Journal of Internal Medicine最新文献

{"title":"Treatment of hyperphagia and obesity in Prader-Willi syndrome.","authors":"Charlotte Höybye, Janice Foster, Anthony P Goldstone, Linda Gourash, Jennifer Miller, Maithé Tauber","doi":"10.1111/joim.70173","DOIUrl":"https://doi.org/10.1111/joim.70173","url":null,"abstract":"<p><p>Prader-Willi syndrome (PWS) is a rare, neurodevelopmental, multisystemic syndrome caused by lack of expression of paternal genes on chromosome 15q11.2-13. PWS is characterized by muscular hypotonia, abnormal body composition, hormone deficiencies, cognitive dysfunction and behavioural issues, including hyperphagia, increasing the risk of severe obesity. A single causative gene for hyperphagia has not been identified, and regulation of hunger and satiety is complex and multifactorial, making it difficult to identify a specific neuropeptide or hormone as the most important. Cornerstone treatments are a strict, controlled diet and regular physical activity. Several clinical trials with different pharmacological agents have been performed attempting to reduce or treat hyperphagia and obesity. However, many drug programmes have been discontinued due to adverse events or not reaching endpoints. In this review, we have focused on phenomenology and management of hyperphagia, treatment with oxytocin (OT), glucagon-like-peptide-1 receptor agonists (GLP-1RA) and diazoxide choline. We conclude that controlled food access is crucial; managing expectations about food mitigates food-related behaviour; OT treatment of infants with PWS results in less severe hyperphagia at ages 3 and 4 years old; and that the effects of GLP-1RA on body weight seem modest. Studies of diazoxide choline extended-release (DCCR), the first approved treatment of hyperphagia in PWS, have shown promising results, particularly in managing severe hyperphagia, reducing fat mass and improving behavioural issues. Thus, although progress is being made in targeted pharmacological therapies to control hyperphagia, controlled food access remains crucial to prevent obesity but is not sufficient for management of food and behaviour.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 receptor agonists and serious adverse events: Evidence, uncertainty and clinical implications.","authors":"Peter Ueda","doi":"10.1111/joim.70170","DOIUrl":"https://doi.org/10.1111/joim.70170","url":null,"abstract":"<p><p>Glucagon-like peptide-1 (GLP-1) receptor agonists provide benefits in weight reduction, glycaemic control in Type 2 diabetes, and cardiovascular and renal outcomes. Their widespread use has given rise to concerns regarding rare but potentially serious adverse events. This narrative review appraises evidence regarding seven serious adverse events linked to GLP-1 receptor agonists: thyroid cancer, non-arteritic anterior ischaemic optic neuropathy (NAION), suicidal behaviours and self-harm, diabetic retinopathy complications, acute pancreatitis, gallbladder and biliary disease and intestinal obstruction. Evidence from mechanistic studies, spontaneous reports, randomized trials and cohort studies is considered. Gallbladder and biliary disease has the most consistent evidence supporting a causal association. Worsening of diabetic retinopathy appears most consistent with early worsening after rapid glycaemic improvement in patients with pre-existing retinopathy. For thyroid cancer, NAION, suicidal behaviour and self-harm, acute pancreatitis and intestinal obstruction, evidence regarding causality remains uncertain. Rare events, incomplete ascertainment in trials and residual confounding in observational studies limit inference. Because these events are rare, even substantial relative risk increases generally correspond to small absolute risk increases in broad populations but may become relevant in patients with high baseline risk. Treatment decisions should consider the strength and uncertainty of safety evidence, individual baseline risk, expected benefits relative to available alternatives and patient preferences.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond maternal remission: Placental dysfunction in systemic lupus erythematosus pregnancy.","authors":"Stefania Triunfo","doi":"10.1111/joim.70171","DOIUrl":"https://doi.org/10.1111/joim.70171","url":null,"abstract":"","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High urine osmolality and elevated urine sodium predict early nonresponse to fluid restriction in patients with the syndrome of inappropriate antidiuresis.","authors":"Michelle Patricia Müller, Laura Potasso, Ewout J Hoorn, Julie Refardt, Mirjam Christ-Crain","doi":"10.1111/joim.70167","DOIUrl":"https://doi.org/10.1111/joim.70167","url":null,"abstract":"<p><strong>Introduction: </strong>Fluid restriction is the current first-line therapy for hyponatremia induced by the syndrome of inappropriate antidiuresis (SIAD), yet up to 50% of patients do not achieve an adequate plasma sodium correction. Reported predictors of nonresponse include urine osmolality >500 mOsm/kg, the Furst ratio >1 [(UNa + UK)/(PNa)], urine sodium >130 mmol/L, and plasma urea >5 mmol/L. This study aimed to validate these cutoffs in an independent cohort.</p><p><strong>Methods: </strong>This is a predefined secondary analysis of a randomized, controlled, prospective, and multicenter hyponatremia trial (plasma sodium <130 mmol/L). Response to fluid restriction was defined as an increase in plasma sodium of >3 mmol/L within the first 24 h.</p><p><strong>Results: </strong>Of 839 patients with SIAD, 229 were treated with fluid restriction within the first 24 h and had complete laboratory data. Among these patients, 86 (38%) were classified as responders and 143 (62%) as nonresponders. Higher urine osmolality (p = 0.015) and higher plasma sodium levels (p < 0.001) were independently associated with nonresponse in multivariable logistic regression analysis. Urine osmolality >500 mOsm/kg had a specificity of 78% (positive likelihood ratio (LR+) 1.68), whereas urine sodium >130 mmol/L had a specificity of 97% (LR+ 3.81). The combination of both cutoffs markedly improved discriminatory performance (LR+ 9.62, positive predictive value 0.94).</p><p><strong>Conclusion: </strong>The present study validated urine osmolality >500 mOsm/kg and urine sodium >130 mmol/L as cutoffs for predicting nonresponse to fluid restriction in patients with SIAD. Combining both cutoffs identifies patients at high risk of nonresponse, in whom early initiation of second-line therapy should be strongly considered.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Employment status and occupation are associated with liver cirrhosis: A nationwide Swedish case-control study.","authors":"Marie Zalesiak, Juan Vaz, Eralda Asllanaj, Martin Henriksson, Hannes Hagström, Ying Shang","doi":"10.1111/joim.70166","DOIUrl":"10.1111/joim.70166","url":null,"abstract":"<p><strong>Background: </strong>Liver cirrhosis is often diagnosed in working-age adults and carries a poor prognosis. A better understanding of variation by employment status and occupation may support earlier and more targeted diagnostic evaluation.</p><p><strong>Objectives: </strong>To assess the odds of liver cirrhosis across labor-market status and occupations in working-age adults and whether these patterns differed by etiology.</p><p><strong>Methods: </strong>In this nationwide case-control study, individuals aged 35-65 years with cirrhosis during 2002-2021 were identified from Swedish national registries and matched to up to four controls on age, sex, and municipality. Labor-market status in the year before diagnosis was classified as employed, unemployed, disability/activity benefit, long-term sick leave, or other. Employed individuals were classified into occupations. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals, with physical and engineering professionals as the reference group.</p><p><strong>Results: </strong>We included 23,033 cases and 92,106 controls. Cases were less often employed than controls (25.7% vs. 66.2%) and more often belonged to labor-market strata associated with a lower socioeconomic status. In analyses, including employed and unemployed individuals (7485 cases; 63,747 controls), unemployment was associated with the highest odds of cirrhosis. Among employed individuals, food preparation workers and refuse and recycling workers had the highest odds. Stratified by etiologies, associations were strongest for alcohol-related cirrhosis. Patterns across sex strata were similar, with generally larger effect sizes in men.</p><p><strong>Conclusion: </strong>Among working-age adults, unemployment and selected occupations were strongly associated with incident cirrhosis. Routinely collected employment information may help identify groups who could benefit from earlier liver evaluation.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk and outcomes of adrenal crisis in primary adrenal insufficiency: Evidence from a 24-year nationwide cohort study","authors":"Ann-Elin Meling Stokland,&nbsp;Lars Breivik,&nbsp;Ingvild Dalen,&nbsp;Sandra Dis Steintorsdottir,&nbsp;Simon Kildal,&nbsp;Ingrid Nermoen,&nbsp;Kari Lima,&nbsp;Margrethe Svendsen,&nbsp;Åse Bjorvatn Sævik,&nbsp;Aleksandra Debowska,&nbsp;Stina Therese Sollid,&nbsp;Daniel Hannisdal,&nbsp;Trine Elisabeth Finnes,&nbsp;Agnes Judit Horvath,&nbsp;Elin Korsgaard,&nbsp;Hallvard Singsås,&nbsp;Bjørn O. Åsvold,&nbsp;Maria Eriksson Steigen,&nbsp;Sigrid Blika,&nbsp;Petya Milova,&nbsp;Anders Svare,&nbsp;Anja Fog Heen,&nbsp;Lene Katrine Bjerke,&nbsp;Marianne Stedje,&nbsp;Siri Carlsen,&nbsp;Bjørn Gunnar Nedrebø,&nbsp;Anders Palmstrøm Jørgensen,&nbsp;Grethe Å. Ueland,&nbsp;Marianne Øksnes,&nbsp;Eystein Sverre Husebye","doi":"10.1111/joim.70153","DOIUrl":"10.1111/joim.70153","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adrenal crisis is a life-threatening emergency. Despite preventive strategies, previous reports suggest increasing incidence and substantial mortality, but robust validated data are limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess temporal trends in adrenal crisis incidence and identify associated risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied 1040 patients with autoimmune or idiopathic primary adrenal insufficiency enrolled in the Norwegian Addison Registry. Medical records were reviewed for crisis-related hospitalizations between 2000 and 2023. Overt adrenal crisis was defined by acute clinical deterioration with hemodynamic or biochemical abnormalities, whereas incipient crisis was defined by typical symptoms without objective abnormalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During a median follow-up of 15 years, 660 patients (63%) experienced crisis-related hospitalizations, and 265 (25%) had an overt adrenal crisis after diagnosis. The incidence of overt crises was 3.2 per 100 person-years and that of incipient crises was 6.9 per 100 person-years. Admission rates for incipient crises increased significantly over time (<i>p</i> &lt; 0.001), whereas overt crisis rates remained stable. Among 1754 admissions, five deaths (0.3%) were attributed to adrenal crisis. Both younger and older age (<i>p</i> &lt; 0.001) and type 1 diabetes (incidence rate ratio 2.09, 95% confidence interval 1.45–3.01; <i>p</i> &lt; 0.001) were associated with increased overt crisis risk. Daily corticosteroid dose was not associated with crisis risk. Prehospital stress dosing was used in about 50% of admissions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overt adrenal crisis was uncommon and crisis-related in-hospital mortality was exceptionally low. Crisis risk was independent of replacement dose but increased in patients with type 1 diabetes. Strengthening education and implementation of prehospital stress dosing may further reduce the burden of adrenal crises.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 5","pages":"675-688"},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can the gut microbiome help ‘digest’ insomnia? A novel target in sleep medicine","authors":"André P. Pacheco,&nbsp;Christian Benedict","doi":"10.1111/joim.70131","DOIUrl":"10.1111/joim.70131","url":null,"abstract":"&lt;p&gt;Insomnia disorder, characterized by persistent difficulties in sleep initiation or maintenance accompanied by daytime impairment, affects 16.2% of the global population [&lt;span&gt;1&lt;/span&gt;]. Cognitive behavioural therapy for insomnia (CBT-I), a structured psychological intervention targeting maladaptive sleep-related cognitions and behaviours, is the recommended first-line treatment [&lt;span&gt;2&lt;/span&gt;], yet therapeutic response is achieved in approximately 70%–80% of patients during acute treatment, with a substantial minority remaining symptomatic [&lt;span&gt;3&lt;/span&gt;]. Pharmacological treatments are further limited by risks of tolerance and dependence, as well as daytime drowsiness and cognitive impairment [&lt;span&gt;2&lt;/span&gt;]. Consequently, novel therapeutic approaches are needed, particularly for patients with refractory insomnia, given the disorder's substantial and potentially long-term adverse health consequences [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In parallel with these clinical limitations, individuals with insomnia appear to exhibit differences in gut microbiome composition and functional potential compared with healthy sleepers [&lt;span&gt;5&lt;/span&gt;], including alterations in microbial diversity and relative abundance of key taxa. Early interventional studies suggest that modifying the gut microbiome may improve sleep outcomes [&lt;span&gt;6&lt;/span&gt;], and the microbiome is therefore being explored as a potential therapeutic target. However, evidence remains limited, and causality has yet to be established in well-designed clinical and mechanistic studies.&lt;/p&gt;&lt;p&gt;Building on this emerging rationale, in the current issue of the &lt;i&gt;Journal of Internal Medicine&lt;/i&gt;, Gao et al. [&lt;span&gt;7&lt;/span&gt;] report the findings of a multicentre, placebo-controlled randomized trial of a microbiome-targeted intervention in chronic insomnia disorder. Participants received antibiotic-preconditioned faecal microbiota transplantation (FMT) from healthy sleepers. The intervention was generally well tolerated, with no major safety signals reported. Compared with placebo capsules matched for appearance, weight and dosing schedule, FMT was associated with improvements in both objective and subjective sleep outcomes, including reduced wake after sleep onset, increased polysomnographic sleep efficiency and reduced patient-reported insomnia severity at follow-up. Treatment response appeared to relate to baseline microbial composition, suggesting that pre-existing microbiome features may influence efficacy. Although no specific taxa were identified as mechanistic drivers, changes in broader functional pathways, including tryptophan metabolism (a precursor to serotonin and melatonin, key mediators of sleep regulation), provide a biologically plausible link between the gut microbiome and sleep regulation.&lt;/p&gt;&lt;p&gt;Taken together, these findings raise both therapeutic and mechanistic questions. Patients who do not respond to CBT-I represent an unmet clinical need, as long-term pharmacological treatment is genera","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 5","pages":"534-536"},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Snus, nicotine pouches and cardiovascular disease: Evidence, mechanisms, and the challenge of novel nicotine products","authors":"Magnus Olsson,&nbsp;Hanne Tønnesen,&nbsp;Jakob Hedberg,&nbsp;Johan Sundström,&nbsp;Eva Nordendahl,&nbsp;Björn Klinge,&nbsp;Michael Fored,&nbsp;Cecilia Magnusson,&nbsp;Daniel Jönsson,&nbsp;Peter Persson,&nbsp;Aron Naimi-Akbar","doi":"10.1111/joim.70160","DOIUrl":"10.1111/joim.70160","url":null,"abstract":"<p>Conventional Swedish snus is used by millions in Scandinavia and increasingly worldwide, yet its cardiovascular effects remain poorly characterized. The emergence of nicotine pouches—commonly referred to as ‘white snus’ in Sweden—that deliver comparable nicotine without tobacco constituents adds complexity to a heterogeneous landscape and raises questions about whether cardiovascular risk follows nicotine exposure regardless of product type. We explore epidemiological and mechanistic evidence on snus and cardiovascular disease, the contributions of nicotine versus tobacco-specific nitrosamines (TSNAs) to risks, and identify knowledge gaps, with focus on novel nicotine products and the research opportunity offered by the Swedish Tobacco Cohort (SWETOC). Epidemiological evidence suggests elevated cardiovascular disease (CVD) mortality among snus users, with the most consistent signals for fatal myocardial infarction and heart failure. Associations with incident atherosclerotic events are more heterogeneous. Mechanistic evidence points to nicotine-mediated pathways, including sympathetic activation, endothelial dysfunction and increased arterial stiffness, whereas evidence for TSNA-driven CVD risk remains sparse, and declining TSNA levels in modern Swedish snus make that path less likely and harder to study. Nicotine pouches deliver comparable or higher systemic nicotine than conventional snus but lack long-term cardiovascular outcome data. Real-world cessation data from Denmark suggest structured programmes can achieve 6-month abstinence rates of approximately 53% among non-smoking nicotine users. The evidence supports nicotine as the primary driver of snus-associated CVD risk, with important implications for the cardiovascular safety of novel nicotine products. Evidence is needed to inform public health guidance, clinical advice and regulatory decisions. SWETOC represents a unique infrastructure to generate this evidence.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 5","pages":"541-552"},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in polyendocrine metabolic ovarian syndrome, formerly polycystic ovary syndrome, with emphasis on endocrine and metabolic dysfunction and cardiovascular risk","authors":"Maria Forslund,&nbsp;Johanna Melin,&nbsp;Anju E. Joham,&nbsp;Terhi T. Piltonen,&nbsp;D. Aled Rees,&nbsp;Helena J. Teede","doi":"10.1111/joim.70156","DOIUrl":"10.1111/joim.70156","url":null,"abstract":"<p>Polyendocrine metabolic ovarian syndrome (PMOS), previously known as polycystic ovary syndrome, affects 10%–13% of women of reproductive age and remains underdiagnosed despite its substantial health burden. The introduction of the new PMOS nomenclature in 2026 reflects a fundamental shift in understanding the condition as a lifelong endocrine and metabolic disorder with prominent reproductive, psychological, dermatological, and cardiometabolic consequences. Once considered primarily a reproductive disorder, PMOS is now recognized as a multisystem condition. Insulin resistance and compensatory hyperinsulinemia are central pathophysiological mechanisms linking endocrine and metabolic features to reproductive dysfunction. In PMOS, insulin resistance affects 75% of lean and 95% of overweight women. Here we focus on the metabolic features. Recent advances in epidemiology include the first systematic review and meta-analysis examining regional variations in PMOS prevalence. In parallel, contemporary population-based studies of unselected women have confirmed that increased risks of metabolic complications observed in selected clinical cohorts also apply at the population level and have demonstrated increased risk of major adverse cardiovascular events (MACE). These studies report an almost 3-fold increased risk of Type 2 diabetes (OR 2.9) and MACE (HR 1.2–2.5), with cardiovascular risk diverging from approximately 35 years of age. In this review, we summarize recent advances in epidemiology, pathophysiology, metabolic dysfunction, and cardiovascular risk of PMOS, together with their implications for diagnosis and clinical management. Recognizing PMOS as an early-life marker of cardiometabolic disease highlights opportunities for earlier diagnosis, prevention, and individualized risk stratification, supporting integrated, patient-centered care across the life course.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 5","pages":"590-609"},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive performance and neuroimaging markers across the glycemic spectrum in multiethnic Asian older adults","authors":"Jiangbo Cui,&nbsp;Wei Ying Tan,&nbsp;Jiannan Huang,&nbsp;Eddie Jun Yi Chong,&nbsp;Chee Miao Li,&nbsp;Narayanaswamy Venketasubramanian,&nbsp;Tien Yin Wong,&nbsp;Ching-Yu Cheng,&nbsp;Christopher Chen,&nbsp;Saima Hilal","doi":"10.1111/joim.70152","DOIUrl":"10.1111/joim.70152","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Brain health across the glycemic spectrum in older adults remains poorly understood, particularly in prediabetes, a biologically heterogeneous condition. We aimed to explore cognitive performance and neuroimaging markers across the glycemic spectrum and to examine whether these associations vary according to cerebral microvascular dysfunction and diabetes onset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 930 participants (mean age 65.7 years; 52% female) from a population-based study in Singapore with a 6-year follow-up. Participants underwent repeated medical assessments and a single neuropsychological testing and brain magnetic resonance imaging at follow-up. Cerebrovascular disease, brain atrophy, and biological aging were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher HbA1c was associated with poorer brain health, with significant effects observed only at the diabetic stage. HbA1c and (pre)diabetes interacted with white matter hyperintensities, affecting cognition and brain atrophy. Over a mean (standard deviation) follow-up of 5.6 (2.1) years, among 310 participants with prediabetes, 103 (33.2%) reverted to normoglycemia, 151 (48.7%) remained as prediabetes, and 56 (18.1%) progressed to diabetes. Compared with participants who reverted to normoglycemia, those who progressed to diabetes showed greater cognitive impairment and more pronounced structural brain abnormalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Hyperglycemia is strongly associated with poor brain health, particularly reaching the diabetic stage. Despite the absence of a direct effect of prediabetes on brain health, its impact is amplified by cerebral microvascular dysfunction and progression to diabetes. Longitudinal studies are warranted to confirm these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 5","pages":"659-674"},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}