Journal of Clinical and Aesthetic Dermatology

OCT 2017

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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20 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY October 2017 • Volume 10 • Number 10 O R I G I N A L R E S E A R C H 5α-reductase, which converts testosterone to dihydrotestosterone, a sex steroid that is five times more potent than testosterone. 9 In the skin, some follicles might be more acne-prone than others, and these follicles will have different levels of susceptibility to circulating hormones. Increased sensitivity of the sebaceous gland to androgens and the increased metabolization of local androgen hormones into potent androgen metabolites might offer alternative mechanisms in acne pathophysiology. 10,11 Vitamin D. Vitamin D is a fat-soluble prohormone steroid with endocrine, paracrine, and autocrine functions. 12 Seventy-nine percent of Indians are believed to be vitamin D-deficient, 13 and in a study from South India, 76 percent of women were found to be vitamin D deficient. 14 Vitamin D plays a physiologic role in reproduction, including ovarian follicular development and luteinization via altering AMH signaling, FSH sensitivity, and progesterone production in human granulosa cells. 15 Low 25(OH)D levels are significantly correlated with insulin resistance in women with PCOS. 16 There have been a few in-vitro studies that support the theory that vitamin D has a functional role in acne development. 17–19 The identification of vitamin D receptors in human sebocytes and the modulation of lipid and cytokine production by vitamin D suggests a possible association between vitamin D and acne pathophysiology. 17,18 Propionibacterium acnes (P. acnes) is a potent inducer of Th17, and 1,25(OH)2D inhibits P. acnes-induced Th17 differentiation; therefore, vitamin D could be considered an effective tool for modulating acne. 19 Vitamin D(3) supplementation also improves postprandial insulin sensitivity. 20 The level of 25(OH)D has been inversely associated with the severity of acne, and there is a significant negative correlation between 25(OH)D levels and the development of inflammatory lesions. 21 Insulin. Acne is a common component of seborrhea-acne-hirsutism-androgenetic alopecia (SAHA) syndrome, PCOS, and hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN) syndrome, all of which are linked to insulin resistance (Figure 3). Fasting insulin levels and HOMA are significantly higher among patients with acne compared with non-acne controls. 22 Insulin resistance (IR) is a metabolic disorder in which target cells fail to respond to normal levels of circulating insulin, which results in compensatory hyperinsulinemia in order for the human body obtain an appropriate physiological response. It is particularly prevalent in individuals with diabetes mellitus (DM) Type 2, decompensated Type 1 DM, diabetic ketoacidosis, and obesity. In normal populations, IR has a prevalence rate of 20 to 25 percent. 23 There are three types of IR: 1) Type A, caused by a reduced number and dysfunction of insulin receptors; 2) Type B, caused by the formation of antibodies against insulin receptors; and 3) Type C, which corresponds to a post-receptor defect. Patients with obesity and patients with PCOS tend to have Type A insulin resistance. Subsequent DM develops when insulin secretory capacity fails to reduce serum glucose. 24 IR increases during puberty and appears to be related to fat accumulation. 25 The insulin receptor belongs to the family of tyrosine kinase receptors, which includes the insulin-like growth factor (IGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet derived growth factor, colony stimulating factor I, and several cytokine receptors. A high concentration of insulin results in the direct and indirect activation of IGF-1 receptors in keratinocytes and fibroblasts, leading to their proliferation and formation of comedones. Other mediators can also contribute, including other tyrosine kinase receptors (e.g., epithelial growth factor receptor and fibroblast growth factor receptor). 26,27 Hyperinsulinemia increases ovarian androgen, IGF-1, and IGF-2 production in the liver. Insulin and IGF-1 increase the activity of 17-hydroxylase in the ovaries, causing excessive production of androgens, especially 17-hydroxyprogesterone (17- OHP). Indirectly, insulin potentiates the action of LH in the ovaries. 28,29 Another effect of hyperinsulinemia is a decrease in the hepatic production of SHBG (a sex- hormone carrier protein) and IGF-1 binding protein (IGFBP-I), contributing to greater Acne • Direct/indirect activation of IGF1 receptors in keratinocytes and fibroblasts causing infundibular keratinisation • Increased liver IGF 1 & 2 • Increased 17 hydroxylase activity in ovaries leading to ovarian androgen production • Increased 5 alfa reductase activity causing increased intracrine conversion of testosterone to the potent di hydro testosterone • Decreased SHBG and IGF BP1 formation in liver causing increased bioavilability of testosterone and IGF 1 • Formation of pro inflammatory cytokines FIGURE 3. Relationship between insulin resistance and acne. Acne Insulin abnormalities • Physiologic (puberty) • Physical inactivity • High glycemic foods • Dairy (mTORCI stimulators) • Decrease number and dysfunction of insulin receptors (PCO and obesity) Insulin Resistance/Raised Insulin Levels

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