Endocrinology, Diabetes and Metabolism最新文献

{"title":"Combination Pharmacotherapies for Obesity—Current Evidence and Future Directions","authors":"A. B. M. Kamrul-Hasan,&nbsp;Arnav Kalra,&nbsp;Nitin Kapoor,&nbsp;Deep Dutta,&nbsp;Kunal Mahajan,&nbsp;Robin Maskey,&nbsp;Syed Abbas Raza","doi":"10.1002/edm2.70307","DOIUrl":"10.1002/edm2.70307","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Conventional single-agent drugs yield modest, plateauing weight loss and often lead to weight regain. Combination pharmacotherapy is a logical next step to target complementary pathways of weight control while reducing toxicity and treatment burden. This review synthesises mechanisms and clinical evidence for fixed-dose combinations, multi-agonist peptides, add-on regimens and multimodal strategies integrating pharmacotherapy with procedures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a narrative review of clinical trials and observational studies on approved and emerging obesity pharmacotherapy combinations, focusing on mechanistic complementarity, efficacy, safety and practical implementation. Agents were mapped to three domains of energy homeostasis—homeostatic appetite regulation, hedonic-reward circuitry and peripheral metabolic effector pathways—to inform interpretation of combination strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fixed-dose combinations such as phentermine-topiramate and naltrexone-bupropion yield greater weight loss than their individual components but also carry gastrointestinal, cardiovascular and neuropsychiatric risks. Multi-agonist peptides integrating GLP-1, GIP, glucagon, or amylin deliver double-digit weight loss and improve glycemic and cardiometabolic profiles, but increase the risk of gastrointestinal adverse events, requiring close monitoring. Add-on regimens that combine GLP-1 agonists with approved obesity medications or SGLT-2 inhibitors, and multimodal strategies that pair drugs with bariatric or endoscopic procedures, generally show additive rather than truly synergistic effects on weight loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Available data suggest that combination pharmacotherapy can extend current approaches to precision obesity care, generally providing additive benefits alongside increased regimen complexity, costs and adverse-event risks. Thoughtful, phenotype-guided selection and comparative studies versus potent monotherapies, enriched by multi-omics and behavioural insights, may clarify which patients benefit most and sustainably from these strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropeptide Alterations in Type 2 Diabetes Mellitus: A Meta-Analysis of Circulating Spexin and Galanin Levels","authors":"Roshan Kumar Mahat,&nbsp;Sushil Yadav,&nbsp;Kahkashan Naaz,&nbsp;Nand Kishor Prasad Sah,&nbsp;Amrendra P. Kushwaha","doi":"10.1002/edm2.70303","DOIUrl":"10.1002/edm2.70303","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spexin and galanin are neuropeptides involved in glucose homeostasis, insulin sensitivity, appetite, and energy metabolism. We conducted a systematic review and meta-analysis to synthesise evidence on circulating spexin and galanin concentrations in patients with type 2 diabetes mellitus (T2DM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed/MEDLINE, Scopus, and Web of Science were systematically searched from inception to March 22, 2026. Observational studies reporting circulating spexin and/or galanin levels in adults with T2DM and non-diabetic controls were included. Random-effects meta-analyses were performed to calculate pooled standardised mean differences (SMDs) with 95% confidence intervals (CIs). Subgroup analyses, meta-regression, sensitivity analyses, prediction intervals, and publication bias assessments were conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nineteen studies met the inclusion criteria. Thirteen studies (1453 T2DM and 850 controls) showed significantly lower circulating spexin levels in T2DM (SMD = −2.37, 95% CI: −3.21 to −1.53; <i>p</i> &lt; 0.0001), with substantial heterogeneity (I² = 98.3%). Four studies further showed reduced spexin levels in patients with diabetic complications compared with uncomplicated T2DM (SMD = −1.12, 95% CI: −1.75 to −0.49; <i>p</i> = 0.0005). Meta-regression identified age as a significant moderator (<i>p</i> = 0.007), whereas BMI, HbA1c, sex, and publication year were not significant. Four studies (171 T2DM and 172 controls) revealed significantly elevated circulating galanin levels in T2DM (SMD = 1.35, 95% CI: 1.02–1.68; <i>p</i> &lt; 0.0001) with moderate heterogeneity (I² = 47.2%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Circulating spexin levels are significantly decreased, whereas galanin levels are significantly increased in T2DM. These neuropeptides show potential as biomarkers of metabolic dysregulation and diabetic complications; however, the findings should be interpreted with caution owing to the very low certainty of the available evidence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Involvement of Redox and Inflammatory Signalling in the Antihyperglycemic and Antioxidant Effects of Harmaline in Male Mice With Type 2 Diabetes","authors":"Farima Malekinia,&nbsp;Akram Ahangarpour,&nbsp;Khojasteh Hoseinynejad,&nbsp;Seyyed Ali Mard,&nbsp;Maryam Radan,&nbsp;Fereshteh Nejaddehbashi","doi":"10.1002/edm2.70304","DOIUrl":"10.1002/edm2.70304","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Type 2 diabetes mellitus (T2DM) is strongly associated with oxidative stress and inflammation. Harmaline (HAR), an alkaloid with antioxidant and anti-inflammatory properties, has been suggested to possess antidiabetic potential. This study investigated the effects of HAR in experimental T2DM and its association with changes in the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vitro experiments were performed using mouse pancreatic cells cultured under different glucose concentrations to evaluate insulin secretion and antioxidant status. For the in vivo study, T2DM was induced in mice by nicotinamide (120 mg/kg) and streptozotocin (65 mg/kg). Fasting blood glucose (FBG) was measured 1 week after induction. Forty-eight adult male NMRI mice were randomly assigned to four groups: normal control (NC), diabetic control (DC), HAR-treated (30 mg/kg), and metformin-treated (150 mg/kg). Treatments were administered once daily for 10 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HAR enhanced insulin secretion and antioxidant capacity while reducing lipid peroxidation in vitro. In diabetic mice, HAR significantly reduced FBG, improved the lipid profile, and restored pancreatic antioxidant status. These effects were accompanied by increased expression of miR-200a, Nrf2, and NAD(P)H: quinone oxidoreductase 1 and reduced Keap1 expression. In addition, HAR increased miR-125b expression and reduced the expression of NF-κB, TNF-α, IL-1β, and IL-6. Decreased changes in RAS-related markers were also observed after HAR treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HAR improved glycemic control and pancreatic antioxidant status and reduced inflammatory responses in experimental T2DM. These beneficial effects were associated with modulation of Nrf2, NF-κB, and RAS-related signalling pathways, suggesting their potential involvement in the observed protective effects. Further studies are needed to establish the underlying mechanisms and evaluate the long-term efficacy and safety of HAR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Oral Semaglutide on Dietary Intake and Body Composition in Japanese People With Type 2 Diabetes: A Prospective Observational Study in Clinical Practice","authors":"Mika Sawada,&nbsp;Naoko Nakanishi,&nbsp;Masakazu Aihara,&nbsp;Kanako Ohkuma,&nbsp;Shoko Hamano,&nbsp;Yoshitaka Sakurai,&nbsp;Rie Sekine,&nbsp;Satoshi Usami,&nbsp;Toshimasa Yamauchi,&nbsp;Naoto Kubota","doi":"10.1002/edm2.70295","DOIUrl":"10.1002/edm2.70295","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Glucagon-like peptide-1 receptor agonists are effective glucose-lowering agents with established benefits on body weight and cardiometabolic outcomes. However, their precise effects on body composition and dietary intake patterns, including food group consumption and macronutrient energy distribution, particularly in clinical settings, remain incompletely understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective observational study, we enrolled Japanese adults with Type 2 diabetes who were newly initiated on oral semaglutide treatment. Dietary intake patterns were assessed using a food frequency questionnaire, and body composition was assessed by bioelectrical impedance analysis. Handgrip strength and laboratory parameters were also evaluated. All parameters were assessed at both baseline (before the start of semaglutide treatment) and at a 3-month follow-up visit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 25 participants were included in the final analysis. After 3 months of oral semaglutide treatment, significant reductions in HbA1c levels and body weight were noted. Significant reductions in the percent body fat and significant increases in the percent muscle mass were also observed. No significant change was observed in the handgrip strength. While the total energy intake decreased significantly after 3 months of semaglutide treatment, the macronutrient energy distribution remained unchanged. Analysis by food groups revealed significant reductions in the intakes of fats and oils, seasonings and spices, and sweets and snacks. Notably, the daily salt intake also decreased significantly from 8.9 to 7.0 g/day.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Oral semaglutide treatment was associated with reductions in the total energy intake and percent body fat, without significant changes in the macronutrient energy distribution or handgrip strength. Salt intake was also significantly reduced, suggesting potential clinical benefits of this treatment in the management of diabetes and related comorbidities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Acting Growth Hormone Versus Daily Growth Hormone for Growth Hormone Deficiency Patients: A Network Meta-Analysis of Clinical Trials","authors":"Amir Abadi,&nbsp;Usra Ghanem,&nbsp;Hamid Ghanem,&nbsp;Ahmed Jalal Sawafta,&nbsp;Ayah Abulehia,&nbsp;Mohammed Ataya,&nbsp;Rahma Nairat,&nbsp;Alhammam Mohammad Sammour,&nbsp;Hazem Ayesh","doi":"10.1002/edm2.70301","DOIUrl":"https://doi.org/10.1002/edm2.70301","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Current guidelines recognize daily recombinant human growth hormone (rhGH) as standard care and long-acting growth hormone (LAGH) as an alternative for paediatric growth hormone deficiency (CHD). In this network meta-analysis (NMA), we updated the evidence to evaluate comparative efficacy and safety of multiple dosing nodes of LAGH versus daily somatropin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Major databases, including PubMed, Embase, Cochrane Central, Scopus, Web of Science, and http://ClinicalTrials.Gov, were searched through April 2026 for randomized controlled trials (RCTs)in children with CHD. Outcomes included height velocity (HV), height SDS, and adverse events. Direct and indirect evidence was synthesized using a frequentist random-effects NMA (OSF: https://doi.org/10.17605/osf.io/nugpe).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighteen RCTs (<i>n</i> = 3137) were analysed. In the primary random-effects model for HV, weekly YPEG-rhGH 0.1 mg/kg/week showed a significantly higher velocity compared to daily Somatropin (SMD: 5.02), whereas Somatrogon 0.25/0.48/0.66 mg/kg/week and Somapacitan 0.04 mg/kg/week showed lower HV. No significant differences were observed across treatments for height SDS. For IGF-1 SDS, Lonapegsomatropin 0.24 mg/kg/week significantly increased levels (SMD: 0.74 [0.36–1.12]), while Somatrogon and Somapacitan 0.04 mg/kg/week demonstrated reductions. Safety profiles showed that Somatrogon significantly increased the risk of localized injection site erythema (RR: 10.55) and pain. However, overall discontinuation rates did not differ significantly between LAGH formulations and daily therapy across the network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Once-weekly LAGH provides an effective frontline alternative to daily acting growth hormone, without compromising overall linear growth or safety, while displaying no differences in overall treatment discontinuation. Selection should be based on the patients' clinical profiles, specifically considering higher localized reactions with Somatrogon. Clinicians should adhere to formulation-specific sampling windows (2–5 days post dose for Lonapegsomatropin; 96 h for Somatrogon) to accurately monitor steady-state IGF-1 levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Müllerian Hormone and Metabolic–Hormonal Profiles in Women With and Without Polycystic Ovary Syndrome: A Population-Based Study","authors":"Fahimeh Ramezani Tehrani,&nbsp;Maryam Mousavi,&nbsp;Marzieh Saei Ghare Naz,&nbsp;Maryam Farahmand,&nbsp;Masoumeh Jorjani,&nbsp;Fatemeh Mahboobifard","doi":"10.1002/edm2.70287","DOIUrl":"https://doi.org/10.1002/edm2.70287","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Evidence regarding age-related variation in anti-Müllerian hormone (AMH) and its associations with hormonal and metabolic parameters in women with polycystic ovary syndrome (PCOS), healthy women, and those with isolated PCOS features remains inconsistent. This study aimed to address these gaps using a cross-sectional, population-based approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 883 women aged 18–45 years were categorized into three groups: PCOS (<i>n</i> = 124; Rotterdam criteria), suspicious (one PCOS criterion, <i>n</i> = 274), and healthy controls (<i>n</i> = 485). The coefficient of determination (R²) assessed age-related AMH variation. Linear regression evaluated associations between AMH and hormonal and metabolic profiles. Age-stratified multivariable logistic regression, adjusted for BMI, parity, and physical activity, examined associations between AMH and type 2 diabetes (T2DM), hypertension, metabolic syndrome (MetS), and dyslipidemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Age explained nearly 40% of AMH variation in healthy women, but only 20% in those with PCOS. AMH was inversely correlated with BMI in healthy and suspicious groups, but not in PCOS. Among healthy women aged ≥ 35 years, higher AMH was associated with a 37% reduced likelihood of T2DM (OR: 0.63, 95% CI: 0.41–0.97). In contrast, among women with PCOS aged &lt; 35 years, elevated AMH was associated with 2.6-fold higher odds of MetS (OR: 2.6, 95% CI: 1.20–6.20). In the suspicious group, AMH correlated positively with free androgen index and prolactin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AMH declines less with age in women with PCOS than in healthy women. Higher AMH may be protective against T2DM in older healthy women but indicates elevated metabolic risk in younger women with PCOS, suggesting that AMH may serve as a life-course biomarker for metabolic risk stratification and personalized preventive strategies in women's healthcare.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tirzepatide and SGLT2 Inhibitors for Heart Failure With Preserved Ejection Fraction and Obesity: Entering a New Cardiometabolic Therapeutic Era","authors":"Zakariye Isak Mohamed,&nbsp;Abdinasir Adam Shidane,&nbsp;Abdullahi Mohamud Abdiasis,&nbsp;Mohamed Hassan Hussein,&nbsp;Ayaanle Osman Ibrahim,&nbsp;Anas Ali Abdi,&nbsp;Kowthar Ismail Hashi,&nbsp;Mohamed Abdullahi Mohamud,&nbsp;Ali Jimale Mohamed","doi":"10.1002/edm2.70298","DOIUrl":"https://doi.org/10.1002/edm2.70298","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Heart failure with preserved ejection fraction (HFpEF) accounts for over half of all heart failure hospitalizations, with obesity increasingly recognized as a central driver through expansion of epicardial adipose tissue, chronic low-grade inflammation and obesity-related haemodynamic overload culminating in ventricular hypertrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We synthesized high-impact evidence from pivotal randomized trials and mechanistic studies published between 2015 and 2026, focusing on cardiometabolic outcomes, adipose tissue remodelling and haemodynamic effects of both drug classes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Tirzepatide produced substantial weight loss (&gt; 20%), significant reductions in epicardial and paracardiac adipose tissue and a 19.5-point improvement in Kansas City Cardiomyopathy Questionnaire scores in the SUMMIT trial. SGLT2i, exemplified by empagliflozin, demonstrated foundational benefit through natriuresis, improved myocardial energetics and reduced heart failure hospitalization independent of diabetes status, with additional renal-protective effects. Because SUMMIT and EMPEROR-Preserved differed in design and populations, direct comparison between agents is not statistically valid; each should be assessed on its own evidence base.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Tirzepatide and SGLT2i act through distinct, physiologically complementary pathways converging on the cardio-renal-metabolic axis. While their combined use is mechanistically promising, it has not yet been tested in a dedicated randomized controlled trial, and prospective studies are needed to establish safety and long-term efficacy in obesity-related HFpEF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70298","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Clinically Aligned Two-Stage Machine Learning Framework for Predicting Hungry Bone Syndrome After Parathyroidectomy","authors":"Shih-Min Yin,&nbsp;Yu-Chieh Lin,&nbsp;Tzu-Hsun Hung,&nbsp;Shen-En Chou,&nbsp;Shun-Yu Chi,&nbsp;Fong-Fu Chou,&nbsp;Yi-Ju Wu,&nbsp;Si-Yuan Wu,&nbsp;Jenn-Jier James Lien,&nbsp;Po-Chih Kuo,&nbsp;Yi-Chia Chan","doi":"10.1002/edm2.70297","DOIUrl":"https://doi.org/10.1002/edm2.70297","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hungry bone syndrome (HBS) is a frequent and clinically significant complication following parathyroidectomy (PTX) in patients with secondary hyperparathyroidism (SHPT), often leading to prolonged hypocalcaemia and increased healthcare burden. Existing prediction models are limited by small sample sizes and inability to capture complex clinical interactions. This study aimed to develop and validate a clinically aligned, two-stage machine learning (ML) framework to predict HBS after PTX.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A retrospective cohort of patients undergoing PTX for SHPT between 2008 and 2025 at a tertiary centre was analysed. A two-stage ML framework was constructed: stage 1 used preoperative variables to generate a risk score, and stage 2 integrated this score with intraoperative features. Multiple ML models were evaluated using area under the receiver operating characteristic curve (AUROC), calibration metrics and resampling techniques.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 882 patients were included, with an HBS incidence of 69.9%. EasyEnsemble and logistic regression demonstrated the highest discrimination (AUROC 0.712), outperforming the <i>k</i>-nearest neighbours baseline. EasyEnsemble achieved the best overall performance (accuracy 0.707, F1 score 0.666) and calibration (Brier score 0.186). Key predictors included elevated preoperative alkaline phosphatase, higher intact parathyroid hormone levels and lower serum calcium.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This two-stage ML framework demonstrated acceptable predictive performance and aligns with clinical decision-making processes. It enables early identification of high-risk patients and may support individualised perioperative management to mitigate HBS and its complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on ‘Clinical Presentation and Early Outcomes of Congenital Endocrine Salt-Wasting Syndromes Unrelated to 21-Hydroxylase Deficiency’","authors":"Gulalai Tariq,&nbsp;Muhammad Faizan Khan,&nbsp; Malghalara","doi":"10.1002/edm2.70299","DOIUrl":"10.1002/edm2.70299","url":null,"abstract":"&lt;p&gt;We read with great interest the recent article by Ferrari et al. [&lt;span&gt;1&lt;/span&gt;]. The authors should be congratulated for reporting one of the largest single-centre cohorts of these exceptionally rare endocrine disorders and for providing valuable insights into their clinical presentation, diagnostic challenges and early outcomes. Given the rarity of these conditions, the study represents an important contribution to the paediatric endocrinology literature. However, we believe that several methodological aspects warrant further discussion because they may influence the interpretation of the study's principal conclusions regarding long-term outcomes and disease evolution.&lt;/p&gt;&lt;p&gt;Firstly, we are concerned that the study's conclusions regarding preserved growth outcomes are based on a markedly reduced follow-up cohort. Although 20 patients were initially enrolled, only 8 (40%) remained available for assessment at 36 months [&lt;span&gt;1&lt;/span&gt;], with some diagnostic groups represented by only a single patient. Notably, the most treatment intensive group, systemic pseudohypoaldosteronism type 1 (PHA1s), described as having the greatest treatment burden, was reduced to a single patient at 36 months. Such selective loss to follow-up of high burden cases introduces upward selection bias: the conclusion that growth outcomes were generally preserved may reflect only the subset of patients who tolerated the disease well enough to remain in care, systematically excluding more severely affected children who may have experienced growth impairment. This introduces bias away from the null, artificially inflating the apparent favourable prognosis. As highlighted by Howe et al., substantial loss to follow-up in cohort studies can introduce selection bias and compromise the validity and generalizability of study findings [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Second, the cohort spans a 34-year recruitment period (1989–2023), during which genetic testing evolved from clinical/biochemical diagnosis to molecular confirmation. The authors note that available molecular analyses were performed through targeted single-gene testing, reflecting the diagnostic approach used at the time. This temporal evolution could partly confound the paper's key claim that disease-specific features become more recognizable during follow-up. This apparent emergence of disease-specific features may reflect improved diagnostic capacity in 2023 versus clinical diagnosis in 1989, rather than true biological disease evolution. Consequently, longitudinal diagnostic clarification attributed to disease course may partly represent diagnostic advancement, biasing conclusions about natural disease trajectory away from the null. Numerous methodological studies and reporting guidelines have emphasized that observational studies should explicitly address potential sources of bias that may affect the interpretation of their findings, including temporal bias in long-term retrospective cohorts [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Final","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148608145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing Radioactive Iodine Use After Thyroidectomy in Low-Risk Differentiated Thyroid Cancer: A Systematic Review and Meta-Analysis","authors":"Maheen Asif,&nbsp;Mudasar Nisar,&nbsp;Aliza Asif,&nbsp;Makzooma Batool,&nbsp;Rabia Javed Iqbal,&nbsp;Mohammed Hammad Jaber Amin","doi":"10.1002/edm2.70293","DOIUrl":"10.1002/edm2.70293","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Radioactive iodine (RAI) therapy is often administered post-total thyroidectomy in patients with low-risk differentiated thyroid carcinoma, despite guidelines advising against its routine application. Evidence regarding the efficacy of RAI in reducing recurrence and improving survival in low-risk differentiated thyroid cancer (DTC) remains inconsistent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a systematic review and meta-analysis of observational studies and randomized clinical trials that compare RAI versus no RAI in low-risk DTC patients. Databases such as MEDLINE, Scopus, Cochrane Library, and Google Scholar were searched through December 2025. Outcomes included recurrence, recurrence-free survival, treatment response, biochemical markers, and side effects. We performed statistical analysis using Review Manager (RevMan) 5.4 with a random-effects model, reporting odds ratios (OR) with 95% confidence intervals, and significance set at <i>p</i> &lt; 0.05. Heterogeneity was assessed using <i>I</i>² statistics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ten studies (<i>n</i> = 5260) were included in the analysis. No statistically significant difference was observed between the two groups for recurrence (OR 0.66, 95% CI: 0.41–1.08; <i>p</i> = 0.10), 5-year recurrence-free survival (OR 2.47, 95% CI: 0.63–9.62; <i>p</i> = 0.19), or treatment response (excellent response: OR 1.00, 95% CI: 0.52–1.92; <i>p</i> = 1.00). Secondary outcomes, including serum thyroglobulin &gt; 1 ng/mL (OR 1.20, 95% CI: 0.00–342.55; <i>p</i> = 0.95), elevated thyroglobulin antibodies (OR 0.91, 95% CI: 0.38–2.16; <i>p</i> = 0.83), xerostomia (OR 5.63, 95% CI: 0.05–667.24; <i>p</i> = 0.48), and dysphonia (OR 0.96, 95% CI: 0.53–1.72; <i>p</i> = 0.88), were also not significantly different between groups, although estimates were not precise.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The available randomized and observational evidence does not demonstrate a clear, clinically meaningful benefit of routine RAI ablation in patients classified as low-risk DTC. These findings should be interpreted with caution due to heterogeneity across studies, variability in outcome definitions, and the predominance of observational data.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148608121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}