Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal



Page Path
HOME > Diabetes Metab J > Volume 39(4); 2015 > Article
Complications Peripheral Arterial Disease in Patients with Type 2 Diabetes Mellitus
Sang Youl Rhee, Young Seol Kim
Diabetes & Metabolism Journal 2015;39(4):283-290.
Published online: August 17, 2015
  • 75 Download
  • 44 Web of Science
  • 36 Crossref
  • 46 Scopus

Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea.

Corresponding author: Young Seol Kim. Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.

Copyright © 2015 Korean Diabetes Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • Peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM) exhibits broad clinical characteristics and various consequences and is known as one of the major macrovascular complications of T2DM. Atherosclerosis is recognized as the most direct and important cause of PAD, but acute or chronic limb ischemia may be the result of various risk factors. In light of the increasing number of patients who undergo peripheral vascular procedures, the number of subjects who are exposed to the risks for PAD and related complications is increasing. In this review, we will discuss the clinical and epidemiological characteristics of PAD, as well as the clinical significance of PAD in T2DM subjects.
Peripheral arterial disease (PAD) in people with type 2 diabetes mellitus (T2DM) exhibits broad clinical characteristics and various consequences and is known as one of the major macrovascular complications of T2DM, the prevalence of which is on the rise [1]. Atherosclerosis is recognized as the most direct and important cause of PAD, but acute or chronic limb ischemia may be induced by various risk factors [2].
Due to the increasing number of patients who undergo peripheral vascular procedures due to the aging of the overall population, the worldwide increase in T2DM prevalence, and developments in medical technologies, the number of subjects who are exposed to the risks for PAD and related complications is on the rise [3].
In this review, we will discuss the clinical and epidemiologic characteristics of PAD, as well as the clinical significance of PAD in T2DM subjects.
PAD is a general term for all vascular diseases that lead to abnormal function and structure of the aorta, its branches, and the lower-limb arteries secondary to atherosclerosis and thromboembolism-related pathophysiologies [4]. Typically, atherosclerosis decreases the size of the vascular lumen, leading to deficiencies in arterial perfusion without noticeable symptoms. However, depending on the degree of obstruction, various symptoms, including claudication, resting pain, ulceration, or gangrene, may occur during exercise [5].
PAD is typically classified according to clinical symptoms. The Fontaine and Rutherford classifications are the most well-known systems, under which increased stage describes severe symptoms (Table 1) [678]. PAD typically exhibits a chronic course but may be acutely exacerbated. Depletion of effective vascular volume by thrombosis, embolism, dehydration, and shock may be a cause of acute exacerbation of PAD [2]. This acute arterial occlusion is a fatal disease that requires emergent manipulations, such as amputation [4].
The prevalence of PAD is highly dependent on the definition of the diagnostic method. But, most studies on the prevalence of PAD among general populations used a low ankle-brachial index (ABI, ≤0.9) as a surrogate for PAD. From the analyses of National Health and Nutrition Examination Survey 1999 to 2004 in the United States, prevalence of low ABI was 5.9%, corresponding 7.1 million adults with PAD [9]. Excluding subjects with known cardiovascular disease, prevalence was 4.7% [9]. Similarly, a total of 5.8% of the United States population age ≥40 years had a low ABI or history of lower-extremity revascularization, representing 6.8 million people [10].
Prevalence of PAD was known diverse by ethnicity, with black people having the highest age-adjusted prevalence of low ABI [1011]. Prevalence of low ABI is known to increase with age. In one study, prevalence of low ABI was 1.9% in the age group of 40 to 59 years, 8.1% in the group of 60 to 74 years, and 17.5% in the group of ≥75 years [11]. Although PAD is presumed to be more common in men, the prevalence of low ABI does not estimated to vary significantly by gender [1213].
The PAD prevalence in T2DM subjects is unclear, but in the Framingham heart study, 20% of symptomatic PAD subjects also exhibited diabetes [14]. According to the the prevention of progression of arterial disease and diabetes (POPADAD) study, 20.1% of ≥40-year-old patients with diabetes were associated symptoms exhibited PAD [15]. However, given that a large number of PAD patients are asymptomatic, it is assumed that more subjects with diabetes exhibit PAD. In the study conducted with 6,880 German people whose age ≥65 years, the prevalence of PAD by low ABI in diabetes subjects was 26.3%; whereas, prevalence of PAD in non-diabetic subjects was 15.3% [16]. Similar findings also have been reported [1718].
In Korea, there has been no epidemiologic study on the prevalence of PAD in the total population, although a study was conducted in 14 university hospitals with approximately 1,400 ≥50-year-old T2DM subjects exhibiting risk factors for PAD [19]. In this study, 11.9% of the subjects were found to exhibit PAD estimated by low ABI [19]. This prevalence was somewhat lower than that in other Asian regions (Fig. 1). Besides, there were some epidemiologic evidences which have investigated mainly in the university hospitals in Korea. In the previously diagnosed patients with coronary artery disease or cerebrovascular disease, prevalence of PAD by low ABI was estimated to be 7.8% [20]. In the prospective study among subjects with acute ischemic stroke or transient ischemic attack, prevalence of PAD by low ABI was 13.0% [21]. Additionally, prevalence of PAD by low ABI was 12.8% in the patients with previous percutaneous coronary intervention [22].
Dyslipidemia, smoking, hypertension, and diabetes are known risk factors of PAD, similar to coronary artery disease [45192023]. These risks increase in patients who are ≥70-year-old; in those who are 50- to 69-year-old with a history of diabetes or smoking; and in patients 40- to 49-year-old with diabetes and one or more atherosclerosis-related risk factor(s), intermittent claudication, abnormalities in pulse palpation of the lower limb or atherosclerosis in non-peripheral arteries (e.g., coronary, carotid, and renal artery) [2]. When a symptom of claudication appears, the symptom becomes aggravated in approximately 10% to 20% of patients in 5 years and advances to critical limb ischemia (CLI) in 1% to 2% of patients [2].
The clinical progression of PAD patients with diabetes is worse than that of those who are not. Lesions occur over a wider range of vasculature; the frequency of amputation was higher; and there was a significant difference in mortality [119]. In the results from multicenter study conducted by Asian subjects with type 2 diabetes, obesity, smoking, duration of diabetes and previous cardiovascular disease were identified as independent risk factors of PAD [19].
PAD is associated with cardiovascular disease [56]. Non-fatal myocardial infarction (MI) or stroke occurs in 20% of patients, and 15% to 30% of patients were died [24]. In the results from domestic study, subjects with previous history of coronary artery disease or cardiovascular disease had significantly higher prevalence of diabetes, dyslipidemia, renal insufficiency, and PAD with claudication [20]. CLI occurs in both lower limbs in 50% of patients at 1-year follow-up. CLI is accompanied by lower limb amputation in 25% and by cardiovascular disease in 25% [2425].
The ABI is the standard for the diagnosis of PAD in clinical treatment or epidemiologic studies and represents a useful resource for the salvage of the lower limb, wound healing and survival prediction of patients [24]. ABI is calculated as the ratio of systolic blood pressure in the brachial artery to that in the posterior tibial artery after resting in a supine position, which is considered abnormal when it is below 0.90 [24]. When the diagnostic threshold was set to 0.90, the sensitivity of ABI for the diagnosis of PAD with >50% stenosis was 95%, and its specificity was 100% [26]. An ABI between 0.41 and 0.90 is evaluated as a mildly to moderately decreased blood flow, and an ABI <0.40 is evaluated as severely decreased blood flow [24]. In the recent meta-analysis, the pooled sensitivity and specificity of ABI ≤0.90 for PAD diagnosis were 75% and 86% and the pooled platelet lymphocyte ratio and neutrophil lymphocyte ratio were 4.18 and 0.29, respectively [27]. These results may means that ABI is useful for identifying serious stenosis in clinical practice. However, in patients with diabetes, patients with distal lesions in elderly patients, and patients with mild stenosis less than 75%, diagnostic value of ABI was decreased [28].
Angiography is the most accurate test to examine vascular anatomy and pathology [3] and is, considered an essential evaluation tool prior to surgical management [3]. However, because angiography is an invasive procedure, risks such as bleeding, infection, and rupture as well as side effects associated with contrast media, such as hypersensitivity reaction and nephrotoxicity, may occur. In recent years, non-invasive imaging technologies have been developed, and ultrasound, multidetector computed tomography (MDCT) and magnetic resonance (MR) angiography have been widely used [29303132]. Such non-invasive imaging modalities had reported comparable diagnostic and prognostic accuracy to conventional angiography [3334]. In meta-analyses, sensitivity for detecting more than 50% stenosis or occlusion in MDCT was estimated 95%, and its specificity was 96%, and sensitivity for diagnosing segmental steno-occlusions for MR angiography was estimated 94.7% and specificity was 95.6% [3135].
However, several limitations were also reported. We could observe decreased accuracy by intestinal gas, and decreased sensitivity in multivessel lesion in ultrasound imaging [36]. In MDCT images, the risk of contrast media induced nephrotoxicity is well known in the subjects with chronic kidney disease [35]. Moreover, utility of MR angiography is limited for detection of in-stent restenosis, and risk of gadolinium induced nephrogenic systemic fibrosis is also concerned in the subjects with chronic kidney disease [3637].
The diagnosis of PAD necessitates the regulation of associated risk factors, medical treatment, and intervention of lesions in the lower limb. The management of risk factors of PAD is similar to the regulation of risk factors of disease in the coronary artery.
Exercise is known to be effective for the improvement of symptoms of claudication, the extension of walking distance to the aggravation of pain and the promotion of maximum oxygen consumption [34]. Walking exercise is typically recommended, and patients are asked to partake in this exercise at least three times a week for 30 to 45 minutes for 12 weeks or more [4]. A systematic review identified that compared exercise with usual care or placebo, exercise improved walking ability from 50% to 200%, and significantly improved maximal walking time, pain-free walking distance, and maximum walking distance [38].
Smoking cessation is very important advice for the treatment of PAD patients. The effects of cessation of smoking were studied in 343 patients with intermittent claudication [39]. The cumulative proportions with MIs after 10 years were 11% and 53%; the cumulative rates of cardiac deaths 6% and 43%; and the 10-year survival 82% and 46% among non-smokers and smokers, respectively [39]. For patients who have difficulty in stopping smoking on their own, varenicline, bupropion, and nicotine replacement therapy may be considered [4].
The management of associated diseases, such as diabetes, high blood pressure, and dyslipidemia, has an important impact on the clinical progress of PAD. In particular, meticulous foot care to prevent aggravation, crucial for clinical progress in diabetic patients, is recommended [40]. In diabetic patients, the general goal of blood glucose regulation is to achieve glycosylated hemoglobin <7%, but the goal of treatment is individualized for each patient's characteristics [41]. No controlled trials have directly evaluated the effects of glucose lowering on the natural history of PAD. The goal hypertension therapy is to achieve blood pressure below 140/90 mm Hg, and the use of angiotensin-converting enzyme inhibitor is preferentially considered [4]. There are no data evaluating whether treatment of hypertension alters aggravation in patients with PAD. Nevertheless, hypertension should be controlled in such patients to reduce morbidity from cardiovascular disease [26]. The use of statins for dyslipidemia regulation is preferentially considered, which may be combined with fibric acid derivatives [4]. In a systemic review, specifically evaluated patients with lower limb PAD concluded that lipid-lowering therapy reduced disease progression, helped alleviate symptoms, and improved total walking times and pain-free walking distance [42].
There is an insufficient evidence to suggest a direct relationship between the use of antiplatelet agents and increases in pain or walking distance, but such agent have been proven to be significantly effective in decreasing the incidence of MI, stroke, or cardiovascular death; thus, low-dose aspirin (75 to 325 mg/day) is typically recommended. A systematic review found a similar reduction in mortality for patients with claudication treated with antiplatelet therapy compared with placebo [43]. Clopidogrel is a secondary drug recommended if aspirin cannot be used; 75 mg/day is recommended [34]. The clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) trial found that clopidogrel 75 mg/day had a modest, but significant advantage over aspirin 325 mg/day for the prevention of stroke, MI, and PAD in subjects with a recent stroke, MI, or PAD [44]. Cilostazol is a phosphodiesterase inhibitor that impedes platelet aggregation and exhibits vasodilatory effect and improves dyslipidemia. Treatment with cilostazol for 24 weeks reportedly improved walking distance without claudication by approximately 54% on average compared with a placebo group or a group to which pentoxifylline was administered [45]. In a meta-analysis, the administration of 200 mg/day cilostazol for 12 to 24 weeks increased the maximum walking distance without claudication by up to 50% or 67% [46].
If patient symptoms do not improve despite proper drug treatment and rehabilitation, invasive procedures should be considered. If normal activities are not possible due to claudication and if the lesions exhibit minimal surgery-related risks and the intervention exhibits a high probability of success, re-perfusion should be attempted through a transcutaneous procedure or operation [234]. Early intervention is recommended when resting pain, ischemic ulceration, or necrosis is present. Balloon angioplasty and stent insertion are known to be effective in the alleviation of symptoms in many PAD patients [4748]. In the past, the transcutaneous vascular procedure was used restrictively to cause stenosis of short lesions or occlusive lesions, but with advances in technology, transcutaneous vascular intervention has been widely applied prior to the surgical procedure and widely attempted in patients in whom it is difficult to perform the surgical treatment. For the long-term success of transcutaneous vascular intervention, the position and length of the lesions are important, and surgical treatment is preferred if the lesions are long, if there is stenosis in multiple areas, if the lesion is occlusive and if the lesion is calcified and stenotic [234].
Experimental or investigational agents for PAD include prostaglandins, naftidrofuryl, propionyl levocarnitine, defibrotide, ginkgo biloba, hyperbaric oxygen, and angiogenic growth factors [49]. Naftidrofuryl can be used for treatment of claudication, and it has known to have fewer side effects than cilostazol [26]. However, there had not been any large scale, randomized trial for relevant treatment, and more clear evidences are required for extensive clinical application.
As PAD becomes an increasingly important complication in T2DM subjects, a deeper understanding of the related diseases and the establishment of a standardized method of treatment is particularly important. Indeed, PAD confers poorer prognosis in T2DM patients compared with nondiabetic patients, and early diagnosis, management and positive treatment are necessary. However, with the exception of a few epidemiological studies, there is a lack of data concerning Korean type 2 diabetes patients, and more strategies for the diagnosis and treatment of PAD based on empirical evidence are needed.
This article was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020).

CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.

  • 1. Jude EB, Oyibo SO, Chalmers N, Boulton AJ. Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome. Diabetes Care 2001;24:1433-1437. PubMed
  • 2. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B. American Association for Vascular Surgery. Society for Vascular Surgery. Society for Cardiovascular Angiography and Interventions. Society for Vascular Medicine and Biology. Society of Interventional Radiology. ACC/AHA Task Force on Practice Guidelines Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease. American Association of Cardiovascular and Pulmonary Rehabilitation. National Heart, Lung, and Blood Institute. Society for Vascular Nursing. TransAtlantic Inter-Society Consensus. Vascular Disease Foundation. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation 2006;113:e463-e654. PubMed
  • 3. European Stroke Organisation. Tendera M, Aboyans V, Bartelink ML, Baumgartner I, Clement D, Collet JP, Cremonesi A, De Carlo M, Erbel R, Fowkes FG, Heras M, Kownator S, Minar E, Ostergren J, Poldermans D, Riambau V, Roffi M, Rother J, Sievert H, van Sambeek M, Zeller T. ESC Committee for Practice Guidelines. ESC guidelines on the diagnosis and treatment of peripheral artery diseases: document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J 2011;32:2851-2906. ArticlePubMed
  • 4. Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss L, Golzarian J, Gornik HL, Jaff MR, Moneta GL, Olin JW, Stanley JC, White CJ, White JV, Zierler RE. American College of Cardiology Foundation Task Force. American Heart Association Task Force. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:1555-1570. PubMedPMC
  • 5. Layden J, Michaels J, Bermingham S, Higgins B. Guideline Development Group. Diagnosis and management of lower limb peripheral arterial disease: summary of NICE guidance. BMJ 2012;345:e4947ArticlePubMed
  • 6. Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, Jones DN. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997;26:517-538. ArticlePubMed
  • 7. Fontaine R, Kim M, Kieny R. Surgical treatment of peripheral circulation disorders. Helv Chir Acta 1954;21:499-533. PubMed
  • 8. Korea National Diabetes Program. Clinical practive guideline for diabetic peripheral arterial disease. Seoul: Clinical Research Center for Type 2 Diabetes Mellitus designated by Ministry of Health and Welfare, Republic of Korea; 2007.
  • 9. Pande RL, Perlstein TS, Beckman JA, Creager MA. Secondary prevention and mortality in peripheral artery disease: National Health and Nutrition Examination Study, 1999 to 2004. Circulation 2011;124:17-23. ArticlePubMedPMC
  • 10. Allison MA, Ho E, Denenberg JO, Langer RD, Newman AB, Fabsitz RR, Criqui MH. Ethnic-specific prevalence of peripheral arterial disease in the United States. Am J Prev Med 2007;32:328-333. ArticlePubMed
  • 11. Menke A, Muntner P, Wildman RP, Dreisbach AW, Raggi P. Relation of borderline peripheral arterial disease to cardiovascular disease risk. Am J Cardiol 2006;98:1226-1230. ArticlePubMed
  • 12. Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation 2004;110:738-743. ArticlePubMed
  • 13. Ostchega Y, Paulose-Ram R, Dillon CF, Gu Q, Hughes JP. Prevalence of peripheral arterial disease and risk factors in persons aged 60 and older: data from the National Health and Nutrition Examination Survey 1999-2004. J Am Geriatr Soc 2007;55:583-589. ArticlePubMed
  • 14. Murabito JM, D'Agostino RB, Silbershatz H, Wilson WF. Intermittent claudication. A risk profile from The Framingham Heart Study. Circulation 1997;96:44-49. ArticlePubMed
  • 15. Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, Macfarlane P, Morris A, Jung R, Kelly C, Connacher A, Peden N, Jamieson A, Matthews D, Leese G, McKnight J, O'Brien I, Semple C, Petrie J, Gordon D, Pringle S, MacWalter R. Prevention of Progression of Arterial Disease and Diabetes Study Group. Diabetes Registry Group. Royal College of Physicians Edinburgh. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 2008;337:a1840ArticlePubMedPMC
  • 16. Lange S, Diehm C, Darius H, Haberl R, Allenberg JR, Pittrow D, Schuster A, von Stritzky B, Tepohl G, Trampisch HJ. High prevalence of peripheral arterial disease and low treatment rates in elderly primary care patients with diabetes. Exp Clin Endocrinol Diabetes 2004;112:566-573. ArticlePubMed
  • 17. Marso SP, Hiatt WR. Peripheral arterial disease in patients with diabetes. J Am Coll Cardiol 2006;47:921-929. ArticlePubMed
  • 18. Mostaza JM, Suarez C, Manzano L, Cairols M, Lopez-Fernandez F, Aguilar I, Diz Lois F, Sampedro JL, Sanchez-Huelva H, Sanchez-Zamorano MA. Merito Study Group. Sub-clinical vascular disease in type 2 diabetic subjects: relationship with chronic complications of diabetes and the presence of cardiovascular disease risk factors. Eur J Intern Med 2008;19:255-260. ArticlePubMed
  • 19. Rhee SY, Guan H, Liu ZM, Cheng SW, Waspadji S, Palmes P, Tai TY, Suwanwalaikorn S, Kim YS. PAD-SEARCH Study Group. Multi-country study on the prevalence and clinical features of peripheral arterial disease in Asian type 2 diabetes patients at high risk of atherosclerosis. Diabetes Res Clin Pract 2007;76:82-92. ArticlePubMed
  • 20. Ahn S, Park YJ, Min SI, Kim SY, Ha J, Kim SJ, Kim HS, Yoon BW, Min SK. High prevalence of peripheral arterial disease in Korean patients with coronary or cerebrovascular disease. J Korean Med Sci 2012;27:625-629. ArticlePubMedPMCPDF
  • 21. Chung PW, Kim DH, Kim HY, Park KY, Park TH, Hong JM, Kim GM, Bang OY, Oh K, Lee SJ. Differences of ankle-brachial index according to ischemic stroke subtypes: the peripheral artery disease in Korean patients with ischemic stroke (PIPE) study. Eur Neurol 2013;69:179-184. ArticlePubMedPDF
  • 22. Kim EK, Song PS, Yang JH, Song YB, Hahn JY, Choi JH, Gwon HC, Lee SH, Hong KP, Park JE, Kim DK, Choi SH. Peripheral artery disease in korean patients undergoing percutaneous coronary intervention: prevalence and association with coronary artery disease severity. J Korean Med Sci 2013;28:87-92. ArticlePubMedPMCPDF
  • 23. Lee YH, Shin MH, Kweon SS, Choi JS, Rhee JA, Ahn HR, Yun WJ, Ryu SY, Kim BH, Nam HS, Jeong SK, Park KS. Cumulative smoking exposure, duration of smoking cessation, and peripheral arterial disease in middle-aged and older Korean men. BMC Public Health 2011;11:94ArticlePubMedPMCPDF
  • 24. Dormandy J, Heeck L, Vig S. The fate of patients with critical leg ischemia. Semin Vasc Surg 1999;12:142-147. PubMed
  • 25. Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, Krook SH, Hunninghake DB, Comerota AJ, Walsh ME, McDermott MM, Hiatt WR. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001;286:1317-1324. ArticlePubMed
  • 26. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. TASC II Working Group. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 2007;45(Suppl S):S5-S67. ArticlePubMed
  • 27. Xu D, Zou L, Xing Y, Hou L, Wei Y, Zhang J, Qiao Y, Hu D, Xu Y, Li J, Ma Y. Diagnostic value of ankle-brachial index in peripheral arterial disease: a meta-analysis. Can J Cardiol 2013;29:492-498. ArticlePubMed
  • 28. Nam SC, Han SH, Lim SH, Hong YS, Won JH, Bae JI, Jo J. Factors affecting the validity of ankle-brachial index in the diagnosis of peripheral arterial obstructive disease. Angiology 2010;61:392-396. ArticlePubMedPDF
  • 29. Rofsky NM, Adelman MA. MR angiography in the evaluation of atherosclerotic peripheral vascular disease. Radiology 2000;214:325-338. ArticlePubMed
  • 30. Schernthaner R, Fleischmann D, Lomoschitz F, Stadler A, Lammer J, Loewe C. Effect of MDCT angiographic findings on the management of intermittent claudication. AJR Am J Roentgenol 2007;189:1215-1222. ArticlePubMed
  • 31. Menke J, Larsen J. Meta-analysis: accuracy of contrast-enhanced magnetic resonance angiography for assessing steno-occlusions in peripheral arterial disease. Ann Intern Med 2010;153:325-334. ArticlePubMed
  • 32. Koelemay MJ, den Hartog D, Prins MH, Kromhout JG, Legemate DA, Jacobs MJ. Diagnosis of arterial disease of the lower extremities with duplex ultrasonography. Br J Surg 1996;83:404-409. ArticlePubMedPDF
  • 33. Langenberger H, Schillinger M, Plank C, Sabeti S, Dick P, Cejna M, Lammer J, Minar E, Loewe C. Agreement of duplex ultrasonography vs. computed tomography angiography for evaluation of native and in-stent SFA re-stenosis: findings from a randomized controlled trial. Eur J Radiol 2012;81:2265-2269. ArticlePubMed
  • 34. Leeson CP, Robinson M, Francis JM, Robson MD, Channon KM, Neubauer S, Wiesmann F. Cardiovascular magnetic resonance imaging for non-invasive assessment of vascular function: validation against ultrasound. J Cardiovasc Magn Reson 2006;8:381-387. ArticlePubMed
  • 35. Met R, Bipat S, Legemate DA, Reekers JA, Koelemay MJ. Diagnostic performance of computed tomography angiography in peripheral arterial disease: a systematic review and meta-analysis. JAMA 2009;301:415-424. ArticlePubMed
  • 36. Pollak AW, Norton PT, Kramer CM. Multimodality imaging of lower extremity peripheral arterial disease: current role and future directions. Circ Cardiovasc Imaging 2012;5:797-807. PubMedPMC
  • 37. Pedersen M. Safety update on the possible causal relationship between gadolinium-containing MRI agents and nephrogenic systemic fibrosis. J Magn Reson Imaging 2007;25:881-883. ArticlePubMed
  • 38. Lane R, Ellis B, Watson L, Leng GC. Exercise for intermittent claudication. Cochrane Database Syst Rev 2014;7:CD000990Article
  • 39. Jonason T, Bergstrom R. Cessation of smoking in patients with intermittent claudication. Effects on the risk of peripheral vascular complications, myocardial infarction and mortality. Acta Med Scand 1987;221:253-260. PubMed
  • 40. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Bowering K, Embil JM. Foot care. Can J Diabetes 2013;37(Suppl 1):S145-S149. ArticlePubMed
  • 41. American Diabetes Association. 6. Glycemic targets. Diabetes Care 2015;38(Suppl 1):S33-S40. ArticlePubMedPDF
  • 42. Aung PP, Maxwell HG, Jepson RG, Price JF, Leng GC. Lipid-lowering for peripheral arterial disease of the lower limb. Cochrane Database Syst Rev 2007;(4):CD000123ArticlePubMedPMC
  • 43. Wong PF, Chong LY, Mikhailidis DP, Robless P, Stansby G. Antiplatelet agents for intermittent claudication. Cochrane Database Syst Rev 2011;(11):CD001272ArticlePubMed
  • 44. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996;348:1329-1339. PubMed
  • 45. Dawson DL, Cutler BS, Hiatt WR, Hobson RW 2nd, Martin JD, Bortey EB, Forbes WP, Strandness DE Jr. A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med 2000;109:523-530. ArticlePubMed
  • 46. Thompson PD, Zimet R, Forbes WP, Zhang P. Meta-analysis of results from eight randomized, placebo-controlled trials on the effect of cilostazol on patients with intermittent claudication. Am J Cardiol 2002;90:1314-1319. ArticlePubMed
  • 47. Soder HK, Manninen HI, Jaakkola P, Matsi PJ, Rasanen HT, Kaukanen E, Loponen P, Soimakallio S. Prospective trial of infrapopliteal artery balloon angioplasty for critical limb ischemia: angiographic and clinical results. J Vasc Interv Radiol 2000;11:1021-1031. ArticlePubMed
  • 48. Powell RJ, Fillinger M, Walsh DB, Zwolak R, Cronenwett JL. Predicting outcome of angioplasty and selective stenting of multisegment iliac artery occlusive disease. J Vasc Surg 2000;32:564-569. ArticlePubMed
  • 49. Ouriel K. Peripheral arterial disease. Lancet 2001;358:1257-1264. ArticlePubMed
Fig. 1

Age- and gender-specific direct standardized prevalence of peripheral arterial disease in Asian patients with type 2 diabetes mellitus. Adapted from Rhee et al., with permission from Elsevier [19].

Table 1

Classifications of peripheral arterial disease by clinical symptoms

Fontaine classification Rutherford classification
Stage Clinical symptoms Stage Category Clinical symptoms
I Asymptomatic 0 0 Asymptomatic
IIa Mild claudication I 1 Mild claudication
IIb Moderate to severe claudication I 2 Moderate claudication
III Ischemic rest pain I 3 Severe claudication
IV Ulceration or gangrene II 4 Ischemic rest pain
III 5 Minor tissue loss
IV 6 Major tissue loss

Adapted from Korea National Diabetes Program, Clinical practice guideline for diabetic peripheral arterial disease [8].

Figure & Data



    Citations to this article as recorded by  
    • Predictive model and risk analysis for peripheral vascular disease in type 2 diabetes mellitus patients using machine learning and shapley additive explanation
      Lianhua Liu, Bo Bi, Li Cao, Mei Gui, Feng Ju
      Frontiers in Endocrinology.2024;[Epub]     CrossRef
    • Health Disparities in Nontraumatic Lower Extremity Amputations. A Systematic Review and Meta-Analysis
      Arthur Tarricone, Allen Gee, Karla De La Mata, Louis Primavera, Michael Trepal, Wayne Axman, Vinayak Perake, Prakash Krishnan
      Annals of Vascular Surgery.2023; 88: 410.     CrossRef
    • Peripheral Arterial Disease: A Narrative Review
      Divya Parwani, Mohamed A Ahmed, Anmol Mahawar, Vasavi Rakesh Gorantla
      Cureus.2023;[Epub]     CrossRef
    • Development and validation of a nomogram to predict the risk of peripheral artery disease in patients with type 2 diabetes mellitus
      Jiemei Liang, Jiazhao Song, Tiehui Sun, Lanning Zhang, Shan Xu
      Frontiers in Endocrinology.2022;[Epub]     CrossRef
    • The interrelationship between diabetes mellitus and peripheral arterial disease
      Konstanze Stoberock, Mark Kaschwich, Shiva Sophia Nicolay, Nazeh Mahmoud, Franziska Heidemann, Henrik C. Rieß, Eike Sebastian Debus, Christian-Alexander Behrendt
      Vasa.2021; 50(5): 323.     CrossRef
    • Evaluation of the American Society of Anesthesiologists Physical Status Classification System in Risk Assessment for Lower Extremity Reconstruction with Free Tissue Transfer
      Andrés A. Maldonado, Rabanus Steinebach, M. Carmen Morillo, Michael Sauerbier
      Journal of Reconstructive Microsurgery.2021; 37(07): 622.     CrossRef
    • Sensitivity and Specificity of Ankle Brachial Index (ABI) and Pulse Wave Handheld Doppler (PWHD) Compared with Angiography as Diagnostic Test for Patients with Peripheral Artery Disease (PAD)
      Valdy Thomas, Djony Tjandra, Richard Sumangkut, Billy Karundeng, Grace Korompis
      Journal of Indonesian Society for Vascular and Endovascular Surgery.2021; 2(1): 10.     CrossRef
    • Healthcare Costs Associated with Complications in Patients with Type 2 Diabetes among 1.85 Million Adults in Beijing, China
      Jun-Hui Wu, Yao Wu, Zi-Jing Wang, Yi-Qun Wu, Tao Wu, Meng-Ying Wang, Xiao-Wen Wang, Si-Yue Wang, Jia-Ting Wang, Huan Yu, Yong-Hua Hu
      International Journal of Environmental Research and Public Health.2021; 18(7): 3693.     CrossRef
    • Clinical considerations after endovascular therapy of peripheral artery disease
      Stefanos Giannopoulos, Ehrin J. Armstrong
      Expert Review of Cardiovascular Therapy.2021; 19(5): 369.     CrossRef
    • Intensive Blood Pressure Control and Diabetes Mellitus‐Related Limb Events in Patients With Type 2 Diabetes Mellitus: Reanalysis of ACCORD
      Kenneth Tran, Margaret Stedman, Tara I. Chang
      Journal of the American Heart Association.2021;[Epub]     CrossRef
    • Major adverse cardiovascular and limb events in patients with diabetes and concomitant peripheral artery disease treated with sodium glucose cotransporter 2 inhibitor versus dipeptidyl peptidase-4 inhibitor
      Hsin-Fu Lee, Shao-Wei Chen, Jia-Rou Liu, Pei-Ru Li, Lung-Sheng Wu, Shang-Hung Chang, Yung-Hsin Yeh, Chi-Tai Kuo, Yi-Hsin Chan, Lai-Chu See
      Cardiovascular Diabetology.2020;[Epub]     CrossRef
    • Skeletal muscle microvascular insulin resistance in type 2 diabetes is not improved by eight weeks of regular walking
      Lauren K. Park, Elizabeth J. Parks, Ryan J. Pettit-Mee, Makenzie L. Woodford, Thaysa Ghiarone, James A. Smith, Allan R. K. Sales, Luis A. Martinez-Lemus, Camila Manrique-Acevedo, Jaume Padilla
      Journal of Applied Physiology.2020; 129(2): 283.     CrossRef
    • Clinical Utility of the Ankle-Brachial Index and Toe Brachial Index in Patients with Diabetic Foot Ulcers
      Mutasem Ababneh, Mousab Y. Al Ayed, Asirvatham A. Robert, Mohamed A. Al Dawish
      Current Diabetes Reviews.2020; 16(3): 270.     CrossRef
    • MicroRNA Profile of Patients with Chronic Limb-Threatening Ischemia
      Muzammil H. Syed, Abdelrahman Zamzam, Jason Valencia, Hamzah Khan, Shubha Jain, Krishna K. Singh, Rawand Abdin, Mohammad Qadura
      Diagnostics.2020; 10(4): 230.     CrossRef
    • ¿Pensamos en la enfermedad arterial periférica de los miembros inferiores en nuestros pacientes mayores con diabetes antes de que aparezcan las complicaciones?
      Francesc Formiga, Abelardo Montero, Dolores Lopez Carmona
      Revista Española de Geriatría y Gerontología.2020; 55(4): 236.     CrossRef
    • Higher Mortality Rate in Moderate-to-Severe Thoracoabdominal Injury Patients with Admission Hyperglycemia Than Nondiabetic Normoglycemic Patients
      Wei-Ti Su, Shao-Chun Wu, Sheng-En Chou, Chun-Ying Huang, Shiun-Yuan Hsu, Hang-Tsung Liu, Ching-Hua Hsieh
      International Journal of Environmental Research and Public Health.2019; 16(19): 3562.     CrossRef
    • Quantification of Mitochondrial Oxidative Phosphorylation in Metabolic Disease: Application to Type 2 Diabetes
      Matthew T. Lewis, Jonathan D. Kasper, Jason N. Bazil, Jefferson C. Frisbee, Robert W. Wiseman
      International Journal of Molecular Sciences.2019; 20(21): 5271.     CrossRef
    • Diabetes and risk of peripheral artery disease in patients undergoing first-time coronary angiography between 2000 and 2012 – a nationwide study
      Sadaf Kamil, Thomas S. G. Sehested, Nicholas Carlson, Kim Houlind, Jens F. Lassen, Casper N. Bang, Helena Dominguez, Christian T. Pedersen, Gunnar H. Gislason
      BMC Cardiovascular Disorders.2019;[Epub]     CrossRef
    • Analysis of diabetes quality assessment findings and future directions for the appropriate management of diabetes in Korea
      Yu Jin Kim, Suk Chon, Seungjoon Oh, Jeong-taek Woo, Sung Woon Kim, Sang Youl Rhee
      The Korean Journal of Internal Medicine.2019; 34(1): 125.     CrossRef
    • Evaluation of Risk Factors for Major Amputation in Patients With Diabetes and Peripheral Artery Disease Receiving Antiplatelet Therapy ― Post Hoc Analysis of a Prospective Observational Multicenter Cohort Study (SEASON) ―
      Yukihito Higashi, Tetsuro Miyata, Hiroshi Shigematsu, Hideki Origasa, Masatoshi Fujita, Hiroshi Matsuo, Hiroaki Naritomi, Masahide Nakajima, Satoshi Yuki, Hideto Awano
      Circulation Journal.2019; 83(9): 1929.     CrossRef
    • Preoperative hemoglobin A1c levels and increased risk of adverse limb events in diabetic patients undergoing infrainguinal lower extremity bypass surgery in the Vascular Quality Initiative
      Nikhil Singh, Chubing Zeng, Juan Pablo Lewinger, Aaron M. Wolfson, David Shavelle, Fred Weaver, Parveen K. Garg
      Journal of Vascular Surgery.2019; 70(4): 1225.     CrossRef
    • High Mobility Group Box-1 and Diabetes Mellitus Complications: State of the Art and Future Perspectives
      Biscetti, Rando, Nardella, Cecchini, Pecorini, Landolfi, Flex
      International Journal of Molecular Sciences.2019; 20(24): 6258.     CrossRef
    • Lower sensitivity of ankle-brachial index measurements among people suffering with diabetes-associated vascular disorders: A systematic review
      Ayman Abouhamda, Majid Alturkstani, Yousef Jan
      SAGE Open Medicine.2019; 7: 205031211983503.     CrossRef
    • MiR-323b-5p acts as a novel diagnostic biomarker for critical limb ischemia in type 2 diabetic patients
      Biao Cheng, Ju-yi Li, Xiao-chao Li, Xiu-fang Wang, Zhong-jing Wang, Jue Liu, Ai-ping Deng
      Scientific Reports.2018;[Epub]     CrossRef
    • Selecting living donors for uterus transplantation: lessons learned from two transplantations resulting in menstrual functionality and another attempt, aborted after organ retrieval
      Sara Y. Brucker, Mats Brännström, Florin-Andrei Taran, Silvio Nadalin, Alfred Königsrainer, Katharina Rall, Dorit Schöller, Melanie Henes, Hans Bösmüller, Falko Fend, Konstatin Nikolaou, Mike Notohamiprodjo, Peter Rosenberger, Christian Grasshoff, Eckhard
      Archives of Gynecology and Obstetrics.2018; 297(3): 675.     CrossRef
    • Medical Resource Consumption and Quality of Life in Peripheral Arterial Disease in Korea: PAD Outcomes (PADO) Research
      Seung-Woon Rha, Seung-Hyuk Choi, Doo-Il Kim, Dong Woon Jeon, Jae-Hwan Lee, Kyung-Soon Hong, Tae-Joon Cha, Jang-Hyun Cho, Sang Kon Lee, Yong Hwan Park, Woo Jung Park, Hyun-Joo Kim, Young-Joo Kim, Juneyoung Lee, Donghoon Choi
      Korean Circulation Journal.2018; 48(9): 813.     CrossRef
    • The improvement of oxidative stress by two proprietary herbal medicines in type 2 diabetes
      Yue Zhao, Xiaofei An, Jingshun Liu, Su Liu, Weilong Xu, Xu Yu, Jiangyi Yu
      Complementary Therapies in Medicine.2018; 40: 120.     CrossRef
    • Effects of foot complications in patients with Type 2 diabetes mellitus on public healthcare: An analysis based on the Korea National Diabetes Program Cohort
      So Young Park, Sang Youl Rhee, Suk Chon, Kyu Jeung Ahn, Sung-Hoon Kim, Sei Hyun Baik, Yongsoo Park, Moon Suk Nam, Kwan Woo Lee, Jeong-taek Woo, Ki Hong Chun, Young Seol Kim
      Journal of Diabetes and its Complications.2017; 31(2): 375.     CrossRef
    • Prolonged sitting leg vasculopathy: contributing factors and clinical implications
      Jaume Padilla, Paul J. Fadel
      American Journal of Physiology-Heart and Circulatory Physiology.2017; 313(4): H722.     CrossRef
    • Mortality Rate Associated with Admission Hyperglycemia in Traumatic Femoral Fracture Patients Is Greater Than Non-Diabetic Normoglycemic Patients but Not Diabetic Normoglycemic Patients
      Cheng-Shyuan Rau, Shao-Chun Wu, Yi-Chun Chen, Peng-Chen Chien, Hsiao-Yun Hsieh, Pao-Jen Kuo, Ching-Hua Hsieh
      International Journal of Environmental Research and Public Health.2017; 15(1): 28.     CrossRef
    • Augmented Contractility to Noradrenaline in Femoral Arteries from the Otsuka Long-Evans Tokushima Fatty Rat, a Model of Type 2 Diabetes
      Shota Kobayashi, Takayuki Matsumoto, Makoto Ando, Maika Iguchi, Kumiko Taguchi, Tsuneo Kobayashi
      Biological & Pharmaceutical Bulletin.2017; 40(12): 2061.     CrossRef
    • Comparison of Antidiabetic Medications during the Treatment of Atherosclerosis in T2DM Patients
      Xiaojie Liu, Tao Mei, Wei Chen, Shandong Ye
      Mediators of Inflammation.2017; 2017: 1.     CrossRef
    • The relationship between insulin resistance and periodontitis is not affected by Mediterranean diet in a Spanish population
      M. Pulido-Moran, P. Bullon, J.M. Morillo, M. Battino, J.L. Quiles, MCarmen Ramirez-Tortosa
      Archives of Oral Biology.2017; 77: 62.     CrossRef
    • The Role of Liuwei Dihuang Pills and Ginkgo Leaf Tablets in Treating Diabetic Complications
      Yue Zhao, Jiangyi Yu, Jingshun Liu, Xiaofei An
      Evidence-Based Complementary and Alternative Medicine.2016; 2016: 1.     CrossRef
    • Stent revascularization versus bypass surgery for peripheral artery disease in type 2 diabetic patients – an instrumental variable analysis
      Chia-Hsuin Chang, Jou-Wei Lin, Jiun Hsu, Li-Chiu Wu, Mei-Shu Lai
      Scientific Reports.2016;[Epub]     CrossRef
    • Microsurgical reconstruction for post—traumatic defects of lower leg in the elderly: A comparative study
      Lingyun Xiong, Emre Gazyakan, Matthias Wähmann, Amir Bigdeli, Thomas Kremer, Leila Harhaus, Jiaming Sun, Ulrich Kneser, Christoph Hirche
      Injury.2016; 47(11): 2558.     CrossRef

    • PubReader PubReader
    • Cite
      export Copy
      Download Citation
      Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

      • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
      • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
      • Citation for the content below
      Peripheral Arterial Disease in Patients with Type 2 Diabetes Mellitus
      Diabetes Metab J. 2015;39(4):283-290.   Published online August 17, 2015
    • XML DownloadXML Download
    Related articles

    Diabetes Metab J : Diabetes & Metabolism Journal