Skin Manifestations of Insulin Resistance: From a Biochemical Stance to a Clinical Diagnosis and Management

Abstract

Worldwide, more than 1.9 billion adults are overweight, and around 600 million people suffer from obesity. Similarly, ~382 million individuals live with diabetes, and 40–50% of the global population is labeled at “high risk” (i.e., prediabetes). The impact of these two chronic conditions relies not only on the burden of illnesses per se (i.e., associated increased morbidity and mortality), but also on their increased cost, burden of treatment, and decreased health-related quality of life. For this review a comprehensive search in several databases including PubMed (MEDLINE), Ovid EMBASE, Web of Science, and Scopus was conducted. In both diabetes and obesity, genetic, epigenetic, and environmental factors overlap and are inclusive rather than exclusive. De facto, 70–80% of the patients with obesity and virtually every patient with type 2 diabetes have insulin resistance. Insulin resistance is a well-known pathophysiologic factor in the development of type 2 diabetes, characteristically appearing years before its diagnosis. The gold standard for insulin resistance diagnosis (the euglycemic insulin clamp) is a complex, invasive, costly, and hence unfeasible test to implement in clinical practice. Likewise, laboratory measures and derived indexes [e.g., homeostasis model assessment of insulin resistance (HOMA-IR-)] are indirect, imprecise, and not highly accurate and reproducible tests. However, skin manifestations of insulin resistance (e.g., acrochordons, acanthosis nigricans, androgenetic alopecia, acne, hirsutism) offer a reliable, straightforward, and real-time way to detect insulin resistance. The objective of this review is to aid clinicians in recognizing skin manifestations of insulin resistance. Diagnosing these skin manifestations accurately may cascade positively in the patient’s health by triggering an adequate metabolic evaluation, a timely treatment or referral with the ultimate objective of decreasing diabetes and obesity burden, and improving the health and the quality of care for these patients.

Cross-sectional study of the association between skin tags and vascular risk factors in a bariatric clinic-based cohort of Irish adults with morbid obesity

“…Insulin resistance, the key defect linking obesity and type 2 diabetes [4], also drives increased vascular risk [5]. However precise measurement of insulin resistance in routine clinical practice is usually not feasible [6]. Cutaneous markers of insulin resistance include acanthosis nigricans, androgenetic alopecia, acne, hirsutism and skin tags (acrochordons) [6][7][8].…”

“…However precise measurement of insulin resistance in routine clinical practice is usually not feasible [6]. Cutaneous markers of insulin resistance include acanthosis nigricans, androgenetic alopecia, acne, hirsutism and skin tags (acrochordons) [6][7][8]. These benign, pedunculated papular lesions are commonly located on the neck, axillae, eyelids and groin.…”

“…Skin tags are thought to arise from high levels of insulin and associated growth factors causing proliferation of epidermal fibroblasts [6]. They have been associated with various indicators of increased vascular risk including an adverse lipid profile [12][13][14][15][16], insulin resistance [17,18], impaired glucose metabolism [19,20], elevated blood pressure [14,21] and components of the metabolic syndrome [7,14,[21][22][23].…”

Serum irisin: A prognostic marker for severe acne vulgaris

“…Studies reported that sebocyte as well as adipocyte share the expression of some adipogenic factors as galectin‐12, resistin, stearoyl‐CoA desaturase (SCD), sterol response element binding protein‐1 (SREBP‐1), and the CCAAT enhancer binding protein α (C/EBPα) during their differentiation . Insulin resistance, the reduced responsiveness of target cells to insulin, has a wide range of skin manifestations such as acrochordons, acanthosis nigricans, androgenetic alopecia, acne, and hirsutism . Irisin is a novel adipomyokine, secreted mainly by adipose tissue and muscles after cleavage of fibronectin type III domain‐containing protein 5 (FNDC5) in response to stimuli such as exposure to cold and physical exercise thus it called the “exercise hormone.” It has been found to be associated with anthropometric and biochemical parameters, other hormones and adipokines, obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome .…”

Insulin receptor plays a central role in skin carcinogenesis by regulating cytoskeleton assembly

“…Our research centers on the role of insulin and the IR in skin. Diabetes-associated skin pathologies are well documented (15)(16)(17)(18), including severely impaired wound healing leading to amputations and an increased risk of nonmelanoma skin cancer (6,19,20). However, the role of insulin and the IR in the development of these pathologies ABBREVIATIONS: DDW, double-distilled water; EM, electron microscopy; IF, intermediate filament; IR, insulin receptor; KKO, keratin II knockout keratinoctye; PCNA, proliferating cell nuclear antigen; SIRKO, epidermal skin-specific insulin receptor knockout mouse; WT, wild type is not appreciated by most physicians and researchers.…”