Search Results (261)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the liver fat content in patients with obesity and T2D. However, its effect on liver-specific outcomes such as steatosis and fibrosis remains incompletely characterized. Low-energy ketogenic therapy (LEKT), a nutritional strategy characterized by carbohydrate restriction and nutritional ketosis, may enhance hepatic β-oxidation and reduce hepatic lipogenesis. To date, however, the combination of TZP and LEKT has not been studied in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the hepatic and metabolic effects of TZP combined with either LEKT or a conventional low-calorie diet (LCD) over a 12-week period. Methods: Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group. As primary endpoints, the controlled attenuation parameter (CAP, an index of hepatic steatosis) and liver stiffness measurement (LSM, an index of liver fibrosis) were assessed at the baseline and after 12 weeks using FibroScan^®. Secondary outcomes included changes in body mass index (BMI), glycated hemoglobin (HbA1c), and liver enzymes. Adherence to both diet and pharmacological treatment, as well as tolerability, were systematically monitored throughout the intervention period. Results: Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665). CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP −12.5%, p < 0.001; LSM −22.7%, p < 0.001) versus LCD (CAP −6.7%, p = 0.014; LSM −9.2%, p = 0.022). Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03). Conclusions: Based on these preliminary findings, we support the hypothesis that the combination of TZP and LEKT may be superior to TZP with an LCD in reducing hepatic steatosis and stiffness in individuals with obesity. Full article

Obesity and metabolic disorders remain major global health concerns, traditionally attributed to excessive caloric intake and poor diet quality. Recent studies emphasize that the timing of meals plays a crucial role in determining metabolic health. This review explores chrononutrition, a growing field that examines how food intake patterns interact with endogenous circadian rhythms to influence energy balance, glucose and lipid metabolism, and cardiometabolic risk. The circadian system, which includes a central clock in the suprachiasmatic nucleus and peripheral clocks in metabolic tissues, regulates physiological functions on a 24 h cycle. While light entrains the central clock, feeding schedules act as key synchronizers for peripheral clocks. Disrupting this alignment—common in modern lifestyles involving shift work or late-night eating—can impair hormonal rhythms, reduce insulin sensitivity, and promote adiposity. Evidence from clinical and preclinical studies suggests that early time-restricted eating, where food intake is confined to the morning or early afternoon, offers significant benefits for weight control, glycemic regulation, lipid profiles, and mitochondrial efficiency, even in the absence of caloric restriction. These effects are particularly relevant for populations vulnerable to circadian disruption, such as adolescents, older adults, and night-shift workers. In conclusion, aligning food intake with circadian biology represents a promising, low-cost, and modifiable strategy to improve metabolic outcomes. Integrating chrononutrition into clinical and public health strategies may enhance dietary adherence and treatment efficacy. Future large-scale studies are needed to define optimal eating windows, assess long-term sustainability, and establish population-specific chrononutritional guidelines. Full article

Thyroid hormones (THs) play a central role in cardiovascular and metabolic regulation, influencing lipid metabolism, insulin sensitivity and resting energy expenditure. Inherited disorders of impaired sensitivity to THs—including resistance to thyroid hormone alpha (RTHα) and beta (RTHβ), monocarboxylate transporter 8 (MCT8) deficiency and selenoprotein deficiency—lead to complex, multisystemic clinical features. Although these conditions are rare, with RTHβ being the most common and affecting about 1 in 20,000 newborns, they share clinical features with more prevalent thyroid disorders, such as hypothyroidism and hyperthyroidism, as well as neurological manifestations including muscle wasting and spasticity. These conditions present abnormal patterns of thyroid function and are associated with tissue-specific comorbidities such as arrhythmias, heart failure, dyslipidemia, hepatic steatosis, insulin resistance, and metabolic syndrome. To date, no targeted or controlled studies have evaluated the impact of lifestyle modifications in these patient populations. Therefore, this narrative review proposes plausible management strategies based on pathophysiological insights into the effects of thyroid hormones on target organs, combined with clinical reasoning and evidence extrapolated from related disorders. Physical exercise and diet may complement pharmacological treatments (e.g., levothyroxine or TRIAC) to improve cardiovascular and metabolic outcomes. In RTHβ, aerobic exercise enhances cardiovascular health, while a Mediterranean diet supports lipid control and glycemic parameters. In RTHα, physical exercise may aid neuromotor development, and a fluid-rich, fiber-moderated diet can alleviate constipation. In MCT8 deficiency, physiotherapy may improve mobility and relieve contractures, while nutritional support (e.g., feeding tube, gastrostomy) can be necessary to tackle feeding difficulties and reduce pulmonary complications. In selenoprotein deficiency, low-to-moderate physical exercise and an antioxidant-rich diet may protect against oxidative stress at several tissue levels. Although quantitative evidence is limited, this narrative review synthesizes current insights, providing a meaningful basis for future validation and research. Full article

Despite advances in technology, the overall management of type 1 diabetes mellitus (T1DM) remains suboptimal. The idea of restricting carbohydrate intake to decrease glycemic spikes and insulin requirements has been revisited in recent years. After impressive results in the fields of type 2 diabetes (T2DM) and epilepsy, low-carbohydrate (LCD) and ketogenic (KD) diets have gained renewed interest as a possible treatment option for T1DM. In this narrative review, we discuss the available data regarding LCDs and KDs in both the adult and pediatric populations. Research data is still scarce, as most studies are short-term and show considerable heterogeneity in dietary composition and patient outcomes. In general, carbohydrate restriction enhances glycemic control by reducing postprandial glucose excursions, improving time-in-range, and lowering HbA1c, with conflicting effects on other parameters such as lipid profile and body weight. Adverse effects such as hypoglycemia and diabetic ketoacidosis are rarely reported, although some concerns have been raised regarding growth in children. The correct implementation of these diets requires a multidisciplinary approach by highly specialized healthcare professionals, who will address the medical, social, and psychological concerns that a restrictive diet entails. Large-scale and long-term studies are needed to provide more robust data before carbohydrate restriction can be widely applied to patients with T1DM. Full article

Obesity is a global health concern that elevates the risk of noncommunicable diseases (NCDs) such as type 2 diabetes, cardiovascular disease, and certain cancers. Phaseolus vulgaris (white bean) contains α-amylase inhibitors (αAIs) that can reduce carbohydrate digestion and absorption, potentially mitigating obesity and metabolic syndrome. This study investigated the impact of P. vulgaris extract (PVE) on obese rats. Male Wistar rats were fed either a standard diet (SD) or a cafeteria diet (CAF) for 17 weeks to induce obesity. Subsequently, rats in each dietary group were randomly assigned to receive a vehicle, low-dose PVE (200 mg/kg), high-dose PVE (300 mg/kg), or metformin (200 mg/kg) via an oral gavage for 6 weeks. The CAF group exhibited significantly greater weight gain compared to the SD group. In the CAF group, a low dose of PVE lowered postprandial glycemia during an oral glucose tolerance test (OGTT) at 60 and 120 min and decreased food and energy intake during weeks 17–20 and 18–19, respectively. In the SD group, a high dose of PVE reduced glycemia at 90 min in the OGTT, as well as body weight gain, food intake, and energy intake during week 17. However, the overall areas under the glucose curves in the OGTT were not significantly different across treatment groups (p > 0.05), and while individual time points showed changes, the overall glucose exposure (AUC) was not significantly altered. In conclusion, the αAIs present in P. vulgaris demonstrate the potential to reduce body weight, weight gain, glycemia, total cholesterol, and triglycerides in vivo, but in the CAF group, neither PVE dose significantly altered the TC or TG. This study provides strong support for further exploring Phaseolus vulgaris extract as a valuable functional ingredient in the food industry, particularly for developing products that aid in weight management and glycemic control. Full article

Chronic kidney disease (CKD) is a widespread condition with significant cardiovascular risks and a progression to end-stage kidney failure. In recent years, increasing attention has been paid to the role of dietary interventions as a factor capable of influencing disease trajectory. This review summarizes the current observational and interventional evidence on various dietary approaches in patients with CKD and kidney transplants (KTs), including Mediterranean, plant-based, and low-protein diets. A balanced Mediterranean diet, rich in fruits, vegetables, whole grains, fish, and unsaturated fats, shows promises in improving the prognosis for CKD patients. Plant-based diets, which emphasize legumes, vegetables, and grains while minimizing animal protein, improve blood pressure and the glycemic and lipid control. Low-protein diets (LPDs), typically providing less than 0.6 g/kg/day of protein, may reduce the CKD progression and nitrogen burden, further delaying the initiation of dialysis. In conclusion, diets represent a valuable and underutilized therapeutic strategy in the management of CKD and KTs, influencing disease progression and patient outcomes. Full article

Millets, often known as “nutri-cereals”, have garnered renewed global interest due to their numerous health benefits, rich nutritional composition, resilience to extreme climatic conditions, and minimal environmental footprint. The advent of rice and wheat as staple foods in the 1960s led to drastic decline in millet cultivation worldwide. Recognizing the importance of millet, the United Nations (UN) declared 2023 as the International Year of Millets in an effort to accomplish Sustainable Development Goal 2 (SDG-2), i.e., zero hunger, by increasing millet production and fostering research and development to improve the integration of these grains into mainstream food systems. In recent years, global production of millets has surged, with India leading as the top producer. Millets are nutritionally advantageous, consisting of carbohydrates, antioxidants, and biologically active compounds such as flavonoids, carotenoids, phenolic acids, minerals, and vitamins. Incorporating millets into a balanced diet can help control and prevent diseases such as cardiovascular disease, diabetes, inflammation, and malnutrition due to their enriched vital nutrients, low glycemic index, and gluten-free nature. This indicates a transition of millets from an “orphan crop” to being used as ingredients for products (with or without fermentation) that are nutrient-rich, climate-resilient, sustainable, and health-promoting. Full article

Type 2 diabetes mellitus (DM2) is a metabolic disorder characterized by chronic hyperglycemia associated with low insulin production and/or insulin resistance. A high-fat diet (HFD) combined with a low dose of streptozotocin (STZ) in an animal model produces a disease that mimics type 2 diabetes mellitus in humans. However, there is wide variation in the methods of inducing diabetes in terms of the dose of STZ, the duration of the induction period, and the composition of the diet used, all of which could result in biological responses that are not typical of the disease. This review aims to investigate the characteristics of an experimental model of type 2 diabetes mellitus by combining a high-fat diet with low doses of streptozotocin in Wistar rats. This is an integrative review conducted by searching in the Medline, Lilacs, and Embase databases using the keywords “type 2 diabetes mellitus”, “high-fat diet”, “streptozotocin” and “Wistar rats”. Articles published in English between 2018 and 2025 were included. The induction of DM2 in young male rats with a high-fat HFD for a period of at least 3 weeks followed by a low dose of STZ resulted in metabolic, histological, inflammatory, and oxidative changes, and alterations in the signaling pathways of glycemic and lipid metabolism in different tissues, replicating the characteristics observed in humans. HFD-fed + STZ-induced Wistar rats constitute an effective animal model for studying DM2. Full article

Women exhibit unique vulnerabilities in health, especially regarding mental health and neurodegenerative diseases. Biological, hormonal, and metabolic differences contribute to sex-specific risks that remain underrepresented in clinical studies. Diseases such as major depressive disorder (MDD) and Alzheimer’s disease (AD) are more prevalent in women and may be influenced by hormonal transitions, particularly during menopause. Chronic low-grade inflammation is emerging as a shared mechanism underlying both conditions, and this inflammatory state can be worsened by dietary habits. During menopause, mood and sleep disturbances can influence dietary behavior, leading to enhanced snacking and consumption of high-glycemic and comfort foods. Such foods, low in nutritional value, promote weight gain and elevated inflammatory markers. Their consumption combined (or not) with a preexisting Western diet pattern—already linked to inflammation—could reinforce systemic inflammation involving the gut–brain axis. Moreover, the symptoms “per se” could act on inflammation as well. Peripheral inflammation may cross the blood–brain barrier, sustaining mood disorders and promoting neurodegenerative changes. Finally, MDD and AD are both associated with conditions such as obesity and diabetes, which occur more frequently in women. The review highlights how menopause-related changes in mood, sleep, and diet may heighten susceptibility to mental and neurodegenerative diseases. Full article

Background: Insulin resistance, visceral adiposity, excess body weight, and symptoms of hyperandrogenism often accompanies Polycystic Ovary Syndrome (PCOS). A balanced diet plays a key role in improving the metabolic and biochemical parameters in affected women. This study aims to assess whether dietary improvements in patients with suspected PCOS may affect the severity of the disease and the metabolic and hormonal profile. Methods: The analysis of the relationships between self-declared nutritional changes and biochemical and metabolic parameters included 154 women at the same stage of PCOS diagnosis. Results: Over half of participants reported dietary modifications. Women reducing sweets, fatty red meat, and alcohol intake for >6 months had significantly lower total testosterone (TT) levels compared to those who did not (p < 0.05). Mean TT levels were: 0.375 ± 0.18 ng/mL (median 0.340) vs. 0.787 ± 2.19 ng/mL (median 0.390) for red meat (p = 0.008), 0.359 ± 0.18 ng/mL (median 0.335) vs. 0.681 ± 1.9 ng/mL (median 0.4) for sweets (p = 0.02), and 0.388 ± 0.19 ng/mL (median 0.34) vs. 0.917 ± 2.65 ng/mL (median 0.425) for alcohol (p = 0.004). Patients with dietary changes in the past 6 months had higher androgen levels, BMI, systolic blood pressure and triglycerides than patients with long-term dietary changes (p < 0.05). There were no statistically significant differences in key metabolic and biochemical parameters when comparing self-reported diets based on glycemic index (low vs. high). Conclusions: A healthy, balanced diet for women with PCOS requires a multifaceted approach with clear, defined goals. This leads to better results than broad, general dietary recommendations. Long-term dietary changes improve biochemical and metabolic parameters, but maintaining these benefits requires continuous patient motivation. Full article

Introduction and Objectives: Obesity constitutes a significant public health concern and is frequently linked to metabolic dysfunctions, particularly insulin resistance (IR). Nevertheless, a subset of obese individuals, referred to as metabolically healthy obese (MHO), do not exhibit overt metabolic abnormalities. The present study aims to assess the risk of developing IR among MHO workers and to explore the determinants contributing to this risk. Methods: This cross-sectional investigation utilized data from a cohort of 68,884 obese workers across multiple occupational sectors in Spain. The classification of participants as MHO was based on the number of metabolic syndrome components, in accordance with the criteria established by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII). Anthropometric, clinical, and biochemical parameters—including body mass index (BMI), waist circumference, lipid profile, glycemic levels, and blood pressure—were systematically assessed. The likelihood of developing IR was estimated through various validated risk assessment models. Results: The analysis indicates that, despite having a relatively favorable metabolic profile, individuals classified as MHO also show signs of metabolic deterioration, such as an increased risk of insulin resistance. Key risk factors such as physical inactivity, low adherence to the Mediterranean diet, and socioeconomic disparities were identified as significant contributors to the transition from the MHO phenotype to a metabolically unhealthy state. Logistic regression analyses corroborated that insufficient physical activity and suboptimal dietary habits were strongly associated with an elevated risk of IR. Conclusions: The findings underscore the dynamic and potentially transient nature of the MHO phenotype, emphasizing the necessity of proactive monitoring and early preventive strategies. Encouraging physical activity, promoting adherence to a nutritionally balanced diet, and implementing workplace health initiatives emerge as critical measures to attenuate the risk of IR and metabolic deterioration in MHO individuals. Future longitudinal studies are warranted to enhance risk stratification and to formulate tailored preventive interventions. Full article

Background: Roux-en-Y gastric bypass (RYGB) surgery results in weight reduction and decreased energy intake and can ameliorate type 2 diabetes. These beneficial effects are usually attributed to changes in hunger and satiety and relatively rapid improvements in glycemic control, but these effects may depend on dietary adherence. The aim of this study is to investigate the relatively early effects of RYGB surgery on weight reduction (by focusing on eating patterns) and glycemic control in rats subjected to a healthy maintenance diet or an unhealthy Western-style diet. Methods: Rats were fed a high-fat diet with added sucrose (HF/S) or a low-fat (LF) diet. Body weight, high-resolution tracking of meal-related parameters, and glucose regulation after overnight fasting and during a mixed meal tolerance test (MMTT; 2 mL sweet/condensed milk) were measured before and after RYGB (RYGB+) or sham surgery (RYGB−). Results: HF/S feeding led to an increased body weight just before RYGB surgery, but it also caused enhanced weight loss following RYGB, which led to similar body weights in the HF/S and LF diet groups twenty-four days post-operatively. RYGB surgery and diet dependently and independently influenced meal-related parameter outcomes, where both RYGB+ and HF/S feeding resulted in shorter meal duration (p < 0.01), higher ingestion rates (p < 0.001), and increased satiety ratio (p < 0.05), especially in the HF/S diet group subjected to RYGB. While RYGB surgery generally improved baseline glycemic parameters including HOMA-IR (p < 0.01), it often interacted with diet to affect MMTT-induced hyperglycemia (p < 0.05), beta-cell sensitivity (p < 0.01), and the insulinogenic index (p < 0.01), with the LF rats overall maintaining better glycemic control than the HF/S-fed rats. Conclusions: This study shows the importance of controlling diet after RYGB surgery, as diet type significantly influences ingestive behavior, post-prandial glucose regulation, beta-cell sensitivity, and glucose tolerance after RYGB. Full article

Type 2 diabetes (T2D) is a rapidly growing global health concern, projected to affect 1.3 billion people by 2050, necessitating a multidisciplinary approach. This review examines the epidemiological disparities in T2D, focusing on modifiable and nonmodifiable risk factors, socioeconomic determinants, and healthcare inequities. While genetic predisposition, age, and ethnicity contribute to T2D risk, socioeconomic status (SES) significantly mediates modifiable factors such as diet, physical activity, and access to healthcare. Lower SES is associated with poorer lifestyle choices, limited access to resources, and increased exposure to risk factors, exacerbating T2D prevalence among vulnerable populations. Geographic variations in T2D prevalence are evident, with racial and ethnic minorities and lower-income individuals being disproportionately affected in regions like the United States and Europe. The economic burden of T2D is substantial, with global healthcare expenditures reaching USD 966 billion in 2021 and projected to rise significantly, albeit with variations across different countries and health systems. Despite advancements in treatment, inequities in healthcare access persist, particularly in low- and middle-income countries, hindering optimal glycemic control and consequently contributing to preventable complications and poor health outcomes. This review highlights the critical need for targeted interventions and policy reforms to address the intersection of demographic, economic, and healthcare-related variables influencing T2D disparities. By bridging gaps in prevention, management, and treatment and accounting for the effect of SES on both modifiable and nonmodifiable risk factors, the global disease burden of T2D could be reduced and health equity could be improved. Full article

Objective: This study aimed to review the structural concepts, definition, classification, and macronutrient and food composition of carbohydrate-restricted diets (CRDs) for individuals with type 2 diabetes mellitus (T2DM). Methods: A scoping review was conducted following Joanna Briggs Institute guidelines. Searches were performed in Scopus, PubMed, Web of Science, and Embase, including texts published in Portuguese, English, and Spanish. Official documents from governments, regulatory agencies, and international diabetes organizations were also consulted. Results: In total, 79 articles and 17 official documents were analyzed. The following structural concept was identified: restricted carbohydrate intake decreases the need for endogenous and exogenous insulin, contributing to the maintenance of glycemic control, and justifies its consideration among the nutritional therapy options for individuals with T2DM. CRDs varied in definition, classification, and macronutrient composition. Studies failed to provide detailed information on the food composition of diets, precluding an in-depth understanding of metabolic effects. The existence of several approaches with varying recommendations makes it difficult to generalize the results. International CRD guidelines for T2DM adopt divergent definitions, compromising interpretation, recommendation, and even adherence. Conclusions: Although the concept of CRDs justifies their adoption within the nutritional therapy choices for T2DM, the multiple denominations can hinder understanding and comparison between studies. The lack of information on food composition and carbohydrate types compromises the assessment of the effects and adherence to CRD-based nutritional interventions. We emphasize the need for methodologically consistent studies that evaluate CRDs based on fresh and minimally processed foods with a low glycemic index to support official diabetes guidelines and organizations. Full article

Drug-resistant epilepsy (DRE) affects 20–30% of patients with epilepsy who fail to achieve seizure control with antiseizure medications, posing a significant therapeutic challenge. In this narrative review, we examine the clinical efficacy and safety of the classic ketogenic diet (cKD) and its variants, including the modified Atkins diet (MAD), medium-chain triglyceride diet (MCTD), and low glycemic index treatment (LGIT), in patients with genetically confirmed drug-resistant epilepsy. These diets induce a metabolic shift from glucose to ketones, enhance mitochondrial function, modulate neurotransmitter balance, and exert anti-inflammatory effects. However, genetic factors strongly influence the efficacy and safety of the cKD, with absolute indications including glucose transporter type 1 deficiency syndrome (GLUT1DS) and pyruvate dehydrogenase complex deficiency (PDCD). Preferred adjunctive applications of the KD include genetic epilepsies, such as SCN1A-related Dravet syndrome, TSC1/TSC2-related tuberous sclerosis complex, and UBE3A-related Angelman syndrome. However, because of the risk of metabolic decompensation, the cKD is contraindicated in patients with pathogenic variants of pyruvate carboxylase and SLC22A5. Recent advancements in precision medicine suggest that genetic and microbiome profiling may refine patient selection and optimize KD-based dietary interventions. Genome-wide association studies and multiomics approaches have identified key metabolic pathways influencing the response to the cKD, and these pave the way for individualized treatment strategies. Future research should integrate genomic, metabolomic, and microbiome data to develop biomarker-driven dietary protocols with improved efficacy and safety. As dietary therapies continue to evolve, a personalized medical approach is essential to maximize their clinical utility for genetic epilepsy and refractory epilepsy syndromes. Full article