Diabetes/Metabolism Research and Reviews最新文献

{"title":"Active Free Radical Cold Atmosphere Plasma Promotes Healing of Diabetes Foot Ulcer: Mechanism and Challenge","authors":"Yiran Wang,&nbsp;Junxiao Zhang,&nbsp;Jinting Yan,&nbsp;Wenhua Bi,&nbsp;Jinlong Ma","doi":"10.1002/dmrr.70216","DOIUrl":"10.1002/dmrr.70216","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetic foot ulcers (DFUs) have become an important cause of disability and death in patients with diabetes. Traditional therapies are prone to problems such as recurrence and drug resistance, which result in unsatisfactory healing effects for DFUs. Although antibiotics are not the mainstay of treatment for DFUs, antibiotic resistance poses a critical clinical challenge for DFU patients who require long-term antibiotic therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Text</h3>\u0000 \u0000 <p>This review summarises the mechanism by which Cold Atmosphere Plasma (CAP) kills bacteria and activates healing ability through the production of reactive oxygen/nitrogen species (RONS). RONS, as the key active species of CAP, exert antibacterial effects in a series of bacterial, cellular, and animal experiments, promote cell migration and proliferation, stimulate angiogenesis, and exert anti-inflammatory effects. However, current high-quality clinical trials are still lacking, leaving substantial room for further clinical exploration of CAP in the treatment of DFUs. Finally, the challenges and prospects of CAP in treating diabetic foot ulcers are summarised.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>As a comprehensive and innovative treatment method, the RONS produced by CAP offer a potential approach for treating DFUs and serve as a tool for promoting their healing. However, more clinical studies are needed for further verification.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 6","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671051","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":"Diabetic Foot Ulcer Prevention Priorities Established by Consumers From Low Socioeconomic and Culturally Diverse Communities","authors":"Jayishni N. Maharaj,&nbsp;Jim Woodburn,&nbsp;Annette McLaren-Kennedy,&nbsp;Mohamed A. Kola,&nbsp;Daniel M. G. Winson,&nbsp;Meegan Nevin,&nbsp;Kelly Clanchy","doi":"10.1002/dmrr.70206","DOIUrl":"10.1002/dmrr.70206","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Diabetic foot ulcers (DFU) continue to occur despite established prevention guidelines, yet consumer perspectives, particularly from socioeconomically disadvantaged and culturally and linguistically diverse (CALD) communities, have been underrepresented in shaping prevention. To address this gap, we aimed to co-design a consumer-derived prevention research agenda by identifying barriers and enablers, establishing research priorities, prioritising implementation strategies, and defining meaningful outcome measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four sequential workshops were conducted with 11 consumers with a history of DFU in South East Queensland, including Aboriginal and Pacific Islander participants (<i>n</i> = 4) and those from areas of socioeconomic disadvantage (<i>n</i> = 8). Rapid qualitative analysis informed iterative refinement across workshops, with priorities, implementation strategies, and outcome measures ranked by participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants identified barriers across clinical, self-care, psychosocial, social, and financial domains, including feeling unsupported when trying to prevent DFU, the cognitive burden of constant vigilance, conflicting guidance, and the financial and travel costs of care. The highest-ranked research priorities were better ways to predict problems before they happen (median 2, IQR 1–4.5), formal education support (median 4, IQR 3–9), and tools to support regular foot checks (median 5, IQR 3–6). Across all three priorities, consumers consistently selected technology enabled implementation strategies, including wearable sensors, AI powered personalised learning, and smart interventions. Participants defined prevention success through quality of life, function, and confidence outcome measures rather than clinical endpoints alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>For socioeconomically disadvantaged and CALD populations, effective DFU prevention must be technology enabled, personalised, and developed in partnership with the consumer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 6","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671053","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":"Type 5 Diabetes Mellitus: Pathophysiology, Clinical Phenotype, and Nutritional Management","authors":"İrem Nur Şahin Anılgan,&nbsp;Aslıhan Atar-Uğurlu","doi":"10.1002/dmrr.70212","DOIUrl":"https://doi.org/10.1002/dmrr.70212","url":null,"abstract":"<p>Type 5 Diabetes Mellitus (T5DM) is an emerging diabetes phenotype linked to chronic undernutrition. It predominantly affects young, lean individuals in low- and middle-income countries. After its formal recognition by the International Diabetes Federation in 2025, T5DM resurfaced as a clinically relevant insulin-deficient phenotype. It is now viewed as distinct from classical autoimmune and insulin-resistant forms of diabetes. This review synthesises recent evidence on the epidemiology, pathophysiology, clinical characteristics, and management of T5DM. Recent studies show that T5DM is influenced by early-life nutritional deprivation. This fits within the Developmental Origins of Health and Disease (DOHaD) framework. Undernutrition during key developmental periods harms pancreatic morphogenesis. It creates a permanent reduction of functional beta-cell mass through epigenetic programming. Clinically, T5DM often appears before age 30. Patients have low body mass index, sarcopenia, marked insulinopenia, absence of diabetes-associated autoantibodies, and resistance to ketosis, despite significant hyperglycemia. Diagnostic challenges remain, as patients are frequently misclassified as type 1 or type 2 diabetes. Relying only on body mass index is insufficient. Accurate diagnosis requires a multidimensional assessment including nutritional history, metabolic features, and exclusion of monogenic diabetes. T5DM is a distinct insulin-deficient phenotype caused by chronic undernutrition. Effective management requires more than glycaemic control. Nutritional rehabilitation is key, with a focus on adequate energy intake, high–biological–value protein supplementation, and correction of key micronutrient deficiencies. Given preserved insulin sensitivity, low-dose insulin should be used cautiously to avoid iatrogenic hypoglycemia. Better recognition and tailored management strategies are needed for optimal clinical outcomes.</p>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 6","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616834","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":"Coxsackievirus B Infections Are Associated With the Risk of Islet Autoimmunity in Children With Strong Genetic Susceptibility to Type 1 Diabetes—Results From the TRIGR Divia Study","authors":"Maarit Oikarinen,&nbsp;Amirbabak Sioofy-Khojine,&nbsp;Leena Puustinen,&nbsp;David Cuthbertson,&nbsp;Jussi Lehtonen,&nbsp;Niila V. V. Jouppila,&nbsp;Johnny Ludvigsson,&nbsp;Leena Hakola,&nbsp;Sari Niinistö,&nbsp;Iris Erlund,&nbsp;Mikael Knip,&nbsp;Jeffrey P. Krischer,&nbsp;Suvi M. Virtanen,&nbsp;Heikki Hyöty,&nbsp;the TRIGR Investigators","doi":"10.1002/dmrr.70207","DOIUrl":"10.1002/dmrr.70207","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Especially, the coxsackievirus B group of enteroviruses has been linked to the development of islet autoimmunity and type 1 diabetes in genetically susceptible individuals. Our aim was to study the possible associations of 10 different microbial infections with islet autoimmunity in a large international prospective study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In a nested case-control study within the TRIGR study, follow-up serum samples from 240 islet autoantibody-positive case children and 436 age- and country-matched control children were analysed for IgG class antibodies against 10 different respiratory and gastrointestinal microbes using an enzyme immunoassay, and for neutralising antibodies against all six coxsackievirus B types. The samples were obtained at several time points prior to and at the time of seroconversion for multiple islet autoantibodies. All children had a first-degree relative with type 1 diabetes, and they carried risk-associated HLA-DQ alleles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Coxsackievirus B5 was associated with an increased risk of islet autoimmunity (OR 2.22, 95% CI 1.29–3.80, <i>p</i> = 0.004, corrected <i>p</i> = 0.024), which remained after adjustment for HLA, sex, and maternal type 1 diabetes. This association was particularly seen for infections occurring more than 12 months (OR 2.02, 95% CI 1.06–3.84, <i>p</i> = 0.032) and 0–6 months (OR 2.66, 95% CI 1.11–6.35, <i>p</i> = 0.028) before the first detection of multiple islet autoantibodies. After correction for multiple comparisons, none of the other viruses showed an association with islet autoimmunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study supports previous evidence of the risk association of coxsackievirus B infections. These results support the role of certain virus infections as possible modulating factors in the pathogenesis of type 1 diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 6","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148609175","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":"Di(2-Ethylhexyl) Phthalate Exposure and Risk of Diabetic Kidney Disease: Epidemiological Association and Mechanistic Insights","authors":"Dapeng Yin,&nbsp;Yan Li,&nbsp;Wei Wu,&nbsp;Xiaojuan Wang,&nbsp;Junhua He,&nbsp;Yikun Zhu,&nbsp;Jin Li","doi":"10.1002/dmrr.70209","DOIUrl":"10.1002/dmrr.70209","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to explore the association between exposure to di-(2-ethylhexyl) phthalate (DEHP) and diabetic kidney disease (DKD), and to elucidate its potential molecular mechanisms. The study findings provide scientific evidence for the prevention and control of environmental risk factors related to DKD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We utilised the United States National Health and Nutrition Examination Survey (NHANES) database to evaluate the correlations of DEHP exposure with DKD risk and renal function indices. Candidate targets were screened using network toxicology, and functional enrichment analysis was conducted. The binding ability of DEHP to the candidate mechanistic targets was verified through molecular docking. The toxicity and target effects of DEHP and its metabolites were verified using HK-2 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The NHANES analysis demonstrated a positive correlation between DEHP exposure and the risk of DKD, with a significant dose-response relationship observed. Network toxicology identified ALB, ESR1, and MMP9 as candidate mechanistic targets in DEHP-induced DKD. In vitro experiments confirmed that DEHP and its metabolite MEHP reduced HK-2 cell viability, induced lipid deposition, and altered the expression of candidate mechanistic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DEHP is an important environmental risk factor for DKD. It may promote the development and progression of DKD by regulating key targets and interfering with lipid metabolism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 6","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148609193","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":"Insights Into Gut Microbiota and Metabolic Alterations in Type 1 Diabetes Mellitus","authors":"Caroline Fogagnolo,&nbsp;Gabriela Ueta Ortiz,&nbsp;Adelino Sanchez Ramos da Silva,&nbsp;Ellen Cristini de Freitas","doi":"10.1002/dmrr.70211","DOIUrl":"10.1002/dmrr.70211","url":null,"abstract":"&lt;p&gt;Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease marked by immune responses against pancreatic β-cell antigens, activating autoreactive T and B cells and leading to progressive β-cell destruction, impaired insulin secretion, and hyperglycemia [&lt;span&gt;1&lt;/span&gt;]. In T1DM, evidence suggests a synergistic interaction between altered gut microbiota, increased intestinal permeability, and immune dysregulation, contributing to loss of immune tolerance and β-cell destruction [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Chronic hyperglycemia and low-grade inflammatory profile in T1DM individuals may impair intestinal barrier function, increasing permeability [&lt;span&gt;2&lt;/span&gt;], promoting immune activation and perpetuating β-cell autoimmunity [&lt;span&gt;3&lt;/span&gt;]. This supports a bidirectional relationship in which T1DM-related immune and metabolic changes disrupt gut microbiota homoeostasis, while dysbiosis further amplifies immune dysfunction and disease severity.&lt;/p&gt;&lt;p&gt;In this context, we read with great interest the cross-sectional study conducted by Li et al. [&lt;span&gt;4&lt;/span&gt;] published in August 2025 in &lt;i&gt;Diabetes/Metabolism Research and Reviews&lt;/i&gt; (41:6). The study examined the relationship between gut microbiota and T1DM duration, suggesting duration-specific microbiome alterations. In long-standing T1DM, microbial shifts reflect functional imbalance rather than isolated taxonomic changes, marked by reduced butyrate- and short-chain fatty acid (SCFA)-producing taxa and broader alterations in metabolically relevant bacteria. Notably, depletion of SCFA producers, including &lt;i&gt;Faecalibacterium&lt;/i&gt;, &lt;i&gt;Fusicatenibacter&lt;/i&gt;, &lt;i&gt;Lachnospira&lt;/i&gt;, and &lt;i&gt;Subdoligranulum&lt;/i&gt;, was consistently associated with poorer glycaemic control.&lt;/p&gt;&lt;p&gt;SCFAs play a central role in modulating the immune response, particularly through the regulation of B-cell function and metabolism [&lt;span&gt;5&lt;/span&gt;]. By attenuating excessive immune activation while promoting metabolic reprogramming towards plasma cell differentiation via pathways such as glycolysis, SCFAs favour more controlled and tolerogenic humoral responses [&lt;span&gt;6&lt;/span&gt;]. Plasma cells, the terminally differentiated form of B cells, are fundamental to humoral immunity due to their capacity for sustained antibody secretion and immunological memory [&lt;span&gt;7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;SCFAs also regulate cellular function through the inhibition of histone deacetylases (HDACs), leading to increased histone acetylation, which plays a key role in gene transcription. Among SCFAs, butyrate is the most potent HDAC inhibitor [&lt;span&gt;8&lt;/span&gt;]. These epigenetic mechanisms have been associated with the regulation of essential metabolic pathways, including glycolysis and mitochondrial oxidative phosphorylation, critical for plasma cell differentiation and function [&lt;span&gt;5&lt;/span&gt;]. Consequently, increased immunoglobulin production, particularly IgG and IgA, enhances immune protection. Moreover, SCFAs promote the expansion and activity of regulatory B","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 6","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13405004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148609169","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":"Network and Pairwise Meta-Analysis of the Association Between Novel Hypoglycemic Agents and Atrial Fibrillation Risk in Patients With Type 2 Diabetes Mellitus","authors":"Xuejiao Ye,&nbsp;Qian Wu,&nbsp;Linye Hou,&nbsp;Xinzheng Hou,&nbsp;Yingtian Yang,&nbsp;Chenyan Yang,&nbsp;Mingyu Huang,&nbsp;Shihan Wang","doi":"10.1002/dmrr.70202","DOIUrl":"10.1002/dmrr.70202","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate the atrial fibrillation (AF) risk of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagonlike peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with Type 2 Diabetes Mellitus (T2DM) with network meta-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Systematic literature searches were conducted of MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Clinical Trials.gov covering inception till January 31, 2026. Randomized control trials (RCTs) and cohort studies comparing SGLT-2i, GLP-1RA and DPP-4i in diabetes were selected. We performed a network meta-analysis to compare the three drugs indirectly. Results were reported as risk ration (RR) with corresponding 95% confidence interval (CI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>4 RCTs and 21 cohort studies involving 2,171,267 patients were included. Compared with GLP-1RA [RR with 95% CI: 0.86(0.79, 0.95), RR with 95% CI: 0.87(0.78, 0.97)] and DPP-4i[RR with 95% CI: 0.80(0.74, 0.87), RR with 95% CI: 0.81(0.74, 0.88)], SGLT-2i significantly reduced the risk of AF and new-onset AF. While there were no significant difference in the risk of AF recurrence among SGLT-2i, GLP-1RA, and DPP-4i[RR with 95% CI: 0.87(0.68, 1.12), RR with 95% CI: 0.80(0.61, 1.05), RR with 95% CI: 0.92(0.63, 1.33)]. There were also no significant difference in the risk of AF and new-onset AF between GLP-1RA and DPP-4i[RR with 95% CI: 0.93(0.84, 1.03), RR with 95% CI: 0.93(0.83, 1.04)].</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The management of T2DM involves the prevention of subsequent cardiovascular complications. The results of this network meta-analysis indicate that SGLT2i is associated with a lower risk of AF in T2DM patients compared to GLP-1RA and DPP-4i. Sensitivity analysis further confirms that SGLT-2i significantly reduces the risk of AF recurrence statistically. These finding suggests that SGLT-2i should be considered as a preferred antidiabetic regimen for patients with T2DM at high risk of AF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457380","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":"New-Onset Diabetes and Pancreatic Ductal Adenocarcinoma: Implications for Early Recognition and Clinical Management","authors":"Kun Huang,&nbsp;Zhenghong Huang,&nbsp;Yunshen He,&nbsp;Pan Zhao,&nbsp;Xiaofeng Hu","doi":"10.1002/dmrr.70205","DOIUrl":"10.1002/dmrr.70205","url":null,"abstract":"<div>\u0000 \u0000 <p>Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal because most patients are diagnosed after curative treatment is no longer feasible. Diabetes mellitus and PDAC have a bidirectional relationship: long-standing type 2 diabetes mellitus (T2DM) modestly increases background cancer risk, whereas new-onset diabetes (NOD), particularly after 50 years of age, may represent a paraneoplastic manifestation of occult PDAC. Population-based data suggest that approximately 0.6%–0.85% of older adults with NOD are diagnosed with PDAC within 3 years. This absolute risk is too low to justify universal imaging, but high enough to support phenotype-based triage. This review clarifies the distinction among T2DM, PDAC-associated diabetes, type 3c diabetes mellitus related to non-malignant exocrine pancreatic disease, and post-pancreatectomy dysglycemia. We also summarise epidemiological and biological evidence connecting dysglycemia with PDAC, including insulin resistance, hyperinsulinemia, impaired insulin secretion, cachexia-related metabolic change, and exocrine-endocrine crosstalk. Particular emphasis is placed on selective diagnostic escalation. Age at diabetes onset, unintended weight loss, HbA1c or glucose trajectory, insulin resistance indices, biomarkers, and risk-enrichment models, including the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) model, should be interpreted together rather than in isolation. Pancreas-protocol computed tomography remains the first-line diagnostic study when PDAC is suspected, while magnetic resonance imaging and endoscopic ultrasonography play complementary roles. We further discuss implications for pancreatic surgery, perioperative metabolic care, postoperative dysglycemia, and lessons from high-risk surveillance cohorts. A diabetes-centred framework may improve early recognition without promoting indiscriminate screening.</p>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457366","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":"The Sirtuin Network: Linking NAD+ Metabolism, Mitochondrial Function, and Metabolic Homoeostasis","authors":"Ewa Szczęsny-Małysiak,&nbsp;Valentina Schiavoni,&nbsp;Rossella Rotondo,&nbsp;Sabrina Donati Zeppa,&nbsp;Arianna Vignini,&nbsp;Eleonora Moriconi,&nbsp;Monia Cecati,&nbsp;Andrea Armani,&nbsp;Stefania Gorini,&nbsp;Roberto Campagna,&nbsp;Massimiliano Caprio","doi":"10.1002/dmrr.70201","DOIUrl":"10.1002/dmrr.70201","url":null,"abstract":"<div>\u0000 \u0000 <p>Metabolic disorders such as obesity, type 2 diabetes mellitus, and fatty liver disease are associated with a disruption in the coordinated regulation of nutrient sensing, energy metabolism, and cellular homoeostasis. Increasing evidence indicates that sirtuins, a family of NAD⁺-dependent enzymes, play a central role in integrating metabolic and stress-responsive pathways. By coupling the cellular redox state to transcriptional and post-translational regulation, sirtuins coordinate key processes such as glucose and lipid metabolism, mitochondrial function, and inflammatory signalling. Sirtuins are functionally specialised according to their subcellular localisation. Nuclear sirtuins (SIRT1, SIRT6, and SIRT7) regulate transcriptional programs controlling metabolism and inflammation, whereas mitochondrial sirtuins (SIRT3, SIRT4, and SIRT5) directly modulate metabolic enzyme activity and redox homoeostasis. SIRT2 links cytosolic metabolic signalling to cytoskeletal dynamics and cell cycle regulation. Importantly, the activity of all sirtuins is tightly dependent on NAD⁺ availability, positioning NAD⁺ metabolism as a central regulator of the sirtuin network. In this review, we provide a systems-level perspective on sirtuin biology, highlighting how NAD⁺ metabolism, subcellular compartmentalisation, and specific functions converge to form an integrated regulatory network governing metabolic homoeostasis. We further discuss how disruption of this network contributes to the pathogenesis of metabolic disorders through impaired metabolic flexibility, mitochondrial dysfunction, and chronic inflammation. Overall, this network-based framework provides a unified view of sirtuin function in metabolic regulation and helps to explain the complexity and tissue-specific heterogeneity of metabolic diseases.</p>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438522","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":"Assessment of Diabetes Risk in Patients With Hepatitis B: A Machine Learning Approach Integrating 11 Inflammatory and Immune Indicators","authors":"Zhisheng Cai,&nbsp;Jingtao Liu,&nbsp;Wenjie Zhang,&nbsp;Yutong Lu,&nbsp;Yumeng Su,&nbsp;Tengyue Zhang,&nbsp;Yangyi Zhang,&nbsp;Xiaochi Wang,&nbsp;Linyi Ye,&nbsp;Ying Tao,&nbsp;Junjie Liu","doi":"10.1002/dmrr.70193","DOIUrl":"10.1002/dmrr.70193","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic hepatitis B virus (HBV) infection is associated with an increased risk of diabetes; however, early detection of diabetes remains challenging due to silent progression in early stages. Given that 30%–50% of diabetic patients develop severe complications such as cardiovascular disease, renal failure, and neuropathy, timely risk assessment is critical for prevention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We developed a machine learning model using data from 14,287 HBV-positive adults across eight NHANES cycles (2003–2018) to identify diabetes. Eleven inflammation-immune composite indicators were integrated with demographic and biochemical parameters. Following LASSO variable selection and a 7:3 train-test split, seven algorithms were compared. Model performance was evaluated using the area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Artificial Neural Network (ANN) emerged as the optimal model for diabetes risk assessment. It achieved an AUC of 0.83 (95% CI: 0.80–0.85) and an accuracy of 82% (95% CI: 0.79–0.85). SHAP analysis identified age and UHR as the most influential predictors, while HRR showed significant protective effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study presents a robust, interpretable model for diabetes risk assessment in HBV patients that integrates novel inflammation-immune composite indicators. These findings highlight the model's utility as a potential clinical tool for screening individuals with undiagnosed diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148413440","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}