Background: Polycystic ovary syndrome (PCOS) is a frequent reproductive disease characterized by hyperandrogenism, oligo /anovulation, and polycystic aspects at ultrasound. In these last years, a body of evidence disclosed the frequent occurrence in PCOS patients of insulin resistance (IR) and compensatory hyperinsulinemia. Aim: To evaluate whether any relationship exists between IR, compensatory hyperinsulinemia and familial predisposition to diabetes. Methods: A group of overweight/obese PCOS patients (n = 84) was selected from our Clinic database according to the Rotterdam criteria and the following parameters were extracted from the database: insulin, C Peptide, aspartate amino transferase (AST), alanine amino transferase (ALT), HOMA (Homeostasis Model Assessment) index, total cholesterol, LDL (Low Density Lypoprotein), HDL (High Density Lypoprotein), and body mass index (BMI). The presence and absence of diabetes among first grade relatives (parents and/or grandparents) were also considered. The Hepatic Insulin Extraction (HIE) index was computed as a ratio between insulin and C-Peptide plasma levels. Results: PCOS patients with familial diabetes showed higher levels of ALT, AST, HOMA index, and HIE. Baseline insulin levels above 12 μU/mL were more frequently observed in PCOS with familial diabetes. HIE index, ALT, and AST were higher in these latter PCOS patients than in PCOS without diabetic first grade relatives, sustaining the hypothesis of an impaired liver clearance of insulin in the case of familial diabetes. Conclusions: According to our study, the presence of anamnestic evidence of familial diabetes together with baseline levels of insulin higher that 12 µIU/mL and elevated transaminase levels should be considered as a consistent clinical suspect of liver impairment that might trigger compensatory hyperinsulinemia and lead to NAFLD and liver steatosis.

Polycystic ovary syndrome (PCOS) is the most frequent endocrine-metabolic disorder among women at reproductive age. The diagnosis is based on the presence of at least two out of three criteria of the Rotterdam criteria (2003). In the last decades, the dysmetabolic aspect of insulin resistance and compensatory hyperinsulinemia have been taken into account as the additional key features in the etiopathology of PCOS, and they have been widely studied. Since PCOS is a complex and multifactorial syndrome with different clinical manifestations, it is difficult to find the gold standard treatment. Therefore, a great variety of integrative treatments have been reported to counteract insulin resistance. PCOS patients need a tailored therapeutic strategy, according to the patient’s BMI, the presence or absence of familiar predisposition to diabetes, and the patient’s desire to achieve pregnancy or not. The present review analyzes and discloses the main clinical insight of such complementary substances.

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