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E-IJD® - ORIGINAL ARTICLE
Year : 2022  |  Volume : 67  |  Issue : 4  |  Page : 477
Serum irisin: A potential diagnostic marker for insulin resistance in acne vulgaris


1 From the Department of Dermatology, Affiliated Hospital of Southwest Medical University, Luzhou, China
2 Department of Dermatology, Sixth People's Hospital, Deyang, Sichuan, China

Date of Web Publication2-Nov-2022

Correspondence Address:
Changqiang Li
Department of Dermatology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.ijd_251_22

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   Abstract 

Background: Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous unit. Many factors are involved in the occurrence of acne. It has been confirmed that some adipokines play an important role in the development of AV. Irisin is a novel adipokine, which is highly expressed in skeletal muscle, liver, and fat. It improves insulin resistance (IR) by inducing the browning of white adipose tissue, increasing heat production and energy expenditure. Objective: The purpose of this study was to investigate the role of serum irisin as an adipokine to explore its function in the pathogenesis of AV and its correlation with IR, and whether it can be used as a potential biomarker of insulin sensitivity. Although the hyperinsulinemic-euglycemic clamp remains the gold standard for accurate determination of IR, it cannot be performed routinely. Various alternative simpler measures have been used, the most common being homeostasis model assessment. However, these metrics are limited by their accuracy, cost, and blood collection requirements.[1] Therefore, an effective and feasible serum biomarker is an attractive and relatively straightforward method, which may provide clinicians with a more accurate and simple method for the prediction and diagnosis of IR. IR can often be detected before other symptoms appear, so establishing an early diagnosis method will allow for the appropriate treatment of patients before the disease develops. Patients and Methods: The study included 171 subjects; 115 patients with newly diagnosed AV and 56 apparently healthy subjects. The contents of irisin and interleukin-1 alpha in serum were determined by enzyme-linked immunosorbent assay. The IR index was calculated by the homeostasis model. Results: Serum irisin levels in AV patients and control group were (24.0 ± 11.3) and (104.3 ± 27.0) ng/dl, respectively, which were significantly lower than those in control group (P < 0.001). Serum irisin was negatively correlated with IR (r = −0.711, P 0.001). The sensitivity of irisin was 100.0%, the specificity was 92.8%, and the cutoff point was 53.32. The decrease of serum irisin level could predict the patients with IR in acne. Conclusion: Serum irisin levels in AV patients were significantly decreased. Serum irisin showed acceptable performance criteria in the diagnosis of AV with IR. Serum irisin seems to be a good diagnostic and prognostic marker for IR. Further multi-center studies are needed to confirm this link, which could pave the way for new treatment options.


Keywords: Acne vulgaris, biomarkers, diagnosis, insulin resistance, irisin, prognosis


How to cite this article:
Tang L, Yu B, Liao Y, Long S, Yan H, He Q, Li C. Serum irisin: A potential diagnostic marker for insulin resistance in acne vulgaris. Indian J Dermatol 2022;67:477

How to cite this URL:
Tang L, Yu B, Liao Y, Long S, Yan H, He Q, Li C. Serum irisin: A potential diagnostic marker for insulin resistance in acne vulgaris. Indian J Dermatol [serial online] 2022 [cited 2022 Nov 26];67:477. Available from: https://www.e-ijd.org/text.asp?2022/67/4/477/360322



   Introduction Top


Acne vulgaris (AV) is a progressive chronic disease with mild symptoms. It is a disease caused by inflammation of the pilosebaceous glands in hair follicles. It often occurs on the face, chest and back, and other sebaceous gland-rich parts. Clinically, it can be manifested as papules, nodules, pustules, cysts, and even scarring in severe cases.[2],[3] Studies at home and abroad have found that 83–95% of adolescents are affected by acne.[4],[5] Acne is believed to be the result of a combination of multiple factors, in which androgens play an important role. Steroids in human skin are mainly synthesized at sebaceous glands, which contain enzymes required for the synthesis and metabolism of androgen and cholesterol.[4],[6] The activity of sebaceous glands increases with androgens, which leads to increased sebum production and stimulates keratinocyte proliferation.[7] In addition to androgens, many hormones such as estrogen, growth hormone, prolactin, insulin, and insulin-like growth factor-1 (IGF-1) are known to play important roles in the development and differentiation of sebaceous glands. Abnormal expression of one or more of these factors can affect the formation of acne.[8] The high incidence of acne in patients with polycystic ovary syndrome (PCOS) supports the role of insulin resistance (IR) in the development of acne.[9] IR is defined as the reduced responsiveness of target tissues to normal insulin levels and is widely accepted as the primary mechanism in the pathophysiology of metabolic syndrome. Fibroblasts and keratinocytes in the skin are the two main insulin target cells. IR and compensatory hyperinsulinemia reduce the expression of insulin-like growth factor binding proteins (IGFBPs).[10] IGFBP binds to IGF and prolongs its half-life, thereby controlling the transport of IGF to target tissues and regulating the level of circulating IGF.[11] High levels of free IGF-1 will make the above two main target cells continue to proliferate and differentiate, thereby promoting sebum synthesis and aggravating the condition of acne.[12]

IR is an important feature of metabolic diseases. Hyperinsulinemic-euglycemic clamp (HEC) is the gold standard for accurate assessment of IR status, but its routine use in clinical practice is limited due to its technical complexity and potential risk of hypoglycemia. An alternative test commonly used at present is (homeostasis model assessment) HOMA, which uses fasting insulin and glucose concentrations to assess IR. The procedure is simpler, less invasive, and correlates well with HEC. However, HOMA cannot detect early IR,[13] and new markers are urgently needed to achieve a more reliable assessment of insulin metabolism. Currently, many proteins are considered as alternative markers for the assessment of IR in AV, such as adiponectin, resistin, leptin, and other adipocytokines, which can reduce costs and side effects, but their roles are still controversial and further researches are needed to better clarify the role of these proteins in AV with IR.

Irisin is a newly discovered myokine with adipokine characteristics, which is secreted into the circulation in response to stimuli such as cold and physical exercise, so it is also known as the “exercise hormone”. Irisin is a cleavage and secreted fragment of a membrane protein, fibronectin type III domain-containing protein 5 (FNDC5). The C-terminal tail of FNDC5 is located in the cytoplasm, while the extracellular N-terminal part is cleaved and released as irisin.[14] Although the research of irisin has received extensive attention in the past few years, the cleavage mechanism of FNDC5 protein and the regulatory pathway of irisin remain unclear. Preliminary studies have shown that irisin expression is associated with obesity, type 2 diabetes, and metabolic syndrome. It may work by stimulating “browning,” the conversion of white fat tissue to brown adipose tissue, resulting in increased energy expenditure. Studies have found that increased levels are associated with lower IR. Irisin can improve IR and type 2 diabetes by increasing the sensitivity of insulin receptors in skeletal muscle and heart, improving hepatic glucose and lipid metabolism, and pancreatic β-cell function.[12],[15],[16],[17],[18] Irisin is closely related to many metabolic diseases and may serve as a potential new target against type 2 diabetes and IR, among others. This study attempts to explore the role of irisin in acne and IR by quantitatively measuring the level of irisin in the serum of acne patients and healthy people. We analyzed potential associations between irisin and various demographic, anthropometric, and clinical parameters. To investigate the relationship between irisin and acne, and to evaluate the ability of serum irisin levels to discriminate between acne patients and controls, as well as the potential correlation between irisin and IR.


   Objectives and Methods Top


A total of 171 subjects were included in this case-control study: 115 patients with newly clinically diagnosed acne and 56 apparently healthy subjects. Both groups were matched for age and gender. The exclusion criteria are as follows: (1) various malignant tumors; (2) severe heart, liver, and kidney dysfunction; (3) diabetes, thyroid, PCOS, and other metabolic diseases; (4) mental disorders or taking anti-inflammatory drugs; (5) pregnant and lactating women; (6) oral isotretinoin, hormone therapy for any reason within the past 3 months. This study was conducted from June 2020 to December 2020. All participants accepted sharing and signed informed consent. All subjects received a complete medical history and clinical examination. Acne severity was assessed using the Global Acne Grading System.

A standard questionnaire was administered by trained staff to obtain demographic information, personal characteristics, lifestyle risk factors, and personal medical history. Smoking was defined as smoking at least one cigarette per day for more than 1 year. Body mass index (BMI) is calculated as weight (kg) divided by height (m) squared (kg/m)2. Peripheral venous blood was collected at 8:00 am the next morning after fasting for 12 h for all subjects. After standing at room temperature for 30 min, the blood samples were centrifuged at 3000 r/min for 10 min, and the serum in the first test tube was detected by an automatic biochemical analyzer, which was used to measure fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), sex hormones, and other indicators. The second tube of serum was centrifuged and stored at −80°C for irisin analysis. Serum irisin levels were determined using a commercial enzyme-linked immunosorbent assay (ELISA) kit (E015581-96T (1KIT), Shanghai, China). These steps are performed in accordance with the manufacturer's recommendations. Serum fasting insulin levels were also determined by corresponding ELISA (XY-E80147H, Shanghai, China). Homeostasis model assessment-insulin resistance (HOMA-IR) index determined IR and insulin levels using a simple mathematically derived nonlinear equation [HOMA-IR: fasting insulin (mU/mL)] × fasting glucose (mmol/l)/22.5. IR was defined as HOMA-IR ≥2.69.

Statistical analysis

The obtained data were analyzed by Statistical Package for Social Sciences (SPSS26.0) software. Results for categorical variables are expressed as n or percentages. Results for continuous variables are presented as mean ± standard deviation (SD) and median (interquartile range). Categorical variables were compared using Chi-square test or Fisher's exact test, and continuous variables were compared using Student's t-test. Bivariate correlation uses Spearman's rank correlation. Logistic stepwise regression analysis was used to evaluate the relationship between serum irisin concentration and clinical characteristics. Cutoff index for serum irisin levels and HOMA-IR index were determined by receiver operating characteristic (ROC) curves, and cutoff point analysis was used to determine the optimal value of irisin to differentiate IR in acne patients. The threshold was defined by the maximum distance from the diagonal of the ROC (sensitivity × (1-specificity)). It has the best sensitivity and specificity in predicting AV with IR. Sensitivity was defined as the probability that irisin levels were equal to or lower than a certain value in acne patients with IR, while specificity was defined as the probability that irisin levels were higher than a certain value in acne patients without IR. A two-tailed P value ≤ 0.05 was considered to be an acceptable level of significance in this study.


   Results Top


Baseline clinical characteristics of subjects

[Table 1] shows the baseline demographic and clinical parameters of acne patients and healthy controls.
Table 1: Demographic and clinical variables of study subjects

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A total of 56 healthy controls and 115 AV patients were included in this study. The baseline clinical characteristics of all subjects are shown in [Table 1]. There was no statistically significant difference in gender composition between the two groups. Compared with the control group, the acne group had a lower mean age, but the acne group had a higher BMI index, IR index, and the incidence of IR than the control group. Serum irisin levels in AV patients were significantly lower than those in controls (84.7 ± 42.2 ng/mL and 169.3 ± 83.0 ng/mL, respectively, P < 0.001). The mean IL-1α in the acne group was 3.8 ± 2.0 pg/mL, and the mean in the control group was 3.1 ± 1.2 pg/mL, P = 0.005 <0.05, there was a significant difference between the two groups. According to the classification of acne severity, there were 93 cases (80.87%) of mild to moderate acne patients in the acne group, and 22 cases (19.13%) of severe and very severe acne patients. Patients exhibited significantly lower serum irisin levels and higher HOMA-IR index and IL-α levels [Table 1].

Comparison of clinical variables in acne patients with IR and without IR

The average level of irisin in the IR group was 24.0 ± 11.3 ng/mL, and that in the non-IR group was 104.3 ± 27.0 ng/mL. The irisin level in the IR group was lower than that in the non-IR group, and the difference was statistically significant (t = 22.328, P < 0.001). The mean values of IL-1α in IR group and control group were 3.2 ± 1.1 pg/mL and 4.0 ± 2.2 pg/mL, respectively, P = 0.02 <0.05, indicating a significant difference between the two groups. The age, sex hormone binding globulin (SHBG), and high-density lipoprotein in the IR group were lower than those in the common acne group; the BMI was higher than that in the common acne patients; Other qualitative data showed no significant difference between the two groups [Table 2].
Table 2: Comparison of IR and normal acne patients

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According to our research and analysis, it was found that there was a significant negative correlation between serum irisin level and HOMA-IR index in acne patients, the correlation coefficient r = −0.711, the correlation was statistically significant (P < 0.001). [Figure 1]
Figure 1: Scatter plot of IR index and irisin

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Multiple linear regression analysis of IR on irisin

After controlling for confounders with inconsistent distribution between the two groups, according to multiple linear logistic regression analysis, there was a significant independent association between irisin levels and IR. Irisin in patients with IR was 75.884 units lower than those without IR. The effect of IR on irisin was statistically significant (P < 0.001) [Table 3]. According to statistics, there are 93 patients (80.87%) with mild to moderate acne, and 22 patients (19.13%) with severe and extremely severe acne. After stratification according to the severity of acne, the influence of IR on irisin in both mild to moderate patients and severe patients was statistically significant. A decrease of 75.709 and 74.142 units respectively (P < 0.001) [Table 4] and [Table 5].
Table 3: Multiple linear regression analysis of the effect of IR on irisin

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Table 4: Multiple linear regression analysis of the effect of IR on irisin in mild to moderate patients (n=93)

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Table 5: Multiple linear regression analysis of the effect of IR on irisin in severe patients (n=22)

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Multiple linear regression analysis of the effect of IR on IL-1α

After controlling for confounders with inconsistent distribution between the two groups, multiple linear regression analysis showed that the effect of IR on IL-1α was not statistically significant [Table 6]. Stratified by acne severity, the effect of IR on IL-1α was not statistically significant [Table 7] and [Table 8].
Table 6: Multiple linear regression analysis of the effect of IR on IL-1α

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Table 7: Multiple linear regression analysis of the effect of IR on IL-1α in mild to moderate patients (n=93)

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Table 8: Multiple linear regression analysis of the effect of IR on IL-1α in severe patients (n=22)

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Correlation analysis of acne severity with irisin, IL-1α, and IR index

It was found that there was no significant correlation between the severity of acne and irisin, IL-1α, and IR index [Table 9].
Table 9: Correlation analysis of acne severity with irisin, IL-1α and IR index

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Irisin as a diagnostic marker for acne with IR

According to the results of this study, it was found that the cutoff point of irisin for predicting IR was 53.32 ng/mL, the area under the curve was 0.981 (0.936, 0.997), the sensitivity was 100.0% (87.7%, 100.0%), the specificity was 92.8% (82.7%, 95.9%), and the Youden index was 0.908 [Figure 2].
Figure 2: ROC curve of irisin predicting IR

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Acne and IR

AV is a chronic inflammatory disease of the pilosebaceous unit. Studies have shown that mTORC1 activity increases in the lesions of the skin and sebaceous glands of acne patients, and increased mTORC1 signaling is a characteristic of IR, obesity, type 2 diabetes, cancer, and neurodegenerative diseases.[19] Our study showed that there were 28 patients (24.3%) with IR in AV patients and 2 patients (3.6%) with IR in the control group, and the difference between the two groups was statistically significant (P = 0.001). The IR index of the acne group was 1.82 (1.22, 2.64), and that of the control group was 1.52 (1.19, 1.97), and the difference was statistically significant. This is consistent with the findings of Liao et al.,[20] who conducted a cross-sectional study by comparing the metabolic status of 100 male acne patients and 100 male controls, showing that the prevalence of metabolic syndrome in acne patients (17%) was higher than that in the control group (9%) (P = 0.09). The prevalence of IR in acne patients (22%) was significantly higher than that in control group (11%) (P = 0.03). This study did not find a significant relationship between the severity of AV and IR, which was basically consistent with the findings of Balta et al.[21] Their study on post-adolescent males found a significant correlation between IR and acne, but not with the severity of the disease. While Del Prete et al.[22] did not find any association between IR and acne in adult patients, which was different from Emiroğlu et al.[23] They observed a positive correlation between IR and the severity of AV. We speculate that these differences may be due to differences in the gender and age groups of acne patients and the number of studies. To determine IR in acne, Balta et al.[21] recruited 35 male and female acne patients over 25 years of age, with an average age of 30.8 years. Balta et al.[21] did not observe significant differences between the acne group and the control group in terms of the mean values of any study parameters (BMI, HDL-C, triglycerides, fasting blood glucose, insulin levels, and HOMA-IR). Del Prete et al.[22] observed systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose, HOMA-IR and other indicators between the patients and the controls group, and found statistically significant differences in these indicators between the two groups. They observed significant increases in BMI, waist circumference, HDL-C levels and plasma insulin levels in the patients. In our study, acne group with IR of age, SHBG, and HDL-C were lower than those of the acne group without IR, and their BMI was higher than that of the acne without IR group. No significant difference was found in the measurement of estradiol, luteinizing hormone, progesterone, follicle-stimulating hormone, and pituitary prolactin between the two groups, which is consistent with the study by Tsai MC et al.[24] Alan et al.[25] observed a positive correlation between BMI and acne severity. However, a national study conducted in Israel showed a complex relationship between acne and metabolism. In this study, which included 600,404 adolescents, the researchers found that being overweight or obesity was inversely associated with acne in a dose-dependent manner, suggesting that excess body mass index (BMI) has a protective effect on acne,[26] possibly through increased aromatase activity, which leads to greater conversion of testosterone to estradiol.[27] Estrogens are known to inhibit sebum secretion and attenuate the activity of pro-inflammatory cytokines through its anti-androgen effect.[28] These findings suggest that IR is prevalent in acne patients, but it has proved difficult to easily and accurately assess IR in routine clinical practice. Therefore, it is crucial to have diagnostic parameters that accurately reflect early IR in clinical practice, as early identification of IR may lead to better treatment of acne patients.

Acne and Irisin, IL-1α

Irisin is a novel hormone-like peptide that promoting health or performing the regulation of multiple metabolites. It has been found to be associated with anthropometric and biochemical parameters, other hormones and adipokines, obesity, IR, type 2 diabetes and metabolic syndrome.[29] The effect of irisin on subcutaneous adipose tissue is to increase thermogenesis and energy expenditure, thus preventing obesity and IR.[14] Irisin is an exercise-mediated actin that regulates the metabolic rate of muscle cells and adipocytes, thus acting as an exercise-induced insulin sensitizer. At present, there are few studies on the relationship between irisin and acne. Therefore, here we investigated the possible role of irisin in the development of acne patients, the severity of irisin and its correlation with IR. Many studies have focused on the relationship between irisin and metabolic diseases, and it has been found that it may serve as a potential new target for combating type 2 diabetes and IR, among others. There are currently few studies on the relationship between serum irisin and AV, and only one study has explored it. Here, we will further investigate the occurrence and severity of serum irisin in AV patients and its correlation with IR. This study found that irisin in the acne group (84.7 ± 42.2) was lower than that in the normal control group (169.3 ± 83.0), and the difference was statistically significant. The mean level of irisin in the IR group was 24.0 ± 11.3 ng/mL and in the non-IR group was 104.3 ± 27.0 ng/mL. Compared with the non-IR group, the IR group had lower irisin levels. Emiroğlu et al.[30] also reached consistent conclusions during their research. Previous studies have reported significantly lower levels of irisin in patients with new-onset, long-term, or uncertain type 2 diabetes compared with non-diabetic controls, which may be due to the diabetes itself or the metabolic conditions contributing to type 2 diabetes.[31],[32],[33]

IL-1α and IL-6 are the main inflammatory cytokines in acne and are the main participants in the inflammatory response. IL-1α is a member of the inflammatory cytokines IL-1 family and is the predominant form of IL-1 in skin. The main role of IL-1α is to cause hyperkeratosis of hair follicles and sebaceous ducts, mediating the occurrence and development of acne. Bohm et al.[34] found that IL-1α can accelerate the aggregation of various adhesion molecules in vascular endothelial cells, and its combination with leukocytes facilitates the adhesion of leukocytes to the vascular endothelium and mediates inflammatory exudation.[35] Ji et al.[36] also found that the expression levels of SRY-Box Transcription Factor 9 (SOX9), IGF-1, IL-1α and IL-6 in acne skin lesions were significantly higher than those in normal skin lesions, which may be caused by the Inflammatory response at the lesion site after the occurrence of acne, and the high expression of SOX9 and IGF-1 was closely related to the inflammatory response. As an effective upstream cytokine in the signaling pathway, IGF-1 will increase the transcriptional and translational expression levels of the transcription factor SOX9, while the highly expressed SOX9 further activates the downstream phosphatidylinositide 3-kinases (PI3K)/ pkb,also named protein kinase b (AKT), mitogen-activated protein kinase (MAPK)/ extracellular regulating kinase (ERK) and other signaling pathways, which are closely related to inflammation, leading to increased expression levels of inflammatory cytokines such as IL-1α and IL-6. It is worth noting that in the absence of other suspicious factors, the effect of IR on IL-1α was not statistically significant, and there was no significant correlation between IL-1α and acne severity, suggesting that IR and IL-1α may affect the occurrence and development of acne through different mechanisms. Furthermore, IL-1α may have no significant relationship with the severity of acne, or may be affected by the age, gender, and number of patients and other factors, so further research is needed.

Irisin and IR

Irisin is a newly discovered myosin. At present, many studies focus on the relationship between irisin and metabolic diseases, and this adipokine as a potential new target against type 2 diabetes and IR has aroused great interest of researchers. However, the current evidence for the role of irisin in IR is limited and controversial, and the pathways between them remains unclear.Many studies have reported a negative correlation between serum irisin and IR. Boström et al. reported that in animal models, proteolytic release of irisin membrane protein FNDCS from skeletal muscle into the blood stimulates the expression of uncoupling protein 1 (UCP1), increases total energy expenditure, reduces fasting insulin, and then improves glucose tolerance.[14],[37] In obese mice induced by a high-fat diet, Yang et al.[38] reported decreased secretion of irisin, leading to muscle IR. Moreno-Navarrete JM and colleagues were the first to report that serum irisin levels were inversely associated with obesity and IR in men.[33] Hu W and Huth et al. also reported an inverse correlation between circulating irisin levels and HOMA-IR.[39],[40] A cross-sectional study conducted by Shi et al.[41] on 1115 obese Chinese adults living in the community found that serum irisin levels were significantly lower than that of the control groups. After adjustment for potential confounders, increased irisin level in the circulation was significantly associated with reduced risk of IR. It also suggests that elevated circulating irisin may indirectly improve IR by reducing fasting insulin levels. In diabetic patients, circulating irisin levels were significantly lower than in non-diabetic controls and were significantly negatively correlated with IR.[31],[42],[43] Mustafa et al.[44] in their study, which included 120 subjects (60 acne patients of varying severity and 60 healthy controls) serum irisin levels were found to be significantly lower in patients with acne. Our study also reached a similar conclusion, the serum irisin (24.0 ± 11.3) in the acne group with IR was lower than that in the acne without IR group (104.3 ± 27.0), and the difference was significant. Meanwhile, IR index decreased with the increase of irisin, and the correlation coefficient r = −0.711, which is statistically significant. These findings are supported by studies showing that the insulin sensitization of irisin is mediated by increased AMPK phosphorylation and glucose/fatty acid uptake.[45],[46],[47] However, Park et al.[4] found a positive correlation between irisin and fasting glucose and HOMA-IR in 151 subjects. Other scholars have reported similar findings. Reinehr et al. found that irisin levels were highest in obese children with impaired glucose tolerance, followed by obese children with normal glucose tolerance, and lowest in children with normal weight, and concluded that serum irisin concentrations are positively correlated with IR and metabolism syndromic parameters.[48],[49],[50] These findings contradict our findings, and the reason for this discrepancy is unclear. Besides other unknown confounding factors, for these confusing found some possible explanations are that the object of study by the diseases themselves, of different metabolic states, as well as related to whether in adolescence, also may be in a state of irisin resistance participants, namely irisin compensatory increase in fat and muscle tissue, to restore the glucose metabolism to overcome or counteract increased IR. At present, the regulation of irisin in the human body and its role in different metabolic diseases remain to be further elucidated.

IR is closely related to metabolic diseases, and the current methods for assessing IR are complicated and expensive. Although HEC for hyperglycemia is recognized as the gold standard for the diagnosis of IR. But their limited application in routine clinical practice has serious limitations that make them a rather inappropriate method for screening and diagnosing IR. HOMA-IR and quantitative insulin sensitivity check index (QUICKI) are both indirect methods to evaluate IR based on fasting insulin. And they have a good correlation with the “gold standard” of IR evaluation—the euglycemic clamp. They are both effective indexes for preliminary evaluation of IR.[51] Although there are various simple alternatives, they do not detect early states of IR and are less accurate. The current understanding of the function of irisin and the mechanisms by which it functions is very limited, and the behavior and interactions of irisin in physiological or disease states are unclear. One hypothesis we observed was that irisin secretion and metabolism might be influenced by other as yet unidentified related pathways and factors following acne onset. Therefore, this association between irisin and acne that we have observed is quite promising, which may help to further support the potential diagnostic value of irisin.

Our study has certain limitations. First of all, our study subjects were from a single region and the sample size was relatively small. PCOS itself can cause IR, which is a major confounding factor in this study. However, in our research, subjects diagnosed with PCOS were excluded only by asking about their medical history, and corresponding examinations were not conducted according to strict diagnostic criteria. Second, exercise can affect irisin levels, and we did not exclude subjects who had recently participated in vigorous exercise. Third, some drugs have potential effects on serum irisin levels, but we did not collect patients' medication status. Fourth, HOMA was only used to classify IR status of subjects, and HOMA findings were not cross-validate by oral glucose tolerance (OGTT) and other testing methods such as the euglycemic clamp. Fifth, all relevant indicators were measured only once, so we cannot evaluate whether these biomarkers change over time. In addition, some biomarkers, such as leptin and adiponectin, have been confirmed to be closely related to IR. However, in this study, their levels were not tested and their possible correlations were not known.


   Conclusion Top


Important evidence is accumulating for the role of irisin in a variety of diseases, including metabolic and other chronic diseases. However, there is still a lack of knowledge about its exact function and mode of action, both in healthy and diseased states. We conducted a preliminary study on the relationship between serum irisin and acne with IR, providing new ideas for clarifying the pathogenesis of acne with IR, and also for the treatment of acne and other metabolic diseases. This study is a cross-sectional study. Although the causal relationship between serum irisin, IR, and severity of AV patients cannot be assessed, it can be inferred from the results of this study that serum irisin may be a reliable indicator of IR and related metabolic complications, which can warn us whether the disease is accompanied by the development of IR. Irisin may also play an important role in improving IR, becoming a new protein drug for improving acne with IR, glucose metabolism disorders, and other related metabolic diseases. However, since the exploration of the therapeutic effect of irisin is still in its infancy, there are few reports on the results of human studies in this area. The specific mechanism of irisin improving IR still needs more animal and clinical trials to improve.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Project of Luzhou Science and Technology Bureau(2016-S-67). Project of the Affiliated Hospital of Southwest Medical University(19029). Project of Sichuan Provincial Health Commission(16PJ555).

Conflicts of interest

There are no conflicts of interest.



 
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