Editor’s Choice Articles

Background: Cerebrovascular accidents (stroke) remain a leading global cause of death and disability, with its burden increasingly overlapping the rising prevalence of obstructive sleep apnea (OSA) and diabetes mellitus (DM). These highly prevalent cardiometabolic conditions frequently coexist and may jointly amplify cerebrovascular risk through shared and interacting pathophysiologic pathways. This narrative review synthesizes current evidence on the independent and combined contributions of OSA and DM to cerebrovascular complications, with emphasis on mechanisms, stroke outcomes and implications for screening and integrated management. Methods: A narrative review was conducted using PubMed, MEDLINE, and the Cochrane Library to identify English-language articles published between January 2000 and December 2024. Search terms combined OSA or sleep-disordered breathing with stroke or cerebrovascular disease and DM or hyperglycemia. Secondary searches targeted mechanistic domains including intermittent hypoxia, insulin resistance, metabolic syndrome, atrial fibrillation, hypercoagulability, and bariatric surgery. Priority was given to systematic reviews and meta-analyses, randomized controlled trials, and large prospective cohort studies, with smaller studies included when mechanistically informative. Findings were synthesized thematically across OSA-related mechanisms, DM-related mechanisms, bidirectional interactions, combined risk through metabolic syndrome, stroke outcomes, and clinical management considerations. Results: OSA is associated with increased cerebrovascular risk through intermittent hypoxemia-related oxidative stress and inflammation, sympathetic activation with blood pressure surges and sustained hypertension, endothelial dysfunction and atherosclerosis, impaired cerebral autoregulation, arrhythmogenesis, particularly atrial fibrillation and prothrombotic changes. DM increases stroke risk via accelerated atherosclerosis, cerebral small vessel disease, endothelial injury, hypercoagulability, glycemic variability, and cardioembolic mechanisms. Evidence indicates that coexisting OSA and DM are common and associated with greater vascular injury markers, higher rates of cerebrovascular events, and poorer post-stroke recovery. Conclusions: OSA and DM contribute to cerebrovascular complications through convergent mechanisms centered on metabolic syndrome, obesity, inflammation, vascular dysfunction, and thrombosis. These findings support proactive screening and coordinated management strategies to reduce cerebrovascular risk and improve outcomes. Full article

Background: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder in which gut microbiota dysbiosis contributes to insulin resistance, metabolic inflammation, and impaired glucose homeostasis. Dietary fibers and prebiotics selectively modulate gut microbiota composition and function and may offer metabolic benefits in T2DM. This review examines the mechanistic links between dietary fibers, prebiotics, gut microbiota modulation, and metabolic outcomes in T2DM. Methods: Relevant experimental and clinical studies were reviewed to assess the effects of dietary fibers and prebiotics on microbial diversity, short-chain fatty acid production, intestinal barrier function, bile acid signaling, and glycemic control in T2DM. Results: Evidence indicates that T2DM is associated with reduced abundance of SCFA-producing bacteria, increased intestinal permeability, metabolic endotoxemia, and altered bile acid metabolism. Dietary fibers and prebiotics enhance SCFA production, support gut barrier integrity, and modulate inflammatory and metabolic pathways. Clinical evidence demonstrates modest improvements in glycemic and inflammatory parameters, though outcomes vary according to fiber type, dose, and baseline microbiota composition. Conclusions: Dietary fibers and prebiotics are promising, low-risk strategies for gut microbiota modulation in T2DM. Further standardized, long-term randomized studies integrating microbiome profiling and clinically meaningful endpoints are required to support precision nutrition approaches. Full article

Diabetes mellitus (DM) is highly prevalent among patients undergoing foot and ankle surgery and is associated with substantially increased perioperative and postoperative risk. This narrative review synthesizes the current literature on optimization of DM patients undergoing foot and ankle surgery. Complications of chronic hyperglycemia, including neuropathy and peripheral vascular disease, make the foot and ankle particularly vulnerable to ulceration, infection, and deformity, contributing to high rates of both operations and postoperative complications such as surgical site infection and readmission. Glycemic control and obesity are modifiable predictors of surgical outcomes and represent key targets for preoperative optimization. Lifestyle modification and pharmacologic therapy play central roles in DM optimization. Traditional agents such as metformin, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors remain foundational therapies, while newer therapies such as sodium–glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 (GLP-1) agonists offer meaningful improvements to glycemic control and weight loss. Pharmacologic regimens must be individualized, and many agents require careful perioperative management. Despite advances in medical therapy, high-quality evidence specific to foot and ankle surgery remains limited. Future research should focus on developing procedure- and agent-specific guidelines to reduce the substantial clinical and economic burden of DM in foot and ankle surgical patients. Full article

Reactive oxygen species (ROS) are an essential component for the maintenance of cellular function. However, if produced in excess, ROS can drive cellular dysfunction and compromise cell viability. Indeed, uncontrolled ROS production plays a pivotal role in the pathogenesis of type 2 diabetes (T2D), contributing to the loss of β-cell function and the impairment in insulin signalling, as well as driving the development of diabetic complications, which can severely compromise quality of life. T2D is characterised by persistent hyperglycaemia, which is a leading contributor to ROS overproduction in this disease state. This enhanced, almost uncontrolled, increase in glucose metabolism upregulates several ROS-producing pathways, including the hexosamine pathway, protein kinase C, NADPH oxidase and the mitochondrial electron transport chain. There is accumulating evidence to suggest that in a bid to preserve redox homeostasis, ROS acts to suppress glucose metabolism by inactivating several enzymes involved in the regulation of glycolytic flux, including glucokinase, glyceraldehyde 3-phosphate dehydrogenase, phosphofructokinase-1 and pyruvate kinase. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a multi-faceted transcription factor, with a central role in ROS signalling and redox homeostasis. Whilst NF-κB mediates the transcriptional regulation of many pro-oxidants, NF-κB activity is also regulated by the oxidative status, with ROS having both inhibitory and stimulatory roles in these signalling pathways. Interestingly, NF-κB is also involved in controlling the delicate balance between glycolytic flux and mitochondrial respiration. This review will summarise the interplay linking hyperglycaemia with ROS formation, emphasising the role of glucose metabolism in the process, and the crosstalk of these pathways with NF-κB. Full article

Type 2 diabetes mellitus (T2DM) and obesity affect hundreds of millions of adults worldwide and represent leading drivers of cardiovascular disease, chronic kidney disease, and escalating healthcare expenditures. Incretin-based therapies have fundamentally reshaped cardiometabolic disease management, with dual- and triple-receptor agonists extending the benefits of traditional glucagon-like peptide-1 (GLP-1) receptor agonism. By synthesizing clinical, mechanistic, and real-world data, this review examines the evolving therapeutic landscape of GLP-1-based multi-agonists. Dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists demonstrate superior metabolic efficacy compared with GLP-1 receptor agonists alone, achieving greater reductions in body weight and glycemic indices across diverse patient populations. Emerging triple agonists targeting GLP-1, GIP, and glucagon receptors further enhance metabolic outcomes, with weight loss approaching that observed following bariatric surgery in late-phase clinical trials. Mechanistically, multi-receptor co- agonism produces synergistic effects through complementary pathways, including appetite suppression, glucose-dependent insulin secretion, improved adipose tissue metabolism, increased energy expenditure, enhanced hepatic lipid oxidation, and reductions in hepatic steatosis. Beyond glycemic and weight endpoints, GLP-1-based therapies confer clinically meaningful cardiovascular and renal protection. Trials consistently demonstrate reductions in major adverse cardiovascular events across populations with and without T2DM, while kidney-specific trials show significant slowing of disease progression. However, gastrointestinal adverse events remain common and contribute to substantial treatment discontinuation, particularly in real-world settings. Despite their transformative efficacy, the population-level impact of these therapies is constrained by significant implementation barriers, including high drug costs, limited insurance coverage, restrictive utilization management policies, and pronounced racial and socioeconomic disparities in access. Emerging innovations including oral formulations, longer-acting injectables, and novel peptide combinations look to improve tolerability, adherence, and scalability, while therapeutic indications continue to expand to conditions such as metabolic dysfunction-associated steatohepatitis, chronic kidney disease, obstructive sleep apnea, and neurodegenerative disease. This review provides a comprehensive framework for understanding the clinical potential, mechanistic basis, and real-world challenges of GLP-1-based multi-agonists and outlines key priorities for optimizing implementation and maximizing their impact on global cardiometabolic health. Full article

Offloading remains the cornerstone of diabetic foot ulcer (DFU) management. This review traces the evolution of mechanical offloading from early plaster casting in South Asian leprosy clinics to modern removable walkers and emerging “SmartBoot” technologies. We examine the historical progression from total contact casting (TCC) through the era of randomized trials and instant TCC (iTCC), up to the current integration of wearable sensors and digital adherence tools. Contemporary evidence—including meta-analyses—is discussed to compare the effectiveness of offloading modalities (non-removable vs. removable devices, knee-high vs. ankle-high boots, therapeutic footwear, and adjunctive surgeries). Current challenges, such as patient adherence, frailty, and balance, are linked to technological responses like smart insoles, remote monitoring, and gamification strategies. Through this historical and evidence-based lens, we highlight how decades-old biomechanical principles are being reimagined with 21st-century innovations, aiming to improve healing rates and patient engagement in DFU care. Full article

Aldose Reductase (AR; AKR1B1) is an enzyme that plays a key role in the metabolism of glucose and other carbonyl compounds, and whose hyperactivity contributes to oxidative stress and vascular dysfunction. Despite decades of investigation into this enzyme, inhibitors have failed to translate into clinical application for Diabetic Retinopathy (DR). We argue that these failures might arise from non-selective inhibition, considering the dual roles of AR, which contribute not only to DR pathology but also support retinal health, as AR is an important detoxifying enzyme for aldehydes produced during oxidative stress. Here, we discuss missing structural information, despite more than one hundred crystal structures of AR in complex with inhibitors. Our review bridges this gap by discussing how recent advances in structural biology, e.g., fragment-based drug discovery and MicroED, provide novel ways to selectively modulate AR functions, offering advantages for the detection of weak, allosteric, or conformation-dependent binding events. Despite past challenges, we suggest that therapeutic targeting of AR to find new-generation inhibitors will become more effective once we have a clearer understanding of the requirements for selective inhibition of AR, blocking its pathological impact while preserving its physiological functions. By integrating fragment screening and structural biology, we outline a strategy to reinvigorate AR modulation as a viable retina-specific approach for managing DR, with potentially broader relevance toward multiple diabetic microvascular complications. Full article

Background: Dysglycemia remains a persistent challenge in hospital care. Despite advances in outpatient diabetes technology, inpatient insulin management largely depends on intermittent point-of-care glucose testing, static insulin dosing protocols and rule-based decision support systems. Artificial intelligence (AI) offers potential to transform this care through predictive modeling and adaptive insulin control. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines, a scoping review was conducted to characterize AI algorithms for insulin dosing and glycemic management in hospitalized patients. An interdisciplinary team of clinicians and engineers reached consensus on AI definitions to ensure inclusion of machine learning, deep learning, and reinforcement learning approaches. A librarian-assisted search of five databases identified 13,768 citations. After screening and consensus review, 26 studies (2006–2025) met the inclusion criteria. Data were extracted on study design, population, AI methods, data inputs, outcomes, and implementation findings. Results: Studies included ICU (N = 13) and general ward (N = 9) patients, including patients with diabetes and stress hyperglycemia. Early randomized trials of model predictive control demonstrated improved mean glucose (5.7–6.2 mmol/L) and time in target range compared with standard care. Later machine learning models achieved strong predictive accuracy (AUROC 0.80–0.96) for glucose forecasting or hypoglycemia risk. Most algorithms used data from Medical Information Mart for Intensive Care (MIMIC) databases; few incorporated continuous glucose monitoring (CGM). Implementation and usability outcomes were seldom reported. Conclusions: Hospital AI-driven models showed strong algorithmic performance but limited clinical validation. Future co-designed, interpretable systems integrating CGM and real-time workflow testing are essential to advance safe, adaptive insulin management in hospital settings. Full article

Type 2 diabetes mellitus (T2D) affects hundreds of millions worldwide, with recent estimates indicating approximately 589 million adults living with diabetes, most with type 2 disease. Beyond classical insulin signaling pathways, increasing evidence implicates altered protein glycosylation in metabolic dysfunction. The solute carrier 35 (SLC35) family of nucleotide sugar transporters mediates the import of activated sugars into the endoplasmic reticulum and Golgi lumen, thereby influencing global glycosylation patterns. Dysregulation of these transporters can perturb glucose homeostasis, insulin responsiveness, and nutrient-sensing pathways through changes in glycosylation flux. In this review, we dissect the molecular mechanisms by which these transporters modulate glucose homeostasis, insulin signaling pathways, protein O-GlcN acylation, and broader glycosylation processes. We integrate findings from human genetic studies, rodent models, and in vitro functional analyses to characterize how altered SLC35 activity is associated with T2D and metabolic syndrome. Four members demonstrate particularly compelling evidence: SLC35B4 modulates hepatic glucose metabolism, SLC35D3 mutations impair dopaminergic signaling and energy balance, and SLC35F3 variants interact with high-carbohydrate intake to increase metabolic-syndrome risk. SLC35A3, though less studied, may influence glycosylation-dependent insulin signaling through its role in N-glycan biosynthesis. Beyond these characterized transporters, this review identifies potential metabolic roles for understudied family members, suggesting broader implications across the entire SLC35 family. We also discuss how such alterations can lead to disrupted hexosamine flux, impaired glycoprotein processing, aberrant cellular signaling, and micronutrient imbalances. Finally, we evaluate the therapeutic potential of targeting SLC35 transporters, outlining both opportunities and challenges in translating these insights into novel T2D treatments. Full article

Background: The use of continuous glucose monitoring (CGM) offers several benefits. Compared to point-of-care (POC) capillary glucose tests, user acceptability is greater, and time in the target glucose range is improved. If these advantages can be transferred from outpatient to in-patient settings, CGM could assist clinicians in making timely, proactive treatment decisions. Scope of the review: This scoping review focuses on clinical studies of CGM use in hospital settings among non-pregnant adults, with a particular focus on studies from 2023 to 2025. It examines the latest evidence and guidelines and sets out the clinical and analytical considerations involved in implementing in-patient CGM. Main findings: In-hospital CGM facilitates hypoglycemia detection, especially asymptomatic and nocturnal episodes. Data on the impact of CGM use on clinical outcomes are scarce, and most studies focus on the reliability of CGM technology rather than clinical outcomes. Several factors affect CGM accuracy in hospitals, such as medications, fluid management, and hemodynamic disturbances. Despite between-device and settings-related variability, CGM devices generally show reasonable accuracy, with Mean Absolute Relative Differences (MARDs) ranging from 10% to 23%. In-hospital CGM has also improved workflows and reduced personnel exposure in infectious disease settings. Key implementation challenges: The MARD thresholds for safe in-hospital CGM use without confirmatory POC testing and evidence-based protocols for CGM application in ICU and non-ICU settings are not yet established. Despite challenges related to implementation, including personnel training, integrating diabetes technology with electronic health records, and costs, the benefits of improved monitoring and in-patient safety make CGM use worthwhile to pursue. Full article

Microvascular complications of diabetes include retinopathy (DR), diabetic kidney disease (DKD), and neuropathy (DN), which play a crucial role in diabetes management, as they significantly impair the functionality of the patient and remain major causes of morbidity despite advances in glycaemic control. The aim of this review was to summarize multi-omics findings in DR, DKD, and DN. Multi-omics studies consist of genomic, epigenomic, transcriptomic, proteomic, and metabolomic research. These studies provided comprehensive insights into the complex mechanisms underlying microvascular complications of diabetes, such as inflammation, angiogenesis, and apoptosis in the retina, kidneys, and nervous system. They also enabled the search for emerging diagnostic, prognostic, and therapeutic biomarkers. Moreover, changes in microRNA levels were found to differentiate patients with non-proliferative and proliferative DR. In addition, different proteins and metabolites concentrations were noticed in diabetes macular oedema and tractional retinal detachment—serious complications of DR. Specific molecular signatures, such as miR-146a and miR-27 dysregulation, changes in levels of HLA-DRA, AGER, and HSPA1A proteins, and alterations in tyrosine, alanine, 2,4-dihydroxybutanoic acid, ribonic acid, myoinositol, ribitol, 3,4-dihydroxybutanoic acid, valine, glycine, and 2-hydroxyisovaleric acid, were found to be characteristic for all microvascular complications of diabetes. In the future, more studies in multi-omics are expected to help improve precision medicine approaches to treating diabetes, allowing for personalized prediction, prevention, and treatment of microvascular complications. Full article

Background/Objectives: Type 1 diabetes (T1D) is a common childhood condition with rising global incidence. Because early-onset T1D coincides with key periods of brain maturation, affected children may face neurocognitive risks. This review summarizes current evidence on the neurocognitive impact of pediatric T1D and related clinical implications. Methods: A structured search of PubMed, Scopus, and Web of Science (inception–October 2025) used combinations of terms related to T1D, cognitive outcomes, and brain imaging. Studies involving participants under 18 years that reported cognitive or neuroimaging findings were included. Results: Diabetic ketoacidosis (DKA) at diagnosis is consistently linked with acute and longer-term neurological injury, including reduced brain volume and potential persistent deficits in memory and executive functioning. Severe or recurrent hypoglycemia disproportionately affects the hippocampus, contributing to lasting learning and memory impairments. Chronic hyperglycemia is a major driver of progressive neurocognitive decline; higher HbA1c is associated with smaller brain volumes and poorer executive function, attention, and processing speed. Early-onset disease and longer duration further increase vulnerability. These neurocognitive effects translate into modest reductions in academic performance and quality of life, especially with poor glycemic control. Emerging evidence suggests that continuous glucose monitoring, insulin pumps, and hybrid closed-loop systems improve metabolic stability and may support healthier brain development. Conclusions: T1D children experience subtle but meaningful neurocognitive risks shaped by glycemic extremes and early disease onset. Routine neuropsychological monitoring, strengthened academic support, and wider use of advanced diabetes technologies may help preserve cognitive development. Larger, longitudinal neuroimaging studies are needed to guide targeted neuroprotective strategies. Full article

Background/objective: Deep learning systems (DLSs) may improve access to screening for diabetic retinopathy (DR), a leading cause of vision loss. Therefore, the aim was to prospectively compare the performance of three DLSs, Google ARDA, Thirona RetCAD^TM, and EyRIS SELENA+, in the detection of referable DR in a real-world setting. Methods: Participants with self-reported diabetes presented to a mobile facility for DR screening in the remote Pilbara region of Western Australia, which has a high proportion of First Nations people. Sensitivity, specificity, and other performance indicators were calculated for each DLS, compared to grading by an ophthalmologist adjudication panel. Results: Single field colour fundus photographs from 188 eyes of 94 participants (51% male, 70% First Nations Australians, and mean ± SD age of 60.3 ± 12.0 years) were assessed; 39 images had referable DR, 135 had no referable DR, and 14 images were ungradable. The sensitivity/specificity of ARDA was 100% (95% CI: 91.03–100%)/94.81% (89.68–97.47%), RetCAD was 97.37% (86.50–99.53%)/97.01% (92.58–98.83%) and SELENA+ was 91.67% (78.17–97.13%)/80.80% (73.02–86.74%). Conclusions: In a small, real-world service evaluation, comprising majority First Nations people from remote Western Australia, DLSs had high sensitivity and specificity for detecting referable DR. A comparative service evaluation can be useful to highlight differences between DLSs, especially in unique settings or with minority populations. Full article

Background/Objectives: Diabetes mellitus is increasingly prevalent among adults aged over 80 years; however, this population remains substantially underrepresented in clinical research on diabetes complications. This scoping review synthesises current evidence on diabetes-related complications and comorbidities in this older age group (>80 years), reported prevalence, and key evidence gaps. Methods: A systematic search of MEDLINE, Embase, and Web of Science was conducted for studies published between 1992 and 2024 reporting diabetes-related complications in individuals aged ≥80 years. Two reviewers independently screened titles, abstracts, and full texts. Data were extracted and summarised using narrative synthesis, and descriptive statistics (SPSS v29) were conducted. Results: Fifty-one studies were included, comprising 17,630,083 individuals aged ≥80 years. Macrovascular complications were most frequently reported, followed by microvascular and peripheral outcomes. Hypertension was the most reported comorbidity. Macrovascular outcomes were assessed in over 17 million individuals, while microvascular complications were studied in fewer than 400,000. Only five studies focused exclusively on adults aged ≥80 years. Reporting was also limited by retrospective designs, heterogeneity in definitions, and frequent omission of key variables, including diabetes duration, HbA1c, frailty, and cognitive status. Conclusions: There is a critical mismatch between research focus and the complications most relevant to function and quality of life in older populations with diabetes. Easily measurable yet clinically impactful outcomes, such as retinopathy, neuropathy, nephropathy, and foot disease, remain under-investigated in this cohort. Standardised, age-stratified reporting that incorporates functional and geriatric domains is needed to inform person-centred care in this expanding population. Full article

Background: Diabetic bone disease affects over 537 million people with diabetes worldwide, characterized by increased fracture risk despite paradoxically normal or elevated bone mineral density (BMD) in Type 2 diabetes. This narrative review synthesizes current evidence on pathophysiology, diagnostic approaches, and management strategies. Methods: We performed a comprehensive literature search of the PubMed, Embase, and Cochrane databases (2007–2025), prioritizing systematic reviews, meta-analyses, large-scale population studies, and clinical trials examining bone health in diabetes, including bone density, quality, fracture risk, imaging techniques, biomarkers, and therapeutic interventions. Results: Advanced glycation end products fundamentally alter bone metabolism through mechanisms distinct from traditional osteoporosis. Type 1 and Type 2 diabetes produce contrasting skeletal phenotypes requiring tailored management. Recent umbrella reviews of 71 meta-analyses demonstrated skeletal benefits of metformin and GLP-1 receptor agonists, while confirming thiazolidinedione risks. Trabecular bone score enhances fracture prediction when DXA appears normal. Large-scale studies revealed heterogeneous risk patterns, with specific subgroups showing substantially elevated fracture risk. Advanced imaging revealed distinct microarchitectural changes between diabetes types. Diabetic patients experienced doubled healing complications, necessitating specialized perioperative protocols. Conclusions: Diabetic bone disease represents a distinct clinical entity requiring enhanced diagnostic strategies beyond traditional densitometry, evidence-based treatment selection considering skeletal and metabolic effects, and specialized management protocols extending beyond conventional osteoporosis care. Full article

Background: Diabetic foot ulcers (DFUs) carry high risks of infection, amputation, and mortality. We systematically reviewed randomized controlled trials (RCTs) of negative-pressure wound therapy (NPWT), including single-use systems, for clinically uninfected DFUs (with sensitivity analyses for mixed/infected cohorts). Methods: We searched PubMed and Scopus (1 January 2004–30 June 2024). Dual reviewers performed screening and extraction; risk of bias was assessed with Cochrane Risk of Bias 2 (RoB 2) and certainty of evidence with GRADE. When ≥2 trials reported comparable outcomes, we used random-effects meta-analysis. The DiaFu cohort reported in two publications was counted once across analyses. Results: Eleven RCT publications (n = 1699; 10 unique cohorts) met criteria; eight trials (n = 1456) informed the primary endpoint. Trials largely excluded severe ischemia; findings therefore apply mainly to neuropathic or mixed-etiology DFUs with adequate perfusion. NPWT increased complete healing at 12–16 weeks (risk ratio [RR] 1.46, 95% CI 1.21–1.76; I² = 48%) and shortened time to healing (mean difference –18 days, 95% CI −28 to −8). Effects were similar for conventional and single-use NPWT. Outcomes did not vary systematically within commonly used pressure ranges (approximately −80 to −125 mmHg). Only two RCTs reported direct cost data (exploratory). Moderate heterogeneity (Higgins’ I² 48–68%) reflected variation in ulcer severity, device type/settings, dressing-change frequency, and off-loading protocols. Conclusions: NPWT probably improves short-term healing of clinically uninfected DFUs compared with standard care and may reduce minor amputations, without increasing adverse events. Certainty is moderate for healing and low for most secondary outcomes. Benefits appear consistent across device classes and may support earlier discharge and community-based care. Evidence gaps include ischemia-dominated ulcers, long-term outcomes (recurrence and limb preservation), adherence mechanisms, and contemporary cost-effectiveness. Full article

By 2045, approximately 783.2 million people are projected to be diagnosed with type 2 diabetes mellitus (T2DM). In addition, obesity is expected to affect up to 22% of the world’s population or one in four people. The diabesity epidemic, a worrying trend in which T2DM and obesity co-occur, is becoming increasingly evident and could be the most significant epidemic of non-communicable chronic diseases in human history. The salutogenic pattern of health, which emphasises well-being and resistance resources, could be a promising solution to address this alarming worldwide problem. The salutogenic pattern of health has numerous positive effects on the health of persons with T2DM. These include reducing the risk of it, lowering some biomarkers and laboratory parameters related to its control, and promoting a better lifestyle, ultimately improving the overall quality of life. The salutogenic pattern of health offers an effective and evidence-based approach to address the growing global problem of chronic non-communicable diseases such as T2DM. Integrating this theory into standard modern medical practice has the potential to significantly improve health outcomes and overall patient well-being, making it an important direction for modern medicine. Accordingly, the aim is to explore and analyse the salutogenic pattern of health associated with T2DM in order to prevent it, but also the better management of it. Full article

Background/Objectives: The relationship between diabetes and pancreatic cancer (PCa) is controversial. In this meta-analysis and systematic review, we investigated diabetes and time since diagnosis as risk factors for PCa. Methods: Cohort and case-control studies were retrieved through a literature search. RevMan 5.4 software and a random effects model were used to estimate summary risks with their 95% confidence intervals (CIs), and the Newcastle–Ottawa Scale (NOS) was used to assess study quality. Results: Included were 23 studies representing 30,875,355 participants and 86,980 cases of PCa. The summary risk for the 14 case-control studies was 2.30 (95% CI: 2.03–2.62) and for the 9 cohort studies was 2.39 (95% CI: 2.09–2.73). The risk decreased with time after diabetes diagnosis: 3.27, 2.25, 1.55, and 1.12 for <2, 2–5, 5–10, and >10 years, respectively, in the case-control studies. The cohort studies also showed an increased risk of PCa in the first 2 years (4.29) and a decrease over time. Quality scores according to the NOS were 6–9 (good and fair quality), for an overall average of 7.82. Conclusions: Diabetes is a risk factor for PCa and this risk is much higher in the 2 years following diabetes diagnosis. In this period, the subgroup of patients who, through clinical follow-up and/or cancer screening, would have better clinical outcomes should be identified. Bearing in mind the poor survival rate for PCa, diabetes interventions focused on preventing onset and delaying progression via modifiable risk factors to reduce PCa incidence. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as cornerstone therapies for type 2 diabetes mellitus and obesity, offering significant cardiovascular and renal protection. However, recent evidence has sparked interest and concern regarding their potential ocular effects. This review critically synthesizes current data on the impact of GLP-1RAs on diabetic retinopathy (DR), nonarteritic anterior ischemic optic neuropathy (NAION), age-related macular degeneration (AMD), and glaucoma or ocular hypertension. While preclinical studies suggest GLP-1RAs exert anti-inflammatory and neuroprotective effects in retinal tissues, clinical data remain mixed. Several large observational studies suggest a protective role against DR and glaucoma, while others raise safety concerns, particularly regarding semaglutide and NAION. Evidence on AMD is conflicting, with signals of both benefit and risk. We also discuss plausible pathophysiological mechanisms and the relevance of metabolic modulation on retinal perfusion. Overall, while GLP-1RAs hold promise for ocular protection in some contexts, vigilance is warranted, especially in patients with pre-existing eye disease. Further ophthalmology-focused prospective trials are essential to clarify long-term safety and guide clinical decision making. Full article

Background/Objectives: Understanding prescribing patterns for type 2 diabetes mellitus, a complex condition affecting over 10% of the global adult population, can optimise prescribing practices, guide policymakers in promoting evidence-based medicine, and help tailor first-line treatments to individual characteristics or specific subgroups, improving patient outcomes. This study aimed to identify factors influencing the prescription and non-prescription of metformin, the recommended first-line therapy in Western guidelines, and to evaluate whether these prescribing patterns align with evidence-based recommendations. It also explores factors associated with initial combination therapy, a more recent and controversial approach compared to stepwise therapy. Methods: We conducted a systematic search in PubMed, Scopus, and Web of Science on 25 August 2023, without language or time restrictions, to identify observational analytical studies assessing factors associated with the initiation of metformin or combination therapy in adults with type 2 diabetes mellitus who were naïve to antidiabetic medications. Studies involving pregnant or breastfeeding women were excluded. A narrative synthesis was conducted. Study quality was assessed using the Joanna Briggs Institute critical appraisal checklists (PROSPERO registration number CRD42023438313). Results: Thirty studies were included, evaluating 105 variables, most of which (62%) were assessed in one study. The 25 variables using combination therapy as the outcome were mostly (72%) evaluated also in one study. Initial metformin prescription was strongly and positively associated with younger age, lower glycated haemoglobin levels, higher body mass index, and absence of renal impairment. Initial combination therapy was associated with higher HbA1c levels and a lower burden of comorbidities. Findings also highlighted a discrepancy between clinical practice and evidence-based recommendations. However, concerns were raised regarding both the internal and external validity of the included studies. Conclusions: Our systematic review, which offers insights into real-world clinical practices, indicated that there is a misalignment between clinical practices and evidence-based recommendations, supporting the need for interventions in this field. Full article

Background/Objectives: Accurate blood glucose forecasting is critical for closed-loop insulin delivery systems to support effective disease management in people with type 1 diabetes (T1D). While long short-term memory (LSTM) neural networks have shown strong performance in glucose prediction tasks, the relative performance of individualized versus aggregated training remains underexplored. Methods: In this study, we compared LSTM models trained on individual-specific data to those trained on aggregated data from 25 T1D subjects using the HUPA UCM dataset. Results: Despite having access to substantially less training data, individualized models achieved comparable prediction accuracy to aggregated models, with mean root mean squared error across 25 subjects of 22.52 ± 6.38 mg/dL for the individualized models, 20.50 ± 5.66 mg/dL for the aggregated models, and Clarke error grid Zone A accuracy of 84.07 ± 6.66% vs. 85.09 ± 5.34%, respectively. Subject-level analyses revealed only modest differences between the two approaches, with some individuals benefiting more from personalized training. Conclusions: These findings suggest that accurate and clinically reliable glucose prediction is achievable using personalized models trained on limited individual data, with important implications for adaptive, on-device training, and privacy-preserving applications. Full article

Oxidative stress and chronic low-grade inflammation are recognized key drivers of diabetic complications. Lysosomal dysfunction, cellular senescence, and inter-organ stress signaling further aggravate the Redox–Inflammation–Organ Stress Axis in type 2 diabetes mellitus (T2DM). Recent studies suggest that reactive oxygen species (ROS) are not always harmful. Through mitohormesis, mild and transient increases in ROS levels can trigger antioxidant defenses, strengthen mitochondrial function, and limit chronic inflammation. Evidence from caloric restriction, exercise, and ketone body studies supports this adaptive redox balance, underscoring the importance of maintaining a “hormetic window” rather than indiscriminate antioxidant supplementation. In our prospective study, sodium-glucose cotransporter 2 inhibitor treatment significantly reduced albuminuria and serum levels of inflammatory markers, e.g., tumor necrosis factor receptors 1 and 2, while paradoxically increasing urinary 8-hydroxy-2′-deoxyguanosine levels and biological antioxidant potential (BAP), suggestive of adaptive ROS responses consistent with mitohormesis. Concomitant glucagon-like peptide-1 receptor agonist use emerged as an independent explanatory factor for increased urinary levels of oxidative stress markers, suggesting that multiple metabolic therapies converge on shared hormetic pathways. Emerging evidence that stressed adipocytes can communicate mild ROS signals via extracellular vesicles expands this paradigm to inter-organ mitohormesis. Collectively, these insights caution against indiscriminate antioxidant use and underscore the therapeutic potential of controlled redox modulation to disrupt the vicious cycle of senescence, inflammation, and organ stress. Incorporating redox biomarkers like urinary 8-hydroxy-2′-deoxyguanosine, reactive oxygen metabolite derivatives, and BAP into clinical monitoring, alongside pharmacological and lifestyle interventions, may facilitate the realization of precision metabolic medicine for multi-organ protection in T2DM. Full article

Objectives: This study sought to understand dietary behaviors among US Muslim people with Type 2 diabetes while managing diabetes and fasting during Ramadan, identify key psychosocial factors influencing behaviors, and examine how identified factors influence diet behaviors and health outcomes from the patient’s perspective. Methods: The study employed community-engaged research principles and qualitative research design. Twenty-two adult Muslim adults living with Type 2 diabetes for over 6 months participated in semi-structured one-on-one interviews. Participants were recruited from five US communities using purposive sampling. Three trained researchers used abductive coding, combining deductive and inductive approaches, to analyze the data. Results: Six main themes emerged from the data: (1) changes in dietary habits during Ramadan; (2) strong influence of religious, cultural and social practices on dietary behaviors; (3) variable self-efficacy in managing dietary behaviors; (4) impact of prior habits and current blood glucose status; (5) decision-making based on diabetes-related health outcomes (e.g., experiencing low blood sugar); (6) participants’ perception of Ramadan as an opportunity for sustainable behavioral changes. Conclusions: This study is among the first to document the dietary behaviors and key psychosocial factors influencing dietary behaviors and health outcomes for US Muslim people with Type 2 diabetes during Ramadan. The study suggests that interventions to improve diabetes control and promote diabetes remission among Muslims can benefit from cultural tailoring that draws on Ramadan religious, cultural and social practices to encourage sustainable behavioral change. Full article

Background/Objectives: Type 2 diabetes (T2D) is associated with elevated cardiovascular risk and mortality. While physical activity can reduce cardiovascular risk, sustaining behavioral change remains challenging. Wearable activity trackers offer a scalable approach to promote physical activity, but their effects on cardiovascular outcomes in adults with T2D have not been well studied. To evaluate the impact of a wrist-worn activity tracker on physical activity, cardiovascular markers, and metabolic outcomes in adults with T2D over four weeks. Methods: This pilot randomized controlled trial included eight adults with T2D (mean age 54.9 ± 12.6 years; intervention (FIT) group: n = 5; control (CON) group: n = 3). The intervention group received an activity tracker. Both groups used the Fitbit app to track daily activity. Physical activity metrics (steps, walking distance, energy expenditure) and cardiovascular markers (blood pressure, augmentation index, pulse wave velocity, subendocardial viability ratio [SEVR]) were assessed pre- and post-intervention. Non-parametric tests and Spearman correlations were used due to the small sample size. Results: The FIT group showed significant increases in walking distance and energy expenditure and reductions in systolic/diastolic blood pressure, pulse pressure, and mean arterial pressure (all p < 0.04). SEVR trended toward improvement (p = 0.07). No significant changes were seen in the CON group. Increased physical activity was strongly correlated with reductions in pulse pressure (ρ = −0.88) and fasting glucose (ρ = −0.82; both p < 0.05). Conclusions: A brief wearable-based intervention improved physical activity and cardiovascular markers in adults with T2D, supporting feasibility for diabetes care. Full article

Background/Objectives: Multimorbidity, where patients have ≥2 comorbidities, is recognized as a major challenge for health systems worldwide, driving up morbidity and cost. The differences in multimorbidity burden between those with and without type-2 diabetes mellitus (T2DM) in the Veteran population are not well studied. This large retrospective cohort study fills the existing gap. Methods: Using a retrospective cohort of adult Veterans with and without T2DM, we examined 29 comorbidities defined by Elixhauser criteria for 10,499,394 Veterans from 1 January 2008 to 31 December 2009. We then ascertained diabetes status for 10 years of follow-up from 1 January 2010 to 31 December 2019. Multimorbidity status was categorized using the Elixhauser comorbidity index (0, 1, ≥2) and logistic regression was used to estimate the odds ratio (OR) for its association with risk of diabetes, adjusting for covariates. Results: Compared to those with zero comorbidities, the odds of having diabetes were more than doubled (2.53, CI: 2.51–2.54) for those with ≥2 comorbidities. Conclusions: The doubling of the odds of T2DM among those with more than one comorbidity is typical of Veterans with T2DM. In addition, the odds were significantly higher for Hispanics compared to other groups when adjusting for covariates. This calls for more attention to reduce the risk of T2DM through improved management and effective use of treatments informed by disparities that exist in the VHA. Full article

Youth-onset type 2 diabetes (T2D) is a growing public health challenge. This narrative review aims to provide a comprehensive overview of epidemiology, pathophysiology, diagnosis, complications, and therapeutic strategies in children and adolescents with T2D, highlighting the most recent evidence and the distinctive features that differentiate youth-onset from adult-onset disease. Over recent decades, its incidence has increased worldwide, closely linked to rising rates of childhood obesity, sedentary behavior, and socioeconomic disparities. The disease typically emerges around puberty, a period marked by physiological insulin resistance, and is influenced by a complex interplay of genetic, environmental, and developmental factors. Diagnosis can be delayed or missed due to overlapping features with type 1 diabetes and limitations in current screening tools. The clinical course is often aggressive, with early onset of microvascular and macrovascular complications. Management is particularly challenging due to the limited number of pharmacologic agents approved for pediatric use and the psychological and behavioral complexities of adolescence. While metformin remains the first-line treatment, newer therapies such as GLP-1 receptor agonists and SGLT2 inhibitors show promise in improving metabolic outcomes. In conclusion, early diagnosis, multidisciplinary management, and equitable access to effective therapies are essential to improve long-term outcomes in this vulnerable population. Full article

Background: The present study aims to evaluate the effectiveness of ESYSTA^® (Emperra GmbH E-Health Technologies, Germany), a CE-certified digital health application made to support insulin-treated diabetes patients to improve their disease management through better self-empowerment. Methods: To evaluate the effectiveness of ESYSTA^®, data from patients who used ESYSTA^® for at least 12 months and participated in an originally prospective one-arm study were evaluated. This study was conducted in cooperation with the German health insurance company AOK Nordost (2012–2015). From a real-world data pool of insured AOK Nordost patients, a control group was matched to mimic a controlled trial that allows the use of ESYSTA^® to be compared with standard care in the context of a disease management program (DMP). Results: The study results show significant and clinically relevant reductions in HbA1c values of at least 0.4% in ESYSTA^® users after 6 months. After 12 months, users achieved, on average, an HbA1c reduction of approximately 0.7%. These reductions are more pronounced compared to the matched control group. Conclusions: The present study shows the effectiveness of the digital health application ESYSTA^®. Using a matched control group further increased the internal and external validity of the study results. Full article

Background/Objectives: Primary liver cancer (PLC), encompassing hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), constitutes a growing global health concern. Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) and Type 2 diabetes mellitus (T2DM) represent a recurrent epidemiological overlap. Individuals with MASLD and T2DM (MASLD-T2DM) are at a higher risk of PLC. This scoping review highlights the epidemiological burden, the classic and novel pathogenetic frontiers, and the potential strategies optimizing the management of PLC in MASLD-T2DM. Methods: A systematic search of the PubMed, Medline, and SCOPUS electronic databases was conducted to identify evidence investigating the pathogenetic mechanisms linking MASLD and T2DM to hepatic carcinogenesis, highlighting the most relevant targets and the relatively emerging therapeutic strategies. The search algorithm included in sequence the filter words: “MASLD”, “liver steatosis”, “obesity”, “metabolic syndrome”, “body composition”, “insulin resistance”, “inflammation”, “oxidative stress”, “metabolic dysfunction”, “microbiota”, “glucose”, “immunometabolism”, “trained immunity”. Results: In the MASD-T2DM setting, insulin resistance (IR) and IR-induced mechanisms (including chronic inflammation, insulin/IGF-1 axis dysregulation, and autophagy), simultaneously with the alterations of gut microbiota composition and functioning, represent crucial pathogenetic factors in hepatocarcinogenesis. Besides, the glucose-related metabolic reprogramming emerged as a crucial pathogenetic moment contributing to cancer progression and immune evasion. In this scenario, lifestyle changes, simultaneously with antidiabetic drugs targeting IR-related effects and gut-liver axis, in parallel with novel approaches modulating immunometabolic pathways, represent promising strategies. Conclusions: Metabolic dysfunction, classically featuring MASLD-T2DM, constitutes a continuously expanding global issue, as well as a critical driver in PLC progression, demanding integrated and personalized interventions to reduce the future burden of disease. Full article

Background and Aim: Type 2 diabetes (T2D) continues to pose a significant public health challenge worldwide. Among therapeutic options, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have proven effective in optimizing glycemic control and improving cardiometabolic profiles. Semaglutide, now available in an oral formulation, represents a modern strategy to improve patient adherence while supporting glucose and weight regulation. This study primarily investigated the effects of oral semaglutide on key metabolic indicators and secondary endpoints included cardiovascular risk markers (blood pressure and lipid profile) and patient-reported quality of life (QoL). Study Design and Methods: A longitudinal, prospective observational study was conducted involving patients with T2D across two Italian healthcare facilities. Participants were assessed at baseline (T0) and at three subsequent intervals—6 months (T1), 12 months (T2), and 18 months (T3)—following the initiation of oral semaglutide use. Key Findings: Out of 116 participants enrolled, 97 had complete and analyzable data. Across the 18-month follow-up, significant improvements were observed in glycemic parameters, with a notable reduction in HbA1c levels (T0 vs. T3, p = 0.0028; p ≤ 0.05, statistically significant). Self-reported outcomes showed enhanced quality of life, especially in treatment satisfaction and perceived flexibility (T0 vs. T3, p < 0.001). Conclusions: Daily administration of 14 mg oral semaglutide in individuals with T2D resulted in substantial benefits in glycemic regulation, weight reduction, cardiovascular risk management, and overall patient satisfaction. These findings reinforce its potential role as a sustainable and effective option in long-term diabetes care from both a clinical and public health perspective. Full article

Background/Objectives: Physical activity is a cornerstone of diabetes mellitus (DM) management and is strongly recommended in the American Diabetes Association (ADA)’s guidelines. This study aims to investigate the self-reported physical activity levels of individuals with DM in Germany, as well as the barriers and facilitators they encounter. Methods: Individuals with type 1 DM (T1DM) and type 2 DM (T2DM) were asked to fill out an online questionnaire that was partly based on the International Physical Activity Questionnaire (IPAQ). Results: The questionnaire was completed by 338 persons with either T1DM (57.1%) or T2DM (42.9%) (females: 56.2%, males: 42.0%, gender diverse persons: 1.8%) of all age groups (at least 18 years). In total, 80.5% of respondents were aware of the current physical activity recommendations. Among the respondents, 58% reported meeting the recommendations for endurance-type physical activity, while only 30.5% reported meeting those for strength training. The three most frequently cited barriers to physical activity were lack of time, lack of motivation and current state of health. Supporting factors included coverage of costs, availability of exercise programs in close proximity to the patient’s home and target group specific exercise programs. Conclusions: The results imply that many individuals with DM in Germany do not meet ADA’s physical activity recommendations, especially considering that self-reports often overestimate actual behavior. In particular, the actual number of individuals who regularly engage in strength training may be too low. There is a clear need to better communicate the benefits of different forms of physical training and to provide physical activity programs aligned with patients’ individual needs. Full article

According to the National Institutes of Health, approximately 465 million individuals are affected by type II diabetes mellitus (T2DM) and could benefit from managing their condition with a high-quality diet based on proper, nutrient-rich food choices. A plant-based diet not only has health benefits but also helps mitigate climate change by reducing greenhouse gas emissions, but the Mediterranean diet has the most beneficial effect on overall health. In contrast, ultra-processed foods have a negative impact on T2DM outcomes. Reviewing the nutritional profile of different meals, snacks and desserts would be helpful in enhancing their quality, strengthening the role of dietitians and doctors and protecting against T2DM complications. This approach would also increase simplification and education for consumers. The PubMed-Medline, Web of Science, Scopus and Cochrane Library databases were searched for relevant articles published up to May, from 2000 (based on publication date). The results support the need to reinforce health claims and highlight public demand for food choices while also improving patient quality of life. Full article

Background: Advanced hybrid closed-loop (AHCL) systems have improved the glycemic control in type 1 diabetes (T1D). While time in range (TIR) (70–180 mg/dL) is the standard metric, time in tight range (TITR) (70–140 mg/dL) offers a stricter assessment. Real-world comparisons using the TITR are limited. This study compared the TIR and TITR metrics between the MiniMed™ 780G and Tandem Control-IQ™ in adults with T1D. Methods: This retrospective, single-center study included 42 propensity-score-matched adults with T1D (28 MM780G users and 14 Tandem Control-IQ users), each with ≥3 months of AHCL system use. Glycemic metrics from continuous glucose monitoring (CGM) were analyzed over a 14-day period. Comparisons between groups were conducted using Mann–Whitney U tests, adjusted linear regression, and linear mixed-effects models accounting for repeated measures. Results: At three months, the MM780G users achieved significantly higher TITR (60.1% ± 12 vs. 49.5% ± 9.3; p = 0.005) and TIR (83.7% ± 7.6 vs. 72.1% ± 7.5; p < 0.001) values, along with lower glucose variability, compared to these values in the Tandem Control-IQ users. The linear regression model confirmed that the MM780G was independently associated with a higher TITR (β = 14.2; p = 0.005). Mixed-effects modeling for the TIR showed a significant interaction between timepoint and device type (β = 4.81; p = 0.006), favoring the MM780G. Conclusions: In this real-world analysis, both AHCL systems improved glycemic control, but the MiniMed 780G could be associated with a superior performance in achieving tighter glucose targets without increasing hypoglycemia. TITR may serve as a valuable complementary metric alongside TIR in evaluating AHCL systems’ effectiveness. However, these findings should be interpreted cautiously due to limitations such as the retrospective design, small sample size, potential residual confounding, and lack of standardization in the device settings. Further studies are warranted to confirm these results and assess their generalizability. Full article

Background/Objectives: This study aimed to evaluate adipose tissue dysfunction, assessed through adipocytokines and proinflammatory cytokines, in relation to hepatic steatosis (HS) in patients with newly diagnosed type 2 diabetes (T2D). Methods: An observational study evaluated 155 consecutive patients with new-onset T2D; 118 (76.1%) were found to have HS, while the remaining 37 served as the control group without steatosis. Anthropometric status and body mass index (BMI) were evaluated. The biochemical assessment encompassed the measurements of fasting serum lipids, fasting plasma glucose (FPG), liver function tests, adiponectin, leptin, resistin, tumor necrosis factor (TNF-α), and interleukin 6 (IL-6). Insulin resistance (IR) was determined using the homeostasis model assessment (HOMA). HS was evaluated using ultrasonographic criteria. Quantitative evaluation of HS was performed by calculating the hepatic steatosis index (HSI). Results: There were statistically significant differences between the groups for age, BMI, weight, waist circumference (WC) and hip circumference, HSI, glucose profile (fasting plasma glucose (FPG), HOMA-IR), liver function tests, adiponectin, leptin, resistin, TNF-α, and IL-6. In multivariate logistic regression analysis, age, smoking, BMI, WC, HOMA-IR, and hypoadiponectinemia were the only independent factors associated with HS. Conclusions: The adipose tissue dysfunction assessed through adipocytokines and proinflammatory cytokines is part of the associated disorders in HS and new-onset T2D. In patients with newly diagnosed T2D, age, smoking, and hypoadiponectinemia consistently emerged as independent predictors of hepatic steatosis. More prospective trials are needed to clarify the “the temporal onset” of adipose tissue dysfunction. Full article

Background/Objectives: Hypoglycemia remains the most frequent acute complication of diabetes, particularly among insulin-treated patients, with significant implications for morbidity, length of hospital stay, and healthcare costs. Nurses play a critical frontline role in its recognition and management, yet their competence varies widely. This study aimed to assess the knowledge and attitudes of Croatian nurses regarding hypoglycemia management and to identify key demographic and professional predictors. Methods: We conducted a cross-sectional online survey following CHERRIES guidelines of 317 nurses across Croatia using a validated 26-item knowledge test and a 6-item attitude scale. Descriptive statistics, Mann–Whitney U tests, and standardized effect sizes were used to assess group differences. Multivariable logistic and linear regression models examined the independent effects of education, sex, experience, and workplace setting. Results: The mean knowledge score was 66.9% (SD = 17.8), and the mean attitude score was 3.42 (SD = 0.70) on a 5-point scale. Nurses with tertiary education had significantly higher odds of achieving adequate knowledge (OR = 68.3, 95% CI: 19.9–234.2) and more favorable attitudes (β = +1.02, p < 0.001). Female sex had a small independent effect on knowledge (OR = 2.59, 95% CI: 1.02–6.62), while experience and workplace setting were not significant predictors. Conclusions: Although overall knowledge and attitudes were moderately positive, substantial disparities persist, particularly across educational levels. Clinical Practice Implications: These findings support integrating structured hypoglycemia training into nursing curricula and in-service programs to improve patient safety. Full article

Background/Objectives: DEXCOM™ continuous glucose monitoring devices (DCGMs) have been shown to improve glycaemic control and complication rates in people with Type 1 diabetes (T1DM). However, little qualitative data exists regarding user satisfaction, useful features and the overall lived experience of using a DCGM which will strongly impact one’s quality of life (QOL), compliance and the self-management of diabetes. This study aimed to assess DCGM users’ satisfaction rates and experiences with device features in patients with T1DM in Ireland. Methods: A questionnaire consisting of open- and closed-ended questions together with a glucose monitoring satisfaction survey (GMSS) was offered to all patients attending Sligo University Hospital (SUH) diabetes clinic who used a DCGM for at least six months. Results: Data was analysed for 73 participants. Self-reported QOL improved in 88% of participants and 52% of participants reported fewer hypoglycaemic events. The features most liked by participants were alerts given when the glycaemic target was not in range, improved quality of life, improved hypoglycaemia awareness and the need for reduced finger pricking. However, concerns were also identified about redundant alarms and sensor failures, phone incompatibility and skin reactions. DCGM was associated with good levels of glucose monitoring satisfaction with an overall satisfaction score of 3.67 ± 1.24 out of 5. Participants reported high openness (4.01 ± 0.91), increased trust (3.77 ± 1.16) and low emotional (1.70 ± 0.97) and behavioural burden (2.38 ± 1.10) with DCGM usage. Male participants who had diabetes for a mean duration of 20.06 ± 0.89 years and used DEXCOM^TM for approximately 2 years demonstrated significantly higher levels of satisfaction (p < 0.05). Conclusions: The findings of this study provide a first exploration of patients’ perspectives on DCGM devices in an Irish setting. Results suggest that DCGM users are highly satisfied with the device with an increase in self-reported QOL. Adaptations to features based on patient feedback should be considered to further enhance user satisfaction and maximise QOL benefits. Full article

Background/Objective: The body roundness index (BRI) has emerged as a novel anthropometric parameter with potential utility in the assessment of obesity and its associated metabolic complications. This study aimed to identify the optimal BRI cut-off point for the diagnostic process of metabolic syndrome (MetS) in a cohort of postmenopausal women with obesity and to compare its predictive capacity with that of the homeostasis model assessment of insulin resistance (HOMA-IR). Methods: A cross-sectional analysis was conducted in 468 Caucasian postmenopausal women with obesity. Clinical and biochemical assessments included anthropometric measurements, blood pressure, fasting plasma glucose, insulin levels, the HOMA-IR, lipid profile, C-reactive protein, and adipokines. MetS was diagnosed according to the Adult Treatment Panel III (ATP III) criteria. Results: MetS was identified in 270 patients (57.5%). Stratification by the median BRI revealed that individuals in the higher-BRI group had a significantly increased odds of MetS (OR 2.65; 95% CI: 1.99–3.53; p = 0.03). A Receiver Operating Characteristic (ROC) curve analysis showed that the HOMA-IR had an area under the curve (AUC) of 0.72 (95% CI: 0.67–0.77; p = 0.01), with a cut-off value of 2.64 (sensitivity: 64.9%; specificity: 69.7%). In contrast, the BRI exhibited a higher AUC of 0.75 (95% CI: 0.71–0.80; p = 0.001), with an optimal cut-off of 8.15, demonstrating superior sensitivity (85.6%) and specificity (72.5%). Conclusions: The BRI is a promising and practical alternative anthropometric index for identifying MetS in Caucasian postmenopausal women with obesity. Its strong association with markers of adiposity and metabolic dysregulation underscores its potential value in clinical and epidemiological settings. Full article

Type 1 diabetes mellitus (T1D) is increasingly recognised not only as an autoimmune metabolic disorder but also as a condition associated with accelerated biological ageing. Among the hallmarks of ageing, telomere shortening has emerged as a key feature, driven by multiple molecular pathological pathways linked to T1D onset and progression. This review explores the molecular mechanisms contributing to telomere attrition in T1D, including cytokine-induced β-cell damage, ROS-mediated DNA damage, impaired mitochondrial dynamics, and dysregulated DNA damage response pathways. Empirical evidence supports a consistent association between shortened telomeres and T1D, vascular complications, nephropathy, and mortality in T1D patients. Furthermore, the bidirectional relationship between telomere biology and immune-metabolic stress suggests novel directions for intervention. Understanding these pathways may enhance the predictive value of telomere length as a biomarker and inform targeted therapeutic strategies aimed at mitigating premature ageing and disease progression in T1D. Full article

Background/Objectives: Hormonal fluctuations during the menstrual cycle can affect glycemic control in women with type 1 diabetes (T1D), especially during the luteal phase, when increased insulin resistance may lead to prolonged hyperglycemia. Advanced Hybrid Closed-Loop (AHCL) systems could help manage these hormone-driven fluctuations. This study aimed to assess glycemic control across menstrual phases and explore the role of AHCL systems in counteracting the related glucose variability. Methods: A retrospective study was conducted including women with T1D and regular menstrual cycles (study group) and women on estroprogestin therapy (control group). Each group was subdivided by insulin delivery method (AHCL vs. non-AHCL). Glycemic metrics and insulin requirements were compared between the follicular and luteal phases, and between groups. Results: The study included 94 women (62 in the study group, 32 in the control group). In the study group, glycemic control worsened during the luteal phase, with increased average glucose, glycemic variability, and time above range > 250 mg/dL (+0.93%, p = 0.03) and reduced time in range 70–180 mg/dL. These changes were more pronounced among AHCL users, who also showed a significant increase in bolus insulin. No phase-related differences were observed in the control group or among non-AHCL users. Significantly higher insulin needs during the follicular phase were found in the study group compared with the controls. Conclusions: This study confirmed a worsening in glycemic control in women affected by T1D during the luteal phase of the menstrual cycle, suggesting a need for more tailored management. The clear efficacy of AHCL systems in counteracting hormone-related glycemic fluctuations has not been proved, highlighting the need for further research in larger, more homogeneous cohorts. Full article

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1 RAs) have transformed disease management, particularly in diabetes and obesity. However, recent shortages have disrupted patient care. This review explores the current evidence regarding their direct impact on patient populations and reviews the mitigation strategies recommended by relevant health organizations. Materials and Methods: We systematically searched PubMed, Scopus, and Web of Science for studies published from the earliest available data to 10 January 2025, using these terms: “GLP-1 AND shortage”, “liraglutide AND shortage”, “dulaglutide AND shortage”, “semaglutide AND shortage”, “exenatide AND shortage”, and “tirzepatide AND shortage”. Eligible studies needed to report measurable outcomes like prescription counts, specific laboratory findings, or the proportion of a study population achieving a defined outcome related to the shortage. Only English-language clinical research was considered, while other manuscripts were not included. The risk of bias was assessed using the Critical Appraisal Skills Programme checklist. Study characteristics and findings were summarized in tables. Results: Out of 295 identified manuscripts, 85 works were retained for further screening. Consequently, 8 studies met the inclusion criteria, covering 1036 participants with type 2 diabetes and 573 treated for obesity. In addition, two studies reported prescription prevalence, and one examined prescription counts. Key findings included reduced prescription rates and shifts in treatment practices. No studies assessed impacts on cardiovascular, renal outcomes, or mortality. Discussion and Conclusions: Evidence on the health effects of these shortages is limited. Existing studies highlight disruptions in diabetes and obesity care, but broader impacts remain unclear. Preventing future shortages requires coordinated efforts among all stakeholders. Therefore, we advocate for ethical planning, sustainable production, and fair distribution strategies to mitigate long-term consequences. Full article

The Glycemia Risk Index (GRI) aims to summarize the overall quality of a patient’s glycemic control in a single number, and it is calculated from the hypo- and hyperglycemia times from continuous glucose monitoring, weighted by coefficients. Despite its recent appearance in 2022, this new parameter has strong international support, with almost half a hundred indexed articles already incorporating this metric into their studies. The following is a breakdown of the main papers that have used GRI, divided according to the type of treatment used, the population studied, the type of diabetes, its association with other parameters, and its relationship with chronic complications and the quality of life of people living with diabetes. Full article

Cellular senescence, a phenomenon characterized by the accumulation of dysfunctional, metabolically active cells, is increasingly recognized to be a key player in aging-related metabolic disorders. It is accelerated by hyperglycemia through various molecular pathways, positioning it as a critical mechanism in the pathophysiology of type 2 diabetes mellitus (T2D) and a potential therapeutic target. Emerging evidence from animal and clinical studies suggests that the usage of senolytic drugs, which selectively deplete senescent cells, can improve blood glucose regulation and mitigate diabetic complications. However, despite the conceptual feasibility of this approach, several challenges remain in their translation to the clinic: the molecular mechanisms underlying the pathogenicity of cellular senescence in vivo remain incompletely understood, and organ-specific effects of senolytic administration are yet to be fully elucidated to ensure their safety and efficacy in clinical applications. This review explores the characteristics of cellular senescence and the senescence-associated secretory phenotype (SASP) in key tissues involved in glucose homeostasis, including the pancreas, liver, adipose tissue, and skeletal muscle and the potential applications of targeting cellular senescence as a therapeutic strategy for T2D management. Full article

The global prevalence of obesity and type 2 diabetes has increased considerably in recent decades, primarily due to behavioral changes associated with societal progress, such as increased consumption of high-calorie foods and sedentary lifestyles. Obesity is a disease of the energy homeostasis system, not merely a passive accumulation of fat. The hypothalamus serves as the regulatory center for energy balance, and together with peripheral organs, such as liver, pancreas, muscle and adipose tissue, controls food intake, energy expenditure, and whole-body metabolism. Adenosine, a product of ATP catabolism, exerts its effects through various G-protein-coupled receptors: A1R, A2AR, A2BR, and A3R. It plays a key role in regulating peripheral metabolism, including glucose homeostasis, insulin sensitivity, fat beta-oxidation, and lipolysis in adipose tissue. Beyond its roles in the CNS, adenosine receptors are also crucial in metabolic tissues, where they regulate glucose and lipid homeostasis and contribute to overall metabolic function. Several studies have been analyzing the role of adenosine system, specifically the adenosine receptors in the regulation of whole-body metabolism, and the importance of adenosine receptors in context of metabolic diseases and obesity. In this review, we provide an overview of the adenosine signaling system, highlighting its role in metabolic regulation as well as the pathophysiological mechanisms underlying obesity and type 2 diabetes. Full article

Thyroid disorders (TDs) and diabetes mellitus (DM) represent significant metabolic pathologies with an important global burden. Diabetes, characterized by chronic hyperglycemia, induces widespread dysregulation of lipid, protein, and carbohydrate metabolism. The thyroid gland, a central regulator of endocrine homeostasis, modulates metabolic processes through the secretion of thyroid hormones (THs). A complex bidirectional relationship exists between type 2 diabetes mellitus (T2DM) and thyroid dysfunction, wherein each condition may exacerbate the pathophysiological consequences of the other. At the core of this interplay lies insulin resistance (IR), a fundamental mechanism underlying their coexistence and mutual aggravation. A thorough investigation into the underlying mechanisms of thyroid function could reveal new insights into the development and progression of T2DM. Grasping the clinical correlation between these widespread endocrine disorders is crucial for customizing treatments for individuals confronting both conditions. This narrative review seeks to offer an understanding of the epidemiological, pathophysiological, and clinical dimensions of the relationship between TD and T2DM. Considering the substantial clinical ramifications of concurrent T2DM and TD, it is imperative to institute suitable screening and management approaches for both endocrine disorders to guarantee optimal care for patients. Full article

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, impulsivity and/or hyperactivity. In recent years, metabolic alterations, primarily obesity, insulin resistance, and diabetes, have emerged as frequent comorbidities in individuals with ADHD, suggesting a bidirectional relationship between neurodevelopmental and metabolic dysfunctions. Emerging evidence indicates that dysregulation of dopaminergic signaling, disturbances in the hypothalamic-pituitary-adrenal (HPA) axis, and chronic low-grade inflammation are central to both ADHD symptomatology and metabolic impairments. For instance, alterations in dopamine-related genes (e.g., DRD4, DAT1) not only affect cognitive and behavioral functions but also play a role in appetite regulation and glucose homeostasis. Epidemiological studies further demonstrate that individuals with ADHD exhibit poorer glycemic control and a higher prevalence of both type 1 and type 2 diabetes, while early-life metabolic challenges such as maternal diabetes may predispose offspring to ADHD. This review aims to comprehensively synthesize the epidemiological, genetic, and pathogenetic evidence linking ADHD to metabolic alterations. We discuss key pathophysiological pathways—including dopaminergic dysregulation, HPA axis disturbances, inflammation, and oxidative stress—and evaluate their contributions to the co-occurrence of ADHD and metabolic disorders. In addition, we explore the clinical implications and integrated treatment approaches that encompass lifestyle modifications, pharmacological therapies, and multidisciplinary care. Finally, we outline future research directions to develop personalized and holistic interventions. Full article

Background: Among individuals with type 2 diabetes (T2D), cardiovascular disease (CVD) is the leading cause of death, demanding prevention approaches. Exercise is a powerful option for non-pharmacological strategies to improve cardiovascular outcomes. This systematic review aims to evaluate the effects of aerobic, resistance, and combined training on CVD in individuals with T2D. Methods: From 2013 through the end of 2023, PubMed, Scopus, and Web of Science were systematically searched for articles. The studies included 15 articles lasting at least eight weeks and involving 1794 participants each. The cardiac events measured were blood pressure, lipid levels, heart rate variability (HRV), and inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6). Results: Aerobic training reduced systolic and diastolic blood pressure by 6 mmHg and 3 mmHg, respectively, while significantly enhancing lipid profiles, evidenced by an 8% reduction in LDL cholesterol and a 5% rise in HDL cholesterol. In addition, improvements in lean muscle mass, insulin sensitivity, and slight changes in inflammatory markers support the benefits of resistance training. The most pronounced effects emerged from combined training, which resulted in a 9 mmHg decrease in systolic blood pressure, a 6 mmHg decrease in diastolic pressure, a 10% reduction in LDL cholesterol, a 15% increase in HRV, and a 10% reduction in CRP and IL-6 levels. Conclusions: Combined training has more favorable effects on several key CVD risk factors than aerobic or resistance training alone. It can be regarded as the most effective exercise modality for decreasing CVD risk in adults with T2D. Full article

Background: Tuberculosis (TB) and diabetes mellitus (DM) comorbidity (TB-DM) presents a significant global health challenge, with diabetes increasing susceptibility to TB, worsening clinical outcomes, and impairing immune responses. Among these dysfunctions, macrophages—the primary immune cells responsible for pathogen recognition, phagocytosis, and bacterial clearance—exhibit profound alterations in TB-DM. However, the complex interplay between metabolic dysregulation, immune impairment, and macrophage dysfunction remains poorly defined. Objective: This scoping review systematically maps the literature on macrophage dysfunction in TB-DM, identifying key immunological impairments affecting phagocytosis, cytokine production, antigen presentation, macrophage polarisation, reactive oxygen species (ROS) and nitric oxide (NO) regulation, and chronic inflammation. Methods: A systematic search was conducted in PubMed, Web of Science, and Embase, covering studies from 2014 to 2024. Inclusion criteria focused on human studies investigating macrophage-specific mechanisms in TB-DM. Data extraction and synthesis were performed using Covidence, with findings grouped into key immunological themes. Results: A total of 44 studies were included, revealing significant impairments in macrophage function in TB-DM. Findings indicate reduced NO production, variable ROS dysregulation, altered M1/M2 polarisation, defective antigen presentation, and chronic inflammation. Elevated IL-10 and VEGF were associated with immune suppression and granuloma destabilisation, while eicosanoids (PGE2, LXA4) contributed to sustained inflammation. Conclusions: Macrophage dysfunction emerges as a central driver of immune failure in TB-DM, creating a self-perpetuating cycle of inflammation, immune exhaustion, and bacterial persistence. Understanding these mechanisms is essential for developing biomarker-driven diagnostics, host-directed therapies, targeted immunomodulation, and improving TB outcomes in diabetic populations. Future research should explore macrophage-targeted interventions to enhance immune function and mitigate TB-DM burden. Full article

The literature describes an increased risk of eating disorders (EDs) in patients with Type 1 diabetes mellitus (T1DM) compared to the general population. This risk is mainly related to physical and psychosocial problems related to diabetes. EDs should be carefully assessed and treated in these patients since they are associated with poor glycemic control and significant repercussions of pathology. Background/Objectives: To study the presence of EDs in young Portuguese adults and adults with T1DM, and how gender; age group; method of insulin administration; carbohydrate counting; and body mass index [BMI] variables influence the risk of developing an ED. Methods: Data collection was carried out using an online questionnaire, which was disseminated through the media of several Portuguese diabetes associations. Results: The sample consisted of 47 participants, mostly female, with the age group between 26 and 35 years being most representative. A statistically significant association was found between the Eating Attitudes Test [EAT-26] scores and the BMI of the participants [p = 0.003]; other variables did not show statistically significant differences. Conclusions: To better understand the relationship between these two pathologies, further studies are needed, as well as the development of more screening instruments to assess the risk of EDs specific to T1DM, and preventive interventions and guidelines that can assist the various areas of health that support the population with T1DM. Full article

Background: Diabetes induces osteoporosis primarily by impairing osteoblast function. Intracellular zinc homeostasis, which is controlled by zinc transporters, plays a significant role in osteoblast differentiation. In the present study, we aimed to explore the role of zinc homeostasis in the pathogenesis of diabetic bone loss using a diabetic mouse model. Methods: Streptozotocin (STZ)-induced diabetic female mice were used for in vivo experiments. In vitro, the effects of zinc transporter knockdown using small interfering RNA was investigated in MC3T3E1 pre-osteoblastic cells. Results: STZ-induced diabetic mice exhibited severe bone loss and decreased expression of osteogenic genes, as well as a decrease in zinc content and the expression of several zinc transporters localized in the cellular membrane, including Zip6, Zip9, and Zip10 in the tibia. Moreover, the messenger RNA (mRNA) levels of Zip6, Zip9, and Zip10 were positively correlated with trabecular bone mineral density in the tibiae of diabetic mice. This in vitro study, using MC3T3E1 pre-osteoblastic cells, revealed that knockdown of Zip6 reduced the expression of osteogenic genes in pre-osteoblastic cells. Additionally, Zip6 knockdown downregulated protein levels of phosphorylated p38 mitogen-activated protein kinase (p38MAPK) in pre-osteoblastic cells, and this change was observed in the tibiae of diabetic mice. Conclusions: Our data suggest that the downregulation of zinc transporters localized in the cellular membrane, such as Zip6, may be involved in the impairment of osteoblastic differentiation through the inhibition of p38 MAPK signaling, leading to osteoporosis under diabetic conditions. Maintaining zinc homeostasis in bone tissues may be vital for preventing and treating diabetic bone loss, and zinc transporters may serve as novel therapeutic targets for diabetic osteoporosis. Full article

Background/Objectives: The association between sexual dysfunctions and diabetes is largely known, but few studies investigated its prevalence in Type 1 Diabetes (T1D). The aim of this study was to evaluate the prevalence of sexual dysfunction in a group of men with T1D regardless of their age and to compare the prevalence in men treated with different intensive insulin regimens. Methods: The study population included 68 men affected by T1D, of whom 17 were on Multiple Daily Injections (MDI) and 51 were on Continuous Subcutaneous Insulin Infusion (41 on Advanced Hybrid Closed Loop System with catheters and 10 on patch pumps). All participants completed the International Index of Erectile Function (IIEF-15), which evaluates several domains of sexual function. Another questionnaire that evaluated general features, diabetes-specific features, and sexual-specific features was proposed to every participant. Results: The overall prevalence of erectile dysfunction was 48.5%, and the overall prevalence of a severe grade of erectile dysfunction was 26.5%. Correlations were demonstrated between the prevalence of erectile dysfunction and age and between the prevalence of erectile dysfunction and dyadic status. Age and dyadic status were also correlated with lower scores in several other domains of the IIEF-15 questionnaire. Conclusions: Men with Type 1 Diabetes present a high prevalence of erectile dysfunction, independent of glycometabolic control of the disease and insulin regimens; on the contrary, a great correlation is demonstrated with age and dyadic status. Full article

Background/Objectives: Glycemic control is essential for preventing both short- and long-term complications of type 2 diabetes (T2D), requiring strict adherence to pharmacological therapy. Medication adherence directly influences therapeutic effectiveness, making its assessment in clinical practice crucial. This study aimed to evaluate medication adherence in elderly patients with T2D and its association with glycemic control. Methods: A descriptive cross-sectional study was conducted in the Algarve, Portugal, involving 133 elderly patients (≥60 years) with T2D. Cardiometabolic parameters and medication adherence (global, intentional, and unintentional) were assessed. Statistical analyses were performed using IBM SPSS Statistics 28.0. Results: The study population had a mean age of 71.7 ± 5.7 years, with a predominance of male participants (57.9%) and a high prevalence of dyslipidemia and/or hypertension. Cardiometabolic control was generally poor, with only 26.3% achieving blood pressure targets (≤140/90 mmHg), 8.5% maintaining fasting glycemia within the recommended range (70–110 mg/dL), and 13.6% attaining glycated hemoglobin (HbA1c) values ≤ 7%. Despite this, medication adherence was notably high (97.7%), with no significant association with cardiometabolic control (p > 0.05). Unintentional non-adherence behaviors, such as forgetfulness and inconsistent medication schedules, were the most frequently reported. Conclusions: Although elderly patients with T2D demonstrated high medication adherence rates, their cardiometabolic control remained suboptimal. Unintentional non-adherence behaviors may contribute to poor glycemic control. However, medication adherence alone does not fully explain these outcomes, highlighting the need to assess adherence to other self-care behaviors, particularly dietary and physical activity patterns. Future interventions should integrate comprehensive lifestyle modifications alongside pharmacological management to enhance overall disease control. Full article