Diabetes/Metabolism Research and Reviews最新文献

{"title":"Lower Risk of Type 2 Diabetes Mellitus With PCSK9 Inhibitors Compared With Other Lipid-Lowering Agents Among Patients With Hyperlipidaemia","authors":"Jiun-Lu Lin,&nbsp;Christine Hsu,&nbsp;Shao-Wei Lo,&nbsp;Nishtha Nigam,&nbsp;Mahima Shenoi,&nbsp;Yung-Fang Tu,&nbsp;Hardikkumar Bhanderi,&nbsp;Chien-Chin Chen,&nbsp;Yu-Jung Su,&nbsp;Hui-Chin Chang,&nbsp;Shuo-Yan Gau","doi":"10.1002/dmrr.70188","DOIUrl":"10.1002/dmrr.70188","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The purpose of this paper is to compare the risk of incident type 2 diabetes mellitus (T2DM) among patients with hyperlipidaemia treated with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors versus statins and other nonstatin lipid-lowering agents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>This target trial emulation study used a retrospective, propensity score–matched cohort design based on the TriNetX Global Collaborative Network. Adults (≥ 18 years) with hyperlipidaemia diagnosed between January 2015 and December 2024 were included. Patients with preexisting diabetes, malignancy, or death during follow-up were excluded. Three active-comparator analyses compared PCSK9 inhibitors with statins, ezetimibe and fenofibrates under a per-protocol framework. Propensity score matching (1:1) balanced demographics, comorbidities, BMI, lipid profiles and healthcare utilization. Incident T2DM was identified using ICD-10 codes and analysed. Multiple sensitivity analyses including intention-to-treat analysis were performed. In the main analysis model, PCSK9 inhibitor use was associated with a significantly lower risk of incident T2DM than statins (HR 0.815; 95% CI 0.764–0.869), ezetimibe (HR 0.919, 95% CI 0.867–0.974), and fenofibrates (HR 0.517; 95% CI 0.493–0.542). Findings were consistent across subgroups and sensitivity analyses. No significant difference was observed between different PCSK9 inhibitor modalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this large-scale real-world cohort, PCSK9 inhibitors were associated with a lower risk of new-onset T2DM compared with other lipid-lowering therapies, supporting their metabolic safety and clinical use in patients at risk for diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220358","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":"A Comparison of the Effects of the Timing of Resistance Exercise on Glucose Levels Within the Target Range in People With Type 1 Diabetes (TREX Study): A Randomized Crossover Trial","authors":"Ebaa S. Al Ozairi,&nbsp;Yasmine G. Hamdan,&nbsp;Ameenah A. Al Awadhi,&nbsp;Nourah B. Al Otaibi,&nbsp;Aliea H. Baqer,&nbsp;Daniel J. West,&nbsp;Dennis R. Taliping,&nbsp;Jumana A. Al Kandari,&nbsp;Stuart R. Gray","doi":"10.1002/dmrr.70190","DOIUrl":"10.1002/dmrr.70190","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The purpose of this paper is to examine the acute and nocturnal glycaemic response to morning fasted, fed or afternoon fed resistance exercise in people with type 1 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a crossover RCT, people with type 1 diabetes performed three acute bouts of resistance exercise in (1) morning (8 AM–10:30 AM) in a fed state, (2) morning (8 AM–10:30 AM) in a fasted state and (3) afternoon (3–8 PM) in a fed state, with interstitial glucose levels measured 6-h post-exercise and in the nocturnal period (11 PM–6 AM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In all participants (<i>n</i> = 66), mean glucose levels were lower in the 6-h period after afternoon fed versus morning fasted resistance exercise (9.46 ± 2.56 vs. 8.65 ± 2.04 mmol/L, <i>P</i> = 0.04), with no other differences noted. In multiple daily injections (MDI), users (<i>n</i> = 47), but not insulin pump users (<i>n</i> = 19), in the 6-h period post-exercise mean glucose levels were higher (9.63 ± 2.58 vs. 8.44 ± 1.93 mmol/L, <i>P</i> = 0.007), time-in-range (3.9–10.0 mmol/L) lower (50.9 ± 29.5% vs. 67.0 ± 27.6%, <i>P</i> = 0.007) and time above range (&gt; 10.0 mmol/L) higher (44.4 ± 32.1% vs. 26.3 ± 25.3%, <i>P</i> = 0.003) in morning fasted versus afternoon fed state; no other differences were noted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Resistance exercise timing and feeding status (fed vs. fasted) independently influence post-exercise glycaemic responses in people with type 1 diabetes. Performing resistance exercise in the afternoon under fed conditions was associated with a more favourable glucose profile, particularly among MDI users. These findings indicate that consideration of both time of day and feeding status is important when optimising resistance exercise prescription in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov Identifier: NCT05884814 (Registered on 10 May 2023)</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212908","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":"Plasma Aryl Hydrocarbon Receptor Agonist Activity Is Associated With Inflammation and Metabolic Dysregulation in Obesity: A Cross-Sectional Study","authors":"Fatemah Bahman,&nbsp;Shihab Kochumon,&nbsp;Ashraf Al Madhoun,&nbsp;Areej Al-Roub,&nbsp;Abdullah Bennakhi,&nbsp;Monira Arouj,&nbsp;Fahd Al-Mulla,&nbsp;Rasheed Ahmad","doi":"10.1002/dmrr.70181","DOIUrl":"10.1002/dmrr.70181","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The aryl hydrocarbon receptor (AhR) is linked to inflammation, but its plasma agonist activity and association with metabolic and inflammatory markers in obesity remain unclear. This cross-sectional study aimed to determine the level of plasma AhR agonistic activity and its association with systemic inflammation and metabolic dysregulation in obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Plasma samples were collected from 80 non-diabetic (39-obese, 23-overweight, and 18-normal/healthy weight) individuals. AhR agonist activity was assessed using a cell-based luciferase reporter assay. Plasma AhR was quantified by ELISA. Inflammatory markers were assessed using a multiplex Luminex platform.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings indicate that plasma AhR agonist activity is elevated in obese (92.77 ± 4.002 fold activation) compared with normal/healthy weight (51.39 ± 2.335) and overweight participants (67.54 ± 5.24 fold activation). Moreover, the AhR protein was also elevated in obese (94.88 ± 7.62 pg/ml) compared to normal/healthy weight (65.88 ± 6.78 pg/ml) and overweight participants (67.54 ± 5.24 pg/ml), which was positively correlated with AhR activity (<i>r</i> = 0.441, <i>p</i> &lt; 0.0001). AhR activity was positively correlated with inflammatory markers including IL-1β, IL-6, TNF-α, TNF-β, and MCP-1, as well as metabolic markers such as BMI, total cholesterol, TG, insulin, FBG, and HbA1c. In contrast, it was negatively associated with HDL cholesterol. Notably, HOMA-IR was positively correlated with AhR activity. In the regression model, TNF-α, MCP-1, BMI, and HDL cholesterol emerged as significant predictors of AhR activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate that elevated plasma AhR agonist activity is associated with obesity, systemic inflammation, and metabolic dysregulation. These results highlight AhR activity as a biomarker of interest and support further studies to clarify its mechanistic role and potential clinical relevance in metabolic disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148195162","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":"Beyond Hyperglycaemia in Diabetic Bone Disease: Refining Experimental Models of Diabetes-Induced Osteopathy","authors":"Faiz Qamar,&nbsp;Manju Sharma","doi":"10.1002/dmrr.70186","DOIUrl":"10.1002/dmrr.70186","url":null,"abstract":"<p>Diabetes-induced osteopathy represents a clinically significant but under recognised complication of both type 1 and type 2 diabetes, characterised by increased fracture risk despite normal or modestly reduced bone mineral density. This paradox reflects deterioration in bone quality driven by advanced glycation end products, oxidative stress, chronic inflammation, impaired osteoblast function, enhanced osteoclast activity and disrupted osteocyte signalling. Although experimental models have provided valuable mechanistic insights, current chemically induced, diet-induced, and genetic systems each reproduce only selective aspects of the human disease. Most models prioritise metabolic validation, particularly hyperglycaemia, while skeletal endpoints are often secondary and incompletely characterised. Moreover, reductions in bone mineral density do not consistently correlate with microarchitectural or biomechanical deficits. A mechanism-oriented framework that integrates metabolic, structural, molecular, and biomechanical assessments may better capture disease complexity. Refining experimental design and endpoint standardisation could enhance translational relevance and support the development of therapeutic strategies targeting bone fragility beyond glycaemic control.</p>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139513","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":"Muscular Fitness Components in Adults With Type 1 Diabetes: A Cross-Sectional Study","authors":"Francesca Greco,&nbsp;Giovanni Guarascio,&nbsp;Concetta Irace,&nbsp;Agostino Gnasso,&nbsp;Antonio Cutruzzolà,&nbsp;Federico Quinzi,&nbsp;Raffaella Fiorentino,&nbsp;Maria Grazia Tarsitano,&nbsp;Gian Pietro Emerenziani","doi":"10.1002/dmrr.70187","DOIUrl":"10.1002/dmrr.70187","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We aimed to determine whether muscular fitness, focussing on power-related components, is reduced in adults with type 1 diabetes (T1D) compared with the group without T1D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adults with T1D and healthy controls were enroled in the study. Muscular fitness was evaluated using Handgrip strength (HG), knee extensor isometric maximal torque (PeakT), and 10-repetition sit-to-stand (STS). Moreover, the specific power index of the lower limb was obtained from the ratio between STS and skeletal muscle mass.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixty-seven individuals with T1D (32 females, 35 males; age: 38.9 ± 14.6 years) were matched for age, sex, body mass index and physical activity level with a non-diabetic Control Group (CG, <i>n</i> = 67). The T1D group was significantly slower than the control group (CG) during the STS test (20.2 ± 3.8 vs. 18.6 ± 3.3 s, <i>p</i> &lt; 0.01) and exhibited a lower specific power (5.3 ± 1.2 vs. 5.9 ± 1.3 W/kg, <i>p</i> &lt; 0.01). No significant differences were observed in HG and PeakT (<i>p</i> &gt; 0.05) between the T1D and CG groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adults with T1D show a reduction in dynamic muscle function (STS), whereas isometric function appears to be preserved.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139583","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":"Predicting the Complex, Multilevel Ecology of US County-Level Diabetes Prevalence: A Cross-Sectional, Artificial Intelligence Analysis","authors":"Nicolaas P. Pronk,&nbsp;Shuaijie Wang,&nbsp;Richard Bergenstal,&nbsp;Anders Carlson,&nbsp;Colin Woodard,&nbsp;Ross Arena","doi":"10.1002/dmrr.70184","DOIUrl":"10.1002/dmrr.70184","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetes and its risk factors are embedded in a complex multilevel ecology. Upstream factors (i.e., ‘forcing factors’ that refer to fundamental population-based social, economic, and political structures shaping health outcomes long before disease develops) and downstream risk factors (i.e., the individual-level characteristics and outcomes that result from upstream forcing factors) are to be considered when predicting diabetes. This study aims to predict diabetes prevalence at the United States' (US) county level using analytical methods that account for the contextual complexity of diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>US county-level datasets incorporating 27 predictor variables were analysed cross-sectionally. A Light Gradient Boosting Machine (LightGBM) model was trained to predict county-level diabetes prevalence, after which model performance and feature importance were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>The final model retained 17 features and explained 95% (<i>R</i>² = 0.952) of the variance in county-level diabetes prevalence. Physical inactivity, racial and ethnic minority status, frequent physical distress, and obesity showed the highest Shapley (SHAP) importance values, which exceeded all remaining SHAP values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study delineates the most important predictors of diabetes prevalence based on a complex multilevel ecology. Efforts to reduce diabetes prevalence should address both upstream and downstream risk factors emphasising physical activity, obesity, equity, and cultural considerations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145331","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":"Tissue and Serum Concentrations of Time-Dependent Antibiotics in Infected Diabetic Foot Ulcers by Bolus or Continuous Administration: The Randomised DFIATIM Trial","authors":"Radka Jarošíková,&nbsp;Dominika Sojáková,&nbsp;Simona Antalová,&nbsp;Petr Tůma,&nbsp;Jan Polák,&nbsp;Michal Dubský,&nbsp;Andrea Němcová,&nbsp;Veronika Wosková,&nbsp;Pavol Beca,&nbsp;Istvan Modos,&nbsp;Jan Mareš,&nbsp;Jakub Mrázek,&nbsp;Chahrazed Mekadim,&nbsp;Markéta Skružná,&nbsp;Vladimíra Fejfarová","doi":"10.1002/dmrr.70185","DOIUrl":"https://doi.org/10.1002/dmrr.70185","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The clinical effectiveness of antibiotic (ATB) therapy in patients with infected diabetic foot ulcers (iDFUs) depends on achieving sufficient ATB concentrations in both serum and peripheral tissues. This study evaluated the availability and bactericidal activity of the time-dependent ATBs—ceftazidime (CTZ) and amoxicillin/clavulanate (AMC) in serum and peripheral tissues by comparing bolus versus continuous administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixty patients with iDFUs were randomised into four subgroups according to ATB and administration method: CTZ bolus (CTZ_bolus), CTZ continuous infusion (CTZ_continuous), AMC bolus (AMC_bolus), and AMC continuous infusion (AMC_continuous). Once steady-state concentrations were reached, microdialysis was used to assess ATB levels in tissue adjacent to the ulcer. Serum and tissue samples were collected over a 6-h period. Bactericidal activity was assessed by peak concentrations (Cmax), area under the curve (AUC), and the proportion of time free drug concentrations remained above the minimum inhibitory concentration (fT &gt; MIC). Target thresholds were fT &gt; MIC ≥ 60% for CTZ and ≥ 50% for AMC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All patients achieved serum fT &gt; MIC targets for CTZ and AMC in 100% of AMC_bolus and 89% of AMC_continuous. In tissue, target attainment was 60% (CTZ_bolus), 73% (CTZ_continuous), 79% (AMC_bolus), and 83% (AMC_continuous). Bolus administration led to rapid serum peaks (5 min) and delayed tissue peaks (30–60 min), with subsequent declines. Continuous infusion produced gradual concentration increases over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>While all patients achieved serum fT &gt; MIC targets for CTZ and AMC (100% for AMC_bolus and 89% for AMC_continuous), target attainment in tissue was substantially lower. These findings suggest that although serum pharmacodynamic targets are reliably achieved, tissue exposure remains suboptimal.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148100402","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":"Comment on ‘Glycaemic Status Modifies the Association Between Cardiometabolic Index and Cardio-Kidney Outcomes: A Multi-Cohort Analysis’","authors":"Mengdi Zhang","doi":"10.1002/dmrr.70182","DOIUrl":"10.1002/dmrr.70182","url":null,"abstract":"&lt;p&gt;To the Editor,&lt;/p&gt;&lt;p&gt;I read with great interest the multi-cohort analysis by Xie and colleagues evaluating the cardiometabolic index (CMI) and cardio-kidney outcomes across glycaemic strata [&lt;span&gt;1&lt;/span&gt;]. This topic is clinically relevant for CKM risk stratification. However, two analytical aspects may affect the interpretation of the reported associations and effect modification.&lt;/p&gt;&lt;p&gt;First, the primary endpoint ‘cardio-kidney events (CKE)’ is defined as the co-occurrence of cardiovascular disease (CVD) and chronic kidney disease (CKD), with event time effectively determined by the second component to occur [&lt;span&gt;1&lt;/span&gt;]. This definition differs from a conventional time-to-first-event construct. Patients who develop one component and then die (or are lost) before the other occurs may be treated as censored rather than as informative clinical trajectories, which can introduce survivor/selection mechanisms. It would be helpful if the authors could re-present results using time-to-first-event analyses for incident CVD, incident CKD, and a conventional composite endpoint (first occurrence of CVD or CKD), alongside the original co-occurrence definition. In addition, a multi-state framework (baseline → CVD-first/CKD-first → both, with death as an absorbing state) could better match the clinical concept of cardio-kidney comorbidity [&lt;span&gt;2&lt;/span&gt;]. Reporting these alternative estimands would allow readers to judge robustness to outcome definition.&lt;/p&gt;&lt;p&gt;Second, the attenuation of associations across glycaemic strata may reflect time-varying structure rather than biology alone. Over long enrolment windows, evolving cardioprotective therapies, particularly SGLT2 inhibitors and GLP-1 receptor agonists, may differentially modify CVD/CKD risk by glycaemic status. If medication class and exposure duration are incompletely captured, interaction estimates may be distorted [&lt;span&gt;3&lt;/span&gt;]. Glycaemic status can also change during follow-up; baseline-only stratification may misclassify participants and dilute subgroup contrasts. It would be of interest if sensitivity analyses could incorporate time-varying diabetes status (or restrict analyses to participants with stable glycaemic classification), and explicitly account for contemporary therapies where feasible, for example through therapy-adjusted models or calendar-era analyses [&lt;span&gt;3&lt;/span&gt;]. These additions clarify whether effect modification persists after addressing time-varying confounding and misclassification.&lt;/p&gt;&lt;p&gt;Although further work may be required to refine estimands for cardio-kidney risk prediction, I thank the authors for this important study and look forward to their response.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Mengdi Zhang:&lt;/b&gt; conceptualization, drafting of the manuscript, review and editing of the manuscript.&lt;/p&gt;&lt;p&gt;The author has nothing to report.&lt;/p&gt;&lt;p&gt;The author declares no conflicts of interest.&lt;/p&gt;&lt;p&gt;Data sharing not applicable to this article as no datasets were generated or analysed during the cu","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057780","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":"Medication Adherence in Diabetes Management in Sub-Saharan Africa: A Systematic Review of Determinants and Strategies for Improvement","authors":"Roland Muhindo Muyisa,&nbsp;Emile Justin Watumwa,&nbsp;Amos Kaghoma Sivulyamenge,&nbsp;Jean Paul Paluku Mwalitsa","doi":"10.1002/dmrr.70183","DOIUrl":"10.1002/dmrr.70183","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Diabetes mellitus poses a significant public health challenge in Sub-Saharan Africa (SSA), exacerbated by healthcare limitations, socioeconomic disparities and sociocultural factors affecting disease management. Medication adherence is critical for glycaemic control but remains suboptimal in this region. This review synthesises evidence on adherence to antidiabetic medications in SSA, identifies key determinants and suggests strategies to improve adherence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic review was conducted following PRISMA 2020 guidelines by searching PubMed, Scopus, Web of Science and African Journals Online for studies published between January 2015 and May 2025. Studies involving diabetic patients in SSA and assessing medication adherence were included. Data were extracted using a standardized form, and methodological quality was assessed using the Newcastle–Ottawa Scale.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-six studies with over 6500 participants from 10 SSA countries were included. Adherence rates varied from 13.9% to 84.5%, with most settings reporting moderate to low adherence. Key determinants of non-adherence included socioeconomic barriers, therapy-related factors, health system limitations, and sociocultural influences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Effective interventions need to be culturally sensitive and address these multidimensional barriers. Future research should focus on longitudinal and interventional designs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057718","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148081867","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}