Insulin resistance in moderate to severe acne vulgaris.

Introduction: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit usually affects adolescents. It is seen on the face, neck, trunk and arms. The main pathogenic factors of acne are high sebaceous gland secretion, follicular hyper proliferation, high androgen effects, propionibacterium acnes colonization and inflammation.
Objectives: To determine the presence of insulin resistance in moderate to very severe acne vulgaris. Material and
Methods: One hundred sixty subjects were enrolled in the study consisting of 80 patients with moderate to very severe acne vulgaris and 80 age and sex-matched controls without acne. Fasting serum insulin and glucose levels were measured and insulin resistance was calculated by Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) Index. The values were compared with the healthy control group.
Results: Significant difference was observed in HOMA values and fasting insulin among the two groups (P < 0.001). The levels were significantly higher in the patient group than in the control group, whereas no significant difference was present in fasting glucose levels between the two group. Conclusions: In conclusion, insulin resistance was seen in majority of patients with acne. These results can add to the evidence regarding a potential association between metabolic dysregulation and acne. Copyright:

Introduction

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. It usually affects adolescents. It is seen on the face, neck, trunk and arms. Most cases of acne present with a pleomorphic variety of lesions consisting of comedones, papules, pustules, nodules and cyst. Four major factors play role in the pathogenesis of acne vulgaris, that is, hyperplasia of sebaceous glands and increased sebum production, hyperkeratinisation of pilosebaceous ducts, propionibacterium acnes colonization and periglandular inflammation and high androgen effects.

The role of insulin in acne is that it induces the production of androgens, which play a major role in the production of excessive sebum, hyperkeratinisation and proliferation of sebaceous glands. Therefore, insulin may have a role in aetiology and severity of the acne.

As there is lack of studies to find out insulin resistance in acne patients especially among the Indian population, the present study was aimed at to observe insulin resistance in moderate to very severe acne patients without having any other systemic complains, which may affect body insulin level.

Aim and Objectives

The present study was done to determine the presence of insulin resistance in patients with acne for which HOMA-IR was calculated, which is a composite outcome based on the product of fasting glucose and insulin.

Material and Methods

It was a cross-sectional observational study of a cohort of patients with and without acne, conducted in the Department of Dermatology, STD & Leprosy at a tertiary care hospital at Jaipur, Rajasthan, India from March 2016 to October 2017 with a sample size 160 of total study subjects. Eighty eligible male and female untreated patients with moderate to very severe acne vulgaris with normal body mass index (BMI) were included in the study and 80 age, and sex-matched controls attended the OPD with minor cutaneous complains unrelated to acne were recruited in the study. While subjects on any medications known to affect insulin metabolism, previous treatment with oral retinoids or any hormonal treatment for any reason in previous 3 months, cigarette smoking, history of thyroid dysfunction or a history of diabetes mellitus, hypertension, known case of malignancy, pregnancy, atherosclerotic vascular disease, psoriasis, polycystic ovarian disease or any other known metabolic disorders were excluded from the study. Written consent was taken from all the participants. Peripheral venous blood sample was collected from all the participants under aseptic conditions after >8 h of fasting. Insulin resistance was assessed using Homeostasis model assessment of insulin resistance (HOMA-IR). All baseline routine investigations were done at the beginning of the study including fasting blood glucose, fasting insulin level, complete blood count, ESR, total lipid profile, liver function test, renal function test, routine urine examination and a written informed consent was taken from all the participants. A detailed demographic data along with clinical history was recorded on a predesign proforma with the following points mentioned such as duration of acne, any aggravating factors, family history of acne, history of previous treatment for acne, any systemic illness, occupational history, diet history, BMI. Cutaneous examination including site of acne, type of acne (comedones/papules/pustules/nodules/cysts) and severity of acne. Patients of acne vulgaris were examined under good illumination and graded on the basis of severity as described by Global acne grading system (GAGS).[1] HOMA and GAGS were calculated by using the following formula:

HOMA-IR = fasting glucose × fasting insulin/405

Fasting glucose was measured in mg/dL and insulin in μIU/mL. Values of more than 2.7 were taken as an indicator of insulin resistance.

Statistical analysis was performed with the SPSS, Trial version 23 for Windows statistical software package (SPSS Inc., Chicago, IL, USA) and Primer for the generation of descriptive and inferential statistics. Continuous variables were summarized as mean ± standard variation (SD). The Categorical data were presented as numbers (percent). Chi- square test was used for data analysis. Student's ‘t’ test was calculated by taking into consideration the difference between the mean values and the standard deviation of each group. Probability P value < 0.05 was considered statistically significant.

Results

In our study, we included 80 cases and 80 controls, male outnumbered the females in both the groups making 72% of cases and 59% in controls. The GAGS was used for assessing the severity of acne [Table 1]. Among cases, 17.5% had moderate, 32.5% severe and majority belonged to the very severe acne vulgaris with 50% of the involved patients. There was no significant difference between the patient and control groups regarding sex or age (P > 0.05). The mean ± SD of age was 21 ± 3.9 years in cases and 22 ± 4.9 in controls. There was no difference between two groups in terms of weight, height or BMI (all P values > 0.05). While fasting, blood glucose levels were not different among the two groups (P > 0.05) Table 2; the fasting insulin levels were significantly higher in the patient group than in the control group (P < 0.001), and a significant difference is found in P values of HOMA between the two groups (P < 0.001) [Table 2]. Our study concluded that insulin resistance was present in patients with acne but no direct relationship was found between acne severity and insulin resistance [Table 3].

Table 1

GAGS

Global acne grading system
Location		Factor
Forehead	Right cheek	2	2
Left cheek	Nose	2	1
Chin	Chest and upper back	1	3

NOTE=Each type of lesion is given value given according to severity. No lesion=0; Comedones=1; Papules=2; Pustules=3; Nodules=4; Score of each area is (local score) calculated using the formula: Local score=factor×grade (0-4). The global score is sum of local scores and acne severity is graded using the global score. Mild: 1-18; Moderate: 19-30; Severe: 31–-38; Very severe: >39

Table 2

P-value analysis

Features	Cases (Mean±SD)	Control (Mean±SD)	P
Fasting glucose	81.48±9.3	80.14±10.1	0.38 NS
Fasting insulin	33.85±1.5	7.14±2.4	<.001 S
HOMA-IR >2.7	3.3±1.7	1.5±1.9	<.001 S

Table 3

Acne severity and insulin resistance

HOMA-IR >2.7 as insulin resistance
	n	Mean	Std. deviation	P LS	Moderate vs. Severe	Moderate vs. Very severe	Severe vs. Very severe
Moderate (n=14) 17.5%	14	2.816	0.7638	0.066 NS
Severe (n=26) 32.5%	26	2.960	1.1237		NS	NS	NS
Very severe (n=40) 50%	40	3.813	2.1852
Total	80	3.361	1.7497

Discussion

Acne vulgaris is a self-limiting chronic inflammatory condition of the pilosebaceous follicles and is characterized by comedones, papules, pustules, nodules and scars. It can manifest at any time during life but usually present between ages of 12–24 years. Pathogenesis of acne is known since a very long time as hyperseborrhea, follicular hyperkeratinization, Propionibacterium acne colonization and inflammation, yet the mechanism of acne is not fully understood.[2] In this study, we aim at investigating the relationship between moderate to very severe acne vulgaris and insulin resistance.

Previous studies suggest that high insulin level because of intake of high glycemic load diet may trigger acne by inducing hyperinsulinemia.[345] Low glycemic load diet is having a role in the prevention of hyperinsulinemia by lowering the postprandial insulin.[45] Another clinical example about the relation between acne and IGF is Laron syndrome (LS). LS is characterized by congenital IGF-1 deficiency. In his study, Ben-Amitai and Laron[6] observed that IGF-1 deficiency prevents the occurrence of acne. They suggested that IGF-1 and androgens are necessary for the development of acne.

Studies done by Anderson et al.[7] and by Adebamowo et al.[8] showed the same results that hyperinsulinemia induced by giving increasing amount of chocolates day by day to the patients resulted in the flaring of acne.

Acne is also a common occurrence in PCOS patients, as are high levels of IGF-1 and androgens. Both insulin and IGF induce the production of androgens while simultaneously inhibiting the hepatic synthesis of sex hormone-binding globulin (SHBG); therefore, the bioavailability of androgens increases. Hyperinsulinemia increases serum levels of IGF-1 and reduces serum levels of insulin-like growth factor binding protein 3. These two factors directly influence proliferation and apoptosis of keratinocytes. Insulin-like growth factor may also stimulate some comedogenic factors such as androgens, growth hormone and glucocorticoids.[91011] The incidence of acne corresponds more closely to insulin and IGF-1 levels than plasma androgens.[1213]

Insulin resistance may occur during various clinical conditions such as physiological conditions, for example, puberty, pregnancy, old age or as a side effect of certain medications, for example, corticosteroids, some oral contraceptives, diuretics or as a symptom of certain diseases, for example, type 2 diabetes, cardiovascular disease, essential hypertension, PCOS, nonalcoholic fatty liver disease, certain cancer.[14]

In our study, the average age of the subjects enrolled was 20 years; hence, it is unlikely that most of the abovementioned chronic conditions are the causes of insulin resistance found in our patients and apart from that the diseases that had also been ruled out by the physical examinations and investigations advised as set in predesigned proforma.

Study done by Munichandrappa et al.[15] did not find any significant correlation between acne and insulin resistance in Indian population, which contradicts the many of studies; the reasons for that can be the small population size and bulk of patients mainly belonged to the mild category of acne, while in our study, we have taken patients having moderate to very severe acne vulgaris. While the study conducted by Nagpal et al.[16] concluded that postadolescent male patients with acne are more prone to have higher mean HOMA-IR values, higher mean fasting plasma glucose levels and higher prevalence of insulin resistance compared with the controls in their study. And Kartal et al.[17] did a study where they enrolled only female patients with acne and found a positive relationship between female acne and insulin resistance.

Here, in our study, we used HOMA-IR index for evaluating insulin resistance. The HOMA-IR index has been an accepted formula for measuring insulin resistance since its original publication by Matthews et al.[18] in 1985. There are many various methods to describe insulin sensitivity. Among other models, gold standard methods are euglycemic clamp and modified minimal model, but they are used for research only because they are too invasive for general epidemiologic studies.[1920] Therefore, methods such as fasting insulin level, fasting glucose/insulin ratio, HOMA-IR and quantitative insulin-sensitivity check index are suggested to be used in population studies.[21] HOMA-IR is a frequently used parameter in clinical research.[21]

In taken view of our study, there was no difference between the two groups in terms of demographic profile including, sex, age, BMI etc. In our study, patients with acne were showing insulin resistance as compared to the controls. There are only a few studies done to assess insulin resistance in acne patients. In our study, we found statistically significant values of serum insulin despite of normal fasting glucose levels in patients with moderate to very severe acne in compare to the control group.

The study showed a significant difference between mean insulin and HOMA-IR between the two groups, but no significant difference was obtained in terms of fasting glucose level in between the two groups. The rising insulin may initiate the earliest change of acne before hyperandrogenism. This trend can be seen in cases that develop acne before other signs of puberty. This insulin resistance in these patients may be due to the adoption of western diet rich in carbohydrate and other factors like sedentary lifestyle, spending more time on electronic gadgets and lack of outdoor activities. It may be one of the possible mechanisms involved in pathogenesis of acne. These results can add to the evidence regarding potential association between metabolic dysregulation and acne. Hence, we believe that insulin resistance should be determined in acne especially on those patients who are not responding to the conventional treatment. These patients should be advised to take low glycaemic diet along with the drugs that reverse insulin resistance.

Conclusion

In our study, we found statistically significant values of serum insulin despite of normal fasting glucose levels in our patients compared to the control group and concluded that insulin resistance was present in our study in acne patients. Therefore, with conventional treatment of acne, anti-insulin drugs may be used as an adjunctive to treat moderate and severe acne vulgaris. Food with high glycaemic index are advised to avoid. Insulin resistance may be a stage of prediabetes, and the patients may develop type 2 diabetes or metabolic syndrome in future, so those patients showing insulin resistance should be followed-up to determine whether they develop any other conditions associated with insulin resistance.

Limitation

This result cannot be generalised to all patients as mild acne patients were excluded from the study.

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

Nil.

Conflicts of interest

There are no conflicts of interest.