Search Results (62)

The study of incretins spans more than a century and has revealed their essential role in glucose homeostasis and metabolic regulation. This understanding has led to the development of incretin receptor agonists as highly effective pharmacological agents for the treatment of such cardiometabolic diseases as type 2 diabetes and obesity, showing substantial benefits in glycemic control, body weight reduction, and cardiometabolic outcomes. However, their use is limited by adverse events, most commonly gastrointestinal intolerance, along with ongoing safety concerns regarding pancreatic, renal, and ophthalmologic effects. Although incretin-based therapies have fundamentally reshaped the management of diabetes and obesity, continued innovation in drug design and delivery holds promise for expanding their applicability, improving patient adherence, and reinforcing their role as a cornerstone of metabolic disease management and beyond. This review summarizes the historical development, molecular design, and clinical relevance of incretin-based therapies, with particular emphasis on approved agents used in current clinical practice. Full article

Background/Objectives: Prediabetes (PreDM) is a heterogeneous condition, impacting hundreds of millions worldwide, associated with a substantially high risk of Type 2 Diabetes Mellitus (T2DM) and cardiovascular complications. Early identification of subgroups within the PreDM population may support tailored prevention strategies. Methods: We conducted a cross-sectional study using data from annual health check-ups of 419 university staff (aged 27–69) in Kazakhstan. Latent Class Analysis (LCA) was applied to identify subgroups of individuals with PreDM based on cardiovascular risk factors. Differences in glucose metabolism markers (fasting glucose, OGTT, HOMA-IR, HOMA-β) were compared across identified classes. Results: PreDM prevalence was 43.4%. LCA revealed four distinct classes: Class 1: healthy, low-risk individuals; Class 2: overweight with moderate metabolic risk; Class 3: older, overweight individuals with high cardio-metabolic risk; and Class 4: obese, middle-aged to older individuals with very high cardio-metabolic risk. Significant differences were found in glucose metabolism profiles across the classes. IFG predominated in Class 1 (95%), while Classes 3 and 4 had higher rates of β-cell dysfunction and combined IFG/IGT patterns. HOMA-β differed significantly between classes (p  <  0.001), while HOMA-IR did not. Conclusions: PreDM is highly prevalent in this working-age Kazakh population and demonstrates marked heterogeneity. Based on easily obtainable cardiovascular risk factors, we have identified four subgroups with distinct glucose profiles that may inform personalized interventions. These distinct subgroups may require differentiated prevention strategies, moving beyond a one-size-fits-all approach. Full article

Background: Graves–Basedow disease (GBD) is an autoimmune thyroid disorder characterized by loss of tolerance to the thyrotropin receptor, with clinical manifestations such as a hyperadrenergic state, goiter, orbitopathy, and myxedema, inter alia. Selenium is a micronutrient, essential for the synthesis of selenoproteins. Selenium deficiency has been linked to an increased risk and exacerbation of GBD and GBD orbitopathy; therefore, it has been suggested that supplementation with this micronutrient could modify some outcomes associated with both conditions. Objectives: The objective of this scoping review was to synthesize and analyze the clinical trials that have evaluated the effectiveness of selenium on different outcomes in patients with GBD or GBD orbitopathy. Methods: The following databases were consulted: PubMed/Medline, Scopus, Biosis, ProQuest, Web of Science, and Google Scholar; and the search terms ‘Graves-Basedow disease’ or ‘Graves’ disease’ or ‘hyperthyroidism’ or ‘Graves’ hyperthyroidism’ or ‘selenium or selenium supplementation’ and ‘effectiveness’ were used. The search was limited to articles published in English between January 2000 and March 2025. To reduce selection bias, each article was reviewed independently by three authors using the Rayyan web tool and the JBI Critical Appraisal Checklist. Results: A total of 15 studies were identified (11 on patients with GBD and 4 on patients with GBD orbitopathy). In GBD, selenium supplementation was associated with significant improvements in TSH, FT4, FT3, TPOAb, TgAb, and TRAb levels; while in GBD orbitopathy, a positive effect of selenium supplementation was found on multiple clinical outcomes. Conclusions: Selenium supplementation in patients with GBD or GBD orbitopathy is associated with favorable biochemical and clinical outcomes. Full article

Obesity-induced insulin resistance and type 2 diabetes mellitus (T2DM) represent complex systemic disorders marked by chronic inflammation, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. These pathophysiological processes disrupt insulin signaling and β-cell function, leading to impaired glucose homeostasis across multiple organs. Conventional therapies often target isolated pathways, overlooking the intricate molecular crosstalk and organelle-level disturbances driving disease progression. Citrus-derived polyphenols—including hesperidin, naringenin, nobiletin, and tangeretin—have emerged as promising agents capable of orchestrating a multi-targeted “metabolic reprogramming.” These compounds modulate key signaling pathways, including AMPK, PI3K/Akt, NF-κB, and Nrf2, thereby enhancing insulin sensitivity, reducing pro-inflammatory cytokine expression, and restoring redox balance. Furthermore, they improve mitochondrial biogenesis, stabilize membrane potential, and alleviate ER stress by modulating the unfolded protein response (UPR), thus supporting cellular energy homeostasis and protein folding capacity. Evidence from preclinical studies and select clinical trials suggests that citrus polyphenols can significantly improve glycemic control, reduce oxidative and inflammatory markers, and preserve β-cell function. Their pleiotropic actions across molecular and organ-level targets position them as integrative metabolic modulators. This review presents a systems-level synthesis of how citrus polyphenols rewire metabolic signaling networks and organelle resilience, offering a holistic therapeutic strategy to mitigate the root causes of obesity-induced insulin resistance. Full article

Emerging evidence suggests that vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors exert synergistic immunomodulatory, anti-inflammatory and antioxidant actions. Moreover, intervention studies showed that combination therapy based on the concomitant use of vitamin D and DPP-4 inhibitors (VIDPP-4i) may preserve beta-cell function in patients with type 1 diabetes mellitus (T1D) and latent autoimmune diabetes in adults (LADA). These effects are particularly relevant in the context of beta-cell replacement strategies, whose long-term efficacy can be hampered by various factors, such as immune-mediated graft rejection, inadequate vascularization, hypoxia, trauma-induced cell apoptosis, fibrosis, host immune response, and recurrence of autoimmunity. Based on preclinical and clinical studies conducted in the fields of autoimmune diabetes and solid organ/cell transplantation, the present narrative review aims to describe the rationale behind the investigation of VIDPP-4i combination therapy as an adjuvant treatment strategy to enhance the efficacy of novel beta-cell replacement therapies for T1D. In this regard, we discuss the potential immune and metabolic mechanisms through which vitamin D and DPP-4 inhibitors can promote the long-term function and survival of transplanted islets in patients with T1D receiving various types of beta-cell replacement therapies, including therapeutic approaches using encapsulated stem cell-derived beta cells. Full article

Background: Hashimoto’s thyroiditis (HT) is the most common autoimmune thyroid disease (AITD) and is characterized by the presence of thyroid autoantibodies against thyroid peroxidase and/or thyroglobulin. Several studies have found that the global prevalence of HT has increased in recent decades, while others show the opposite. Methods and Results: The objective of this scoping review was to synthesize and analyze the different studies that have evaluated the prevalence of HT (in adults) and the possible associated factors. The following databases were consulted, as follows: MEDLINE, Web of Science, PubMed, and Scopus. The search terms “epidemiology”, “prevalence”, and “Hashimoto disease” and “Hashimoto thyroiditis” were used. The search was limited to articles published between January 1965 and October 2024, and only articles in English were considered. In order to reduce selection bias, each article was scrutinized using the JBI Critical Appraisal Checklist independently by two authors. Studies were included if the number of participants (study population and/or cases and controls, depending on the study design) was clearly described and duplicate studies were excluded. A total of 59 studies were identified, the vast majority of them used a cross-sectional design, using different methods of disease assessment. Conclusions: Globally, the prevalence of HT is estimated to be between 5–10%; some areas with prevalences > 20% and others < 0.5% were identified. Prevalence is also higher in women than in men. Multiple underlying factors (genetic, epigenetic, environmental, and lifestyle), together with socioeconomic, nutritional, overdiagnosis, inter alia, may explain (at least in part) the wide variability in the prevalence of HT. Full article

India’s population complexity presents varied challenges in genetic research, and while facilities have gained traction in tier-1 and -2 cities, reliance on international collaborations often delays such investigations. COVID-19 further exacerbated the issues with such sample sharing. Congenital Hyperinsulinism (CHI) is a rare genetic disorder of pancreatic β-cells causing hypoglycaemia in children due to abnormal insulin secretion. Given India’s high birth rate and consanguineous populations, annual CHI cases are estimated to be around up to 10,000, with up to 50% having unexplained genetic causes. Diffuse or atypical lesions in such patients often necessitate near-total-pancreatectomy, risking pancreatic exocrine insufficiency and diabetes, requiring lifelong therapy. Also, novel genetic variations complicate accurate diagnosis, risk assessment, and counselling, emphasising the need for rapid genetic assessment to prevent neurological injuries and inform treatment decisions. Despite significant efforts at many institutes, there are no dedicated organisations for CHI in India. With the implementation of the National Policy for Rare Diseases 2021, we plan to form a non-profit organisation, “Congenital Hyperinsulinism India Association (CHIA)”, comprising paediatric endocrinologists, paediatricians, geneticists, and independent researchers. The aims of this association are to generate a national database registry of patients, formulate a parent support group and CHIA consortium, design patient information leaflets, as well as foster genomic collaborations and promote clinical trials. Such steps will help sensitise the health authorities and policy makers, urging them to improve the allocation of health budgets for rare diseases, as well as empower patients and their families, contributing towards a better quality of life. Full article

Secondary hypertension and resistant hypertension may result from potentially treatable acquired or hereditary diseases. Inherited Metabolic Disorders are not routinely included in the differential diagnosis of these contexts associated with hypertension, despite the key importance of diagnosis for several of them which enable the early treatment of them. We aim to discuss the current evidence that indicates that a significant portion of cases of unknown resistant hypertension or suspected secondary hypertension may result from unrecognized Acute Hepatic Porphyria (AHP). Diagnostic work-up for AHP is not routinely performed during the evaluation of patients with resistant or refractory hypertension nor in the investigation of secondary hypertension. AHP may present both with neurological and systemic involvement, and hypertension may be observed as part of acute dysautonomia during acute neurovisceral attacks and as a chronic complication during disease course. As AHP represent a potentially treatable group of metabolic disorders, clinicians should consider the inclusion of this group in the diagnostic evaluation of patients with secondary or resistant hypertension. Full article

The prevalence of overweight and obesity is increasing worldwide. Common comorbidities related to obesity, significantly polygenic disorders, cardiovascular disease, and heart conditions affect social and monetary systems. Over the past decade, research in drug discovery and development has opened new paths for alternative and conventional medicine. With a deeper comprehension of its underlying mechanisms, obesity is now recognized more as a chronic condition rather than merely a result of lifestyle choices. Nonetheless, addressing it solely through lifestyle changes is challenging due to the intricate nature of energy regulation dysfunction. The Federal Drug Administration (FDA) has approved six medications for the management of overweight and obesity. Seaweed are plants and algae that grow in oceans, rivers, and lakes. Studies have shown that seaweed has therapeutic potential in the management of body weight and obesity. Seaweed compounds such as carotenoids, xanthophyll, astaxanthin, fucoidans, and fucoxanthin have been demonstrated as potential bioactive components in the treatment of obesity. The abundance of natural seaweed bioactive compounds has been explored for their therapeutic potential for treating obesity worldwide. Keeping this view, this review covered the latest developments in the discovery of varied anti-obese seaweed and its bioactive components for the management of obesity. Full article

Maintaining a healthy lifestyle can extend life expectancy and improve a person’s health status. In addition to physical activity and bad habits related to smoking and alcohol, diet is also a determining factor. Following a healthy diet pattern over time and supporting a healthy body weight contributes to reducing the risk of developing more severe complications associated with very common diseases such as chronic kidney disease (CKD), diabetes, or cardiovascular diseases. The 2015–2020 Dietary Guidelines for Americans promote the adoption of fat-free or low-fat diets and discourage the consumption of foods with added sugar and solid fats, such as ice creams and other frozen desserts. On the other hand, ice cream, from a nutritional and healthy point of view, can be considered a possible food choice, due to its greater palatability and high nutritional content, but its consumption must be scheduled in a balanced diet. In this retrospective study, 36 patients with chronic renal failure were enrolled. Two different diets were proposed (A and B). In Diet B, lemon sorbet was added twice a week as an alternative food to replace fruit or snacks making the diet more varied and palatable. Nutritional status and biohumoral, immunological, and blood parameters were evaluated after 6 months. A statistical analysis shows a significant inter-group difference in creatinine and azotemia between T0 and T1. Intra-group significant differences were found in lymphocytes (p = 0.005) and azotemia (p < 0.001) in Diet A, and in azotemia (p < 0.001) and transferrin (p < 0.001) in Diet B. The results indicated that ice cream represented a good alternative food in both groups of patients regarding nutritional values and patient satisfaction. Furthermore, the treatment with ice cream allowed for better control of azotemia, maintaining stable levels even in patients with advanced CKD. This study concludes that ice cream could exert beneficial effects in addition to CKD patients’ dietary regimens. Full article

Background: Maternal diabetes mellitus (MDM) is associated with increased risks for adverse neonatal outcomes. However, the impact of MDM on neonatal outcomes in Bisha, a city in Saudi Arabia, is not well documented. This study aims to investigate the impact of MDM on neonatal outcomes in the Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia. Methods: A retrospective cohort study was conducted on 181 pregnant women with diabetes and their neonates who were diagnosed at the Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia, between 5 October 2020 and 5 November 2022. The primary outcome was a composite of adverse neonatal outcomes, including stillbirth, neonatal death, macrosomia, preterm birth, respiratory distress syndrome, hypoglycemia, and congenital anomalies. Logistic regression analyses were used to adjust for potential confounders. Results: The total sample size was 181. The average age of patients was 34 years (SD = 6.45). The majority of the patients were diagnosed with GDM, 147 (81.2%), and pre-GDM, 34 (18.8%). Neonates born to mothers with MDM had a higher risk of adverse neonatal outcomes compared to those born to mothers without MDM (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.25–1.70). The risks of macrosomia (aOR = 1.74, 95% CI: 1.38–2.19), LBW (aOR = 1.32, 95% CI: 1.06–1.66), and RDS (aOR = 1.57, 95% CI: 1.28–1.93) were significantly higher among neonates born to mothers with MDM. The types of DM were statistically significant in terms of their correlation with the following neonatal outcomes: hypoglycemia (p-value = 0.017), macrosomia (p-value = 0.050), and neonatal death (p-value = 0.017). Conclusions: MDM is associated with an increased risk of adverse neonatal outcomes in Bisha. The early identification and management of MDM may improve neonatal outcomes and reduce the burden of neonatal morbidity and mortality in this population. Full article

Background: Pituitary adenomas are benign brain tumors that impose a heavy burden on patients worldwide. The local burden of disease is yet to be established due to scarcity of data. In line with this, this study aims to present the challenges and gaps in the treatment of pituitary adenomas in the Philippines. Methods: A scoping review of available relevant literature on epidemiology, clinical experience with treatment, health financing, and healthcare delivery system based on the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines extension for Scoping Reviews was conducted. Results: The scarcity of updated local clinical data, inequity of distribution of resources, inadequate government support, and lack of affordable diagnostic testing, medications, and neurosurgical procedures are the factors that hinder provision of adequate care of pituitary adenomas in the Philippines. Conclusion: There are notable treatment gaps in the management of pituitary adenomas in the Philippines, which may be addressed by strengthening universal healthcare. Strategies to address these gaps were proposed, including improving public-private insurance coverage, increasing manpower, enhancing accessibility to resources, and spreading more awareness. Full article

Defects in how excess nutrients are stored as triglycerides can result in several diseases including obesity, heart disease, and diabetes. Understanding the genes responsible for normal lipid homeostasis will help understand the pathogenesis of these diseases. RNAi screens performed in Drosophila cells identified genes involved in vesicle formation and protein sorting as important for the formation of lipid droplets; however, all of the vesicular trafficking proteins that regulate lipid storage are unknown. Here, we characterize the function of the Drosophila Charged multivesicular protein 1 (Chmp1) gene in regulating fat storage. Chmp1 is a member of the ESCRT-III complex that targets membrane localized signaling receptors to intralumenal vesicles in the multivesicular body of the endosome and then ultimately to the lysosome for degradation. When Chmp1 levels are decreased specifically in the fly fat body, triglyceride accumulates while fat-body-specific Chmp1 overexpression decreases triglycerides. Chmp1 controls triglyceride storage by regulating the number and size of fat body cells produced and not by altering food consumption or lipid metabolic enzyme gene expression. Together, these data uncover a novel function for Chmp1 in controlling lipid storage in Drosophila and supports the role of the endomembrane system in regulating metabolic homeostasis. Full article

Background: Obesity is associated with increased all-cause mortality and cardiovascular disease (CVD). An electrocardiogram (ECG) may be used to screen for subtle signs of CVD or altered cardiac morphology in the obese. Methodology: This observational cross-sectional analysed ECG changes in patients with obesity at a tertiary care centre in southern India. Results: One hundred and fifty adult patients with a mean (SD) BMI of 39.9 (6.7) kg/m² were recruited in the study after excluding those with comorbidities (diabetes mellitus, systemic hypertension) or on chronic medications (ACE inhibitors). The cohort showed a female predominance (69.3%), with a mean (SD) age of 45.4 (11.2) years. Most patients exhibited a sinus rhythm (78%), with one patient showing features of first-degree conduction block. Sinus tachycardia was seen in 32 (21.3%) patients. We observed left and right ventricular hypertrophy in five (3.3%) and three (2%) patients, respectively. Observed ECG patterns included a prolonged QTc in 16 (10.7%) patients, inverted T-waves (mostly in the inferior leads) in 39 (26%) patients and ST-segment depression (predominantly in the lateral leads) in 14 (9.3%) patients. A greater prevalence was noted for morbid obesity. No deaths were reported in our cohort. Conclusions: The predominant ECG variations in this cohort included tachycardia, atrial enlargement, ventricular hypertrophy, conduction defects, LAD, features of ischemia or old infarction and repolarization abnormalities, with a greater prevalence in morbid obesity. Further studies are needed to assess the impact of weight reducing measures on reversibility of these changes and determine the association with outcomes in obese patients. Full article

Background: Guidelines for the management of polycystic ovary syndrome (PCOS) focus on lifestyle changes, incorporating exercise. Whilst evidence suggests that aerobic exercise may be beneficial, less is known about the effectiveness of resistance training (RT), which may be more feasible for those that have low fitness levels and/or are unable to tolerate/participate in aerobic exercise. Objectives: To identify the available evidence on RT in women with PCOS and to summarise findings in the context of a scoping review. Eligibility criteria: Studies utilising pre-post designs to assess the effectiveness of RT in PCOS; all outcomes were included. Sources of evidence: Four databases (PubMed, CENTRAL, CINAHL and SportDiscus) were searched and supplemented by hand searching of relevant papers/reference lists. Charting methods: Extracted data were presented in tables and qualitatively synthesised. Results: Searches returned 42 papers; of those, 12 papers were included, relating to six studies/trials. Statistical changes were reported for multiple pertinent outcomes relating to metabolic (i.e., glycaemia and fat-free mass) and hormonal (i.e., testosterone and sex hormone-binding globulin) profiles. Conclusions: There is a striking lack of studies in this field and, despite the reported statistical significance for many outcomes, the documented magnitude of changes are small and the quality of the evidence questionable. This highlights an unmet need for rigorously designed/reported and sufficiently powered trials. Full article