Metabolic Status, Obesity, and Quality of Life in Patients with Acne Vulgaris: A Cross-Sectional Case-Control Study.

BACKGROUND: Acne vulgaris is a chronic inflammatory disease primarily affecting the adolescents, with a profound impact on their quality of life. There is conflicting data regarding its association with metabolic syndrome.
OBJECTIVE: To assess the prevalence of metabolic syndrome (MetS) and obesity in patients with acne vulgaris, and determine its impact on the patient's quality of life.
METHODS: We conducted a cross-sectional, case-control study involving 50 patients with acne vulgaris (cases) and 50 age and sex-matched controls without acne. Acne vulgaris was graded according to clinical severity using the GAGS scale. NCEP-ATP III criteria and modified classification of body mass index (BMI) for Asian Indians were used to diagnose MetS and obesity, respectively, in both cases and controls. We used the DLQI questionnaire to evaluate its impact on the quality of life.
RESULTS: Cases and controls were comparable with respect to parameters like age, BMI, systolic blood pressure (SBP), diastolic blood pressure (DSBP), and serum triglyceride while fasting blood sugar (FBS, case > control) and serum high-density lipoprotein (HDL, control > case) were significantly different (P < 0.05, independent t-test). Prevalence of MetS was higher in cases (32%) than controls (14%), though comparable (P = 0.06, Chi-square). Only SBP, FBS, and serum HDL showed a significant correlation with the severity of acne. Obesity was comparable between cases (18%) and controls (10%), without any relation to acne severity. Acne exerted a moderate impact on the quality of life (mean DLQI 9.3). Severe acne showed higher DLQI, although their correlation was not statistically significant (P = 0.8, ANOVA).
CONCLUSION: Although acne patients may develop MetS and obesity, there is a lack of significant association. Thus, we should examine all obese patients, irrespective of dermatological disorder, to rule out metabolic syndrome. Acne also affects the patient's quality of life, thus emphasizing the need for additional psychosocial counselling. Copyright:

Introduction

Acne, a chronic, inflammatory disorder of the pilosebaceous unit is a common skin problem globally, primarily affecting the adolescents, but may also progress to or arise de-novo in adults.[12] Acne is a multifactorial disorder, its main etiopathogenic factors include follicular hyperkeratinization, increased sebum production, increased bacterial (Propionibacterium acnes) colonization of the pilosebaceous unit, all culminating into the release of several proinflammatory mediators like tumor necrosis factor (TNF)-α, IL-1 β, IL-8, and IL-10.[2] The role of androgens and insulin-like growth factor 1 (IGF1) to perpetrate this inflammatory process has been highlighted by several authors.[12]

Acne can present itself in varying severities ranging from noninflammatory lesions (comedones) to inflammatory lesions (papules, pustules, nodules, and cysts). Several scoring systems have been used to grade the severity of acne, the global acne grading system (GAGS) being one of the commonest.[3]

As chronic inflammation forms the backbone of acne vulgaris irrespective of its severity, long-term metabolic alteration seems likely, thus increasing the possibility of metabolic syndrome (MetS). Metabolic syndrome (MetS) or syndrome X is a symptom complex that increases the risk of developing type 2 diabetes mellitus (DM), cardiovascular disease (CVD), obesity, and other morbidities. Recently, several authors have highlighted the association of this syndrome with several dermatological disorders like psoriasis, androgenetic alopecia, acanthosis nigricans, skin tags, lichen planus, hidradenitis suppurativa, rosacea, systemic lupus erythematosus, and acne vulgaris.[145] Although the exact pathophysiology remains unknown, several proinflammatory cytokines, prothrombotic factors, increased homocysteine, leptin, and resistin levels, decreased serum adiponectin, and occurrence of nonalcoholic fatty liver disease have been implicated as possible links.[6] In case of acne vulgaris, peripheral insulin resistance and hormonal imbalance associated with polycystic ovarian syndrome (in cases of adult acne in females) are important additional factors.[16] Moreover, acne patients show increased activity of mTORC1 (mechanistic target of rapamycin complex 1) signaling which is also associated with peripheral insulin resistance, type 2 DM, and obesity, thus further strengthening the link of acne with obesity and MetS.[7]

Acne vulgaris predominantly affects the adolescent age group, favoring the face and other exposed areas of body, thus having a detrimental effect on their psychological status and quality of life (QoL).[8] This effect is especially important as this age group is psychologically labile, and often lead to social embarrassment resulting in skipping of schools and colleges. Measurement of QoL can also be a measure of treatment success. Although there are several studies regarding the psychosocial impact of acne in the Western literature, there is a paucity of data in the present set-up.

We have undertaken the present study to assess the relationship of acne vulgaris with MetS and obesity along with its impact on the patient's quality of life. All the parameters have been correlated to the severity of acne to determine any pattern. The scarcity of similar data in the present set-up has prompted this study.

Materials and Methods

We conducted a prospective, cross-sectional case-control study involving 50 consecutive patients of acne vulgaris (cases) and 50 age and sex matched controls (subjects without acne or its previous history recruited from those attending the dermatology out-patient department of our hospital). The study was conducted in the department of Dermatology of a tertiary care institute, after attaining requisite approval from the institutional ethical committee from April 2019 to June 2019 (3 months).

Extremes of ages (<12 years and >60 years), presence of comorbidities like diabetes mellitus/thyroid disorders/liver disease/renal disease and/or malignancy, pregnancy, lactation, history of addiction, viz., smoking, alcohol, substance abuse, and treatment history with systemic isotretinoin within the last 1 year (which may have altered the lipid profile and metabolic status) served as the exclusion criteria for both cases and controls. Written informed consent from all study participants served as the inclusion criteria. We conducted the study in accordance with the Declaration of Helsinki (Brazil, 2013), the International Committee on Harmonization of Good Clinical Practice (ICH-GCP) (1996) guidelines, and Schedule Y of the Drugs and Cosmetics Act, 1940 amendment 2005.

Acne vulgaris was diagnosed by clinical examination exclusively by the same dermatologist (I.P) in all patients (cases), while age and sex matched nonacne controls were recruited by another dermatologist (K.A). All study participants (cases and controls) were subjected to detailed history taking regarding sociodemographic factors, duration of disease, family history, and subsequent anthropometric measurements and biochemical investigations. We also assessed the clinical severity of acne using the Global acne grading system (GAGS)[3] in cases and their quality of life using the Dermatology quality life index,[9] after obtaining requisite permissions. Accordingly, all acne patients were segregated into four groups: mild, moderate, severe, and very severe.

Anthropometric measurements

We recorded height (cm) and weight (kg) using a stadiometer (SECA 213 Stadiometer) and a digital weighing machine (SECA 874 U digital scale), respectively. Waist circumference was measured by a measuring tape, placed snugly around the abdomen at the level of iliac crest. Blood pressure (mmHg) was measured at the left brachial artery using a standard sphygmomanometer cuff in sitting position, thrice in each subject to obtain the mean value. Body mass index (BMI) was calculated as weight in kilograms divided by height in meter squared (kg/m2). The modified classification of BMI for Asian Indian populations was used in this study to define overweight (23–24.99 kg/m2), moderate obesity (25–29.9 kg/m2), and severe obesity (≥30 kg/m2).[10]

Biochemical investigations

Venous blood was collected through venepuncture of left anterior cubital vein. Twelve hour fasting blood was taken for the estimation of glucose, triglyceride (TG), and high density lipoprotein-cholesterol (HDL-C). Concentrations were determined with kits by Erba Mannheim XL System Pack, EM 360 Transasia Autoanalyzer (Germany), in the Department of Biochemistry, which is included in Grade “A” category by Biorad Quality Assurance System (USA).

We used the modified National Cholesterol Education Program's Adult treatment panel III (NCEP-ATP III) to diagnose MetS in both cases and controls. It requires at least 3 of the following 5 criteria:[11] (1) abdominal obesity: Waist circumference in men >102 cm (>40 inches) and in women >88 cm (>35 inches); (2) serum triglycerides >150 mg/dL (>3.82 mmol/L); (3) high-density lipoprotein (HDL) cholesterol <40 mg/dL (<1.03 mmol/L) in men and <50 mg/dL (<1.30 mmol/L) in women; (4) systemic arterial blood pressure ≥130/≥85 mm Hg; and (5) fasting blood glucose ≥110 mg/dL.

Statistical analysis

Data were entered in a Microsoft Excel spreadsheet. All the entries were double entered checking consistency. All the data obtained has been statistically analyzed using MedCalc v12.5.0 and preserved for future reference. We used mean and standard deviation for descriptive statistics. Normal distribution of numerical variables was determined using the Shapiro-Wilk test. Chi-square test was used for nonparametric data, while ANOVA and Kruskal-Wallis tests were applied for parametric data. A P value < 0.05 has been taken as significant.

Results

We included 50 patients with acne vulgaris (cases) and 50 age and sex matched controls without acne for our case-control study. There was no significant statistical difference between cases and controls with respect to age, BMI, waist circumference, and sexual distribution [Table 1]. Mean (SD) systolic blood pressure (SBP) and diastolic blood pressure (DSBP) of cases were 117.3 ± 11.2 mmHg and 78.2 ± 9.2 mmHg, respectively, and were comparable to those of controls (118.8 ± 3.5 mmHg and 80.9 ± 3.4 mmHg, respectively) [P = 0.4 and 0.05 respectively, t-test]. However, fasting blood sugar (FBS) [mean (SD)] was significantly higher in cases (94.1 ± 6.6 mg/dL) compared to controls (88.7 ± 4.4 mg/dL) [P < 0.0001, t-test]. Among lipid profile parameters, serum triglyceride level was comparable between cases and controls, but mean serum HDL-C was significantly higher in controls than cases (50.4 ± 5.8 mg/dL vs. 47.2 ± 6.7 mg/dL; P = 0.01, t-test). We assessed the metabolic status of both cases and controls using the NCEP-ATP III criteria. MetS was detected in [16 (32%)] cases and [7 (14%)] controls; however, the difference was not statistically significant (P = 0.06, Chi-square). All the clinic-demographic parameters have been tabulated in Table 1.

Table 1

Study parameters in cases and controls (data presented as mean±SD, unless specified)

Parameters	Cases (n=50)	Controls (n=50)	P
Age (years)	21±4.9	22.3±0.8	0.2
Sex (M:F)	1:1.9	1:1.3	0.9*
BMI (kg/m2)	24.2±26.1	20.6±2.9	0.3
Waist circumference (cm)	31.7±3.6	30.8±2.2	0.13
SBP (mmHg)	117.3±11.2	118.8±3.5	0.4
DSBP (mmHg)	78.2±9.2	80.9±3.4	0.05
Fasting blood glucose (mg/dL)	94.1±6.6	88.7±4.4	<0.0001
Serum HDLC (mg/dL)	47.2±6.7	50.4±5.8	0.01
Serum Triglycerides (mg/dL)	98.7±30.8	96.8±25.1	0.7
Metabolic syndrome assessed by NCEPATP III (%)	32	14	0.06*

*P-values obtained by Chi-square test; all other P-values obtained by independent t-test BMI: Body mass index, SBP: Systolic blood pressure, DSBP: Diastolic blood pressure, HDL-C: High-density lipoprotein-cholesterol, NCEP-ATP III: National Cholesterol education programme Adult Treatment panel III

We detected obesity in 9 (18%) of our cases (16%- moderate obesity; 2%- severe obesity), while 7 (14%) and 5 (10%) of our controls presented with overweight and moderate obesity, respectively. All the remaining subjects were normal across both groups. There was no significant statistical difference between cases (18%) and controls (10%) with respect to obesity (P = 0.4, Chi-square).

We assessed the duration of acne and also graded its severity using the global acne grading system (GAGS) score in cases. The mean duration of acne was 18.4 ± 17.3 months (range 1–72 months; 95% CI 13.5–23.3). The GAGS score ranged from 8–34, mean being 18.54 ± 6.6 (95% CI 16.7–20.4). Mild acne was commonest in 32 (64%) patients, followed by moderate [13 (26%)] and severe [5 (10%)] variants (n = 50), while none presented with very severe acne. No significant statistical correlation was obtained between duration and severity of acne (P = 0.3, ANOVA).

Mean age was statistically comparable across the three groups/grades of acne (mild, moderate, and severe). There were no significant statistical differences in BMI, waist circumference, diastolic blood pressure, and serum triglyceride level across the acne severity groups (P = 0.2, 0.3, 0.1, and 0.2 respectively, ANOVA). However, systolic blood pressure (SBP), fasting blood sugar (FBS), and serum HDL-C were significantly different among the severity groups (P = 0.04, 0.03, and 0.008, respectively, ANOVA) [Table 2]. Post-hoc testing revealed SBP to be significantly higher in patients with severe acne compared to mild acne, while mild and moderate groups were comparable. FBS was significantly elevated in mild and severe groups compared to moderate group. Serum HDL was severely depressed in severe acne, statistically significant with respect to mild and moderate groups, while the latter 2 groups were comparable. MetS was detected in 16% of patients with mild acne, while 8% each of moderate and severe groups were affected, and this difference was statistically significant (P = 0.04, Chi-square for trend). Thus, MetS needs to be ruled out irrespective of the severity of acne [Table 2]. Obesity was recorded in 9 (18%) acne patients; however, there was no significant association with the severity of acne (P = 0.2, Chi-square).

Table 2

Relationship between study parameters and severity of acne (GAGS) (n=50, all data in mean±SD, unless specified otherwise)

Parameters	Mild acne (n=32)	Moderate acne (n=13)	Severe acne (n=5)	P
Age (years)	20.9±3.9	21.8±6.7	20.2±4.9	0.8
BMI (kg/m2)	20.3±4.2	34.8±50.7	21.4±3.9	0.2
Waist circumference (cm)	31.3±3.5	32±3.7	34±3.23	0.3
SBP (mmHg)	114.7±10.9	119.9±11.6	127.2±3.0	0.04
DSBP (mmHg)	76.6±9.7	79.8±8.2	84.8±4.6	0.1
Fasting blood glucose (mg/dL)	94.8±6.03	90.5±5.5	98.6±8.9	0.03
Serum HDLC (mg/dL)	48.9±6.6	46.1±5.5	39.4±4.4	0.008
Serum triglycerides (mg/dL)	104.5±32.3	87.3±27.4	91.8±23.6	0.2
Metabolic syndrome assessed by NCEPATP III (%)	16	8	8	0.04*

*P-values obtained by Chi-square test; all other P-values obtained by ANOVA with post Hoc Dun's test. BMI: Body mass index, SBP: Systolic blood pressure, DSBP: Diastolic blood pressure, HDL-C: High-density lipoprotein-cholesterol, NCEP-ATP III: National Cholesterol education programme Adult Treatment panel III

We also assessed the quality of life in acne patients using the Dermatology quality life index (DLQI). The mean (SD) DLQI was 9.3 ± 4.8, scores for mild, moderate, and severe acne being 9 ± 5.1, 9.5 ± 4.9, and 10.4 ± 1.5, respectively. However, there was no significant association between DLQI score and severity of acne (P = 0.8, ANOVA).

Discussion

In our cross-sectional study, demographic characteristics including age, BMI, and waist circumference were comparable between the cases and controls, consistent with the findings of Nagpal et al.[1] and Balta et al.[12] In contrast, Del Prete et al.[13] and Tsai et al.[14] reported higher BMI and waist circumference among the cases in comparison to the controls.

The SBP and DBP were comparable in both groups (cases and controls) in our study. However, both Nagpal et al.[1] and Del Prete et al.[13] reported significantly higher SBP and DBP in acne patients (cases).

We found FBS to be significantly elevated in cases compared to the control group (P < 0.0001, t-test), consistent with the findings of Nagpal et al.[1] and Del Prete et al.[13] However, Balta et al.[12] failed to detect any significant difference in FBS between the two groups.

Among lipid profile parameters, we recorded significantly higher serum HDL-C in controls than cases (P = 0.01, t-test), corroborating the findings of most other studies.[131516] However, some authors reported higher values in cases, though statistically comparable.[112] Most authors reported comparable serum TG values between cases and controls, similar to us.[151213]

We observed a statistically significant correlation of SBP, FBS, and HDL-C with the severity of acne. SBP and FBS were significantly higher in severe acne, while HDL-C was significantly higher in mild and moderate acne compared to the severe variant. There is a scarcity of studies correlating these parameters with the severity of acne; however, Nagpal et al.[1] failed to detect any statistically significant correlation. Alan and Cenesizoglu[17] reported a positive correlation between BMI and acne severity, in contrast to Balta et al.[12] or the present study, where no such observation was made.

We did not observe any statistically significant difference between the two groups with respect to obesity and there was no positive correlation between obesity and severity of acne. Interestingly, Snast et al.[18] observed a protective effect of obesity against acne. This protective effect may be attributed to increased aromatase activity in obese individuals augmenting the peripheral conversion of androgens to estrogens within adipose tissue. Estrogen, in turn, opposes the action of androgens and decreases sebum production. Moreover, obesity may suppress the activity of 5-alpha-reductase 2, responsible for the conversion of testosterone to the more active dihydrotestosterone, an important mediator of acne pathogenesis.

In our study, acne patients (cases) showed a higher prevalence of MetS (32% vs. 14% in controls), according to the NCEP-ATPIII criteria, although the difference was not statistically significant (P = 0.06, Chi-square). The prevalence of MetS is higher than that of Nagpal et al. (17%),[1] but lower than Del Prete et al. (36%).[13] However, all studies detected higher MetS in cases, none being statistically significant, consistent with our findings. There are limited studies evaluating the correlation of MetS to the severity of acne. In our study, MetS was detected in 16% patients with mild acne, while 8% in each of moderate and severe groups, and this difference was statistically significant (P = 0.04, Chi-square for trend). Nagpal et al.[1] did not observe any significant correlation between MetS and severity of acne, whereas Biagi et al.[5] reported a positive correlation between severe acne and MetS. A recent pooled-analysis has indicated the growing prevalence of MetS in young adults (4.8%–7%),[19] irrespective of any disease and increased risk of complications in adult life even if a single component is present. Thus, we should assess all young adults for metabolic syndrome, especially those with obesity, irrespective of the associated dermatological disorders or their severity. Lack of significant association between MetS and acne vulgaris in the present study further supports this view.

Acne primarily affects the face and other exposed parts of adolescents, a psychologically labile age group, thus leading to considerable psychological morbidity and adversely affecting the QOL.[8] In our patients, the mean DLQI score was 9.3 (range 1–18; 95% CI 8–11). Half of our patients [21 (50%)] reported a very large effect on their QoL (DLQI score 11–20), followed by mild effect (30%, DLQI score 2–5), moderate effect (26%, DLQI score 6–10), while remaining 1 patient did not have any effect (DLQI score 1) and no patient showed an extreme large effect on their QoL. Several studies have reported a lower mean DLQI score, ranging from 4–8.[82021] Hazarika and Archana[22] documented maximum acne patients with moderate impact on the quality of life, in contrast to our findings where 50% patients reported very large effect on their quality of life. We failed to find any statistically significant correlation between impairment of QOL and severity or duration of acne, but we did observe worsening DLQI scores with increasing severity. This finding is consistent with Ilgen and Derya[23]; however, several authors have reported a significant positive correlation between worsening DLQI scores and acne severity.[82122] The different findings may be attributed to heterogeneous study populations with varying levels of education, socioeconomic, cultural conditions and individual perception of stress.

Limitations

The major limitations of our study include a cross-sectional study design with low sample size. A larger study population with follow-up would have enabled us to assess the prevalence of MetS with the risk of its subsequent development. Another drawback was our inability to address serum insulin level and insulin resistance in our patients.

Conclusion

Acne patients are significantly more prone to develop higher values of FBS and lower serum HDL-C compared to controls. Although MetS and obesity are more common in patients with acne vulgaris, they lack any significant association. SBP and FBS tend to be higher in those with severe grades of acne. Prevalence of obesity and MetS does not vary significantly with the severity of acne. Thus, we should examine and investigate all dermatological patients to rule out MetS and obesity, irrespective of their disease severity, and not restrict ourselves to any particular disorder. Acne vulgaris exerts a moderate effect on patient's quality of life regardless of severity; thus, psychosocial counselling is of paramount importance in all patients, in addition to standard medical care.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for 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.