• Mehreen Arshad Ziauddin medical university
  • Dr Faisal khan Ziauddin medical university
  • Dr Jawwad Azeem Khan Dow medical university




Lower limb complications associated with diabetes are peripheral sensory neuropathy and peripheral artery diseases. Amputation risk increases with diabetes and mostly happens in the lower limb. Disabilities occur due to lower limb complications which then affect patients' health and social lives. Diabetes is associated with other diseases like cardiovascular issues, cancer, etc. Death risk in diabetes type 2 patients having lower limb complications is highly associated with cancer. When the interaction between peripheral neuropathy and peripheral artery diseases (PAD) with cancer death risk is measured, it showed a high association with PAD having a hazard ratio of 8.9 and peripheral neuropathy patients having a hazard ratio of 8.4. Among them, lower limb arterial thrombosis is highly associated with all cancer deaths. Lower-extremity complications are the leading cause of macrovascular and microvascular diseases. Other minor risk factors linked with lower limb complications are age, smoking, and obesity. The risk of lower limb complications and cancer is prevalent among smokers as compared to non-smokers. However, there is no particular study on this factor. Lower-limb malignancies are associated with many biological disorders like increased glycation end products, chronic inflammation, and oxidative stress. In one study, cancer risk was measured among various diabetic patients having lower limb complications. The results showed less cancer death risk among the group of patients having proper glucose level and blood pressure level controls. Among all the cancers affecting diabetic patients, almost 4% are melanoma which if misdiagnosed during early stages due to various reasons can lead to biopsy. Acral melanoma is usually misdiagnosed in up to 40% of cases. The purpose of a biopsy is the diagnosis of the problem as well as the prediction of the exact stage of melanoma.


. Barrera, G. (2012). Oxidative stress and lipid peroxidation products in cancer progression and therapy. J International Scholarly Research Notices, 2012.

. Bennett, D. R., Wasson, D., MacArthur, J. D., & McMillen, M. A. (1994). The effect of misdiagnosis and delay in diagnosis on clinical outcome in melanomas of the foot. J Journal of the American College of Surgeons179(3), 279-284.

. Boulton, A. J., Vileikyte, L., Ragnarson-Tennvall, G., & Apelqvist, J. J. T. L. (2005). The global burden of diabetic foot disease. 366(9498), 1719-1724.

. Brownrigg, J. R., Griffin, M., Hughes, C. O., Jones, K. G., Patel, N., Thompson, M. M., & Hinchliffe, R. J. (2014). Influence of foot ulceration on cause-specific mortality in patients with diabetes mellitus. J Journal of Vascular Surgery, 60(4), 982-986. e983.

. Committee, A. M. (2001). Study rationale and design of ADVANCE: action in diabetes and vascular disease–preterax and diamicron MR controlled evaluation. J Diabetologia, 44(9), 1118-1120.

. Eelen, G., de Zeeuw, P., Treps, L., Harjes, U., Wong, B. W., & Carmeliet, P. (2018). Endothelial cell metabolism. J Physiological reviews, 98(1), 3-58.

. Fortin, P. T., Freiberg, A. A., Rees, R., Sondak, V. K., & Johnson, T. M. (1995). Malignant melanoma of the foot and ankle. J The Journal of Bone Joint surgery. American Volume 77(9), 1396-1403.

. Huisman, M. (2007). Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. J Netherlands heart journal, 15(1), 25-27.

. Johannesson, A., Larsson, G.-U., Ramstrand, N., Turkiewicz, A., Wiréhn, A.-B., & Atroshi, I. J. D. c. (2009). Incidence of lower-limb amputation in the diabetic and nondiabetic general population: a 10-year population-based cohort study of initial unilateral and contralateral amputations and reamputations. 32(2), 275-280.

. John, K. J., Hayes Jr, D., Green, D. R., & Dickerson, J. (2000). Malignant melanoma of the foot and ankle. J Clinics in podiatric medicine surgery 17(2), 347-360, vi.

. Kerr, M., Barron, E., Chadwick, P., Evans, T., Kong, W., Rayman, G., . . . Jeffcoate, W. J. D. M. (2019). The cost of diabetic foot ulcers and amputations to the National Health Service in England. 36(8), 995-1002.

. Kong, M. F., Jogia, R., Jackson, S., Quinn, M., McNally, P., & Davies, M. (2008). When to biopsy a foot ulcer? Seven cases of malignant melanoma presenting as foot ulcers. J Practical Diabetes International, 25(1), 5-8.

. Lloyd-Jones, D. M., Hong, Y., Labarthe, D., Mozaffarian, D., Appel, L. J., Van Horn, L., . . . Tomaselli, G. F. (2010). Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond. J Circulation, 121(4), 586-613.

. Lozano, R., Naghavi, M., Foreman, K., Lim, S., Shibuya, K., Aboyans, V., . . . Ahn, S. Y. (2012). Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. J The lancet, 380(9859), 2095-2128.

. Metzger, S., Ellwanger, U., Stroebel, W., Schiebel, U., Rassner, G., & Fierlbeck, G. (1998). Extent and consequences of physician delay in the diagnosis of acral melanoma. J Melanoma research, 8(2), 181-186.

. Mohammedi, K., Bellili-Muñoz, N., Marklund, S. L., Driss, F., Le Nagard, H., Patente, T. A., . . . Marre, M. (2015). Plasma extracellular superoxide dismutase concentration, allelic variations in the SOD3 gene and risk of myocardial infarction and all-cause mortality in people with type 1 and type 2 diabetes. J Cardiovascular diabetology, 14(1), 1-10.

. Mohammedi, K., Harrap, S., Mancia, G., Marre, M., Poulter, N., Chalmers, J., & Woodward, M. (2021). History of lower-limb complications and risk of cancer death in people with type 2 diabetes. J Cardiovascular diabetology, 20(1), 1-12.

. Onega, T., Baron, J. A., Johnsen, S. P., Pedersen, L., Farkas, D. K., Sørensen, H. T., & Prevention. (2015). Cancer Risk and Subsequent Survival after Hospitalization for Intermittent ClaudicationIntermittent Claudication and Cancer Risk. J Cancer Epidemiology, Biomarkers, 24(4), 744-748.

. Rao Kondapally Seshasai, S., Kaptoge, S., Thompson, A., Di Angelantonio, E., Gao, P., Sarwar, N., . . . Holme, I. (2011). Diabetes mellitus, fasting glucose, and risk of cause-specific death. J The New England journal of medicine, 364(9), 829-841.

. Soon, S. L., Solomon Jr, A. R., Papadopoulos, D., Murray, D. R., McAlpine, B., & Washington, C. V. (2003). Acral lentiginous melanoma mimicking benign disease: the Emory experience. J Journal of the American Academy of Dermatology, 48(2), 183-188.

. Stefansdottir, G., Zoungas, S., Chalmers, J., Kengne, A.-P., Knol, M., Leufkens, H., . . . De Bruin, M. (2011). Intensive glucose control and risk of cancer in patients with type 2 diabetes. J Diabetologia, 54(7), 1608-1614.

. Sundbøll, J., Veres, K., Horvath-Puho, E., Adelborg, K., & Sørensen, H. T. (2018). Risk and prognosis of cancer after lower limb arterial thrombosis. J Circulation, 138(7), 669-677.

. Tesfaye, S., Boulton, A. J., Dyck, P. J., Freeman, R., Horowitz, M., Kempler, P., . . . Vinik, A. (2010). Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. %J Diabetes care, 33(10), 2285-2293.

. Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet‐Tieulent, J., & Jemal, A. (2015). Global cancer statistics, 2012. J CA: a cancer journal for clinicians 65(2), 87-108.

. Walsh, J., Hoffstad, O., Sullivan, M., & Margolis, D. J. D. M. (2016). Association of diabetic foot ulcer and death in a population‐based cohort from the United Kingdom. 33(11), 1493-1498.

. Walsh, S. M., Fisher, S. G., & Sage, R. A. (2003). Survival of patients with primary pedal melanoma. J The Journal of foot ankle surgery 42(4), 193-198.

. Wong, G., Zoungas, S., Lo, S., Chalmers, J., Cass, A., Neal, B., . . . Williams, B. (2012). The risk of cancer in people with diabetes and chronic kidney disease. J Nephrology Dialysis Transplantation 27(8), 3337-3344.

. Youn, J.-C., Chung, W.-B., Ezekowitz, J. A., Hong, J. H., Nam, H., Kyoung, D.-S., . . . Jung, H. O. (2020). Cardiovascular disease burden in adult patients with cancer: an 11-year nationwide population-based cohort study. J International Journal of Cardiology 317, 167-173.