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Diabetes Watch

Essential Keys To Diagnosing And Treating PAD In Patients With Diabetes

Peripheral arterial disease (PAD) is an extremely prevalent, substantially underdiagnosed condition, which has a significant risk of morbidity and mortality. Recent data suggests that PAD affects nearly 18 million Americans and greater than 202 million globally.1,2 Patients with diabetes at highest risk include those age 50 or older, or those under age 50 with comorbid hypertension, hyperlipidemia or obesity. Individuals with a history of cardiovascular disease and those over age 65 are also at high risk.1,3

Complicating the ability to diagnose PAD, approximately 50 percent of PAD patients are asymptomatic while another 33 percent have atypical symptomatology.4 Unfortunately, once diagnosed with PAD, 20 percent will experience a life-altering cardiovascular complication such as a myocardial infarction or cerebrovascular accident while 30 percent will experience a life-ending cardiovascular complication.5

Why Diabetes And PAD Are Frequent Comorbid Conditions

Diabetes mellitus is also a global health emergency.6 As of 2016, 422 million people had diabetes worldwide, up from an estimated 382 million people in 2013 and 108 million in 1980.7,8 The prevalence of diabetes varies worldwide. It is greater in middle-aged people in developing countries and people over 65 years of age in developed countries such as the United States.9  

The U.S. has the unfortunate distinction of having the third largest number of adults suffering from diabetes.6 Currently, 14.3 percent of the U.S. population has diabetes with over 36 percent undiagnosed.10 Over the last 17 years, the U.S. prevalence of diabetes has approximately doubled in the two key age groups afflicted by PAD: those 45 to 64 years old and those 65 and older.10-15 By 2012, one-third of the elderly had diabetes while another 50 percent had pre-diabetes.10 In those between 45 to 64 years of age, 17.5 percent had diabetes and 45 percent had pre-diabetes.10

Diabetes mellitus and peripheral arterial disease do not just independently increase the risk for each other. Diabetes is synergistic with PAD. In the Framingham study, there was a 3.5 to 8.6 percent increase in developing PAD if the patient had diabetes.16 In the Hoorn study, the prevalence rate of an ankle brachial index (ABI) of <0.9 in individuals with normal glucose tolerance was 7 percent, which increased to 20.9 percent in patients with diabetes.17 Recent research demonstrates that these diseases share a common pathological pathway: insulin resistance.18  

Simply put, PAD afflicts a greater percentage of people with diabetes than people without diabetes.19-24 In patients with diabetes age 50 and older, 30 to 40 percent suffer from PAD.19,20,23,25,26 In contrast, the prevalence of PAD in those with normal glucose levels appears to be about 10 to 20 percent.19-22,24

In patients with diabetes, the risk of PAD increases with age, duration of diabetes and the presence of peripheral neuropathy.27 African-Americans and Hispanics with diabetes have a higher prevalence of PAD than non-Hispanic Caucasians.27 Diabetes increases the risk of developing PAD by 1.5 to 4 times.28 In addition, the likelihood of developing PAD increases with the severity of diabetes as measured by hemoglobin A1c (HbA1c).29

In the past, the thinking was that the type of diabetes did not necessarily affect the prevalence of PAD with essentially identical prevalences found with type 1 and type 2 diabetes.30 However, more recent studies have found a much higher prevalence of PAD (23.5 percent) in patients with type 1 diabetes than in those with type 2 diabetes.31 The vascular disease that arises from diabetes is primarily microangiopathy (abnormalities at the capillary level) and macroangiopathy (the result of arteriosclerosis).

Further complicating the diagnosis of PAD in patients with diabetes is the presence of peripheral neuropathy. Peripheral neuropathy and PAD are known risk factors for foot ulceration. Moulik and colleagues found that between 40 and 60 percent of patients with diabetic foot ulcers have PAD, which increased their risk of amputation and mortality.32 As the vascular disease progresses, tissue ulceration and ultimately gangrene develop if reperfusion does not occur.

Diabetes mellitus dramatically increases the morbidity and mortality associated with PAD, doubling the risk of cardiovascular disease and leading to a profoundly increased incidence of stroke and coronary artery disease.33 Nearly 75 percent of deaths in patients with diabetes are due to coronary artery disease.34 Similarly, the majority of patients with PAD die from coronary artery disease (55 percent) or stroke (25 percent).35 Less than 10 percent die from peripheral vascular events, most commonly from a ruptured aortic aneurysm.35

A Closer Look At Adverse Outcomes With Diabetes And CLI

There is an even closer relationship between diabetes and critical limb ischemia (CLI), the most severe and deadly form of PAD. Although somewhat more than 14 percent of the U.S. population have diabetes, 60 to 80 percent of patients with CLI have diabetes.10,36,37

Critical limb ischemia occurs when there is a sustained, severe decrease in leg blood flow, which, if untreated, leads to rest pain, ulcers and limb loss.38 Unless patients with CLI have successful revascularization, the six-month mortality rate is 20 percent and the amputation rate is 40 percent.37  

Patients with diabetes present with advanced CLI because of the complex interplay of neuropathy, ischemia, microvascular dysfunction and infection.39 In addition, patients with diabetes and PAD are more prone to developing sudden critical ischemia due to thrombosis or a pivotal event that rapidly leads to ulcers or infection.27  

Lower limb atherosclerotic disease is much more virulent in patients with diabetes. Patients with diabetes have more severe ischemia, a greater number of amputations, experience higher mortality and die at a younger age.40 A higher percentage of patients with diabetes and PAD develop CLI and are at greater risk of progression to gangrene and amputation.37,41-43

In the U.S., diabetes is the cause of 50 to 67 percent of all nontraumatic lower extremity amputations.44,45 Diabetes increases the risk of nontraumatic amputation by 28 times. The rate of amputation increases with age with the highest rates occurring in patients with diabetes age 75 and older.45

Diabetes is an independent risk factor for amputation.37 In patients with CLI, the presence of diabetes increases the odds of undergoing amputation by more than twice.46 Patients with diabetes also undergo major amputations at an earlier age, are more likely to require higher level initial amputations and frequently require contralateral amputations.37,47 In addition, the risk of amputation increases with the severity of diabetes as measured by HbA1c.48  

Diagnosing PAD In The Patient With Diabetes

Diagnosing PAD in the patient with diabetes begins with a comprehensive history identifying the risk factors, a family history of diabetes as well as noting any ulcerations, chronic wounds, prior vascular testing or prior diagnosis of PAD. Inquiring as to any lower extremity pain or cramping, especially with walking, may help to diagnose PAD.32

Lower extremity clinical findings of PAD may include thin and trophic changes of the skin, increased distal cooling, diminished or absent digital hair, diminished or absent pulses, dependent rubor or pallor with limb elevation. Vascular assessment initially begins with non-invasive arterial studies of the lower extremities including an ABI, an exercise ABI, arterial Doppler with pulse volume recording (PVR) testing, and may necessitate more invasive vascular studies including computed tomography (CT) angiography, magnetic resonance angiography (MRA), and ultimately an angiogram.

A Quick Guide To PAD Treatment Options

Aggressive risk factor modification is needed to reduce cardiovascular mortality. Risk factor modification includes smoking cessation, weight reduction in those who are obese, blood glucose control in patients with diabetes and antihypertensive agents in those with abnormal blood pressure. Antiplatelets and antilipids are also part of standard medical management.5,49

One can relieve intermittent claudication symptoms with supervised exercise therapy as well as cilostazol and statins.49 Patients with severe progressive claudication and those suffering from CLI should have revascularization to reduce the risk of limb loss, relieve symptoms and improve quality of life.49 Revascularization includes surgical bypass, endarterectomy and endovascular interventions.5,49

Dr. Tursi is the Chief of Foot and Ankle Surgery at Our Lady of Lourdes Medical Center in Camden, N.J. He is a Fellow of the American College of Foot and Ankle Surgeons, and is the Foot and Ankle Specialist for the Philadelphia Flyers. Dr. Tursi is a Clinical Instructor with the University of Pennsylvania/Presbyterian Residency Program. He is the Podiatric and Wound Care Chairman for the New Cardiovascular Horizons annual conference, and the Chairman of the American Professional Wound Care Association.

Dr. Walker is the President of the Cardiovascular Institute of the South. He is a Clinical Professor of Medicine at the Louisiana State University School of Medicine in New Orleans and a Clinical Professor of Medicine at the Tulane University School of Medicine in New Orleans. Dr. Walker is the Chairman of the New Cardiovascular Horizons annual conference.

Ms. Yost is the President of the Sage Group, LLC in Beaufort, S.C. She is the Business of Peripheral Vascular Disease Chairman for the New Cardiovascular Horizons annual conference.

1.     Fowkes FG, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013; 382(9901):1329-40.
2.     Yost ML. Critical limb ischemia, Volume I. United States epidemiology 2016 supplement. The Sage Group. Available at / . Published 2016.
3.     National Heart, Lung and Blood Institute. What is Peripheral Arterial Disease? Available at . Published August 2, 2011.
4.     PubMed Health. Abdominal aortic aneurysm. Available at .
5.     Weitz JI, Byrne J, Clagett GP, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation. 1996; 94(11):3026-49.
6.     International Diabetes Federation (IDF). IDF Diabetes Atlas 2015, Seventh Edition. Available at: .
7.     World Health Organization. Global Report on Diabetes. Available at . Published 2016.
8.     Gale EA, Gillespie KM. Diabetes and gender. Diabetologia. 2001;44(1):3-15.
9.     Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047-1053.
10.     Menke A, Casagrande S, Geiss L, Cowie CC. Prevalence of and trends in diabetes among adults in the United States, 1988-2012. JAMA. 2015; 314(10):1021-9.
11.     Cowie CC, Rust KF, Byrd-Holt DD, et al. Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population. Diabetes Care. 2006; 29(6): 1263-8.
12.     Cowie CC, Williams DE, Rust KF, et al. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005-2006. Diabetes Care. 2009; 32(2):287-94.
13.     Centers for Disease Control and Prevention. Early release of selected estimates based on data from the January-March 2006 National Interview Survey. Available at .
14.     Centers for Disease Control and Prevention (CDC). Prevalence of diabetes and impaired fasting glucose in adults--United States, 1999-2000. Morb Mortal Wkly Rep. 2003; 52(35):833-7.11.
15.     Savji N, Rockman CB, Skolnick AH, et al. Association between advanced age and vascular disease in different arterial territories. J Am Col Cardiol. 2013; 61(16):1735-43.
16.     Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. J Am Geriatr Soc. 1985;33(1):13-18.
17.     Beks PJ, Mackaay AJ, de Neeling JN, de Vries H, Bouter LM, Heine RJ. Peripheral arterial disease in relation to glycaemic level in an elderly Caucasian population: the Hoorn study. Diabetologia. 1995; 38(1):86–96.
18.     Utsunomiya K. Treatment strategy for type 2 diabetes from the perspective of systemic vascular protection and insulin resistance. Vasc Health Risk Manag. 2012;8:429-436.
19.     Barzilay JI, Gottdiener JS, Spiekerman CF, et al. Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders. Diabetes Care. 2001; 24(7):1233-9.
20.     Mackaay AJ, Beks PJ, Dur AH, et al. The distribution of peripheral vascular disease in a Dutch Caucasian population: comparison of type II diabetic and non-diabetic subjects. Eur J Vasc Endovasc Surg. 1995; 9(2):170-5.
21.     Beach KW, Strandness DE Jr. Arteriosclerosis obliterans and associated risk factors in insulin-dependent and non-insulin-dependent diabetes. Diabetes. 1980; 29(11):882-8.
22.     Lange S, Diehm C, Darius H, et al. High prevalence of peripheral arterial disease but low antiplatelet treatment rates in elderly primary care patients with diabetes. Diabetes Care. 2003; 26(12):3357-8.
23.     Faglia E, Caravaggi C, Marchetti R, et al. Screening for peripheral arterial disease by means of the ankle-brachial index in newly diagnosed Type 2 diabetic patients. Diabet Med. 2005; 22(10):1310-14.
24.     Nilsson SE, Nilsson JE, Frostberg N, Emilsson T. The Kristianstad Survey II. Acta Med Scand. 1967; (Suppl.) 469: 1-42.
25.     Brandle M, Burke R, Zhou H, et al. The direct medical cost of type 2 diabetes. Diabetes Care. 2003; 26(8):2300-4.  
26.     Norman PE, Davis WA, Bruce DG, Davis TME. Peripheral arterial disease and the risk of cardiac death in Type 2 diabetes. Diabetes Care. 2006; 29(3):575-80.
27.     American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care. 2003; 26(12):3333-41.
28.     Bartholomew JR, Olin JW. Pathophysiology of peripheral arterial disease and risk factors for its development. Cleveland Clinic J Med. 2006; 73(Suppl4):S8-14.
29.     Adler AI, Boulton AJM, Stevens RJ, et al. UKPDS 59: Hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes. Diabetes Care. 2002; 25(5):894-99.
30.     Welborn TA, et al. Clinical macrovascular disease in Caucasoid diabetic subjects: logistic regression analysis of risk variables. Diabetologia. 1984; 27(6):568-573.
31.     Walters DP, et al. The prevalence, detection, and epidemiological correlates of peripheral vascular disease: a comparison of diabetic and non-diabetic subjects in an English community. Diabet Med. 1992;9(8):710-715.
32.     Moulik PK, Mtonga R, Gill GV. Amputation and mortality in new-onset diabetic foot ulcers stratified by etiology. Diabetes Care. 2003;26(2):491-494.
33.     Sarwar N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010; 375(9733):2215-22.
34.     O’Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-425.
35.     Ouriel K. Peripheral arterial disease. Lancet. 2001; 358(9289):1257-64.
36.     Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2007. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2008.
37.     Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TransAtlantic Inter-Society Consensus (TASC) Working Group. TASC document. J Vasc Surg. 2000; 31(Suppl):S1-S296.
38.     Biamino G, Scheinert D, Schmidt A, et al. Critical limb ischemia: new techniques for complex intervention. HMP Communications, Malvern, PA, 2004.
39.     Akbari CM, LoGerfo FW. Diabetes and peripheral vascular disease. J Vasc Surg. 1999; 30(2):373-84.
40.     Jude EB, Oyibo S, Chalmers N, Boulton AJM. Peripheral arterial disease in diabetic and nondiabetic patients. A comparison of severity and outcomes. Diabetes Care. 2001; 24(8):1433-7.
41.     Faglia E, Favales F, Quarantiello A, et al. Angiographic evaluation of peripheral arterial occlusive disease and its role as a prognostic determinant for major amputation in diabetic subjects with foot ulcers. Diabetes Care. 1998; 21(4):625-30.
42.     Jonason T, Ringqvist I. Diabetes mellitus and intermittent claudication. Relation between peripheral vascular complications and location of occlusive atherosclerosis in the legs. Acta Med Scand. 1985; 218(2):217-21.
43.     Jonason T, Ringqvist I. Factors of prognostic importance for subsequent rest pain in patients with intermittent claudication. Acta Med Scand. 1985; 218(1):27-33.
44.     Reiber GE, Boyko EJ, Smith DG. Lower extremity foot ulcers. In: Diabetes in America, 1995. NIH Publication No. 95-1468, pp. 409-28.
45.     Centers for Disease Control and Prevention. Hospital discharge rates for nontraumatic lower extremity amputation by diabetes status-United States, 1997. Morb Mortal Wkly Rep. 2001; 50(43):954-8.
46.     Henry AJ, Hevelone ND, Belkin MB, Nguyen LL. Socioeconomic and hospital-related predictors of amputation for critical limb ischemia. J Vasc Surg. 2011; 53(2):330-9el.
47.     Dillingham TR, Pezzin LE, Shore AD. Reamputation, mortality, and health care costs among persons with dysvascular lower-limb amputations. Arch Phys Med Rehabil. 2005; 86(3):480-6.
48.     Stratton IM, Adler AI, Neil HAW, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000; 321(7258):405-12.
49.     Shammas NW. Epidemiology, classification, and modifiable risk factors of peripheral arterial disease. Vascular Health Risk Manage. 2007; 3(2):229–34.

Diabetes Watch
Frank J. Tursi, DPM, FACFAS, Craig Walker, MD, and Mary Yost, MBA
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