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The introduction of the term "Metabolic Steatotic Liver Disease" (MASLD) underscores the critical role of metabolic dysfunction in the development and progression of chronic liver disease and emphasizes the need for strategies that address both liver disease and its metabolic comorbidities. In recent years, a liver-focused perspective has revealed that altered endocrine function of the fatty liver is a key contributor to the metabolic dysregulation observed in MASLD. Due to its secretory capacity, the liver's increased production of proteins known as "hepatokines" has been linked to the development of insulin resistance, explaining why MASLD often precedes dysfunction in other organs and ultimately contributes to systemic metabolic disease. Among these hepatokines, fibroblast growth factor 21 (FGF21) and fetuin-A play central roles in regulating the metabolic abnormalities associated with MASLD, explaining why their dysregulated secretion in response to metabolic stress has been implicated in the metabolic abnormalities of MASLD. This review postulates why their modulation by GLP1-Ras may mediate the beneficial metabolic effects of these drugs, which have increased attention to their emerging role as pharmacotherapy for MASLD. By discussing the crosstalk between GLP1-Ras-FGF21-fetuin-A, this review hypothesizes that the possible modulation of fetuin-A by the novel GLP1-FGF21 dual agonist pharmacotherapy may contribute to the management of metabolic and liver diseases. Although research is needed to go into the details of this crosstalk, this topic may help researchers explore the mechanisms by which this type of pharmacotherapy may manage the metabolic dysfunction of MASLD.

Background: Type 2 diabetes (T2D) is a risk factor for female breast cancer (FBC). Obesity has also been associated with FBC, also depending on menopausal status. This study aimed to evaluate the impact of obesity and T2D on the development, aggressiveness, and invasiveness of FBC., Methods: Demographic, clinical, and histopathological data from 335 women with FBC were collected, and analyzed according to weight category (102 normal weight, 117 overweight, and 116 living with obesity) and the presence/absence of T2D., Results: Age at oncologic diagnosis was not statistically significantly different for body weight; women with overweight or obesity were more likely to have an oncologic diagnosis after menopause than normal weight ( p  < 0.001). The presence of overweight/obesity and T2D seemed to be associated with a higher incidence of metastasis, recurrence, and triple-negative breast cancer (TNBC) subtype ( p  < 0.001). Excess body weight was also associated with high histologic grade (G3) ( p  < 0.005)., Conclusions: These results confirm excess body weight and T2D as unfavorable prognostic factors in terms of the presence of the TNBC subtype, tumor metastasis, recurrence, and aggressiveness (G3 and Ki-67 > 20%). This study highlights the importance of prevention in all women, with early screening, and adequate nutritional programs., Competing Interests: We have no conflicts of interest to disclose., (© 2024 The Author(s). Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Background : Sex differences characterize the prevalence and attitudes toward weight management. Despite limited evidence suggesting greater weight loss in women with anti-obesity pharmacotherapy, sex-specific analysis remains underexplored. This retrospective study aimed to evaluate the sex-specific response to liraglutide 3.0 mg treatment in people with obesity without type 2 diabetes (T2D). Methods : Data were collected from 47 patients (31 women, 16 men) with age > 18 years; BMI ≥ 30 kg/m 2 ; absence of T2D; and exclusion of prior anti-obesity treatment, comorbidities, or bariatric surgery. Only patients who maintained the liraglutide 3.0 mg dose for at least 6 months were included. Results : Both sexes showed significant reductions in weight and BMI at 3 and 6 months. Men achieved greater weight loss (WL), BMI reduction, %WL, WL > 5%, and >10% than women, and they also showed more significant improvements in metabolic parameters (total and LDL cholesterol, Fibrosis-4 Index FIB-4). No significant sex differences were observed in glucose metabolism or renal function. Conclusions : This study showed a greater therapeutic effect of liraglutide 3.0 mg in men. Given men's higher risk of cardiovascular disease (CVD), and underrepresentation in clinical weight loss programs, these findings may increase male engagement and improve their CVD risk.

Insulin resistance is the main mechanism in a whole series of pathological conditions, which are not only of metabolic interest but also of a systemic type. This phenomenon means that the body's cells become less sensitive to the hormone insulin, leading to higher levels of insulin in the blood. Insulin resistance is a phenomenon that can be found in both men and women and in particular, in the latter, it is found mainly after menopause. Premenopause, hormonal fluctuations during the menstrual cycle, and the presence of estrogen can affect insulin sensitivity. Androgens, such as testosterone, are typically higher in men and can contribute to insulin resistance. In both sexes, different human body types affect the distribution and location of body fat, also influencing the development of diabetes and cardiovascular disease. Insulin resistance is also associated with some neurological and neurogenerative disorders, polycystic ovary syndrome, atherosclerosis, and some of the main neoplastic pathologies. A healthy lifestyle, including regular physical activity, a balanced diet, and self-maintenance, can help to prevent the onset of insulin resistance, regardless of gender, although the different habits between men and women greatly affect the implementation of preventative guidelines that help in fighting the manifestations of this metabolic disorder. This review may help to shed light on gender differences in metabolic diseases by placing a necessary focus on personalized medical management and by inspiring differentiated therapeutic approaches.

Background: Monoclonal antibodies are designed to target specific proteins of COVID-19 and can be used as a treatment for people with mild to moderate infection and at a high risk of severe disease. Casirivimab/imdevimab, sotrovimab, and Bamlanivimab/etesevimab have been authorized for emergency use in the treatment of COVID-19. However, during pregnancy, these drugs have not been extensively studied., Methods: A total of 22 pregnant women with mild to moderate infection were treated with three different monoclonal antibodies, and efficacy and safety were evaluated in the first period and until six months of follow-up., Results: No infusion/allergic reactions occurred. No fatal or adverse events were observed in the pregnant women or fetus. The time of negativization with sotrovimab was shorter in comparison to Imdevimav/casirivimab ( p = 0.0187) and Bamlanivimab/etesevimab ( p < 0.00001). The time of negativization with sotrovimab was earlier in comparison to Imdevimav/casirivimab (t-value: 2.92; p = 0.0052) in vaccinated patients and similar in comparison to Imdevimav/casirivimab (t-value: 1.48; p = 0.08). In unvaccinated patients, sotrovimab was faster to achieve negativization in comparison to Bamlanivimab/etesevimab (t-value: 10.75; p < 0.0005)., Conclusions: Pregnant COVID-19 patients receiving sotrovimab obtained better clinical outcomes. Pregnancy or neonatal complications were not observed after monoclonal treatment, confirming the safety and tolerability of these drugs in pregnant women.

Introduction: gut microbiota (GM) seems to be involved in the pathophysiology and progression of both metabolic syndrome (MS) and obesity. The aim was to investigate GM's composition in patients with severe obesity, candidates for bariatric/metabolic surgery BMS., Materials and Methods: Multicentre, prospective, cohort study, enrolling 84 patients with BMI 40-55 kg/m 2 , divided bymetabolic status (MS) inhealthy(group A), pre-MS (B), or MS (C)., Results: No differences were foundregarding anthropometric,nutritional parameters, except for vitamin D.As a whole the alpha and beta diversity examinations showed no statistical differences in GM profile. A total of 5/7 phyla with relative frequencies were identified above 0.1% (Actinobacteria,Bacteroidetes,Firmicutes,Proteobacteria,Verrucomicrobia).FusobacteriaandPatescibacteriarepresented the less abundant. There were no significant differences in the top ten genera.Data onBacteroidetes(inversely related to triglycerides and LDL and directly related to HDL levels) and onFirmicutes(opposite trend) relative abundances suggest no differences among the three conditions.No correlation between the relative abundance of themain phylaand plasmatic glucose levels was observed., Conclusions: In a selected cohort of patients with obesity, MS did not affect the preoperative GM's profile. Severe obesity, per se, seems to be an independent condition affecting GM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Aim: To assess the effect of the coronavirus disease 2019 (COVID-19) lockdown on glycaemic control in subjects with type 2 diabetes (T2D)., Materials and Methods: In this observational, multicentre, retrospective study conducted in the Lazio region, Italy, we compared the differences in the HbA1c levels of 141 subjects with T2D exposed to lockdown with 123 matched controls with T2D who attended the study centres 1 year before. Basal data were collected from 9 December to 9 March and follow-up data from 3 June to 10 July in 2020 for the lockdown group, and during the same timeframes in 2019 for the control groups. Changes in HbA1c (ΔHbA1c) and body mass index (ΔBMI) during lockdown were compared among patients with different psychological well-being, as evaluated by tertiles of the Psychological General Well-Being Index (PGWBS)., Results: No difference in ΔHbA1c was found between the lockdown and control groups (lockdown group -0.1% [-0.5%-0.3%] vs. control group -0.1% [-0.4%-0.2%]; p = .482). Also, no difference was found in ΔBMI (p = .316) or ΔGlucose (p = .538). In the lockdown group, subjects with worse PGWBS showed a worsening of HbA1c (p = .041 for the trend among PGWBS tertiles) and BMI (p = .022)., Conclusions: The COVID-19 lockdown did not significantly impact glycaemic control in people with T2D. People with poor psychological well-being may experience a worsening a glycaemic control because of restrictions resulting from lockdown. These findings may aid healthcare providers in diabetes management once the second wave of COVID-19 has ended., (© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Purpose: In morbid obesity nonalcoholic fatty liver disease (NAFLD) is endemic. Aim of this study is to evaluate the diagnostic accuracy of the most common noninvasive methods for identify NAFLD and fibrosis in a cohort of morbid obese population., Methods: Ninety morbid obese patients undergoing bariatric surgery (BS) and intraoperative liver biopsy were evaluated preoperatively with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and serum biomarkers for steatosis and fibrosis and liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) elastography. All nondiabetic patient (n = 77) underwent OGTT and calculation of Oral Glucose Insulin Sensitivity index (OGIS)., Results: In the entire cohort prevalence of NAFLD was 77%, NASH 24%, moderate/severe steatosis 50%, and significant fibrosis 14%. New cut-offs were evaluated for all steatosis score assessed in this population. In all patients with moderate/severe steatosis HOMA IR was significantly greater than 3.5. ALT, GGT, Triglycerides, HOMA IR, and ARFI increased with fibrosis grade (p 0.03, p 0.008, p 0.04, p 0.05, respectively) and AST to Platelet ratio (APRI) was the only noninvasive fibrosis score significantly increased in significant fibrosis (p 0.04). A combination of 1/OGIS and VAI was able to discriminate NASH from simple steatosis (NAFL) (p 0.02)., Conclusions: In morbid obese subjects, we calculated new cut-offs of the most common steatosis indexes and found that a score based on insulin resistance (1/OGIS) and abdominal obesity (VAI) could represent a way to identify morbid obese subjects at risk of NASH.

Background and Aim: Obese subjects are at high risk of nonalcoholic fatty liver disease (NAFLD) and diabetes (T2D) due to insulin resistance (IR). Since high glucose levels are as toxic as lipids for hepatic metabolism, we hypothesize that altered response to oral glucose tolerance test (OGTT) is associated to more severe NAFLD with significant/advanced liver damage., Methods and Results: We studied 90 subjects with morbid obesity (73F/17M, BMI = 43.2 ± 5,9 kg/m 2 ) undergoing bariatric surgery and intraoperative liver biopsy, and measured HbA1c, HOMA-IR (fasting Glucose x Insulin/22.5), OGTT glucose and insulin profile, and calculated OGIS (muscle insulin sensitivity), hepatic-IR (glucose [AUC 0-30 ] x insulin [AUC 0-30 ]) during OGTT, insulin response as (insulin [dAUC 0-120 ]/glucose [dAUC 0-120 ] or Insulinogenic Index (IGI = (I 30 -I 0 )/(G 30 -G 0 )). Patients were divided in 3 groups according to liver biopsy: A (no-NAFLD, 23%), B (simple steatosis (SS), 53%) and C (NASH, 24%) with similar age, gender and BMI. Diabetes was 0% in no-NAFLD, 13% in SS, 35% in NASH. During OGTT, OGIS decreased from A to C (422 vs 360 vs 338, p < 0.01). Increased insulin concentrations, HbA1c, HOMA-IR and OGIS, not Hep-IR, were strongly associated to hepatic steatosis (p = 0.03, p = 0.0001 and p = 0.01 respectively). Hepatic fibrosis stage was mild as most of the patients had fibrosis grade-1 (69% vs. 8% no fibrosis) and associated to fasting insulin, HbA1c and HOMA-IR. dAUC-I/dAUC-G was similar in the 3 groups, while only AUC-I was strongly associated to steatosis (r = 0.35, p = 0.005), but not to fibrosis., Conclusions: In morbid obesity indexes of IR, and not of insulin response, are markers of histological severity of liver disease., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objective: Obesity is one of the major health challenges throughout the world. The association between obesity and diabetes is well established because 90% of patients with type 2 diabetes mellitus (T2DM) show excess body weight. The aim of the study was to evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on morbid obesity and type 2 diabetes (T2DM) in the long-term follow-up., Methods: One hundred ninety-five obese patients, 78 with T2DM, were evaluated before and after LSG up to 10 years, to identify complete diabetes remission (FPG < 100 mg/dl, A1c < 6.0%), partial remission (FPG 100-125 mg/dl, A1c < 6.5%), or relapse., Results: Before surgery, body weight and BMI were 123 ± 21 kg and 44.6 ± 6.8 kg/m 2 respectively; at a mean follow-up of 7 years (range 4-10), body weight was 104.9 ± 18 kg and BMI 37 ± 6 kg/m 2 . Minimum weight was reached after 2 years. T2DM remission was observed in 66, 57, and 52% at short (< 2 years), medium (2-5 years), and long-term (> 5 years) follow-up respectively. Furthermore, 45.2% maintained complete remission for at least 5 years and about 36% showed a persistent but improved diabetes. None of the patients cured from diabetes had a duration disease greater than 8 years and a glycemic control requiring insulin. The prevalence of hypertension and dyslipidemia significantly decreased from 49 to 35% and from 51 to 40% respectively., Conclusions: LSG significantly improves body weight, diabetes, hypertension, and dyslipidemia in long-term follow-up.