• Users Online: 178
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 1  |  Issue : 1  |  Page : 28-35

Study of serum apelin and its relation to obesity-associated hypertension


1 Endocrinology Unit, Department of Internal Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt
2 Department of Cardiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Web Publication6-Jul-2015

Correspondence Address:
Marwa A Salah
199 Teeba st., Sporting, Alexandria
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2356-8062.159990

Rights and Permissions
  Abstract 

Introduction
Over the past few decades obesity has become a major burden on health worldwide. The prevalence of hypertension has increased with a significant increase in the prevalence of overweight and obesity. Recent studies indicate an important role of adipose tissue hormones called adipokines in obesity-associated complications. Apelin has recently been added to the family of adipokines. One of the physiologic functions of the apelin/APJ system is regulation of the cardiovascular function. The aim of this study was to determine the relation of serum apelin to obesity-associated hypertension as well as to myocardial performance.
Patients and methods
The study included 30 obese hypertensive patients, 30 obese nonhypertensive patients, and 25 age-matched and sex-matched controls. In all studied participants we determined the lipid profile, serum insulin, fasting blood glucose level, HOMA-IR, serum apelin, and echocardiographic results of left ventricular systolic and diastolic function.
Results
Higher levels of fasting blood glucose, fasting serum insulin, HOMA-IR, triglycerides, total cholesterol, and low-density lipoprotein were detected in obese hypertensive and nonhypertensive patients. Left ventricular mass index (LVMI) was increased in both obese hypertensive and nonhypertensive patients in comparison with healthy individuals. Left ventricular ejection fraction and E/A ratio were significantly lower in hypertensive obese versus nonhypertensive obese individuals (P = 0.004 and <0.001, respectively), whereas LVMI was higher in hypertensive versus nonhypertensive patients (P < 0.001). Apelin levels were significantly equally higher in obese hypertensive and nonhypertensive patients (6.10 ± 1.88 and 6.40 ± 1.60 ng/ml) compared with controls (4.22 ± 0.86 ng/ml, P < 0.001). In hypertensive obese individuals, serum apelin correlated negatively with left ventricular ejection fraction (P = 0.02) and directly with E/A ratio (P = 0.03).
Conclusion
Apelin levels are significantly higher in obese hypertensive and nonhypertensive patients. This increase might be a compensatory mechanism against myocardial dysfunction with obesity.

Keywords: adipokines, apelin, hypertension, obesity


How to cite this article:
Assaad SN, El-Aghoury AA, El-Sharkawy EM, Azzam EZ, Salah MA. Study of serum apelin and its relation to obesity-associated hypertension. Egypt J Obes Diabetes Endocrinol 2015;1:28-35

How to cite this URL:
Assaad SN, El-Aghoury AA, El-Sharkawy EM, Azzam EZ, Salah MA. Study of serum apelin and its relation to obesity-associated hypertension. Egypt J Obes Diabetes Endocrinol [serial online] 2015 [cited 2017 Aug 18];1:28-35. Available from: http://www.ejode.eg.net/text.asp?2015/1/1/28/159990


  Introduction Top


Over the past few decades obesity has become a major burden on health worldwide. Its prevalence in developing countries that have adopted a western lifestyle has tripled in 20 years. At present, more than 1.1 billion adults worldwide are overweight (BMI >25 kg/m 2 ) and 312 million of them are obese (BMI >30 kg/m 2 ) [1] .

Obesity is a multifactorial disease; several factors including genetic predisposition, misregulation of energy balance, and environmental and social factors contribute to its development. Excess energy intake and decreased energy consumption due to a sedentary lifestyle are the main contributors to the obesity epidemic. Energy balance is regulated by a complex network of neurons in the central and lateral hypothalamus. In obesity, these regulatory mechanisms fail to inhibit excess food intake and storage of energy [2] .

Obesity is a major factor in the development of the metabolic syndrome, a state characterized by overweight, insulin resistance, hypertension, and impaired lipid metabolism and body fat distribution. Individuals with metabolic syndrome have marked risks for the development of type 2 diabetes mellitus and they possess high cardiovascular mortality [3] . Because of these adverse consequences, obesity has been estimated to decrease life expectancy by 7 years at the age of 40. In addition, obesity predisposes to the development of cancer, asthma, osteoarthritis, sleep apnea, pregnancy complications, and depression, leading to overall decrease in the quality of life [4] .

In obesity, the size and number of adipocytes are increased, and this is accompanied by changes in the gene expression profile in large adipocytes [5] . Adipose tissue is infiltrated with macrophages and the macrophage quantity has been correlated with measures of insulin resistance. In addition to stimulation of low-grade inflammation, the secretion of adipokines regulating food intake, insulin sensitivity, blood pressure, and inflammation is altered in obesity [6] .

The increasing prevalence of hypertension occurred in conjunction with a dramatic increase in the prevalence of overweight and obesity. Data from the NHANES show a strong linear relationship between BMI and systolic and diastolic blood pressure. The Framingham Heart Study showed that a 5% weight gain increases hypertension risk by 30% in 4 years [7],[8],[9] . Not only is obesity linked with hypertension, but weight loss in obese individuals is associated with a decline in blood pressure [10] .

Recent studies indicate an important role of adipose tissue hormones called adipokines in obesity-associated complications. A number of adipokines such as leptin, adiponectin, and resistin have been identified, and apelin has recently been added to the family of adipokines; expression of both apelin and apelin receptor (APJ) has been described in adipocytes [11],[12] .

In 1998, apelin-36 was isolated from bovine stomach extracts and used to sequence the cDNA of human and bovine apelin. It was subsequently identified as the endogenous ligand of the APJ receptor, one of the G protein-coupled receptors (GPCRs), whose function had been unknown until the discovery of its ligand. The APJ receptor was first cloned by homology to another known receptor (GPCRs), and the human APJ amino acid sequence is 31% identical to that of the angiotensin II type-1A receptor [13],[14] .

Biologically active apelin is found in the epithelial cells of the gastric mucosa, the myocardium, and endocardial endothelium, in the lungs, kidneys, and adrenals, and in the endothelium of large and small blood vessels. In the heart, it is found in endothelial cells in both small and large coronary vessels, in the endocardial endothelium, and in smaller quantities in cardiomyocytes and vascular smooth muscle cells [15],[16] .

One of the physiologic functions of the apelin/APJ system is regulation of cardiovascular function. Although apelin is widely distributed, the main target of its action appears to be the cardiovascular system. It induces temporary falls in systolic and diastolic blood pressure, mediated by endothelium-dependent vasodilation, accompanied by a slight rise in heart rate and contractility following intravenous injection [17] .

Apelin peptides mediate three major actions in tissues from patients with cardiovascular disease: endothelium-dependent vasodilatation, direct vasoconstriction, and increased cardiac contractility [18] .

Insulin directly regulates apelin production in adipocytes, demonstrating the potential link with obesity-associated variations of insulin sensitivity status [11] . It was shown that apelin inhibited insulin secretion in mice, suggesting a link between apelin and glucose homeostasis [19] .

In humans, higher plasma apelin levels were found in obese compared with leaner individuals [11] . In patients with essential hypertension, circulating apelin levels are reduced, and lower plasma apelin is independently associated with more profound left ventricular systolic and diastolic function impairment [20] .

The aim of this study was to determine the relation of serum apelin to obesity-associated hypertension as well as to myocardial performance.


  Patients and methods Top


Patients

The study was carried out on 60 obese patients (BMI ≥30 kg/m 2 ) of both male and female sex, aged between 20 and 50 years, attending the Internal Medicine and the Endocrinology Outpatient Clinics in Alexandria Main University Hospital. The patients were categorized into two groups: group I included 30 obese hypertensive patients (blood pressure >140/90) and group II included 30 obese nonhypertensive individuals (blood pressure <140/90). In addition, the study included 25 healthy individuals of matched age and sex as a control group. All participants signed a written informed consent form after being explained the nature and aim of the study.

Exclusion criteria

Patients with a history of cardiac disease [coronary artery disease, rheumatic heart disease, diabetes mellitus, left ventricular systolic dysfunction (ejection fraction <40%), renal diseases, hepatic diseases, other endocrinal dysfunctions] and patients receiving antihypertensive drugs affecting the renin-angiotensin-aldosterone system were excluded from the study.

Methods

History and examination

History of hypertension, cardiovascular disease, coronary artery disease, and diabetes mellitus was taken. Complete physical examination was performed, including blood pressure measurement. Height, weight, and waist and hip circumference were measured and BMI was calculated using the formula weight in kg/height in m 2 . Body fat mass percentage was calculated using the Deurenberg equation as follows: body fat percentage = 1.2 (BMI)+0.23 (age)−10.8 (sex)-5.4, with age being in years and sex being designated as 1 for male and 0 for female patients [21] .

Biochemical assays

Venous sampling was carried out in the morning (8.00-10.00 a.m.) after an overnight fast of 8-10 h. The blood was drawn into an empty tube and then centrifuged for 10 min. The separated serum was used for the following assays: lipid profile [triglycerides, cholesterol, high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C)], fasting serum insulin by ELISA [22] , and fasting glucose level. Homeostasis Model Assessment 2 (HOMA2) calculator was used to estimate insulin resistance (HOMA-IR) [23] : fasting insulin (mIU/l) ×fasting glucose (mg/dl)/405. Plasma apelin levels were quantified by an enzyme immunoassay [Apelin-36 (Human) EIA kit (EK-057-15); Phoenix Pharmaceuticals Inc., Burlingame, California, USA] with intra-assay and interassay coefficients of variation less than 10% and less than 15%, respectively. The kit can identify the different active isoforms of apelin, including apelin-36 and apelin-13, as it targets the C terminus peptide present in all active forms of apelin with a normal range of 0-100 ng/ml [11] .

Echocardiography

Echocardiographic imaging was performed. Cardiac dimensions and wall thicknesses were measured according to standard recommendations. Left ventricular mass was calculated by the following formula: LVMI (Penn) = 1.04[(LVIDD+PWTD+IVSTD) 3 -LVIDD 3 ]−13.6 g. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening were estimated. Left ventricular diastolic function was assessed by measuring mitral flow E wave, A wave, E/A ratio, and mitral annulus tissue velocities. Pulmonary artery pressure was derived from pulmonary flow acceleration time.


  Results Top


All studied groups were matched for age and sex. A significant increase in BMI, waist circumference, hip circumference, and body fat percentage was detected among obese patients with or without hypertension in relation to normal individuals. Waist circumference was significantly higher in obese hypertensive versus obese nonhypertensive patients [Table 1].
Table 1 Clinical and laboratory characteristics of the studied groups and control

Click here to view


There were statistically significantly higher levels of fasting blood glucose, fasting serum insulin, HOMA-IR, triglycerides, total cholesterol, and LDL in obese hypertensive and nonhypertensive patients. In contrast, the level of HDL was statistically significantly lower in obese nonhypertensive patients than in healthy controls [Table 1] and [Figure 1].
Figure 1: Comparison between the three studied groups according to fasting serum insulin (¦ÌIU/ml) (group I: obese hypertensive patients; group II: obese nonhypertensive patients; group III: control participants). *P < 0.001 versus group III.

Click here to view


LVEF was statistically significantly lower in obese hypertensive patients versus obese nonhypertensive patients. LVMI was increased in both group I and group II in comparison with healthy individuals. A significantly higher level was noticed in group I versus group II. E/A ratio and pulmonary acceleration time (PAT) were significantly lower in group I in comparison with groups II and III [Table 2].
Table 2 Echocardiographic characteristics of the studied groups and control

Click here to view


In the studied obese hypertensive patients (n = 30), there was a statistically significant direct correlation between BMI and LVMI (r = 0.44, P < 0.015) [Figure 2].
Figure 2: Correlation between BMI and LVMI in group I (obese hypertensi ve).

Click here to view


The mean serum apelin level was statistically significantly higher in obese patients (groups I and II) in comparison with healthy controls (group III) [Figure 3]. In the studied obese hypertensive patients (n = 30), there was a statistically significant inverse correlation between serum apelin and LVEF (r = −0.423, P = 0.020) and there was a statistically significant direct correlation between serum apelin and E/A ratio [Figure 4] and [Figure 5]. In the studied obese nonhypertensive patients (n = 30), there was a statistically significant inverse correlation between serum apelin and LVMI (r = 0.44, P < 0.015) [Figure 6].
Figure 3: Comparison between the three studied groups according to fasting serum apelin (group I: obese hypertensive patients; group II: obese nonhypertensive patients; group III: control individuals). *P < 0.001 versus group III.

Click here to view
Figure 4: Correlation between serum apelin and left ventricular ejection fraction (LVEF) in group I (obese hypertensi ve).

Click here to view
Figure 5: Correlation between serum apelin and E/A ratio in group I (obese hypertensive).

Click here to view
Figure 6: Correlation between serum apelin and left ventricular ejection fraction (LVMI) in group II (obese nonhypertensi ve).

Click here to view



  Discussion Top


In the present study we observed that the waist circumference of obese hypertensive patients was significantly higher than that of obese normotensive individuals. Guagnano et al. [24] documented that waist circumference was the most important anthropometric factor associated with hypertensive risk. The authors concluded that intra-abdominal fat accumulation itself may play an important role in the pathogenesis of hypertension in obesity.

In the present study, after observing the glycemic profile we have found that obese patients had high fasting blood glucose, serum insulin, and HOMA-IR with no difference between obese hypertensive and obese normotensive patients. These findings are in concordance with those of Mahadik [25] , who found that serum insulin levels, HOMA-IR measure of IR, leptin, and hsCRP levels increased significantly and serum adiponectin levels decreased significantly in obese and obese hypertensive patients compared with nonobese control individuals; no difference was found in insulin and HOMA-IR levels between the two groups [25] . Our findings are supported by Heinonen and colleagues [26],[27],[28] , who confirmed the association between hyperinsulinemia and obesity. Insulin resistance is often linked to obesity. Excess adipose tissue plays a central role in the induction of insulin resistance [29] .

In the current study, it was observed that obese hypertensive and normotensive patients had significantly higher serum triglycerides, LDL-C levels, and serum cholesterol levels when compared with nonobese individuals, whereas obese nonhypertensive individuals had significantly lower HDL-C when compared with the control group. The same findings were observed by many authors [28],[30],[31],[32],[33] . Obesity is associated with increased free fatty acid resulting in impaired glucose use and increased hepatic glucose output; increased free fatty acid also affects the lipid metabolism by increasing VLDL and LDL production from the liver with lowering of HDL level; thus, atherogenic risk will be high and ischemic heart disease risk will increase, as reported by Després and Lemieux [34] .

The serum apelin level was found to be equally high in obese hypertensive and normotensive patients included in our study. These findings are in concordance with most studies demonstrating that adipose tissue apelin mRNA and plasma apelin levels are increased in patients with obesity, impaired glucose tolerance, and diabetes [35],[36],[37] . In contrast to our findings, Erdem et al. [38] reported plasma apelin levels to be decreased in overweight patients with newly diagnosed diabetes, suggesting that factors other than adiposity may regulate apelin levels. The discrepancies of the studies are unclear, but it has been suggested that obese adults with disturbed glucose metabolism demonstrate a decrease in apelin.

In our study, we did not observe significant correlation between apelin concentration and BMI, waist circumference, and HOMA-IR. Although BMI is a good measure for overweight, one needs to be aware of its limitation as an indirect measure of fat mass. The missing relationship between plasma apelin and obesity-related parameters might be explained by different sources of apelin secretion. Adipose tissue is not the only determinant in circulating apelin levels. Other sources (i.e. central nervous system, heart, lung, testis, ovary, mammary gland, and gastrointestinal system) may also play a multifactorial role in the pathophysiological settings.

The absence of association with HOMA-IR may be explained by the observation that the strongest association is found with type 2 diabetes mellitus, in which both insulin resistance and impaired insulin secretion are present and necessary. Thus, it is possible that HOMA-IR alone cannot determine the increase of apelin in diabetic individuals.

In our study, we were unable to find a significant correlation between apelin and insulin levels; the same results were found by Maria et al. [39] and Ba et al. [40] . Moreover, we found that, in obese patients, both plasma apelin and insulin levels are significantly higher, indicating that apelin homeostasis is impaired in the obese state and suggesting that the rise in plasma insulin could promote an increase in blood concentrations of apelin, as also suggested by Boucher et al. [11] .

In the present study, we observed comparable increase in serum apelin in obese hypertensive and nonhypertensive obese individuals, and no correlation between systolic blood pressure, diastolic blood pressure, and serum apelin. The same results were reported by Rittig et al. [41] , who examined the association of apelin serum levels with insulin sensitivity/resistance and body fat distribution as dependent cardiovascular risk factors; blood pressure was reported to be unaffected by serum apelin levels. Further, neither parameters of insulin sensitivity nor parameters of fat distribution, such as BMI and grade of adiposity, were associated with apelin serum levels [41] .

In contrast, Sonmez et al. [42] measured the circulating apelin level in patients with essential hypertension. A total of 30 young nonobese male patients with newly established and untreated hypertension and 30 healthy controls matched for age and BMI were studied. They found that apelin levels were significantly lower in hypertensive patients compared with controls. They could only speculate on the interaction of altered apelin with high blood pressure. However, the results cannot be deemed to belong to all hypertensive populations because of the small sample size and narrow selection criteria [42] .

The current study showed that obese individuals exhibited abnormalities in left ventricular structure and function, including a pattern of left ventricular hypertrophy and decreased diastolic function. Left ventricular hypertrophy was evidenced by increased LVMI in obese hypertensive and nonhypertensive patients in comparison with healthy individuals. A significantly higher level was noticed in obese hypertensive patients compared with obese nonhypertensive individuals. Our finding of low E/A ratio, which suggests a diastolic dysfunction, is similar to previous studies of Zarich et al. [43] and Stoddard et al. [44] on moderate and severely obese individuals and to a study by Peterson et al. [45] that showed depressed diastolic function in young obese women.

In the current study a negative significant correlation between serum apelin level and LVMI was observed and there was a significant positive correlation between serum apelin level and E/A ratio.

In agreement with our findings, Przewlocka et al. [20] studied 232 hypertensive patients without concomitant diseases affecting cardiovascular functions and 76 healthy controls. Patients with hypertension presented significantly higher values of left ventricular end-diastolic dimension, interventricular septal thickness, left ventricular posterior wall thickness, left atrial dimension, LVMI, and relative wall thickness compared with referents. Decreased values of E/A ratio in hypertension were indicative of left ventricular diastolic function impairment. Besides patient age, BMI, blood pressure, and LVMI, apelin was an independent determinant of left ventricular systolic and diastolic function parameters.

Experimental evidence indicates that apelin is one of the most potent endogenous inotropic agents [46],[47],[48] . An increase in myocardial contractility in response to the administration of apelin was seen both in normal and failing hearts with no accompanying left ventricular hypertrophy even during long-term observations [49],[50],[51] .

The biological potential of apelin demonstrated in experimental studies makes it necessary to consider this peptide as a relevant regulator of vascular tone and cardiac function in health and disease [19] . Hypertension, with its hemodynamic alterations and cardiac complications, might be an interesting field of exploration; however, the activity of the apelinergic system in this entity has not yet been extensively investigated. These results suggest that apelin might act as an endogenous protective regulator in the heart. The relative importance of the central and peripheral actions of apelin on normal cardiovascular physiology and cardiovascular disease is also undetermined [52] .

Taking into account the physiological roles of apelin in the cardiovascular system and in the control of glucose homeostasis, we can hypothesize that overproduction of apelin in the obese could be one of the last protections before the emergence of well-known obesity-related disorders such as type 2 diabetes mellitus or cardiovascular dysfunctions.


  Conclusion Top


Apelin levels are significantly higher in obese hypertensive and nonhypertensive patients. This increase might be as a compensatory mechanism against myocardial dysfunction with obesity.


  Acknowledgements Top


Conflicts of interest

None declared.

 
  References Top

1.
Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world a growing challenge. N Engl J Med 2007; 356:213-215.  Back to cited text no. 1
    
2.
Stein CJ, Colditz GA. The epidemic of obesity. J Clin Endocrinol Metab 2004; 89:2522-2525.  Back to cited text no. 2
    
3.
Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288:2709-2716.  Back to cited text no. 3
    
4.
Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A, Bonneux L, et al. The Netherlands Epidemiology and Demography Compression of Morbidity Research Group. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med 2003; 138:24-32.  Back to cited text no. 4
    
5.
Bluher M, Michael MD, Peroni OD, Ueki K, Carter N, Kahn BB, et al. Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev Cell 2002; 3:25-38.  Back to cited text no. 5
    
6.
Otto TC, Lane MD. Adipose development: from stem cell to adipocyte. Crit Rev Biochem Mol Biol 2005; 40:229-242.  Back to cited text no. 6
    
7.
Must A, Spadano J, Coakley EH. The disease burden associated with overweight and obesity. JAMA 1999; 282:1523-1529.  Back to cited text no. 7
    
8.
World Health Organization. Obesity: preventing and managing the global epidemic report of a WHO consultation. World Health Organ Tech Rep Ser 2000; 894:1-253.  Back to cited text no. 8
    
9.
Vasan RS, Larson MG, Leip EP. Assessment of frequency of progression to hypertension in non-hypertensive participants in the Framingham Heart Study: a cohort study. Lancet 2001; 358:1682-1686.  Back to cited text no. 9
    
10.
Huang Z, Willett WC, Manson JE, Rosner B, Stampfer MJ, Speizer FE, et al. Body weight, weight change and risk for hypertension in women. Ann Intern Med 1998; 128:81-88.  Back to cited text no. 10
    
11.
Boucher J, Masri B, Daviaud D, Gesta S, Guigné C, Mazzucotelli A, et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology. 2005; 146:1764-1771.  Back to cited text no. 11
    
12.
Garcia-Diaz D, Campion J, Milagro F, et al. Adiposity dependent apelin gene expression: relationships with oxidative and inflammation markers. Mol Cell Biochem 2007; 305:87-94.  Back to cited text no. 12
    
13.
Tatemoto K, Hosoya M, Habata Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun 1998; 251:471-476.  Back to cited text no. 13
    
14.
O'Dowd BF, Heiber M, Chan A, et al. A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene 1993; 136:355-360.  Back to cited text no. 14
    
15.
Kleinz MJ, Davenport AP, Skepper JN. Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells. Regul Pept 2004; 118:119-125.  Back to cited text no. 15
    
16.
Kleinz MJ, Davenport AP, Skepper JN. Emerging roles of apelin in biology and medicine. Pharmacol Ther 2005; 107:198-211.  Back to cited text no. 16
    
17.
Katugampola SD, Maguire JJ, Matthewson SR, et al. [(125)I] (Pyr(1)) Apelin-13 is a novel radioligand for localizing the APJ orphan receptor in human and rat tissues with evidence for a vasoconstrictor role in man. Br J Pharmacol 2001; 132:1255-1260.  Back to cited text no. 17
    
18.
Janet JM, Matthias JK, Sarah LP, et al. Apelin-13 identified as the predominant apelin isoform in the human heart: vasoactive mechanisms and inotropic action in disease. Hypertension 2009; 54:598-604.  Back to cited text no. 18
    
19.
Sorhede WM, Magnusson C, Ahren B. The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice. Regul Pept 2005; 131:12-17.  Back to cited text no. 19
    
20.
Przewlocka M, Kotwica T, Mysiak A, et al. Reduced circulating apelin in essential hypertension and its association with cardiac dysfunction. J Hypertens 2011; 29:971-979.  Back to cited text no. 20
    
21.
Deurenberg P, Weststrate JA, Seidell JC. Body mass index as a measure of body fatness: age and sex specific prediction formulas. J Nutr 1991; 65:105-114.  Back to cited text no. 21
    
22.
Clemmons DR. Role of insulin-like growth factor binding proteins in controlling IGF actions. Mol Cell Endocrinol 1998; 140:19-24.  Back to cited text no. 22
    
23.
Bonora E, Targher G, Alberiche M, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000; 23:57-63.  Back to cited text no. 23
    
24.
Guagnano MT, Ballone E, Colagrande V, Della VR, Manigrasso MR, Merlitti D, et al. Large waist circumference and risk of hypertension. Int J Obes Relat Metab Disord 2001; 25:1360-1364.  Back to cited text no. 24
    
25.
Mahadik SR. Association between adipocytokines and insulin resistance in Indian hypertensive patients. Indian Heart J 2012; 64:35-39.  Back to cited text no. 25
    
26.
Soriguer F, Garrido-Sanchez L, Garcia-Serrano S, Garcia-Almeida JM, Garcia-Arnes J, Tinahones FJ, et al. Apelin levels are increased in morbidly obese subjects with type 2 diabetes mellitus. Obes Surg 2009; 19:1574-1580.  Back to cited text no. 26
    
27.
Heinonen MV, Purhonen AK, Miettinen P, Pääkkönen M, Pirinen E, Alhava E et al. Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding. Regul Pept 2005; 130:7-13.  Back to cited text no. 27
    
28.
Yadav NK, Thanpari C, Shrewastwa MK, Mittal RK. Comparison of lipid profile in type-2 obese diabetics and obese non-diabetic individuals. A hospital based study from Western Nepal. Kathmandu Univ Med J (KUMJ) 2012;10: 44-47.  Back to cited text no. 28
    
29.
Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006; 444:840-846.  Back to cited text no. 29
    
30.
Thakur JS, Bisht S. Blood lipid profile of obese and non-obese sedentary college men. VSRD-TNTJ 2010; 1:26-29.  Back to cited text no. 30
    
31.
Nagila A, Bhatt M, Poudel B, Mahato P, Gurung D, Prajapati S, et al. Thyroid stimulating hormone and its correlation with lipid profile in the obese Nepalese population. J Clin Diagn Res 2008; 2:932-937.  Back to cited text no. 31
    
32.
Samatha P, Venkateswarlu M, Siva Prabodh V. Lipid profile levels in type 2 diabetes mellitus from the tribal population of Adilabad in Andhra Pradesh, India. J Clin Diagn Res 2012; 6:590-592.  Back to cited text no. 32
    
33.
Idogun ES, Unuigbe EI, Ogunro PS, Akinola OT, Famodu AA. Assessment of the serum lipids in Nigerians with type 2 diabetes mellitus complications. Pak J Med Sci (Part 1) 2007; 23:708-712.  Back to cited text no. 33
    
34.
Després JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006; 444:881-887.  Back to cited text no. 34
    
35.
Habchi M, Duvillard L, Cottet V, Brindisi MC, Bouillet B, Beacco M, et al. Circulating Apelin is increased in patients with type 1 or type 2 diabetes and is associated with better glycaemic control. Clin Endocrinol (Oxf) 2014; 81:696-701.  Back to cited text no. 35
    
36.
Castan-Laurell I, Vítkova M, Daviaud D, Dray C, Kováciková M, Kovacova Z, et al. Effect of hypocaloric diet-induced weight loss in obese women on plasma apelin and adipose tissue expression of apelin and APJ. Eur J Endocrinol 2008; 158:905-910.  Back to cited text no. 36
    
37.
Li L, Yang G, Li Q, Tang Y, Yang M, Yang H, et al. Changes and relations of circulating visfatin, apelin, and resistin levels in normal, impaired glucose tolerance, and type 2 diabetic subjects. Exp Clin Endocrinol Diabetes 2006; 144:544-548.  Back to cited text no. 37
    
38.
Erdem G, Dogru T, Tasci I, Sonmez A, Tapan S. Low plasma apelin levels in newly diagnosed type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2008; 116:289-292.  Back to cited text no. 38
    
39.
Maria GC, Federica S, Ilaria B, Carmine C, Michela I, Laura P, et al. Altered glucose homeostasis is associated with increased serum apelin levels in type 2 diabetes mellitus. PLoS One 2012; 7:e51236.  Back to cited text no. 39
    
40.
Ba HJ, Chen HS, Su Z, Du ML, Chen QL. Associations between serum apelin-12 levels and obesity-related markers in Chinese children. PLoS One 2014; 9:e86577.  Back to cited text no. 40
    
41.
Rittig K, Hildebrandt U, Thamer C, Staiger H, Peter A, Stefan N, et al. Apelin serum levels are not associated with early atherosclerosis or fat distribution in young subjects with increased risk for type 2 diabetes . Exp Clin Endocrinol Diabetes 2011; 119:358-361.  Back to cited text no. 41
    
42.
Sonmez A, Celebi G, Erdem G. Plasma apelin and ADMA levels in patients with essential hypertension. Clin Exp Hypertens 2010; 32:179-183.  Back to cited text no. 42
    
43.
Zarich SW, Kowalchuk GJ, McGuire MP. Left ventricular filling abnormalities in asymptomatic morbid obesity. Am J Cardiol 1991;68:377-381.  Back to cited text no. 43
    
44.
Stoddard MF, Tseuda K, Thomas M. The influence of obesity on left ventricular filling and systolic function. Am Heart J 1992; 124:694-699.  Back to cited text no. 44
    
45.
Peterson LR, Waggoner AD, Schechtman KB. Alterations in left ventricular structure and function in young healthy obese women. J Am Coll Cardiol 2004; 43:1399 -1404.  Back to cited text no. 45
    
46.
zokodi I, Tavi P, Foldes G, Voutilainen MS, Ilves M, Tokola H, et al. Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ Res 2002; 91:434-440.  Back to cited text no. 46
    
47.
Ashley EA, Powers J, Chen M, Kundu R, Finsterbach T, Caffarelli A, et al. The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo. Cardiovasc Res 2005; 65:73-82.  Back to cited text no. 47
    
48.
Berry MF, Pirolli TJ, Jayasankar V, Burdick J, Morine KJ, Gardner TJ, et al. Apelin has in vivo inotropic effects on normal and failing hearts. Circulation 2004; 110:II187-II193.  Back to cited text no. 48
    
49.
Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986; 57:450-458.  Back to cited text no. 49
    
50.
50 Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 2000; 102:1788-1794.  Back to cited text no. 50
    
51.
Kowalski M, Kukulski T, Jamal F, D'hooge J, Weidemann F, Rademakers F, et al. Can natural strain and strain rate quantify regional myocardial deformation? A study in healthy subjects. Ultrasound Med Biol 2001; 27:1087-1097.  Back to cited text no. 51
    
52.
Chong KS, Gardner RS, Morton JJ, Ashley EA, McDonagh TA. Plasma concentrations of the novel peptide apelin are decreased in patients with chronic heart failure. Eur J Heart Fail 2006; 8:355-360.  Back to cited text no. 52
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2]


This article has been cited by
1 Serum apelin levels and metabolic risk markers in obese women
Moushira Zaki,Sanaa Kamal,Wafaa Ezzat,Naglaa Hassan,Walaa Yousef,Hanaa Ryad,Ramy Mohamed,Eman Youness,Walaa Basha,Yasser Elhosary
Journal of Genetic Engineering and Biotechnology. 2017;
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and methods
Results
Discussion
Conclusion
Acknowledgements
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed2459    
    Printed14    
    Emailed0    
    PDF Downloaded27    
    Comments [Add]    
    Cited by others 1    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]