Usual walking speed may predict cardiovascular disease in type 2 diabetes, but it is not routinely assessed in UK primary care.

To examine the feasibility of three methods of assessing walking speed in patients with diabetes in general practice: timed walking, accelerometry, and treadmill walking.

We approached consecutive mobile patients attending a general practice diabetes clinic. Consenting participants performed a timed 28-m walk (4 × 7 m) at their usual pace in the surgery corridor while wearing an accelerometer, followed by a 3-minute treadmill walk. Measures were repeated after 6 months. Differences in walking speeds between methods and between timepoints were assessed by Bland-Altman limits of agreement.

Recruitment rate was 91% (30/33). Mean age of participants was 59.6 years (range 37-75), mean body mass index was 30.6 kg/m2 (21.0-46.4), and 17% had a history of cardiovascular disease. Average duration of diabetes was 10 years (range 1-40). Twenty-five participants (83%) repeated assessments at 6-month follow-up.Average (SD) walking speed on the timed walk was similar to both accelerometer and treadmill: 1.12 (0.13), 1.15 (0.16), and 1.01 (0.39) m/s, respectively. Bland-Altman analysis showed good agreement for repeat tests and, on average, between methods. Limits of agreement between timed walk and treadmill were wide. Feedback from seven participants and three practice staff indicated acceptability of all tests, but treadmill testing took longer and least feasible.

Timed walk was the most feasible and acceptable to patients and staff. Results were similar on average to accelerometry and treadmill.

To investigate the joint associations of life satisfaction, loneliness and social isolation in relation to the risk of incident major depressive disorder (MDD) in diabetes patients.

A total of 7712 participants with diagnosed diabetes at baseline from the UK Biobank were included. Cox proportional hazards models and interaction analyses were used to examine associations of loneliness, social isolation, and life satisfaction with MDD.

During a median follow-up time of 11.1 years, 442 participants developed MDD (incidence rate: 5.73%). Participants with high loneliness, high social isolation, and low life satisfaction were associated with 176%, 82%, and 493% higher risks of MDD compared to those with low loneliness, low social isolation, and high life satisfaction, respectively (all P < 0.001). Several statistically significant interactions between loneliness and different aspects of life satisfaction were identified in relation to incident MDD. Participants with both low life satisfaction and high loneliness were at 8.06 times the risk of MDD than those with high life satisfaction and low loneliness.

In individuals with diabetes, higher loneliness and social isolation are associated with increased MDD risk, whereas higher life satisfaction was associated with a lower risk. The joint associations varied across levels and domains of life satisfaction, although interaction patterns were not consistent across all measures or statistical scales. These findings may help identify individuals at elevated risk of MDD but should be interpreted cautiously given the observational design, potential residual confounding, and measurement limitations.

Respiratory syncytial virus (RSV) causes significant disease in older and comorbid adults. Current UK vaccination recommendations restrict eligibility to adults ≥ 75 years, 65-74 years with chronic respiratory disease or immunosuppression, and those in care homes, but evidence on clinical burden in adults < 75 years with comorbidities is limited. This study assessed patient characteristics, healthcare resource utilization (HCRU), and mortality in adults hospitalized with RSV in England.

Population-based retrospective cohort study using linked Clinical Practice Research Datalink Aurum and Hospital Episode Statistics. Adults ≥ 60 years hospitalized with RSV between October 2014 and March 2019 were included. We defined RSV episodes as 90 days post-diagnosis. We defined cases using diagnosis codes for confirmed RSV (RSV-specific) or acute lower respiratory tract infection with exclusion of other causative pathogens (RSV-possible). All-cause HCRU (hospitalizations, critical care admissions, outpatient attendance, primary care consultations, and prescriptions) and case fatality rates were assessed. Results were stratified by age (60-74 and ≥ 75 years), case definitions (RSV-specific, RSV-possible), and comorbidity profiles (chronic respiratory disease, immunocompromised, cardiovascular disease).

A total of 97,712 hospitalized episodes in those aged ≥ 60 years were included in the analysis, of which 785 (0.8%) were RSV-specific cases (n = 338 aged 60-74 years, n = 447 aged ≥ 75 years). In RSV-specific cases, median (IQR) cumulative length of stay (LoS) for those ≥ 75 years was 10.00 (6.00-22.00) days, which was equivalent to or lower than each comorbidity subgroup in those aged 60-74 years, with the longest LoS in those immunocompromised (11.50 [7.00-26.00] days). Critical care admissions were more often observed across comorbidity stratifications (13.85-22.34%) compared to those ≥ 75 years (5.03%). All-cause and RSV-related case fatality rates for RSV-specific cases were highest among those ≥ 75 years (all-cause: 19.3%; RSV-related: 10.3%).

HCRU within RSV episodes in those aged 60-74 years across comorbidity profiles was equal to or greater than that in those aged ≥ 75 years. These findings highlight the need to prioritize consideration of comorbidity groups that could benefit from RSV vaccination.

Diabetes mellitus (DM) may affect postoperative recovery, but evidence in pituitary tumor surgery remains limited. We investigated the association between DM and short-term outcomes after transsphenoidal surgery for pituitary tumors.

We retrospectively analyzed adults in the Taiwan Pituitary Tumor Registry who underwent transsphenoidal surgery for benign pituitary tumors between 2009 and 2019. Patients were categorized into DM and non-DM groups. Associations between DM, prolonged length of hospital stays (LOS), 14-day readmission rate, and complications were determined using regression analyses. Tumor-type stratified analyses and receiver operating characteristic (ROC) analyses of glycated hemoglobin (HbA1c), fasting glucose, and random glucose were also performed.

Data of 970 patients were analyzed, of whom 144 (15%) had DM. DM was not significantly associated with prolonged LOS or 14-day readmission, but was significantly associated with higher odds of CSF leak (adjusted odds ratio [aOR] = 3.35, 95% confidence interval [CI]: 1.18-9.51, p = 0.023) and antibiotic use for ≥ 7 days (aOR = 5.41, 95% CI: 1.13-25.87, p = 0.034) in age-adjusted analysis. In the non-functioning tumor subgroup, the association with antibiotic use for ≥ 7 days persisted (aOR 7.37, 95% CI 1.46-37.12), whereas the association with CSF leak was not statistically significant. Among patients with DM and non-functioning tumors, glycemic markers showed apparent discrimination for postoperative infection and CSF leak, with area under the curve values ranging from 0.83 to 0.93.

DM was associated with selected short-term complications after transsphenoidal surgery, particularly CSF leak and prolonged antibiotic use. These exploratory findings require confirmation in larger prospective studies with comprehensive surgical data.

Supporting the World Health Organization's (WHO) 2021 Global Diabetes Compact's goals, we conducted three systematic reviews on type 1 diabetes (T1D) in adults concerning (1) diagnostic biomarkers, (2) insulin regimens and (3) insulin delivery devices, focusing on emergency and humanitarian settings.

Multiple databases were searched in October 2024 without language or date restrictions. Two reviewers independently selected studies, extracted data and assessed risk of bias using study-specific tools. Critical outcomes included Haemoglobin A1c (HbA1c), hypoglycaemia, microvascular and macrovascular complications, diabetic ketoacidosis, mortality, adverse events, alongside diagnostic accuracy measures and patient-centred outcomes. Where appropriate, random-effects meta-analyses were performed, and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

The biomarkers review (n = 15 studies) found C-peptide and other autoantibodies showed high specificity but variable sensitivity for T1DM diagnosis. The insulin regimen review (three reports from one small trial) suggested possible differences in glycaemic control and nephropathy outcomes between multiple daily and twice-daily regimens. The insulin delivery devices review (n = 8 studies) showed strong patient preference for pens; pooled analyses of HbA1c, hypoglycaemia and quality of life demonstrated outcomes comparable to syringes. Overall, the evidence was sparse, low quality and limited to high-income countries, with none of the studies addressing emergency or humanitarian settings. Certainty of evidence was very low for the biomarkers and delivery devices reviews and low for the insulin regimen review.

Evidence for T1D care in emergency and humanitarian settings remains very limited. Evidence for biomarker use for diagnoses is constrained by very low-certainty evidence and infrastructure barriers. Multiple daily insulin regimens may confer glycaemic benefits, whereas pens and syringes yield similar outcomes despite patients' preference for pens. Evidence gaps underscore the need for pragmatic, context-sensitive guidance balancing clinical and logistical considerations.

PROSPERO (CRD420250649000).

Differentiating diabetes subtypes is essential for long-term management; however, overlapping features among type 1 diabetes (T1D), type 2 diabetes (T2D), and maturity-onset diabetes of the young (MODY) complicate diagnosis. Clinical characteristics and temporal trends according to childhood-onset diabetes subtype were investigated over a 20-year period.

We retrospectively reviewed 662 patients diagnosed with T1D, T2D, or MODY at Seoul National University Children's Hospital between 2003 and 2022 at ages ≥6 months and <19 years, excluding secondary and other specific forms. Subtypes were classified based on autoantibody status, insulin dependence, adiposity, family history, and genetic testing.

Of patients, 477 (72.1%) had T1D, 143 (21.6%) had T2D, and 39 (5.9%) had MODY; 3 had coexisting T1D and MODY. Ten patients underwent diabetes subtype reclassification during follow-up. T1D was associated with more frequent diabetic ketoacidosis (DKA) and less family history than T2D or MODY (both P < 0.001). T2D showed higher BMI z-scores and a greater prevalence of overweight and obesity (both P < 0.001). The proportion of T2D increased over time (P for trend < 0.001), whereas MODY remained stable (P for trend = 0.116). Among 21 genetically confirmed MODY cases, GCK variants were the most common, followed by HNF1A variants.

Over the 20-year study period, the proportion of T2D increased among children and adolescents. Expanded insurance coverage for autoantibody testing, along with more affordable access to next-generation sequencing (NGS) panels when clinically indicated, may facilitate earlier and more accurate diagnosis and enable individualized treatment.

The Diabetes Remission Clinical Trial (DiRECT) demonstrated that remission of type 2 diabetes can be achieved through substantial weight loss using a total diet replacement (TDR) intervention combined with structured support. Whether this approach can be delivered exclusively via eHealth has not been well studied.

This pilot study aimed to evaluate whether a TDR intervention delivered solely via eHealth could induce clinically meaningful weight loss and achieve type 2 diabetes remission.

This was a single-arm, nonblinded, single-center pilot study conducted at the clinical research facilities of Umeå University Hospital. Individuals with type 2 diabetes diagnosed within the past 6 years were included. Participants followed a TDR (~850 kcal/d) for 12 weeks, and then gradually reintroduced food, with a total study duration of 6 months. Diabetes medications were discontinued at the start of the study. Daily body weight and fasting glucose were measured at home and transmitted to the study team via connected devices. All clinical support was delivered through video calls and chat. The 2 prespecified coprimary outcomes were a reduction in weight of 15 kg or more and remission of diabetes, defined as glycated hemoglobin below 6.5% without glucose-lowering medication, from baseline to 6 months. A 75 g oral glucose tolerance test and indirect calorimetry were performed at baseline and at 6 months to assess resting energy expenditure (REE) and respiratory quotient (RQ).

Ten participants (mean age 58.5, SD 7.4 y; mean BMI 35.3, SD 5.9 kg/m²; n=9 men and n=1 woman) were enrolled. After 6 months, 6 of 10 participants achieved the prespecified coprimary outcome of ≥15 kg weight loss, and all 10 participants achieved the prespecified coprimary outcome of diabetes remission. Mean weight loss was 16.9 (SD 5.4; P=.005) kg, and glycated hemoglobin decreased by 1.0% (SD 0.8%; P=.008). Daily home measurements showed a marked reduction in fasting glucose within the first week of the intervention. Median REE decreased by 19% (IQR 17%-22%), while median fasting RQ increased by 15% (IQR 5%-27%) and median post-glucose-load RQ increased by 12% (IQR 9%-18%) at 6 months.

In this pilot study, an eHealth-delivered TDR intervention was associated with substantial weight loss and diabetes remission at 6 months without the use of glucose-lowering medication. These findings support further evaluation of fully eHealth-delivered dietary interventions in larger and longer-term randomized controlled trials.

The mechanisms underlying type 2 diabetes-associated cognitive dysfunction (DACD) remain poorly understood, hindering therapeutic progress. Here, we integrated spatial transcriptomics and single-nucleus RNA sequencing to delineate the spatiotemporal molecular and cellular landscape of DACD in brain tissues from 3- and 6-mo-old mouse models. Our findings revealed region- and cell-type-specific transcriptomic alterations, with excitatory neurons in the hippocampus and isocortex emerging as the most severely affected populations with pronounced synaptic dysfunction. Further analysis of these two regions identified disease-associated transcription factors, such as Rfx3 and Mef2c. In parallel, we uncovered multiple ligand-receptor pairs, including Hsp90b1-Lrp6 and S100a1-Ryr2, whose downstream signaling networks converged on lactate dehydrogenase B (Ldhb) as a shared effector, thereby prompting functional validation. Notably, brain-wide and excitatory neuron-specific Ldhb overexpression alleviated DACD-induced mitochondrial dysfunction, oxidative stress, neuronal apoptosis, and cognitive impairment. Collectively, our study delineates the spatiotemporal transcriptomic landscape of DACD, offers a valuable resource for mechanistic exploration, and highlights Ldhb as a potential therapeutic target in DACD.

Polycythemia vera (PV) and secondary polycythemia are clinical conditions characterized by erythrocytosis, but their biological basis and clinical course differ. Whether this difference is reflected in long-term kidney function is not well defined. We aimed to compare longitudinal estimated glomerular filtration rate (eGFR) trajectories and kidney function loss in patients with PV and secondary polycythemia.

In this retrospective, single-center cohort, adult patients with PV or secondary polycythemia were evaluated from baseline through 4 years. Repeated eGFR measurements were examined using a linear mixed-effects model; the group-time interaction was the primary inferential test, with adjustment for age, sex, diabetes mellitus, hypertension, coronary artery disease, and baseline chronic kidney disease.

The cohort included 1,616 patients: 258 with PV and 1,358 with secondary polycythemia. The global group-time interaction indicated different eGFR trajectories (p = 0.049). The adjusted PV-secondary polycythemia eGFR contrast was small at baseline but indicated lower eGFR in PV by the fourth year (- 3.86 mL/min/1.73 m²; 95% CI, - 6.39 to - 1.33; Holm-corrected p = 0.014). The fourth-year contrast remained in the same direction in most sensitivity analyses.

PV was associated with a late and modest eGFR separation compared with secondary polycythemia. These findings support consideration of kidney function monitoring in selected patients with PV and prospective assessment of factors influencing renal progression.

Chiglitazar was approved by the China National Medical Products Administration (NMPA) in 2021 for the treatment of patients with type 2 diabetes mellitus, and may also benefit from metabolic dysfunction-associated steatohepatitis (MASH).

To characterise the role of Chiglitazar in MASH, in vitro experiments examining monocyte activation and migration were conducted, alongside liver and stellate cell proliferation assays. Three distinct MASH animal models (db/db mouse model, MCD model, CCl4 model) for conducting in vivo studies were established.

The results indicated that Chiglitazar reduced MCP-1-induced THP-1 migration and down-regulated TNF-α and MCP-1 expression. It also blocked TGF-β-driven proliferation in dermal fibroblasts and hepatic stellate cells while suppressing α-SMA and CTGF expression. In vivo, Chiglitazar alleviates hepatic steatosis and inflammation in the MCD model, whilst improving hepatic inflammation and fibrosis in both the CCL4 and HFD+CCL4 models.

In the study, it has been demonstrated that chiglitazar suppresses monocyte activation and chemotaxis, thereby attenuating chronic inflammation-elicited vascular and tissue damage. It also blocks fibroblast proliferation and differentiation, curbing toxin- or metabolite- induced inflammation and fibrosis. Although CCl4, MCD, and HFD+CCl4 models were used, they only partially reproduce human MASH pathology. Future work should employ more physiologically faithful systems.

As the world's first pan-PPAR agonist approved for the treatment of Type 2 Diabetes Mellitus (T2DM), Chiglitazar has also demonstrated potential for treating MASH by modulating steatosis, inflammation, and fibrosis. This potential may be translatable into clinical treatments in the foreseeable future.