasized in subsequent chapters. Clearly, there has been great improvement in limb salvage rates worldwide in the past several decades. This phenomenon cannot be attributed to the efforts of any group of specialists in isolation. Rather, there is considerable evidence to suggest that a multidisciplinary approach is mandated to achieve successful limb salvage.

Logerfo and colleagues at the Beth Israel Deaconess Medical Center (formerly the New England Deaconess Hospital) and Joslin Diabetes Center were pioneers in the implementation of a team approach to limb salvage in patients in PAD and DM [51, 52]. Numerous reports from this group and other pioneers, utilizing a team-centered approach, identified reduced amputation rates, shorter hospitalizations, and total cost reduction [52, 53].

At a minimum, the team approach to diabetes must consist of a vascular surgeon or vascular specialist dedicated to treating CLI and podiatrist [48, 54, 55]. In reality, the multidisciplinary team should include these specialists, in addition to an orthopedist, wound care specialist, diabetologist, infectious disease specialist, prosthetist, and associated internists, cardiologists and allied health professionals.

The podiatrist is frequently the point of contact for the diabetic patient with a potentially limb-threatening condition. As a vital member of the so-called toe and flow construct (Fig. 1.1), the podiatrist’s duties frequently include initial management of diabetic foot infections, initiation of the neurovascular evaluation, and wound management. The vascular surgeon must have a commitment to aggressive management of PAD, and in the present era should be well versed in both surgical and endovascular techniques as applied to PAD. In addition, vascular surgeons are frequently involved in wound care, and perform minor or major amputations, as necessary.

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Fig. 1.1

The toe and flow model of the multidisciplinary team is designed to coordinate care of the diabetic wound, the diabetic foot, and perfusion through cooperation between a podiatrist and a vascular surgeon. The addition of other specialists enables more comprehensive and more detailed attention to all aspects of the disease process [based on data from Rogers LC, Andros G, Caporusso J, et al. Toe and flow: essential components and structure of the amputation prevention team. J Am Podiatr Med Assoc. 2010;100(5):342–8]

The commitment of an infectious disease specialist is essential. While medical management and antibiotic therapy should never supplant aggressive surgical debridement in the setting of complex diabetic foot infection, selection of appropriate antibiotics for an adequate duration is of great importance in the treatment of acute infections as well as osteomyelitis. Given the ever-changing microbial environment, evolving antibiotic resistance patterns, immunocompromised state associated with diabetes, and prevalence of multiresistant organisms in nursing facilities and hospitals, the infectious disease specialist plays a critical role on the team.

The endocrinologist or diabetologist has a crucial role. While management of diabetes is frequently straightforward, in many patients—particularly in the setting of infection—blood glucose levels may prove markedly difficult to normalize. In addition to management of DM in the inpatient setting, the diabetologist will frequently play a critical role in the outpatient management of these patients, assuming a leadership role in the risk factor modification and general medical care.

Depending on institutional particularities, general surgeons and orthopedists may have a role in the multidisciplinary team, particularly as adjunctive specialists in wound care management.

The conception of diabetic vascular disease, from molecular pathophysiology to clinical outcomes, is one of multiplicity. From one cause come many disease pathways, culminating in the phenomenon of clinical diabetic peripheral vascular disease. For that clinical disease to be adequately treated, then, all contributing disease pathways must be addressed and treated. The social and economic context of diabetes has presented an obstacle to the sufficient treatment of all of the elements of diabetic peripheral vascular disease, leaving those most at risk of vascular complications with the least comprehensive care. For these reasons, our institution among others has adopted a multidisciplinary approach to the prevention, assessment (Fig. 1.2), and treatment of diabetic PAD. The result of this method has, around the world, proven to be both efficacious and economically sound. The understanding of diabetic vascular disease as fundamentally multifactorial and deserving of correspondingly multidisciplinary care is the single most important consideration of peripheral vascular disease in diabetic patients.

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Fig. 1.2

The stairway to amputation. The evolution of the infected diabetic foot involves neuropathy and ischemia acting to progress from the ulcer to infection treatable only by infection. This sequence can be arrested by treatment of both neuropathy and ischemia as well as the consequent traumatic ulceration or infection [based on data from Rogers LC, Andros G, Caporusso J, et al. Toe and flow: essential components and structure of the amputation prevention team. J Am Podiatr Med Assoc. 2010;100(5):342–8]

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