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A narrative systematic review of definitions and diagnostic criteria for disordered eating and eating disorders in type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes and disordered eating (T1DE) affects 8-37.1% of adults and is associated with high rates of morbidity and mortality. The absence of a standardised case definition of T1DE and its severity hinders effective screening, diagnosis and treatment. This systematic review aimed to (1) synthesise existing case definitions and diagnostic criteria for T1DE in adults and (2) identify key characteristics to inform consensus for future diagnostic criteria. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Eligible studies involved adults (≥18 years) with type 1 diabetes assessing disordered eating; paediatric studies, mixed samples without disaggregated data, non-empirical designs and non-English publications were excluded. PubMed, MEDLINE, EMBASE, CINAHL and PsycINFO were searched up to November 2025 for peer-reviewed studies involving adults with T1DE. Qualitative and quantitative data on definitions, diagnostic criteria and assessment tools were extracted. Study quality was appraised using a modified Graphical Appraisal Tool for Epidemiological studies (GATE) checklist. Due to heterogeneity of data, a narrative synthesis of findings was performed to describe current definitions of T1DE. RESULTS: Sixty-one studies met the inclusion criteria, with a pooled sample of 111,208 participants (76% women) from over 22 countries. T1DE was defined using a heterogeneous array of terms, diagnostic frameworks and assessment tools (29 distinct methods). The Diabetes Eating Problem Survey-Revised (DEPS-R) was the most used questionnaire, but many studies relied on criteria adapted from general eating disorder classifications or generic questionnaires. Approximately three-quarters of the studies assessed insulin omission behaviours, but the operationalisation of the cognitions for insulin omission varied widely. Beyond physiological markers such as HbA1c and BMI, studies explored various diabetes-related and psychological constructs, although often considering diabetes and disordered eating separately rather than as an integrated condition. CONCLUSIONS/INTERPRETATION: This systematic review highlights the lack of a unified, evidence-based definition of T1DE, resulting in inconsistent screening, diagnostic and reporting practices. Establishing clear, consistent, evidence-based diagnostic criteria and screening questionnaires for T1DE is critical to improving early detection and developing targeted interventions. These findings provide a foundation for refining T1DE definitions as a stepping stone to an international consensus definition. STUDY REGISTRATION: PROSPERO registration no. CRD420250223622 FUNDING: King's College London and King's College Hospital through the KMRT KCH Joint Research Committee studentship. This work was also conducted as part of the National Institute for Health Research (NIHR; CS-2017-17-023)-funded STEADY project (Safe management of people with Type 1 diabetes and EAting Disorders studY). NZ's salary was part-funded by the NIHR via the NIHR Clinician Scientist award to MS; JT and KI are part-funded by the NIHR Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. MS was funded through her NIHR Clinician Scientist Fellowship (CS-2017-17-023).

Humans

Construction of precision clinical-proteomics risk model based on machine learning for predicting heart failure in type II diabetes mellitus.

BACKGROUND AND AIMS: Heart failure (HF) is a severe complication in type 2 diabetes mellitus (T2DM), but current risk stratification scores have limited predictive accuracy. We aimed to develop novel prediction tools integrating clinical variables with proteomics to improve risk stratification of hospitalization for HF in T2DM. METHODS AND RESULTS: In this study, we included 2111 UK Biobank participants with T2DM but no prior HF, and profiled 2920 proteins to predict 10-year incident HF hospitalization. Participants were randomly divided into training (70%), tuning (10%), and validation (20%) sets.Three prediction models were developed: a Clinical model based on demographic characteristics, comorbidities, medication use, and laboratory indices; a Protein model based on 40 proteins selected by the Light Gradient Boosting Machine (LGBM); and the Clinical OMics and Protein ASSessment for Heart Failure (COMPASS-HF) model, which integrated both clinical variables and the LGBM-selected proteins. Models were evaluated for area under the curve (AUC), sensitivity, and specificity. During follow-up, 168 participants (7.96%) developed incident HF. The COMPASS-HF model showed better discrimination than the Clinical model, with an AUC of 0.897 (95% CI: 0.850-0.945) versus 0.790 (95% CI: 0.723-0.856). It also demonstrated higher sensitivity (0.882; 95% CI: 0.725-0.967) and consistent performance in subgroups. COMPASS-HF effectively stratified risk of hospitalization for HF, with cumulative incidence rates of 31.9% in the high-risk group and 1.2% in the low-risk group. CONCLUSIONS: By combining clinical and proteomic variables, we developed a high-performance HF prediction model for T2DM, enabling precise risk stratification and informing early intervention strategies.

Humans

Acute Stevia Consumption does not Alter Endocrine Responses in Individuals with Normal Weight, Overweight, and Type 2 Diabetes Mellitus.

BACKGROUND: Stevia is a plant-based non-nutritive sweetener. Acute effects of stevia ingestion on glycemia and hormonal responses have not been fully investigated. OBJECTIVE: This objective of this study was to evaluate the acute effects of beverages containing stevia alone and in combination with glucose on glycemic, hormonal, and appetite responses. METHODS: This study evaluated three cohorts of n=23 individuals with either normal weight (NW), overweight (OW), or type 2 diabetes mellitus (T2DM) for which each individual completed four test conditions in a randomized sequence crossover study design. The four test conditions were beverages containing stevia (75.6 mg steviol equivalents), water, glucose (30 g), and stevia+glucose (30 g glucose+75.6 mg steviol equivalents). Blood samples were collected before and for 180 min after beverage consumption. Assessments included net area under the curve (niAUC) and incremental maximal concentration values for plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1, glucagon, and PYY. Appetite was assessed with visual-analog scale questions and energy consumption during an ad libitum meal. RESULTS: Responses to the stevia beverage did not differ significantly from those for water alone, and stevia + glucose did not differ significantly from glucose alone for any of the three groups. CONCLUSION: Acute stevia consumption did not materially alter responses for glycemia or hormones involved in glucose and appetite regulation, appetite ratings, or energy intake at a subsequent meal. Clinical Trial Registry number and website where it was obtained: Clinical Trials.gov Identifier: NCT05287906. Study Details | NCT05287906 | A Trial to Assess Steviol Glycosides on Acute Appetite Hormone Release | ClinicalTrials.gov.

Appetite

Effect of walking training on blood glucose control and metabolic health in patients with type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the improvement effect of walking training on blood glucose control and metabolic health indicators in type 2 diabetes patients, and to explore the effect of different intervention program characteristics on the efficacy through subgroup analysis. METHOD: The system searched PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO databases, with a search period from the establishment of the database to March 15, 2026. Include a randomized controlled trial with the main intervention measures of walking behavior, with an intervention period of &#x2265;8&#xa0;weeks. Two researchers independently conducted literature screening, data extraction, and bias risk assessment. Meta-analysis was conducted using RevMan 5.4 software, with mean difference (MD) and its 95% confidence interval (CI) as effect measures for continuous variables. Select fixed effects model or random effects model for combined analysis based on heterogeneity size, and conduct subgroup analysis according to intervention program characteristics. RESULTS: Totally 5 randomized controlled trials were included, including 483 patients with type 2 diabetes (241 cases in the intervention group and 242 cases in the control group). Participants had a mean age of 54.2&#xa0;&#xb1;&#xa0;6.5&#xa0;years, BMI of 29.1&#xa0;&#xb1;&#xa0;3.2&#xa0;kg/m2, and 48.5% were male. The meta-analysis results showed that walking training significantly reduced glycated hemoglobin levels, with a combined effect of -0.48% (95% CI: -0.60 to -0.36, P&#xa0;<&#xa0;0.00001), There is moderate heterogeneity among the studies (I2&#xa0;=&#xa0;67%). Subgroup analysis showed that the "walking&#xa0;+&#xa0;other interventions" subgroup (combined effect size -0.58%, 95% CI: -0.96 to -0.20) and the "clear step target" subgroup (combined effect size -0.52%, 95% CI: -0.65 to -0.39) had larger effect sizes and lower heterogeneity within the subgroups. The bias risk assessment shows that the overall quality of the included research methodology is good. CONCLUSION: Walking training can significantly improve the blood glucose control in patients with type 2 diabetes. Combined with diet or behavioral intervention, setting clear goals for the number of steps may achieve better results. Walking training can be used as an effective auxiliary treatment for the management of type 2 diabetes in clinical promotion. Due to limitations in the number and quality of studies included, the above conclusions still require more high-quality research to validate.

Humans

Early Worsening of Diabetic Retinopathy Following Initiation of Hybrid Closed-Loop/Automated Insulin Delivery Systems in Type 1 Diabetes: A Systematic Review and Structured Study-Level Synthesis.

BACKGROUND: Hybrid closed-loop (HCL) systems achieve rapid, algorithm-driven improvements in glycaemia in type 1 diabetes (T1D). Paradoxically, rapid improvement in glycaemic control is associated with early worsening of diabetic retinopathy (EWDR), a phenomenon established in the intensive insulin therapy era. Whether HCL initiation carries a clinically meaningful EWDR risk is unknown. No systematic review has previously addressed this question. METHODS: A systematic review and structured quantitative synthesis was performed using study-level estimates only (PROSPERO CRD:420261391951). MEDLINE, SCOPUS and Web of Science were searched to 14th May 2026. Studies reporting retinal outcomes in people with T1D initiating any HCL system were eligible. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using ROBINS-I and certainty of evidence using the GRADE framework. EWDR incidence was summarised using study-level proportions, and comparative studies were summarised using study-specific risk ratios for HCL versus control therapy. Given substantial heterogeneity in EWDR definitions, retinal assessment timing, follow-up duration, and comparator groups, no pooled or meta-analytic estimates were derived. RESULTS: Eight studies (n&#x2009;=&#x2009;1487 participants; 860 HCL users) were included; all were observational and six were retrospective. EWDR varied markedly with the timing of retinal assessment. In studies assessing the retina within &#x2264;&#x2009;12&#x2009;months of HCL initiation, EWDR rates ranged from 8.9% to 26.5%. Studies with longer follow-up reported lower rates of retinal worsening or incident DR, 6.7% at 24&#x2009;months and 6.1% over a mean follow-up of 4.9&#x2009;years, suggesting that these studies may capture background DR progression rather than true early worsening. Three comparative studies included 177 HCL users and 315 controls; EWDR study-specific risk ratios were directionally inconsistent, ranging from 0.32 to 1.51, and were therefore not pooled. The most consistently identified risk factors were higher baseline HbA1c and older age. The magnitude of HbA1c reduction was not a consistent predictor of EWDR in the HCL context, in contrast to pre-HCL era evidence. Risk of bias ranged from moderate to critical and certainty of evidence was very low for all outcomes. CONCLUSIONS: Study-defined retinal worsening was reported in a minority of participants. The current evidence base is dominated by retrospective studies, variable retinal assessment timing, and inconsistent EWDR definitions. Well-designed prospective studies with protocol-specified retinal surveillance anchored to HCL initiation are required to generate reliable incidence estimates, identify risk factors, determine visual consequences, and inform standardised screening guidance.

Humans

Influence of soil types with different soil-forming process on the qualitative and quantitative detection of microplastics by near-infrared spectroscopy.

Microplastics (MPs) have become a pressing global environmental threat, with soils-acting as sinks for MPs from multiple sources-gaining increasing attention. Near-infrared (NIR) spectroscopy offers a promising tool for MPs detection due to its rapid, non-destructive, and field-applicable features. Although previous studies have focused on the effects of individual soil components on the NIR detection performance of MPs, there is still a lack of systematic research on how the complex background-formed by the coupling of multiple physicochemical properties in natural soils-affects detection performance. This study focuses on soil types with different soil-forming processes, selected five representative agricultural soils to systematically evaluate how the combinations of physicochemical properties they represented affect the performance of NIR-based qualitative and quantitative analysis of MPs in soils. The results demonstrated that soil type significantly affected both the spectral response and detection performance of MPs. Brown Pedocals and Brown Earth exhibited clearer characteristic absorption and stronger linear responses, achieving higher identification accuracy under low (<1.5 %) or zero MPs concentrations and the best quantitative performance (R2 &#x2265; 0.988, prediction set root mean square error (RMSEP) &#x2264; 0.110 %). In contrast, Phaeozem and Red Soil were more prone to misclassification at low concentrations, while Fluvo-aquic Soil showed the poorest quantitative performance. This study is the first to reveal, at a holistic level, the critical constraints posed by natural soil complexity on the NIR detection of MPs, offering targeted empirical evidence to support the application of NIR technology in real-world soil environments.

Soil

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n&#xa0;=&#xa0;15,765) consisted of UK Biobank participants (MDD only n&#xa0;=&#xa0;1230; T2DM only n&#xa0;=&#xa0;3644; comorbid T2DM&#xa0;+&#xa0;MDD n&#xa0;=&#xa0;721). Individuals with T2DM&#xa0;+&#xa0;MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR&#xa0;=&#xa0;4.44, 95% CI&#xa0;=&#xa0;[3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM&#xa0;+&#xa0;MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM&#xa0;+&#xa0;MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM&#xa0;+&#xa0;MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans

Plasma proteome profiling identifies XPNPEP3 as a novel biomarker associated with metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To identify plasma protein differences between type 2 diabetes mellitus (T2DM) patients with and without metabolic dysfunction-associated steatotic liver disease (MASLD), and to evaluate the diagnostic potential of X-prolyl aminopeptidase 3 (XPNPEP3) for identifying MASLD in T2DM patients. METHODS: Twenty T2DM inpatients were categorized into groups with and without MASLD and their plasma samples&#xa0;were analyzed using data-independent acquisition mass spectrometry, followed by bioinformatics analysis to identify differentially expressed proteins. The cohort was then expanded to 84 patients, and plasma XPNPEP3 levels were validated by enzyme-linked immunosorbent assay. Correlation between XPNPEP3 and clinical indicators were evaluated, and diagnostic performance was determined via receiver operating characteristic (ROC) analysis. Immunohistochemistry was employed to compare hepatic XPNPEP3 expression between the two groups. RESULTS: Proteomic analysis identified 176 differentially expressed proteins, with XPNPEP3 exhibiting the most significant down-regulation by fold change. In the validation cohort, plasma XPNPEP3 was significantly lower in T2DM+MASLD versus T2DM alone. XPNPEP3 levels were negatively correlated with diabetes duration, liver function markers, and triglyceride levels, and was identified as an independent factor inversely associated with MASLD in T2DM.ROC analysis demonstrated strong diagnostic performance for XPNPEP3, further enhanced when combined with BMI and diabetes duration.&#xa0; Immunohistochemistry confirmed reduced hepatic XPNPEP3 expression in T2DM+MASLD patients. CONCLUSIONS: Lower plasma XPNPEP3 is independently associated with MASLD in T2DM patients and demonstrates strong diagnostic potential, positioning XPNPEP3 as a promising biomarker for diagnosing MASLD in T2DM patients and a novel target for non-invasive diagnostic tool development.

Humans

LitCTL1: A novel C-type lectin involved in the mucosal and cellular immunity of the common periwinkle Littorinalittorea.

C-type lectins (CTLs) are vital pattern-recognition receptors (PRRs) that mediate innate immune responses in mollusks, yet their characterization in Caenogastropoda, the largest gastropod group, remains limited. This study characterizes LitCTL1, a novel secreted single-domain C-type lectin from the common periwinkle, Littorina littorea. The 199-amino acid polypeptide contains a conserved carbohydrate recognition domain with canonical QPD and WND motifs and is predicted to form a homodimer. Uniquely, LitCTL1 was localized in both circulating hemocytes and mucus-secreting epithelial cells of the foot, mantle, and hypobranchial gland - the first report of such dual localization for a molluscan lectin, linking systemic and mucosal defense. Expression analysis revealed that LitCTL1 is constitutively expressed in hemocytes. Functional assays with recombinant LitCTL1 demonstrated its role as a potent opsonin with hemagglutinating activity, significantly enhancing hemocyte spreading and the phagocytosis of zymosan. Genomic analysis reveals that LitCTL1 belongs to a rapidly diversifying, genus-specific expansion distinct from conserved perlucin-like lineages. These results identify LitCTL1 as a key effector molecule in both systemic and mucosal innate immunity, likely reflecting an evolutionary adaptation to the microbial challenges of the intertidal environment.

Animals

How prevalent is fear of cancer recurrence beyond 5 years: a systematic review of validated assessments across tumour types.

PURPOSE: Fear of cancer recurrence (FCR) is an established challenge for cancer survivors. Research however has largely focussed early in treatment, with varying assessments and often single tumour sites. This systematic review set out to determine prevalence of FCR in survivors beyond 5 years across all tumour types. METHOD: We designed a search strategy to identify publications assessing FCR in survivors beyond 5 years with sample size greater than 50, using validated measures. Applying PRISMA methodology and with defined inclusion and exclusion criteria two authors independently assessed the studies for eligibility. Data extraction recorded number of participants, tumour type, study design, FCR tool, time points for assessment and reported prevalence. Risk of bias was assessed to address quality. RESULTS: Ten papers were included, reporting FCR from 5 years to beyond 20 years. Validated tools employed were FCRI-SF and FOP-Q-SF. Sample sizes ranged from 64 to 5983 participants, with a heterogeneous mix of tumour types and age. Only two studies reported longitudinal measurements. Prevalence of FCR above defined threshold ranged from 13 to 33.9% for those studies with acceptable risk of bias reporting distinct cohorts beyond 5 years. CONCLUSION: The limited evidence suggests that clinically relevant FCR persists in some survivors at 5&#xa0;years. Our review demonstrates the challenge of heterogeneous patient populations in FCR research emphasising the need for improved consensus on measurements and more prospective longitudinal research representing a comprehensive variety of tumour types. We address the clinical implications of persistent FCR and the need to implement effective interventions.

Humans

Associations of red blood cell fatty acids with personality traits: 10-year follow-up in the Kibbutzim Family Study (KFS).

BACKGROUND: The ability of hostility and type-A personality to predict cardiovascular outcomes makes understanding antecedents of these personality traits an important public health objective. OBJECTIVES: This study aimed to examine whether blood-measured fatty acids (the exposure) are associated with hostility and type-A personality (the outcome), while accounting for lifestyle, sociodemographic factors, and polygenic background. METHODS: Personality traits, sociodemographic, and lifestyle data were obtained in 1992-1993 from 452 family members living in kibbutz settlements in Israel (visit 1) and remeasured 8 to 10 y later in 379 individuals (visit 2). Red blood cell (RBC) fatty acid concentrations were determined in visit 1 by gas chromatography. Longitudinal associations of visit 1 fatty acids with visit 2 personality traits were examined using linear models, before and after controlling for baseline personality scores. The contribution of environmental factors to personality scores beyond heritability was estimated by variance decomposition. RESULTS: In longitudinal analysis, 1% increase in visit 1 total n-6 (&#x3c9;-6) fatty acid was associated with a 0.328-unit decrease in visit 2 type-A score [95% confidence interval (CI): -0.571, -0.085]. After adjustment for baseline personality levels, the association was slightly attenuated (&#x3b2;= -0.204; CI: -0.399, -0.009). One percent higher total n-6 was also associated with 1.119 units lower visit 2 hostility score (CI: -2.777, 0.038; P = 0.055). Finally, independent of the genetic contribution (32%-38% of adjusted variability in hostility and type-A personality), 1% increase in total n-3 and total n-6 was associated with 2.539 (CI: -3.907, -1.171) and 0.201 (CI: -0.365, -0.037) units lower hostility and type-A scores, respectively. CONCLUSIONS: Higher RBC total n-6 fatty acid concentrations are associated with lower type-A personality scores. After adjustment for baseline personality levels, the associations between total n-6 and hostility and between total n-3 and hostility are attenuated. These findings support further investigation of the relationship between fatty acid biology and personality traits using study designs better suited to causal inference.

Humans

Comparative evaluation of oxidative stress biomarkers F2-isoprostanes and 8-OHdG in Parkinson's disease and Type 2 Diabetes Mellitus: a systematic review and meta-analysis of human studies.

BACKGROUND: Oxidative stress is central to type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). However, the utility of biomarkers for lipid peroxidation (F2-isoprostanes) and DNA damage (8-OHdG) in the comorbidity of PD and T2DM remains unclear. METHODS: We conducted a systematic review and meta-analysis of 54 unique studies of human subjects aged &#x2265; 50&#x2009;years (n&#x2009;=&#x2009;7,521: 3,522 with T2DM, 722 with PD, and 3,277 controls), measuring biomarkers in serum, plasma, or leukocytes. Mixed-effects models quantified standardized differences (Hedges' g) across subgroups. RESULTS: In T2DM, F2-isoprostanes (g&#x2009;=&#x2009;1.60, 95% CI: 0.95-2.25) and 8-OHdG (g&#x2009;=&#x2009;2.64, 95% CI: 2.13-3.14) were markedly elevated (p&#x2009;<&#x2009;0.001). Stronger effects were observed in younger cohorts and serum/plasma samples, with complications like nephropathy exhibiting extreme oxidative stress (g&#x2009;=&#x2009;5.24). In PD, 8-OHdG was moderately elevated (g&#x2009;=&#x2009;0.78, 95% CI: 0.18-1.39; p&#x2009;=&#x2009;0.011), particularly in randomized controlled trials and plasma samples, whereas F2-isoprostanes were not significantly elevated (g&#x2009;=&#x2009;0.47, 95% CI: -0.43-1.38). High heterogeneity in T2DM (I2 > 90%) reflected methodological variability. CONCLUSION: Distinct profiles - both markers elevated in T2DM but only 8-OHdG in PD - underscore 8-OHdG's potential in PD-T2DM comorbidity. Future research should focus on standardized assays, multi-compartmental or multi-modal sampling, and longitudinal studies to clarify mechanisms and therapeutic targets.

Humans

Durability and Safety of Imeglimin as an Add-On to DPP-4 Inhibitors in Japanese Type 2 Diabetes: The 104-Week FAMILIAR Trial.

AIMS: To evaluate the long-term efficacy and safety of imeglimin added to dipeptidyl peptidase-4 (DPP-4) inhibitors in Japanese patients with type 2 diabetes, focusing on glycemic durability and safety in elderly patients over 104&#x2009;weeks. MATERIALS AND METHODS: This multicenter, randomized, placebo-controlled trial comprised a 24-week double-blind phase (imeglimin 1000&#x2009;mg or placebo twice daily) followed by an 80-week open-label extension in which all patients received imeglimin. Eligible patients had inadequate glycemic control despite DPP-4 inhibitor monotherapy. The main assessment measured HbA1c changes from baseline to week 104. Secondary assessments included meal tolerance tests (MTT) for evaluating physiological changes in &#x3b2;-cell function and insulin resistance and safety monitoring. RESULTS: Of 117 randomized patients, 81 completed 104&#x2009;weeks. In the early-start group that received imeglimin from week 0, the significant HbA1c reduction observed at week 24 (-0.65%) was maintained through week 104 (-0.55%; p&#x2009;<&#x2009;0.001 vs. baseline). The delayed-start group that switched to imeglimin at week 24 achieved similar glycemic control thereafter. Elderly patients (&#x2265;&#x2009;65&#x2009;years) in the early-start group maintained stable HbA1c reduction (-0.58%) without hypoglycemic events over 2&#x2009;years. MTT analysis in the early-start group showed sustained improvements in glucose AUC and insulin sensitivity without unnecessary insulin secretion over time. CONCLUSIONS: Imeglimin added to DPP-4 inhibitors appeared to improve glycemic control for 104&#x2009;weeks, without clear attenuation. The combination was well-tolerated with a low risk of hypoglycemia even in elderly patients. The long-term effect may be associated with improvements in insulin sensitivity. TRIAL REGISTRATION: jRCTs061210082.

Humans

BRAIN-Diabetes: Acceptability of an adapted FINGER multidomain intervention among adults living with type 2 diabetes in rural border regions across the island of Ireland.

BackgroundIndividuals with type 2 diabetes mellitus (T2DM) face increased risk of cognitive decline and dementia. Multidomain lifestyle interventions offer a non-pharmacological strategy to support brain health in this high-risk group.ObjectiveThis study examined the acceptability of a culturally adapted FINGER-based intervention among adults living with T2DM in rural border regions of Ireland (BRAIN-Diabetes Trial).MethodsA 6-month pilot randomized controlled trial was conducted. The intervention group received a multidomain program targeting diet, physical activity, and computerized cognitive training (CCT). The control group received standard care. Acceptability was assessed using questionnaires (all participants) and semi-structured interviews (intervention participants). Quantitative data were analyzed descriptively and qualitative data using template analysis, guided by four a-priori themes: trial participation and engagement, dietary behavior change, exercise behavior change, and CCT behavior change.ResultsQuestionnaire data (intervention: n&#x2009;=&#x2009;28; control: n&#x2009;=&#x2009;36) indicated high overall acceptability. Dietary and exercise components were rated most positively, while CCT component was less well received. Interviews (n&#x2009;=&#x2009;25) highlighted facilitators to trial engagement, including perceived health improvements, and social connection, with time constraints and limited personalization as barriers. Dietary change was supported by tailored guidance but hindered by cost and availability. Facilitators for exercise included accessible resources and perceived benefits, with barriers including competing priorities. CCT engagement was mixed, with challenges including digital access and repetitiveness.ConclusionsThe Brain-Diabetes intervention was acceptable and feasible among adults with T2DM. Personalized support and accessible resources were key to engagement. Future work should refine delivery to enhance scalability and long-term adherence among high-risk groups.

Humans

Effects of time-restricted eating on markers of glucose metabolism and regulation in individuals with prediabetes or type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials.

AIMS/HYPOTHESIS: This systematic review and meta-analysis aimed to investigate the effects of time-restricted eating (TRE) on glucose metabolism and regulation in individuals with prediabetes (fasting blood glucose of 5.6-6.9 mmol/l or HbA1c of 39-47 mmol/mol [5.7-6.4%]) or type 2 diabetes (fasting blood glucose &#x2265;7 mmol/l or HbA1c &#x2265;48 mmol/mol [6.5%]). METHODS: A literature search was performed in MEDLINE, Embase and CENTRAL from inception to 5 August 2025. Moreover, forward and backward citation searches were performed. Eligible studies were RCTs in adults with prediabetes or type 2 diabetes, lasting &#x2265;2 weeks, reporting markers of glucose metabolism and regulation, comparing TRE (&#x2264;12 h eating window) with a non-time-restricted control diet. Studies involving pregnancy, other fasting regimens, or non-peer-reviewed publications were excluded. Data were pooled as weighted mean differences with 95% CIs using random-effects generic inverse variance models in Cochrane Review Manager Web, and results are presented as forest plots. The certainty of evidence was defined using Grading of Recommendations, Assessment, Development and Evaluations methodology, and risk of bias was estimated by using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2). RESULTS: Out of 2043 records identified through the database search, as well as 1249 from forward and backward citation searches, ten RCTs including 599 participants were included. The mean length of the studies was 4 months, and the eating windows ranged from 4 to 10 h per day. The pooled meta-analysis showed no overall effect of TRE on HbA1c (-3.33 mmol/mol; 95% CI -6.87, 0.20 (-0.30% points; -0.63, 0.02); p=0.06, moderate certainty). Nevertheless, following stratification by subgroups, TRE resulted in a reduction in HbA1c of 0.93 mmol/mol (-1.70, -0.17 [-0.09% points; -0.16, -0.02]; p=0.02) in individuals with prediabetes but not in individuals with type 2 diabetes (-4.68 mmol/mol; -10.08, 0.72 (-0.43% points; -0.92, 0.07); p=0.09). TRE reduced fasting blood glucose in the pooled analysis (-0.30 mmol/l; -0.53, -0.07; p<0.01, moderate certainty) as well as in the subgroup analyses in individuals with prediabetes (-0.14 mmol/l; -0.27, -0.01; p=0.03) and with type 2 diabetes (-0.48 mmol/l; -0.78, -0.17; p<0.01). Moreover, TRE lowered body weight by 1.6 kg (-2.2, -1.0; p<0.001) in the pooled analysis. The evidence was limited by imprecision arising from wide confidence intervals in some of the included studies, which may be due to small sample sizes. Lastly, the effects of TRE on markers of insulin sensitivity, beta cell function and continuous glucose monitoring measurements were inconclusive. CONCLUSIONS/INTERPRETATION: Moderate-certainty evidence indicates that TRE reduces fasting blood glucose but not HbA1c. The subgroup analyses revealed that TRE improved HbA1c and fasting glucose in individuals with prediabetes and improved fasting glucose in individuals with type 2 diabetes. Future large-scale studies should investigate long-term effects of TRE in prevention and treatment of type 2 diabetes. TRIAL REGISTRATION: PROSPERO CRD42024523591 FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Three authors (JS, A-DT, THA) are employed at Steno Diabetes Center Copenhagen, a public hospital and research institution under the Capital Region of Denmark, partly funded by a grant from the Novo Nordisk Foundation.

Humans

Baseline Computed Tomography Coronary Angiography and Polygenic Risk Profiles in Adults With Type 2 Diabetes: A Cross-Sectional Analysis From the VOLTAIRE Study.

AIMS: To characterise baseline clinical, anatomical, and genetic cardiovascular risk profiles in participants enrolled in the VOLTAIRE (Evaluation of Polygenic Scores and CT Imaging in Risk Factor Modification in Patients with Type 2 Diabetes) study and examine concordance across these domains. METHODS: This analysis included adults with T2D who completed baseline computed tomography coronary angiography (CTCA) and polygenic risk score (PRS) assessment prior to randomisation in the VOLTAIRE study. Coronary atherosclerosis was evaluated using coronary artery calcium (CAC) score and CTCA-derived stenosis severity. Clinical risk was assessed using the New Zealand Society for the Study of Diabetes 5-year cardiovascular risk calculator. Polygenic risk for coronary artery disease was assessed using a genome-wide PRS and categorised into tertiles. RESULTS: Among 126 participants with T2D (mean age 57.5&#x2009;&#xb1;&#x2009;8.7&#x2009;years; 62.7% male), coronary atherosclerotic burden was highly heterogeneous: 34.9% had CAC&#x2009;=&#x2009;0, whereas 19.8% had CAC &#x2265;&#x2009;400. Moderate-to-severe coronary stenosis (&#x2265;&#x2009;50%) was present in 40.5% of participants overall, including 20.4% of those classified as low clinical risk. PRS distribution was variable (low 37.3%, intermediate 35.7%, high 27.0%). Overlap between anatomical, genetic, and clinical domains&#xa0;was limited, with only 8.7% of participants classified as high risk across all three. CONCLUSIONS: Substantial heterogeneity and limited overlap&#xa0;exist between anatomical, genetic, and clinical cardiovascular risk measures in T2D. These findings support a multimodal approach to risk assessment integrating imaging and genetic profiling. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov; ID: NCT07091162.

Aged

The Association Between NT-Pro BNP, Nephropathy and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) is an established biomarker of heart failure and has been recommended for cardiovascular risk stratification in type 2 diabetes mellitus (T2DM). However, its relationship with diabetic nephropathy and endothelial dysfunction across varying stages of kidney impairment remains unclear. This study examined the associations of NT-Pro BNP, renal impairment, albuminuria and endothelial dysfunction in patients with T2DM without overt heart failure. METHODS: A comparative cross-sectional study was conducted among 192 adults with T2DM. Participants were stratified by KDIGO eGFR groups (&#x2265;&#x2009;90, 60-89, 30-59&#x2009;mL/min/1.73m2). NT-Pro BNP was considered abnormal at a cut-off of &#x2265;&#x2009;125&#x2009;pg/mL. Albuminuria was categorized using the urinary albumin-to-creatinine ratio (uACR). Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD). Logistic regression analysis was performed to identify independent factors of elevated NT-Pro BNP, with p-values <&#x2009;0.05 considered statistically significant. RESULTS: NT-Pro BNP levels were significantly higher in the lower eGFR groups compared with normal eGFR (204.3 vs. 96.8 vs. 62.2&#x2009;pg/mL, p&#x2009;<&#x2009;0001). A weak but significant positive correlation was observed between NT-Pro BNP and uACR (r&#x2009;=&#x2009;0.31, p&#x2009;<&#x2009;0.001). However, no significant association was found between NT-Pro BNP and FMD (p&#x2009;=&#x2009;0.388). Following multivariable adjustments, older age (adjusted OR 1.14, 95% CI: 1.06-1.23, p&#x2009;<&#x2009;0.001), higher systolic blood pressure (adjusted OR 1.05, 95% CI: 1.02-1.08, p&#x2009;=&#x2009;0.010), lower eGFR (adjusted OR 0.97, 95% CI: 0.95-0.99, p&#x2009;=&#x2009;0.003) and beta-blocker use (adjusted OR 4.65, 95% CI: 1.61-13.45, p <&#x2009;0.001) were independently associated with elevated NT-Pro BNP. CONCLUSION: In patients with T2DM without overt heart failure, elevated NT-Pro BNP showed a statistically significant association with lower eGFR and higher albuminuria. Moderate to severe albuminuria becomes an independent factor for elevated NT-Pro BNP after adjustment excluding eGFR. The lack of association with endothelial dysfunction suggests that NT-Pro BNP may reflect different pathophysiological pathways. NT-Pro BNP may serve as a useful biomarker for early cardiovascular risk stratification and identification of individuals at risk of pre-heart failure in diabetic kidney disease.

NT&#x2010;Pro BNP

Genome-wide characterisation of the myosin light chain gene family in Chinese perch (Siniperca chuatsi) and its expression patterns in muscle fibre types and injury response.

The Class II myosin light chain (myl) genes in Chinese perch (Siniperca chuatsi) have not yet been systematically characterised, and relationships with muscle fibre specification, development, and injury-associated remodelling remain unclear. In this study, fast and slow muscle fibres were initially distinguished using myofibrillar ATPase histochemistry. Subsequently, genome-wide mining identified 16 Class II myl genes, comprising eight essential and eight regulatory light-chain subunits. Their conserved-domain features, chromosomal distribution, phylogenetic relationships and expression profiles were analysed. Transcriptomic profiling showed that summed myl transcript abundance was higher in fast muscle than in slow muscle, accounting for 67.2% of the pooled myl transcript pool across the two muscle types (paired t-test, raw P&#xa0;=&#xa0;0.036). mylpfa, myl1 and mylz3 were the major fast-muscle-associated genes, whereas myl10, myl2b and myl13 were preferentially expressed in slow muscle at the transcript level. These patterns support these genes as candidate fibre-type-associated expression markers. Developmental profiling identified stage-associated myl expression patterns, including a possible expression shift between mylpfb and mylpfa. In the descriptive injury-repair time course (d0-d7), FPKM profiles indicated that fast-muscle-associated genes (mylpfa, mylz3 and myl1) were lower at d1 and recovered by d3, whereas several slow-muscle-associated genes showed biphasic transcript-level increases. The slow-muscle-associated RLC gene mylpfb showed a delayed expression peak at d7. Notably, the embryonic isoform myl6l showed a modest increase from approximately 2 FPKM at d0 to 4-5 FPKM after injury, suggesting a possible injury-associated expression pattern that requires further validation. Together, these findings provide a genome-wide description of the Chinese perch myl gene family and identify candidate fibre-type-associated genes and descriptive injury-associated isoform expression patterns.

Animals