Peripheral arterial disease in patients with diabetes mellitus.

Diabetes mellitus magnifies the risk of cardiovascular morbidity and mortality. (1) Besides the well-recognized microvascular complications of diabetes, such as nephropathy and retinopathy, there is a growing epidemic of macrovascular complications, including diseases of the coronary arteries, peripheral arteries and carotid vessels, particularly in the burgeoning type 2 diabetic population. (2) Despite this challenge, many primary care physicians have not yet adopted evidence-based management strategies. The traditional therapeutic approaches emphasize glycemic control, which limits microvascular disease but lacks an established benefit in macrovascular disease. Understanding atherosclerosis in diabetes and instituting therapy guided by emerging evidence should improve patient outcomes. The evidence supports aggressive antiatherosclerotic management strategies upon diagnosis of type 2 diabetes to minimize the risk of cardiovascular morbidity and mortality. (3)

Epidemiologic evidence confirms an association between diabetes and an increased prevalence of peripheral arterial disease (PAD). Individuals with diabetes have a two- to fourfold increase in PAD rates, (4) as well as an increased incidence of femoral bruits and absent pedal pulses, (5) and many have abnormal rates of ankle-brachial indices ranging from 11.9 to 16%. (6,7) The duration and severity of diabetes correlate with the incidence and extent of PAD. (8) In type 2 diabetes, an average interval of arterial impairment is 9 to 10 years; in type 1 diabetes, it is approximately 17 to 22 years. (9)

Diabetes changes the nature of PAD. Diabetic patients more commonly have infrapopliteal arterial occlusive disease and vascular calcification than their nondiabetic cohorts. (8) The Hoorn study (10) examined the rates of PAD among groups ranging from patients with normal glucose tolerance to those with diabetes requiring multiple medications. The 7% prevalence of abnormal ankle-brachial indices in individuals with normal glucose tolerance increased to 20.9% in those requiring multiple hypoglycemic medications.

Patients with diabetes develop the symptomatic forms of PAD, intermittent claudication and amputation more frequently than nondiabetics. (11) In the Framingham cohort, (12) the presence of diabetes increased the risk of claudication by 3.5-fold in men and 8.6-fold in women. Worse, diabetes causes most nontraumatic lower extremity amputations in the United States. The relative risk for lower extremity amputation in patients with diabetes was 12.7 (95% CI, 10.9-14.9) compared with that of nondiabetic patients in the Medicare population and as high as 23.5 (95% CI, 19.3-29.1) for diabetic persons aged 65 to 74 years. (13)

Despite the marked increase in lower extremity atherosclerosis risk, we have inadequate information regarding the role of medical therapies in diabetic patients with PAD. No evidence shows that tight glycemic control, aggressive blood pressure management, or the use of antiplatelet agents decreases the incidence of intermittent claudication or critical limb ischemia. (14) Although simvastatin decreased the rates of claudication in patients with CAD in the Scandinavian Simvastatin Survival Study, the trial did not report data specific to patients with diabetes. (15) Even in the absence of definitive data, we recommend that patients with diabetes receive therapies of proven benefit in broader patient populations because cardiovascular events remain the principal cause of death in patients with PAD.

In the June issue of the Journal, Ahmadi et al (16) discussed the prevalence of peripheral arterial diseases in Asian Indian diabetics in different age groups and compared the prevalence of PAD in diabetics on different therapies. They indicated that the prevalence of PAD was directly proportional to the duration of diabetes mellitus and the age of the patients. The prevalence of PAD was not limited by the treatment modality in diabetics.

References

1. Resnick HE, Shorr RI, Kuller L, et al. Prevalence and clinical implications of American Diabetes Association-defined diabetes and other categories of glucose dysregulation in older adults. J Clin Epidemiol 2001;54:869-876.

2. Sobel BE, Schneider DJ. Cardiovascular Complications in Diabetes Mellitus. Curr Opin Pharmacol 2005;5:143-148.

3. Weiss JS, Sumpio BE. Review of prevalence and outcome of vascular disease in patients with diabetes mellitus. Eur J Vase Endovasc Surg 2006;31:143-150.

4. Newman AB, Siscovick DS, Manolio TA. et al. Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Circulation 1993;88:837-845.

5. Abbott RD. Brand FN, Kannel WB. Epidemiology of some peripheral arterial findings in diabetic men and women. Am J Med 1990;88:376-381.

6. Meijer WT, Hoes AW. Rutgers D, et al. Peripheral arterial disease in the elderly: the Rotterdam Study. Arterioscler Thromb Vasc Biol 1998;18:185-192.

7. Hiatt WR, Hoag S, Hamman RF. Effect of diagnostic criteria on the prevalence of peripheral arterial disease: the San Luis Valley Diabetes Study. Circulation 1995;91:1472-1479.

8. Jude EB, Oyibo SO, Chalmers N, et al. Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome Diabetes Care 2001;24:1433-1437.

9. Hofirek I, Vojtisek B. Diabetic peripheral arterial disease. Vnitr Lek 2003;49:911-915.

10. Beks PJ, Mackaay AJ, de Neeling JN, et al. Peripheral arterial disease inrelation to glycaemic level in an elderly Caucasian population: the Hoorn study. Diabetologia 1995;38:86-96.

11. Uusitupa MI, Niskanen LK, Siitonen O, et al. Five-year incidence of atherosclerotic vascular disease in relation to general risk factors, insulin level, and abnormalities in lipoprotein composition in noninsulin-dependent diabetic and nondiabetic subjects. Circulation 1990;82:27-36.

12. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. J Am Geriatr Soc 1985;33:13-18.

13. Centers for Disease Control (CDC). Diabetes-related amputations of lower extremities in the Medicare population: Minnesota, 1993 to 1995. MMWR Morb Mortal Wkly Rep 1998;47:649-652.

14. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703-713.

15. Pedersen TR, Kjekshus J, Pyorala K, et al. Effect of simvastatin on ischemic signs and symptoms in the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol 1998;81:333-335.

16. Ahmadi AB, Bembi V, Singh S, et al. Prevalence of peripheral arterial disease in a cohort of diabetic patients. South Med J 2006;99:564-569.

The whirlwinds of revolt will continue to shake the foundations of our
nation until the bright day of justice emerges.
--Martin Luther King, Jr.

Ashkan Mowla, MD, Amir Bahrami, MD, and Seyed Alireza Dastgheib, MD

From the School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Reprint requests to Ashkan Mowla, MD, School of Medicine, Shiraz University of Medical Sciences. Shiraz, Iran. E-mail: [e-mail]

Accepted April 12, 2006.