Oral anemia treatments are preferred by patients on home-based peritoneal dialysis (PD). We evaluated the effectiveness and safety of oral roxadustat in Chinese patients with chronic kidney disease (CKD)-associated anemia on PD.

In this phase 4 study, patients with CKD-anemia on PD received roxadustat thrice weekly for 24 weeks. We assessed the proportion with hemoglobin ≥100 g/L at Weeks 20 and 24 (overall and stratified by type 2 diabetes mellitus [T2DM] vs. non-diabetes mellitus [DM]), quality of life changes according to the Functional Assessment of Cancer Therapy-Anemia (FACT-An), and 36-Item Short Form Health Survey (SF-36), and safety.

Overall, 195 patients (116 male [59.5%]; mean ± standard deviation age, 46.3 ± 12.3 years) were enrolled; 189 (96.9%) were erythropoiesis-stimulating agent-treated and 43 (22.1%) had T2DM. Baseline hemoglobin was 98.1 ± 10.7 g/L and was <80 g/L in 10 (5.1%). The mean (95% confidence interval) proportion who achieved a hemoglobin concentration ≥100 g/L was 85.1% (79.8%, 90.5%) (T2DM: 89.2% [78.5%, 99.9%]; non-DM: 84.0% [77.8%, 90.1%]). The change in Total FACT-An score (baseline to Week 24), but not SF-36 scores, was clinically significant (-6.2 [-9.0, -3.4]), with a greater decrease in the T2DM subgroup. Residual renal function declined slightly from baseline to Week 24 (-0.2 mL/min/1.73 m²). Treatment-emergent adverse events occurred in 158 patients (81.0%) and were roxadustat-related in 20 (10.3%).

Roxadustat corrected anemia in Chinese patients with CKD on PD, irrespective of baseline T2DM. Adverse events were consistent with roxadustat's known safety profile and with PD patients' characteristics.

To investigate the therapeutic potential of recombinant thrombomodulin domain 1 (rTMD1) in diabetic corneal wound healing and to elucidate its underlying mechanisms using in vitro and in vivo models.

rTMD1 was produced using the Pichia pastoris expression system and purified. Human corneal epithelial cells (HCECs) were cultured under normal glucose (NG) and high glucose (HG) conditions, with or without rTMD1 treatment. Wound healing rates were evaluated using a scratch assay. Diabetes was induced in C57BL/6 mice via streptozotocin (STZ) injections. Corneal wounds were created and treated with rTMD1 or PBS, and wound healing was assessed via fluorescein staining. Inflammatory markers, including HMGB1, TLR4, NLRP3, and IL-1β, were analyzed via quantitative PCR (qPCR), Western blot, and immunofluorescence staining.

In vitro, HCECs treated with rTMD1 under HG conditions demonstrated a higher wound healing rate compared to untreated cells (p = 0.0049). In vivo, rTMD1 significantly enhanced corneal wound healing in diabetic mice, with faster wound closure compared to PBS-treated controls at 24 h (p = 0.005) and 48 h (p < 0.0001). rTMD1 treatment reduced the expression of HMGB1, TLR4, NLRP3, and IL-1β at both mRNA and protein levels, indicating suppression of inflammation.

Topical application of rTMD1 promotes corneal epithelial wound healing in diabetic conditions by inhibiting HMGB1/TLR4/NLRP3-mediated inflammation. rTMD1 holds promise as a potential therapeutic agent for diabetic keratopathy, although further studies are needed to validate its clinical efficacy and safety.

Hypertension (HTN) and dyslipidemia (DYS) frequently complicate type 2 diabetes mellitus (T2DM), increasing cardiovascular risk. Genetic variation within the DPP4-ABCC8-INSR-IGF1 axis may underlie this clustering.

A total of 444 T2DM patients were stratified into T2DM (n = 256), T2DM with HTN (T2MH, n = 134), and T2DM with HTN and DYS (T2MH-DYS, n = 54). Six single nucleotide polymorphisms (SNPs) were genotyped, and associations were assessed by logistic regression and haplotype analysis with Bonferroni correction.

Clinical profiling showed higher C-reactive protein (CRP) and adrenocorticotropic hormone (ACTH) in T2MH and more severe metabolic derangements in T2MH-DYS. DPP4 rs3788979 was strongly linked to hypertension: CT (adjusted OR = 0.370, P = 0.001) and CC (adjusted OR = 0.424, P = 0.001) were protective versus TT, while in the T2MH vs T2MH-DYS comparison, the same CT and CC genotypes conferred increased dyslipidemia risk (adjusted OR = 5.418, P = 0.001; OR = 5.620, P = 0.002). In the comparison between T2DM and T2MH-DYS, the same genotypes also increase the susceptibility risk. IGF1 rs972936 TC genotype also reduced T2MH risk (adjusted OR = 0.460, P = 0.006). Haplotype analysis identified GAATGT as protective against hypertension (OR = 0.312, P = 0.0014) and GACCGT as a risk haplotype for dyslipidemia (OR = 4.113, P = 0.0021); both remained significant after Bonferroni correction.

Variants within the DPP4 axis influence susceptibility to HTN and DYS in T2DM, with GAATGT and GACCGT emerging as robust haplotype markers. Notably, the risk conferred by DPP4 rs3788979 genotypes was modulated by lipid status: CT/CC were protective against hypertension alone but became risk factors when dyslipidemia co-occurred.

Obesity in patients with type 1 diabetes mellitus (T1DM) and kidney disease presents unique challenges, particularly after transplantation, where weight gain can compromise graft function and metabolic control. Bariatric surgery has emerged as a therapeutic option in transplant recipients with obesity, though its role in T1DM remains less explored.

We report the case of a 45-year-old man with longstanding T1DM complicated by hypertension, diabetic retinopathy, and end-stage renal disease, who underwent a deceased-donor kidney transplant at age 40. Post-transplant, he developed type III obesity (BMI 44.5 kg/m²), poor glycemic control (HbA1c 9.8 %), and severe hepatic steatosis despite intensive medical therapy.

Laparoscopic sleeve gastrectomy was performed without intraoperative complications (operative time 70 minutes, specimen weight 100 g, minimal blood loss). The postoperative course was notable only for a transient ileus requiring two days of hospitalization. At follow-up, the patient demonstrated significant weight loss, resolution of albuminuria, improved glycemic stability with marked reduction in insulin requirements, and improvement of hepatic steatosis. Importantly, immunosuppressant drug levels consistently remained within therapeutic range throughout follow-up.

This case highlights the safety and efficacy of sleeve gastrectomy in a kidney transplant recipient with longstanding T1DM, resulting in significant metabolic, renal, and hepatic improvements without compromising graft function or immunosuppressive therapy. To our knowledge, this is the first reported case of sleeve gastrectomy in a patient with T1DM following kidney transplantation, underscoring its feasibility and the need for further research in this complex population.

Sustained lifestyle changes are crucial for the remission of type 2 diabetes (T2D) but remain challenging. Citizen initiatives using peer coaching and self-management may offer a promising alternative to professional medical care. This study evaluated Your Lifestyle As Medicine (YLAM), a Dutch citizen initiative for people with T2D. We aimed to assess its impact on metabolic parameters and to examine participants' engagement.

This observational study analysed self-reported data on weight, waist circumference, fasting glucose and glycated haemoglobin (HbA₁c) from participants in YLAM's online community. Participants could report their self-measured data on a weekly basis. Linear mixed-model analyses, stratified by sex, were used to assess changes in metabolic parameters over time. Additionally, we evaluated participants' engagement through reporting duration and weekly reporting rates.

We assessed all 232 people with T2D who reported multiple measurements for at least 3 months. The median reporting duration was 11.2 months (IQR 4.6-26.5). Weekly reporting rates were 59% for weight, 55% for waist circumference and 52% for fasting glucose, and 12-weekly reporting rates were 49% for HbA₁c. Overall, mean weight, waist circumference, fasting glucose and HbA₁c improved in the first year in both women and men. More specifically, weight decreased by 7.2 kg in women (95% CI -7.6 to -6.8) and by 7.4 kg in men (95% CI -8.0 to -6.8). This represented a mean relative weight loss of 9.0% (SD 7.7) and 8.6% (SD 6.5), respectively. Waist circumference decreased by 8.9 cm in women (95% CI -9.4 to -8.5) and by 8.5 cm in men (95% CI -9.1 to -7.8). Fasting glucose decreased by 1.15 mmol/L in women (95% CI -1.32 to -0.98) and by 0.49 mmol/L in men (95% CI -0.75 to -0.23). HbA₁c decreased by 14.5 mmol/mol in women (95% CI -17.4 to -11.6) and by 9.1 mmol/mol in men (95% CI -13.2 to -5.0). Of all participants, 44% reported data for longer than a year and demonstrated sustained improvements in weight and waist circumference in the long term.

This study provides evidence for substantial and sustained improvements in self-reported metabolic parameters in people with T2D engaged in a citizen initiative without medical supervision. Initiatives like YLAM offer a promising, accessible and scalable strategy to address the growing burden of lifestyle-related diseases.

Amyloid-beta 1-40 peptide (Aβ40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). However, whether plasma levels of Aβ40 are associated with metabolic traits in humans without established CVD remains poorly understood.

Aβ40 was measured in plasma by ELISA and metabolic traits (waist circumference, fasting triglycerides, fasting HDL cholesterol and fasting glucose) were determined in a general population (n = 449) of individuals who did not have clinically overt CVD. Triglyceride-glucose index (TyG) was used to calculate the risk for insulin resistance. BARD score was used to calculate the risk for metabolic liver disease.

Aβ40 levels were associated with the presence of metabolic syndrome (OR: 1.41 95% CI: 1.13-1.76, p = .003), and with higher odds for increasing incidence of metabolic syndrome components, characterized by decreased HDL-C levels (OR: 1.31 95% CI: 1.03-1.58, p = .017) and increased triglyceride levels (OR: 1.30 95% CI: 1.04-1.57, p = .033) after adjustment for traditional cardiovascular risk factors. Further, Aβ40 levels were associated with increased odds for TyG (OR: 1.26 95% CI: 1.03-1.57, p = .042) and increased odds for the presence of diabetes mellitus (OR: 1.35 95% CI: 1.04-1.76, p = .018) after adjustment for age and sex, smoking status, hypertension and dyslipidemia. Increased Aβ40 levels were associated with increased odds for BARD score ≥2 (OR: 1.41 95% CI: 1.04-2.04, p = .045) after adjustment for traditional cardiovascular risk factors.

Our findings suggest that Aβ40 peptide is associated with metabolic traits and risk for metabolic disease. Future longitudinal studies are warranted to determine the prognostic value of Aβ40 for the development and progression of metabolic diseases.

India is facing a growing burden of stroke due to population aging, lifestyle changes, and increased exposure to risk factors. However, longitudinal data on stroke patterns and outcomes in India are limited.

This study assessed stroke patterns, risk factors, management practices, and outcomes using data from the Hospital-Based Stroke Registries (HBSRs) in India.

This prospective hospital-based registry included 34,792 stroke cases from 30 centers across India, recorded between 2020 and 2022. Data on demographics, clinical features, risk factors, diagnostics, treatments, and outcomes were collected, with follow-up at 28 days and three months. Functional outcome was assessed using the modified Rankin Scale (mRS), along with data on recurrence.

The mean age was 59.4 years; 13.8% were aged under 45, 63.4% were male, and 72.1% were from rural areas. Hypertension (74.5%) was the most common risk factor, followed by smokeless tobacco use (28.5%) and diabetes mellitus (27.3%). Ischemic stroke accounted for 60% of cases. Only 20.1% were presented within 4.5 hours of symptom onset, while 37.8% cases presented after 24 hours. Motor impairment (74.8%) followed by speech disturbance (51.2%) were the commonest symptoms at onset. Thrombolysis was given in 4.6%, and thrombectomy in 0.7%, of ischemic strokes. At three months, 27.8% had died, 29.7% had significant disability (mRS 3-5), and 1.1% had a recurrent stroke.

In this study, one in seven stroke were in the young, two in five patients arrived after 24 hours of symptom onset, and thrombolysis and mechanical thrombectomy were underutilized. Over half had poor 3-month outcomes, highlighting the need for improving comprehensive stroke care across India.

Type 2 diabetes mellitus (T2D) is associated with cardiac dysfunction caused by oxidative stress, inflammation, and fibrosis. Exercise has shown cardioprotective effects in T2D. However, the impact on the Advanced Glycation End Products (AGE) and its receptors remains unclear. In this study, we investigated whether aerobic exercise modulates the AGE signaling pathway in the hearts of diabetic mice and whether it is associated with oxidative and inflammatory damage.

Male C57BL/6 mice were fed a control (CTL) diet or a high-fat, high-carbohydrate (HFHC) diet to induce T2D. A subset of the T2D mice underwent aerobic training for 12 weeks (T2D EX), whereas the other mice remained sedentary (T2D). Cardiac tissues were analyzed for AGE deposition, AGE receptors expression, oxidative stress markers, cytokine profiles, and histological changes, including fibrosis and inflammation.

Aerobic exercise in T2D mice reduced the cardiac deposition of fluorescent AGEs and CML, decreased RAGE protein and gene expression, downregulated CD36 and galectin-3 receptors, while not affecting GLO-1 detoxification system. Exercise in T2D mice suppressed cardiac inflammation and fibrosis. Improvements in inflammatory profiles included reduced expression of IL-6, TNF-α, and NF-kB. However, markers of oxidative stress, such as malondialdehyde, remained largely unaffected by exercise. Pearson's correlation analysis showed strong associations between AGE signaling pathway components and cardiac fibrosis, inflammation, and oxidative stress parameters.

Aerobic exercise mitigates cardiac changes in T2D by downregulating the AGE signaling pathway and reducing fibrosis and inflammation. These findings highlight the therapeutic potential of exercise in interfering with AGE-mediated mechanisms to alleviate T2D-associated cardiovascular complications.

The 2021 military coup and the accompanying armed conflicts in Myanmar have disrupted the country's health systems, particularly in conflict-affected rural areas. Anti-junta healthcare providers innovated alternative systems to address the needs. This study aims to provide insights into the experiences and perspectives of the anti-junta healthcare providers and community members regarding the prevailing health issues in conflict settings of Sagaing Region, how the anti-junta healthcare providers have established alternative care systems in the region, and the challenges the providers and community members encounter in healthcare provision and access.

We conducted qualitative, semi-structured, in-depth online interviews with 26 healthcare workers providing, managing or supporting healthcare services and six community members receiving these services from the Sagaing Region, Myanmar. We analysed the data thematically.

Prevailing health issues included conflict-related injuries, infectious diseases, chronic non-communicable diseases and mental health concerns. In resistance force-controlled rural areas, junta-controlled rural health centres have stopped functioning, and anti-junta healthcare workers and local communities have established new systems to provide primary care to the local communities, although secondary care was still limited. However, limited workforce, supplies, funding and infrastructure, restricted travel and communication and safety concerns impeded their efforts. Moreover, the politicisation of healthcare, targeted attacks and interference by the junta further hindered effective responses to these challenges.

The post-coup conflict has severely devastated Sagaing Region's healthcare systems and health status, disproportionately affecting rural areas, demanding immediate action. Failure to address these issues promptly could worsen the region's health outcomes and deepen the humanitarian crisis. Improving healthcare in the region will require effective interventions from international stakeholders to stop junta attacks on healthcare and civilians and innovative ways to support new local healthcare initiatives technically, financially and logistically.

Objective: To investigate the multidimensional glycemic profiles and their associations with chronic complications in patients with type 1 diabetes (T1D) of over 10 years' duration. Methods: This cross-sectional study used data from the prospective Peer Support for Long-standing T1D (PS-LT1D) cohort. T1D patients with a disease duration of 10-30 years were enrolled from the Chinese Type 1 Diabetes Consortium between 2022 and 2024. In addition to hemoglobin A_1c (HbA_1c) and continuous glucose monitoring metrics, advanced glycation end products (AGEs) were non-invasively measured as a surrogate marker for cumulative metabolic memory. Logistic regression analysis was employed to identify potential correlations between multidimensional glycemic indicators and diabetic microvascular/macrovascular complications. K-Means clustering was then applied to explore characteristic differences in complication prevalence across distinct glycemic patterns. Results: A total of 128 patients (median age 31.5 years; 41 men, 87 women) with a median disease duration of 14.3 years were included. Despite a median time-in-range (TIR) of 70.9%, the prevalence of microvascular complications remained high (42.2%, 54/128). Logistic regression analysis revealed that an elevated metabolic memory burden, represented by skin AGEs, was a significant risk factor for both microvascular and macrovascular complications (OR=1.04, 95%CI 1.01-1.07, P=0.009; OR=1.06, 95%CI 1.03-1.10, P=0.001, respectively), whereas TIR or HbA_1c were not. Based on the clustering of multidimensional glycemic indicators, patients were categorized into three glycemic control phenotypes. The subgroup characterized by a high metabolic memory burden demonstrated the highest risks of retinopathy and macrovascular complications. Conclusions: A significant "metabolic memory" effect persists in patients with T1D even during the mid-to-long term course of the disease. AGEs are strongly associated with the risk of chronic complications. Complication risks vary markedly across glycemic control patterns. In assessing complication risk among patients with long-duration T1D, AGE accumulation, serving as a cumulative metabolic memory indicator, holds greater predictive value than short-to-medium term glycemic markers such as HbA_1c.