Lower extremity amputation is a source of morbidity and mortality among diabetic patients. This meta-analysis aimed to identify significant laboratory data in patients with diabetic foot ulcer with high rates of lower extremity amputation. We performed a systematic literature review and meta-analysis using MEDLINE, EMBASE, and Cochrane databases. We extracted and evaluated 11 variables from the included studies based on amputation rates. This study used the Newcastle-Ottawa Scale to assess the quality of the studies. The search strategy identified 101 publications from which we selected 16 articles for review. We identified HbA1c, fasting blood glucose, white blood cells, C-reactive protein, and erythrocyte sedimentation rate as predictive variables of higher major amputation rate. Although further investigation of long-term and prospective studies is needed, we identified 5 variables as predisposing factors for higher major amputation in diabetic patients through meta-analysis.
WildSRoglicGGreenASicreeRKingH. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047-1053.
2.
SinghNArmstrongDGLipskyBA. Preventing foot ulcers in patients with diabetes. JAMA. 2005;293:217-228.
3.
Global Lower Extremity Amputation Study G. Epidemiology of lower extremity amputation in centres in Europe, North America and East Asia. The Global Lower Extremity Amputation Study Group. Br J Surg. 2000;87:328-337.
4.
McCabeCJStevensonRCDolanAM. Evaluation of a diabetic foot screening and protection programme. Diabet Med. 1998;15:80-84.
5.
LaganiVKoumakisLChiarugiFLakasingETsamardinosI. A systematic review of predictive risk models for diabetes complications based on large scale clinical studies. J Diabetes Complications. 2013;27:407-413.
6.
AzizZLinWKNatherAHuakCY. Predictive factors for lower extremity amputations in diabetic foot infections. Diabet Foot Ankle. 2011;2. doi:10.3402/dfa.v2i0.7463.
7.
Dos SantosVPda SilveiraDRCaffaroRA. Risk factors for primary major amputation in diabetic patients. Sao Paulo Med J. 2006;124:66-70.
8.
MiyajimaSShiraiAYamamotoSOkadaNMatsushitaT. Risk factors for major limb amputations in diabetic foot gangrene patients. Diabetes Res Clin Pract. 2006;71:272-279.
9.
ChuanFZhangMYaoYTianWHeXZhouB. Anemia in patients with diabetic foot ulcer: prevalence, clinical characteristics, and outcome. Int J Low Extrem Wounds. 2016;15:220-226.
10.
LiberatiAAltmanDGTetzlaffJet al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6:e1000100.
11.
StangA.Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603-605.
12.
DeeksJJDinnesJD’AmicoRet al; International Stroke Trial Collaborative Group; European Carotid Surgery Trial Collaborative Group. Evaluating non-randomised intervention studies. Health Technol Assess. 2003;7:iii-x,1-173.
13.
HigginsJPThompsonSG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539-1558.
14.
JiangYRanXJiaLet al. Epidemiology of type 2 diabetic foot problems and predictive factors for amputation in China. Int J Low Extrem Wounds. 2015;14:19-27.
15.
LiXXiaoTWangYet 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.
16.
PemayunTGNaibahoRMNovitasariDAminNMinuljoTT. Risk factors for lower extremity amputation in patients with diabetic foot ulcers: a hospital-based case-control study. Diabet Foot Ankle. 2015;6:29629.
17.
LipskyBAWeigeltJASunXJohannesRSDerbyKGTabakYP. Developing and validating a risk score for lower-extremity amputation in patients hospitalized for a diabetic foot infection. Diabetes Care. 2011;34:1695-1700.
18.
KarakasAArslanECakmakTAydinIAkgulEODemirbasS. Predictive value of soluble CD14, interleukin-6 and procalcitonin for lower extremity amputation in people with diabetes with foot ulcers: a pilot study. Pak J Med Sci. 2014;30:578-582.
19.
AydinKIsildakMKarakayaJGürlekA. Change in amputation predictors in diabetic foot disease: effect of multidisciplinary approach. Endocrine. 2010;38:87-92.
20.
TaburSErenMACelikYet al. The major predictors of amputation and length of stay in diabetic patients with acute foot ulceration. Wien Klin Wochenschr. 2015;127:45-50.
21.
ZubairMMalikAAhmadJ. Incidence, risk factors for amputation among patients with diabetic foot ulcer in a North Indian tertiary care hospital. Foot (Edinb). 2012;22:24-30.
22.
WattsSADalyBAnthonyMMcDonaldPKhouryADaharW. 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;13:230-235.
23.
LacleAValero-JuanLF. Diabetes-related lower-extremity amputation incidence and risk factors: a prospective seven-year study in Costa Rica. Rev Panam Salud Publica. 2012;32:192-198.
24.
ShojaiefardAKhorgamiZLarijaniB. Independent risk factors for amputation in diabetic foot. Int J Diabetes Dev Ctries. 2008;28:32-37.
25.
HämäläinenHRönnemaaTHalonenJPToikkaT. Factors predicting lower extremity amputations in patients with type 1 or type 2 diabetes mellitus: a population-based 7-year follow-up study. J Intern Med. 1999;246:97-103.
26.
LehtoSRonnemaaTPyoralaKLaaksoM. Risk factors predicting lower extremity amputations in patients with NIDDM. Diabetes Care. 1996;19:607-612.
27.
ApelqvistJLarssonJAgardhCD. Long-term prognosis for diabetic patients with foot ulcers. J Intern Med. 1993;233:485-491.
28.
AkinciBYenerSYesilSYaparNKucukyavasYBayraktarF. Acute phase reactants predict the risk of amputation in diabetic foot infection. J Am Podiatr Med Assoc. 2011;101:1-6.
29.
MarcovecchioMLLucantoniMChiarelliF. Role of chronic and acute hyperglycemia in the development of diabetes complications. Diabetes Technol Ther. 2011;13:389-394.
30.
AdlerAIErqouSLimaTARobinsonAH. Association between glycated haemoglobin and the risk of lower extremity amputation in patients with diabetes mellitus-review and meta-analysis. Diabetologia. 2010;53:840-849.
31.
GaedePLund-AndersenHParvingHHPedersenO. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358:580-591.
32.
ZubairMMalikAAhmadJ. Plasma adiponectin, IL-6, hsCRP, and TNF-α levels in subject with diabetic foot and their correlation with clinical variables in a North Indian tertiary care hospital. Indian J Endocrinol Metab. 2012;16:769-776.
33.
MetinerenHDulgerogluTC. Comparison of the neutrophil/lymphocyte ratio and C-reactive protein levels in patients with amputation for diabetic foot ulcers. Int J Low Extrem Wounds. 2017;16:23-28.
34.
JeandrotARichardJLCombescureCet al. Serum procalcitonin and C-reactive protein concentrations to distinguish mildly infected from non-infected diabetic foot ulcers: a pilot study. Diabetologia. 2008;51:347-352.
35.
FleischerAEDidykAAWoodsJBBurnsSEWrobelJSArmstrongDG. Combined clinical and laboratory testing improves diagnostic accuracy for osteomyelitis in the diabetic foot. J Foot Ankle Surg. 2009;48:39-46.
36.
ErtugrulBMSavkOOzturkBCobanogluMOncuSSakaryaS. The diagnosis of diabetic foot osteomyelitis: examination findings and laboratory values. Med Sci Monit. 2009;15:CR307-CR312.
37.
MichailMJudeELiaskosCet al. The performance of serum inflammatory markers for the diagnosis and follow-up of patients with osteomyelitis. Int J Low Extrem Wounds. 2013;12:94-99.
38.
KaletaJLFleischliJWReillyCH. The diagnosis of osteomyelitis in diabetes using erythrocyte sedimentation rate: a pilot study. J Am Podiatr Med Assoc. 2001;91:445-450.
39.
MutluogluMUzunGIpciogluOMet al. Can procalcitonin predict bone infection in people with diabetes with infected foot ulcers? A pilot study. Diabetes Res Clin Pract. 2011;94:53-56.
40.
ReinerMMKhouryWECanalesMBet al. Procalcitonin as a biomarker for predicting amputation level in lower extremity infections. J Foot Ankle Surg. 2017;56:484-491.
41.
LaveryLAPetersEJArmstrongDGWendelCSMurdochDPLipskyBA. Risk factors for developing osteomyelitis in patients with diabetic foot wounds. Diabetes Res Clin Pract. 2009;83:347-352.
42.
YoungBALinEVon KorffMet al. Diabetes complications severity index and risk of mortality, hospitalization, and healthcare utilization. Am J Manag Care. 2008;14:15-23.
43.
ChaturvediNStevensLKFullerJHLeeETLuM. Risk factors, ethnic differences and mortality associated with lower-extremity gangrene and amputation in diabetes. The WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia. 2001;44(suppl 2):S65-S71.
44.
IkuraKHanaiKShinjyoTUchigataY. HDL cholesterol as a predictor for the incidence of lower extremity amputation and wound-related death in patients with diabetic foot ulcers. Atherosclerosis. 2015;239:465-469.
45.
CabanaVGSiegelJNSabesinSM. Effects of the acute phase response on the concentration and density distribution of plasma lipids and apolipoproteins. J Lipid Res. 1989;30:39-49.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
