CLINICAL SIGNIFICANCE OF PROCALCITONIN AND C-REACTIVE PROTEIN IN THE PREDICTION OF CARDIOVASCULAR COMPLICATIONS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
DOI:
https://doi.org/10.22159/ajpcr.2017.v10i9.19524Keywords:
Procalcitonin, Diabetes mellitus, C-reactive protein, Cardiovascular complicationsAbstract
Â
 Objective: This work was delineated to assess procalcitonin (PCT) and C-reactive protein (CRP) as prognostic markers for cardiovascular complication in type 2 diabetic patients.
Methods: Forty diabetic patients without cardiovascular disease (CVD), 40 diabetic patients with CVD, and 20 healthy control counterparts were participated in this study. Serum PCT and CRP levels were assayed and correlated with metabolic parameters. Receiver operating characteristic (ROC) curve analysis was done for each biochemical marker.
Results: The mean level of PCT was 707.17±99.19 ng/l in diabetic patients versus 881.30±123.56 ng/l for the cardio-diabetic patients (p<0.0001). The mean value of CRP was 34.43±17.27 mg/l in diabetic patients versus 50.32±20.19 mg/l for the cardio-diabetic patients (p=0.0003). PCT levels were significantly amplified in the cardio-diabetic patients with increasing CRP, triglycerides (TG), fasting blood glucose (FBG), and cholesterol (p=0.004, 0.0005, 0.002, and 0.01, respectively). CRP levels were significantly enhanced in the cardio-diabetic patients with increasing TG, FBG, cholesterol, and microalbumin (p=0.002, 0.047, 0.003, and 0.001 respectively). ROC curve analysis for PCT and CRP revealed that the area under curve (AUC) was 0.878 and 0.727, respectively. These findings indicate the good validity of the above biomarkers especially PCT as a prognostic marker for cardiovascular complication in type 2 diabetic patients.
Conclusion: This study evidences the usefulness of measuring serum levels of PCT and CRP in diagnosis of cardiovascular complication in type 2 diabetic patients.
Downloads
References
What is hemoglobin A1c? An analysis of glycated hemoglobins by electrospray ionization mass spectrometryClin Chem J. 272:International Diabetes Federation. IDF Diabetes Atlas. 7th ed. Brussels, Belgium: International Diabetes Federation; 2015.
Wolfs MG, Hofker MH, Wijmenga C, van Haeften TW. Type 2 diabetes mellitus: New genetic insights will lead to new therapeutics. Curr Genomics 2009;10(2):110-8.
Somepalli M, Vinukonda K, Panugandla R, Shankar SB, Lakshmi C. Prevalence of acute cardiac and renal complications in poorly controlled diabetics and role of clinical pharmacist in modifying disease outcome in a tertiary care hospital. Int J Pharm Pharm Sci 2015;79(6):92-6.
Bartels DW, Davidson MH, Gong WC. Type 2 diabetes and cardiovascular disease: Reducing the risk. J Manag Care Pharm 2007;13 2 Suppl A: S2-15.
Fox CS, Golden SH, Anderson C, Bray GA, Burke LE, de Boer IH, et al. Update on prevention of cardiovascular disease in adults with type 2 diabetes mellitus in light of recent evidence: A scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 2015;38(9):1777-803.
Bakker W, Eringa EC, Sipkema P, van Hinsbergh VW. Endothelial dysfunction and diabetes: Roles of hyperglycemia, impaired insulin signaling and obesity. Cell Tissue Res 2009;335(1):165-89.
Lebovitz HE. Insulin resistance – A common link between type 2 diabetes and cardiovascular disease. Diabetes Obes Metab 2006;8(3):237-49.
Souza JR, Oliveira RT, Blotta MH, Coelho OR. Serum levels of interleukin-6 (Il-6), interleukin-18 (Il-18) and C-reactive protein (CRP) in patients with type-2 diabetes and acute coronary syndrome without ST-segment elevation. Arq Bras Cardiol 2008;90(2):86-90.
Al-Muhtaseb N, Al-Kaissi E, Muhi-Eldeen Z, Arafat T, AL-Muhtaseb S, Atiyah H. Oxidants and antioxidants as risk factors in young arabian male patients with acute myocardial infarction. Int J Pharm Pharm Sci 2016;8(6):273-7.
Massaro KS, Costa SF, Leone C, Chamone DA. Procalcitonin (PCT) and C-reactive protein (CRP) as severe systemic infection markers in febrile neutropenic adults. BMC Infect Dis 2007;7:137.
Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: Associations with obesity, insulin resistance, and endothelial dysfunction: A potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999;19(4):972-8.
Gendrel D, Bohuon C. Procalcitonin as a marker of bacterial infection. Pediatr Infect Dis J 2000;19(8):679-87.
Maisner M. Procalcitonin – A New, Innovative Infection Parameter. Biochemical and Clinical Aspects. Stuttgart: Georg Thième; 2000.
Weglöhner W, Struck J, Fischer-Schulz C, Morgenthaler NG, Otto A, Bohuon C, et al. Isolation and characterization of serum procalcitonin from patients with sepsis. Peptides 2001;22(12):2099-103.
Birnbaum RS, Mahoney WC, Burns DM, O’Neil JA, Miller RE, Roos BA. Identification of procalcitonin in a rat medullary thyroid carcinoma cell line. J Biol Chem 1984;259(5):2870-4.
Jacobs JW, Lund PK, Potts JT Jr., Bell NH, Habener JF. Procalcitonin is a glycoprotein. J Biol Chem 1981;256(6):2803-7.
Nishikura T. Procalcitonin (PCT) production in a thyroidectomized patient. Intensive Care Med 1999;25(9):1031.
Ittner L, Born W, Rau B, Steinbach G, Fischer JA. Circulating procalcitonin and cleavage products in septicaemia compared with medullary thyroid carcinoma. Eur J Endocrinol 2002;147(6):727-31.
Meisner M, Müller V, Khakpour Z, Toegel E, Redl H. Induction of procalcitonin and proinflammatory cytokines in an anhepatic baboon endotoxin shock model. Shock 2003;19(2):187-90.
Ridker PM. Inflammatory biomarkers and risks of myocardial infarction, stroke, diabetes, and total mortality: Implications for longevity. Nutr Rev 2007;65(12 Pt 2):S253-9.
Yarnell JW, Baker IA, Sweetnam PM, Bainton D, O’Brien JR, Whitehead PJ, 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):836-44.
Sentürk T, Cordan J, Baran I, Ozdemir B, Güllülü S, Aydinlar A, et al. Procalcitonin in patients with acute coronary syndrome: Correlation with high-sensitive C-reactive protein, prognosis and severity of coronary artery disease. Acta Cardiol 2007;62(2):135-41.
Maruna P, NedelnÃková K, Gürlich R. Physiology and genetics of procalcitonin. Physiol Res 2000;49 Suppl 1:S57-61.
Hatherill M, Tibby SM, Turner C, Ratnavel N, Murdoch IA. Procalcitonin and cytokine levels: Relationship to organ failure and mortality in pediatric septic shock. Crit Care Med 2000;28(7):2591-4.
Clec’h C, Fosse JP, Karoubi P, Vincent F, Chouahi I, Hamza L, et al. Differential diagnostic value of procalcitonin in surgical and medical patients with septic shock. Crit Care Med 2006;34(1):102-7.
Meisner M, Rauschmayer C, Schmidt J, Feyrer R, Cesnjevar R, Bredle D, et al. Early increase of procalcitonin after cardiovascular surgery in patients with postoperative complications. Intensive Care Med 2002;28(8):1094-102.
Thomas L, editor. Clinical Laboratory Diagnostics. 1st ed. Frankfurt: TH-Books Verlagsgesellschaft; 1998. p. 131-7.
Richmond W. Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin Chem 1973;19(12):1350-6.
Assmann G. HDL-cholesterol precipitant. Randox Labs. Ltd. Crumlin Co. Antrim, N. Ireland. Internist 1979;20:559-64.
Okada M, Matsui H, Ito Y, Fujiwara A, Inano K. Low-density lipoprotein cholesterol can be chemically measured: A new superior method. J Lab Clin Med 1998;132(3):195-201.
Jacobs NJ, Van Denmark PJ. Triglycerides liquicolor. Arch Biochem Biophys 1960;88:250-5.
Trivelli LA, Ranney HM, Lai HT. Hemoglobin components in patients with diabetes mellitus. N Engl J Med 1971;284(7):353-7.
Hedlund P. Clinical and experimental studies on C-reactive protein (acute phase protein). Acta Med Scand Suppl 1961;361:1-71.
Mogensen CE, Schmitz A. Microalbumin for the quantitative determination of albumin in urine. Med Clin North Am 1988;72:1465-92.
Arkader R, Troster EJ, Lopes MR, Júnior RR, Carcillo JA, Leone C, et al. Procalcitonin does discriminate between sepsis and systemic inflammatory response syndrome. Arch Dis Child 2006;91(2):117-20.
MartÃn-Timón I, Sevillano-Collantes C, Segura-Galindo A, Del Cañizo-Gómez FJ. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World J Diabetes 2014;5(4):444-70.
Ali TM, Al Hadidi K. Chemerin is associated with markers of inflammation and predictors of atherosclerosis in Saudi subjects with metabolic syndrome and type 2 diabetes mellitus. Beni Suef Univ J Basic Appl Sci 2013;2:86-95.
Krauss RM. Lipids and lipoproteins in patients with type 2 diabetes. Diabetes Care 2004;27(6):1496-504.
Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 1997;46(1):3-10.
Kelley DE, Simoneau JA. Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus. J Clin Invest 1994;94(6):2349-56.
Blüher M, Kratzsch J, Paschke R. Plasma levels of tumor necrosis factor-alpha, angiotensin II, growth hormone, and IGF-I are not elevated in insulin-resistant obese individuals with impaired glucose tolerance. Diabetes Care 2001;24(2):328-34.
Reaven GM, Chen YD. Role of abnormal free fatty acid metabolism in the development of non-insulin-dependent diabetes mellitus. Am J Med 1988;85(5A):106-12.
Tan CE, Foster L, Caslake MJ, Bedford D, Watson TD, McConnell M, et al. Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL subfraction patterns in normolipemic men and women. Arterioscler Thromb Vasc Biol 1995;15(11):1839-48.
Zambon A, Austin MA, Brown BG, Hokanson JE, Brunzell JD. Effect of hepatic lipase on LDL in normal men and those with coronary artery disease. Arterioscler Thromb 1993;13(2):147-53.
Mayerson AB, Hundal RS, Dufour S, Lebon V, Befroy D, Cline GW, et al. The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes 2002;51(3):797-802.
Miyazaki Y, Mahankali A, Matsuda M, Mahankali S, Hardies J, Cusi K, et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2002;87(6):2784-91.
Makris K, Spanou L, Rambaouni-Antoneli A, Koniari K, Drakopoulos I, Rizos D, et al. Relationship between mean blood glucose and glycated haemoglobin in type 2 diabetic patients. Diabet Med 2008;25(2):174-8.
Peterson KP, Pavlovich JG, Goldstein D, Little R, England J, Peterson CM. What is hemoglobin A1c? An analysis of glycated hemoglobins by electrospray ionization mass spectrometry. Clin Chem 1998;44(9):1951-8.
Miedema K. Standardization of HbA1c and optimal range of monitoring. Scand J Clin Lab Invest Suppl 2005;240:61-72.
Belfki H, Ben Ali S, Bougatef S, Ben Ahmed D, Haddad N, Jmal A, et al. Association between C-reactive protein and type 2 diabetes in a Tunisian population. Inflammation 2012;35(2):684-9.
Morohoshi M, Fujisawa K, Uchimura I, Numano F. Glucose-dependent interleukin 6 and tumor necrosis factor production by human peripheral blood monocytes in vitro. Diabetes 1996;45(7):954-9.
Guha M, Bai W, Nadler JL, Natarajan R. Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via
hyperglycemia-induced oxidant stress-dependent and -independent pathways. J Biol Chem 2000;275(23):17728-39.
Grunfeld C, Feingold KR. Regulation of lipid metabolism by cytokines during host defense. Nutrition 1996;12 1 Suppl: S24-6.
Hirschfield GM, Pepys MB. C-reactive protein and cardiovascular disease: New insights from an old molecule. QJM 2003;96(11):793-807.
Soylemez MA, Seyment O, Yigit G. A novel mechanism between type II diabetes mellitus and procalcitonin gene expression. Mol Ther 2005;11:S346.
Schiopu A, Hedblad B, Engström G, Struck J, Morgenthaler NG, Melander O. Plasma procalcitonin and the risk of cardiovascular events and death: A prospective population-based study. J Intern Med 2012;272(5):484-91.
Chowta NK, Pant P, Chowta MN. Microalbuminuria in diabetes mellitus: Association with age, sex, weight, and creatinine clearance. Indian J Nephrol 2009;19(2):53-6.
Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: The candesartan and lisinopril microalbuminuria (CALM) study. BMJ 2000;321(7274):1440-4.
Bucala R, Cerami A. Advanced glycosylation: Chemistry, biology, and implications for diabetes and aging. Adv Pharmacol 1992;23:1-34.
Tan KC, Chow WS, Ai VH, Metz C, Bucala R, Lam KS. Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care 2002;25(6):1055-9.
Haddad FH, Omari AA, Shamailah QM, Malkawi OM, Shehab AI, Mudabber HK, et al. Lipid profile in patients with coronary artery disease. Saudi Med J 2002;23(9):1054-8.
Celermajer DS. Endothelial dysfunction: Does it matter? Is it reversible? J Am Coll Cardiol 1997;30(2):325-33.
Dokken BB. The pathophysiology of cardiovascular disease and diabetes: Beyond blood pressure and lipids. Diabetes Spectr 2008;21:160-5.
Chan AC. Vitamin E and atherosclerosis. J Nutr 1998;128(10):1593-6.
Napoli C, Triggiani M, Palumbo G, Condorelli M, Chiariello M, Ambrosio G. Glycosylation enhances oxygen radical-induced modifications and decreases acetylhydrolase activity of human low density lipoprotein. Basic Res Cardiol 1997;92(2):96-105.
Cai A, Li G, Chen J, Li X, Wei X, Li L, et al. Glycated hemoglobin level is significantly associated with the severity of coronary artery disease in non-diabetic adults. Lipids Health Dis 2014;13:181.
Brownlee M, Cerami A, Vlassara H. Advanced products of nonenzymatic glycosylation and the pathogenesis of diabetic vascular disease. Diabetes Metab Rev 1988;4(5):437-51.
Brownlee M. The pathobiology of diabetic complications: A unifying mechanism. Diabetes 2005;54(6):1615-25.
Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005;353(25):2643-53.
Geluk CA, Post WJ, Hillege HL, Tio RA, Tijssen JG, van Dijk RB, et al. C-reactive protein and angiographic characteristics of stable and unstable coronary artery disease: Data from the prospective PREVEND cohort. Atherosclerosis 2008;196(1):372-82.
Inoue T, Kato T, Uchida T, Sakuma M, Nakajima A, Shibazaki M, et al. Local release of C-reactive protein from vulnerable plaque or coronary arterial wall injured by stenting. J Am Coll Cardiol 2005;46(2):239-45.
Dunn EJ, Philippou H, Ariëns RA, Grant PJ. Molecular mechanisms involved in the resistance of fibrin to clot lysis by plasmin in subjects with type 2 diabetes mellitus. Diabetologia 2006;49(5):1071-80.
Ridker PM. Cardiology Patient Page. C-reactive protein: A simple test to help predict risk of heart attack and stroke. Circulation 2003;108(12):e81-5.
Liang Z, Yu K, Wu B, Zhong Y, Zeng Q. The elevated levels of plasma chemerin and C-reactive protein in patients with acute coronary syndrome. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2015;31(7):953-6.
Shrivastava AK, Singh HV, Raizada A, Singh SK. C-reactive protein, inflammation and coronaryheart disease. Egypt Heart J 2015;67:89-97.
Paffen E, DeMaat MP. C-reactive protein in atherosclerosis: A causal factor? Cardiovasc Res 2006;71(1):30-9.
Pfützner A, Schöndorf T, Hanefeld M, Forst T. High-sensitivity C-reactive protein predicts cardiovascular risk in diabetic and nondiabetic patients: Effects of insulin-sensitizing treatment with pioglitazone. J Diabetes Sci Technol 2010;4(3):706-16.
Sinning CR, Sinning JM, Schulz A, Schnabel RB, Lubos E, Wild PS, et al. Association of serum procalcitonin with cardiovascular prognosis in coronary artery disease. Circ J 2011;75(5):1184-91.
Sponholz C, Sakr Y, Reinhart K, Brunkhorst F. Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: a systematic review of the literature. Crit Care. 2006;10(5):145-55.
Erren M, Reinecke H, Junker R, Fobker M, Schulte H, Schurek JO, et al. Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries. Arterioscler Thromb Vasc Biol 1999;19(10):2355-63.
Schlitt A, Heine GH, Blankenberg S, Espinola-Klein C, Dopheide JF, Bickel C, et al. CD14+ CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels. Thromb Haemost 2004;92(2):419-24.
Ataoglu HE, Yilmaz F, Uzunhasan I, Cetin F, Temiz L, Döventas YE, et al. Procalcitonin: A novel cardiac marker with prognostic value in acute coronary syndrome. J Int Med Res 2010;38(1):52-61.
Remskar M, Horvat M, Hojker S, Noc M. Procalcitonin in patients with acute myocardial infarction. Wien Klin Wochenschr 2002;114(5-6):205-10.
Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, Jensen G, Clausen P, Scharling H, et al. Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 2004;110(1):32-5.
Jensen JS, Borch-Johnsen K, Feldt-Rasmussen B, Appleyard M, Jensen G. Urinary albumin excretion and history of acute myocardial infarction in a cross-sectional population study of 2,613 individuals. J Cardiovasc Risk 1997;4(2):121-5.
Stehouwer CD, Schalkwijk CG. Endothelial function and dysfunction. In: DeFronzo RA, Ferrannini E, Keen H, Zimmet P, Chichester JW, editors. International Textbook of Diabetes. 3rd ed. New York: Wiley; 2004. p. 1409-23.
Stehouwer CD, Smulders YM. Microalbuminuria and risk for cardiovascular disease: Analysis of potential mechanisms. J Am Soc Nephrol 2006;17(8):2106-11.
Jager A, van Hinsbergh VW, Kostense PJ, Emeis JJ, Nijpels G, Dekker JM, et al. C-reactive protein and soluble vascular cell adhesion molecule-1 are associated with elevated urinary albumin excretion but do not explain its link with cardiovascular risk. Arterioscler Thromb Vasc Biol 2002;22(4):593-8.
Stehouwer CD, Gall MA, Twisk JW, Knudsen E, Emeis JJ, Parving HH. Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: Progressive, interrelated, and independently associated with risk of death. Diabetes 2002;51(4):1157-65.
Seo SM, Baek SH, Jeon HK, Kang SM, Kim DS, Kim WS, et al. Correlations between the level of high-sensitivity C-reactive protein and cardiovascular risk factors in Korean adults with cardiovascular disease or diabetes mellitus: The CALLISTO study. J Atheroscler Thromb 2013;20(7):616-22.
Bahceci M, Tuzcu A, Ogun C, Canoruc N, Iltimur K, Aslan C. Is serum C-reactive protein concentration correlated with HbA1c and insulin resistance in Type 2 diabetic men with or without coronary heart disease? J Endocrinol Invest 2005;28(2):145-50.
Amanullah S, Jarari A, Govindan M, Basha MI, Khatheeja S. Association of hs-CRP with diabetic and non-diabetic individuals. Jordan J Biol Sci 2010;3:7-12.
Rahmani F, Rastian ML, Ghanbarzehi A, Behnammoghadam M, Abdollahimohammad A. Procalcitonin: A novel blood marker in coronary artery disease. Indian J Fundam Appl Life Sci 2015;5:2887-93.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
