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Abstract

Background:

The research evaluating adipokines are very few in patients with acne vulgaris. The hypothesis that hyperinsulinemic and high glycemic index diet plays a role in the pathogenesis of acne is still controversial. In this study, we aimed to evaluate adipokines such as leptin (L), adiponectin (A), ghrelin and A levels, and A/L rates that indicate insulin resistance in nonobese patients with severe acne vulgaris.

Material and Method:

Thirty patients who are nonobese with moderate acne vulgaris, aged 18 to 25 years, and 15 age–sex compatible controls were included in our study. The acne lesions were assessed using the Global Acne Grading Scale (GAGS). All participants were evaluated for the parameters that may affect the metabolism of serum L, A, and ghrelin levels in blood, and their body mass index were calculated. The significance level was determined as p ≤ 0.05.

Results:

Of the 30 patients, 17 were women and 13 were men. The mean age was 20.60 years and the mean duration of the disease were 2.8 years. All of patients had moderate acne vulgaris (GAGS 19–30). Of the 15 controls, 11 were women and 4 were men. The mean age was 21.20 years. There were not a statistically significant difference in L, ghrelin, A levels, and A/L ratio between the two groups.

Conclusions:

Adipokines may have a role in the pathogenesis of acne vulgaris. L, A, ghrelin, and insulin resistance may not participate in the responsible mechanisms in nonobese patients with moderate acne vulgaris.

Keywords

Acne vulgaris leptin adiponectin ghrelin insulin resistance

Introduction

Acne vulgaris is a multifactorial disease that affects mostly adolescent population. Acne appears very early in puberty during the preteen years, often before menarche in girls. Because many adolescents have acne, it is difficult to predict which individuals are prone to severe cases. The pathogenesis of acne is complex, with strong evidence supporting the involvement of follicular hyperkeratinization, hyperactivity of the sebaceous glands, colonization of Propionibacterium acnes and yeast, and inflammation.^1
–3 Although the importance of androgens in the pathophysiology of acne has been supported by both clinical studies and experimental data, the research evaluating adipokines are very few in patients with acne vulgaris.^4,5 Some experiments have demonstrated that leptin (L) directly controls the secretory activity of human ovarian cells, with an interrelationship between L and insulin-like growth factor (IGF).^6

–9 Serum L levels in human beings depend on sex, age, and body fat mass. Oral food intake and diet composition such as carbohydrate-rich food influence L concentrations.^10,11 An association between diet and acne has long been put forward, but studies that have examined the impact of diet on acne have produced controversial results. Some have indicated that diets rich in carbohydrates and fat worsen acne, while others did not detect such a relationship.^12,13 The hypothesis regarding hyperinsulinemic and high glycemic index diets plays a role in the pathogenesis of acne is still controversial. In this study, we aimed to evaluate adipokines such as L, adiponectin (A), ghrelin, and A levels and A/L rates that indicate insulin resistance in nonobese patients with severe acne vulgaris.

Material and method

The study was performed by the dermatology unit of Afyon Kocatepe University, after obtaining the approval of the local ethical committee. Thirty patients who are nonobese with moderate–severe acne vulgaris, aged 18 to 25 years, and 15 age–sex compatible controls were included in our study. The control group was selected from people without any systemic disease, acne lesions, or medication. We assessed acne lesions using the Global Acne Grading Scale (GAGS). The body mass index of patients with acne vulgaris and control groups was calculated. We also asked for the parameters that may affect the metabolism of serum L, A, and ghrelin levels in blood. Body mass index was calculated by weight (in kilograms) divided by square of height (in meters) as a measure of total adiposity.

The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 18.0 software (SPSS Inc., Chicago, Illinois, USA). The distribution of the group was analyzed with the Kolmogorov–Smirnov test. Differences between the groups were determined with either a Student’s t-test or the Mann–Whitney U-test. The correlations between the parameters were analyzed with Pearson and Kendall’s tau correlation tests. All parametric results were expressed as mean ± standard deviation for each group. The significance level was determined as p ≤ 0.05.

The venous blood samples were taken from patient and control groups after fasting for 10–12 h and centrifuged at 3000 rpm for 10 min. The serum samples were divided into two tubes and kept at −80°C till the end of the study. Before studying each test parameter, one sample was resolved at +4°C. Serum L and ghrelin levels were measured using Leptin Human enzyme-linked immunosorbent assay (ELISA) kit (Abcam, Cambridge, Massachusetts, USA) and DRG Human Ghrelin (total) ELISA kit (DRG Int. Inc., Springfield Township, New Jersey, USA) with double antibody sandwich ELISA technique. Both tests were studied according to the manufacturers’ directions. The test results were spectrophotometrically read under 450 nm and results were evaluated by standard curve. Serum L levels are expressed in ng/mL and plasma ghrelin levels are expressed by pg/mL.

Result

Of the 30 patients, 17 were women and 13 were men. The mean age was 20.60 years and the mean duration of the disease was 2.8 years. All of the patients had moderate acne vulgaris (GAGS 19–30). Of the 15 controls, 11 were women and 4 were men. The mean age was 21.20 years. Patient and control groups were matched according to their age and sex. Table 1 shows the sociodemographic characteristics and body mass index of the participants. There was no difference between patients and control groups with respect to age, sex, occupation, socioeconomic status, place of residence, weight, height, waist-to-hip ratio, and body mass index (p > 0.05; Table 1).

Table 1.

Characteristics of patients with acne vulgaris.

	Patients (n = 30)	Controls (n = 15)	p value
Sex (female/male)	17/13	11/4	> 0.05
Age (year)	20.60 ± 3.6	21.20 ± 3.7
BMI (kg/m²)	24.5 ± 5.7	23.9 ± 6.5	> 0.05
GAGS score	19–30	–	–
Total body fat (kg)	20.9 ± 8.3	21.5 ± 5.3	> 0.05
Body fat (%)	30.4 ± 9.1	29.5 ± 4.1	> 0.05
Lean body mass (kg)	46.1 ± 9.8	45.2 ± 10.1	> 0.05
Total body water (kg)	33.2 ± 6.4	29.5 ± 5.4	> 0.05
Body water (%)	49.2 ± 7.2	45.0 ± 6.7	> 0.05
Waist–hip ratio	0.79 ± 0.2	0.80 ± 0.1	> 0.05
Abdominal circumference (cm)	89.7 ± 11.8	88.4 ± 12.0	> 0.05

BMI: body mass index; GAGS: Global Acne Grading Scale.

There was not a statistically significant difference in L, ghrelin, A levels, and A/L ratio between two groups (respectively p = 0.10, p = 0.93, p = 0.84, and p = 0.06). We reported results of laboratory parameters and demographic data of patients and controls in Table 2.

Table 2.

FBG, lipid profile, and hormone levels of patients.

	Patients (n = 30)	Controls (n = 15)	p values
FBG (mg/dL)	86.3 ± 5.6	86.0 ± 7.5	>0.05
TG (mg/dL)	92.1 ± 46.5	116.9 ± 79.8	>0.05
LDL-C (mg/dL)	88.7 ± 17.3	109.8 ± 20.8	>0.05
TC (mg/dL)	148.5 ± 24.2	164.8 ± 29.3	>0.05
L	8.3 ± 13.6	7.5 ± 14.2	0.10
Ghrelin	13.2 ± 3.1	12.9 ± 3.4	0.93
A	81.7 ± 53.8	86.5 ± 49.3	0.84
A/L ratio	29.12 ± 28.19	15.11 ± 19.7	0.06

FBG: fasting blood glucose; TG: triglyceride; LDL-C: low-density lipoprotein cholesterol; TC: total cholesterol; L: leptin; A: adiponectin.

Discussion

Four factors are believed to play a key role in the development of acne vulgaris: excess sebum production, disturbed keratinization within the follicle, colonization of the pilosebaceous duct by Propionibacterium acnes and yeast, and the release of inflammatory mediators into the skin. Additionally, the experimental evidence confirms the importance of androgens in the pathophysiology of acne.^1,14 An association between diet and acne has long been postulated, but studies that have examined the impact of diet on acne have controversial results. Some have indicated that diets high in carbohydrates and fat worsen acne, while others did not detect such a relationship.^12,13 In addition, our study suggests that insulin resistance may not play a major role in the pathogenesis of postadolescent acne.¹⁵ Hyperinsulinemic diets were also thought to be an environmental factor in the development of acne since they influence follicular epithelial growth, keratinization, and androgen-mediated sebum secretion.⁷ In order to effectively and rapidly reduce acne lesions, treatments need to address as many of these underlying factors as possible.

Adipose tissue consists of adipocytes, that is, cells filled with lipid, and is an active endocrine organ which has systemic effects. Various protein molecules, including adipokines are being released into the circulation from adipose tissue. L is one of the most abundant and important adipokines. The most well-known effect of L is to regulate body weight and energy balance, but it also has fundamental roles in glucose and lipid homeostasis, reproduction, immunity, inflammation, bone physiology, and tissue remodeling.¹⁰ Serum L concentrations are significantly elevated proportionally to the degree of adiposity, whereas A levels are paradoxically reduced in individuals with obesity and insulin resistance.^16,17 However, the effects of L on skin physiology and disease are not well known. Several studies have investigated on the effects of L on the physiology of normal skin. At the same time, there have been studies related with wound healing, the pathogenesis of cellulitis, scleroderma, acne vulgaris, soft fibromas, malignant melanoma, and the pathogenesis of cardiovascular mortality of psoriasis and Behcet’s disease.¹⁸ A is also thought to be involved in the regulation of metabolic homeostasis.¹¹ There are both complementary and countereffects of L and A at different stages of metabolic homeostasis. In addition, L appears to have proinflammatory properties, whereas A is considered an anti-inflammatory cytokine.¹⁹ Hence, the A/L ratio has been evaluated and proposed as a potential index linking central obesity. This ratio has been considered as a marker for insulin resistance and atherosclerosis in obese type 2 diabetic patients as well as in subjects without hyperglycemia.^20

–23

Ghrelin, another adipokine, is also a gastric peptide with potent orexigenic effects. Circulating ghrelin concentrations are increased in obese subjects, but increase after weight loss. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has thus attracted attention for its putative involvement in the complex enterohypothalamic regulation of food intake.^24,25 In our study, we evaluated the parameters that may affect the metabolism of these three adipokines levels in blood in the patients with acne vulgaris. There were not a statistically significant difference in L, ghrelin, A levels, and A/L ratio between the nonobese patients and controls groups. Comprehensive studies that investigate the numerous adipokines in nonobese and obese acne patients with their age and sex-matched control groups may reduce uncertainty on this issue.

In contrast to our findings, Karadag et al. reported that basal L levels in the acne group were significantly lower and basal A levels significantly higher compared with the control group. After isotretinoin (ISO) treatment, L levels decreased and A levels increased significantly. They suggested that ISO may affect L and A levels. It does not, however, affect insulin resistance and retinol-binding protein 4 (RBP4) levels.²⁶

Kaymak et al. also reported that dietary glycemic index, glycemic load, and insulin levels in patients with acne were not higher than in control subjects, in contrast to the hypothesis regarding hyperinsulinemic and high glycemic index diets play a role in the pathogenesis of acne. In addition, there had been no significant difference between acne and control groups regarding the serum glucose, IGF-I, and L levels.⁶

In a study by Soğuktaş et al., another adipokine, the omentum levels, were not found to be different in patients with acne vulgaris.²⁷

In limiting aspect of our study, the obese patient with acne vulgaris were not evaluated and only three adipokines were investigated.

Conclusion

Adipokines may have a role in the etiology of acne vulgaris, unlike that known pathogenetic aspects of this disease. L, A, ghrelin, and insulin resistance may not be among the responsible mechanisms in patients with nonobese moderate acne vulgaris. Further studies are necessary to make a comprehensive study including large series of patients on the relationship between acne and adipokines.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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Evaluation of leptin,adiponectin,and ghrelin levels in patients with acne vulgaris

Abstract

Background:

Material and Method:

Results:

Conclusions:

Keywords

Introduction

Material and method

Result

Discussion

Conclusion

Footnotes

Declaration of Conflicting Interests

Funding

References