Type 2 diabetes and its associated complications like nephropathy impose a serious burden on health systems. Several blood glucose-lowering medications have shown to be likely to provide nephroprotective properties, delaying or preventing the onset of kidney damage. Kidney-specific health-economic evaluations, comparing different agents, remain rare for Germany.

A Markov-microsimulation model was developed to obtain the perspective of the German statutory health system regarding cost-effectiveness. The model consists of five health states representing varying degrees of kidney damage with transition probabilities, utilities and costs being taken from published literature. Patient age was set to 62.8 years in the primary cohort; an additional analysis scenario was created with a start age of 50 years. The model outcomes life expectancy, quality adjusted life years, costs and net monetary benefit were discounted at 3% at a willingness-to-pay threshold of 100,000€ per quality adjusted life year gained.

Quality adjusted life years increased from 10.28 years in standard care to 10.48 years with Empagliflozin, 10.58 years with Semaglutide and 10.75 years with Tirzepatide all added on top of standard care. Life expectancy increased from 13.36 years in the base case to 13.66 years, 13.76 years and 14.00 years with Empagliflozin, Semaglutide and Tirzepatide respectively. Total direct cost amounted to 66,343.64€ in the base case, 79,767.42€ with Empagliflozin, 84,328.59€ with Semaglutide and to 155,992.59€ with Tirzepatide. The net monetary benefit was calculated to be 961,445.98€ in the base case, 968,406.95€, 973,647.74€ and 919,972.95€ with Empagliflozin, Semaglutide and Tirzepatide respectively. Multiple one-way sensitivity analyses were performed. The most influencing factors on the cost-effectiveness were found to be quality of life in the type 2 diabetes state and intervention cost.

In this study, the application of second-line glucose-lowering medication in type 2 diabetes patients led to relevant medical improvements regarding kidney damage at higher expenditures. At the chosen willingness-to-pay threshold Empagliflozin and Semaglutide remained cost-effective in all scenarios. Patient age and sex did not change the health-economic implications.

Not applicable.

To codesign a preclinic Diabetes Priorities Questionnaire (DPQ) tool for people with type 2 diabetes and healthcare professionals to identify patient needs in advance and enable efficient, patient-centred consultations for diabetes management.

Participatory approach using codesign focus groups to explore perspectives and develop solutions.

This study was conducted in Western Sydney, Australia, an area with high socioeconomic disadvantage and cultural diversity.

10 adults with type 2 diabetes and 8 healthcare providers including specialists, diabetes educators, general practitioners, dietitians and pharmacists were recruited from a public hospital-based outpatient diabetes service and community-based providers in Western Sydney.

The codesign process was employed to iteratively develop and refine the DPQ. Focus groups were conducted in a hybrid format including in person and online, using semistructured discussions on four key topics: (1) understanding the purpose of the tool, (2) usability of the tool, (3) perceived benefits of completing the tool and (4) asking the right questions (content). Participants were invited to review and provide feedback on the initial set of questions, with the aim of identifying key challenges and potential solutions to enhance the content and uptake of the tool. Feedback was collected through audio recordings and field notes. These insights informed successive revisions of the DPQ following each round of focus groups.

Five focus groups involving 18 participants identified opportunities to improve the initial questions by restructuring their order, simplifying the content and incorporating concerns about diabetes complications, including mental health. Participants highlighted the importance of holistic care and the need for both digital and paper-based formats to enhance accessibility.

The final DPQ was digitised within a patient care portal and integrated with tailored diabetes educational content. By enabling preconsultation screening, the codesigned DPQ supports multidisciplinary teams in delivering patient-centred care. Further research is needed to assess the tool's impact on clinical outcomes, patient satisfaction and healthcare efficiency.

Telemedicine has been increasingly adopted post-COVID-19 to optimise chronic disease management, improving patient outcomes. The multi-component OPTIMUM (Optimising care of Patients via Telemedicine In Monitoring and aUgmenting their control of diabetes Mellitus) tele-monitoring (TM) system yielded favourable health outcomes and was introduced in primary care nationwide in Singapore. This study aims to understand the factors associated with its implementation during the randomised controlled trial (RCT).

A qualitative study was conducted using individual semi-structured interviews. Data were transcribed, audited, coded and analysed using thematic analysis. The CFIR (Consolidated Framework for Implementation Research) framework, consisting of five domains (Intervention characteristic, Outer setting, Inner setting, Characteristics of individuals and Process), was adopted as the underpinning framework.

Primary care setting in Singapore.

Healthcare professionals involved in the care provided to patients enrolled in the OPTIMUM RCT.

TM facilitated behavioural change in patients, and its robust treatment algorithm allowed continuous monitoring and personalised advice. The associated external factors were manpower, costing and data security. Measures to mitigate internal risks included managing additional healthcare professionals' burden, reducing potential adverse events and addressing medicolegal risks related to TM. While TM enhanced provider satisfaction and the patient-healthcare professional relationship, strategies to enhance user experience and streamline the TM processes are required to improve its acceptance and adoption.

The CFIR served as a useful framework to identify factors associated with successful implementation of an intervention in a real-world setting. Understanding these factors enables healthcare leaders to address the challenges before scaling up the intervention in routine clinical services.

α-Glucosidase (α-Glu) inhibitors are important therapeutic agents for the treatment of type 2 diabetes mellitus. However, the rapid discovery of such bioactive compounds from natural products remains challenging.

In this study, a MOF-818@Pt nanozyme-based colorimetric screening strategy was developed for the efficient discovery of α-Glu inhibitors from natural sources. The MOF-818@Pt composite, synthesized via an in-situ reduction-deposition method, exhibited excellent peroxidase-like activity and was thoroughly characterized. Using α-arbutin as the substrate, the proposed nanozyme-based system enabled sensitive detection of α-Glu activity, exhibiting a good linear relationship within the concentration range of 0.05-120 U/L (R² = 0.991), along with strong anti-interference ability, satisfactory reproducibility, and long-term stability. This method was successfully applied to the bioactivity-guided fractionation of Myrciaria cauliflora, leading to the enrichment of ten subfractions (GH1-GH10) with significant α-Glu inhibitory activity. Feature-based molecular networking analysis revealed that these subfractions are predominantly composed of phloroglucinols, terpenoids, polyketides, and meroterpenoids. Molecular docking studies demonstrated that representative compounds from each class could bind within the active site of α-Glu, forming hydrogen bonds with key residues including Arg213, Asp215, Glu277, Gln279, and Asp352.

This work establishes a rapid, simple, and high-throughput strategy for screening α-Glu inhibitors from complex natural product matrices, providing a promising technological platform for natural product-based drug discovery.

Diabetic cataract is a common complication of diabetes, and current clinical management mainly relies on surgical intervention, with limited preventive strategies available. This study aimed to investigate whether liver-targeted low-intensity pulsed ultrasound (LIPUS) can prevent or delay the progression of diabetic cataract and to elucidate the underlying molecular mechanisms.

A type 2 diabetes mellitus rat model was established using a high-fat diet combined with streptozotocin. Animals were divided into Normal, Model, and LIPUS groups. The LIPUS group received liver irradiation (200 mW/cm², 10 min/day for 30 days). Lens opacity was assessed using slit-lamp examination, and blood glucose, branched-chain amino acids (BCAAs), and PRKAR1A expression were measured. In vitro experiments included co-culture of hepatocytes (AML12) and lens epithelial cells (SRA01/04) and siRNA transfection assays. Statistical analysis was performed using independent-samples t-tests and two-way ANOVA.

LIPUS significantly delayed the onset and progression of diabetic cataract, reduced blood glucose levels and hepatic/serum BCAAs, and restored PRKAR1A expression in lens epithelial cells. LIPUS also inhibited epithelial-mesenchymal transition (EMT) by upregulating E-cadherin and downregulating α-SMA. Knockdown of PRKAR1A reversed the inhibitory effect of LIPUS on EMT. Additionally, LIPUS improved liver and pancreatic histopathology without causing detectable tissue damage.

LIPUS prevents diabetic cataract through dual mechanisms: improving glucose homeostasis and reducing BCAAs levels to restore PRKAR1A expression, thereby inhibiting EMT in lens epithelial cells. These findings suggest that LIPUS represents a safe and non-invasive strategy for diabetic cataract prevention and highlight BCAAs and glucose metabolism as potential therapeutic targets.

This study demonstrates that targeted hepatic application of low-intensity pulsed ultrasound (LIPUS) effectively delays diabetic cataract progression in rats by suppressing lens epithelial cell EMT through dual mechanisms-directly lowering blood glucose and reducing hepatic BCAA production to restore PRKAR1A expression via the liver-lens axis-thereby offering a promising non-invasive preventive strategy that concurrently improves systemic glucose metabolism.

Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer, and type 2 diabetes mellitus (T2DM) is a common comorbidity in COPD patients. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have pleiotropic effects beyond glucose lowering. However, their association with lung cancer risk in patients with COPD and T2DM remains uncertain.

Is SGLT2 inhibitor initiation associated with a lower risk of incident lung cancer in patients with COPD and T2DM?

We conducted a nationwide population-based cohort study using the National Health Insurance Database, including adults aged ≥40 years with COPD and T2DM who initiated SGLT2 inhibitors or sulfonylureas between September 2014 and December 2023. The primary outcome was incident lung cancer. Secondary outcomes included severe COPD exacerbation and all-cause mortality.

Among 14,927 patients (5,651 SGLT2 inhibitor initiators and 9,276 sulfonylurea initiators), 234 incident lung cancer events occurred during a median follow-up of 2.97 years. The 4-year cumulative incidence of lung cancer was 1.6% in the SGLT2 inhibitor group and 2.7% in the sulfonylurea group. Initiation of SGLT2 inhibitors was associated with a lower risk of incident lung cancer compared with sulfonylureas (IPTW HR 0.73; 95% CI, 0.60-0.90). SGLT2 inhibitor use was also associated with reduced risks of severe COPD exacerbation (IPTW HR 0.77; 95% CI, 0.71-0.83) and all-cause mortality (IPTW HR 0.81; 95% CI, 0.75-0.88).

In this nationwide cohort of patients with COPD and T2DM, initiation of SGLT2 inhibitors was associated with lower risks of lung cancer, COPD exacerbation, and all-cause mortality compared with sulfonylureas.

Preoperative optimization is widely recommended for patients undergoing ventral hernia repair. However, the clinical impact of individual risk factors remains uncertain. This study aimed to evaluate the association of obesity, diabetes mellitus, and smoking with postoperative outcomes and to compare these findings with surgeon practices and existing literature.

The augmented evidence review (AER) was performed using three evidence streams to answer the unified question "What are the key components of preoperative patient optimization for ventral hernia repair?". Empiric evidence was gathered using a retrospective analysis of the Abdominal Core Health Quality Collaborative database. Social media evidence was gathered by surveying practicing surgeons via the International Hernia Collaboration social media group. Artificial intelligence evidence was obtained from the OpenEvidence platform which performed a data-driven literature review. Each evidence stream was analyzed independently before integrating it in the AER.

Obesity was associated with increased wound complications, but no significant association with systemic complications. Diabetes status and glycemic control were not associated with postoperative complications. Smoking was associated with increased surgical site occurrence and pneumonia. Survey results demonstrated that most surgeons consider these risk factors important. However, implementation varied with individualized approaches favored for obesity and smoking whereas defined thresholds were used for glycemic control. AI-derived evidence demonstrated similar heterogeneity.

The evaluated risk factors demonstrated modest differences in postoperative outcomes, some of which were statistically significance. However, the clinical significance is mainly determined by the surgeon as reflected by our survey. Most surgeons favored an individualized approach for obesity, followed by smoking, and less so for diabetes mellitus.

Diabetes Mellitus is associated with impaired osseous healing following foot and ankle surgery. Although hemoglobin A1c is commonly used to assess surgical risk, its relationship with postoperative union remains unclear.

We performed a retrospective review of consecutive diabetic patients who underwent foot and ankle surgery between January 1, 2015, and May 1, 2020, to evaluate the association between preoperative hemoglobin A1c and union rates.

Demographic and clinical variables were collected, including preoperative and last recorded HbA1c, body mass index, smoking status, peripheral neuropathy, vitamin D level, history of chronic kidney disease, peripheral vascular disease, and surgical location. Patients were categorized according to osseous healing status (union vs nonunion).

Of 106 patients, 87 achieved union and 19 developed a nonunion. Preoperative hemoglobin A1c, last recorded hemoglobin A1c, interval change in hemoglobin A1c, and stratification into clinically relevant A1c categories (<7%, 7-8%, and >8%) were not associated with nonunion (all p>0.05). Age, sex, surgical location, smoking, peripheral neuropathy, peripheral vascular disease, and chronic kidney disease were not associated with healing. Patients with nonunion had significantly greater body weight (p=0.004), higher body mass index (p=0.020), and lower vitamin D levels (p=0.014) than those who achieved union.

Preoperative hemoglobin A1c was not associated with postoperative osseous healing, and no clinically meaningful hemoglobin A1c threshold predictive of nonunion was identified. Elevated body mass index and lower vitamin D levels were associated with impaired healing and may represent more relevant modifiable risk factors than hemoglobin A1c.

3.

Cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), metabolic dysfunction-associated steatotic liver disease (MASLD), and obesity coexist under the cardiovascular-kidney-liver-metabolic (CKLM) framework and account for nearly one third of global deaths, yet long-term projections of their combined burden are lacking.

Using the Global Burden of Disease 2023 study, we projected incidence, prevalence, mortality, and disability-adjusted life years (DALYs) across 204 countries from 2026 to 2050, stratified by age, sex, geography, and sociodemographic index (SDI). The CKLM burden was organised into metabolic antecedents, comprising T2DM, CKD, MASLD and obesity; and downstream atherosclerotic CVD, comprising ischaemic heart disease, stroke, aortic aneurysm, and peripheral artery disease. ARIMA was selected as the primary forecasting model following out-of-sample validation of five candidate time-series models. Risk-deleted analyses estimated burden reduction achievable through elimination of modifiable risk factors.

By 2050, the global CKLM burden is projected to affect 4.7 billion (95%UI: 4.4 to 5.0 billion) aggregate prevalent condition counts, with 220.6 million incident cases (95%UI: 208.9 to 232.3 million), contributing 860.1 million DALYs and 32.4 million deaths. Crude DALYs are projected to rise 52.1% (95%UI: 23.6 to 80.7) from 2026 to 2050, driven by a 25.8% (95%UI: 10.7 to 40.8) rise in atherosclerotic CVD and a doubling of metabolic antecedents (100.0%; 95%UI: 14.9 to 185.0). Age-standardised DALY rates are anticipated to fall 14.9% (95%UI: -37.4 to 7.5), with a 31.4% (95%UI: -45.8 to -16.9) reduction in atherosclerotic CVD offset by a 14.6% (95%UI: -47.4 to 76.6) rise in metabolic antecedents. Metabolic antecedents are projected to expand from 35.7% to 48.1% of total CKLM burden between 2026 and 2050. CKLM burden is highest and fastest-growing in low-middle SDI regions and South Asia. Risk-deleted analyses identify high fasting plasma glucose (39.4% reduction), high systolic blood pressure (34.4% reduction), and dietary risks (28.1% reduction) as the highest-yield modifiable targets.

By 2050, modest improvements in age-standardised cardiovascular-kidney-liver-metabolic morbidity will be overwhelmed by a substantial rise in absolute burden driven by population ageing and growth, as upstream metabolic antecedents expand from one-third to nearly half of the total CKLM composition.

Type 2 diabetes mellitus (T2DM) affects approximately 589 million adults globally, yet mechanisms linking intestinal microbial dysbiosis to metabolic dysfunction remain incompletely understood. Although bacterial alterations have been extensively characterised, the gut mycobiome has received comparatively limited attention despite growing evidence that fungi participate in immune, epithelial, and metabolic homeostasis. This review synthesises evidence linking gut fungal dysbiosis with T2DM from human and experimental studies. Across cohorts, T2DM has been associated with Candida enrichment and depletion of Saccharomyces, alongside glycemia-associated genera including Wickerhamomyces and Kodamaea that correlate with fasting glucose and HbA1c. Experimental studies suggest that fungal dysbiosis may contribute to epithelial barrier disruption, metabolic endotoxaemia, adipose inflammation, hepatic insulin resistance, NLRP3 inflammasome activation, β-cell dysfunction, and Th17/Treg imbalance. Cross-kingdom fungal-bacterial interactions may influence short-chain fatty acid production and bile acid signaling, while hyperglycemia may favour fungal expansion. Recent animal studies suggest that early-life mycobiome colonization may influence pancreatic β-cell development through macrophage-dependent mechanisms. Precision-mycobiome approaches suggest that baseline fungal signatures may be associated with differential metabolic responses to intervention. The available evidence remains associative, geographically concentrated, and methodologically heterogeneous. Future progress will depend on longitudinal studies, standardised profiling protocols, medication-stratified analyses, and rigorously powered clinical trials with mycobiome-specific endpoints.