The aim of this study was to investigate the phenotypic parameters and associated factors characterizing the development of glucose intolerance in polycystic ovary syndrome (PCOS). Among the 121 PCOS female subjects from the Mediterranean region, 15.7 and 2.5% displayed impaired glucose tolerance and type 2 diabetes, respectively. These subjects were included in a single group of overweight or obese subjects presenting with glucose intolerance (GI) states. PCOS women with normal glucose tolerance (81.8%) were subdivided into two groups: those who were overweight or obese and those of normal weight. Metabolic and hormonal characteristics of the GI group included significantly higher fasting and glucose-stimulated insulin levels, more severe insulin resistance, hyperandrogenemia, and significantly higher cortisol and androstenedione responses to 1-24 ACTH stimulation. One important finding was that lower birth weight and earlier age of menarche were associated with GI in PCOS women. Frequency of hirsutism, oligomenorrhea, acne, and acanthosis nigricans did not characterize women with GI. Our findings indicate that PCOS patients with GI represent a subgroup with specific clinical and hormonal characteristics. Our observations may have an important impact in preventative and therapeutic strategies. Diabetes 53: 2353-2358, 2004 P olycystic ovary syndrome (PCOS) affects 5-10% of women during their reproductive age (1,2) and is one of the most common causes of female infertility (1). The major clinical manifestations of the syndrome in adults are chronic anovulation, menstrual abnormalities, and hyperandrogenism (1). Most PCOS women present with insulin resistance and hyperinsulinemia (1), which play an important role in the pathogenesis of PCOS by modulating both ovarian and adrenal androgen production and decreasing sex hormoneϪbinding globulin (SHBG) liver synthesis and blood levels (3).Studies in American and Asian subjects have shown that, compared with the general population, women with PCOS have an increased risk for impaired glucose tolerance (IGT) and type 2 diabetes (4 -6), with a tendency toward early development of glucose intolerance (GI) states (7). However, to our knowledge, no studies have been performed on subjects from the Mediterranean region. The strong connection between PCOS and GI states is further emphasized by the high prevalence of polycystic ovarian morphology found on ultrasound scans in premenopausal women with type 2 diabetes (8) and those with previous gestational diabetes (9).As has been seen in the general population (10), there is evidence that insulin resistance may play a major pathophysiological role in the development of GI in PCOS women (11,12). The decreased insulin sensitivity in PCOS women appears in fact quite similar to that found in type 2 diabetic patients and to be relatively independent of obesity, fat distribution, and lean body mass (13). On the other hand, there is strong evidence that obesity per se, particularly the abdominal phenotype, represents an important indepe...

In a previous study we were the first to describe a negative correlation between circulating ghrelin concentrations and androgen levels in human plasma, suggesting an interaction between ghrelin and the endocrine regulation of reproductive physiology. We now investigated a potential direct regulatory influence of circulating androgens on plasma ghrelin levels. Fourteen obese women with polycystic ovary syndrome (PCOS) on a hypocaloric diet were randomly assigned to treatment groups (open-labeled design), receiving either placebo (no.=7) or the antiandrogen flutamide (no.=7) for 6 months. Anthropometry, visceral (VAT) and subcutaneous (SAT) adipose tissue (quantified by computerized tomography), plasma hormone levels, insulin sensitivity indexes (Quantitative Insulin-Sensitivity Check Index-QUICKI) and Homeostatic Model Assessment applied to the oral glucose tolerance test (HOMA(OGTT)) were evaluated at baseline and at the end of the study. Body weight decreased and insulin resistance indexes improved in both groups. A tendency toward a greater loss of VAT was observed in the flutamide group. Only in the flutamide group was a significant reduction of androgens levels observed. Plasma ghrelin levels significantly increased following treatment with flutamide, while ghrelin remained unchanged in the placebo group. We observed a negative correlation between changes of ghrelin levels and changes of androgen plasma concentration in the flutamide-treated group. In the same group a positive correlation was found between plasma ghrelin changes and insulin sensitivity as expressed by HOMA(OGTT). Analysis in a multiple regression model, however, showed that plasma ghrelin changes were mainly due to changes of androgen levels rather than improved insulin sensitivity. We, therefore, conclude that androgens are independent modulators of circulating ghrelin concentrations.

Aim: In this systematic review, guidelines on non-alcoholic fatty liver disease (NAFLD) were evaluated, aiming at a guideline synthesis focusing on diagnosis and staging.Methods: A systematic literature search was conducted on any relevant database or institutional website to find guidelines on NAFLD assessment intended for clinical use on humans, in English, published from January 2010 to August 2020. Included guidelines were appraised using the AGREE II Instrument; those with higher scores and intended for use in adult patients were included in a comparative analysis.Results: Fourteen guidelines were included in the systematic review, eight of which reached an AGREE II score sufficiently high to be recommended for clinical use, of which one developed for pediatric patients only. British and North American guidelines received the highest scores. Most guidelines recommend a screening or case-finding approach in patients with metabolic risk factors who are at increased risk of steatohepatitis or fibrosis. Ultrasound is mostly recommended to confirm steatosis, while the presence of metabolic syndrome, liver function tests, fibrosis scores, and elastographic techniques may help in selecting high-risk patients to be referred to the hepatologist, who may consider liver biopsy, although referral criteria for liver biopsy are not clearly defined. Most guidelines identify the development of noninvasive tests to replace liver biopsy as a research priority. Conclusion:Several high-quality guidelines exist for NAFLD assessment, with no complete agreement on whether to screen high-risk patients and on the tests and biomarkers suggested to stratify patients and select those to be referred to liver biopsy.

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