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Published in: Cardiovascular Diabetology 1/2012

Open Access 01-12-2012 | Original investigation

Potential association between coronary artery disease and the inflammatory biomarker YKL-40 in asymptomatic patients with type 2 diabetes mellitus

Authors: Hyun Min Kim, Byung-Wan Lee, Young-Mi Song, Won Jin Kim, Hyuk-Jae Chang, Dong-Hoon Choi, Hee Tae Yu, EunSeok Kang, Bong Soo Cha, Hyun Chul Lee

Published in: Cardiovascular Diabetology | Issue 1/2012

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Abstract

Background

Inflammation plays an important role in coronary artery disease from the initiation of endothelial dysfunction to plaque formation to final rupture of the plaque. In this study, we investigated the potential pathophysiological and clinical relevance of novel cytokines secreted from various cells including adipocytes, endothelial cells, and inflammatory cells, in predicting coronary artery disease (CAD) in asymptomatic subjects with type 2 diabetes mellitus.

Methods

We enrolled a total of 70 asymptomatic type 2 diabetic patients without a documented history of cardiovascular disease, and determined serum levels of chemerin, omentin-1, YKL-40, and sCD26. We performed coronary computed tomographic angiography (cCTA) in all subjects, and defined coronary artery stenosis ≥ 50 % as significant CAD in this study.

Results

Subjects were classified into two groups: patients with suspected coronary artery stenosis on cCTA (group I, n = 41) and patients without any evidence of stenosis on cCTA (group II, n = 29). Group I showed significantly higher YLK-40 levels and lower HDL-C levels than group II (p = 0.038, 0.036, respectively). Levels of chemerin, omentin-1, and sCD26 were not significantly different between the two groups. Serum YKL-40 levels were positively correlated with systolic/diastolic BP, fasting/postprandial triglyceride levels, and Framingham risk score. Furthermore, YKL-40 levels showed moderate correlation with the degree of coronary artery stenosis and the coronary artery calcium score determined from cCTA. In multivariate logistic analysis, after adjusting for age, gender, smoking history, hypertension, and LDL-cholesterol, YLK-40 levels showed only borderline significance.

Conclusions

YKL-40, which is secreted primarily from inflammatory cells, was associated with several CVD risk factors and was elevated in type 2 diabetic patients with suspected coronary artery stensosis on cCTA. These results suggest the possibility that the inflammatory biomarker YKL-40 might be associated with coronary artery disease in asymptomatic patients with type 2 diabetes mellitus.
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Literature
1.
go back to reference Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB, Pasternak RC, Smith SC, Stone NJ: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004, 110: 227-239. 10.1161/01.CIR.0000133317.49796.0E.CrossRefPubMed Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB, Pasternak RC, Smith SC, Stone NJ: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004, 110: 227-239. 10.1161/01.CIR.0000133317.49796.0E.CrossRefPubMed
2.
go back to reference Seon CS, Min KW, Lee SY, Nho KW, Park SH, Koo BK, Han KA: Cardiovascular Risk Assessment with Vascular Function, Carotid Atherosclerosis and the UKPDS Risk Engine in Korean Patients with Newly Diagnosed Type 2 Diabetes. Diab Metab J. 2011, 35: 619-627. 10.4093/dmj.2011.35.6.619.CrossRef Seon CS, Min KW, Lee SY, Nho KW, Park SH, Koo BK, Han KA: Cardiovascular Risk Assessment with Vascular Function, Carotid Atherosclerosis and the UKPDS Risk Engine in Korean Patients with Newly Diagnosed Type 2 Diabetes. Diab Metab J. 2011, 35: 619-627. 10.4093/dmj.2011.35.6.619.CrossRef
3.
go back to reference Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, et al: Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008, 359: 2195-2207. 10.1056/NEJMoa0807646.CrossRefPubMed Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, et al: Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008, 359: 2195-2207. 10.1056/NEJMoa0807646.CrossRefPubMed
4.
go back to reference Wong ND, Dede J, Chow VH, Wong KS, Franklin SS: Global cardiovascular risk associated with hypertension and extent of treatment and control according to risk group. Am J Hypertens. 2012, 25: 561-567. 10.1038/ajh.2012.2.CrossRefPubMed Wong ND, Dede J, Chow VH, Wong KS, Franklin SS: Global cardiovascular risk associated with hypertension and extent of treatment and control according to risk group. Am J Hypertens. 2012, 25: 561-567. 10.1038/ajh.2012.2.CrossRefPubMed
5.
go back to reference Herder C, Karakas M, Koenig W: Biomarkers for the prediction of type 2 diabetes and cardiovascular disease. Clin Pharmacol Ther. 2011, 90: 52-66. 10.1038/clpt.2011.93.CrossRefPubMed Herder C, Karakas M, Koenig W: Biomarkers for the prediction of type 2 diabetes and cardiovascular disease. Clin Pharmacol Ther. 2011, 90: 52-66. 10.1038/clpt.2011.93.CrossRefPubMed
6.
go back to reference Rose GA: The diagnosis of ischaemic heart pain and intermittent claudication in field surveys. Bull World Health Organ. 1962, 27: 645-658.PubMedCentralPubMed Rose GA: The diagnosis of ischaemic heart pain and intermittent claudication in field surveys. Bull World Health Organ. 1962, 27: 645-658.PubMedCentralPubMed
7.
go back to reference Kang MK, Chang HJ, Kim YJ, Park AR, Park S, Jang Y, Chung N: Prevalence and determinants of coronary artery disease in first-degree relatives of premature coronary artery disease. Coron Artery Dis. 2012, 23: 167-173. 10.1097/MCA.0b013e3283515538.CrossRefPubMed Kang MK, Chang HJ, Kim YJ, Park AR, Park S, Jang Y, Chung N: Prevalence and determinants of coronary artery disease in first-degree relatives of premature coronary artery disease. Coron Artery Dis. 2012, 23: 167-173. 10.1097/MCA.0b013e3283515538.CrossRefPubMed
8.
go back to reference Mark DB, Nelson CL, Califf RM, Harrell FE, Lee KL, Jones RH, Fortin DF, Stack RS, Glower DD, Smith LR, et al: Continuing evolution of therapy for coronary artery disease. Initial results from the era of coronary angioplasty. Circulation. 1994, 89: 2015-2025. 10.1161/01.CIR.89.5.2015.CrossRefPubMed Mark DB, Nelson CL, Califf RM, Harrell FE, Lee KL, Jones RH, Fortin DF, Stack RS, Glower DD, Smith LR, et al: Continuing evolution of therapy for coronary artery disease. Initial results from the era of coronary angioplasty. Circulation. 1994, 89: 2015-2025. 10.1161/01.CIR.89.5.2015.CrossRefPubMed
9.
go back to reference Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, Paul N, Clouse ME, Shapiro EP, Hoe J, et al: Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med. 2008, 359: 2324-2336. 10.1056/NEJMoa0806576.CrossRefPubMed Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, Paul N, Clouse ME, Shapiro EP, Hoe J, et al: Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med. 2008, 359: 2324-2336. 10.1056/NEJMoa0806576.CrossRefPubMed
10.
go back to reference Gonzalez-Chavez A, Elizondo-Argueta S, Gutierrez-Reyes G, Leon-Pedroza JI: Pathophysiological implications between chronic inflammation and the development of diabetes and obesity. Cir Cir. 2011, 79: 209-216.PubMed Gonzalez-Chavez A, Elizondo-Argueta S, Gutierrez-Reyes G, Leon-Pedroza JI: Pathophysiological implications between chronic inflammation and the development of diabetes and obesity. Cir Cir. 2011, 79: 209-216.PubMed
11.
go back to reference Kim MK, Baek KH, Song KH, Kwon HS, Lee JM, Kang MI, Yoon KH, Cha BY, Son HY, Lee KW: Exercise treadmill test in detecting asymptomatic coronary artery disease in type 2 diabetes mellitus. Diab Metab J. 2011, 35: 34-40. 10.4093/dmj.2011.35.1.34.CrossRef Kim MK, Baek KH, Song KH, Kwon HS, Lee JM, Kang MI, Yoon KH, Cha BY, Son HY, Lee KW: Exercise treadmill test in detecting asymptomatic coronary artery disease in type 2 diabetes mellitus. Diab Metab J. 2011, 35: 34-40. 10.4093/dmj.2011.35.1.34.CrossRef
13.
go back to reference Rathcke CN, Persson F, Tarnow L, Rossing P, Vestergaard H: YKL-40, a marker of inflammation and endothelial dysfunction, is elevated in patients with type 1 diabetes and increases with levels of albuminuria. Diabetes Care. 2009, 32: 323-328.PubMedCentralCrossRefPubMed Rathcke CN, Persson F, Tarnow L, Rossing P, Vestergaard H: YKL-40, a marker of inflammation and endothelial dysfunction, is elevated in patients with type 1 diabetes and increases with levels of albuminuria. Diabetes Care. 2009, 32: 323-328.PubMedCentralCrossRefPubMed
14.
go back to reference Rondbjerg AK, Omerovic E, Vestergaard H: YKL-40 levels are independently associated with albuminuria in type 2 diabetes. Cardiovasc Diabetol. 2011, 10: 54-10.1186/1475-2840-10-54.PubMedCentralCrossRefPubMed Rondbjerg AK, Omerovic E, Vestergaard H: YKL-40 levels are independently associated with albuminuria in type 2 diabetes. Cardiovasc Diabetol. 2011, 10: 54-10.1186/1475-2840-10-54.PubMedCentralCrossRefPubMed
15.
go back to reference Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, Weissleder R, Pittet MJ: Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest. 2007, 117: 195-205. 10.1172/JCI29950.PubMedCentralCrossRefPubMed Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, Weissleder R, Pittet MJ: Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest. 2007, 117: 195-205. 10.1172/JCI29950.PubMedCentralCrossRefPubMed
16.
go back to reference Kastrup J: Can YKL-40 be a new inflammatory biomarker in cardiovascular disease?. Immunobiology. 2012, 217: 483-491. 10.1016/j.imbio.2011.04.007.CrossRefPubMed Kastrup J: Can YKL-40 be a new inflammatory biomarker in cardiovascular disease?. Immunobiology. 2012, 217: 483-491. 10.1016/j.imbio.2011.04.007.CrossRefPubMed
17.
go back to reference Mathiasen AB, Harutyunyan MJ, Jorgensen E, Helqvist S, Ripa R, Gotze JP, Johansen JS, Kastrup J: Plasma YKL-40 in relation to the degree of coronary artery disease in patients with stable ischemic heart disease. Scand J Clin Lab Invest. 2011, 71: 439-447. 10.3109/00365513.2011.586470.CrossRefPubMed Mathiasen AB, Harutyunyan MJ, Jorgensen E, Helqvist S, Ripa R, Gotze JP, Johansen JS, Kastrup J: Plasma YKL-40 in relation to the degree of coronary artery disease in patients with stable ischemic heart disease. Scand J Clin Lab Invest. 2011, 71: 439-447. 10.3109/00365513.2011.586470.CrossRefPubMed
18.
go back to reference Batinic K, Hobaus C, Grujicic M, Steffan A, Jelic F, Lorant D, Hortenhuber T, Hoellerl F, Brix JM, Schernthaner G, et al: YKL-40 is elevated in patients with peripheral arterial disease and diabetes or pre-diabetes. Atherosclerosis. 2012, 222: 557-563. 10.1016/j.atherosclerosis.2012.03.034.CrossRefPubMed Batinic K, Hobaus C, Grujicic M, Steffan A, Jelic F, Lorant D, Hortenhuber T, Hoellerl F, Brix JM, Schernthaner G, et al: YKL-40 is elevated in patients with peripheral arterial disease and diabetes or pre-diabetes. Atherosclerosis. 2012, 222: 557-563. 10.1016/j.atherosclerosis.2012.03.034.CrossRefPubMed
19.
go back to reference Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, Walder K, Segal D: Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology. 2007, 148: 4687-4694. 10.1210/en.2007-0175.CrossRefPubMed Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, Walder K, Segal D: Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology. 2007, 148: 4687-4694. 10.1210/en.2007-0175.CrossRefPubMed
20.
go back to reference Hah YJ, Kim NK, Kim MK, Kim HS, Hur SH, Yoon HJ, Kim YN, Park KG: Relationship between Chemerin Levels and Cardiometabolic Parameters and Degree of Coronary Stenosis in Korean Patients with Coronary Artery Disease. Diab Metab J. 2011, 35: 248-254. 10.4093/dmj.2011.35.3.248.CrossRef Hah YJ, Kim NK, Kim MK, Kim HS, Hur SH, Yoon HJ, Kim YN, Park KG: Relationship between Chemerin Levels and Cardiometabolic Parameters and Degree of Coronary Stenosis in Korean Patients with Coronary Artery Disease. Diab Metab J. 2011, 35: 248-254. 10.4093/dmj.2011.35.3.248.CrossRef
21.
go back to reference Yan Q, Zhang Y, Hong J, Gu W, Dai M, Shi J, Zhai Y, Wang W, Li X, Ning G: The association of serum chemerin level with risk of coronary artery disease in Chinese adults. Endocrine. 2012, 41: 281-288. 10.1007/s12020-011-9550-6.CrossRefPubMed Yan Q, Zhang Y, Hong J, Gu W, Dai M, Shi J, Zhai Y, Wang W, Li X, Ning G: The association of serum chemerin level with risk of coronary artery disease in Chinese adults. Endocrine. 2012, 41: 281-288. 10.1007/s12020-011-9550-6.CrossRefPubMed
22.
go back to reference Tan BK, Adya R, Randeva HS: Omentin: a novel link between inflammation, diabesity, and cardiovascular disease. Trends Cardiovasc Med. 2010, 20: 143-148. 10.1016/j.tcm.2010.12.002.CrossRefPubMed Tan BK, Adya R, Randeva HS: Omentin: a novel link between inflammation, diabesity, and cardiovascular disease. Trends Cardiovasc Med. 2010, 20: 143-148. 10.1016/j.tcm.2010.12.002.CrossRefPubMed
23.
go back to reference Yoo HJ, Hwang SY, Hong HC, Choi HY, Yang SJ, Seo JA, Kim SG, Kim NH, Choi KM, Choi DS, Baik SH: Association of circulating omentin-1 level with arterial stiffness and carotid plaque in type 2 diabetes. Cardiovasc Diabetol. 2011, 10: 103-10.1186/1475-2840-10-103.PubMedCentralCrossRefPubMed Yoo HJ, Hwang SY, Hong HC, Choi HY, Yang SJ, Seo JA, Kim SG, Kim NH, Choi KM, Choi DS, Baik SH: Association of circulating omentin-1 level with arterial stiffness and carotid plaque in type 2 diabetes. Cardiovasc Diabetol. 2011, 10: 103-10.1186/1475-2840-10-103.PubMedCentralCrossRefPubMed
24.
go back to reference Yudkin JS: Inflammation, obesity, and the metabolic syndrome. Horm Metab Res. 2007, 39: 707-709. 10.1055/s-2007-985898.CrossRefPubMed Yudkin JS: Inflammation, obesity, and the metabolic syndrome. Horm Metab Res. 2007, 39: 707-709. 10.1055/s-2007-985898.CrossRefPubMed
25.
go back to reference Gao X, Mi S, Zhang F, Gong F, Lai Y, Gao F, Zhang X, Wang L, Tao H: Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis. Cardiovasc Diabetol. 2011, 10: 87-10.1186/1475-2840-10-87.PubMedCentralCrossRefPubMed Gao X, Mi S, Zhang F, Gong F, Lai Y, Gao F, Zhang X, Wang L, Tao H: Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis. Cardiovasc Diabetol. 2011, 10: 87-10.1186/1475-2840-10-87.PubMedCentralCrossRefPubMed
26.
go back to reference DeFronzo RA: Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia. 2010, 53: 1270-1287. 10.1007/s00125-010-1684-1.PubMedCentralCrossRefPubMed DeFronzo RA: Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia. 2010, 53: 1270-1287. 10.1007/s00125-010-1684-1.PubMedCentralCrossRefPubMed
27.
go back to reference Fantuzzi G, Mazzone T: Adipose tissue and atherosclerosis: exploring the connection. Arterioscler Thromb Vasc Biol. 2007, 27: 996-1003. 10.1161/ATVBAHA.106.131755.CrossRefPubMed Fantuzzi G, Mazzone T: Adipose tissue and atherosclerosis: exploring the connection. Arterioscler Thromb Vasc Biol. 2007, 27: 996-1003. 10.1161/ATVBAHA.106.131755.CrossRefPubMed
28.
go back to reference Chu SH, Lee MK, Ahn KY, Im JA, Park MS, Lee DC, Jeon JY, Lee JW: Chemerin and adiponectin contribute reciprocally to metabolic syndrome. PLoS One. 2012, 7: e34710-10.1371/journal.pone.0034710.PubMedCentralCrossRefPubMed Chu SH, Lee MK, Ahn KY, Im JA, Park MS, Lee DC, Jeon JY, Lee JW: Chemerin and adiponectin contribute reciprocally to metabolic syndrome. PLoS One. 2012, 7: e34710-10.1371/journal.pone.0034710.PubMedCentralCrossRefPubMed
29.
go back to reference Yan P, Liu D, Long M, Ren Y, Pang J, Li R: Changes of serum omentin levels and relationship between omentin and adiponectin concentrations in type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2011, 119: 257-263. 10.1055/s-0030-1269912.CrossRefPubMed Yan P, Liu D, Long M, Ren Y, Pang J, Li R: Changes of serum omentin levels and relationship between omentin and adiponectin concentrations in type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2011, 119: 257-263. 10.1055/s-0030-1269912.CrossRefPubMed
30.
go back to reference Mentlein R, Gallwitz B, Schmidt WE: Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7–36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem. 1993, 214: 829-835. 10.1111/j.1432-1033.1993.tb17986.x.CrossRefPubMed Mentlein R, Gallwitz B, Schmidt WE: Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7–36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem. 1993, 214: 829-835. 10.1111/j.1432-1033.1993.tb17986.x.CrossRefPubMed
31.
go back to reference Augustyns K, Bal G, Thonus G, Belyaev A, Zhang XM, Bollaert W, Lambeir AM, Durinx C, Goossens F, Haemers A: The unique properties of dipeptidyl-peptidase IV (DPP IV/CD26) and the therapeutic potential of DPP IV inhibitors. Curr Med Chem. 1999, 6: 311-327.PubMed Augustyns K, Bal G, Thonus G, Belyaev A, Zhang XM, Bollaert W, Lambeir AM, Durinx C, Goossens F, Haemers A: The unique properties of dipeptidyl-peptidase IV (DPP IV/CD26) and the therapeutic potential of DPP IV inhibitors. Curr Med Chem. 1999, 6: 311-327.PubMed
32.
go back to reference Lamers D, Famulla S, Wronkowitz N, Hartwig S, Lehr S, Ouwens DM, Eckardt K, Kaufman JM, Ryden M, Muller S, et al: Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes. 2011, 60: 1917-1925. 10.2337/db10-1707.PubMedCentralCrossRefPubMed Lamers D, Famulla S, Wronkowitz N, Hartwig S, Lehr S, Ouwens DM, Eckardt K, Kaufman JM, Ryden M, Muller S, et al: Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes. 2011, 60: 1917-1925. 10.2337/db10-1707.PubMedCentralCrossRefPubMed
Metadata
Title
Potential association between coronary artery disease and the inflammatory biomarker YKL-40 in asymptomatic patients with type 2 diabetes mellitus
Authors
Hyun Min Kim
Byung-Wan Lee
Young-Mi Song
Won Jin Kim
Hyuk-Jae Chang
Dong-Hoon Choi
Hee Tae Yu
EunSeok Kang
Bong Soo Cha
Hyun Chul Lee
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2012
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-11-84

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