Seboreik Keratozu Olan Hastalarda İnsülin Direnci, Metabolik Sendrom Riski ve IGF-1 ve IGFBP-3 Düzeyleri ile İlişkisinin Araştırılması
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Seborrheic keratosis is the most common benign epidermal tumor of the skin. Its incidence increases with advancing age; however, the exact pathogenesis has not been fully enlightened. The relationship between seborrheic keratosis and insulin resistance or metabolic syndrome has not yet been investigated. EGFR expression is found to be increased in seborrheic keratosis in diabetic patients and intersection pathways between EGF and IGF-1 are shown during the development of benign skin tumors in the mouse model of diet-induced obesity. In this study, we aimed to compare the risk of insulin resistance and metabolic syndrome, and serum IGF-1 and IGFBP-3 levels in seborrheic keratosis patients with the control group and to investigate tissue IGF-1 and IGBP-3 expression in seborrheic keratosis. We also investigated the possible correlations of dermoscopic features with these clinical and histopathological findings. The study included 100 patients with at least one seborrheic keratosis and an equal number of age- and sex-matched controls. Patients with a previous diagnosis of diabetes, polycystic ovary syndrome and those who use drugs' known effects on insulin and carbohydrate metabolism were excluded. Fasting insulin, fasting blood sugar (FBS), HbA1c, serum lipids, liver enzymes, serum IGF-1, and IGFBP-3 levels were measured in all subjects, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated. Anthropometric measurements were performed in all subjects and metabolic syndrome diagnosis was made using National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and International Diabetes Federation (IDF) criteria. One of the lesions from each patient was removed with shave excision after dermoscopic examination and tissue IGF-1 and IGFBP-3 immunohistochemical stainings were performed. In the results, fasting insulin levels and HOMA-IR values were significantly higher in patients than in controls, and an increased risk for insulin resistance was found in the patient group (p<0.01). Metabolic syndrome frequency was found to be significantly higher in patients compared to controls according to both NCEP ATP III and IDF criteria (p<0.001). Body mass index (BMI), waist circumference measurements, and ALT, GGT, and LDL levels were significantly higher in the patient group than in the control group (p<0.05). Serum IGFBP-3 level was significantly higher in the patient group than in the control group (t=2,213, p=0,028). There was no significant difference between the groups in terms of serum IGF-1 levels (p>0,05), but the negative correlation with age seen in the normal population disappeared for serum IGF-1 in the patient group (p>0.05). In immunohistochemical examinations, positive cellular staining for IGF-1 at the granular layer was observed in both lesional and the adjacent normal skin. In addition, focal positivities with IGF-1 in lesion compared to normal skin were detected in one area in 23 cases (23.2%), in two areas in 19 cases (19.2%), and in three or more areas in 13 cases (13.1%). For IGFBP-3 immunohistochemistry, all cases demonstrated nuclear immunoreactivity of equal intensity and level and there was no statistically significant difference. In dermoscopic findings, negative correlations between hairpin vessels and fasting insulin level (p=0.038) and between fat fingers and fasting insulin level, FBS and HOMA-IR (p<0.01), between milium-like cysts and serum IGF-1 and IGFBP-3 levels (p=0,033 and p=0,002), and finally between the sharply demarcated borders and tissue IGF-1 expression (p<0.01) were found. A positive correlation was found between the total number of lesions and the serum IGF-1 level (r=0.250, p=0.012). In conclusion, our results suggest that patients with seborrheic keratosis have an increased risk of insulin resistance and metabolic syndrome, and in this respect, it may represent a cutaneous sign. In these patients, it will be useful to investigate the insulin resistance through fasting insulin level and HOMA-IR. Considering the results we have obtained, IGF-1 and IGFBP-3 may have a role in the pathogenesis of seborrheic keratosis in both serum and tissue. Further studies are needed to reinforce the association.