红细胞分布宽度、纤维蛋白原与D-二聚体预测糖尿病足发生发展风险的价值
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摘要
背景:血栓形成相关指标红细胞分布宽度、纤维蛋白原、D-二聚体可能是预测糖尿病足发生发展的重要标志。目的:分析红细胞分布宽度、纤维蛋白原、D-二聚体预测糖尿病足发生发展风险的临床价值。方法:收集糖尿病足患者81例、2型糖尿病患者82例、健康人67例做回顾性病例-对照分析。临床研究的实施符合南方医科大学第三附属医院对研究的相关伦理要求。所有受试者及家属对试验过程均知情同意,并签署知情同意书。对比3组受试者红细胞分布宽度、纤维蛋白原、D-二聚体;Logistic回归分析糖尿病患者糖尿病足的相关危险因素;应用受试者工作特征曲线得出红细胞分布宽度、纤维蛋白原、D-二聚体对预测糖尿病足发生的最佳切点及其敏感性、特异性;利用Spearman相关分析分析红细胞分布宽度、纤维蛋白原与D-二聚体的相关性。结果与结论:①糖尿病足组红细胞分布宽度、纤维蛋白原、D-二聚体均高于2型糖尿病组及健康组(P=0.000);②二元逻辑回归分析提示纤维蛋白原升高是糖尿病足的独立危险因素(OR=4.253,P=0.046);红细胞分布宽度、纤维蛋白原、D-二聚体与糖尿病足的相关系数分别为0.616,0.724,0.797,P均小于0.001。③受试者工作特征曲线分析提示,红细胞分布宽度、纤维蛋白原、D-二聚体预测糖尿病足发生的切点分别为40%、3g/L、329mg/L,敏感度分别为77.78%,72.73%、93.33%,特异度分别为71.95%、92.98%,88.24%;④结果说明,红细胞分布宽度、纤维蛋白原、D-二聚体对预测糖尿病足的发生发展风险具有一定的临床意义。
BACKGROUND: Thrombosis-related indexes red blood cell distribution width, fibrinogen and D-dimer may be the important markers of predicting the occurrence and development of diabetic foot.OBJECTIVE: To investigate the clinical value of red blood cell distribution width, fibrinogen and D-dimer in predicting the occurrence and development risk of diabetic foot.METHODS: Eighty-one patients with diabetic foot and 82 patients with type 2 diabetes mellitus, and 67 healthy people were enrolled to conduct respective case-control analysis. The study was in accordance with the ethical guidance of the Third Affiliated Hospital of Southern Medical University. All patients and their relatives signed the informed consents. The red blood cell distribution width, fibrinogen, and D-dimer were compared among groups. The related risk factors of diabetic foot were analyzed by logistic regression. The best cut-off points, sensitivity and specificity of red blood cell distribution width, fibrinogen and D-dimer for predicting the occurrence of diabetic foot were obtained by receiver operating characteristic curve. The correlation of red blood cell distribution width, fibrinogen and D-dimer was analyzed by Spearman correlation analysis.RESULTS AND CONCLUSION:(1) The red blood cell distribution width, fibrinogen and D-dimer in the diabetic foot group were significantly higher than those in the type 2 diabetes mellitus group and healthy group(P=0.000).(2) Binary logistic regression analysis indicated that elevated fibrinogen was an independent risk factor for diabetic foot(OR=4.253, P=0.046). The correlation coefficients of red blood cell distribution width, fibrinogen, and D-dimer with diabetic foot were 0.616, 0.724 and 0.797, respectively(all P < 0.001).(3) Receiver operating characteristic curve analysis showed that the cut-off points of red blood cell distribution width, fibrinogen and D-dimer for predicting the occurrence of diabetic foot were 40%, 3 g/L and 329 mg/L, with sensitivity of 77.78%, 72.73%, 93.33% and specificity of 71.95%, 92.98% and88.24%, respectively.(4) To conclude, red blood cell distribution width, fibrinogen and D-dimer have certain clinical significance in predicting the occurrence and development risk of diabetic foot.
BACKGROUND: Thrombosis-related indexes red blood cell distribution width, fibrinogen and D-dimer may be the important markers of predicting the occurrence and development of diabetic foot.OBJECTIVE: To investigate the clinical value of red blood cell distribution width, fibrinogen and D-dimer in predicting the occurrence and development risk of diabetic foot.METHODS: Eighty-one patients with diabetic foot and 82 patients with type 2 diabetes mellitus, and 67 healthy people were enrolled to conduct respective case-control analysis. The study was in accordance with the ethical guidance of the Third Affiliated Hospital of Southern Medical University. All patients and their relatives signed the informed consents. The red blood cell distribution width, fibrinogen, and D-dimer were compared among groups. The related risk factors of diabetic foot were analyzed by logistic regression. The best cut-off points, sensitivity and specificity of red blood cell distribution width, fibrinogen and D-dimer for predicting the occurrence of diabetic foot were obtained by receiver operating characteristic curve. The correlation of red blood cell distribution width, fibrinogen and D-dimer was analyzed by Spearman correlation analysis.RESULTS AND CONCLUSION:(1) The red blood cell distribution width, fibrinogen and D-dimer in the diabetic foot group were significantly higher than those in the type 2 diabetes mellitus group and healthy group(P=0.000).(2) Binary logistic regression analysis indicated that elevated fibrinogen was an independent risk factor for diabetic foot(OR=4.253, P=0.046). The correlation coefficients of red blood cell distribution width, fibrinogen, and D-dimer with diabetic foot were 0.616, 0.724 and 0.797, respectively(all P < 0.001).(3) Receiver operating characteristic curve analysis showed that the cut-off points of red blood cell distribution width, fibrinogen and D-dimer for predicting the occurrence of diabetic foot were 40%, 3 g/L and 329 mg/L, with sensitivity of 77.78%, 72.73%, 93.33% and specificity of 71.95%, 92.98% and88.24%, respectively.(4) To conclude, red blood cell distribution width, fibrinogen and D-dimer have certain clinical significance in predicting the occurrence and development risk of diabetic foot.
引文
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[6]Isik T,Uyarel H,Tanboga IH,et al.Relation of red cell distribution width with the presence, severity, and complexity of coronary artery disease.Coron Artery Dis.2012;23(1):51-56.
[7]Akin F,Kose N,Ayca B,et al.Relation Between Red Cell Distribution Width and Severity of Coronary Artery Disease in Patients With Acute Myocardial Infarction.ANGIOLOGY. 2012;64(8):592-596.
[8]Wonnerth A, Krychtiuk KA, Mayer FJ, et al. Red cell distribution width and mortality in carotid atherosclerosis. Eur J Clin Invest. 2016;46(2):198-204.
[9]Veeranna V,Zalawadiya SK, Panaich S, et al. Comparative analysis of red cell distribution width and high sensitivity C-reactive protein for coronary heart disease mortality prediction in multi-ethnic population:Findings from the1999–2004 NHANES. Int J Cardiol. 2013;168(6):5156-5161.
[10]Wells PS,Owen C,Doucette S,et al.Does this patient have deep vein thrombosis?.Jama. 1998;279(14):1094.
[11]Wells PS,Anderson DR,Rodger M,et al.Excluding pulmonary embolism at the bedside without diagnostic imaging:management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med. 2001;135(2):98-107.
[12]Lowe GD.Fibrinogen and cardiovascular disease:historical introduction. Eur Heart J. 1995;16 Suppl A:2-5.
[13]Smith EB.Fibrinogen, Fibrin and the Arterial Wall. Eur Heart J.1995;16 Suppl A:11-4; discussion 14-15. Review.
[14]Zubair M, Malik A, Ahmad J. Incidence, risk factors for amputation among patients with diabetic foot ulcer in a North Indian tertiary care hospital.The Foot.2012;22(1):24-30.
[15]Karrer S.Diabetisches Fu?syndrom.Der Hautarzt.2011;62(7):493-503.
[16]Gupta AK,Humke S.The prevalence and management of onychomycosis in diabetic patients. Eur J Dermatol. 2000;10(5):379-84. Review..
[17]Geerlings SE, Hoepelman AI.Immune dysfunction in patients with diabetes mellitus(DM). FEMS Immunol Med Microbiol.1999;26(3-4):259-265.
[18]Cole-King A,Harding KG.Psychological factors and delayed healing in chronic wounds. Psychosom Med. 2001;63(2):216-220.
[19]Harrington AM,Ward PC,Kroft SH.Iron deficiency anemia,beta-thalassemia minor, and anemia of chronic disease:a morphologic reappraisal. Am J Clin Pathol. 2008;129(3):466-471.
[20]Romero AJ,Carbia CD,Ceballo MF,et al.[Red cell distribution width(RDW):its use in the characterization of microcytic and hypochromic anemias].Medicina.1999;59(1):17-22.
[21]Symeonidis A,Athanassiou G,Psiroyannis A,et al.Impairment of erythrocyte viscoelasticity is correlated with levels of glycosylated haemoglobin in diabetic patients.Clin Lab Haematol. 2001;23(2):103-109.
[22]Livshits L,Srulevich A,Raz I,et al.Effect of Short-Term Hyperglycemia on Protein Kinase C Alpha Activation in Human Erythrocytes. Rev Diabet Stud. 2012;9(2-3):94-103.
[23]Patel KV, Mohanty JG, Kanapuru B. Association of the Red Cell Distribution Width with Red Blood Cell Deformability.Adv Exp Med Biol.2013;(765):211-216.
[24]RodraGuez-Carrio J, Alperi-LaPez M, LaPez P, et al.Red cell distribution width is associated with endothelial progenitor cell depletion and vascular-related mediators in rheumatoid arthritis. Atherosclerosis.2015;240(1):131-136.
[25]Solak Y,Yilmaz MI,Saglam M,et al.Red cell distribution width is independently related to endothelial dysfunction in patients with chronic kidney disease.Am J Med Sci. 2014;347(2):118-124.
[26]Demirkol S,Balta S, Celik T, et al. Assessment of the relationship between red cell distribution width and cardiac syndrome X. Kardiol Pol. 2013;71(5):480-484.
[27]Nada AM.Red cell distribution width in type 2 diabetic patients.Diabetes, Metabolic Syndrome and Obesity:Targets and Therapy.2015;(8):525-533.
[28]Xiong X,Yang Y,Chen X,et al.Red cell distribution width as a significant indicator of medication and prognosis in type 2diabetic patients. Sci Rep. 2017;7(1):2709.
[29]Li XH,Guan LY, Lin HY, et al. Fibrinogen:A Marker in Predicting Diabetic Foot Ulcer Severity. J Diabetes Res.2016;2016:2358321.
[30]Howard SC, Algra A, Rothwell PM. Effect of age and glycaemic control on the association between fibrinogen and risk of acute coronary events after transient ischaemic attack or stroke. Cerebrovasc Dis. 2008;25(1-2):136-143.
[31]Lip GY,Lowe GD.Fibrin D-dimer:a useful clinical marker of thrombogenesis?. Clin Sci(Lond). 1995;89(3):205-214.
[32]Yarnell JW,Baker IA,Sweetnam PM,et al.Fibrinogen, viscosity,and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies. Circulation. 1991;83(3):836-844.
[33]Thaulow E,Erikssen J,Sandvik L,et al.Blood platelet count and function are related to total and cardiovascular death in apparently healthy men. Circulation. 1991;84(2):613-617.
[34]Papageorgiou N,Tousoulis D,Siasos G,et al.Is fibrinogen a marker of inflammation in coronary artery disease?. Hellenic J Cardiol. 2010;51(1):1-9.
[35]Kotbi S,Mjabber A,Chadli A,et al.Correlation between the plasma fibrinogen concentration and coronary heart disease severity in Moroccan patients with type 2 diabetes.Prospective study. Ann Endocrinol(Paris). 2016;77(5):606-614.
[36]Yao HQ,Wang FJ,Kang Z.Effects of endovascular interventions on vWF and Fb levels in type 2 diabetic patients with peripheral artery disease. Ann Vasc Surg. 2016;33:159-166.
[37]Wells PS, Owen C,Doucette S,et al.Does this patient have deep vein thrombosis?.Jama. 1998;279(14):1094.
[38]Lippi G,Franchini M,Targher G,et al.Help me, Doctor! My D-dimer is raised. Ann Med. 2008;40(8):594-605.
[39]Fu Z, Yao F, Abou-Samra AB,et al.Lipasin, thermoregulated in brown fat, is a novel but atypical member of the angiopoietinlike protein family. Biochem Biophys Res Commun. 2013;430(3):1126-1131.
[40]Hess K.The vulnerable blood. Coagulation and clot structure in diabetes mellitus. Hamostaseologie. 2015;35(1):25-33.
[41]Nwose EU,Richards RS,Jelinek HF,et al.D-dimer identifies stages in the progression of diabetes mellitus from family history of diabetes to cardiovascular complications. Pathology.2007;39(2):252-257.
[2]Londahl M. Hyperbaric Oxygen Therapy as Adjunctive Treatment of Diabetic Foot Ulcers. MED CLIN N AM.2013;97(5):957-980.
[3]Lipsky BA, Berendt AR, Cornia PB, et al.Executive Summary:2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections. 2012. Clin Infect Dis. 2012;54(12):1679-84
[4]Demetriou M,Papanas N,Panopoulou M,et al.Determinants of Microbial Load in Infected Diabetic Foot Ulcers:A Pilot Study.Int J Endocrinol. 2013;2013:858206.
[5]Tabur AS,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(1-2):45-50.
[6]Isik T,Uyarel H,Tanboga IH,et al.Relation of red cell distribution width with the presence, severity, and complexity of coronary artery disease.Coron Artery Dis.2012;23(1):51-56.
[7]Akin F,Kose N,Ayca B,et al.Relation Between Red Cell Distribution Width and Severity of Coronary Artery Disease in Patients With Acute Myocardial Infarction.ANGIOLOGY. 2012;64(8):592-596.
[8]Wonnerth A, Krychtiuk KA, Mayer FJ, et al. Red cell distribution width and mortality in carotid atherosclerosis. Eur J Clin Invest. 2016;46(2):198-204.
[9]Veeranna V,Zalawadiya SK, Panaich S, et al. Comparative analysis of red cell distribution width and high sensitivity C-reactive protein for coronary heart disease mortality prediction in multi-ethnic population:Findings from the1999–2004 NHANES. Int J Cardiol. 2013;168(6):5156-5161.
[10]Wells PS,Owen C,Doucette S,et al.Does this patient have deep vein thrombosis?.Jama. 1998;279(14):1094.
[11]Wells PS,Anderson DR,Rodger M,et al.Excluding pulmonary embolism at the bedside without diagnostic imaging:management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med. 2001;135(2):98-107.
[12]Lowe GD.Fibrinogen and cardiovascular disease:historical introduction. Eur Heart J. 1995;16 Suppl A:2-5.
[13]Smith EB.Fibrinogen, Fibrin and the Arterial Wall. Eur Heart J.1995;16 Suppl A:11-4; discussion 14-15. Review.
[14]Zubair M, Malik A, Ahmad J. Incidence, risk factors for amputation among patients with diabetic foot ulcer in a North Indian tertiary care hospital.The Foot.2012;22(1):24-30.
[15]Karrer S.Diabetisches Fu?syndrom.Der Hautarzt.2011;62(7):493-503.
[16]Gupta AK,Humke S.The prevalence and management of onychomycosis in diabetic patients. Eur J Dermatol. 2000;10(5):379-84. Review..
[17]Geerlings SE, Hoepelman AI.Immune dysfunction in patients with diabetes mellitus(DM). FEMS Immunol Med Microbiol.1999;26(3-4):259-265.
[18]Cole-King A,Harding KG.Psychological factors and delayed healing in chronic wounds. Psychosom Med. 2001;63(2):216-220.
[19]Harrington AM,Ward PC,Kroft SH.Iron deficiency anemia,beta-thalassemia minor, and anemia of chronic disease:a morphologic reappraisal. Am J Clin Pathol. 2008;129(3):466-471.
[20]Romero AJ,Carbia CD,Ceballo MF,et al.[Red cell distribution width(RDW):its use in the characterization of microcytic and hypochromic anemias].Medicina.1999;59(1):17-22.
[21]Symeonidis A,Athanassiou G,Psiroyannis A,et al.Impairment of erythrocyte viscoelasticity is correlated with levels of glycosylated haemoglobin in diabetic patients.Clin Lab Haematol. 2001;23(2):103-109.
[22]Livshits L,Srulevich A,Raz I,et al.Effect of Short-Term Hyperglycemia on Protein Kinase C Alpha Activation in Human Erythrocytes. Rev Diabet Stud. 2012;9(2-3):94-103.
[23]Patel KV, Mohanty JG, Kanapuru B. Association of the Red Cell Distribution Width with Red Blood Cell Deformability.Adv Exp Med Biol.2013;(765):211-216.
[24]RodraGuez-Carrio J, Alperi-LaPez M, LaPez P, et al.Red cell distribution width is associated with endothelial progenitor cell depletion and vascular-related mediators in rheumatoid arthritis. Atherosclerosis.2015;240(1):131-136.
[25]Solak Y,Yilmaz MI,Saglam M,et al.Red cell distribution width is independently related to endothelial dysfunction in patients with chronic kidney disease.Am J Med Sci. 2014;347(2):118-124.
[26]Demirkol S,Balta S, Celik T, et al. Assessment of the relationship between red cell distribution width and cardiac syndrome X. Kardiol Pol. 2013;71(5):480-484.
[27]Nada AM.Red cell distribution width in type 2 diabetic patients.Diabetes, Metabolic Syndrome and Obesity:Targets and Therapy.2015;(8):525-533.
[28]Xiong X,Yang Y,Chen X,et al.Red cell distribution width as a significant indicator of medication and prognosis in type 2diabetic patients. Sci Rep. 2017;7(1):2709.
[29]Li XH,Guan LY, Lin HY, et al. Fibrinogen:A Marker in Predicting Diabetic Foot Ulcer Severity. J Diabetes Res.2016;2016:2358321.
[30]Howard SC, Algra A, Rothwell PM. Effect of age and glycaemic control on the association between fibrinogen and risk of acute coronary events after transient ischaemic attack or stroke. Cerebrovasc Dis. 2008;25(1-2):136-143.
[31]Lip GY,Lowe GD.Fibrin D-dimer:a useful clinical marker of thrombogenesis?. Clin Sci(Lond). 1995;89(3):205-214.
[32]Yarnell JW,Baker IA,Sweetnam PM,et al.Fibrinogen, viscosity,and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies. Circulation. 1991;83(3):836-844.
[33]Thaulow E,Erikssen J,Sandvik L,et al.Blood platelet count and function are related to total and cardiovascular death in apparently healthy men. Circulation. 1991;84(2):613-617.
[34]Papageorgiou N,Tousoulis D,Siasos G,et al.Is fibrinogen a marker of inflammation in coronary artery disease?. Hellenic J Cardiol. 2010;51(1):1-9.
[35]Kotbi S,Mjabber A,Chadli A,et al.Correlation between the plasma fibrinogen concentration and coronary heart disease severity in Moroccan patients with type 2 diabetes.Prospective study. Ann Endocrinol(Paris). 2016;77(5):606-614.
[36]Yao HQ,Wang FJ,Kang Z.Effects of endovascular interventions on vWF and Fb levels in type 2 diabetic patients with peripheral artery disease. Ann Vasc Surg. 2016;33:159-166.
[37]Wells PS, Owen C,Doucette S,et al.Does this patient have deep vein thrombosis?.Jama. 1998;279(14):1094.
[38]Lippi G,Franchini M,Targher G,et al.Help me, Doctor! My D-dimer is raised. Ann Med. 2008;40(8):594-605.
[39]Fu Z, Yao F, Abou-Samra AB,et al.Lipasin, thermoregulated in brown fat, is a novel but atypical member of the angiopoietinlike protein family. Biochem Biophys Res Commun. 2013;430(3):1126-1131.
[40]Hess K.The vulnerable blood. Coagulation and clot structure in diabetes mellitus. Hamostaseologie. 2015;35(1):25-33.
[41]Nwose EU,Richards RS,Jelinek HF,et al.D-dimer identifies stages in the progression of diabetes mellitus from family history of diabetes to cardiovascular complications. Pathology.2007;39(2):252-257.