Journal of Diabetes最新文献

{"title":"Effects of FTO Gene rs9939609 and rs17817449 Polymorphisms on Insulin Resistance in Turkish Children With Obesity","authors":"Merve Köksal,&nbsp;Mehtap Ünlü Söğüt,&nbsp;Sevtap Kabalı","doi":"10.1111/1753-0407.70213","DOIUrl":"10.1111/1753-0407.70213","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgrounds</h3>\u0000 \u0000 <p>Fat mass and obesity-related gene (FTO) has been associated with glucose homeostasis and insulin sensitivity in some populations. The aim of this study was to evaluate the association of FTO gene rs9939609 and rs17817449 polymorphisms with insulin resistance, some cardiometabolic parameters, and body mass index (BMI) in Turkish children with obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The cross-sectional observational study included 83 children with obesity genotyped for variants of the FTO gene (rs9939609 and rs17817449). Children were divided into two groups as control and insulin resistant according to the homeostatic model assessment of insulin resistance (HOMA-IR). The relationship between the genotypes of rs9939609 and rs17817449 polymorphisms and insulin resistance was determined using binary logistic regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the control group and insulin-resistant obese group, the majority of the rs9939609 polymorphism was AT (69.2%) and AA (64%) genotypes, and the majority of the rs17817449 polymorphism was GT (65.4%) and TT (70%) genotypes, respectively. Fasting glucose and insulin values were lower, and quantitative insulin sensitivity calculation index (QUICKI) values were higher in the risk genotype (GG) of rs17817449 polymorphism (<i>p</i> &lt; 0.05). Additionally, rs9939609 (AT genotype, OR = 0.063; 95% CI: 0.006–0.707, <i>p</i> = 0.025 and AA genotype, OR = 0.111; 95% CI: 0.021–0.576, <i>p</i> = 0.009) and rs17817449 (GT genotype, OR = 12.250; CI: 9.720–84.383, <i>p</i> &lt; 0.001) polymorphisms were strongly associated with insulin resistance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study supports that FTO gene rs9939609 and rs17817449 polymorphisms are associated with insulin resistance independently of age, gender, and BMI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483875","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":"Correlation of Thyroid Hormone Levels and Sensitivity With Metabolic Syndrome in Older Adults","authors":"Fengjuan Hu,&nbsp;Hu Liu,&nbsp;Linlin Gu,&nbsp;Shuli Jia,&nbsp;Lixing Zhou,&nbsp;Wanyu Zhao,&nbsp;Xiaolei Liu,&nbsp;Birong Dong","doi":"10.1111/1753-0407.70208","DOIUrl":"10.1111/1753-0407.70208","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Previous studies have shown that thyroid function is associated with metabolic syndrome (MetS), but this association remains poorly understood in older adults. This study aimed to explore the relationships between thyroid hormone levels and sensitivity with MetS and its components in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The 2018 baseline data of the West China Health and Aging Trends study were used. MetS was diagnosed according to the International Diabetes Federation definition. Central thyroid hormone sensitivity was assessed by the TSH Index (TSHI), Thyrotrophic T4 Resistance Index (TT4RI), Thyroid Feedback Quantile-based Index (TFQI), and Parametric TFQI (PTFQI). Peripheral thyroid hormone sensitivity was assessed by the FT3 to FT4 ratio (FT3/FT4 ratio).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 3796 participants were included. The prevalence of MetS was 40.31%. High FT3 levels and FT3/FT4 ratios were associated with abdominal obesity and hypertension; decreased FT3 levels were associated with hyperglycemia, hypertriglyceridemia and low HDL-C; low FT4 levels were associated with abdominal obesity and hypertriglyceridemia; increased TSH, TSHI and TT4RI levels were associated with hypertriglyceridemia and hypertension; and increased TFQI and PTFQI were associated with hypertension (<i>p</i> &lt; 0.05, for all). Increased FT3 (OR = 1.13, 95% CI: 1.05–1.22), TSH (OR = 1.12, 95% CI: 1.04–1.20), TSHI (OR = 1.09, 95% CI: 1.01–1.17), TT4RI (OR = 1.09, 95% CI: 1.01–1.16), FT3/FT4 (OR = 1.25, 95% CI: 1.16–1.35) and low FT4 (OR = 0.87, 95% CI: 0.81–0.94) were associated with MetS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Thyroid hormone levels are correlated with MetS and its components. Reduced central thyroid hormone sensitivity and increased peripheral thyroid hormone sensitivity are risk factors for MetS in older adults.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483813","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":"Associations of Sarcopenia and Sarcopenic Obesity Using Different Obesity Definitions With Memory Decline","authors":"Ying Yue Huang,&nbsp;Wei Sen Zhang,&nbsp;Jiao Wang,&nbsp;Ya Li Jin,&nbsp;Kar Keung Cheng,&nbsp;Tai Hing Lam,&nbsp;Lin Xu","doi":"10.1111/1753-0407.70210","DOIUrl":"10.1111/1753-0407.70210","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To explore the associations of sarcopenia and sarcopenic obesity (SO) with memory.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Data from the Guangzhou Biobank Cohort Study (GBCS) were used to conduct both cross-sectional (<i>n</i> = 6390) and longitudinal (<i>n</i> = 3979) analyses. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019, while obesity was defined by 20 obesity indicators. Memory was assessed by the Delayed Word Recall Test (DWRT). Linear regression was used to analyze these associations. Two-sample Mendelian randomization (2SMR) was used to investigate potential causal associations of sarcopenia-related traits with memory.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to participants without sarcopenia, those with sarcopenia had lower baseline and follow-up DWRT score, and greater decrease in mean annual change (MAC) and MAC rate of DWRT score, with adjusted βs (95% CIs) being −0.24 (−0.33 to −0.14), −0.10 (−0.20 to −0.004), −0.03 (−0.06 to −0.001) and −0.79 (−1.57 to −0.01), respectively. Among all the SO definitions, the associations of SO defined by waist-to-hip-to-height ratio (WHHR) appeared to be the strongest (−0.36 [−0.50 to −0.22], −0.31 [−0.45 to −0.17], −0.09 [−0.14 to −0.05] and −2.70 [−3.81 to −1.59]), and stronger than those with sarcopenia only or obesity only. In 2SMR, walking pace (one of the sarcopenia indicators) was positively associated with working memory (1.61 [0.59, 2.62]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Sarcopenia and SO were associated with faster memory decline. Using the central obesity indicator WHHR to define SO may better predict late-life memory.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442137","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 Macrophage Polarization and M1/M2 Balance in Diabetic Foot Ulcers","authors":"Jing Zhang,&nbsp;Hong Li,&nbsp;Yulin Dong,&nbsp;Zhuoyan Zhou,&nbsp;Yuhan Wang,&nbsp;Xia Chen,&nbsp;Yulan Cai","doi":"10.1111/1753-0407.70205","DOIUrl":"10.1111/1753-0407.70205","url":null,"abstract":"<p>Macrophage polarization, encompassing classically activated (M1) and alternatively activated (M2) states, is a critical determinant of immune response in wound healing. In diabetic foot ulcers (DFUs), a persistent imbalance favoring pro-inflammatory M1 over anti-inflammatory M2 macrophages drives chronic inflammation and impedes tissue repair. This review delineates the central role of macrophage polarization in DFU pathogenesis and systematically summarizes the key signaling pathways that govern this process, including PI3K/AKT, PPARγ, Notch, and Toll-like receptors (TLRs). We further synthesize these cascades into a novel hierarchical network model, identifying NF-κB and JAK–STAT as the core regulatory hubs. Beyond mechanism, we discuss emerging therapeutic strategies—including pharmacological agents and biomaterial-based approaches—that target macrophage polarization, positioning them as promising adjuvants to standard wound care. By integrating mechanistic insights with therapeutic potential, this review provides an updated framework for developing targeted immunomodulatory therapies to break the cycle of non-healing in DFUs.</p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429952","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":"Local Versus Systemic Antibiotics for Diabetic Foot Infection—A Systematic Review and Meta-Analysis","authors":"Anas Khan,&nbsp;Hester Lacey,&nbsp;Helena Michels,&nbsp;Mohamed Elahwal,&nbsp;Bjorn Telgenkamp","doi":"10.1111/1753-0407.70201","DOIUrl":"10.1111/1753-0407.70201","url":null,"abstract":"<p>Diabetic foot infection (DFI) includes soft tissue infection and osteomyelitis below the ankle and is a leading cause of lower limb amputation and mortality in diabetic patients. Treatment involves prolonged antibiotic therapy with surgical debridement or amputation. Local antimicrobial therapy offers an adjunct or alternative to systemic therapy. This systematic review and meta-analysis assessed the efficacy of systemic antibiotic therapy compared with local and combination (local and systemic) therapy in DFI. A meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A systematic search for studies was performed in eight sources (PROSPERO: CRD42024518421). The primary outcome was clinical cure rates, with secondary outcomes including clinical improvement, time to clinical cure, recurrence, amputation rates, and pathogen eradication. Twenty-one studies with 2188 participants met the inclusion criteria, including 12 randomized controlled trials and 9 observational studies. Combination antibiotics were associated with increased clinical cure rates compared with systemic antibiotics alone (OR 2.08; 95% CI 1.30–3.35; <i>p</i> &lt; 0.05) and faster healing times (Mean −9.8 days; 95% CI −15.1 to −4.4; <i>p</i> &lt; 0.05); however, results failed to reach significance when looking at randomized studies alone. Results for local antibiotics alone were non-significant for all outcomes. This meta-analysis suggests that definitive conclusions about the use of local antibiotics in DFI are limited by bias and heterogeneity within included studies. Combined local and systemic antibiotic treatment may allow for direct tissue infiltration of antimicrobial therapy. However, high-quality, blinded randomized controlled trials are required before routine clinical adoption.</p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12973258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388922","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":"Nonlinear Association Between THs, TSH, and HbA1c in Patients With Type 2 Diabetes Mellitus: A Retrospective Study","authors":"Mengjie Chen,&nbsp;Yuqin Gan,&nbsp;Fengxiang Tian,&nbsp;Yun Bao,&nbsp;Zhonglan Chen","doi":"10.1111/1753-0407.70200","DOIUrl":"10.1111/1753-0407.70200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to investigate the potential non-linear relationships between thyroid hormones and thyroid-stimulating hormone levels on glycemic control levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis of electronic medical records was performed on patients with T2DM who received treatment at a tertiary care hospital in Chengdu, Sichuan Province, between 2018 and 2023. RCS regression and threshold effect analyses were employed to assess potential nonlinear associations among THs, TSH, and glycemic control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data from a total of 1413 patients were included in the analysis. RCS regression revealed a significant non-linear association between FT3 and HbA1c (<i>p</i> for nonlinearity &lt; 0.05). Threshold effect analysis demonstrated no statistically significant inflection point for FT3 in relation to HbA1c (FT3 &lt; 5.92 pmol/L, <i>β</i> = 0.008, 95% CI (−0.122, 0.281); FT3 &gt; 5.92 pmol/L, <i>β</i> = −0.109, 95% CI (−0.261, 0.042)). FT4 exhibited a significant non-linear relationship with HbA1c (<i>p</i> for nonlinearity &lt; 0.05), identifying an inflection point at 14.82 pmol/L. Below this threshold, each 1 pmol/L increase in FT4 was associated with a 0.263% elevation in HbA1c (<i>β</i> = 0.263, 95% CI 0.189–0.337). Similarly, TSH demonstrated a non-linear association with HbA1c (<i>p</i> for nonlinearity &lt; 0.05), with an inflection point identified at 5.53 mIU/L. When TSH was below 5.53 mIU/L, each 1 mIU/L increase was associated with a 0.179% reduction of HbA1c (<i>β</i> = −0.179, 95% CI −0.281 to −0.076).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Nonlinear associations were observed between thyroid function markers (FT3, FT4, and TSH) and HbA1c levels in patients with T2DM. These findings provide novel evidence for understanding thyroid-glucose metabolic interactions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388892","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":"Reply: Time-Related Biases in Observational Studies of GLP-1 Agonists and Cancer Risk","authors":"Zhiyuan Cheng,&nbsp;Jiesheng Lin,&nbsp;Dongfeng Gu,&nbsp;Fengchao Liang","doi":"10.1111/1753-0407.70203","DOIUrl":"10.1111/1753-0407.70203","url":null,"abstract":"&lt;p&gt;We thank the authors of the letter for their thoughtful comments on our work [&lt;span&gt;2&lt;/span&gt;] and appreciate the opportunity to clarify our methodological choices.&lt;/p&gt;&lt;p&gt;Our real-world, population-based study suggests an association between GLP-1 receptor agonist (GLP-1RA) use and increased risks of adverse outcomes like pancreatitis, kidney issues, and thyroid disorders [&lt;span&gt;3&lt;/span&gt;]. Regarding exposure definition, the correspondents correctly note that we adopted a predominant-user rather than a strict incident new-user design. New-user designs are preferred for single-outcome causal inference, particularly for cancer. However, its feasibility is constrained by real-world treatment patterns and data availability in multi-outcome safety evaluations. In China, GLP-1RAs are typically prescribed as add-on third-line (2010–2017) or second-line (2017–2024) treatment for type 2 diabetes. Requiring patients to be free of all antidiabetic medications at cohort entry would exclude a large proportion of GLP-1RA users and compromise representativeness. In addition, prescription data before 2016 were unavailable in Shenzhen health information systems, limiting reliable identification of true incident users. Under these conditions at the time of publication, a strict new-user design was not practically feasible, although such designs may become increasingly viable as data accrual and follow-up continue. Notably, several large observational studies of GLP-1RA safety similarly did not apply a pre-baseline washout period, reflecting comparable real-world considerations [&lt;span&gt;4, 1&lt;/span&gt;]. As real-world experience with GLP-1RAs accumulates, further research specifically focused on the initiation of therapy remains warranted.&lt;/p&gt;&lt;p&gt;We acknowledge that the absence of a washout requirement to exclude pre-existing or early-diagnosed cancers could indeed introduce prevalent-user bias, which is a valid methodological concern. However, in unsupervised real-world settings, treatment interruption and re-initiation are common and are largely driven by tolerance and adherence. Thus, imposing a washout period under these conditions may introduce additional selection bias and further reduce statistical power, particularly for uncommon outcomes. As data coverage expands with longer follow-up, alternative exposure definitions merit further evaluation.&lt;/p&gt;&lt;p&gt;A lag period appropriately addresses detection bias, which is especially relevant for cancer outcomes where early diagnosis might coincide with treatment initiation rather than being caused by the treatment itself. However, our study assessed a broad spectrum of 20 adverse outcomes, with latencies ranging from short-term (≤ 12 months) to long-term (&gt; 12 months), as part of a comprehensive safety evaluation. We rechecked our data on incident cases of thyroid cancer, and only 11.5% (3/26) of incidents in the GLP-1RA group occurred under 12 months of follow-up, compared with 33.3% (8/24) in the metformin group. Thus,","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375528","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":"Time-Related Biases in Observational Studies of GLP-1 Agonists and Cancer Risk","authors":"Fei Lu","doi":"10.1111/1753-0407.70202","DOIUrl":"10.1111/1753-0407.70202","url":null,"abstract":"&lt;p&gt;We read with great interest the recent study by Cheng et al. examining the association between the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the risk of multiple cancers among patients with type 2 diabetes [&lt;span&gt;1&lt;/span&gt;]. Given the rapidly expanding use of GLP-1RAs in diabetes management, evaluations of their long-term safety profiles are of substantial clinical and public health importance. While the study addresses a timely and relevant question, several methodological aspects merit careful consideration when interpreting the reported findings.&lt;/p&gt;&lt;p&gt;First, the definition of GLP-1RA exposure in the study differs from that of a conventional incident new-user design [&lt;span&gt;2, 3&lt;/span&gt;]. The authors classified patients based on the predominant antidiabetic therapy from baseline to the end of follow-up, defining GLP-1RA, insulin-only, and metformin-only groups while allowing limited use (≤ 6 months) of other glucose-lowering agents during follow-up. This approach reflects a predominant-user design rather than initiation of therapy at cohort entry. Consequently, although follow-up time was similar across groups, this design does not explicitly ensure that all patients were free of prior exposure to the study drugs before baseline, and the temporal alignment between treatment initiation and outcome onset may be less clearly defined. In pharmacoepidemiologic research, the absence of a pre-baseline washout period to identify incident users may introduce prevalent user bias, as individuals already established on therapy are selectively included, potentially influencing estimated risk associations [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Second, the absence of a lag period is particularly relevant in the context of cancer outcomes [&lt;span&gt;4&lt;/span&gt;]. Initiation of GLP-1RA therapy is often accompanied by intensified clinical monitoring and increased healthcare utilization, which may increase the likelihood of detecting previously asymptomatic or indolent malignancies. Without excluding early follow-up time, observed associations, especially those occurring within the first year of treatment, may therefore reflect detection bias rather than a causal drug effect. In this study, stratified analyses by cumulative duration of GLP-1RA use (&lt; 12 months vs. ≥ 12 months) suggested that elevated risks were primarily observed in shorter exposure durations, whereas longer-term use was not consistently associated with increased risk. This pattern warrants cautious interpretation, particularly given the relatively short and comparable mean follow-up times across treatment groups (approximately 24 months).&lt;/p&gt;&lt;p&gt;Notably, several recent population-based studies have adopted design features specifically intended to address these time-related biases [&lt;span&gt;5, 6&lt;/span&gt;]. For example, Pasternak et al. implemented an active-comparator new-user design with predefined lag periods of one and two years in as-treated analyses [&lt;span&gt;5&lt;/span&gt;]. By explicitly excluding ea","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375566","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":"Sodium-Glucose Cotransporter 2 Inhibitors for Metabolic Dysfunction-Associated Steatohepatitis","authors":"Jiayang Lin,&nbsp;Yan Huang,&nbsp;Bingyan Xu,&nbsp;Chensihan Huang,&nbsp;Fei Teng,&nbsp;Youwen Yuan,&nbsp;Jinhua Zhang,&nbsp;Huijie Zhang","doi":"10.1111/1753-0407.70206","DOIUrl":"10.1111/1753-0407.70206","url":null,"abstract":"<p>MASH denotes metabolic dysfunction-associated steatohepatitis. MASH improvement was defined as a decrease in the non-alcoholic fatty liver disease activity score (NAS) of ≥ 2 points or NAS ≤ 3 at week 48 after treatment, with no worsening of fibrosis (i.e., no increase in fibrosis stage). MASH resolution was defined as a hepatocellular ballooning score of 0 and a lobular inflammation score of 0 or 1 at week 48, with no worsening of fibrosis. Fibrosis improvement was defined as a reduction in fibrosis of ≥ 1 stage at week 48, with no worsening of MASH (i.e., no increase in steatosis, ballooning, or inflammation scores).\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12966765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369040","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":"The Interaction Between Mitophagy Dysregulation and the Diabetic Bladder Microenvironment","authors":"Shi Li,&nbsp;Zongyao Fan,&nbsp;Zheng Duan,&nbsp;Jun Xue,&nbsp;Zhongqing Wei","doi":"10.1111/1753-0407.70199","DOIUrl":"10.1111/1753-0407.70199","url":null,"abstract":"<p>Diabetic bladder dysfunction (DBD) is a prevalent and multifactorial urological complication of diabetes, with pathogenesis driven by complex interactions between hyperglycemia-induced oxidative stress, mitochondrial dysfunction, and bladder microenvironment dysregulation. Mitophagy, a selective autophagic process critical for mitochondrial quality control, has been linked to various metabolic diseases, but its precise role and the bidirectional interactions with the diabetic bladder microenvironment remain underexplored. This review outlines a novel, self-reinforcing feedback loop central to DBD progression. In this cycle, hyperglycemia impairs both the PINK1/Parkin-mediated mitophagy pathway and ubiquitin-independent pathways like FUNDC1 under hypoxic conditions, leading to the accumulation of damaged mitochondria. Mitochondrial dysfunction then exacerbates microenvironmental damage through excessive mitochondrial reactive oxygen species (mtROS) production, release of damage-associated molecular patterns (DAMPs), and activation of the NLRP3 inflammasome, which further drives inflammation, fibrosis, and extracellular matrix (ECM) remodeling. This aggravated microenvironment inhibits mitophagy, thereby accelerating the pathogenic cycle. Beyond elucidating this loop, this review suggests that targeting it offers a promising therapeutic strategy. A breakthrough in DBD treatment may necessitate a combined approach that both restores mitophagy and modulates the microenvironment. Additionally, this study critically reviews several promising, yet underexplored, interventions, including pharmacological mitophagy activation with urolithin A, NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome inhibition via MCC950, and advanced techniques like nanoparticle-mediated PINK1 mRNA delivery and CRISPR/Cas9-based Parkin gene editing. Future research should incorporate spatial transcriptomics to resolve cellular heterogeneity, develop targeted nanodelivery systems, and establish mechanism-driven, highly specific combination therapies to enable precision medicine for DBD.</p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12966769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369034","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}