Report

Insulin resistance in patients with post-adolescent acne

Ilknur Balta1, MD, Ozlem Ekiz2, MD, Pınar Ozuguz3, MD, Ihsan Ustun4, MD,Semsettin Karaca3, MD, Seval Dogruk Kacar3, MD, and Meral Eksioglu5, MD

1Department of Dermatology, Kecioren

Training and Research Hospital, Ministry of

Health, Ankara, 2Department of

Dermatology, Tayfur Ata Sokmen School of

Medicine, Mustafa Kemal University, Hatay,3Department of Dermatology, School of

Medicine, Afyon Kocatepe University,

Afyon,Turkey, 4Department of

Endocrinology, Tayfur Ata Sokmen School

of Medicine, Mustafa Kemal University,

Hatay, and 5Ankara Training and Research

Hospital, Ministry of Health, Department of

Dermatology, Ankara, Turkey

Correspondence

Ilknur Balta, MD

Department of Dermatology

Kecioren Training and Research Hospital

Ministry of Health,

Ankara 06290

Turkey

E-mail: drilknurderm@yahoo.com

Funding: None.

Conflicts of interest: None.

doi: 10.1111/ijd.12426

Abstract

Background Post-adolescent acne has been defined as acne in a patient aged >25 years.

Acne vulgaris first develops at the onset of puberty as a result of hormonal changes.

During puberty, there is a transient decline in insulin sensitivity. We hypothesized that

insulin resistance might persist after puberty in patients with post-adolescent acne.

Objectives This study was conducted in order to investigate the relationship between

post-adolescent acne and insulin resistance.

Methods The study population comprised 35 patients with post-adolescent acne and 35

healthy control subjects. The parameters measured were fasting blood glucose, insulin,

aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total cholesterol

(TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein

cholesterol (LDL-C). The homeostasis model assessment of insulin resistance (HOMA-IR)

index was calculated for each individual.

Results No significant differences were observed between patients with post-adolescent

acne and control subjects in fasting blood glucose, fasting insulin, AST, ALT, triglyceride

and HDL-C levels, and HOMA-IR index. There were also no correlations between these

parameters and the severity of acne.

Conclusions This study suggests that insulin resistance may not play a major role in the

pathogenesis of post-adolescent acne. Hormonal changes, genetic susceptibility, stress,

the use of cosmetics, drugs, and environmental factors should be considered in the

development of post-adolescent acne.

Introduction

Acne is usually recognized as a disorder of adolescence.However, the prevalence of adult patients with acne isincreasing. Traditionally, post-adolescent acne has beendefined as acne in an individual beyond the age of25 years.1–5 Post-adolescent acne is more common inwomen.6 It affects approximately 14% of women betweenthe ages of 25 and 50 years. It is described as a predomi-nantly inflammatory, mild-to-moderate form, character-ized by papules and pustules, mainly located on the lowerthird of the face, jaw line, and neck, with rare andnon-prominent comedonal lesions.6,7 The pathogenesis ofpost-adolescent acne is still not exactly understood. Therole of circulating hormones remains controversial. Sev-eral hormones implicated in the regulation of sebaceousgland activity have been related to acne. These includeandrogens, estrogens, progesterone, growth hormone,insulin, insulin-like growth factor-1 (IGF-1), corticotro-

pin-releasing hormone, adrenocorticotropic hormone,melanocortins, and glucocorticoids.7–9

The role of insulin in the development of acne is alsosupported by the high prevalence of acne in women withpolycystic ovary syndrome (PCOS), a condition associatedwith insulin resistance, hyperinsulinemia, and hyperan-drogenism. Clinical and experimental evidence suggeststhat insulin resistance and compensatory hyperinsulinemiarepresent the underlying disturbance in PCOS becauseinsulin resistance generally precedes and gives rise tohyperandrogenism. Insulin and IGF-1 have been shown tostimulate adrenal androgen synthesis and inhibit thehepatic production of sex hormone-binding globulin,allowing for an increase in androgen bioavailability.Treatments aimed at reducing insulin secretion and/orincreasing insulin sensitivity, such as with metformin oracarbose, have been demonstrated to reduce serum andro-gen levels and gonadotrophins, and to improve acne andhirsutism, the menstrual cycle, ovulation, and fertility.8,9

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1

Even without overt PCOS, women with post-adolescentacne maintain elevated serum concentrations of IGF-1and are mildly insulin-resistant.10 Clinically, IGF-1 hasalso been shown to correlate with acne lesion counts inadult women, and significantly higher IGF-1 levels havebeen described in women with acne compared with con-trol subjects.11

The link between sebaceous gland activity and pubertyhas been recognized for many years. Sebum productionbegins during puberty and corresponds to peaks in thelevels of growth hormone and IGF-1 that occur in mid-puberty.9 During puberty, there is also a transient declinein insulin sensitivity. Acne begins about the same time asthe gradual increase in plasma insulin, the pre-adolescentincrease in body mass index (BMI) and the increase inIGF-1 concentrations. Acne incidence corresponds moreclosely to the changing course of insulin and IGF-1 levelsthan it does to changes in plasma androgens. This isbecause insulin and IGF-1 levels peak during late pubertyand gradually decline until the third decade. Acne gener-ally resolves by this time, although circulating androgensremain unchanged.9,12,13 We hypothesized that insulinresistance might also persist after puberty in patients withpost-adolescent acne. Thus, insulin resistance might con-tribute to the development of post-adolescent acne. There-fore, we aimed to investigate the relationship betweenpost-adolescent acne and insulin resistance in this study.

Materials and methods

The study population comprised 35 patients with post-

adolescent acne and 35 healthy control subjects. Both the acne

and control groups were started on an optimal diet (low

glycemic index) at least two weeks prior to the HOMA-IR test.

Potential study participants were excluded if they reported

previous treatment with oral retinoids, medications known to

affect insulin metabolism, hormone treatment for any reason in

the previous three months, cigarette smoking, thyroid

dysfunction, or a history of diabetes mellitus, hypertension,

atherosclerotic vascular disease, malignancy, amyloidosis, or

any other systemic inflammatory diseases.

Acne was graded using the International Consensus

Conference on Acne Classification System in the following

categories: mild (few to several comedones, papules, and

pustules, and no nodules); moderate (several comedones,

papules, and pustules, and few nodules), and severe

(numerous comedones, papules, and pustules, and many

nodules).14 The examination included an acne assessment of

the face, chest, neck, and back in all patients.

There are two types of post-adolescent acne: persistent

acne and late-onset acne. Adolescent acne that persists in

patients beyond the age of 25 years is called “persistent post-

adolescent acne,” whereas acne that develops for the first

time after the age of 25 years is called “late-onset post-

adolescent acne.”6,7

The BMI was calculated by dividing the subject’s body weight

(kg) by the square of his or her height (m2). Venous blood was

collected in EDTA tubes after a 12-hour fast. The parameters

measured were fasting blood glucose, fasting insulin, aspartate

aminotransferase (AST), alanine aminotransferase (ALT), total

cholesterol (TC), triglycerides, high-density lipoprotein

cholesterol (HDL-C), and low-density lipoprotein cholesterol

(LDL-C). Normal ranges for these parameters were accepted as

follows: fasting blood glucose: 74–106 mg/dl; fasting insulin:

6–27 lIU/ml; AST: 0–35 IU/l; ALT: 0–35 IU/l; TC: 0–200 mg/dl;

triglycerides: 0–150 mg/dl; HDL-C: 40–60 mg/dl; and LDL-C:

0–130 mg/dl. The criteria used to define insulin resistance

according to the published guidelines proposed by the

European Group for the Study of Insulin Resistance. The

homeostasis model assessment of insulin resistance

(HOMA-IR) index (fasting insulin 9 fasting blood glucose/405)

was calculated for each individual.15

Statistical analysis

Statistical analyses were performed using SPSS Version 17.0

(SPSS, Inc., Chicago, IL, USA). All numeric variables are

expressed as the mean � standard deviation (SD). The

statistical significance of differences between groups was

determined using an independent-samples t-test. The chi-

squared test was used for proportional correlations. Correlation

analysis between serum fasting glucose, fasting insulin, HOMA-

IR index, and acne severity was performed using one-way

analysis of variance (ANOVA). A P-value of <0.05 was

accepted as indicating statistical significance.

Results

Of the 35 patients with post-adolescent acne, nine(25.7%) were male and 26 (74.3%) were female. Theirmean � SD age was 30.82 � 5.39 years (range: 25–46 years). The control group constituted 35 people, ofwhom 10 (28.6%) were male and 25 (71.4%) female,with a mean � SD age of 30.8 � 5.7 years (range:25–51 years). The patient and control groups werematched according to age and sex. Table 1 shows thesociodemographic and BMI characteristics of the sample.There was no significant difference between the twogroups with respect to BMI (P > 0.05).The mean duration of acne was 8.5 years (range: 1–

25 years). Eighteen (51.4%) patients had mild, 14(40.0%) had moderate, and three (8.6%) had severe acne.In 48.6% of patients, only the face was involved; in22.9% the face and neck were involved; and in 28.6%the face and back were involved. A total of 22 (62.9%)patients had late-onset acne, and 13 (37.1%) had persis-tent acne. Laboratory findings in the study groups are

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Report Insulin resistance in post-adolescent acne Balta et al.2

summarized in Table 2. No significant differences wereobserved between patients with post-adolescent acne andcontrol subjects in fasting blood glucose, fasting insulin,AST, ALT, triglyceride and HDL-C levels, and theHOMA-IR index. Serum TC and LDL-C levels weresignificantly increased in patients with post-adolescentacne (P = 0.04 and P = 0.01, respectively). There wereno significant correlations between acne severity and anyof fasting blood glucose (P = 0.39), fasting insulin(P = 0.07), TC (P = 0.18), triglyceride (P = 0.18), HDL-C (P = 0.49) and LDL-C (P = 0.15) values, or theHOMA-IR index (P = 0.07).

Discussion

Acne vulgaris has been proposed to be a disease mediatedby IGF-1. IGF-1 rises during puberty through the actionof increased growth hormone secretion and correlateswell with the clinical course of acne. Insulin/IGF-1 recep-tors are expressed in epidermal keratinocytes. Therefore,hyperinsulinemia may lead to an increased proliferationof basal keratinocytes within the pilosebaceous duct andabnormal desquamation of follicular corneocytes. IGF-1stimulates 5a-reductase, adrenal and gonadal androgensynthesis, androgen receptor signal transduction, sebocyteproliferation, and lipogenesis.9

Blood glucose levels have been reported to be elevatedin patients with acne vulgaris in comparison with healthycontrols. This occurs primarily because an increase inblood glucose levels stimulates the secretion of insulin,which decreases the binding protein for IGF-1, facilitatingthe effects of IGF-1 on cell proliferation. High insulinconcentrations in the fasting and/or post-prandial statesmay exacerbate acne by increasing the proliferation ofbasal keratinocytes. Insulin also stimulates the synthesisof androgens, leading to high sebum production, a recog-nized correlate of acne severity.16,17

Although dietary factors have long been consideredunimportant, insulin resistance and dietary carbohydrateshave recently been implicated in the etiology of acne. Theglycemic index (GI) of meals has been directly correlatedto insulin response, and low GI diets have been shown todecrease insulin resistance.18 Smith et al.12 showed that alow GI diet induced an improvement in acne severity anda parallel improvement in insulin sensitivity in youngmales with acne vulgaris. By contrast, a study by Reynoldset al.18 suggested that a low GI diet does not significantlyimprove facial acne any more than a macronutrient-matched high GI diet, although there was a trend for thelow GI diet to improve acne to a greater extent than thehigh GI diet. Reynolds et al.18 also showed that a low GIdiet did not induce an improvement in insulin sensitivityin young males with acne vulgaris. Low GI carbohydrateswere not responsible for the improvements in facial acnereported by Smith et al.12 Increased weight loss, andhigher protein and fiber intake may explain the declines infasting insulin and HOMA-IR indices.Insulin resistance is known to represent an impaired

biological response to either exogenous or endogenousinsulin. Although the glucose–insulin relationship is clini-cally pertinent, it is also important to recognize that, con-ceptually, insulin resistance does not have to be confinedto the parameters of the glucose metabolism. The conceptof insulin resistance should apply to any of the biologicalactions of insulin and might include its effects on lipidand protein metabolism, vascular endothelial function

Table 1 Sociodemographic characteristics of patients withpost-adolescent acne and healthy control subjects

Characteristic

Patient group

(n = 35)

Control group

(n = 35)

P-value

(chi-squared

test)

Gender, n (%)

Female 26 (74.3%) 25 (71.4%) 0.78

Male 9 (25.7%) 10 (28.6%)

Age, years, mean � SD

Female subjects 31.38 � 5.65 32.08 � 6.27 0.67

Male subjects 29.22 � 4.46 27.60 � 2.27 0.34

All subjects 30.82 � 5.39 30.80 � 5.77 0.98

Body mass index, mean � SD

Female subjects 24.16 � 4.28 24.96 � 4.56 0.51

Male subjects 25.92 � 2.62 25.10 � 2.64 0.50

All subjects 24.61 � 3.96 25.01 � 4.07 0.68

SD, standard deviation.

Table 2 Comparison of laboratory findings in patients withpost-adolescent acne and healthy control subjects

Parameter

Patient group

(n = 35)

Mean ± SD

Control group

(n = 35)

Mean ± SD P-value

Body mass index, kg/m2 24.6 � 3.9 25.0 � 4.0 0.68

Fasting blood glucose,

mg/dl

89.7 � 7.4 90.0 � 12.6 0.90

Insulin, lIU/ml 9.0 � 4.9 9.8 � 3.5 0.41

HOMA-IR 2.0 � 1.2 2.1 � 0.8 0.51

AST, IU/l 21.0 � 6.4 21.5 � 8.5 0.77

ALT, IU/l 18.9 � 13.4 22.3 � 17.9 0.37

Total cholesterol, mg/dl 189.4 � 38.8 169.8 � 42.1 0.04a

LDL-C, mg/dl 118.0 � 32.8 96.6 � 38.6 0.01a

HDL-C, mg/dl 53.4 � 19.6 53.0 � 12.2 0.91

Triglycerides, mg/dl 123.7 � 94.6 94.0 � 59.5 0.12

SD, standard deviation; HOMA-IR, homeostasis modelassessment of insulin resistance; AST, aspartate aminotrans-ferase; ALT, alanine aminotransferase; HDL-C, high-densitylipoprotein; LDL-C, low-density lipoprotein.aP < 0.05.

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Balta et al. Insulin resistance in post-adolescent acne Report 3

and gene expression.19–21 The reference standard for theevaluation of insulin sensitivity is the glucose clamp test.However, this test is limited to research use and is diffi-cult to perform at all medical institutions.15 Homeostasismodel assessment, first described by Matthews et al.,15 isa method for estimating insulin sensitivity. In this study,insulin resistance was evaluated using the HOMA-IRindex in patients with post-adolescent acne.We showed that post-adolescent acne is not associated

with insulin resistance. In addition, there were no signifi-cant differences between fasting blood glucose or fastinginsulin levels, or HOMA-IR indices, and acne severity.Kaymak et al.22 reported that serum glucose, insulin lev-els, and HOMA-IR indices in younger patients with acnevulgaris and control subjects did not differ significantly,which represents a set of findings similar to those in thepresent study. In addition, Kaymak et al.22 did not findany statistically significant association between acneseverity and insulin resistance. Cetin€ozman et al.23 evalu-ated androgens and insulin sensitivity markers before andafter treatment with isotretinoin in women with severepost-adolescent acne. They reported that all parameterswere similar in patients and controls at baseline.23 Isotre-tinoin therapy increased BMI and triglyceride levels with-out any effect on androgens or insulin sensitivity. As aresult, these authors reported that severe acne itself is notassociated with hyperandrogenemia or insulin resis-tance.23 Ertugrul et al.24 also reported that three monthsof isotretinoin treatment did not change insulin sensitivityin patients with acne vulgaris. By contrast with thesestudies, Del Prete et al.13 reported fasting blood glucose,insulin levels, and HOMA-IR indices to be elevated in youngmales with acne vulgaris compared with healthy controls.The relationships between blood lipids such as TC and

triglycerides, and acne are not clear. Akawi et al.25 foundthat TC levels were not significantly increased but thatLDL-C levels were significantly increased in patients withsevere acne vulgaris in comparison with controls. How-ever, Arora et al.26 found that TC and LDL-C levels weresignificantly increased in patients with severe acne. Simi-larly, we found that serum TC and LDL-C levels weresignificantly increased in post-adolescent acne patients.Previous studies found that serum HDL-C levels weresignificantly decreased in acne patients.25–27 By contrastwith the findings reported in the literature, we did notfind any statistically significant difference in serum HDL-C levels between subjects with and without post-adoles-cent acne. In accordance with other studies,25–27 wefound no statistically significant difference in serumtriglyceride levels between acne patients and control sub-jects. These differences may reflect the effects on serumlipid concentrations of dietary habit, socioeconomicstatus, smoking habit, and racial and genetic factors.

The major limitations of the present study concern itscomparatively small study population. In addition, thenumber of patients with severe acne was relatively lowcompared with the numbers of patients with mild andmoderate acne. These proportions reflect the real distribu-tion of acne severity in the population.

Conclusions

This study suggests that insulin resistance may not play amajor role in the pathogenesis of post-adolescent acne.Hormonal changes, genetic susceptibility, stress, the useof cosmetics, the use of drugs, and environmental factorsshould be considered in the development of post-adoles-cent acne.

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