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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 3  |  Page : 926-931

Serum level of apelin-36 in psoriatic patients


1 Department of Dermatology, Andrology and STIs, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Dermatology, Mansoura General Hospital, Mansoura, Egypt

Date of Submission02-Apr-2020
Date of Decision22-Jun-2020
Date of Acceptance26-Jun-2020
Date of Web Publication18-Oct-2021

Correspondence Address:
Mona A Mohamed
Department of Dermatology, Mansoura General Hospital, Mansoura
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_115_20

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  Abstract 


Objective
To shed light on the possible role of apelin-36 in psoriasis and to evaluate the propensity of the psoriatic population to a prediabetic condition through determining the serum level of apelin-36 in psoriatic patients.
Background
Psoriasis is a chronic, inflammatory skin disease characterized by the formation of sharply demarcated, scaly, erythematous plaques. Research over the last few decades has shown the relation of psoriasis pathogenesis to systemic diseases and metabolic syndrome (obesity, hypertension, dyslipidemia, and diabetes).
Patients and methods
This case–control study was carried out on 60 cases with psoriasis and 60 age-matched and sex-matched healthy individuals as a control group. All were subjected to full history taking, general examination, local examination with determination of site of lesions and assessment of psoriasis area and severity index score. Serum apelin-36 and glycosylated hemoglobin (HbA1c) was done for all cases and control (P < 0.001).
Results
The serum level of apelin-36 was lower in psoriatic patients than controls (mean: 37.17 ± 75.93 vs. 221.85 ± 483.40 ng/ml; P = 0.028), while the blood level of HbA1c was higher in psoriatic patients than controls (mean: 5.98 ± 0.62 vs. 5.55 ± 0.54%; P < 0.001). The best cutoff value of apelin-36 in the prediction of prediabetic cases in psoriatic patients was lesser than or equal to 37.50 ng/ml, with a sensitivity of 94.4%, specificity of 66.7%, and total accuracy of 91.7%.
Conclusion
Apelin-36 serum level was decreased and HbA1c was increased in psoriasis patients that indicated impairment in glucose metabolism in psoriatic patients.

Keywords: apelin-36, glycosylated hemoglobin, metabolic syndrome, prediabetic, psoriasis


How to cite this article:
Farag AG, Hassan RA, Soliman SE, Mohamed MA. Serum level of apelin-36 in psoriatic patients. Menoufia Med J 2021;34:926-31

How to cite this URL:
Farag AG, Hassan RA, Soliman SE, Mohamed MA. Serum level of apelin-36 in psoriatic patients. Menoufia Med J [serial online] 2021 [cited 2024 Mar 29];34:926-31. Available from: http://www.mmj.eg.net/text.asp?2021/34/3/926/328289




  Introduction Top


Psoriasis is a chronic immune-mediated inflammatory disease of the skin, affecting 1–3% of the population. The skin lesions of psoriatic patients are sharply demarcated erythematous papules and plaques covered with silvery scales [1].

In psoriasis, insulin resistance may occur. Insulin resistance is associated with cytokines and adipokines produced by truncal adipose tissue. Adipokines, some of which are anti-inflammatory and others are proinflammatory, have various roles in the systemic inflammation observed in psoriasis. It has been observed that adipokine levels in psoriatic patients are similar to those observed in prediabetic individuals [2].

Apelin is a newly discovered peptide hormone that has protective cardiovascular properties including vasodilatation by activating endothelial nitric oxide synthase and reducing peripheral vascular resistance. Furthermore, it promotes a favorable effect on glucose metabolism. The predominant circulating isoforms are apelin-13 and apelin-36 [3].

Glycosylated hemoglobin (HbA1c) is a glucose bond with hemoglobin. HbA1c describes the average blood glucose concentration for 3 months. The amount of HbA1c is formed according to the blood glucose concentration. Compared with the fluctuating blood sugar levels almost every time, HbA1c tends to be stable. Consequently, it can be used as an objective measurement to detect the occurrence of insulin resistance [4].

A possible explanation for the association between psoriasis and diabetes is the presence of chronic inflammation that occurs due to the secretion of tumor necrosis factor-alpha and other proinflammatory cytokines such as interleukin-1 and interleukin-6, which precipitate both psoriasis and diabetes [5].

The aim of this study was to shed light on the possible role of apelin-36 in psoriasis and to evaluate the propensity of the psoriatic population to a prediabetic condition through determining the serum level of apelin-36 in psoriatic patients.

Patients and methods

The study was approved by the ethics committee of the Faculty of Medicine, Menoufia University and the patients were given an informed consent. This case–control study included 120 individuals who were attending the Menoufia Skin and Andrology Outpatient Clinic during the period from October 2018 to March 2019.

They were classified into two groups: group 1 (case group) included 60 patients with psoriasis and group 2 (control group) included 60 age-matched and sex-matched healthy individuals.

All who participated were subjected to the following after taking written consent: complete history taking, general examination, local examination with determination of the site of lesions, and assessment of psoriasis area and severity index (PASI) score. Serum apelin-36 was measured by the ELISA kit supplied by SunRed (Shanghai, China), catalog no: 201-12-2038. HbA1c was measured by ion exchange resin chromatography kits supplied by StanBio (Boehme, Texas USA), Procedure No 0350.

Patients who were suffering from any other dermatological disease, systemic disease, for example liver, kidney, heart diseases, obese patients, or patients receiving drugs for psoriasis for less than 1 month before enrolling in the study were excluded.

Statistical analysis

Data were collected, tabulated, and statistically analyzed using a personal computer with Statistical Package for the Social Sciences (SPSS), version 15, program (SPSS Inc., Chicago, Illinois, USA). Qualitative data were expressed as: number and percentage, while quantitative data were expressed as: arithmetic mean, median, range, SD, and percentage. For comparing qualitative variables, we used a χ2 test. For comparison between nonnormally distributed quantitative variables we used the Mann–Whitney U test (U test). For comparison between two independent groups having parametric variables we used Student's t test. Additionally, Spearman's correlations were used for presenting correlation coefficients between apelin and selected variables. P value less than 0.05 was considered statistically significant.


  Results Top


This study included 60 cases with chronic plaque psoriasis and 60 age-matched and sex-matched healthy controls. The age of the patients ranged between 20 and 65 years with a mean of 46.5 ± 12.12 years and a median of 49 years. Among the 60 psoriatic patients, 30 were men and 30 were women with a male to female ratio of 1: 1. Regarding controls, their age ranged between 28 and 59 years with a mean of 43.17 ± 9.57 years and a median of 43 years, which included 26 men and 34 women. There is no statistically significant difference between cases and control groups regarding their age (P = 0.09, 0.46, respectively). The duration of the disease varied from 0.08 to 30.0 years with a mean of 6.14 ± 5.78 years and a median of 4.0 years. The PASI score of the patients ranged between 3.6 and 40.4 with a mean of 13.69 ± 6.30 and a median of 12.60. The severity of psoriasis was mild in 12 (20%), moderate in 41 (68.33%), and severe in seven (11.66%) patients. There was a positive family history of psoriasis in only seven (11.7%) cases. Also, 13.3% of the studied cases had hypertension; 58 (96.7%) psoriatic patients were previously treated [Table 1].
Table 1: Demographic and clinical data of the participants of the study

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The level of apelin-36 in the studied psoriatic patients ranged between 7.89 and 600.2 ng/ml with a mean of 37.17 ± 75.93 ng/ml and a median of 25.23 ng/ml. In controls, it ranged between 4.95 and 2231.40 ng/ml with a mean of 221.85 ± 483.40 ng/ml and a median of 30.48 ng/ml. There was a statistically significant decrease in the serum level of apelin-36 in psoriatic patients than controls (P = 0.028). The level of HbA1c in the studied psoriatic patients ranged between 4.70 and 7.80% with a mean of 5.98 ± 0.62% and a median of 6.15%. In controls, it ranged between 4.53 and 6.45% with a mean of 5.55 ± 0.54% and a median of 5.76%. There was a statistically significant increase in blood HbA1c levels in psoriatic patients than controls (P < 0.001) [Figure 1] and [Figure 2].
Figure 1: Box and Whisker plot showing median apelin-.36 distribution among the studied groups.

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Figure 2: HbA1c distribution among the studied groups. HbA1c, glycosylated hemoglobin.

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There was no statistically significant correlation between studied parameters and serum apelin-36. There was a statistically significant positive correlation between disease duration and HbA1c [Table 2].
Table 2: Correlation between age, disease duration, and psoriasis area and severity index score with apelin-36 serum level and glycosylated hemoglobin among the studied psoriatic patients

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The best cutoff value of apelin-36 in the prediction of prediabetic cases in psoriatic patients was lesser than or equal to 37.50 ng/ml, with a sensitivity of 94.4%, specificity of 66.7%, total accuracy of 91.7%, positive predictive value of 96.2%, and a negative predictive value of 57.1% [Table 3].
Table 3: Validity of serum apelin-36 in differentiating normal and prediabetic psoriatic patient groups

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  Discussion Top


Psoriasis is a chronic, inflammatory skin disease characterized by the formation of sharply demarcated, scaly, erythematous plaques. Research over the last few decades has revealed the relation of psoriasis pathogenesis to systemic diseases and metabolic syndrome (obesity, hypertension, dyslipidemia, and diabetes) [6].

Apelin, an endogenous peptide, is identified as a ligand of the G protein-coupled receptor (APJ). Apelin belongs to the family of adipokines, which are bioactive mediators released by adipose tissue [7]. Its extensive tissue distribution suggests that the apelin/APJ system, also known as an apelinergic system, might be involved in many physiological processes, such as regulation of body fluid homeostasis, blood pressure, endocrine stress response, cardiac contractility, and angiogenesis [8]. Apelin/APJ system plays a certain role in inflammation-related diseases such as regulating oxidative stress. The effects of apelin and oxidative stress are similar. On one hand, vascular endothelial shear stress, oxidative stress, inflammation, and other factors can alter apelin expression and on the other hand, apelin has an impact on insulin sensitivity and cardiovascular function, exerting anti-inflammatory and antioxidant effects, acting as an adipokine. Also, overproduction of reactive oxygen species can lead to a series of inflammatory reactions, and apelin can regulate the production of reactive oxygen species. Thus, there is a close link between apelin, oxidative stress, and inflammation [9].

The aim of this study was to shed light on the possible role of apelin-36 in psoriasis and to evaluate the propensity of the psoriatic population to a prediabetic condition through determining the serum level of apelin-36 in psoriatic patients.

In the current study, the age of psoriasis patients ranged between 20 and 65 years, with a mean of 46.5 ± 12.12 years and a median of 49 years. Similarly, Icen et al. [10] in their study on 90 Italian psoriatic patients reported that the range of age in psoriasis cases was between 18 and 80 years with a mean value of 43.2 ± 17.0 years and a median value of 49 years. However, Tollefson et al.[11] investigated 100 Turkish psoriatic cases. They observed that psoriatic patients' age ranged between 4 and 18 years with a mean value of 9.43 ± 2.39 years and a median value of 11 years. This difference may be attributed to the fact that psoriasis is a common disease, less common in children and more common in adults with prevalence rates that showed a worldwide geographic variation, which is probably influenced by genetic and environmental factors [12].

Among our studied psoriatic patients, 30 were men and 30 were women with a male to female ratio of 1: 1. In accordance with the present findings, a recent study has found no consensus regarding sex and psoriasis association [13]. On the other hand, a higher prevalence of psoriasis was found in women [14]. This difference in results may be due to differences in many factors like weather and ethnicity and genetic factors among the population [15].

In this study, hypertension was evident in 13.3% of our psoriatic patients. Confirming this finding, Cohen et al.[5] reported hypertension in 27.5% in their study on 16 851 Israeli psoriatic patients. The pathophysiologic mechanisms of hypertension in patients with psoriasis remain unknown, although several biological pathways have been implicated, including overexpression of endothelin 1 (a potent vasoconstrictor expressed in vascular endothelium and keratinocytes), increased oxidative stress, and common inflammatory pathways. Upregulation of the renin–angiotensin signaling pathway may also promote the development of more difficult-to-control hypertension in patients with psoriasis. This hypothesis is supported by the observations of increased expression of the renin gene in lesional skin of patients with moderate to severe psoriasis compared with matched nonlesional skin and greater plasma renin activity, as well as increased urinary aldosterone excretion in patients with psoriasis [16].

In this study we found that there was a positive family history of psoriasis in seven (11.7%) cases. However, Solmaz et al.[17] reported a positive family history of psoriasis among 1393 Turkish patients with psoriasis, out of which 444 (31.9%) had a family history for psoriasis. This finding supports the concept of genetic predisposition in psoriasis [18].

There are no validated clinical measures for the assessment of psoriasis severity. As there is no supreme measure, different measures might be ideal for different situations and dermatologists might need all of them. PASI score may not be particularly sensitive for mild diseases, but it may be suitable for severe diseases [19]. In this study, PASI score ranged between 3.6 and 40.4 with a mean of 13.69 ± 6.30 and a median of 12.6. In addition, most of our cases (68.33%) showed a moderate form of psoriasis. Similarly, EL-Taweel et al.[20] found that mean of the PASI score of the studied group was 11.1 and moderate psoriasis was the most common presented form (46.86%).

In this study, the HbA1c level was significantly higher in the studied psoriatic patients than controls. In accordance with our result, Mala et al.[21] who studied 40 Indian psoriatic patients found that HbA1c was significantly high among the psoriatic group. Also, Milčić et al.[22] examined 244 psoriasis patients for 2 years for metabolic syndrome. The authors demonstrated a significant association between the incidence of type 2 diabetes mellitus (DM) and psoriasis. In this study, we found a positive correlation between HbA1c and PASI although this relation does not reach statistical significance. However, Adiguna et al.[4] who studied 33 psoriatic patients, six (18.2%) were with severe psoriasis and showed a significant correlation with positive direction and the strength of a medium correlation regarding the severity of psoriasis vulgaris based on the PASI score with blood HbA1c levels. This may be attributed to the difference in sample size and degree of psoriasis severity in each study.

We observed that HbA1c had a statistically significant positive correlation with disease duration. In agreement with our result, Inci et al.[23] reported that HbA1c was significantly associated with the duration of disease. This can be explained by the association between the chronic inflammation in psoriasis and DM that may support the notion that insulin resistance, DM, and metabolic syndrome are triggered by chronic inflammation and its associated cytokines [24].

Adipokines appear to represent a mechanistic link in the interaction between skin alterations and metabolic comorbidity in psoriasis patients. They can be roughly divided into bad and good ones. The bad adipokines are proinflammatory molecules that drive insulin resistance, disturbance of glucose and lipid metabolism, vascular dysfunction, and immune cell tissue infiltration and activation. They also may support skin inflammation and skin cell dysfunction. The good adipokines have opposite properties. The pattern of adipokines in the body largely depends on the activity state of the producing cells. Proinflammatory cytokines specifically increase the secretion of many bad adipokines while decreasing the secretion of good adipokines [25].

In this study, the level of apelin-36 in cases ranged between 7.89 and 600.2 ng/ml with a mean of 37.17 ± 75.93 ng/ml and a median of 25.23 ng/ml that was significantly low in the studied psoriatic patients than controls. In accordance with our findings Capo et al.[26] found that apelin-36 had lower levels in the psoriatic population than their matched peers. However, Alataş and Kökçam[27] showed that apelin levels were significantly higher in patients with psoriasis than those in the control group and suggested that adiponectin, leptin, and apelin may play a role in the pathogenesis of psoriasis. This difference in results may be due to the difference in the inflammatory state assessed by PASI.

In this study we found that serum apelin-36 demonstrates a statistically significant negative correlation with HbA1c. In accordance with our findings, Zhang et al.[28] found a negative correlation of apelin with HbA1c, fasting glucose, and HOMA-IR. However, Kara et al.[29] found positive correlations between serum apelin-36 levels and HbA1c in patients with impaired fasting glucose, and they concluded that apelin-36 levels could reflect the changes in glucose metabolism and it may be a useful marker in combination with other parameters to prevent complications of diabetes. Also, it may be an indicator for insulin resistance and impairment in glucose metabolism. It may also have a probable potential role in the treatment of type 2 DM in the future.

In this study, it has been observed that apelin-36 is a good valid test in the detection of prediabetic cases in the psoriatic patient group with a cutoff point of less than or equal to 37.50 ng/ml, sensitivity of 94.4%, specificity of 66.7%, and total accuracy of 91.7%. Confirming our results, Ma et al.[30] observed that apelin concentration could predict incident diabetes (the sensitivity was 63.2% and specificity was 58.9%).


  Conclusion Top


Apelin-36 serum level was decreased and HbA1c was increased in psoriasis patients, which indicated an impairment in glucose metabolism in psoriatic patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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