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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21 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 action of free testosterone and IGF-1, respectively, in target cells. In-vitro studies have shown that insulin and IGF-1 might act with androgens to stimulate growth of hair follicles. Hyperinsulinemia can also increase the action of 5α-reductase, leading to increased conversion of testosterone into dihydrotestosterone. 30,31 A Western diet is characterized by high glycemic load and increased levels of milk/ dairy protein, containing abundant amounts of branched-chain amino acids (leucine, isoleucine, and valine). These two dietary stimuli overstimulate a kinase termed mammalian target of rapamycin complex 1 (mTORC1). The activation of mTORC1 signaling is involved in both acne pathogenesis (altering sebaceous gland homeostasis with the promotion of cell growth and proliferation) and IR (stimulating the kinase S6K1, which negatively controls insulin signaling at the level of insulin receptor substrate-1 phosphorylation). 32 Insulin resistance has been recognized as an inflammatory disease, and there is a close relation between inflammatory acne and insulin resistance. 33,34 To date, there is no single test that can diagnose insulin resistance. A World Health Organization (WHO) consensus group concluded that the Insulin Sensitivity Index (SI) of the lowest 25 percent of a general population can be considered insulin-resistant. Insulin sensitivity shows ethnical- and gender- based variations. 35–37 The hyperinsulinemic euglycemic clamp technique, considered the gold standard for diagnosing insulin resistance, is impractical in a clinical setting. HOMA IR might be a more practical alternative as its value is calculated using an equation (Figure 4) and is considered to replicate the clamp technique. 38 A HOMA IR cut-off value of 2.5 has been identified to diagnose metabolic syndrome in urban Indian adolescents. 39 An Indian study of adults identified a cut-off value of 2.41 to diagnose insulin resistance. 40 The OGTT with insulin measurements at fasting and two hours after 75g glucose ingestion is a practical approach to diagnose insulin resistance. WHO defines the upper level of normal fasting blood glucose as 110mg/ dL; the American Diabetes Association has defined it as 100mg/dL. 41 An Indian consensus group has recommended that for the diagnosis of impaired fasting glucose, a cut-off value of 100mg/dL should be applied to Asian Indians. 42 A fasting insulin level above 25mg/ dL is considered abnormal. 43 In a study of Caucasian women with obesity, a level of fasting insulin above 9µIU/mL was determined as a marker of pre-diabetes. 44 A recent study from Western India (where our study was conducted) recommends a cut-off level of 17mg/dL for diagnosis of hyperinsulinemia. 45 As insulin response pattern, post-glucose, varies considerably in patients with impaired fasting glucose and impaired glucose tolerance, fasting measurements are generally recommended in population studies. Measuring only fasting insulin levels is sometimes inadequate for a diagnosis of mild insulin resistance in women with acne. 46 There are very few studies defining cut-offs for post-load insulin. The cut-off value of 41µIU/ mL was used here in the present study and in another Indian study as well. 47 Other non- Indian studies have used a cut-off value of 35µIU/mL. 48,49 The glucose-insulin (GI) ratio at baseline, one, and two hours is lower in women with PCOS than in healthy controls. 50 A fasting GI ratio of less than 4.5 47 and a two-hour GI ratio less than 1 is supportive of a diagnosis of insulin resistance in women with PCOS. 51 It seems wise to perform an OGTT with HOMA IR calculation to avoid missing insulin resistance in patients with acne. Most of the data for cut-offs available to us are for patients with PCOS. Large-scale, cross-control studies in subjects who are acne prone compared to normal controls are needed to determine the cutoff levels of fasting and post-load insulin, HOMA IR, and GI ratios for diagnosis of insulin resistance in patients with acne. AMH. Excessive production of AMH secreted by growing follicles is now considered a feature of PCOS. Acne is the most common cutaneous manifestation of PCOS, 52 so dermatologists can play an important role in TABLE 2. Biochemical and hormone markers LABORATORY MARKER n (%) Fasting glucose >100mg/dL 7 (19.4%) Fasting insulin >17IU/mL 4 (11.1%) Post-load glucose >140mg/mL 0 Post-load insulin >41IU/mL 9 (25%) HOMA IR >2.5 17 (47%) Fasting GI ratio <4.5 1 (2.7%) Post-load GI ratio <1 1 (2.7%) LH levels > FSH levels 15 (41.6%) Serum testosterone (total) >56.94mg/dL 5 (13.8%) Serum AMH >6.8ng/mL 10 (27.7%) Serum vitamin D (D2+D3) <20ng/mL 28 (82.3%) Serum prolactin >25 ng/mL 11 (30.5%) TSH >6µIU/mL 2 (5.5%) HOMA IR: Homeostasis Model of Assessment of Insulin Resistance; GI: glucose-insulin; LH: leutinizing hormone; FSH: follicle stimulating hormone; AMH: anti-Müllerian hormone ; TSH: thyroid stimulating hormone Fasting Insulin (IU/L) x Fasting Glucose (mmol/L) 22.5 Or Fasting Insulin (IU/L) x Fasting Glucose (mg/dL) 405 FIGURE 4. HOMA IR (Homeostasis Model of Assessment of Insulin Resistance) equation

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