Type 2 diabetes mellitus (T2DM) is a growing public‑health challenge in Greece, yet validated tools to assess care quality in primary settings are lacking. We aimed to develop a context‑specific set of consensus‑based quality indicators (QIs) for T2DM in Greek primary care, with an eye toward broader applicability in comparable European and low‑ and middle‑income country (LMIC) systems.

A two-phase study was conducted: (1) a focused bibliographic search (Medline/PubMed and Scopus; January 2019-August 2020) to identify existing T2DM QI sets suitable for primary care; and (2) a three-round modified Delphi survey with 10 stakeholders (general practitioners, diabetologist, dietician, health policy expert, patients) to evaluate indicator importance and feasibility and reach consensus. Candidate indicators were contextually adapted for European relevance prior to Delphi rating.

The bibliographic search identified 16 records; only one study met eligibility criteria and provided 43 candidate QIs. The Delphi process yielded 39 QIs across nine domains: access (2), monitoring (13), health counseling (3), treatment and prevention (2), patient safety (3), records (1), health status (11), patient satisfaction (2), and self-management (2).

We present the first context-adapted, consensus-based T2DM QI set for Greek primary care, covering clinical, organizational, and patient-reported aspects of care. This framework lays the groundwork for wider implementation, electronic health record integration, and international benchmarking.

Cardiac dysfunction in elderly diabetes, due to superimposition of age-related myocardial senescence and diabetes-induced injury, lacks effective therapeutic strategies. Ferroptosis may be a key mechanism underlying cardiomyocyte injury in diabetic cardiomyopathy. Mesenchymal stem cells (MSCs) and their exosomes show potential for repairing cardiomyocytes, restoring cardiac function, improving insulin sensitivity, and mitigating diabetes-related complications, but their mechanisms and relationship with ferroptosis remain unclear. The present study aimed to investigate reparative effects and ferroptosis-mediated mechanism of exosomes derived from VCAM-1 high-performance MSCs on aged diabetic cardiomyocyte injury. High-glucose-damaged senescent cardiomyocyte and aged rat model of diabetic cardiomyopathy were established and treated with VCAM-1⁺-UC-MSCs or -derived exosomes. Assessments of cell phenotypes, RNA sequencing, cardiac function, and markers of senescence and ferroptosis revealed significant mitochondrial damage, iron-ion accumulation, reactive oxygen species (ROS), and cardiac troponin (c-TnT) elevation in the damaged myocardial cells and rat heart tissues, along with weakened cardiac function and pronounced senescence and ferroptosis features, and activation of Ras/Raf/MEK/ERK/c-FOS pathway. VCAM-1⁺ MSCs or exosome administration significantly alleviated these effects, and improved cardiac function. Notably, the reparative effect of VCAM-1⁺-UC-MSCs-derived exosomes was superior to that of conventional MSCs-derived exosomes. In conclusion, VCAM-1⁺-UC-MSCs-derived exosomes attenuate cardiomyocyte ferroptosis by suppressing Ras/Raf/MEK/ERK/c-FOS pathway, thereby ameliorating myocardial injury resulting from superimposition of aging-caused myocardial senescence and diabetes-induced damage in elderly diabetic cardiomyopathy. This may lay a foundation for identifying potential prevention and treatment strategies and targets of MSCs and -derived exosomes on myocardial injury.

Minimally invasive floating metatarsal osteotomy has been proposed as a surgical strategy to address recurrent or persistent diabetic foot ulcers (DFUs) by correcting underlying biomechanical deformities. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, querying four databases through September 2025 for studies involving adult patients with neuropathic DFUs treated with minimally invasive floating metatarsal osteotomy and followed for at least 12 months. Six studies comprising 184 subjects (176 with DFUs, 8 prophylactic) met inclusion criteria. Pooled outcomes demonstrated a healing rate of 98% (95% CI: 0.94-1.00) with a mean time to closure of 31.7 days (95% CI: 24.1-39.3). Ulcer recurrence occurred in 4% (95% CI: 0.02-0.09), while transfer lesions developed in 14% (95% CI: 0.08-0.20) and nonunion was observed in 14% (95% CI: 0.06-0.29). The overall infection rate was 7% (95% CI: 0.04-0.12). These findings indicate that minimally invasive floating metatarsal osteotomy is a safe and effective surgical option for off-loading neuropathic DFUs; demonstrating high healing rates, rapid time to closure and low recurrence when compared with conservative care. Larger randomised controlled trials are warranted to validate these results and establish standardised surgical indications.

Aim: To stratify children with T1D according to their risk of developing and progressing DN using cluster analysis of clinical and laboratory indicators.

Materials and Methods: Cluster analysis was performed in a cohort of 60 children (mean age 13 } 3 years; 17 [28,3%] boys and 43 [71,7%] girls) with T1D, with (n = 30) or without (n = 30) early-stage DN, based on parameters such as T1D duration, estimated glomerular filtration rate, microalbuminuria (MAU), urinary kidney injury molecule-1 (KIM-1), and episodes of diabetic ketoacidosis (DKA).

Results: Three clusters with distinct renal risk profiles were identified in children with T1D with or without DN. The risk group for DN development in T1D children showed moderate T1D duration, random MAU and DKA episodes, and slightly increased KIM-1 levels. The risk group for further DN progression in children with early DN was characterized by prolonged T1D duration, pronounced MAU, frequent DKA, hyperfiltration, and markedly elevated urinary KIM-1.

Conclusions: Cluster analysis allows early identification of the risk group for DN in children with T1D and the risk group for DN progression in children with early DN. Urinary KIM-1 may be implemented as a biomarker of tubular injury, providing opportunities for earlier intervention before clinical nephropathy develops.

Aims: To determine the concentrations of interleukins (IL1β, IL4, IL6, IL8) in the aqueous humor and their association with diabetic retinopathy severity.

Materials and Methods: Singlecenter crosssectional study with prospective sampling of 110 adults with type 2 diabetes mellitus spanning five categories of diabetic retinopathy and 25 nondiabetic controls. Aqueous humor (0.1 mL) obtained during phacoemulsification was analyzed by ELISA. Nonparametric tests assessed group differences; optimal thresholds were derived by multiclass onevsall ROC-analysis, followed by clinically relevant binary stratification (mild/ moderate vs severe DR). Spearman rank correlations evaluated relationships with age, diabetes duration, fasting glucose, HbA1c, and Cpeptide.

Results: All interleukins differed between groups (p < 0.001). IL1β and IL6 increased with stage; IL8 peaked at severe nonproliferative disease and declined in proliferative disease; IL4 decreased. Multiclass accuracies were modest: 56%, 58%, 53%, and 44% for IL-6, IL8, IL1β, and IL4. In the binary model, IL6 achieved 72.6% accuracy (95% CI 64.3-79.9), with cutoffs of 34.4-86.2 and >86.2 pg/mL for mild/moderate and severe disease. IL8 was supportive (62.2%; severe >216.9 pg/mL). IL1β and IL4 each yielded about 55.6%. Correlations were weak to moderate: IL6 and IL8 tracked diabetes duration and glycemia, while IL4 inversely tracked Cpeptide.

Conclusions: IL6 is the most informative single local biomarker for binary severity stratification of diabetic retinopathy, with IL8 as an adjunct and IL1β/ IL4 of limited standalone value. IL6 thresholds may guide riskadapted followup and monitoring with optical coherence tomography and optical coherence tomography angiography. External validation, preanalytical standardization, and prospective outcome studies are needed.

Fibroblast growth factor 1 (FGF1), a well-characterized member of the FGF family, effectively lowers blood glucose levels in animal models of type 2 diabetes by stimulating glucose uptake. However, its significant mitogenic potential poses a major challenge for clinical application. Here, we present engineered variants of FGF1 designed to dissociate its potent glucose-lowering effects from its undesired proliferative activity, aiming for a future therapeutic agent for type 2 diabetes. Through a series of rational mutations focused on modulating receptor binding and heparan interactions, coupled with enhanced thermodynamic stability, we developed two lead FGF1 variants. Comprehensive in vitro studies confirmed that these variants exhibit significantly reduced mitogenic potential across various cell types compared to wild-type FGF1. Specifically, one variant showed profound loss of proliferation due to disrupted FGFR binding, while the other displayed attenuated mitogenicity linked to decreased heparin affinity. Critically, both fully maintained potent glucose-lowering properties in db/db mice without inducing hypoglycemia or changes in body weight. Furthermore, these engineered proteins demonstrate superior thermodynamic stability and markedly improved pharmacokinetic profile, critical attributes for drug development. Our findings highlight a successful strategy to uncouple the therapeutic benefits of FGF1 from its mitogenic side effects, offering promising, stable, and safe protein-based drug candidates for type 2 diabetes treatment.

The development of vascular calcification (VC) in diabetes is closely related to the endothelial-to-mesenchymal transition (EndMT). We found that microRNA-32-5p (miR-32) was elevated in the plasma of calcification patients. However, it is unclear whether miR-32 mediates the function of bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) in type 2 diabetes (T2D) VC.

BMSC-EVs were characterized by TEM, NTA, Western blotting, and confocal microscopy. Alizarin Red and ALP staining assessed the severity of VC. qRT-PCR and Western blotting evaluated the expression of BMP2, RUNX2, GPX4, SLC7A11, VE-cadherin, and N-cadherin, while immunofluorescence was used for detecting VE-cadherin and N-cadherin. In vivo validation was performed using miR-32^-/- and ApoE^-/- mice. RNA sequencing (RNA-seq) and bioinformatics analysis was conducted to explore underlying mechanisms.

We demonstrated that BMSC-EVs attenuate VC in endothelial cells (ECs) and inhibit EndMT. In vivo, histological analysis showed that treatment with BMSC-EVs significantly reduced the severity of VC associated with T2D. Notably, knockout of miR-32 further enhanced the inhibitory effect of BMSC-EVs on VC. Mechanistically, transcriptomic and functional analyses suggest that the protective effect of BMSC-EVs on VC is associated with regulation of the MAPK/FoxO signaling pathway, potentially mediated by modulation of ferroptosis.

These findings demonstrate that BMSC-EVs attenuate T2D-associated VC, partially through miR-32-mediated suppression of EC ferroptosis.

Patient-centered therapy, with shared decision making (SDM) as a fundamental principle, is recommended in clinical guidelines for the care of individuals with type 2 diabetes mellitus but is often not implemented in practice. "arriba Diabetes" was developed as a decision aid to support shared decision-making (SDM) regarding therapy intensity. The underlying linear model requires four inputs: (1) age, (2) comorbidities, (3) preference preferences regarding treatment efforts, and (4) preferences regarding the avoidance of organ damage. Based on these inputs, the program calculates an appropriate therapy intensity. This study aimed to examine how GPs perceive "arriba Diabetes".

This qualitative interview study aimed to explore general practitioners' (GPs') perceptions of "arriba Diabetes", specifically (1) whether the therapy intensity suggested by the model was considered appropriate, (2) whether the tool was perceived as comprehensible, and (3) whether it was regarded as complete. Interviews were conducted at two time points-before and after the application of the tool. The interview performed before the application followed the cognitive pretest approach. Data were analyzed thematically according to Braun and Clarke.

We conducted five interviews before and 18 interviews after the application of "arriba Diabetes". GPs generally perceived the recommended therapy intensity as appropriate. In some cases, it was initially regarded as not strict enough but, upon reflection, was considered comprehensible and even educational in terms of supporting de-escalation. The four input parameters (age, comorbidities, preference regarding treatment efforts, and preference regarding the avoidance of complications) were largely viewed as meaningful and complete, although the assessment of comorbidities and treatment efforts was sometimes described as challenging. Overall, GPs considered "arriba Diabetes" to be a practical and comprehensible tool for supporting SDM.

"arriba Diabetes" has the potential to support shared decision-making on therapy intensity for individuals with type 2 diabetes mellitus.

Type 2 diabetes mellitus is a risk factor for incident dementia including Alzheimer's disease (AD) dementia, but the mechanism is not clear. Abnormalities in brain default mode network (DMN) connectivity are associated both with T2DM and with increased risk for AD dementia. We explore the response of the DMN to acute glucose ingestion in diabetic versus non-diabetic older adults to better understand the brain's neurovascular response to glucose and ultimately relate that response to longitudinal cognitive and brain changes.

We scanned (3T Siemens Prisma MRI) N = 59 cognitively unimpaired older (50-65 years) adults (N = 26 with T2DM, N = 33 non-diabetic). Each received a fasting resting-state functional MRI (rs-fMRI) scan, a 75g glucose tolerance test, a two-hour break and then a post-glucose rsfMRI scan. Rs-fMRI analyses were performed using FSL software with a posterior cingulate cortex/precuneus seed to identify the DMN in each participant. First, we investigated individual participant differences in DMN connectivity between fasting and 120 minutes post-glucose states to evaluate where each participant had more or less DMN connectivity post-glucose than while fasting. We then compared those individual differences in the brains' response to glucose within and between diabetic and non-diabetic groups. All analyses were adjusted for age and sex. We corrected for voxel-wise multiple comparisons (cluster-wise threshold z>3.1; corrected p-threshold = 0.001).

We found significant differences between diabetic and non-diabetic participants in the brains' response to glucose ingestion broadly throughout the brain (Figure 1). Within-group analyses provided context for those differences. In diabetic participants, glucose ingestion caused an increase in DMN connectivity with the cerebellum and superior frontal gyrus but a decrease with parietal, occipital, and orbitofrontal regions. In contrast, in non-diabetic participants, glucose ingestion caused in increase in DMN connectivity with the lateral occipital cortex and middle temporal gyrus, but a decrease in connectivity with the cerebellum, medial prefrontal cortex, and anterior thalamus.

Our findings highlight distinct DMN connectivity responses to glucose ingestion in older adults with and without T2DM. Relating these differences to longitudinal brain and cognitive changes will help elucidate possible mechanisms and uses of rs-fMRI connectivity as a predictive biomarker.