Does Perioperative Hemoglobin A1c Level Affect the Incidence, Pattern and Mortality of Lower Extremity Amputation?

Author(s): Hassan Al-Thani, Moamena El-Matbouly, Maryam Al-Sulaiti, Noora Al-Thani, Mohammad Asim, Ayman El-Menyar*.

Journal Name: Current Vascular Pharmacology

Volume 17 , Issue 4 , 2019

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Graphical Abstract:


Background: We hypothesized that perioperative HbA1c influenced the pattern and outcomes of Lower Extremity Amputation (LEA).

Methods: A retrospective analysis was conducted for all patients who underwent LEA between 2000 and 2013. Patients were categorized into 5 groups according to their perioperative HbA1c values [Group 1 (<6.5%), Group 2 (6.5-7.4%), Group 3 (7.5-8.4%), Group 4 (8.5-9.4%) and Group 5 (≥9.5%)]. We identified 848 patients with LEA; perioperative HbA1c levels were available in 547 cases (Group 1: 18.8%, Group 2: 17.7%, Group 3: 15.0%, Group 4: 13.5% and Group 5: 34.9%). Major amputation was performed in 35%, 32%, 22%, 10.8% and 13.6%, respectively.

Results: The overall mortality was 36.5%; of that one quarter occurred during the index hospitalization. Mortality was higher in Group 1 (57.4%) compared with Groups 2-5 (46.9%, 38.3%, 36.1% and 31.2%, respectively, p=0.001). Cox regression analysis showed that poor glycemic control (Group 4 and 5) had lower risk of mortality post-LEA [hazard ratio 0.57 (95% CI 0.35-0.93) and hazard ratio 0.46 (95% CI 0.31-0.69)]; this mortality risk persisted even after adjustment for age and sex but was statistically insignificant. The rate of LEA was greater among poor glycemic control patients; however, the mortality was higher among patients with tight control.

Conclusion: The effects of HbA1c on the immediate and long-term LEA outcomes and its therapeutic implications need further investigation.

Keywords: Lower extremities amputation, diabetes mellitus, HbA1c, mortality, ADA, hemoglobin.

Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA 2005; 293: 217-28.
Thewjitcharoen Y, Krittiyawong S, Porramatikul S, et al. Outcomes of hospitalized diabetic foot patients in a multi-disciplinary team setting: Thailand’s experience. J Clin Transl Endocrinol 2014; 1: 187-91.
Rai NK. Suryabhan, Ansari M, Kumar M, Shukla VK, Tripathi K. Effect of glycaemic control on apoptosis in diabetic wounds. J Wound Care 2005; 14: 277-81.
van Houtum WH, Lavery LA, Harkless LB. The impact of diabetes-related lower-extremity amputations in The Netherlands. J Diabetes Complications 1996; 10: 325-30.
Dillingham TR, Pezzin LE, MacKenzie EJ. Limb amputation and limb deficiency: Epidemiology and recent trends in the United States. South Med J 2002; 95: 875-83.
American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care 2013; 36: 1033-46.
van Dieren S, Beulens JW, van der Schouw YT, Grobbee DE, Neal B. The global burden of diabetes and its complications: An emerging pandemic. Eur J Cardiovasc Prev Rehabil 2010; 17(Suppl. 1): 3-8.
Kowall B, Rathmann W. HbA1c for diagnosis of type 2 diabetes. Is there an optimal cut point to assess high risk of diabetes complications, and how well does the 6.5% cutoff perform? Diabetes Metab Syndr Obes 2013; 6: 477-91.
Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ 2000; 321: 405-12.
Davis WA, Norman PE, Bruce DG, Davis TM. Predictors, consequences and costs of diabetes-related lower extremity amputation complicating type 2 diabetes: The Fremantle diabetes study. Diabetologia 2006; 49: 2634-41.
Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358: 2560-72.
Ali FM, Nikoloski Z, Reka H, Gjebrea O, Mossialos E. The diabetes-obesity-hypertension nexus in Qatar: Evidence from the world health survey. Popul Health Metr 2014; 12: 18.
Swaminathan A, Vemulapalli S, Patel MR, Jones WS. Lower extremity amputation in peripheral artery disease: Improving patient outcomes. Vasc Health Risk Manag 2014; 10: 417-24.
International Diabetes Federation, "I IDF Diabetes Atlas 6th ed, Diabetes Estimates, Diabetes Prevalence (%), 2035 Available at. [Accessed on April 06, 2014].
International Diabetes Foundation (IDF). Diabetes Atlas. 8th ed. (updated). 2017. Available at: resources/2017-atlas.html
Adler A, Erqou S, Lima T, Robinson A. Association between glycated haemoglobin and the risk of lower extremity amputation in patients with diabetes mellitus review and meta-analysis. Diabetologia 2010; 53: 840-9.
UK Prospective Diabetes Study (UKPDS) Group.Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-53.
Zhou Z, Liu Y, Chen H. HbA1c and lower extremity amputation risk in patients with diabetes: A meta-analysis. Int J Low Extrem Wounds 2015; 14: 168-77.
Hsu CY, Chen YT, Su YW, Chang CC, Huang PH, Lin SJ. Statin therapy reduces future risk of lower-limb amputation in patients with diabetes and peripheral artery disease. J Clin Endocrinol Metab 2017; 102: 2373-81.
Stavroulakis K, Borowski M, Torsello G. Association between statin therapy and amputation-free survival in patients with critical limb ischemia in the CRITISCH registry. J Vasc Surg 2017; 66: 1534-42.
Westin GG, Armstrong EJ, Bang H, et al. Association between statin medications and mortality, major adverse cardiovascular event, and amputation-free survival in patients with critical limb ischemia. J Am Coll Cardiol 2014; 63: 682-90.
Kumbhani DJ, Steg PG, Cannon CP, et al. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: Insights from the REACH registry. Eur Heart J 2014; 35: 2864-72.
Chung J, Timaran DA, Modrall JG, et al. Optimal medical therapy predicts amputation-free survival in chronic critical limb ischemia. J Vasc Surg 2013; 58: 972-80.
Sohn MW, Meadows JL, Oh EH. Statin use and lower extremity amputation risk in nonelderly diabetic patients. J Vasc Surg 2013; 58: 1578-85.
DeCarlo C, Scher L, Shariff S. Statin use and other factors associated with mortality after major lower extremity amputation. J Vasc Surg 2017; 66: 216-25.
Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Risk factors predicting lower extremity amputations in patients with NIDDM. Diabetes Care 1996; 19: 607-12.
Coppini DV1,Young PJ, Weng C, Macleod AF, Sönksen PH. Outcome on diabetic foot complications in relation to clinical examination and quantitative sensory testing: A case-control study. Diabet Med 1998; 15: 765-71.
Watts SA, Daly B, Anthony M, McDonald P, Khoury A, Dahar W. The effect of age, gender, risk level and glycosylated hemoglobin in predicting foot amputation in HMO patients with diabetes. J Am Acad Nurse Pract 2001; 13: 230-5.
Olson JC, Erbey JR, Forrest KY, Williams K, Becker DJ, Orchard TJ. Glycemia (or, in women, estimated glucose disposal rate) predict lower extremity arterial disease events in type 1 diabetes. Metabolism 2002; 51: 248-54.
Li X, Xiao T, Wang Y, et al. Incidence, risk factors for amputation among patients with diabetic foot ulcer in a Chinese tertiary hospital. Diabetes Res Clin Pract 2011; 93: 26-30.
Lacle A, Valero-Juan LF. Diabetes-related lower-extremity amputation incidence and risk factors: A prospective seven-year study in Costa Rica. Rev Panam Salud Publica 2012; 32: 192-8.
Fei YF, Wang C, Chen DW, et al. Incidence and risk factors of amputation among inpatients with diabetic foot. Zhonghua Yi Xue Za Zhi 2012; 92: 1686-9.
Zubair M, Malik A, Ahmad J. Incidence, risk factors for amputation among patients with diabetic foot ulcer in a North Indian tertiary care hospital. Foot (Edinb) 2012; 22: 24-30.
Tabur S, Eren MA, Celik Y, et al. The major predictors of amputation and length of stay in diabetic patients with acute foot ulceration. Wien Klin Wochenschr 2015; 127: 45-50.
Zhao W, Katzmarzyk PT, Horswell R, et al. HbA1c and lower-extremity amputation risk in low-income patients with diabetes. Diabetes Care 2013; 36: 3591-8.
Callaghan BC, Feldman E, Liu J, et al. Triglycerides and amputation risk in patients with diabetes: Ten-year follow up in the distance study. Diabetes Care 2011; 34: 635-40.
Muhlhauser I, Overmann H, Bender R, Jorgens V, Berger M. Predictors of mortality and end-stage diabetic complications in patients with type 1 diabetes mellitus on intensified insulin therapy. Diabet Med 2000; 17: 727-34.
Adler AI, Boyko EJ, Ahroni JH, Smith DG. Lower-extremity amputation in diabetes. The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers. Diabetes Care 1999; 22: 1029-35.
Moss SE, Klein R, Klein BE. The 14-year incidence of lower-extremity amputations in a diabetic population. The Wisconsin epidemiologic study of diabetic retinopathy. Diabetes Care 1999; 22: 951-9.
Katsiki N, Purrello F, Tsioufis C, Mikhailidis DP. Cardiovascular disease prevention strategies for type 2 diabetes mellitus. Expert Opin Pharmacother 2017; 18: 1243-60.
Dietrich I, Braga G, de Melo F, et al. The diabetic foot as a proxy for cardiovascular events and mortality review. Curr Atheroscler Rep 2017; 19: 44.
Huang ES, Liu JY, Moffet HH, John PM, Karter AJ. Glycemic control, complications, and death in older diabetic patients: The diabetes and aging study. Diabetes Care 2011; 34: 1329-36.
Sebranek JJ, Lugli AK, Coursin DB. Glycaemic control in the perioperative period. Br J Anaesth 2013; 111(Suppl. 1): 18-34.
Buchleitner AM, Martínez-Alonso M, Hernández M, Solà I, Mauricio D. Perioperative glycaemic control for diabetic patients undergoing surgery. Cochrane Database Syst Rev 2012; 9: CD007315.
Shojaiefard A, Khorgami Z, Larijani B. Independent risk factors for amputation in diabetic foot. Int J Diabetes Dev Ctries 2008; 28: 32-7.
Al-Rubeaan K, Almashouq MK, Youssef AM, et al. All-cause mortality among diabetic foot patients and related risk factors in Saudi Arabia. PLoS One 2017; 12: e0188097.
Martins-Mendes D, Monteiro-Soares M, Boyko EJ, et al. The independent contribution of diabetic foot ulcer on lower extremity amputation and mortality risk. J Diabetes Complications 2014; 28: 632-8.
Rajagopalan S, Brook R. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 2098-9.

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Year: 2019
Page: [354 - 364]
Pages: 11
DOI: 10.2174/1570161116666180123112529
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