|Year : 2020 | Volume
| Issue : 2 | Page : 123-124
Insulin resistance and insulin-like growth factor-1 level in patients with acne: A systematic review and meta-analysis
Tsung-Yu Tsai1, Yuan-Chen Chao2, Wei-Ting Chou1, Yu-Chen Huang3
1 Department of Dermatology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
2 School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
3 Department of Dermatology, Wan Fang Hospital; Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
|Date of Submission||31-Mar-2019|
|Date of Decision||06-Nov-2019|
|Date of Acceptance||06-Dec-2019|
|Date of Web Publication||29-May-2020|
Dr. Yu-Chen Huang
Department of Dermatology, Wan Fang Hospital, Taipei Medical University, No. 111, Hsing-Long Road Sec. 3, Wenshan District, Taipei 116
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Tsai TY, Chao YC, Chou WT, Huang YC. Insulin resistance and insulin-like growth factor-1 level in patients with acne: A systematic review and meta-analysis. Dermatol Sin 2020;38:123-4
|How to cite this URL:|
Tsai TY, Chao YC, Chou WT, Huang YC. Insulin resistance and insulin-like growth factor-1 level in patients with acne: A systematic review and meta-analysis. Dermatol Sin [serial online] 2020 [cited 2021 Aug 5];38:123-4. Available from: https://www.dermsinica.org/text.asp?2020/38/2/123/285355
Acne vulgaris is an inflammatory disease of pilosebaceous units. The pathogenesis of acne involves multiple mechanisms, one of which is sebum overproduction. Serum insulin-like growth factor (IGF)-1 is a polypeptide hormone that has effects on sebocyte differentiation and proliferation. Moreover, acne is related to certain endocrine disorders such as polycystic ovary syndrome (PCOS). PCOS is characterized by peripheral insulin resistance (IR) and hyperinsulinemia, indicating a potential interplay between IR and acne. Previous studies investigated the IR and IGF-1 levels in patients with acne have produced inconsistent results. The current systematic review and meta-analysis were, therefore, conducted to address this issue.
We searched online databases (PubMed, Embase, and the Cochrane Library) on March 1, 2019, to include studies that compared the homeostasis model assessment of IR (HOMA-IR) values and serum IGF-1 levels between patients with acne and controls. Review articles, case reports, and conference reports were excluded. Two authors independently screened the titles and abstracts of articles, extracted data and assessed the quality of included studies using an adapted version of the Newcastle-Ottawa Scale for case–control studies [Supplemental Table 1]. A random-effects model was fitted to estimate the standardized mean difference (SMD) in HOMA-IR values and serum IGF-1 levels between patients with acne and controls.
Twenty studies involving 1026 patients with acne were included [Supplemental Figure 1]. The characteristics of the included studies are summarized in [Supplemental Table 2]. The quality score ranged from 7 to 9. Pooled analysis of 13 studies comparing HOMA-IR between patients with acne and controls revealed that HOMA-IR values in patients with acne were significantly higher than those in controls [SMD = 0.45, 95% confidence interval (CI) = 0.209–0.699, I2 = 76.4%; [Figure 1]. Eleven studies providing serum IGF-1 levels in patients and controls were pooled and revealed a significantly higher level of serum IGF-1 level in patients with acne than controls (SMD = 0.68, 95% CI = 0.214–1.146, I2 = 89.2%; [Figure 2]). Two studies expressed IGF-1 in U/ml, which cannot be converted to ng/ml, and one study showed extremely different data from those of other studies. A sensitivity analysis excluding these studies revealed a consistent result (SMD = 0.76, 95% CI = 0.126–1.391, I2 = 92.2%). Publication bias was not detected with Egger's test.
|Figure 1: The forest plot showed that compared with controls, patients with acne had significantly higher homeostasis model assessment of insulin resistance values (standardized mean difference, 0.45; 95% confidence interval, 0.209–0.699; I2, 76.4%). Std: Standardized|
Click here to view
|Figure 2: The forest plot showed that compared with controls, patients with acne had higher serum insulin-like growth factor-1 level (standardized mean difference, 0.68; 95% confidence interval, 0.214–1.146; I2, 89.2%). Std: Standardized|
Click here to view
Acne incidence is believed to correlate more significantly with changes in serum IGF-1 and insulin levels than with those in androgen. The onset of acne is usually in adolescence, when there is reduced insulin sensitivity, along with increased serum IGF-1 and insulin levels. Serum IGF-1 and insulin levels reach their peaks in late adolescent and gradually decline in adulthood. The disease course of acne follows similar temporal sequence. Acne usually resolves in the third decade in spite of unchanged circulating androgen level.
Insulin decreases IGF-binding protein (IGFBP)-1, thereby releasing free IGF-1. IGF-1 binds to IGF-1 receptors and activates multiple downstream signaling pathways such as the phosphoinositide-3-kinase (PI3K) and Akt kinase pathway, enhancing sebaceous lipogenesis and sebocyte proliferation. In the meantime, the activation of PI3K/Akt pathway reduces nuclear transcription factor FoxO1, leading to comedogenesis, lipogenesis, and synthesis of inflammatory cytokines. IGF-1 also stimulates androgen synthesis through both adrenal and peripheral androgen signaling pathways.
Immunocytochemistry study suggested the role of IGF-1 as sebaceous mitogen and morphogen in human skin appendages as IGF-1 was strongly expressed in maturing sebocytes and suprabasal cells of sebaceous ducts.
Smith et al. revealed that compared with patients with acnes on a conventional high glycemic-load diet, patients on a low glycemic-load diet had significantly more decreased acne counts, higher insulin sensitivity, and increased IGFBP-1. This further corroborates the roles that IR and IGF-1 play in the pathogenesis of acne.
The current study was limited by significant heterogeneity. Sensitivity analysis was, therefore, performed. Cappel et al. suggested that IGF-1 plays a more critical role in women with acne, whereas androgens have more substantial influence on men with acne. This could be attributable to higher androgen levels that override the effects of IGF-1 in men. However, we could not confirm this assumption because subgroup analysis based on gender could not be performed due to limited data provided in the included studies. Metaregression could not be conducted for the same reason.
In conclusion, this study demonstrated a significant association between IR and acne and elevated serum IGF-1 levels in patients with acne. Clinicians are encouraged to monitor the metabolic profile of patients with acne and proactively offer advice for lifestyle modifications or even pharmacological treatments. Future studies are encouraged to explore the efficacy of medications targeting IGF-1 in treating patients with acne.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Melnik BC. FoxO1 – The key for the pathogenesis and therapy of acne? J Dtsch Dermatol Ges 2010;8:105-14.
Lee AT, Zane LT. Dermatologic manifestations of polycystic ovary syndrome. Am J Clin Dermatol 2007;8:201-19.
Smith CP, Dunger DB, Williams AJ, Taylor AM, Perry LA, Gale EA, et al
. Relationship between insulin, insulin-like growth factor I, and dehydroepiandrosterone sulfate concentrations during childhood, puberty, and adult life. J Clin Endocrinol Metab 1989;68:932-7.
Powell DR, Suwanichkul A, Cubbage ML, DePaolis LA, Snuggs MB, Lee PD. Insulin inhibits transcription of the human gene for insulin-like growth factor-binding protein-1. J Biol Chem 1991;266:18868-76.
Fan W, Yanase T, Morinaga H, Okabe T, Nomura M, Daitoku H, et al
. Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J Biol Chem 2007;282:7329-38.
Rudman SM, Philpott MP, Thomas GA, Kealey T. The role of IGF-I in human skin and its appendages: Morphogen as well as mitogen? J Invest Dermatol 1997;109:770-7.
Smith RN, Mann NJ, Braue A, Mäkeläinen H, Varigos GA. The effect of a high-protein, low glycemic-load diet versus a conventional, high glycemic-load diet on biochemical parameters associated with acne vulgaris: A randomized, investigator-masked, controlled trial. J Am Acad Dermatol 2007;57:247-56.
Cappel M, Mauger D, Thiboutot D. Correlation between serum levels of insulin-like growth factor 1, dehydroepiandrosterone sulfate, and dihydrotestosterone and acne lesion counts in adult women. Arch Dermatol 2005;141:333-8.
[Figure 1], [Figure 2]