Metformin is considered, in conjunction with lifestyle modification, as a first-line treatment modality for type 2 diabetes mellitus (DM). Recently, several clinical studies have reported reduced incidence of neoplastic diseases in DM type 2 patients treated with metformin, as compared to diet or other antidiabetic agents. Moreover, in vitro studies have disclosed significant antiproliferative and proapoptotic effects of metformin on different types of cancer. Metformin acts by activating AMP-activated protein kinase (AMPK), a key player in the regulation of energy homeostasis. Moreover, by activating AMPK, metformin inhibits the mammalian target of rapamycin complex 1 (mTORC1) resulting in decreased cancer cell proliferation. Concomitantly, metformin induces activation of LKB1 (serine/threonine kinase 11), a tumor suppressor gene, which is required for the phosphorylation and activation of AMPK. These new encouraging experimental data supporting the anti-cancer effects of metformin urgently require further clinical studies in order to establish its use as a synergistic therapy targeting the AMPK/mTOR signaling pathway.

Background: The task of diagnosing growth hormone deficiency (GHD) in adults is cumbersome because of the paucity of biological endpoints. Consequently, over the past decade different organizations have attempted to develop homogeneous criteria and methodology for worldwide use. GHD should be biochemically confirmed within an appropriate clinical context – but only if there is the intention to treat. Clinically, patients investigated for GHD should include those with signs and symptoms or a past history of hypothalamo-pituitary dysfunction and those with a history of cranial irradiation, tumour treatment, traumatic brain injury or subarachnoid haemorrhage. Conclusions: Subjects with ≥3 pituitary hormone deficiencies plus a low insulin-like growth factor I level do not need provocative testing. For those who must be tested, arguably the most commonly used provocative tests are the insulin tolerance test and the glucagon, GH-releasing hormone (GHRH) + arginine and GHRH + GH-releasing hexapeptide tests. Cutoffs differ across tests and results may be influenced by gender, age, body mass index and the assay reference preparation.

Increase in obesity pandemic all over the world consequently leads to the investigation of possible causes. In addition to the traditional explanation using the so-called caloric model, the field of endocrine disruptors (EDs), especially subgroup called obesogens, offered more light on the pathogenetic mechanisms involved. After the Second World War a correlation between an increased production of exogenous pollutants and actual obesity epidemic was suggested. "Obesogen hypothesis" implies that molecules called obesogens inadequately stimulate the development of adipose cells and lipid accumulation in existing adipose cells, as well as change metabolic balance or hormonal control of appetite and satiety, leading to an increase in body fat mass. The list of obesogens includes some industrial chemicals, biocides, pharmaceuticals, pollutants, and smoke. EDs from the group of obesogens may exert their effects by the impairment in the programming development of adipocytes, by an increase in energetic depot in the adipose tissue, and by influencing neuroendocrine control of appetite and satiety. Increased scientific evidence on obesogens and their mechanisms of action may help to prevent obesity and mitigate deleterious effects of the environment on human life and development. New translational studies are needed to explain the possible mechanism proposed.

Women with polycystic ovary syndrome (PCOS) are at increased risk for dysglycemia and type 2 diabetes compared to healthy BMI-matched women of reproductive age: robust evidence exists supporting this notion. The presence of altered glycemic status in young women with the syndrome presents a distinct challenge for the clinician for several reasons. Firstly, the reported incidence of this disorder varies among the limited available studies. Furthermore, there is a lack of consensus on the best screening method, which women to screen, at what frequency, and which strategies need to be implemented to reduce the above risk. We provide data regarding the prevalence of dysglycemia in young women suffering from PCOS and the pathophysiological mechanisms underlying the disorder. In addition, we present evidence suggesting universal screening with the oral glucose tolerance test in young women with the syndrome, irrespective of age or BMI status, to identify and manage glycemic abnormalities in a timely manner. Regarding follow-up, oral glucose testing should be carried out at regular intervals if there are initial abnormal findings or predisposing factors. Finally, the efficacy of a well-balanced diet in conjunction with regular exercise and the use of non-pharmacologic agents in this specific population is discussed.

Summary Background National guidelines for treating type 2 diabetes in the Balkans generally follow European guidelines. The current study was undertaken to estimate the rate of glycated hemoglobin (HbA1c) measurements and level of HbA1c control in diabetic patients treated in regular clinical practice settings in the Balkans and to evaluate if providing HbA1c measurements improves adherence to treatment guidelines. Methods This cross-sectional study enrolled type 2 diabetic patients treated by 79 primary care physicians and 102 specialists. The participants were provided with HbA1c measuring devices to measure HbA1c during regular office visits and a physician survey evaluated HbA1c the results feedback. Relevant clinical, demographic, drug treatment and specialist referral data were extracted from patient charts. Descriptive statistics and stepwise multivariate regression analysis were used. Results Among 1853 patients included (average age 63.5 ± 10.7 years, 51% male) the average diabetes duration was 8.9 ± 7.1 years, 40% of patients had HbA1c measured every 6 months and 34% every 12 months (or less frequently). The rate of 6‑month measurement was higher among specialists (43%) vs. primary care physicians (32%, p < 0.01). The average HbA1c was 7.3 ± 1.5 and 35% of patients achieved the target HbA1c level of < 6.5%. Metformin monotherapy was prescribed to 28% of patients and metformin + sulphonylurea to 23%, 55% of patients on metformin monotherapy and 32% of patients on dual therapy metformin + sulphonylurea achieved the target HbA1c < 6.5%. Treatment remained unchanged in 91% and was stepped up in only 7.2% of patients. Physicians were not surprised (in 79% of patients) or were pleasantly surprised (in 11%) by the HbA1c results at the time of visit. Average diabetes duration and patient use of home glucometers were associated with the level of disease control. Conclusions The rates of HbA1c measurements remain low in the Balkans, although higher among specialists. Over 60% of patients, mostly treated with traditional oral antidiabetics did not achieve disease control. Providing convenient HbA1c measurement devices was not associated with a marked change in diabetes management. Future research is needed to evaluate the impact of these treatment patterns on long-term outcomes and costs to society.