Association between Psychological Stress and Insulin like Growth

Factor-1 (IGF-1) with Acne Vulgaris

Made Wardhana

, Ratih Vebryanti

, G. A. Karmila

, G. A. Praharsini

and Ratna S. Tallo

Dept of Dermatology and Venereology, Udayana, Medical Faculty/Sanglah General Hospital, Denpasar, Bali

Dept of Dermatology and Venereology, Undana Medical Faculty/Prof Dr. W.Z. Johanes, Goneral Hospital, Kupang

Keywords: Psychological Stress, IGF-1, Acne Vulgaris.

Abstract: Psychological stress could act as a precursor of acne. Insulin-like growth factor-1 (IGF-1) is a hormone that

released as a result of stress. This study aimed to determine the association between psychological stress and

IGF-1 with acne vulgaris. This study employed a case-control design, involved 56 adult subjects with acne

vulgaris aged 14-65 years old who came to the Dermato-Venereology Outpatients Units of Sanglah General

Hospital, Denpasar and had not received treatment. Blood sample was collected for IGF-1 examination The

stress index was conducted with in-depth interviews with the Holmes-Rahe stress scale test method. From a

total of 56 subjects, 31 (55.4%) subjects were included as case group (acne) and 25 (44.6%) subjects as control

group (without acne). The median IGF-1 of acne and without acne groups was 146 (90-179) ng/ml and 110

(18-165) ng/ml, respectively (p < 0.001). The stress index in patients with acne was significantly higher

compared to control group (p < 0.001). Analysis with logistic regression revealed that BMI ≥ 25 was a factor

which associated with severe acne. It can be concluded that blood levels of IGF-1 in acne patients were

significantly higher than those without acne. Patients with acne have higher stress index than the patients

without acne. Furthermore, body mass index is associated with severe acne vulgaris, but not for high IGF-1

and stress.

1 INTRODUCTION

Acne vulgaris is a chronic inflammatory disease of

pilosebaceous follicles characterized by blackheads

and/or inflammation. Acne occurs due to increased

sebum production, hypercornification of the

pilosebaceous duct, the activity of Staphylococcus

epidermidis and Propionibacterium acnes bacteria

and the inflammation of the pilosebaceous unit

(Tuchayi et al., 2015). Various factors involved in

such mechanisms, e.g., psychological stress. Stress

may respond to the hypothalamus-pituitary-adrenal

axis and lead to the release of insulin-like growth

factor-1 (IGF-1) hormone, which promotes the

activity of sebocytes and inflammation. This study

aimed to determine the association between

psychological stress and IGF-1 with acne vulgaris

(Marketon & Glaser, 2008).

2 METHODS

This study was conducted with case-control study

design. The subjects of the study were adult with acne

vulgaris aged 14-65 years old who came to the

Dermato-Venereology Outpatients Units of Sanglah

General Hospital, Denpasar and had not received

treatment. Acne vulgaris diagnosed based on typical

clinical features, diagnosis and scoring of acne were

based on a study by Adityan (2009). All subjects were

subjected to venous blood collection for IGF-1

examination. The cutoff for IGF-1 was determined

with a median. IGF-1 of > 125 ng/ml was considered

as high. The stress index was conducted with in-depth

interviews in accordance with the Holmes-Rahe

stress scale test method.

Data analysis was performed with Statistical

Package for Social Sciences version 23.0. Descriptive

analysis was performed for all variables. Numerical

data with normal distribution was presented in mean

± standard deviation (SD), while numerical data

without normal distribution was presented in median

(minimum-maximum). Independent T-test and

Wardhana, M., Vebryanti, R., Karmila, G., Praharsini, G. and Tallo, R.

Association between Psychological Stress and Insulin Like Growth Factor-1 (IGF-1) with Acne Vulgaris.

DOI: 10.5220/0008150600520055

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 52-55

ISBN: 978-989-758-494-7

Mann-Whitney test were used for bivariate analysis

of numerical data. Chi-square was used for

categorical data. A p value of less than 0.05 was

considered significant.

Multivariate analysis by logistic regression with

backward LR method was conducted to determine

factors which associated with severe acne, i.e.,

gender, family history, facial care habits, body mass

index (BMI), serum IGF-1 and stress category. Prior

to analysis with logistic regression, those variables

were analyzed with bivariate analysis. Those with a

p-value of < 0.25 were included in multivariate

analysis.

3 RESULT

The study was conducted for six months. From a total

of 56 subjects, 31 (55.4%) subjects were included as

case group (acne) and 25 (44.6%) subjects as control

group (without acne). The sociodemographic

characteristics were presented in table 1. The median

IGF-1 of acne and without acne groups was 146 (90-

179) ng/ml and 110 (18-165) ng/ml, respectively.

While the stress index for acne and without acne

groups was 118.9 ± 33.0 and 92.8 ± 23.5,

respectively. Serum IGF-1 and stress index in patients

with acne significantly higher compared to control

group.

Variables of gender, family history, facial care

habits, body mass index (BMI), serum IGF-1 and

stress category were included for multivariate

analysis with logistic regression to determine factors

which associated with severe acne. After bivariate

analysis, BMI and serum IGF-1 was included in the

multivariate analysis (p = 0.036 and p = 0.128,

respectively). Variables of gender, family history,

facial care habits and stress were not included (p =

0.524, p = 0.701, p = 0.449, p = 1.0, respectively).

After analysis with logistic regression, BMI ≥ 25 was

a factor which associated with severe acne (table 2).

Table 1: Sociodemographic characteristics of study subjects.

Characteristics

Case

n= 31

Control

n= 25

p-value/

Odds ratio

(OR)

Gender, n (%)

p < 0.05

OR =

0.304 (95% CI

0.09-1.02)

Female

17 (30.4)

20 (35.7)

Male

14 (25.0)

5 (8.9)

Age (years), n (%)

12-20

19 (33.9)

7 (12.5)

>20-35

11 (19.6)

15 (26.8)

> 35

1 (1.8)

3 (5.4)

Family History, n (%)

p > 0.05

Yes

10 (17.9)

5 (8.9)

21 (37.5)

20 (35.7)

Duration of Acne, n (%)

< 1 month

9 (16.0)

1-3 month

12 (21.4)

> 3 month

10 (17.8)

Clinical type, n (%)

Comedonal

18 (32.1)

Papulo-pustuller

9 (16.0)

Nodulocystic

4(7.1)

Severity of acne, n (%)

Not Severe

13 (23.2)

Severe

18 (32.1)

Facial Care habits, n (%)

p < 0.05

OR =

7.273 (95% CI

2.136-24.768)

Never/rarely

20 (35.7)

5 (8.9)

Frequently

11 (19.6)

20 (35.7)

Body Mass Index (Kg/m

), n (%)

p > 0.05

< 25

14 (25.0)

> 25

17 (30.4)

11 (19.6)

Dietary Habit, n (%)

p > 0.05

Low GI < 55

15 (26.8)

13 (23.2)

Association between Psychological Stress and Insulin Like Growth Factor-1 (IGF-1) with Acne Vulgaris

High GI ≥ 55

16 (28.6)

12 (21.4)

Serum IGF-1 (ng/ml), mean ± SD

146 (90-179)

110 (18-

165)

p < 0.001

Serum IGF-1 Category, n (%)

p < 0.05

OR =

5.758 (95% CI

1.776-18.668)

High

20 (35.7)

6 (10.7)

Not High

11 (19.6)

19( 33.9)

Stress Level, mean ± SD

118.9 ± 33.0

92.8 ± 23.5

p < 0.05

Stress Category, n (%)

p < 0.001

OR =

9.778 (95% CI

2.802-34.118)

Stress

22 (39.3)

5 (8.9)

No Stress

9 (16.1)

20 (35.7)

Table 2: Logistic regression analysis of factors which associated with severe acne.

Variables

Coefficient

OR (95% CI)

BMI ≥ 25

-1.948

0.036

0.143

(0.023-0.883)

High IGF-1

(> 125 ng/ml)

1.740

0.062

5.697

(0.919-35.309)

BMI, body mass index; IGF-1, insulin-like growth factor-1.

4 DISCUSSION

Lots of studies have reported stress as a precursor to

acne. The result of this study obtained that stress was

associated with acne vulgaris. People with

psychological stress tend to have acne 9.778 times

higher compared to people without stress. Substance

P, which can be elicited by stress, may stimulate the

proliferation of sebaceous precursor cells and

increase sebaceous cell size (Tuchayi et al., 2015).

According to Konduru IGF-1 could be used as a

biomarker of stress (Konduru, 2011). Another study

by Isard et al. reported an excessive expression of

IGF-1 in acne lesions compared to healthy skin

lesions (Isard et al., 2011). In this study, IGF-1 levels

in acne patients were higher when compared to

patients without acne (p < 0.001). Furthermore, high

IGF-1 increase the risk of acne by 5.758 times when

compared to people with IGF-1 of less than 125

ng/ml.

P. acnes may also stimulate the expression of IGF-

1 and IGF-1 receptors on keratinocytes and increase

the secretion of IGF-1. These indicate that IGF-1 is

the target for P. acnes in the formation of acne lesions,

in which P. acnes plays a role in the formation of

blackhead lesions through activation of IGF-1

(Melnik & Schmitz, 2009). Insulin-like growth

factor-1 is a potent mitogen for tissues.

Increased concentrations of IGF-1 stimulate

growth primarily in bone, muscle, liver, kidneys,

nerves, hematopoietic cells, lung, skin, and sebaceous

follicles. IGF-1 is produced throughout life; the

highest production of IGF-1 occurs during puberty

and the lowest rate occurs in infants and old age. IGF-

1 levels vary by age and sex. IGF-1 levels peaked at

puberty and then decrease with age in both men and

women (Saleh, 2012). Study indicated that IGF-1

induced sebaceous lipogenesis in sebaceous gland

organ cultures (Downie et al., 2002). IGF-1 also

increased lipogenesis by the induction of sterol

response element-binding protein-1 (SREBP-1

(Smith et al., 2006).

Studies indicate that higher BMI associated with

acne development. A study by Tsai et al. in

schoolchildren found that BMI-for-age > or = 95%

had a significantly higher rate of acne development

(Tsai et al., 2010). In terms of severity of acne, one

study found that moderate to severe acne was

positively associated with overweight and obesity in

people aged 18-25 years, particularly in women (Lu

et al., 2017). In contrast to that, Lajevardi et al. found

a different result. They found no significant

correlation between acne severity and BMI (p=0.806)

(Lajevardi et al., 2014). The current study found that

BMI associated with severe acne in patients with

acne.

5 CONCLUSIONS

Blood levels of IGF-1 in acne patients were

significantly higher than those without acne. Patients

with acne have higher stress index than the control

group (patients without acne). Body mass index more

than or equal to 25 was a factor which associated with

severe acne in patients with acne.

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

ACKNOWLEDGEMENTS

The authors would like to express their sincere thanks

to the Dermatology Outpatient´s Clinic of the Sanglah

General Hospital and families of patients who

participated in this study.

REFERENCES

Adityan, B., Kumari, R. and Thappa, D.M., 2009. Scoring

systems in acne vulgaris. Indian Journal of

Dermatology, Venereology, and Leprology, 75(3),

p.323.

Downie, M.M.T., Sanders, D.A. and Kealey, T., 2002.

Modelling the remission of individual acne lesions in

vitro. British journal of Dermatology, 147(5), pp.869-

878.

Isard, O., Knol, A.C., Ariès, M.F., Nguyen, J.M.,

Khammari, A., Castex-Rizzi, N. and Dréno, B., 2011.

Propionibacterium acnes activates the IGF-1/IGF-1R

system in the epidermis and induces keratinocyte

proliferation. Journal of Investigative

Dermatology, 131(1), pp.59-66.

Konduru, L., 2011. Biomarker of Chronic Stress

[dissertation on the internet]. Pittsburgh: University of

Pittsburgh [cited 2017 Oct 07]. Available from:

http://d-

scholarship.pitt.edu/10858/1/Laalithya_Thesis_Revise

d_%282%29.pdf

Lajevardi, V., Ghodsi, SZ., Daneshpazhooh, M., Kazemi,

H., Aryanian, Z., Goodarzi, A., 2014. The relationship

between body mass index and the severity of acne.

Iranian Journal Dermatology, 17, pp. 13-7.

Lu, L.Y., Lai, H.Y., Pan, Z.Y., Wu, Z.X., Chen, W.C. and

Ju, Q., 2017. Obese/overweight and the risk of acne

vulgaris in Chinese adolescents and young adults. Hong

Kong J Dermatol Venereol, 25, pp.5-12..

Marketon, J.I.W. and Glaser, R., 2008. Stress hormones and

immune function. Cellular immunology, 252(1-2),

pp.16-26.

Melnik, B.C. and Schmitz, G., 2009. Role of insulin,

insulin‐ like growth factor‐ 1, hyperglycaemic food

and milk consumption in the pathogenesis of acne

vulgaris. Experimental dermatology, 18(10), pp.833-

841.

Saleh, B.O., 2012. Role of growth hormone and insulin-like

growth factor-I in hyperandrogenism and the severity

of acne vulgaris in young males. Saudi medical

journal, 33(11), pp.1196-1200.

Smith, T.M., Cong, Z., Gilliland, K.L., Clawson, G.A. and

Thiboutot, D.M., 2006. Insulin-like growth factor-1

induces lipid production in human SEB-1 sebocytes via

sterol response element-binding protein-1. Journal of

investigative dermatology, 126(6), pp.1226-1232.

Tsai, M.C., Chen, W., Cheng, Y.W., Wang, C.Y., Chen,

G.Y. and Hsu, T.J., 2006. Higher body mass index is a

significant risk factor for acne formation in

schoolchildren. European Journal of

Dermatology, 16(3), pp.251-253.

Tuchayi, S.M., Makrantonaki, E., Ganceviciene, R.,

Dessinioti, C., Feldman, S.R. and Zouboulis, C.C.,

2015. Acne vulgaris. Nature Reviews Disease

Primers, 1, p.15029.

Association between Psychological Stress and Insulin Like Growth Factor-1 (IGF-1) with Acne Vulgaris