Endocrinology, Diabetes and Metabolism最新文献

{"title":"Metabolic Changes During a Calorie-Restricted, Fish-Rich Ketogenic Diet Associated With Increased Circulating TMAO in Healthy Adults","authors":"Katarzyna Siedzik, Kamil Góral, Damian Flis, Maciej Jaguszewski, Robert A. Olek, Wiesław Ziółkowski","doi":"10.1002/edm2.70360","DOIUrl":"10.1002/edm2.70360","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A ketogenic diet (KD) is increasingly investigated as a nutritional approach for improving glycemic control and metabolic health. However, relatively few studies have examined fish-rich ketogenic interventions. Fish consumption may substantially increase circulating trimethylamine N-oxide (TMAO), while habitual fish intake is generally associated with favourable cardiometabolic outcomes. The metabolic significance of a short-term diet-induced increase in TMAO therefore remains unclear. This study aimed to characterize changes in circulating TMAO and related metabolites, glycemic and insulin-related biomarkers, oxidative stress markers, and lipid profiles during a fish-rich, calorie-restricted KD in healthy adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nine men and five women (mean age 45 ± 3 years) participated in a 2-week, single-arm, within-subject pre–post dietary intervention. TMAO and related metabolites, selected glycemic and insulin-related biomarkers, oxidative stress markers, and lipid-profile parameters were assessed before and after the intervention. Participants followed individualized fish-rich ketogenic meal plans providing an approximately 500 kcal/day energy deficit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following the intervention, circulating TMAO and betaine concentrations increased significantly, whereas carnitine and glycerophosphocholine (GPC) concentrations decreased. Favourable changes were observed in fasting glucose, insulin, C-peptide, leptin, and resistin. HDL cholesterol decreased significantly, while total cholesterol, LDL cholesterol, and triglycerides remained unchanged. No evidence of increased oxidative stress was observed. The direct estimate of insulin sensitivity (HOMA-%S) did not reach statistical significance after correction for multiple comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A 2-week, calorie-restricted, fish-rich ketogenic intervention was associated with a marked increase in circulating TMAO together with favourable changes in selected glycemic, insulin-related, and adipokine biomarkers, without evidence of increased oxidative stress. HDL cholesterol decreased, whereas other lipid-profile parameters remained largely unchanged. Because caloric restriction, ketogenic macronutrient composition, high fish intake, and reductions in body weight and adiposity occurred simultaneously, the independent contribution of TMAO to these metabolic changes cannot be determined. These findings should therefore be considered preliminary and hypoth","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70360","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196902","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":"Real-World Metabolic Improvements in Women With and Without Polyendocrine Metabolic Syndrome via a Multidisciplinary Telehealth Care Platform","authors":"Heather G. Huddleston,&nbsp;Rachel Blank,&nbsp;Nandita Sommers,&nbsp;Nicole Hellman,&nbsp;Felice Ramallo,&nbsp;Tiffany Pham,&nbsp;Karla Lindquist","doi":"10.1002/edm2.70332","DOIUrl":"10.1002/edm2.70332","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate metabolic outcomes in women with and without Polyendocrine Metabolic Ovarian Syndrome (PMOS, formerly Polycystic Ovary Syndrome (PCOS))) receiving multidisciplinary care through a women's health telehealth platform that combines physician and registered dietitian support.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective cohort analysis of 919 women with BMI ≥ 25 initiating care in 2024, with ≥ 6 months follow-up (mean 9.6 months). Participants included 557 with PMOS and 362 without. Outcomes extracted from the electronic health record (EHR) included change in weight, HbA1c, HOMA-IR, fasting insulin, fasting glucose, ALT, AST and total cholesterol between baseline and last measured value. Linear regression models adjusted for baseline values of each outcome, age, BMI, race/ethnicity and follow-up time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant improvements were observed across all metabolic markers for the group overall: HOMA-IR (−14.0%), fasting insulin (−15.6%), fasting glucose (−13.0%), HbA1c (−6.2%), ALT (−21.2%), AST (−25.5%), total cholesterol (−8.0%) and weight (−4.9%). PCOS status was not associated with differential improvement in any outcome after adjustment. GLP-1 receptor agonist use was associated with greater weight loss; however, improvements were also observed in the no-medication group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Women with PCOS achieved metabolic improvements equivalent to those without PMOS through a multidisciplinary telehealth model despite presenting with a more adverse metabolic profile at baseline.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184646","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":"Efficacy and Safety of Enlicitide in Hypercholesterolemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","authors":"Muhammad Farhan,&nbsp;Muhammad Murtaza,&nbsp;Muhammad Mujtaba Rasool,&nbsp;Farah Khan,&nbsp;Hammad Amjad,&nbsp;Kuldeep Dalpat Rai,&nbsp;Sheikh Muhammad Ebtehaj Ali,&nbsp;Ahmed Asad Raza,&nbsp;Muhammad Ahmad Sohail,&nbsp;Abedin Samadi,&nbsp;Furqan Hassan","doi":"10.1002/edm2.70358","DOIUrl":"10.1002/edm2.70358","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Atherosclerotic cardiovascular disease remains a leading cause of global mortality, with low-density lipoprotein cholesterol (LDL-C) reduction being the cornerstone of prevention. Despite effective therapies, many high-risk patients do not achieve recommended LDL-C targets. Enlicitide (MK-0616), an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, offers a potential alternative to injectable PCSK9-directed therapies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To evaluate the efficacy and safety of enlicitide in adults with hypercholesterolemia and assess its dose-dependent effects on lipid parameters.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) according to PRISMA 2020 guidelines. PubMed, Embase, Scopus, ClinicalTrials.gov, and Google Scholar were searched from inception through March 2026. Random-effects meta-analysis using restricted maximum likelihood estimation was performed. The primary outcome was the percentage change in LDL-C from baseline. Secondary outcomes included non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), lipoprotein(a), triglycerides, and safety outcomes. Risk of bias and certainty of evidence were assessed using RoB 2.0 and GRADE.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Three placebo-controlled RCTs involving 3593 participants were included. Enlicitide significantly reduced LDL-C compared with placebo (mean difference [MD], −56.19%; 95% CI, −64.14 to −48.25; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), with moderate heterogeneity (&lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 56.9%). Significant reductions were also observed in non-HDL-C (MD, −51.36%), ApoB (MD, −47.09%), lipoprotein(a) (MD, −20.10%), and triglycerides (MD, −13.12%). A numerical dose–response gradient was observed, although subgroup differences were not statistically significant. Sensitivity analyses supported the robustness of the findings. Rates of adverse events, serious adverse events, and treatment discontinuation were comparable between groups.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Enlicitide produced substantial reductions in LDL-C and other atherogenic lipid parameters without an apparent increase in adverse events. However, findings should be interpreted cautiously given the limited number of trials, moderate heterogeneity, and reliance on surrogate endpoints. Dose–response, duration-related lipo","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184355","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 Higher Post-Operative L-Thyroxine Dosage Needed After Right Compared to Left-Lobe Hemithyroidectomy","authors":"Nayab Ikram,&nbsp;Madeeha Amir","doi":"10.1002/edm2.70362","DOIUrl":"10.1002/edm2.70362","url":null,"abstract":"&lt;p&gt;We have read with interest the study by Deischinger et al. [&lt;span&gt;1&lt;/span&gt;] investigating the association between the side of hemithyroidectomy and postoperative levothyroxine requirements. It provides comparative evidence between right- and left- sided hemithyroidectomy and suggests that right- sided hemithyroidectomy may be associated with higher postoperative levothyroxine requirement. Unlike other studies focusing on patient-related factors, this study also considers surgical site and we commend the authors for this contribution. We would like to raise points that deserve further consideration.&lt;/p&gt;&lt;p&gt;First, postoperative TSH was higher following right-sided surgery than left-sided surgery (1.70 vs. 1.40 μIU/mL, &lt;i&gt;p&lt;/i&gt; = 0.011), yet the model adjusted for preoperative rather than postoperative TSH. Thus, the groups were compared at different postoperative biochemical levels. Additionally, a dose recorded at a single visit, without documented titration, may not accurately reflect a stable dose requirement [&lt;span&gt;2, 3&lt;/span&gt;]. A sensitivity analysis restricted to patients with TSH within the target range would help determine whether the observed effect persists after accounting for postoperative biochemical differences.&lt;/p&gt;&lt;p&gt;Secondly, thyroid volume measurements were available in only 112/426 patients (26%). The authors suggested thyroid volume resection as a main reason for the higher levothyroxine requirement [&lt;span&gt;1&lt;/span&gt;], but thyroid volume assessment was performed in only a limited number of patients. Previous evidence has also linked thyroid remnant volume with post-operative hypothyroidism [&lt;span&gt;4&lt;/span&gt;]. So, it limits the dependence of higher levothyroxine on resected thyroid volume. Future studies should obtain standardized thyroid volume measurements in the full cohort.&lt;/p&gt;&lt;p&gt;Third, the adjusted difference (+7.9ug/day; 95% Cl, 1.38–14.45) is smaller than a typical levothyroxine titration increment of 12.5–25 μg [&lt;span&gt;2&lt;/span&gt;], while the observed correlation was weak (&lt;i&gt;r&lt;/i&gt;&lt;sub&gt;s&lt;/sub&gt; = −0.103) [&lt;span&gt;1&lt;/span&gt;]. The clinical significance of this relatively small difference for postoperative management therefore remains uncertain.&lt;/p&gt;&lt;p&gt;We raised these points not to diminish authors' work, but to highlight that future studies should assess LT4 requirements after stable biochemical optimization, with TSH and LT4 measurements alongside thyroid-volume assessment. This may help clarify whether the observed higher LT4 dose after right-sided hemithyroidectomy represents a true side-related requirement and strengthen the evidence for this association.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Nayab Ikram:&lt;/b&gt; writing – review and editing, writing – original draft, resources, project administration, visualization, funding acquisition, supervision, formal analysis, validation, investigation, software, data curation, methodology, conceptualization. &lt;b&gt;Madeeha Amir:&lt;/b&gt; writing – review and editing.&lt;/p&gt;&lt;p&gt;The authors have nothing to report.&lt;/p&gt;&lt;p&gt;The authors have ","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184292","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":"Liraglutide Dose Affordability and Durability in Real-World Obesity Care","authors":"Azhar Zafar,&nbsp;Carina Scarlata","doi":"10.1002/edm2.70364","DOIUrl":"10.1002/edm2.70364","url":null,"abstract":"&lt;p&gt;Tu and colleagues provide valuable prospective, multicentre post-marketing evidence on liraglutide for adults with obesity in Taiwan. These findings suggest that clinically meaningful benefit may occur below 3.0 mg, supporting personalised rather than universal dose escalation [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The key implementation finding is that 49% of participants who did not reach 3.0 mg cited medication cost. Affordability is therefore a system-level determinant of dose attainment, treatment continuity and real-world effectiveness. Obesity care must consider whether a sustainable dose can be achieved and maintained, not simply whether treatment is effective at the target dose. Cost-limited dosing risks inequitable treatment intensity based on ability to pay rather than clinical need. Interpretation requires caution. This single-arm study excluded participants who withdrew before follow-up; around half withdrew before week 13 and only 60 contributed to the week-26 analysis. Results in continuing users are encouraging but cannot establish comparative effectiveness, discontinuation outcomes or long-term weight maintenance. Randomised studies support liraglutide 3.0 mg with lifestyle intervention [&lt;span&gt;2&lt;/span&gt;], while maintenance studies underline the need to consider persistence rather than short-term loss alone [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;A further question is whether lower-dose success represents a reproducible, clinically appropriate strategy or an artefact of selection bias. In this surveillance cohort, lower exposure may have reflected four distinct mechanisms: intentional dose limitation due to gastrointestinal tolerability (clinically appropriate), cost constraints (a barrier to equitable care), clinical preference based on individual risk–benefit assessment or other unmeasured factors. Real-world evidence increasingly documents the complex barriers to treatment persistence; discontinuation rates for GLP-1 receptor agonists are substantial, with cost and tolerability emerging as principal drivers of dose escalation failure and early discontinuation [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The distinction between tolerability-limited dosing and cost-limited dosing is crucial for policy: the former represents appropriate personalised medicine, while the latter represents an avoidable barrier to equitable treatment. Analyses that stratify these mechanisms, relating achieved dose, duration, discontinuation reason and individual weight trajectory, would help distinguish tolerable, sustainable treatment from treatment limited by systemic financial barriers. Reporting denominators at each time point, including weight outcomes for those who discontinue where feasible, would make the real-world picture more complete.&lt;/p&gt;&lt;p&gt;The implications extend beyond Taiwan. Although access pathways, reimbursement and service capacity differ between health systems, the affordability principle identified in Taiwan is directly applicable to NHS systems, where formulary restrictions and ","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184671","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":"Gene-Guided Therapy in Type 2 Diabetes Mellitus: An Integrative Review of the Pharmacogenetics of Metformin and Sodium-Glucose Cotransporter-2 Inhibitors","authors":"Imran Hossain,&nbsp;Mahnoor Haidar,&nbsp;Mahfuj Ahmed Ratul,&nbsp;Jannatul Ferdous Sumona,&nbsp;Sraboni Shabnaz,&nbsp;Abul Fojal Nokib,&nbsp; Fatema-Tuz-Zohora","doi":"10.1002/edm2.70343","DOIUrl":"10.1002/edm2.70343","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inter-individual variability in the therapeutic response to antidiabetic drugs is still a big problem in the management of type 2 diabetes mellitus (T2DM). Genetic polymorphisms of drug transporters, metabolizing enzymes and molecular targets have become significant factors in drug efficacy, pharmacokinetics and adverse effects. This review aims to provide a summary of the current evidence on the pharmacogenomics of metformin and sodium-glucose cotransporter-2 (SGLT2) inhibitors and their implications for precision medicine in T2DM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Published human studies examining genetic polymorphisms related to the various effects of metformin and SGLT2 inhibitors in patients with T2DM were systematically searched in PubMed, Scopus and EBSCO and analysed using an integrative review. Qualitative synthesis was used to compare the pharmacogenetic profiles of the two drug classes and to look for potential biomarkers for precision therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Metformin has the most comprehensive pharmacogenetic evidence, including variants in SLC22A1 (OCT1), SLC22A2 (OCT2), SLC22A3 (OCT3), SLC47A1 (MATE1), SLC47A2 (MATE2), ATM and other genes that affect drug disposition, glycemic response and adverse effects. However, pharmacogenetic research on SGLT2 inhibitors is still scarce. Modest variations in drug exposure, glucose homeostasis and cardiorenal or hepatic outcomes have been reported for variants of UGT1A9, UGT2B4, SLC5A2, PNPLA3, and some glucose transporters, but most of these effects have not been strong enough to recommend routine genotype-based therapy. Metformin has more robust and consistent pharmacogenetic associations overall, while SGLT2 inhibitors have emerging but less definitive associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Pharmacogenomics has great promise to enhance the selection of antidiabetic drugs, maximize therapeutic effect and minimize side effects. There is current evidence for the clinical relevance of several pharmacogenetic markers for metformin, but evidence for SGLT2 inhibitors is preliminary. Further, large, prospective, multiethnic studies and genotype-based clinical trials are needed to confirm candidate biomarkers and to help incorporate pharmacogenomics into precision medicine for T2DM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169856","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":"Impact of Evolocumab on LDL-Cholesterol and Cardiovascular Outcomes in Patients With Established CVD: Systematic Review and Meta-Analysis","authors":"Anika Goel,&nbsp;Muhammad Abdullah Naveed,&nbsp;Hemeesh Tandel,&nbsp;Affaf Mahmood,&nbsp;Muhammad Mukhlis,&nbsp;K. Sai Varun Reddy,&nbsp;Arun Kumar Maloth,&nbsp;Anchit Chauhan,&nbsp;Ameer Ashwara,&nbsp;Amogh Verma,&nbsp;Haris Bin Tahir","doi":"10.1002/edm2.70355","DOIUrl":"10.1002/edm2.70355","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality, and many high-risk patients fail to reach LDL-cholesterol (LDL-C) targets on statins alone. Evolocumab, a PCSK9 inhibitor, offers potent LDL-C lowering, but a synthesis of its lipid and clinical benefits in secondary prevention is needed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a systematic review and meta-analysis of randomised controlled trials evaluating evolocumab in adults with established cardiovascular disease. PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched through April 2025. Outcomes included lipid parameters, major adverse cardiovascular events (MACE), individual cardiovascular endpoints, and safety, with pooled risk ratios (RR) and mean differences calculated using random-effects models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nine trials enrolling 67,662 patients were included. Evolocumab significantly reduced LDL-C (mean difference −57.73 mg/dL), total cholesterol (−52.27 mg/dL), triglycerides (−21.21 mg/dL), and lipoprotein(a) (−10.99 mg/dL), while increasing HDL-cholesterol (3.69 mg/dL). Evolocumab was associated with lower MACE (RR 0.53; 95% CI 0.40–0.71), though this estimate should be interpreted cautiously given heterogeneity in endpoint definitions and study designs. Myocardial infarction (RR 0.74) and coronary revascularisation (RR 0.80) were significantly reduced, while cardiovascular mortality and stroke showed no statistically definitive reduction. Serious adverse events and neurocognitive effects were comparable between groups, though injection-site reactions were more frequent with evolocumab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In patients with established cardiovascular disease, evolocumab provides substantial lipid lowering and reduces ischemic events without major safety concerns, supporting its use as an adjunct to statin therapy in secondary prevention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70355","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137841","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":"Diabetic Autonomic Neuropathy and Impaired Inflammatory Reflex","authors":"Narges Dastmalchi,&nbsp;Mohammad Amin Doustvandi,&nbsp;Reza Rahbarghazi,&nbsp;Khalil Hajiasgharzadeh","doi":"10.1002/edm2.70349","DOIUrl":"10.1002/edm2.70349","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Diabetes mellitus is increasingly recognised as a chronic metabolic-inflammatory disorder. Diabetic autonomic neuropathy (DAN) is a prevalent yet underdiagnosed complication associated with significant morbidity and mortality. Rather than acting solely as an end-stage downstream consequence of hyperglycemia, DAN may serve as an active driver of neuroimmune dysfunction by disrupting the inflammatory reflex and its efferent arm, the cholinergic anti-inflammatory pathway (CAP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review synthesises current preclinical and clinical literature examining the physiological architecture of the inflammatory reflex, the molecular mechanisms linking hyperglycemia-induced neurovascular damage to CAP failure (including α7 nicotinic acetylcholine receptor (α7nAChR) signalling), and diagnostic modalities (e.g., heart rate variability) used to evaluate autonomic-immune crosstalk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Evidence indicates that metabolic stress, oxidative damage, and microvascular ischemia compromise vagal structural integrity and suppress cholinergic anti-inflammatory signalling. This loss of autonomic restraint exacerbates systemic cytokine production (e.g., TNF-α, IL-6), establishing a self-perpetuating, bidirectional pathophysiological loop that accelerates both neural injury and end-organ complications. Emerging therapeutic strategies—such as exercise-induced autonomic reactivation, bioelectronic vagus nerve stimulation (VNS), and targeted α7nAChR agonists—demonstrate promising potential to interrupt this cycle and restore neuroimmune homeostasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DAN represents a critical state of autonomic-mediated immune dysregulation rather than isolated neural damage. While causal mechanisms require further validation through prospective and interventional human trials, reframing DAN as a neuroimmune failure provides novel opportunities for precision phenotyping and targeted therapeutic interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70349","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138588","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":"Comparison of Clinical, Metabolic, and Hormonal Profiles in Obese Versus Lean Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis","authors":"Fatema Tuz Zahura Aalpona,&nbsp;Apurba Sarker,&nbsp;Lutfun Nahar,&nbsp;Md Abdul Bari Robel,&nbsp;A. B. M. Kamrul-Hasan","doi":"10.1002/edm2.70350","DOIUrl":"10.1002/edm2.70350","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Obesity substantially influences clinical and metabolic manifestations of polycystic ovary syndrome (PCOS). However, differences in clinical, metabolic, and hormonal profiles between obese and lean women with PCOS have not been explored in large-scale meta-analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Databases were searched from inception through 31 December 2025 for studies reporting clinical, metabolic, and hormonal profiles in obese and lean PCOS phenotypes. Random-effects meta-analyses in R yielded mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty-two studies (<i>N</i> = 5363; 3078 obese, 2285 lean PCOS) met inclusion criteria. Menstrual irregularity (84.7% vs. 70.9%; RR 1.19), hirsutism (65.9% vs. 58.8%; RR 1.10), acne (44.9% vs. 36.8%; RR 1.25), acanthosis nigricans (52.7% vs. 22.6%; RR 1.94), and biochemical hyperandrogenism (45.6% vs. 31.8%; RR 1.49) were more prevalent in obese than in lean PCOS. Obese PCOS was associated with a less favourable cardiometabolic profile, with higher HOMA-IR (MD 2.03), fasting (MD 5.12 mg/dL), and 2-h (MD 9.91 mg/dL) plasma glucose, and greater risks of prediabetes (25.3% vs. 12.1%; RR 1.84), diabetes (8.6% vs. 2.7%; RR 2.58), and metabolic syndrome (51.2% vs. 11.9%; RR 3.59). Mean lipid levels were worse in obese PCOS, with higher total cholesterol, triglycerides, and LDL cholesterol, and lower HDL cholesterol. Nonetheless, lean PCOS exhibited substantial burdens of menstrual dysfunction, hyperandrogenism, insulin resistance, dysglycemia, and dyslipidemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Obesity in PCOS is associated with more severe reproductive, metabolic, and hormonal abnormalities, but lean PCOS still carries substantial reproductive and metabolic burdens. However, the observational design of the included studies and substantial heterogeneity across several outcomes warrant cautious interpretation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The meta-analysis was registered with PROSPERO under registration number CRD420251240521. The review protocol summary is available on the PROSPERO website</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138558","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":"Glycaemic Variability and C-Peptide in Bangladeshi Children, Adolescents, and Young Adults With Diabetes: A Prospective Study","authors":"Ajmina Hasan Flabe,&nbsp;Bedowra Zabeen,&nbsp;Shatil Amirat,&nbsp;Jing Luo","doi":"10.1002/edm2.70347","DOIUrl":"10.1002/edm2.70347","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To characterise the magnitude of glycaemic variability and to examine the factors associated with it, with particular attention to residual beta-cell function measured by fasting C-peptide, in children, adolescents, and young adults with diabetes in Bangladesh.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design and Setting</h3>\u0000 \u0000 <p>Prospective observational study at the BADAS Paediatric Diabetes Care and Research Centre, BIRDEM, Dhaka, using 14 days of blinded professional continuous glucose monitoring (CGM). Participants were enrolled between March and November 2024.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Participants</h3>\u0000 \u0000 <p>Ninety-seven participants aged 1–25 years (68 with Type 1 and 29 with Type 2 diabetes) had at least seven valid CGM days and a paired HbA1c within 2 weeks of CGM initiation. Fasting C-peptide was available for 46 participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Outcome Measures</h3>\u0000 \u0000 <p>The coefficient of variation (CV) of glucose as the primary metric of variability; time in range, time above range, and time below range as secondary metrics; and independent predictors of CV on multivariable regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mean CV was 39.4% (SD 9.2), and 59 of 97 participants (60.8%) were at or above the recommended target of 36%. CV was higher in Type 1 than Type 2 diabetes (41.9% vs. 33.3%). Lower fasting C-peptide was independently associated with higher CV after adjustment for diabetes type, age, and insulin dose (−1.94 percentage points per ng/mL, 95% CI −3.35 to −0.53; model R-squared 0.52), with a graded relationship across pre-specified C-peptide categories for CV, time in range, and time below range.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Glycaemic variability substantially exceeds international targets in this setting. Fasting C-peptide, available for fewer than half of the cohort, showed a graded association with variability that is best regarded as hypothesis-generating; if confirmed in larger studies, it could offer a low-cost means of identifying children at highest variability risk where CGM access is limited.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115993","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}