|Year : 2018 | Volume
| Issue : 2 | Page : 474-480
Serum chemerin and its association with coronary heart disease in diabetic and nondiabetic patients
Mostafa M Elnajjar1, Alaaeldin A Dawood1, Mahmoud A Soliman2, Gihane I Khalil3, Khaled M Amin Elzorkany1, Mohamed F.M. Aglan4
1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Cardiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Chemical Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt
4 Intensive Care Unit, Sharq-Elmadina Hospital, Ministry of Health, Alexandria, Egypt
|Date of Submission||18-Dec-2016|
|Date of Acceptance||03-Mar-2017|
|Date of Web Publication||27-Aug-2018|
Mohamed F.M. Aglan
Intensive Care Unit, Sharq-Elmadina Hospital, Ministry of Health, Alexandria
Source of Support: None, Conflict of Interest: None
Chemerin is a novel adipokinine that is associated with inflammation and adipogenesis. Our aim was to study the relationship between serum chemerin and coronary artery disease (CAD) in angiographically documented participants and participants without CAD among patients with diabetes mellitus and those without diabetes mellitus.
Chemerin is one of the adipokines that is linked to fat metabolism and thought to be linked to atherosclerosis and CAD.
Patient and methods
This cross-sectional study was conducted on 80 patients recruited from among patients presenting to the catheter laboratory of Sharq Al-Madina Hospital in Alexandria. Participants were divided into the following groups: group 1 included 20 diabetic patients with CAD; group 2 included 20 diabetic patients without CAD; group 3 included 20 nondiabetic patients with CAD; and group 4 included 20 participants as controls. Patients of groups 1 and 3 had angiographically documented CAD. Serum chemerin, glycemic control parameters (fasting blood sugar, glycated hemoglobin, fasting insulin, and homeostasis model assessment for insulin resistance), lipid profile, and urinary albumin–creatinine ratio were assessed.
The results of the present study showed that there was a statistically significant increase in mean serum chemerin level in group 1 compared with groups 2 and 4 (P = 0.007and 0.001, respectively), as well as compared with group 3, but this increase was not statistically significant. There was also a statistically significant increase in serum chemerin in group 3 compared with groups 2 and 4 (P = 0.001 and 0.003, respectively). However, there was no statistically significant difference between the two CAD groups (groups 1 and 3) with regard to the Gensini score. There was no statistically significant correlation among the other studied parameters.
Serum chemerin level was increased in CAD patients, irrespective of whether they were diabetic or nondiabetic, but did not increase as the severity of CAD increased when assessed by the Gensini score.
Keywords: chemerin, coronary artery disease, coronary angiography, homeostasis model assessment for insulin resistance, type 2 diabetes mellitus
|How to cite this article:|
Elnajjar MM, Dawood AA, Soliman MA, Khalil GI, Amin Elzorkany KM, Aglan MF. Serum chemerin and its association with coronary heart disease in diabetic and nondiabetic patients. Menoufia Med J 2018;31:474-80
|How to cite this URL:|
Elnajjar MM, Dawood AA, Soliman MA, Khalil GI, Amin Elzorkany KM, Aglan MF. Serum chemerin and its association with coronary heart disease in diabetic and nondiabetic patients. Menoufia Med J [serial online] 2018 [cited 2018 Nov 16];31:474-80. Available from: http://www.mmj.eg.net/text.asp?2018/31/2/474/239769
| Introduction|| |
Coronary artery disease (CAD), also known as CAD, is the narrowing of the blood vessels that supply blood and oxygen to the heart as a result of atherosclerosis. CAD can lead to unstable angina, myocardial infarction, and heart failure . During the past few decades, a great amount of knowledge concerning the pathophysiology of CAD has been achieved, and age (older than 40 years for men, 45 years for women), male sex, family history of CAD, smoking, hypertension, diabetes, obesity, high total cholesterol, low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol (LDL-C), high triglycerides (TGs), low physical activity, and accumulation of abdominal fat are some of the major risk factors .
Atherosclerosis, the underlying pathology responsible for CAD, is an inflammatory disease. Recent observations suggest that the atherosclerotic process is characterized by low-grade inflammation altering the endothelium of the coronary arteries and is associated with an increase in the level of markers of inflammation such as acute-phase proteins and cytokines. Cumulative evidence indicates that inflammation, at both focal and systemic levels, plays a key role in destabilization and rupture of atherosclerotic plaques, leading to acute cardiovascular events . Abdominal obesity is associated with low-grade inflammation, as the visceral adipose tissue acts as an endocrine organ secreting bioactive substances, collectively termed adipokines . Adipokines regulate adipose-tissue function, influence glucose metabolism, and influence energy balance at the systemic level . Secretion of high adipokine levels in obese participants contributes to the development of a chronic inflammation state that impairs normal adipose tissue function .
Insulin resistance arises from two mechanisms: secretion of adipokines and excessive lipolysis and release of free fatty acids from adipose tissue . Data suggest that accumulation of fat in the abdominal area is the cause of reduced insulin sensitivity and impairment of the insulin signaling pathway .
Participants with type 2 diabetes have a six-fold increased risk for macrovascular disease compared with that of nondiabetic participants, making cardiovascular disease a common cause of morbidity and mortality in diabetic patients .
Adipokines act as a link between obesity and cardiovascular disease: obesity leads to increased expression of proinflammatory adipokines and diminished expression of anti-inflammatory adipokines, resulting in the development of a chronic, low-grade inflammatory state. This adipokine imbalance is thought to be a key event in promoting both systemic metabolic dysfunction and cardiovascular disease .
Atherosclerosis is considered as a central pathological mechanism in the development of macrovascular diabetic complications. It starts very early and progresses throughout life, with firm evidence suggesting that chronic inflammation may play a vital role in the development of atherosclerosis .
Chemerin, one of the adipokines, has been found to enhance insulin signaling, to increase insulin-stimulated glucose transport, and to regulate insulin sensitivity in the adipose tissue. On the other hand, chemerin has been identified for its role of inducing insulin resistance from studies on human skeletal muscles . It has three types of receptors: chemokine-like receptor 1 (CMKLR1), serpentine chemokine (CC motif) receptor-like 2 (CCRL2), and G protein-coupled receptor 1 (GPR1). All these receptors bind chemerin with high affinity, but the downstream functional consequences of ligand binding are quite different .
Chemerin has proinflammatory and chemoattractant properties through binding to its receptors. In addition, it regulates adipogenesis and adipocyte metabolism, and thus may contribute to adipocyte expansion in obese individuals ,. Chemerin level has been shown to increase in obese participants, which correlates with obesity markers, and thus its alteration may have a pathological relevance to adipose dysfunction-associated disorders such as dyslipidemia and insulin resistance. Therefore, studying the relationship between chemerin and atherosclerosis, as well as insulin resistance, is increasingly an important research point to focus on .
The aim of the present study was to evaluate the relationship between serum chemerin and CAD in patients with diabetes mellitus and those without diabetes mellitus.
| Patients and Methods|| |
The present study was approved by our institution's Local Ethics Committee, and written informed consent was obtained from all patients.
This cross-sectional study was conducted on 80 participants who were divided into four groups by simple randomization: group 1 included 20 diabetic patients with CAD; group 2 included 20 diabetic patients without CAD; group 3 included 20 nondiabetic patients with CAD; and group 4 included healthy participants as controls. All participants were recruited from among patients presenting to the catheter laboratory of Sharq Al-Madina hospital in Alexandria. Patients of groups 1 and 3 had angiographically documented CAD with a degree of stenosis greater than or equal to 50%, which was considered as significant CAD in this study. We assessed serum chemerin , glycemic control parameters [fasting blood sugar (FBS), glycated hemoglobin (HbA1c), fasting insulin , and homeostasis model assessment for insulin resistance (HOMA-IR) , lipid profile , and urinary albumin–creatinine ratio (UACR) .
Data were fed to a computer, and analyzed using IBM SPSS software package (version 20.0; IBM Corp. Released 2011. IBM Corp., Armonk, NY) ,. Qualitative data are described using numbers and percentages. Quantitative data are described using ranges (minimum and maximum), means, SDs, and medians. Significance of the obtained results was judged at the 5% level.
| Results|| |
There were statistically significant differences between all groups with regard to serum chemerin (P = 0.001). We found a statistically significant increase in the mean serum chemerin level in participants of group 1 compared with groups 2 and 4 (P = 0.007and 0.001, respectively). We also found increased chimerin levels in group 1 compared with group 3, but this increase was not statistically significant (P2 = 0.929). There was also a statistically significant increase in serum chemerin in group 3 compared with groups 2 and 4 (P = 0.001 and 0.003, respectively) [Table 1] and [Figure 1]. There was no statistically significant difference between the two CAD groups (groups 1 and 3) with regard to the Gensini score (P = 0.316) [Table 2].
|Table 1: Comparison between the different groups according to serum chemerin|
Click here to view
|Figure 1: Comparison between the different groups according to chemerin.|
Click here to view
|Table 2: Comparison between the different groups according to the Gensini score|
Click here to view
In addition, there were statistically significant differences between all groups with regard to FBS (P = 0.001), which was statistically significantly increased in group I compared with groups 3 and 4 (P = 0.001 and P = 0.001, respectively), whereas it was not statistically significantly increased compared with group 2 (P = 1.000). In addition, there were statistically significant differences between all groups with regard to HbA1c percentage (P = 0.001), which was statistically significantly higher in group 1 compared with groups 3 and 4 (P = 0.001 and P = 0.001, respectively), whereas it was not statistically significantly increased compared with group 2 (P = 0.092). Regarding HOMA-IR and fasting insulin, there were no statistically significant differences between all groups (P = 0.116 and 0.478, respectively) [Table 3].
|Table 3: Comparison between the different groups according to different parameters related to glycemic status|
Click here to view
There were no statistically significant differences between all groups with regard to total cholesterol, HDL-C, LDL-C, and TG (P = 0.484, 0.557, 0.369, and 0.104, respectively)
|Table 4: Comparison between the different groups according to lipid profile|
Click here to view
The UACR was higher in group 1 compared with the other groups, but the differences between groups were not statistically significant (P = 0.0.68). In addition, there were no statistically significant differences between all groups with regard to the ankle brachial index (P = 0.904).
We performed a correlation analysis to investigate whether serum chemerin levels were related to the other studied parameters. [Table 5] shows that there were no statistically significant correlations between serum chemerin and other studied parameter (age, FBS, HbA1c, fasting insulin, HOMA-IR, total cholesterol, HDL-C, LDL-C, TG, ankle brachial index, or the Gensini score), except that there was a statistically significant negative correlation between serum chemerin and UACR in group 2 only.
|Table 5: Correlation between chemerin and other studied parameters in each group|
Click here to view
| Discussion|| |
Abdominal obesity is associated with low-grade inflammation, as the visceral adipose tissue acts as an endocrine organ secreting bioactive substances, collectively termed adipokines . Adipokines demonstrate different properties: some have proinflammatory activity and enhance insulin resistance and others have anti-inflammatory properties and an insulin-sensitizing effect .
In our study, there was no statistically significant correlation between serum chemerin and lipid profile parameters including total serum cholesterol, LDL-C, HDL-C, and serum TGs as well as glycemic control parameters such as FBS, fasting insulin, HbA1c, and HOMA-IR.
Chemerin was statistically significantly increased in CAD groups 1 and 3 compared with groups 2 and 4.
On further classification of CAD patients (groups 1 and 3) according to their Gensini scores, there was no statistically significant difference in the mean Gensini score between groups 1 and 3, but the correlation between serum chemerin and Gensini score was not statistically significant; therefore, chemerin levels were not proportionally related to the severity of CAD progresses.
Xiaotao et al.  enrolled a total of 132 patients with CAD and 56 patients without CAD who underwent coronary angiography for the evaluation of CAD and had their serum chemerin level measured. In agreement with our results, they showed that serum chemerin levels were significantly elevated in CAD patients compared with those without CAD .
Similar results were obtained by Yan et al.  who conducted a study including a total of 430 participants from a Chinese population (239 with CAD and 191 without CAD) who underwent coronary angiography. Their results showed that serum chemerin levels were associated with CAD independently of other cardiovascular risk factors, but they also showed that serum chemerin levels were significantly increased as the number of diseased coronary artery vessels increased and were positively related to the used Gensini score, which was contradictory to our result, as we found a positive correlation between serum chemerin and Gensini score.
Dong et al.  conducted a study including a total of 112 patients with metabolic syndrome (66 patients with CAD and 46 without CAD) and 52 healthy participants, and all of them underwent coronary angiography. They observed that serum chemerin levels were significantly elevated in metabolic syndrome patients with CAD compared with those without CAD and healthy participants, and concluded that chemerin level could be an independent predictive marker of CAD.
In our study, there was no statistically significant correlation between serum chemerin and lipid profile parameters, including total serum cholesterol, LDL-C, HDL-C, and serum TGs. In contrast to our results, some studies showed a significant positive correlation between chemerin and circulating TGs and LDL-C ,,, as well as a negative correlation with HDL-C . Among our studied participants, there was no statistically significant difference in serum chemerin levels between hypertensive participants and participants without hypertension in each group. In agreement with our results, Lachine et al.  found no significant correlation between hypertension and serum chemerin.
Among our studied groups, there was no statistically significant correlation between serum chemerin and glycemic control parameters. In agreement with our results, Bozaoglu et al.  described that circulating chemerin levels in individuals with type 2 diabetes were not significantly higher than those in normal control. This was attributed to taking antidiabetic drugs by a proportion of their type 2 diabetic study participants. In contrast to our results, Ali and Al Hadidi  showed that serum chemerin level was significantly correlated to fasting plasma glucose, fasting insulin level, and HOMA-IR among Saudi patients with type 2 diabetes and metabolic syndrome.
The results of the present study showed that there was no statistically significant difference in serum chemerin levels in participants with albuminuria (UACR > 30 mg albumin/1 g creatinine) compared with participants without albuminuria (groups 1, 3, and 4). However, there was a statistically significant negative correlation between serum chemerin and degree of albuminuria in group 2, which included 20 patients who were all hypertensive, and this could be explained by use of antihypertensive medications including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins, commonly used by both CAD patients and patients with diabetes, which are known to have anti-inflammatory effects.
For proper interpretation of the results of the present study, we should take into consideration some limitations. The principal limitation of the present study is the relatively small study population, considering that they were further divided into four groups. The cross-sectional nature of this study may have other limitations including the difficulty to evaluate a cause–effect relationship between chemerin and CAD. Our sample included participants of Egyptian nationality only, and we are uncertain whether our findings are applicable to other ethnic groups. Thus, further multicentric studies are required to investigate the relationship between chemerin level and CAD in various populations.
| Conclusion|| |
- Serum chemerin level was increased in CAD patients irrespective of the presence of diabetes, but was not related to the severity of CAD when assessed by the Gensini score.
- Serum chemerin level was not related to various glycemic control parameters; however, whether serum chemerin level is related to type 2 diabetes or not is still a controversial matter that needs further assessment.
- Serum chemerin level was not related to lipid profile (total cholesterol, HDL-C, LDL-C, or TG).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Imes CC, Austin MA. Low-density lipoprotein cholesterol, apolipoprotein B, and risk of coronary heart disease: from familial hyperlipidemia to genomics. Biol Res Nurs 2013; 15
Torpy JM, Burke AE, Glass RM. JAMA patient page. Coronary heart disease risk factors. JAMA 2009; 302
Madjid M, Willerson JT. Inflammatory markers in coronary heart disease. Br Med Bull 2011; 100
Poulos SP, Hausman DB, Hausman GJ. The development and endocrine functions of adipose tissue. Mol Cell Endocrinol 2010; 323
Pardo M, Roca-Rivada A, Seoane L, Casanueva F. Obesidomics: contribution of adipose tissue secretome analysis to obesity research. Endocrine2010; 41
Baldasseroni S, Mannucci E, Di Serio C, Orso F, Bartoli N, Mossello E, et al.
Resistin level in coronary artery disease and heart failure: the central role of kidney function. J Cardiovasc Med (Hagerstown) 2013; 14
Nagle CA, Klett EL, Coleman RA. Hepatic triacylglycerol accumulation and insulin resistance. J Lipid Res 2009; 50 (Supp l):
Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 2011; 11
Cho M, Park JS, Nam J, Kim CS, Nam JH, Kim HJ, et al.
Association of abdominal obesity with atherosclerosis in type 2 diabetes mellitus (T2DM) in Korea. J Korean Med Sci 2008; 23
Nakamura K, Fuster JJ, Walsh K. Adipokines: a link between obesity and cardiovascular disease. J Cardiol 2014; 63
De M Bandeira S, da Fonseca LJ, da S Guedes G, Rabelo LA, et al.
Oxidative stress as an underlying contributor in the development of chronic complications in diabetes mellitus. Int J Mol Sci 2013; 14
Wang D, Yuan GY, Wang XZ, Jia J, Di LL, Yang L, et al.
Plasma chemerin level in metabolic syndrome. Genet Mol Res 2013; 12
Monnier J, Lewén S, O'Hara E, Huang K, Tu H, Butcher EC, Zabel BA. Expression, regulation, and function of atypical chemerin receptor CCRL2 on endothelial cells. J Immunol 2012; 189
Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, Parlee SD, et al.
Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 2007; 282
Park KW, Halperin DS, Tontonoz P. Before they were fat: adipocyte progenitors. Cell Metab 2008; 8
Yang M, Yang G, Dong J, Liu Y, Zong H, Liu H, et al.
Elevated plasma levels of chemerin in newly diagnosed type 2 diabetes mellitus with hypertension. J Investig Med 2010; 58
Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, et al.
Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 2007; 148
Sacks DB. Carbohydrate. In: Burtis CA, Ashwood ER, editors. Tietz textbook of clinical chemistry
ed. Philadelphia: WB Saunders; 1994. pp. 935–949.
Diabetes Trials Unit (DTU). HOMA calculator: endocrinology TOCfD, Metabolism. 2013. Available at: http://www.dtu.ox.ac.uk.
[Last accessed on 2017 Jun 3].
Stein EA, Myers GL. Lipids, lipoproteins and apolipoproteins. In: Burtis CA, Ashwood ER, editors. Tietz textbook of clinical chemistry
ed. Philadelphia: WB Saunders; 1994. pp. 1002–1093.
Kotz S, Balakrishnan N, Read CB, Vidakovic B. Encyclopedia of statistical sciences
ed. Hoboken, NJ: Wiley-Interscience; 2006.
Kirkpatrick LA, Feeney BC. A simple guide to IBM SPSS statistics for version 20.0. Student ed.
Belmont, CA: Wadsworth, Cengage Learning; 2013.
Kotnik P, Fischer-Posovszky P, Wabitsch M. RBP4: a controversial adipokine. Eur J Endocrinol. 2011; 165
Xiaotao L, Xiaoxia Z, Yue X, Liye W. Serum chemerin levels are associated with the presence and extent of coronary artery disease. Coron Artery Dis 2012; 23
Yan Q, Zhang Y, Hong J, Gu W, Dai M, Shi J, et al.
The association of serum chemerin level with risk of coronary artery disease in Chinese adults. Endocrine 2012; 41
Dong B, Ji W, Zhang Y. Elevated serum chemerin levels are associated with the presence of coronary artery disease in patients with metabolic syndrome. Intern Med 2011; 50
Alfadda AA, Sallam RM, Chishti MA, Moustafa AS, Fatma S, Alomaim WS, et al.
Differential patterns of serum concentration and adipose tissue expression of chemerin in obesity: adipose depot specificity and gender dimorphism. Mol Cells 2012; 33
Lachine NA, Elnekiedy AA, Megallaa MH, Khalil GI, Sadaka MA, Rohoma KH, et al
. Serum chemerin and high-sensitivity C reactive protein as markers of subclinical atherosclerosis in Egyptian patients with type 2 diabetes. Ther Adv Endocrinol Metab 2016; 7
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
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]