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The developmental origins of adult disease theory support the concept that undernourished fetuses are at risk of developing metabolic syndrome due to the energy-saving ‘Thrifty Phenotype’. This metabolic plasticity represents an evolutionary adaptation that allows individuals to resist the intense pressure caused by cyclically recurring periods of nutritional deprivation. A comprehensive review was conducted following an extensive literature search in the PubMed/Medline and EMBASE databases concerning reports on fetal/intrauterine growth restriction and its metabolic-related long-term outcomes. We only included articles written in English that were published before 1 July 2024. There are several underlying mechanisms and metabolic and endocrine adjustments shaped by the perinatal environment, and they all contribute to progression towards adult disease. From in utero malnutrition or other insults during the fetal period to fetal programing and postnatal catch-up growth, it is difficult to identify the exact moment when this adaptative phenomenon meant to assure fetal survival and to set children on their own physiological growth curves lose its beneficial effect, establishing the trajectory to obesity, insulin resistance, and other hallmarks of metabolic syndrome. With clinical correspondence to an altered body mass, composition, and eating behaviors, it is evident that the metabolic complications linked to FGR are intricate and arise from disturbances in several pathways and organs, but the underlying processes responsible for the long-term consequences are just starting to be understood. The lack of continuity in perinatal-to-pediatric FGR research sets the challenge of exploring new directions in future scientific opportunities. These will hopefully represent a cornerstone in the management of FGR-related metabolic disorders in children, preventing these disorders from evolving into adult disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a public health concern, linked with immune-metabolic dysfunction. While lifestyle and dietary modifications remain the cornerstone of MASLD management, the optimal dietary approach remains uncertain. Objectives: This systematic review aims to investigate the impact of model dietary patterns on metabolic outcomes in patients with MASLD and evaluate their effects in individuals with coexisting metabolic conditions, such as obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Methods: To conduct the review, PubMed, Scopus, Google Scholar, Cochrane CENTRAL, and ClinicalTrials.gov databases were searched for Randomized Controlled Trials (RCTs) on the adult population, published between January 2019 and September 2024, following PRISMA principles. The quality of the included RCTs was assessed qualitatively based on study characteristics. Results: The main findings of this review demonstrated that the use of interventions with dietary model based on Mediterranean diet (MED) and intermittent fasting (IF) approaches, such as alternative-day fasting (ADF) and time-restricted feeding regimens (TRF) may have potential in reducing body weight, BMI, and waist circumference, with additional benefits of improving glycemic control and reducing inflammation. The effects on hepatic functions, although limited, may be linked with reduced enzyme activity and liver stiffness. Additionally, the use of lacto-ovo-vegetarian diet (LOV-D) and the Dietary Approaches to Stop Hypertension (DASH) diet may offer additional health benefits, including blood pressure management. Conclusions: This review suggests that MED and IF-based strategies may reduce BW, improve glycemic control, and lower inflammation, with potential benefits for hepatic function. Further long-term studies are needed to confirm these effects and underlying mechanisms, which will allow for the optimization of protocols and ensure their safety in MASLD.

Introduction Sarcopenic obesity (SO) is characterised by the confluence of muscle deterioration and high adiposity. When non-surgical interventions prove insufficient, bariatric surgery (BS) becomes the primary approach. This study aimed to address BS effects on SO outcomes 1 year post-surgery among middle-aged women, also considering physical exercise’s impact. Methods Prospective single-centre study of 140 patients who underwent Roux-en-Y gastric bypass or sleeve gastrectomy between November 2019 and December 2022. Participants were categorised into tertiles according to SO’s diagnosis and severity (group 1—patients with the most severe SO; group 2—intermediate; group 3—the least severe or without SO), calculated considering the consensus issued by ESPEN and EASO in 2022. Evaluations of clinical and biochemical parameters were conducted before and 12 months after BS, and the variation was used for comparative purposes. Body composition was assessed using bone density scans. Linear regression analysis accounted for both surgery type and baseline body mass index (BMI). Results Before BS, SO prevalence in the overall sample was 89.3%, decreasing to 2.9% after BS. Group 1 had more body fat mass (56.9 vs 54.8 vs 50.7 kg, p < 0.001), total, trunk and leg fat at baseline and a significantly lower total skeletal muscle mass (47.2 vs 49.4 vs 51.8 kg, p < 0.001). One year post-BS, group 1 presented more weight loss (− 39.8 ± 11.4 kg, p = 0.031), BMI reduction (− 15.9 ± 4.6 kg/m 2 , p = 0.005) and lost more fat mass (− 32.6 vs − 30.5 vs − 27.9 kg, p = 0.005), but not total skeletal muscle mass (− 5.8 vs − 5.9 vs − 6.8 kg, p = 0.130). Remission rates for comorbidities were substantial among all groups, but more marked among patients within group 1 (type 2 diabetes mellitus 75%, hypertension 47.1% and dyslipidemia 52.8%). Engagement in physical exercise of any kind has increased post-BS (33.1% vs 79.1%). Conclusion Despite concerns about malabsorptive mechanisms potentially worsening muscle loss, patients with the most severe SO undergoing BS lost more fat mass while experiencing the smallest reduction in total skeletal muscle mass. Remission rates for comorbidities following BS were notable among all groups. Graphical abstract

Gestational diabetes mellitus (GDM) is a common condition with increasing prevalence worldwide. GDM is associated with an increased risk for maternal and neonatal complications. In this review we provide an overview of the most recent evidence on the long-term metabolic risk associated with GDM in the offspring. We conducted an extensive literature search on PubMed and Embase between February 2019 and December 2019. We performed a narrative review including 20 cohort studies, one cross-sectional study, and two randomized controlled trials. Our review shows that the prevalence of overweight/obesity and glucose intolerance is higher in children exposed to GDM compared to unexposed children. Maternal overweight is an important confounding factor, but recent studies show that in general the association remains significant after correction for maternal overweight. There is limited evidence suggesting that the association between GDM and adverse metabolic profile in the offspring becomes more significant with increasing offspring age and is also more pronounced in female offspring than in male offspring. More research is needed to evaluate whether treatment of GDM can prevent the long-term metabolic complications in the offspring.

It is well established that the maternal diet during the periconceptional period affects the progeny’s health. A growing body of evidence suggests that the paternal diet also influences disease onset in offspring. For many years, sperm was considered only to contribute half of the progeny’s genome. It now appears that it also plays a crucial role in health and disease in offspring’s adult life. The nutritional status and environmental exposure of fathers during their childhood and/or the periconceptional period have significant transgenerational consequences. This review aims to describe the effects of various human and rodent paternal feeding patterns on progeny’s metabolism and health, including fasting or intermittent fasting, low-protein and folic acid deficient food, and overnutrition in high-fat and high-sugar diets. The impact on pregnancy outcome, metabolic pathways, and chronic disease onset will be described. The biological and epigenetic mechanisms underlying the transmission from fathers to their progeny will be discussed. All these data provide evidence of the impact of paternal nutrition on progeny health which could lead to preventive diet recommendations for future fathers.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent liver diseases, affecting up to 40% of adults and strongly associated with obesity and metabolic dysfunction. Despite the lack of approved pharmacological treatments, dietary interventions with plant-based foods, including the Mediterranean diet (MED), rich in numerous bioactive compounds may offer benefits for metabolic health and hepatic function. However, the role of individual plant foods in MASLD management remains unclear. Objectives: This review investigates the effects of specific plant-based foods, consumed as part of the MED and Dietary Approaches to Stop Hypertension (DASHs) diet, on metabolic outcomes, including hepatic function, in MASLD patients alone or in combination with comorbidities such as obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Methods: A systematic search was registered and conducted across nine databases to identify randomized controlled trials (RCTs) carried out in adults with MASLD and published between January 2020 and May 2025, following PRISMA guidelines. Results: Plant-based interventions including oranges, whole-grain products (WGPs), high-fiber buns (HFBs), beetroot juice (BJ), garlic, ginger, flaxseed, spirulina, rapeseed oil, sour tea, and green coffee extract (GCE) demonstrated mixed effects on metabolic and hepatic outcomes. GCE, flaxseed, and rapeseed oil improved anthropometric measures, while sour tea and ginger supported blood pressure control. WGPs, GCE, flaxseed, rapeseed oil, spirulina, ginger, and garlic were beneficial for glycemic regulation, whereas WGPs, HFBs, BJ, golden flaxseed, rapeseed oil, and garlic improved lipid profiles. Liver enzymes improved following consumption of WGPs, BJ, sour tea, flaxseed oil, and garlic, and hepatic steatosis was reduced after intake of oranges, WGPs, HFBs, BJ, flaxseed powder, rapeseed oil, and garlic powder. Conversely, a solely fruit-rich diet (FRD) had negative effects across all outcomes. Conclusions: Plant-based foods improved metabolic outcomes, with WGPs, HFBs, beetroot, oranges, sour tea, flaxseed oil, and garlic providing specific benefits for liver health. Further research is needed to validate these effects and ensure their safety in MASLD management.

Background Metabolic surgery induces rapid remission of type 2 diabetes mellitus (T2DM). There is a paucity of high level evidence comparing the efficacy of the laparoscopic Roux-en-Y gastric bypass (RYGB) and the laparoscopic one-anastomosis gastric bypass (OAGB) in glycemic control. Also, the mechanisms that drive the conversion of T2DM in severe obese subjects to euglycemia are poorly understood. Methods The DIABAR-trial is an open, multi-center, randomized controlled clinical trial with 10 years follow-up which will be performed in 220 severely obese patients, diagnosed with T2DM and treated with glucose-lowering agents. Patients will be randomized in a 1:1 ratio to undergo RYGB or OAGB. The primary outcome is glycemic control at 12 months follow-up. Secondary outcome measures are diverse and include weight loss, surgical complications, psychologic status and quality of life, dietary behavior, gastrointestinal symptoms, repetitive bloodwork to identify changes over time, glucose tolerance and insulin sensitivity as measured by mixed meal tests, remission of T2DM, presence of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in liver biopsy, oral and fecal microbiome, cardiovascular performance, composition of bile acids, and the tendency to develop gallstones. Discussion The DIABAR-trial is one of the few randomized controlled trials primarily aimed to evaluate the glycemic response after the RYGB and OAGB in severe obese patients diagnosed with T2DM. Secondary aims of the trial are to contribute to a deeper understanding of the mechanisms that drive the remission of T2DM in severe obese patients by identification of microbial, immunological, and metabolic markers for metabolic response and to compare complications and side effects of RYGB and OAGB. Trial registration ClinicalTrials.gov NCT03330756 ; date first registered: October 13, 2017.

The effect of age on outcomes after simultaneous pancreas-kidney transplantation (SPK) among type II diabetes (T2DM) recipients remains inconclusive. This study aimed to analyze the relationship between the age at time of transplantation and mortality, graft loss and metabolic profiles of T2DM SPK recipients. A retrospective cohort consisting of T2MD SPK recipients in a single transplant center was established. The baseline clinical characteristics and outcomes were collected and analyzed based on the age groups divided by 55-year-old. Time-to-event data analysis was performed using Kaplan-Meier method, and competing risk method was adopted to calculate the cumulative incidence of graft loss. A mixed regression model was applied to compare metabolic outcomes including glycated hemoglobin (HbA1c), fasting blood glucose, triglyceride, cholesterol, low-density lipoprotein, and higher estimated glomerular filtration rate (eGFR). 103 T2DM SPK recipients were included, of which 35 were > = 55 years old and 68 were < 55 years old. Baseline characteristics were comparable between age groups. The results indicated that comparable 5-year survival outcomes between groups with functioning grafts perioperatively. Additionally, no relationship of age with graft loss, complications and metabolic outcomes was detected.

Background: Pediatric obesity represents a multifactorial condition in which gut microbiota dysbiosis, low-grade systemic inflammation, and metabolic dysfunction are intricately connected. Objectives: This systematic review sought to evaluate and integrate current findings regarding the interactions between gut microbial composition, dietary influences, inflammatory status, and metabolic outcomes in obese pediatric populations. Methods: A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted for studies published from January 2010 onward. Eligible studies comprised randomized controlled trials, and cohort, cross-sectional, and longitudinal designs involving individuals aged ≤18 years. Study quality was appraised using the NIH Study Quality Assessment Tool. Results: Sixteen studies fulfilled the inclusion criteria. Dysbiosis was consistently observed among obese children, characterized by alterations in microbial diversity and abundance associated with increased inflammation and adverse metabolic profiles. Dietary interventions, notably symbiotic supplementation and adherence to Mediterranean diet patterns, were associated with favorable modulation of gut microbiota and inflammatory parameters. The majority of studies demonstrated high methodological quality, although minor observational limitations were noted. Conclusions: Gut microbiota dysregulation plays a central role in the development of metabolic and inflammatory complications associated with pediatric obesity. Although dietary and microbiota-modifying strategies show therapeutic promise, their effectiveness must be substantiated through robust, long-term studies.

This meta-analysis aimed to evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) when compared to metformin and placebo in the management of body weight, glucose homeostasis and hormone levels in women polycystic ovary syndrome (PCOS). A systematic search of “PubMed”, “EMBASE”, “Cochrane Library”, “Web of Science” and “Google Scholar” was conducted up to October 2024 for randomized controlled trials involving adult women with PCOS treated with GLP-1RAs compared to metformin or placebo. The primary outcomes were changes in body mass index (BMI), body weight, waist circumference (WC), waist-to-hip ratio (WHR) and abdominal girth (AG). Secondary outcomes included glucose homeostasis (fasting glucose, fasting insulin, OGTT results and HOMA-IR), hormone levels (DHEAS, SHBG, total and free testosterone and FAI), lipid profiles (total cholesterol, HDL, LDL and triglycerides) and safety. GLP-1RAs significantly reduced BMI, body weight, WC, WHR and AG ( P  < 0.0001 in all cases). For glucose homeostasis, GLP-1RAs significantly reduced fasting insulin, glucose level at 2 h after OGTT, and HOMA-IR. There was also a reduction in HDL. All the other parameters measured were unchanged. In addition, GLP-1RAs increased nausea ( P  = 0.02), vomiting (0.04) and dizziness (0.03). GLP-1RAs effectively reduced body weight, BMI and insulin resistance in patients with PCOS, although they were accompanied by nausea, vomiting and dizziness. Further studies are needed to explore their long-term effects on glucose homeostasis and lipid profiles.