Chronic stress (CS) acts as both an initiating and aggravating factor for depression and osteoporosis. Cumulative evidence indicates that Cathepsin K (Cat K), a cysteine protease, is functionally linked to chronic stress and exerts critical regulatory roles in bone metabolism. Nevertheless, the molecular mechanisms whereby CS promotes osteoporosis in the background of mood-related disturbances remain poorly defined. In the present work, we established a combined mouse model of osteoporosis and chronic stress. We evaluated anxiety- and depression-like behaviors, the expression profiles of Cat K, autophagy-, apoptosis-, and inflammation-associated proteins in bone tissue, as well as vascular senescence in experimental animals. Furthermore, we investigated the biological effects of serum collected from chronically-stressed mice on MC3T3-E1 osteoblast-like cells. Following 8-week chronic stress exposure, ovariectomized (OVX) mice developed prominent anxiety- and depression-like behaviors, accompanied by deteriorated osteoporosis and aortic senescence. Meanwhile, bone tissues exhibited elevated levels of Cat K, p62, pro-inflammatory mediators, and apoptosis-related proteins, whereas the autophagy marker LC3B/A was down-regulated. Administration of E64d, a cysteine protease inhibitor, markedly reversed these pathological alterations. In vitro culture revealed that serum from chronically-stressed mice suppressed the viability of MC3T3-E1 osteoblast-like cells. Pharmacological inhibition of Cat K restored autophagic activity, mitigated the overexpression of pro-inflammatory and pro-apoptotic mediators, and rescued MC3T3-E1 cells from stress-triggered injury. Collectively, our findings demonstrate that chronic stress induces anxiety- and depression-like phenotypes in OVX mice and accelerates bone loss, at least partially via Cat K activation and autophagy suppression.

Non-communicable diseases (NCDs) are rising rapidly in Sub-Saharan Africa. In Guinea-Bissau, nationwide data are scarce. We aimed to estimate the multi-regional prevalence of type 2 diabetes (T2D), obesity, and hypertension and examine associated risk factors within this resource-limited context.

A multi-regional cross-sectional survey was conducted using a hybrid community- and facility-based sampling approach across urban Bissau, including at the National Diabetes Clinic [CND] and in seven interior regions of the country. Recruitment was conducted between August 3th 2022 and June 8th 2024 across these sites. After a verified 12-h fast, participants underwent capillary glucose, blood pressure, and anthropometric measurements. Diabetes was defined as fasting glucose ≥ 126 mg/dL or previous diagnosis; prediabetes as 110-125 mg/dL; obesity as BMI ≥ 30 kg/m²; and hypertension as blood pressure ≥ 140/90 mmHg. Multivariable logistic regression identified factors associated with diabetes.

Among 3929 participants, with median age 41 years, the overall raw diabetes prevalence was 20.8% (817/3929), with 30% being newly screen-detected. The T2D prevalence at the specialized CND was 22.8% (342/1502), compared to 18.0% (174/969) in community settings outside health facilities in Bissau. The prediabetes prevalence was 9.1%; while the obesity prevalence was 14.8%, disproportionately affecting more women, at 20.7% vs. 9.1% in men; and the prevalence of hypertension was exceptionally high at 40.4%. In the multivariable model, key risk drivers included age ≥ 55 years (OR 14.0, 95% CI: 8.57-22.9), family history (OR 3.78, 3.02-4.74), Fula ethnicity (OR 2.47, 1.73-3.53), and low physical activity (OR 1.44, 1.17-1.78).

Guinea-Bissau faces a critical, underreported burden of metabolic and cardiovascular NCDs, particularly T2D and hypertension. Given the recruitment pathways, the overall prevalence reflects a high-risk baseline that warrants cautious national extrapolation. Urgent, context-specific public health strategies and decentralized clinical guidelines are required to manage these chronic conditions amidst severe structural resource constraints.

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.