Obesity and prediabetes affect a substantial part of the general population, but are largely underdiagnosed, underestimated, and undertreated. Prediabetes differs from diabetes only in the degree of hyperglycaemia consequent to the progressive decline in residual beta-cell function. Both prediabetes and diabetes occur as a consequence of insulin resistance that starts several years before the clinical onset of overt diabetes. Macrovascular complications in patients with diabetes are mainly caused by insulin resistance. This is why in prediabetes, the overall cardiovascular risk is, by all means, similar to that in patients with diabetes. It is important, therefore, to identify prediabetes and treat patients not only to prevent or delay the onset of diabetes, but to reduce the cardiovascular risk associated with prediabetes. This review provides an overview of the pathophysiology of prediabetes in patients with obesity and the progression toward overt diabetes. We have reviewed nutritional and pharmacological approaches to the management of obesity and reduced glucose tolerance, and the treatment of the major comorbidities in these patients, including hypertension, dyslipidaemia, and Metabolic dysfunction-associated Steatotic Liver Disease (MASLD), has also been reviewed. In patients with obesity and prediabetes, the nutritional approach is similar to that adopted for patients with obesity and diabetes; treatments of dyslipidaemia and hypertension also have the same targets compared to patients with diabetes. MASLD is a critical issue in these patients; in the prediabetic state, MASLD rarely progresses into fibrosis. This highlights the importance of the early recognition of this pathological condition before patients become diabetic when the risk of fibrosis is much higher. It is necessary to raise awareness of the clinical relevance of this pathological condition in order to prompt early intervention before complications occur. The single most important therapeutic goal is weight loss, which must be early and persistent.

Binge eating disorder (BED) is the most common eating disorder categorized in the DSM-V, but it is often not diagnosed in patients with obesity because it can be difficult to detect in these patients who often have altered eating patterns. In this narrative review, we have highlighted the most recent findings in the screening, diagnosis, and treatment of patients with BED and obesity. The results of our search showed that many BED patients are not obese, and most people with obesity do not have binge behavior. In the diagnostic assessment of these patients, it is important to evaluate not only the clinical and nutritional status and the presence of medical comorbidities, but also the psychological signs and symptoms related to psychiatric comorbidities to define the appropriate diagnosis and the consequent level of treatment. Well-tolerated drugs with action on both body weight and binges can be useful as a second-line complement to cognitive behavioral therapy (CBT). Specific guidelines are needed to obtain consensus on appropriate recommendations in patients with obesity and BED approaching bariatric surgery, taking into account not only weight reduction and clinical data, but also eating behaviors. Identification of BED is important for targeting individuals at high risk of obesity, adverse metabolic patterns, and cardiovascular disease. The challenge is to also achieve lasting weight loss in patients with BED and concomitant obesity.

BACKGROUNDEverolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs.PATIENTS AND METHODSA systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary.RESULTSThe present study included 22 different publications, including 874 patients and 456 extrapancreatic NETs treated with everolimus. Nine different primary sites of extrapancreatic NETs were found. The median progression-free survival ranged from 12.0 to 29.9 months. The median time to progression was not reached in a phase II prospective study, and the interval to progression ranged from 12 to 36 months in 5 clinical cases. Objective responses were observed in 7 prospective studies, 2 retrospective studies, and 2 case reports. Stabilization of the disease was obtained in a high rate of patients, ranging from 67.4% to 100%. The toxicity of everolimus in extrapancreatic NETs is consistent with the known safety profile of the drug. Most adverse events were either grade 1 or 2 and easy manageable with a dose reduction or temporary interruption and only rarely requiring discontinuation.CONCLUSIONTreatment with everolimus in patients with extrapancreatic NETs appears to be a promising strategy that is safe and well tolerated. The use of this emerging opportunity needs to be validated with clinical trials specifically designed on this topic.IMPLICATIONS FOR PRACTICEThe present study reviewed all the available published data concerning the use of everolimus in 456 extrapancreatic neuroendocrine tumors (NETs) and summarized the current knowledge on the efficacy and safety of this drug, not yet approved except for pancreatic NETs. The progression-free survival rates and some objective responses seem promising and support the extension of the use of this drug. The site-by-site analysis seems to suggest that some subtypes of NETs, such as colorectal, could be more sensitive to everolimus than other primary NETs. No severe adverse events were usually reported and discontinuation was rarely required; thus, everolimus should be considered a valid therapeutic option for extrapancreatic NETs.

UNLABELLED Hypertensive patients are at higher risk of pre-diabetes (impaired fasting glucose IFG and impaired glucose tolerance IGT) and type 2 DM. This study was done to examine whether some general, anthropometric, hormone, and metabolic parameters are different between subjects with normal and impaired glucose metabolism (IGM) in hypertensive subjects, thus possibly identifying some variable characterizing glucose metabolism derangement in these patients. A cohort of 134 hypertensive patients, 55 women and 79 men, aged 37-70 years, were examined. IGM patients were considered those showing IFG and/or IGT or type 2 DM after an oral glucose tolerance test (OGTT), and/or HbA1c > 48 mmol/l (6.5%) and/or glucose levels >155 mg/dL after 1 hour of the OGTT. Body mass index (BMI), waist circumference, and fasting insulin, TSH, FT3, FT4, glucose, and lipid (cholesterol, HDL-cholesterol and triglycerides) plasma concentrations were measured. Insulin resistance was also assessed by the homeostasis model assessment (HOMAIR). RESULTS Waist circumference (p < 0.05), fasting glucose (p < 0.05) and insulin levels (p < 0.05) and HOMAIR (p < 0.05) were significantly higher in patients with IGM than in control group. All other investigated parameters, as well as the number of antihypertensive drugs per single patient, were not different between the two groups. CONCLUSIONS The present study, performed in a selected population of hypertensive subjects, shows that derangement of glucose metabolism is associated to central fat accumulation, hyperinsulinemia and insulin resistance.

Monocyte chemoattractant protein 1 (MCP-1) has been implicated in the recruitment of monocytes to atheroma and of monocytes and macrophages to adipose tissue. The aim of the study was to examine whether MCP-1 levels are associated independently with the main thermogenetic hormones (serum TSH and thyroid hormones and 24-h urinary catecholamines) and insulin resistance in a population mainly represented by overweight and obese women. A cohort of 100 consecutive euthyroid women, aged 18–65 years, and with a wide range of BMI, was examined. Central fat accumulation (indirectly measured by waist circumference), fasting MCP-1 plasma levels, and TSH, FT 3 , FT 4 , insulin, glucose, and lipid (cholesterol, HDL-cholesterol and triglyceride) serum concentrations, and 24-h urinary catecholamines were measured. Insulin resistance was estimated by homeostasis model assessment (HOMA IR ). MCP-1 levels were directly associated with BMI ( p < 0.001), waist circumference ( p < 0.001), insulin ( p < 0.001), HOMA IR ( p < 0.001), diastolic blood pressure (DBP) ( p < 0.001), systolic blood pressure (SBP) ( p < 0.001), triglycerides (TG) ( p < 0.05), and 24-h urinary noradrenaline ( p < 0.05), and negatively correlated with HDL-cholesterol ( p < 0.01). When a multiple regression analysis was performed with MCP-1 as the dependent variable, and only parameters showing a significant univariate association with MCP-1 were considered as the independent variables, MCP-1 maintained an independent positive association with insulin ( p < 0.01), and DBP ( p < 0.05). When insulin was replaced by HOMA IR in the regression analysis, MCP-1 maintained an independent positive association with HOMA IR ( p < 0.05), DBP ( p < 0.05), and BMI ( p < 0.05). In conclusion, this study suggests that insulin, BMI, and diastolic blood pressure cooperate independently in increasing MCP-1 levels, whereas thyroid hormones and catecholamines have no apparent influence on this chemokine.