Diabetology

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

Objectives: To describe a structured transition model for individuals with type 1 diabetes mellitus (T1DM) from pediatric to adult care in a tertiary hospital, and to explore demographic, clinical, and psychosocial factors associated with glycemic outcomes. Research Design and Methods: We conducted an observational, cross-sectional study including all patients with T1DM who transitioned from the Pediatric Endocrinology Clinic to the Adult Endocrinology and Nutrition Unit at Virgen del Rocío University Hospital between 2021 and 2024. Demographic, clinical, biochemical, glucometric, and socioeducational variables were collected at the first adult care visit. Statistical analyses included nonparametric tests and exploratory multivariate logistic regression models. Results: A total of 73 patients (45% female) were included, with a median age of 18 years and median diabetes duration of 9 years. The 46.6% of our cohort had an HbA1c > 7.5%. Overweight and obesity were present in 25% and 8% of patients, respectively, and 11% were active smokers. Eighteen percent were receiving mental health follow-up, mainly for anxiety–depressive disorders. Those using hybrid closed-loop insulin delivery and continuous glucose monitoring achieved significantly better glycemic control (TIR 67% vs. 48%; p < 0.01) and lower glycemic variability. In exploratory multivariable analyses, continuous glucose monitoring use > 90% of the time and higher maternal educational level were associated with a lower likelihood of HbA1c > 7.5%. Conclusions: In this cross-sectional transition cohort, intensive use of diabetes technology and higher maternal educational level were associated with better glycemic control at the time of transfer to adult care. These findings should be interpreted as exploratory and hypothesis-generating, and warrant confirmation in larger, prospective studies. Full article

Background/Objectives: Physiological assessment of borderline coronary lesions is recommended by current guidelines for revascularization decision-making. The aim of our study was to assess the prognostic utility of physiological indices and determine whether their predictive value differs between patients with and without diabetes (DM). Methods: A physiological assessment was conducted in 381 patients with borderline coronary artery disease. The study cohort was divided according to the presence or absence of DM, and all individuals were followed over a four-year period. Results: Of the 381 patients, 154 (40.4%) had DM. Patients with DM had a higher BMI (30.1 kg/m² vs. 27.8 kg/m², p < 0.0001) and a lower left ventricular ejection fraction at the time of enrollment (50% vs. 55%, p = 0.0414) compared to the non-diabetic group. Patients diagnosed with DM had significantly more positive FFR results for ischemia, regardless of the assessed vessel, positive non-hyperemic evaluation of LAD and more PCI procedures, including PCI of the LAD. The mortality rate in FU among diabetics was 23.4%, while in patients without diabetes, it was 16.8%; (p = 0.1081). The clinical profile of deceased patients was largely comparable between groups. In patients with diabetes, the non-hyperemic physiological assessment by RFR/iFR (OR 0.68, 95%CI: 0.49–0.96; p = 0.0261) as well as iFR alone (OR 0.55, 95%CI: 0.32–0.97; p = 0.0388) was strongly correlated with the risk of death. In contrast to patients with DM, in the non-DM group, the non-hyperemic assessment using RFR (OR 0.37, 95%CI: 0.18–0.78; p = 0.0085) proved to be a significant prognostic factor. Conclusions: Non-hyperemic physiological indices (RFR/iFR) demonstrated a strong prognostic value in both diabetic and non-diabetic populations. Higher RFR/iFR values were consistently associated with a reduced risk of death. In the group of patients with DM, the iFR value may be considered a significant prognostic factor for long-term mortality. In the group without DM, the RFR assessment is such a factor. Full article

Background: Despite major advances in insulin formulations and delivery systems since 1921, many people with diabetes (PwDs) still fail to achieve recommended glycemic targets. Common reasons include inadequate education, injection errors, and poor adherence due to factors such as needle phobia and pain. Recognition of these barriers has driven the development of improved injection systems, particularly thinner and shorter needles. An experimental study previously identified the Pic Insupen 34 G 3.5 mm needle as high performing. We therefore conducted an observational study to assess its acceptability directly among PwDs. Methods: This multicentre, open-label, real-world study enrolled 300 insulin-treated PwDs who compared their usual pen needle (30–33 G) with the new 34 G × 3.5 mm needle over two two-week periods. The primary outcome was perceived puncture pain. Results: Participants overwhelmingly preferred the 34 G needle, based on the following findings: Pain perception: 62% of 34 G users reported minimal or no pain, compared with only 8% using their previous needle. Conversely, 22% of participants reported the highest pain score with their old needle, compared with just 5% using the 34 G. Ease of use: 77% rated the 34 G needle at the highest level of ease of use, compared with 20% for their previous needle. Complications: The 34 G needle was linked to significantly fewer hypo-/hyperglycemic episodes and local skin complications such as bruising or irritation. Eighty per cent reported no glycemic fluctuations while using the 34 G needle. Robustness: Ninety-four per cent of PwDs never observed the 34 G needle bending during use, compared with 64% using their previous needle, confirming greater robustness despite its thinner profile. Conclusions: The Insupen^® 34 G × 3.5 mm needle substantially reduces puncture pain and improves the overall manageability of insulin injections. Its innovative design—combining reduced thickness with optimised tip geometry—is associated with fewer complications and enhanced injection performance. Because reduced pain and ease of use are critical for improving adherence to insulin therapy, the features of the 34 G needle should inform future prescribing decisions. Full article

Background: Postoperative wounds may arise from several etiologies, including open partial pedal amputation, postoperative infection, and dehiscence of surgical sites from wound failure or patient compliance issues. If negative pressure wound therapy is the gold standard, its application in the toes area could be challenging, and as a consequence, standard care is most likely used. The control of the wound microenvironment, both in terms of pH levels and presence of reactive oxygen species, is a key part of the normal wound-healing process. This study evaluated the effectiveness of an oxygen-enriched oil-based device (OEOd) in post-surgical diabetic foot ulcers (DFUs). Methods: This prospective controlled comparative pilot study enrolled 40 patients with diabetes mellitus and post-surgical foot wounds (narrow and deep lesions, including tunneling ulcers) treated at the Diabetic Foot Unit of San Donato Hospital, Arezzo (March 2024–April 2025). Patients were allocated into two groups: those treated by the standard wound care (n = 20) and those treated by OEOd (n = 20). The primary outcome was complete wound healing at 16 weeks; other exploratory endpoints were wound area reduction at 4 and 16 weeks, onset of infection, need for re-intervention, and adverse events. Results: Complete wound healing was achieved in 85.0% of OEOd patients versus 45.0% in the control group (p = 0.020). At 16 weeks, wound area reduction was significantly greater in the OEOd group compared with standard therapy (89.8% vs. 64.0%, p = 0.013). Although infection rates (10.0% vs. 35.0%, p = 0.130) and need for re-intervention (0% vs. 25.0%, p = 0.056) did not reach statistical significance, both favored the OEOd group. No adverse events were reported. Conclusions: OEOd significantly improved the chance of healing post-surgery and showed favorable trends in reducing complications, with an excellent safety profile. Larger randomized controlled trials are warranted to confirm these findings and assess long-term outcomes. 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

Background: Diabetic foot infections (DFIs) are a major cause of hospitalization, limb loss, and mortality among patients with diabetic foot ulcers (DFUs). This study evaluated the risk of developing DFIs among patients with newly diagnosed DFUs across insurance categories. Methods: Adults ≥18 years with a new DFU diagnosis were identified in the PearlDiver insurance claims database (2010–2020) using validated ICD-9/10 codes. Insurance status at the index DFU was categorized as Medicaid, Medicare, commercial, or self-pay. Propensity score matching (1:3) based on age, sex, Charlson Comorbidity Index, and major comorbidities was used to compare Medicaid vs. non-Medicaid patients. Results: Among 258,122 patients with new DFUs, 20,638 (8.0%) were Medicaid beneficiaries. Medicaid patients were younger (50.1 ± 10.2 vs. 60.6 ± 12.1 years, p < 0.001) but had similar comorbidity burden compared with commercially insured and Medicare patients. In matched analysis post-matching, Medicaid insurance was independently associated with higher odds of DFI-related hospitalization within 12 months (aOR 1.18, 95% CI 1.14–1.24) and major amputation at 3 years (aOR 1.72, 95% CI 1.39–2.13). Higher CCI, chronic kidney disease, congestive heart failure, COPD, and peripheral vascular disease also predicted adverse outcomes. Conclusions: Medicaid insurance was independently associated with increased risks of DFI and major amputation among patients with newly diagnosed DFUs. These findings highlight infection as a potentially modifiable pathway driving limb loss and emphasize the need to improve early ulcer evaluation and infection management for Medicaid beneficiaries. Full article

Background: Depression is approximately twice as prevalent in type 2 diabetes (T2D) compared to non-diabetic individuals, but its underlying mechanisms remain unclear. Insulin resistance (IR) and low-grade inflammation have been proposed as potential contributors. This study investigated whether IR and inflammatory markers are associated with depression in people with T2D. Methods: This cross-sectional study included 189 participants divided into four groups: T2D with depression (A, n = 38), T2D without depression (B, n = 60), depression without T2D (C, n = 44), and healthy controls (D, n = 47). Depression was diagnosed using the MINI-6 and HAMD scale. IR was assessed using the Matsuda index and HOMA-IR, while low-grade inflammation was evaluated by high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6). Results: The Matsuda index was significantly lower in group A compared with B, C and D groups (p < 0.001). HOMA-IR was higher in A than in C and D groups, though not significantly different from group B. Hs-CRP was highest in group A (p < 0.001), with no differences among B, C and D. IL-6 was significantly higher in A than B and D (p < 0.001), and similar between A and C. In multivariable analysis younger age, lower Matsuda index, and higher IL-6 independently predicted depression in people with T2D. ROC analysis detected an AUC of 0.75 (p < 0.001) for IL-6, with a sensitivity of 57% and specificity of 82% at the cutoff of 5.29 pg/mL. Conclusions: Our findings suggest that people with T2D and depression exhibit higher IR and elevated IL-6 and hs-CRP levels as parameters of low-grade inflammation. Depression in T2D was associated with younger age, lower Matsuda ISI, and higher IL-6, highlighting the potential relevance of those metabolic and inflammatory biomarkers in this co-occurrence. Further longitudinal studies are needed to clarify causal relationships. Full article

Incretin hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are essential regulators of glucose homeostasis, energy balance, and metabolic communication between organs. While therapies based on incretins are well established for type 2 diabetes (T2DM), their physiological significance and therapeutic potential in type 1 diabetes (T1DM) are less understood. In T1DM, the autoimmune destruction of pancreatic β-cells greatly reduces but does not abolish insulin production. However, various extrapancreatic actions of incretins continue, including effects on gastric emptying, glucagon secretion, appetite, inflammation, and cardiovascular function. The increasing prevalence of overweight, obesity, and insulin resistance among individuals with T1DM has heightened interest in exploring incretin-based treatments as adjuncts to insulin therapy. Data from randomized controlled trials, retrospective cohorts, and mechanistic studies were analyzed. This narrative review synthesizes available experimental, clinical trial, and real-world evidence on the physiology of incretins, their altered actions in T1DM compared with T2DM, and the effects of GLP-1 receptor agonists (GLP-1RAs) and tirzepatide, a dual GIP/GLP-1 agonist, on glycemic control, body weight, and cardiovascular outcomes in patients with T1DM. The use of GLP-1RAs in T1DM showed a weight reduction between 3.6 kg and 8.8 kg and improved glycated hemoglobin (HbA_1c) by 0.2–0.8%, while treatment with tirzepatide for 6 months resulted in a body weight change of −10.3 to −10.6 kg. Growing evidence suggests a significant role of incretins in certain patients with T1DM, although large-scale, adequately powered randomized controlled trials are necessary to confirm their long-term efficacy and safety. Full article

Background and Objectives: The objectives of this study were to determine the prevalence of diabetes mellitus (DM) and major cardiometabolic comorbidities in adults living in El Trébol, Argentina, and to evaluate their associations using laboratory-confirmed, community-based data. Methods: A cross-sectional, probabilistic, two-phase design was implemented, combining a household survey with clinical and biochemical assessments. Of 1112 surveyed adults aged 20–79 years, 860 completed the clinical phase and formed the effective sample. Cardiometabolic risk factors, including obesity, hypertension, dyslipidemia, and physical inactivity, were assessed through standardized measurements and questionnaires. Multivariate logistic regression explored independent associations with DM. Results: Crude DM prevalence was 10.47%, higher in men and increasing markedly with age; the age-standardized prevalence for the Argentine population was 9.87%. Of all diabetes cases, 23% were previously undiagnosed. Obesity (35.62%), hypertension (38.83%), dyslipidemia, and physical inactivity (83.84%) were highly prevalent. DM was independently associated with older age, higher BMI, elevated triglycerides, lower HDL cholesterol, and insufficient physical activity. Conclusions: This study reveals a substantial cardiometabolic burden in a small urban Argentine population and suggests that self-report-based national surveys may misestimate true DM prevalence. Laboratory-confirmed, community-based surveillance is essential to strengthen early detection, guide targeted interventions, and inform equitable public health strategies. Full article

Background/Objectives: In pregnancy, beta-cell function is of interest since not only insulin resistance but also beta-cell dysfunction is common, especially when gestational diabetes mellitus (GDM) occurs. Typically, model-based beta-cell function is assessed with (at least) five-sample oral glucose tolerance test (OGTT). The aim of this study was to investigate whether the clinically common three-sample OGTT is sufficient for model-based beta-cell function assessment in pregnancy. Methods: We studied a group of pregnant women undergoing a 2 h five-sample OGTT with glucose, insulin, and C-peptide measurement at early and/or mid-pregnancy, for a total of 152 OGTTs. The five-sample OGTT was used for model-based beta-cell function assessment, yielding three beta-cell function parameters, i.e., glucose sensitivity (GSENS), potentiation factor ratio (PFR), and rate sensitivity (RSENS). GSENS, PFR, and RSENS assessment was repeated with the three-sample OGTT (at 0, 60, 120 min) and related values were compared to those from the five-sample OGTT (reference). Results: We found that, for GSENS, regression and Bland–Altman analyses showed satisfactory results (conditional and marginal R² values: 0.56 and 0.75, p < 0.0001, and limits of agreement containing 94.2% of samples). Moreover, five-sample and three-sample OGTT GSENS versions were fully consistent in patient subgroup analyses. Results for PFR were less satisfactory but acceptable, whereas those for RSENS were not reliable. Conclusions: The three-sample OGTT is acceptable for model-based beta-cell function assessment in pregnancy, although not for all parameters. Our methodology may be used to explore the effect of time sample reduction in other in-silico models. Full article

One of the most common and severe complications of diabetes mellitus is diabetic foot, making early detection a public health priority. Infrared thermography is a promising noninvasive technique for identifying abnormal thermal patterns associated with inflammation, neuropathy, angiopathy, and tissue damage. This technique involves acquiring infrared radiation emitted by the skin and processing it to generate thermal maps that reflect underlying physiological changes. However, the reliability of thermographic assessments depends on strict technical conditions, including sensor performance, environmental control, and reproducible measurements. Despite its advantages, the clinical adoption of thermography is limited by the absence of standardized acquisition protocols and the influence of external and physiological factors on temperature measurements. Addressing these challenges is essential to ensure the accurate interpretation and validation of results. Recent advances, such as the incorporation of artificial intelligence algorithms and the development of portable, low-cost devices, offer new opportunities to enhance thermography’s applicability in clinical settings and home monitoring. 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

Background/Objectives: An increasing proportion of patients with Type 2 diabetes mellitus (T2DM) are classified as high risk, often presenting with multimorbidity, functional vulnerability, and complex treatments. This study compared the sociodemographic, functional, clinical, therapeutic, and healthcare utilization profiles of high-risk chronic patients with and without T2DM in primary health care. Methods: A cross-sectional study included adults classified as high-risk chronic patients in primary health care electronic health records in the Madrid Region (30 April 2021). Sociodemographic, functional, clinical, lifestyle, pharmacological variables, and primary health care services utilization were analyzed. Multivariate logistic regression identified factors independently associated with T2DM. Results: Among 163,188 high-risk chronic patients, 41.5% had T2DM. Patients with T2DM were older, more often male, and had a comparable deprivation index values to non-diabetic patients. They showed higher functional dependency and greater need for informal caregiving. Clinically, patients with T2DM had a higher burden of chronic conditions and a predominance of cardiometabolic, hematological and renal comorbidities, whereas non-diabetic patients exhibited more neuropsychiatric, chronic infectious, oncological and respiratory profiles. Polypharmacy was more frequent in T2DM patients, who also showed lower medication adherence. In the explanatory model, older age (OR 1.02/year), cardiometabolic comorbidities (ORs ~1.2–1.6), highest quartile of morbidity complexity (OR 1.27), polypharmacy (OR 1.34), and concern about medications (OR 1.08) were associated with T2DM, while female sex (OR 0.660), depression (OR 0.888), COPD (0.704), neoplasms (0.688), and higher medication adherence (OR 0.53) were associated with not having T2DM. Conclusions: High-risk chronic patients with T2DM exhibit distinct sociodemographic, functional, and clinical profiles compared with those without T2DM, characterized by greater complexity, cardiometabolic burden, therapeutic intensity and use of healthcare services, supporting the need for tailored, integrated primary health care strategies. 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

Background: Diabetes is associated with an increased risk of oral health complications, yet adults with diabetes remain less likely to obtain dental care in the United States. Objective: To examine socioeconomic, demographic, and insurance-related determinants of dental spending among adults with and without diabetes using nationally representative 2023 Medical Expenditure Panel Survey (MEPS) data. Materials and Methods: A two-part model was estimated: (1) a logistic regression predicting the likelihood of any dental spending, and (2) a generalized linear model (GLM) with a Gamma distribution and log link for positive spending. Covariates included age, sex, race/ethnicity, education, income, region, and insurance coverage. Results: The MEPS dataset included 15,071 adults (diabetes n = 2104; no diabetes n = 12,967), Adults with diabetes were less likely to have any dental spending than adults without diabetes (38.6% vs. 43.8%). Mean expenditures among users were higher for adults with diabetes but diabetes was not a statistically significant predictor of conditional spending after adjustment. Insurance coverage and preventive care were strong positive predictors of dental spending. Conclusions: Insurance coverage and preventive dental care are major drivers of dental spending and utilization among U.S. adults. Disparities observed among adults with diabetes appear to be driven primarily by reduced access to dental care rather than differences in spending intensity once care is obtained. 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