Menoufia Medical Journal

ORIGINAL ARTICLE
Year
: 2018  |  Volume : 31  |  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

Correspondence Address:
Mohamed F.M. Aglan
Intensive Care Unit, Sharq-Elmadina Hospital, Ministry of Health, Alexandria
Egypt

Abstract

Objective 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. Background 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. Results 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. Conclusion 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.



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;31:474-480


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 2020 Apr 8 ];31:474-480
Available from: http://www.mmj.eg.net/text.asp?2018/31/2/474/239769


Full Text



 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 [1]. 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 [2].

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 [3]. Abdominal obesity is associated with low-grade inflammation, as the visceral adipose tissue acts as an endocrine organ secreting bioactive substances, collectively termed adipokines [4]. Adipokines regulate adipose-tissue function, influence glucose metabolism, and influence energy balance at the systemic level [5]. Secretion of high adipokine levels in obese participants contributes to the development of a chronic inflammation state that impairs normal adipose tissue function [6].

Insulin resistance arises from two mechanisms: secretion of adipokines and excessive lipolysis and release of free fatty acids from adipose tissue [7]. Data suggest that accumulation of fat in the abdominal area is the cause of reduced insulin sensitivity and impairment of the insulin signaling pathway [8].

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 [9].

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 [10].

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 [11].

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 [12]. 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 [13].

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 [14],[15]. 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 [16].

Aim

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 [17], glycemic control parameters [fasting blood sugar (FBS), glycated hemoglobin (HbA1c), fasting insulin [18], and homeostasis model assessment for insulin resistance (HOMA-IR) [19], lipid profile [20], and urinary albumin–creatinine ratio (UACR) [18].

Statistical analysis

Data were fed to a computer, and analyzed using IBM SPSS software package (version 20.0; IBM Corp. Released 2011. IBM Corp., Armonk, NY) [21],[22]. 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}{Figure 1}{Table 2}

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}

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].{Table 4}

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}

 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 [3]. Adipokines demonstrate different properties: some have proinflammatory activity and enhance insulin resistance and others have anti-inflammatory properties and an insulin-sensitizing effect [23].

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. [24] 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 [24].

Similar results were obtained by Yan et al. [25] 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. [26] 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 [17],[24],[25],[26] as well as a negative correlation with HDL-C [27]. 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. [28] 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. [17] 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 [29] 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.

Study limitations

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

Nil.

Conflicts of interest

There are no conflicts of interest.

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