Diabetes, Obesity & Metabolism最新文献

{"title":"Empagliflozin for the preservation of beta-cell function in women with recent gestational diabetes: A randomized placebo-controlled trial.","authors":"Shamini Murugavel, Ravi Retnakaran, Denice S Feig, Bernard Zinman, Caroline K Kramer","doi":"10.1111/dom.70146","DOIUrl":"https://doi.org/10.1111/dom.70146","url":null,"abstract":"<p><strong>Aims: </strong>Women with a history of gestational diabetes (GDM) frequently have progressive beta-cell dysfunction, which may result in type 2 diabetes. However, there is a paucity of clinical studies on strategies aiming to preserve beta-cell function in this patient population. This trial evaluated whether empagliflozin can preserve beta-cell function and reduce the prevalence of dysglycemia (prediabetes/diabetes) in women with recent GDM.</p><p><strong>Materials and methods: </strong>We conducted a double-blind, randomized, placebo-controlled trial where 91 women with recent GDM (6-36 months postpartum) were randomized 1:1 to either empagliflozin 10 mg/day or placebo for 48 weeks. Beta-cell function was assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2) obtained on an oral glucose tolerance test.</p><p><strong>Results: </strong>The primary outcome of baseline-adjusted ISSI-2 at 48 weeks was not different between the empagliflozin and placebo group (525 ± 30.4 vs. 560 ± 33.4, p = 0.43). Additional measures of beta-cell function, insulinogenic index/HOMA-IR, and ΔCpep_0-120/Δgluc_0-120 × Matsuda index also did not differ between the groups. While there was no difference in the secondary outcome of prevalence of dysglycemia at 48 weeks between the arms (empagliflozin 65.7% vs. 48.2% in placebo, p = 0.18), the glucose tolerance worsened in 9.4% of participants in the empagliflozin group as compared to 28% in the placebo group (p = 0.08).</p><p><strong>Conclusions: </strong>Empagliflozin had no significant effect on beta-cell function in women with recent GDM. Given the sample size evaluated in this trial, the use of SGLT-2 inhibitors warrants further study to elucidate their potential impact on T2DM prevention in women with previous GDM.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov NCT03215069.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079292","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":"Integrative metabolomic and proteomic analysis of diabetic kidney disease progression with younger-onset type 2 diabetes.","authors":"Resham Lal Gurung, Huili Zheng, Jia Le Ivan Tan, Sylvia Liu, Clara Chan, Keven Ang, Clara Tan, Jian-Jun Liu, Tavintharan Subramaniam, Chee Fang Sum, Su Chi Lim","doi":"10.1111/dom.70153","DOIUrl":"https://doi.org/10.1111/dom.70153","url":null,"abstract":"<p><strong>Aim: </strong>Younger-onset type 2 diabetes (YT2D) confers a disproportionately high risk of diabetic kidney disease (DKD), yet early biomarkers and underlying mechanisms remain poorly defined. We aimed to identify metabolites associated with DKD progression and integrate metabolomic and proteomic data to elucidate pathways involved in a multi-ethnic Asian cohort.</p><p><strong>Materials and methods: </strong>In this prospective study, 787 YT2D patients (diagnosed at ≤ age 40) were followed for a median of 5.7 years. DKD progression was defined as an annual decline in estimated glomerular filtration rate (eGFR) of ≥3 mL/min/1.73 m² or ≥ 40% reduction in eGFR from baseline. Plasma metabolites were measured by nuclear magnetic resonance spectroscopy. Multivariable regression analysis was performed in a discovery (N = 550) and internal validation cohort (N = 237). Integrative metabolomic-proteomic analysis (N = 428) was performed using sparse partial least squares discriminant analysis (sPLS-DA).</p><p><strong>Results: </strong>Ninety-eight metabolites were differentially expressed between DKD progressors and non-progressors, of which total branched-chain amino acids (BCAAs) (OR = 0.60, 95% CI 0.46-0.79), valine (OR = 0.62, 95% CI 0.48-0.81), and leucine (OR = 0.56, 95% CI 0.43-0.74) associated with DKD progression, independent of metabolic risk factors. Integrative analysis identified three components comprising 23 proteins and 30 metabolites, involved in the citrate cycle and apoptosis, which improved prediction of DKD progression beyond clinical risk factors (AUC 0.69-0.83).</p><p><strong>Conclusion: </strong>Lower plasma BCAA levels are independently associated with DKD progression in YT2D. Integrative multi-omics analysis highlights disruptions in metabolic and apoptotic pathways, providing insights into DKD pathophysiology and potential biomarkers for early risk stratification.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079343","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":"Discrepancies between current displayed and auto-logged glucose values in FreeStyle Libre 3: Implications for clinical interpretation.","authors":"Lilian Witthauer, Camilo Mendez, José Garcia-Tirado, Manuel Eichenlaub, Delia Waldenmaier, Stefan Pleus, Guido Freckmann","doi":"10.1111/dom.70140","DOIUrl":"https://doi.org/10.1111/dom.70140","url":null,"abstract":"<p><strong>Aims: </strong>The FreeStyle Libre 3 (FSL3) continuous glucose monitoring (CGM) system provides both auto-logged glucose values (AL) and current displayed glucose values (CUR). These values are often assumed to be interchangeable; however, discrepancies and their clinical relevance remain underexplored.</p><p><strong>Materials and methods: </strong>Data from a 15-day study in 24 study participants wearing FSL3 were analysed, including three in-clinic sessions with glycaemic excursions during which CUR values were retrieved every 15 min by study personnel. Paired AL and CUR readings were compared using descriptive statistics, Wilcoxon signed-rank tests, and mean absolute relative difference (MARD) calculations. Display errors defined as instances where the app showed an error message instead of a CUR value were analysed using linear mixed-effects models to assess associations with glucose level and rate of change (RoC).</p><p><strong>Results: </strong>CUR values were comparable to AL in general (mean difference: -1.2 ± 6.4 mg/dL), but slightly lower in the hypoglycaemic range. Discrepancies exceeding ±10 mg/dL occurred in about 10% of cases. MARD was comparable between AL (9.7%) and CUR (10.1%), with greater deviation in hypoglycaemia. Display errors (3.9%) occurred more often at higher glucose levels (mean AL difference: +91.9 mg/dL) and during rapid fluctuations (mean absolute RoC difference: +1.52 mg/dL/min; both p < 0.001).</p><p><strong>Conclusions: </strong>Although differences between AL and CUR were generally small, they were systematic and more pronounced in critical contexts like hypoglycaemia and rapid glucose change. Recognising these patterns may improve CGM data interpretation and alignment between user actions, provider decisions, and automated systems. These differences can reclassify readings across clinical thresholds, affecting patient-clinician alignment despite small average biases.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084576","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":"Sex as a modifier of genetic risk for type 1 diabetes.","authors":"Hui-Qi Qu, Hakon Hakonarson","doi":"10.1111/dom.70124","DOIUrl":"https://doi.org/10.1111/dom.70124","url":null,"abstract":"<p><p>Sex differences influence the pathogenesis of type 1 diabetes (T1D), yet most genetic studies have treated sex as a control covariate rather than a dynamic effect modifier. Sex influences immune cell behaviour, including CD4⁺ and CD8⁺ T cell activation, regulatory T cell stability, B cell autoantibody production, dendritic cell priming and monocyte/macrophage inflammation. Underlying mechanisms include hormone-responsive enhancers, X-escape gene dosage and sex-biassed chromatin states, intersecting with T1D-associated variants to produce sex-specific immune phenotypes. These insights help explain regional variation in sex ratios of T1D incidence, such as male predominance in high-risk populations and female excess in low-risk populations. Biological sex shapes T1D risk across multiple layers, including polygenic load; environmental exposures such as vitamin D deficiency and enteroviral infection; and sex-specific hormonal, chromosomal and epigenetic influences. An integrative G × E × S (genetic × environmental × sex-specific) liability-threshold framework is thus supported. Clinical and translational implications include developing sex-specific polygenic risk scores, biomarker panels and interventional strategies targeting pathways such as hormone signalling, vitamin D metabolism and the microbiome. Future multi-omic, longitudinal studies are warranted to test genotype-sex interactions, integrate sex as a core effect modifier and enable precision prevention and treatment of T1D in both males and females.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084654","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":"Coated glucose microbeads stimulate enteric hormone release and improve glucose tolerance in Phase 1 and 2 clinical trials.","authors":"Kai Deusch, Arthur Deboek, Christian Sina, Coral Capo-Velez, Vivianette Alicea, Stephan Duller, Susanne Grafe, Darcy Lidington, Julia Hanchard, Steffen-Sebastian Bolz","doi":"10.1111/dom.70135","DOIUrl":"https://doi.org/10.1111/dom.70135","url":null,"abstract":"<p><strong>Aims: </strong>Incretin agonists are used to treat obesity and metabolic dysfunction. Instead of systemically delivering high levels of hormone receptor agonists that can lead to adverse effects, we tested and optimized oral microbead formulations that activate endogenous enteroendocrine signalling systems via distal nutrient-sensing cells.</p><p><strong>Materials and methods: </strong>We report two randomized Phase 1 studies (NCT05713773 and NCT05737927) measuring acute pharmacokinetic/pharmacodynamic responses following consumption of microbeads that deliver glucose to the distal small intestine: these studies compared coating variations and glucose dosing. The primary endpoint was plasma glucagon-like peptide 1 (GLP-1) levels; we also measured GLP-2, PYY, glicentin, oxyntomodulin, glucose-dependent insulinotropic peptide, C-peptide, and insulin as exploratory endpoints. In a subsequent randomized Phase 2a trial (NCT05803772), prediabetic subjects consumed a lead formulation or placebo once daily for 6 weeks each in a two-period, two-sequence crossover design. Oral glucose tolerance was measured at baseline and following treatment in each sequence, with the primary endpoint being the change in the area under the curve.</p><p><strong>Results: </strong>Our microbead formulation successfully targeted the distal small intestine and elicited a robust plurihormonal enteroendocrine response; our Phase 2a data show that the lead formulation improved glucose tolerance in pre-diabetic patients, comparable to results using GLP-1 mimetics. Adverse events were infrequent and modest.</p><p><strong>Conclusions: </strong>Targeted glucose release activates endogenous enteroendocrine signalling networks, improves a clinically relevant metabolic endpoint, and has minimal adverse effects. The approach to target native enteroendocrine signalling has disruptive potential for the treatment of metabolic disorders, including obesity.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074037","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":"Contributions of 2-h post-load glucose, fasting blood glucose and glycosylated haemoglobin elevations to the prevalence of diabetes and pre-diabetes in adults: A systematic analysis of global data.","authors":"Xue Xue, Jiaxuan Li, Wenxiao Zheng, Bingrui Zhang, Shuting Wang, Jiayue Zhang, Zuyao Yang","doi":"10.1111/dom.70130","DOIUrl":"https://doi.org/10.1111/dom.70130","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;Some studies found that the association of fasting blood glucose (FPG) or glycosylated haemoglobin (HbA1c) elevation with diabetic complications was not statistically significant after controlling for the confounding caused by 2-h post-load glucose (2hPG) elevation. Furthermore, inclusion of HbA1c as a diagnostic measure for diabetes has raised some concerns about over-diagnosis and over-treatment. This study aimed to quantify the contributions of 2hPG, FPG and HbA1c elevations to the prevalence of diabetes and pre-diabetes respectively, by synthesising global data, which can serve as essential parameters in cost-effectiveness analysis and inform updates of practice guidelines about prevention and control of diabetes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;The levels of 2hPG, FPG and HbA1c were classified as either 'elevated' or 'normal.' Each distinct combination of these markers (e.g., 'elevated 2hPG, normal FPG and normal HbA1c') defined a unique subgroup, resulting in a total of seven subgroups for both diabetes and pre-diabetes. The contribution of 2hPG elevation to diabetes prevalence was calculated as its proportion among all diabetes cases; the same approach was applied to FPG and HbA1c elevations, as well as to pre-diabetes prevalence. To retrieve global data, five electronic databases (i.e., PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure and Wan Fang) were searched from their inception to February 2024. Studies that fulfilled the following criteria were considered eligible: (1) were conducted in adults without previously diagnosed diabetes; (2) were cross-sectional studies or baseline surveys of cohort studies (which can be regarded as a special type of cross-sectional studies); and (3) reported directly or allowed for calculation of the proportion of each subgroup out of all diabetes and/or the proportion of each subgroup out of all pre-diabetes. A 10-item tool selected from literature was used to appraise the quality of included data. The proportions of each subgroup among all diabetes cases were meta-analysed across eligible studies with the random-effects model using the MetaXL software. Similar meta-analyses were conducted for pre-diabetes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Thirty-two eligible studies were identified, with 25 reporting on newly detected diabetes (n = 289 094) and 15 on pre-diabetes (n = 221 988) and the majority of them using identical diagnostic cutoffs proposed by the American Diabetes Association (ADA). The mean age of participants ranged from 24 to 68 years (median of mean ages: 51). Twenty-four studies (75%) were assessed as at low risk for ≥7 out of the 10 quality items. In the general population, based on the ADA criteria, the weighted prevalence of diabetes and pre-diabetes was 15% and 69%, respectively. Among those with newly detected diabetes (n = 24 214), 69% had elevated 2hPG, 44% elevated FPG and 61% elevated HbA1c; 7% had isolated FPG elevation; ","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068715","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":"Efficacy and safety in tirzepatide-treated Korean adults with type 2 diabetes-A post hoc analysis of SURPASS-AP-combo and SURPASS-3.","authors":"Byung Wan Lee, Chang Beom Lee, Soo Lim, Sin Gon Kim, Nan Hee Kim, Jong Chul Won, Woo Je Lee, Min Ju Kang, Ju Young Yuh, Li Ying Du, Hyojin Lim, Kyu Jeung Ahn","doi":"10.1111/dom.70111","DOIUrl":"https://doi.org/10.1111/dom.70111","url":null,"abstract":"<p><strong>Aims: </strong>This post hoc analysis assessed the efficacy and safety data in tirzepatide-treated Korean patients with type 2 diabetes (T2D).</p><p><strong>Materials and methods: </strong>Data specifically from Korean patients treated with tirzepatide 5, 10, or 15 mg in the multicentre, randomised, open-label, parallel-group, phase 3 trials SURPASS-AP-Combo and SURPASS-3 were extracted and analysed. Efficacy (change from baseline in glycated haemoglobin [HbA1c] and body weight, and proportions of participants achieving HbA1c and body weight targets) and safety endpoints were evaluated at week 40 (SURPASS-AP Combo) and week 52 (SURPASS-3).</p><p><strong>Results: </strong>In the SURPASS-AP-Combo and SURPASS-3, 79 of 687 and 27 of 1079 tirzepatide recipients, respectively, were Korean. In Korean participants in SURPASS-AP-Combo across all tirzepatide doses, least squares mean (LSM) HbA1c was reduced from baseline by 2.75% to 3.25% and HbA1c targets of <7.0% and ≤6.5% were achieved by 84.6% to 100% at week 40; LSM body weight reductions of -6.8% to -10.9% from baseline were achieved. The composite endpoint of HbA1c ≤6.5% without body weight gain or clinically significant documented symptomatic or severe hypoglycaemia was achieved by 69.2% to 85.2% of tirzepatide recipients. Findings were similar in Korean participants of SURPASS-3. The safety profile of tirzepatide in Korean participants was generally consistent with that in the overall SURPASS-AP-Combo and SURPASS-3 populations.</p><p><strong>Conclusions: </strong>Consistent with the overall results of the SURPASS-AP-Combo and SURPASS-3 trials, this post hoc subgroup analysis found clinically meaningful reductions in HbA1c and body weight after treatment periods of 40 to 52 weeks in Koreans with T2D treated with tirzepatide.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068749","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":"Combined agonism of nutrient receptors GPR40 and GPR119 with K-757 and K-833 results in weight loss and blood pressure reductions in obese subjects without type 2 diabetes mellitus.","authors":"Michael Crutchlow, Jiajun Liu, Christopher Romero, Elaine Watkins, Harry Zhang, Anna Arreglado, Annemarie Vance, Daniel Boisvert, Giuseppe Terracina, Bryan Chan, Matt J Consolati, Gregory Poterewicz, Jennifer E Talaty, Brett Lauring","doi":"10.1111/dom.70120","DOIUrl":"https://doi.org/10.1111/dom.70120","url":null,"abstract":"<p><strong>Aims: </strong>K-757 and K-833 are novel full agonists of GPR40 and GPR119, respectively, which are nutrient receptors co-expressed on both pancreatic beta cells and gut enteroendocrine cells that signal through complementary mechanisms. We sought to assess the effects beyond glucose control of co-agonism with K-757 and K-833.</p><p><strong>Materials and methods: </strong>A Phase 1 study of the combination of K-757 and K-833 was conducted in overweight-obese participants to identify dose regimens causing maximal secretion of multiple gut hormones. Subsequently, a randomised, double-blind, parallel arm and 13-week Phase 2a study was conducted to assess the effects of K-757 alone and in combination with K-833, in comparison to placebo (n = 155 [51-52/arm]).</p><p><strong>Results: </strong>Co-administration of K-757 120 mg twice daily (BID) and K-833 100 mg BID resulted in elevations of circulating glucagon-like peptide 1 (3.44×), active glucagon-like peptide 1 (5.06×), peptide YY (8.63×), glucagon dependent insulinotropic peptide (1.65×), cholecystokinin (3.06×) and oxyntomodulin (5.66×) relative to placebo. In Phase 2a, placebo-adjusted weight loss with the K-757 + K-833 combination and K-757 alone was -2.78% (p < 0.001) and -1.42% (p = 0.0756), respectively. Though blood pressure, an exploratory endpoint, was not elevated at baseline, placebo-adjusted reductions were observed with the combination (-6.9/-5.4 mmHg) and K-757 alone (-5.3/-3.2 mmHg). Gastrointestinal adverse events (AEs) and discontinuation due to AEs were more common in the active treatment arms. The combination and K-757 alone were otherwise well tolerated.</p><p><strong>Conclusions: </strong>K-757, alone and in combination with K-833, elicited robust elevations in circulating concentrations of multiple satiety peptides, which elicited some weight loss and blood pressure reductions that suggest potential for metabolic benefit independent of weight loss.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068791","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":"Dapagliflozin restores odour-induced functional integration of primary olfactory cortex circuit but not olfactory-related regional brain activation in patients with type 2 diabetes: A 16-week randomised comparative study.","authors":"Xin Li, Yi Zhang, Yan Bi, Jiaming Lu, Zhou Zhang, Cheng Ji, Xin Zhang, Qian Li, Shuang Wang, Jiu Chen, Zhengyang Zhu, Wen Zhang, Bing Zhang","doi":"10.1111/dom.70132","DOIUrl":"https://doi.org/10.1111/dom.70132","url":null,"abstract":"<p><strong>Aims: </strong>Although some hypoglycaemic agents have been suggested to possess neuroprotective effects, their mechanisms and efficacy remain controversial. We aimed to investigate the effects of dapagliflozin, liraglutide or acarbose treatment on the directed functional connectivity (FC) of the primary olfactory cortex (POC) circuit and regional activation under odour stimulation in patients with type 2 diabetes (T2D).</p><p><strong>Materials and methods: </strong>The 16-week randomised, prospective, parallel-group, and open-label trial included 36 patients with T2D inadequately controlled with metformin, who were randomised (1:1:1) to receive dapagliflozin, liraglutide or acarbose. Meanwhile, 36 healthy controls were recruited. All participants underwent olfactory task functional magnetic resonance imaging, along with a battery of olfactory and cognitive tests, both at baseline and postintervention.</p><p><strong>Results: </strong>After 16 weeks, dapagliflozin restored odour-induced functional integration of the POC-sensorimotor cortex-middle temporal cortex circuit (Gaussian random field correction applied), whereas liraglutide and acarbose did not. Dapagliflozin also tended to improve attention (p = 0.071). In contrast, liraglutide enhanced odour-induced activation in the left hippocampus, which was not observed with dapagliflozin and acarbose. The decreased odour-induced directed FC was associated with changes in lipid levels, olfactory threshold, executive function and memory performance (all p < 0.05).</p><p><strong>Conclusions: </strong>These results suggest that dapagliflozin and liraglutide exhibit distinct neuroprotective effects. While liraglutide enhances activation in local olfactory-related regions, dapagliflozin facilitates functional integration within neural circuits. This highlights the importance of targeting both metabolic and neural pathways to manage diabetes-related cognitive decline.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068712","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":"A 7-year prospective analysis of sustained benefits of multicomponent risk assessment and data-driven care in patients with type 2 diabetes: The Malaysian JADE Program.","authors":"Jia-Xin Hoo, Ya-Feng Yang, Eric S H Lau, Luqman Ibrahim, Shireene R Vethakkan, Jeyakantha Ratnasingam, Siew-Pheng Chan, Sharmila S Paramasivam, Yook-Chin Chia, Alexander T B Tan, Andrea O Y Luk, Sanjay Rampal, Juliana C N Chan, Lee-Ling Lim","doi":"10.1111/dom.70125","DOIUrl":"https://doi.org/10.1111/dom.70125","url":null,"abstract":"<p><strong>Aim: </strong>We evaluated the sustained effects of multicomponent risk assessment and data-driven care augmented by the web-based Joint Asia Diabetes Evaluation (JADE) Platform with a built-in template to guide comprehensive assessment (CA) for risk stratification on top of usual care in patients with type 2 diabetes (T2D) from Malaysia.</p><p><strong>Methods: </strong>In 2012-2015, 1196 T2D patients participated in a 1-year JADE Program randomised to (1) CA-only, (2) receipt of a JADE personalised report (CA + R) to empower self-care, or (3) engagement by nurse phone calls (CA + R + T). In 2020-2022, patients underwent repeat CA for evaluation of attainment of ≥2 ABC targets (HbA1c <7%, Blood pressure <130/80 mmHg, low-density lipoprotein Cholesterol [LDL-C] <2.6 mmol/L) and diabetes-related endpoints.</p><p><strong>Results: </strong>After 7.5 ± 0.5 (mean ± SD) years, 138 (11.5%) patients had died, 232 (19.4%) defaulted, and 826 (69.1%) patients returned. The deceased had more complications, while non-returnees were younger, with fewer complications but worse risk factor control than returnees at baseline. Using inverse probability weighting and logistic regression, attaining ≥2 ABC targets was associated with CA + R + T (vs. CA-only) with an odds ratio (OR, 95% confidence interval) of 1.57 (1.02-2.41, p = 0.041). Other predictors included age [1.05 (1.04-1.07, p < 0.001)], diabetes duration [0.97 (0.95-0.99, p = 0.003)], JADE risk category 3 [0.41 (0.26-0.66), p < 0.001] and risk category 4 (vs. category 1 and 2) [0.22 (0.12-0.38), p < 0.001]. Amongst participants without complications at baseline, CA + R + T was associated with an incidence rate ratio of 0.89 (0.78-1.00, p = 0.043) for any diabetes-related endpoints.</p><p><strong>Conclusions: </strong>Technology-assisted multicomponent risk assessment and data-driven care for 1-year identified high-risk patients and improved outcomes after 7 years.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068724","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}