Adiponectin as a Marker of Peripheral Insulin Resistance in Adolescents with Polycystic Ovarian Syndrome (PCOS) and as a Tool to Suspect Insulin Receptor Defects

MARIA G BALLERINI; PAULA ALEJANDRA SCAGLIA; MIRTA GRYNGARTEN; SONIA BENGOLEA; MARIA G ROPELATO; ANALÍA FREIRE; ARCARI, ANDREA; BERGADÁ, IGNACIO

Cusco

Congreso; XXVI Reunión anual de la Sociedad Latinoamericana de Endorinologia Pediatrica; 2018

Decreased serum adiponectin levels are associatedwith obesity and peripheral insulin resistance (IR). PCOS isCharacterized by anovulation and hyperandrogenism and chronicfaq frequently is associated to IR. Some defects of Insulin ReceptorHave Been Proposed as Mechanisms to Explain ovarian hyperandrogenismin PCOS.Objectives: To explore adiponectin levels in PCOS adolescentsand to Evaluate if adiponectin would Identify potential Patientswith hyperandrogenism associated to defects in the insulin receptoror intracellular signal pathway ITS.Patients and Methods: Prospective cross-sectional study.Twenty PCOS adolescents (16.4 ± 2 years) diagnosed ACCORDINGTO AES standard criteria and 10 healthy adolescents cycling(16.0 ± 1.5 years) Were Studied. Fasting glucose, insulin, adiponectin,androgens (total and free testosterone, androstenedione) WereMeasured. HOMA-IR >2.5 was used a surrogate of IR.Results: 11/20 (55%) Patients Showed PCOS IR (4 with NormalBMI and 7 with high BMI). Adiponectin levels in PCOS Patientswith Increased BMI and insulin resistance lower than in WereBoth PCOS and controls with a normal BMI (ANOVA way on p =0.05). Significant correlations Between inverse adiponectin, BMI(r = ?0.79, p = 0.001) and HOMA-IR (r = ?0.53, p = 0.02) WereObserved In Patients with PCOS. Two Patients with high adiponectinlevels Were excluded from the regression model bivariantas outliers. Both unexpectedly high levels of ADH In Spite of adiponectinHaving the highest values of HOMA-IR. In one of them,a novel missense heterozygous variant in the domain of INSR tyrosinekinase was Identified (NM_000208.3 (INSR): c.3449T>C(p.Leu1150Pro)) and classified as likely pathogenic ApplyingACMG guidelines. Molecular study of insulin receptor gene fromthe other patient is under process.Conclusions: Adiponectin levels are negatively associated withBMI and the severity of peripheral insulin resistance, while serumandrogens do not seem to be related to them. Unexpectedly highlevels of Adiponectin in Patients with PCOS exhibit insulin resistanceWHO Should lead towards molecular studies to rule out insulinreceptor defects.