Editor’s Choice Articles

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: 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

Diabetes mellitus constitutes a significant global public health problem. It is a chronic disease characterized by persistent hyperglycemia, which is a consequence of inadequate insulin secretion, deficient insulin action, or a combination of both factors. A crucial component in the effective management of this pathology is therapeutic adherence, as it helps prevent complications, improve patient quality of life, reduce associated mortality, and decrease the need for hospitalization. In this context, it is crucial to implement a comprehensive care model that offers continuous support and a multidisciplinary approach. Primary care should be central, coordinating the entire care process. Understanding the clinical and social characteristics of people with diabetes is key to guiding more effective interventions. Objective: The objective of this study was to describe the sociodemographic and anthropometric characteristics, degree of metabolic control, and treatment adherence in patients with diabetes mellitus enrolled in primary care programs in Ceuta. Materials and Methods: This was a descriptive, observational, and cross-sectional study conducted during the second half of 2024. The study population included individuals enrolled in the primary care diabetes program in Ceuta. We analyzed sociodemographic variables with a self-administered questionnaire, the level of therapeutic adherence using the MMAS-8 scale, and glycemic control through glycosylated hemoglobin (HbA1c) values. Results: The sample consisted of 370 individuals, with 50.3% being men. The average age was 62.82 years (SD = 13.46). A significant portion of participants, 61.07%, had no formal education or had only received primary education. Additionally, 84.9% of the participants had at least one other associated chronic pathology. Regarding adherence, 36.8% of the patients showed a high level, and for all patients, the mean HbA1c value was 7.5% (SD = 1.55). Furthermore, our analysis revealed statistically significant associations between cultural background and both therapeutic adherence (weak positive correlation: r = 0.213, p ≤ 0.001; multivariate significance: sig: <0.001; Exp(B) = 2.448) and glycemic control (multivariate significance: sig: <0.001; Exp(B) = 2.686). Conclusions: We observed high treatment adherence in the study population, with HbA1c values within the limits recommended by the World Health Organization for older adults. Furthermore, a relationship between cultural background and both treatment adherence and glycemic control was identified. This suggests a need for further research into these and other social determinants, like study level or monthly income, in future studies. 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

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

Metabolic syndrome comprises a constellation of comorbidities, including obesity, hypertension, and disorders in carbohydrate and lipid metabolism, associated with an elevated risk of cardiovascular mortality. Obesity is regarded as the principal cause of metabolic syndrome (both collectively and in relation to its components), frequently linked in previous scientific studies with a deficiency of magnesium, one of the most important cations found in the human body. Objectives: The objective of this study was to assess the prevalence of hypomagnesemia in patients with metabolic syndrome and to determine the most significant risk factor among its components for this nutritional deficiency. Methods: Retrospective medical data from 403 patients admitted to the hospital for conditions unrelated to magnesium levels from 2015 to 2019 were evaluated, encompassing serum magnesemia and specific data about components of metabolic syndrome. Data underwent statistical analysis, including linear and logistic regression, to assess the principal risk variables of hypomagnesemia. Results: Hypomagnesemia was observed in 14.89% of the patients with metabolic syndrome, exhibiting a 2.42-fold greater risk of this deficiency (95%CI: 1.40–3.40). Among the components of metabolic syndrome, hyperglycemia emerged as the most significant determinant affecting both the incidence and severity of hypomagnesemia, elevating the risk by a ratio of 2.72 (95%CI: 1.52–4.87). In the multivariate regression model, hyperglycemia was the sole factor independently influencing magnesium concentration (β = −0.145; p < 0.001). Conclusions: Patients presenting signs of metabolic syndrome are at heightened risk for hypomagnesemia. Hyperglycemia appears to be the most important variable affecting the risk of magnesium insufficiency; however, additional research is needed in this area. 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: 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/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: 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

Introduction: Recent technological progress in optical imaging—such as adaptive optics, interferometry and tomography—has greatly improved the resolution of retinal imaging. The ability to capture sequential images over time is particularly valuable for continuous monitoring and assessment of retinal diseases. Methods: This cross-sectional study involved patients with type 2 diabetes mellitus and age-matched controls from the Diabetes and Ophthalmology Department of the Emergency Military Clinical Hospital “Dr. Constantin Papilian” Cluj-Napoca between October 2023 and October 2024. These patients were assessed for inclusion and exclusion criteria and then categorized into two groups: the diabetes group and control group. Each participant underwent a comprehensive ophthalmological examination and retinal evaluation using SS-OCT (Spectralis Heidelberg Engineering, Heidelberg, Germany). The parameters measured included the superficial and deep foveal avascular zones (FAZ) in only one eye for each patient, selected based on image quality. Additionally, each patient underwent quantitative analysis of serum C-reactive protein (CRP) levels. Results: A total of 33 patients (33 eyes) featured, 13 men and 20 women. The DM group showed statistically significant higher results for CRP value compared to healthy subjects (p < 0.001). Also, both superficial and deep FAZ areas were statistically significantly higher for diabetes patients compared to the healthy controls (p < 0.05). The correlation analysis revealed that there was no significant correlation between CRP and either superficial FAZ (p = 0.809) or deep FAZ (p = 0.659). However, a significant positive moderate correlation was found between superficial FAZ and deep FAZ (r = 0.577, p = 0.015). Conclusions: Our findings showed a significantly enlarged FAZ in diabetic patients compared to healthy individuals, highlighting its potential as an early indicator of microvascular alterations in diabetes. While CRP levels were notably elevated in the diabetic group, no significant association was found between CRP and FAZ measurements, suggesting that FAZ changes may occur independently of systemic inflammatory status. Full article

Background/Objectives: 5-Aminolevulinic acid (5-ALA) is a biosynthetic precursor of heme that induces heme oxygenase-1 (HO-1). Therapeutic induction of HO-1 has shown effectiveness in various autoimmune disease models, including type 1 diabetes (T1D). However, the efficacy of 5-ALA as an HO-1 inducer in T1D models remains unexplored. This study aimed to investigate the therapeutic efficacy of oral 5-ALA administration in preventing autoimmune diabetes development in nonobese diabetic (NOD) mice. Methods: We evaluated diabetes incidence, levels of insulin autoantibody, and severity of insulitis in 5-ALA-treated and control NOD mice. HO-1 expression of dendritic cells in the pancreatic islets and spleen of 5-ALA-treated NOD mice was measured. The IFN-γ/IL-17 of islet-infiltrating T cells and IL-10/IL-12 productions of dendritic cells in the spleen of 5-ALA-treated NOD mice were assessed. We stimulated islet antigen-specific CD4⁺ T cells with islet antigen-pulsed dendritic cells in the presence of 5-ALA and examined the proliferation of the T cells. Finally, we adoptively transferred islet antigen-specific CD4⁺ T cells into 5-ALA-treated, immunodeficient NOD-Rag1 knockout mice, and diabetes incidence in recipients was determined. Results: Oral 5-ALA treatment did not significantly impact diabetes incidence, levels of insulin autoantibody, and insulitis. No significant difference was observed in HO-1 expression in dendritic cells and cytokine production of T cells and dendritic cells. Similarly, there was no significant difference in the proliferation of islet antigen-specific CD4⁺ T cells in vitro and diabetes induction in transfer experiments. Conclusions: Oral administration of 5-ALA has a limited effect on suppressing the development of autoimmune diabetes in NOD mice. 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

Background/Objectives: Advanced wound healing biologics for diabetic foot ulcer (DFU) are typically withheld from persons who are at high risk for amputation. However, a prospective, single-center cohort study evaluated the use of an advanced biologic, dehydrated amniotic (DAMA) tissue as early treatment for DFUs in patients with a high risk for amputation, demonstrating benefit for a small sample. This is the report of the five-year follow-up of those high-risk participants. Methods: This chart review provides a 5-year follow-up of 18 of 20 participants in the original study. The data were collected by medical record review. Specific data points included mortality, re-ulceration and additional ulceration, amputation (minor and major), end-stage renal disease with dialysis dependence, hospitalization, and limb-threatening ischemia. Results: The 5-year mortality rate from the time of wound healing was 50% (9/18 deceased). Four of the eighteen participants (22.2%) underwent major amputation within 5 years of study completion. Two had amputations of the study limb and two had amputations of the contralateral limb. Fifty percent (2/4) of those who had amputations died within 5 years after the major amputation. Over fifty percent (55.5% or 10 out of 18) of the participants experienced the re-ulceration of the original study ulcer and 94% (17 out of 18) developed a new site ulceration. A total of 25% of the hospitalizations over the 5 years were related to DFU (infection, osteomyelitis, and sepsis). Conclusions: This small-sample 5-year follow-up shows that early treatment with dehydrated amniotic (DAMA) tissue in patients with diabetic foot ulcers of moderate-to-high amputation risk results in similar outcomes as noted in the current research on patients with low risk for amputation. In fact, this paper may suggest that advanced biologics can safely be used for early treatment in moderate-to-high amputation risk without increasing mortality and amputation over 5 years. Full article

Background/Objectives: Recruiting and retaining low-income participants in community-based diabetes interventions remains a persistent challenge, particularly in medically underserved areas. This study describes engagement strategies and lessons learned recruiting for a 12-month pilot of a community-based, medically tailored nutrition program for diabetes remission and weight loss. Methods: A descriptive, exploratory mixed-methods study was performed to assess the effectiveness of recruitment and engagement strategies in the HEAL Diabetes program and identify areas for improvement. Recruitment and enrollment data were tracked utilizing recruitment logs and field notes. Descriptive statistics were used to analyze recruitment activity and retention rates, while qualitative analysis of fieldnotes identified key barriers and facilitators. Results: Among 83 eligible participants, 63 (75.9%) completed the in-person screening and 35 (55.6% enrollment rate) enrolled. Retention was high, with 30 completing the study. Participants were largely African American (97.1%), female (70.6%), average age of 59.8 years, with a household income below USD 49,000 (74.3%). Recruitment cycles achieved 87.5% of the target before budget constraints halted enrollment. Recruitment was hindered by limited clinical integration, social barriers and life demands, while facilitators to recruiting included trust, flexibility, and tangible support for participation. Conclusions: Conventional recruitment methods, including registry-based approaches, were insufficient for engaging underserved populations. Participant-centric strategies, emphasizing trust, practical support, and structural and cultural relevance, can help enhance enrollment and retention. Effective engagement in community-based diabetes interventions requires multifaceted approaches that address clinical, social, and structural barriers to participation. 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

Aim: The aim of this study was to evaluate the specificity, sensitivity and accuracy of the Indicator Plaster Neuropad in detecting established Diabetic Autonomic Neuropathy (DAN). Methods: We studied 180 patients with Diabetes Mellitus (DM, mean age 49.5 ± 16 years, 82 with DM type 1). All patients underwent the following Cardiovascular Reflex Tests (CARTs): R-R variation during deep breathing (Mean Circular Resultant (MCR) and standard deviation (SD)), Valsalva maneuver, R-R variability after a rapid change from lying to standing position and postural hypotension. The presence of DAN was established if ≥2 CARTs were abnormal. According to the result the patients were divided into two groups, one with DAN and one without DAN. Assessment with Neuropad was performed also in all patients. Results: Abnormal perspiration with Neuropad (uncompleted or no change in color) was detected in 94 patients. Established DAN was detected in 85 patients. The sensitivity, specificity and accuracy of Neuropad for the diagnosis of established DAN were 87.1%, 78.9% and 82.8%, respectively and area under the curve was 0.846 and 95% CI (0.787, 0.905). Conclusions: Neuropad has high sensitivity, specificity, and accuracy in detecting established DAN, as defined by ≥2 abnormal CARTs. Full article

Background: Two changes to gestational diabetes mellitus (GDM) testing were implemented in the Australian Capital Territory in 2015 and 2017. Aims: We aimed to determine the associations between testing regimes and the prevalence of GDM and large-for-gestational-age (LGA) and small-for-gestational-age (SGA) infants and to compare the prevalence of LGA and SGA infants between women with and without GDM in each testing period. Methods: A total of 23,790 singleton live births with estimated GDM testing and birth dates between June 2012 and December 2019 were stratified into groups: pre-testing changes (June 2012–December 2014, group 1, n = 8069), revised diagnostic criteria (January 2015–May 2017, group 2, n = 8035) and changed pathology centrifugation protocol (June 2017-December 2019, group 3, n = 7686). Women were allocated to groups based on their estimated GDM testing date and stratified by their GDM status. A chi-square test, pairwise z-tests and logistic regression tested the associations. Results: The GDM prevalence significantly increased from 9.5% (group 1) to 19.4% (group 2) to 26.3% (group 3) (all: p < 0.001). The LGA infant prevalence significantly decreased in non-GDM women following revised diagnostic criteria implementation (11.6% vs. 9.7%, p = 0.001). Compared to group 1, women with GDM in groups 2 and 3 had significantly reduced odds of having LGA infants (aOR = 0.73, 95% CI of 0.56–0.95 and p = 0.021 and aOR = 0.75, 95% CI of 0.59–0.97 and p = 0.029, respectively). Compared to group 1, non-GDM women in groups 2 and 3 had significantly reduced odds of having LGA infants (aOR = 0.83, 95% CI of 0.74–0.92 and p < 0.001 and aOR = 0.88, 95% CI of 0.79–0.99 and p = 0.026, respectively). There were no significant associations for group 3 compared to group 2 nor for SGA infants. Conclusions: While significantly increasing the GDM prevalence, implementing the testing changes was associated with a reduced whole-population LGA infant prevalence without a change in the SGA infant prevalence. 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

Background/Objectives: Insulin resistance is a key factor in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD), but accurately measuring it in patients with type 2 diabetes (T2D) remains challenging. This study examines the relationship between a recently proposed insulin resistance index and the presence of liver steatosis and fibrosis in individuals with T2D. Methods: This cross-sectional study utilized data from the 2017–2020 National Health and Nutrition Examination Survey. Patients with T2D who did not have chronic viral hepatitis or significant alcohol intake were included. The insulin sensitivity (IS) index was calculated using a formula incorporating body mass index, urine albumin-to-creatinine ratio, triglycerides, and gamma-glutamyl transferase. Liver stiffness and steatosis were assessed through transient elastography. MASLD was defined as a controlled attenuation parameter (CAP) of ≥274 decibels/meter (dB/m), while significant liver fibrosis was defined as a liver stiffness measurement (LSM) of ≥8 kPa. Multivariable logistic regression models, adjusted for potential confounders, were used to evaluate the association between IS and these liver outcomes. Results: A total of 1084 patients with T2D were analyzed. The prevalence of MASLD and significant liver fibrosis was 74.1% (95% CI 68.7–78.9) and 25.4% (95% CI 21.2–30.2), respectively. After adjusting for age, sex, waist circumference, and race/ethnicity, lower IS scores (indicating higher insulin resistance) were independently associated with increased odds of both MASLD (quartile 1 vs. quartile 4: OR 2.66, 95% CI 1.23–5.71) and significant liver fibrosis (quartile 1 vs. quartile 4: OR 3.30, 95% CI 1.45–7.51). These findings remained consistent across subgroups stratified by age, sex, and obesity status. Conclusions: This novel IS model, derived from commonly available clinical and biochemical markers, is independently associated with liver steatosis and fibrosis. Its application may help identify patients with more advanced MASLD, facilitating early intervention and risk stratification. 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 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

Aims and Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder frequently associated with increased inflammation and dysregulated innate immune responses. Thus, patients with T2DM are predisposed to bacterial infections. However, the underlying mechanism is poorly understood. The NAD+-dependent deacetylase Sirtuin1 (SIRT1) plays an important role in regulating cellular metabolism, including T2DM and aging. Furthermore, we have recently demonstrated that SIRT1 critically regulates inflammatory pathways and autophagy during infection. Thus, we aimed to investigate SIRT1 expression and its correlation with autophagy in peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic patients. Methods: Clinical characteristics of the study subjects were obtained. SIRT1 and autophagic markers such as p62 and LC3-I/II were determined using Western blot analysis followed by densitometric analysis. Results: We found that SIRT1 levels were decreased in PBMCs of diabetic patients in an age-dependent manner. Importantly, reduced SIRT1 expression correlated with reduced LC3-II/I ratios, indicating reduced autophagy. Reduced SIRT1 also corresponded to decreased autophagic adaptor protein Sequestome-1/p62. Conclusions: In summary, our results suggest a potential role of SIRT1 in regulating autophagy in PBMCs from T2DM patients. Full article

Background/Objectives: The outcomes of diabetes therapy depend largely on how well patients can implement medical advice in their lives. The main aim of the DiabPeerS study was to evaluate a peer support instant messaging service (IMS) approach to diabetes self-management education and support (DSMES) for people with type 2 diabetes mellitus (T2DM). Methods: Participants with T2DM took part in a randomized controlled trial. Both the intervention group (IG) and the control group (CG) received standard therapy, but the IG additionally participated in the peer support IMS intervention. The duration of the intervention was 7 months, succeeded by a follow-up 7 months later. Eleven biochemical, six behavioral, and six psychosocial parameters were measured at four times. Results: The targeted sample size could not be reached, and 68 participants took part. The following results have been found for the main hypotheses: No influence on HbA1c was detected (IG: −0.27, CG: +0.06, p > 0.05). Diabetes self-management behaviors were unaffected (IG_diet: +0.02, CG_diet: +0.46, p > 0.05; IG_exercise: −0.72, CG_exercise: +0.44, p > 0.05; IG_bloodsugar: −0.21, CG_bloodsugar: +0.65, p > 0.05; IG_footcare: +0.37, CG_footcare: +1.13, p > 0.05). Quality of life increased during the intervention in both the IG (KSK: +8.92, PSK: +7.41, p < 0.001) and the CG (KSK: +8.73, PSK: +7.48, p < 0.001). Medication adherence increased in the IG (+3.31, p < 0.01), although these participants were still classified as non-adherent. Conclusions: A peer support IMS intervention is a promising approach, but we recommend combining the online setting with an initial face-to-face situation. Full article

In the United States, at least one in three adults has prediabetes, a condition categorized by blood glucose levels higher than normal but not high enough to be classified as type 2 diabetes. The Centers for Disease Control and Prevention (CDC) recommends a modest weight loss of 5–7%, a reduction in A1C by 0.2%, and at least 150 min of physical activity per week to prevent or delay the onset of type 2 diabetes in individuals with prediabetes. Eat Smart, Move More, Prevent Diabetes (ESMMPD) is a CDC-recognized lifestyle-change program for individuals with prediabetes or at high risk of developing type 2 diabetes. ESMMPD consists of 26 lessons delivered over the course of a year by trained Lifestyle Coaches using Zoom^TM. Participants are taught strategies to implement health-promoting behaviors related to healthy eating, physical activity, and mindfulness into their daily lives. The core components of the program are planning, tracking, and living mindfully. The aim of this article is to provide insights into the development, delivery, and core components of the ESMMPD program for public health practitioners. 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

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

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/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

Background: Insulin resistance (IR) is a metabolic disorder linked to type 2 diabetes and cardiovascular diseases. Visceral fat is a better predictor of IR than BMI and waist circumference due to its metabolic and inflammatory impact. Methods such as DEXA and bioimpedance (BIA) estimate body fat, while scales such as METS-IR, SPISE, and TyG assess IR risk. This study analyzes the utility of visceral and body fat measured by BIA compared to other indicators. Methods: A cross-sectional study was conducted on 8590 workers in the Balearic Islands, analyzing anthropometric, clinical, and analytical variables. Body fat and visceral fat were measured by bioimpedance, and insulin resistance was assessed using METS-IR, SPISE, and TyG. ROC curves were used to evaluate the predictive value of BMI, WC, and body fat. Results: The areas under the curve (AUCs) were highest for high METS-IR, particularly in women (>0.97), indicating excellent performance. TyG showed the lowest AUC, especially in men. Body and visceral fat showed the highest AUC for all IR scales. Youden’s indices were highest for high METS-IR, with good predictive capacity, while TyG showed low values, limiting its utility in predicting insulin resistance. Conclusions: Measuring body and visceral fat by BIA is superior to BMI or WC for estimating IR risk. Full article

Background: Diabetic foot osteomyelitis (DFO) constitutes a severe and prevalent complication of diabetes mellitus (DM). Individuals afflicted with DM exhibit an elevated risk for DFO development, attributable to a confluence of factors, including peripheral neuropathy, compromised circulation, and impaired immune function. Timely diagnosis and appropriate therapeutic intervention are paramount. In recent years, alongside the ablative approach, the feasibility of substituting compromised bone with a bone substitute has emerged. Methods: We retrospectively analyzed resorbable bone grafting procedures performed at our third-level center for the care of people with diabetes between 2019 and 2024. Forty-nine patients were included in this. The median follow-up period was 13 months (Q1 7, Q3 20). Results: At follow-up, 34 patients (69%) had achieved healing, with a median healing time of 2.3 months (Q1 1.5, Q3 5). Lesion location significantly influenced healing outcomes, with forefoot and midfoot lesions demonstrating an 86% healing rate compared to 50% for hindfoot lesions. Eleven patients (22%) experienced infectious relapse after a median of 1 month (Q1 0.7, Q3 2.9). An analysis of different bone substitutes did not reveal significant differences in terms of healing among the various products and between the presence or absence of a local antibiotic. Conclusions: Bone substitute implantation offers an additional conservative strategy for managing DFO. Healing rates are significantly higher for forefoot and midfoot lesions, suggesting that further research is needed to improve outcomes in hindfoot osteomyelitis. Selection of the most effective bone substitute requires further studies. Full article

Background: This study examined differences in body composition, dietary intake, and exercise habits between people with type 1 diabetes (T1DM) and those without diabetes (NDM). We also sought to clarify the clinical and lifestyle characteristics of overweight people with T1DM. Methods: This controlled cross-sectional study was conducted at a single center, and included 45 people with T1DM and 50 NDM individuals. Body composition, nutrient intake, and exercise habits were evaluated, and exercise habits were compared between people with a T1DM onset before 20 years of age and those with an onset at or after 20 years of age, in relation to the NDM group. Overweight was defined using a BMI of 25.0 kg/m² as the cutoff. Results: The T1DM group had significantly higher BMI and body fat than the NDM group, but no significant difference in muscle mass, and consumed a higher percentage of carbohydrates and a lower percentage of fat. The early-onset T1DM group had significantly lower exercise habits during their school years and in their current life than the NDM group. Individuals in the overweight T1DM group had a lower time in range on a continuous glucose monitor and a higher carbohydrate intake than those in the non-overweight T1DM group. Conclusions: The study suggested that the T1DM group had a significantly higher body fat percentage and carbohydrate intake, and significantly reduced exercise habits as students, compared to the NDM group. Full article

Objectives: Excessive fetal growth is the most common fetal complication associated with gestational diabetes (GDM), resulting in adverse short- and long-term outcomes. Our main objective was to evaluate the influence of excessive fetal growth on Doppler ultrasonographic measurements of the Umbilical Artery (UA) among women with GDM during the third trimester of pregnancy. Methods: A retrospective study among 472 women with GDM was conducted. UA-PI was measured by Doppler ultrasonography three different times during the third trimester of pregnancy at 28, 32, and 36 weeks. Pregnancies were grouped according to the fetal weight centile or birthweight in two groups: large for gestational age (LGA) group (>90th percentile or ≥4000 g at birth) and adequate for gestational age (AGA) group (<90th percentile or <4000 g at birth, not including the intrauterine growth restrictions). Results: In the LGA group (n = 57, 12.1%), women had higher BMI (p = 0.0001) and fasting blood glucose than the AGA group (97.08 ± 40.69 vs. 86.29 ± 39.58 mg/dL; p = 0.0550). They required insulin therapy more frequently to achieve glycemic control (63.2% vs. 34%, p = 0.0001). In LGA, UA-PI decreased progressively from 28 to 36 weeks (p = 0.0048). The most pronounced reduction occurred at 32 weeks (p = 0.0076). Conclusions: All fetuses from mothers with GDM had a significant and progressive decline in UA-PI during the third trimester of pregnancy. LGA fetuses showed lower UA-PI values compared with AGA fetuses. Since maternal hyperglycemia increases the risk of fetal overweight and GDM may represent a fetal vascular disorder, it therefore seems possible that in LGA fetuses, maternal hyperglycemia could influence the fetal vasculature. Full article

Type 2 diabetes (T2D) is a rapidly growing global health concern, projected to affect 1.3 billion people by 2050, necessitating a multidisciplinary approach. This review examines the epidemiological disparities in T2D, focusing on modifiable and nonmodifiable risk factors, socioeconomic determinants, and healthcare inequities. While genetic predisposition, age, and ethnicity contribute to T2D risk, socioeconomic status (SES) significantly mediates modifiable factors such as diet, physical activity, and access to healthcare. Lower SES is associated with poorer lifestyle choices, limited access to resources, and increased exposure to risk factors, exacerbating T2D prevalence among vulnerable populations. Geographic variations in T2D prevalence are evident, with racial and ethnic minorities and lower-income individuals being disproportionately affected in regions like the United States and Europe. The economic burden of T2D is substantial, with global healthcare expenditures reaching USD 966 billion in 2021 and projected to rise significantly, albeit with variations across different countries and health systems. Despite advancements in treatment, inequities in healthcare access persist, particularly in low- and middle-income countries, hindering optimal glycemic control and consequently contributing to preventable complications and poor health outcomes. This review highlights the critical need for targeted interventions and policy reforms to address the intersection of demographic, economic, and healthcare-related variables influencing T2D disparities. By bridging gaps in prevention, management, and treatment and accounting for the effect of SES on both modifiable and nonmodifiable risk factors, the global disease burden of T2D could be reduced and health equity could be improved. Full article

Background: Microvascular disease (MVD) describes systemic changes in small vessels (~100 µm diameter or smaller) that impair tissue oxygenation and perfusion. MVD has been demonstrated to play an independent role in the risk of limb loss. Despite this relevance, MVD is not regularly assessed clinically because tools used to evaluate and quantify the severity of MVD of the foot remain limited. We sought to evaluate if the Semmes-Weinstein 10-g Monofilament (SWM) can be used to stratify clinical MVD severity. Methods: We evaluated a racially diverse cohort of 124 patients (with 248 limbs). SWM testing was performed on the plantar aspect of the feet at 1st, 3rd^, and 5th metatarsophalangeal joints. Clinical MVD was stratified in an ascending order of severity into: no diabetes; type 2 diabetes (DM); diabetes+ neuropathy (DM+N); diabetes + neuropathy + retinopathy (DM+N+R). Logistic regression models were used to examine the association between a patient’s clinical MVD severity and an abnormal SWM test. Results: Sixty-four patients (51.6%) tested had an abnormal sensation. The odds of an abnormal SWM test were significantly higher for patients with DM+N and DM+N+R compared to those with no DM respectively. (DM vs. No DM: OR: 3.58, [0.98–13.09], p = 0.05; DM+N vs. No DM: OR: 30.46, [10.33–105.17], p < 0.001; DM+N+R vs. No DM: OR: 43.00, [9.89–309.17], p < 0.001). Furthermore, we categorized SWM based on the degree of sensation loss and found that the proportion of people with a higher degree of sensation loss increased across the clinical MVD severity spectrum. Conclusions: Abnormal SWM sensation strongly correlates with the severity of clinical MVD. This suggests that a simple, non-invasive, 1-min SWM test that can be done in the clinic is a promising tool in assessing MVD in the feet, which is particularly significant considering MVD involvement in limb loss. Full article

Metabolic-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) are interrelated metabolic disorders with significant global health impacts. MASLD, the hepatic manifestation of metabolic dysfunction, is driven by insulin resistance, ectopic lipid accumulation, and systematic inflammation. T2DM exacerbates the progression of MASLD, increasing the risk of advanced fibrosis, cardiovascular complications, and hepatocellular carcinoma (HCC). This bidirectional relationship highlights the need for integrated management strategies. The pathology of these conditions involves disrupted lipid and glucose metabolism, leading to a cycle of metabolic dysfunction which worsens both hepatic and systemic outcomes. Non-invasive diagnostic tools have improved early detection but lack precision in staging liver disease, emphasizing the need for more accurate biomarkers. Routine screening for MASLD in diabetic populations is critical for early intervention. Management focuses on weight reduction through lifestyle changes, although long-term adherence remains a challenge. Pharmacological advancements, including glucagon-like peptide-1 receptor agonists (GLP-1Ras) and sodium–glucose cotransporter-2 (SGLT2) inhibitors, show promise in reducing liver fat, improving glycemic control, and slowing fibrosis progression. However, these therapies are less effective in advanced stages of fibrosis and cirrhosis, underscoring the need for novel treatment options. In conclusion, the intertwined nature of MASLD and T2DM necessitates a multidisciplinary approach integrating early diagnosis, lifestyle interventions, and targeted therapies. Future research should prioritize refining diagnostic accuracy and developing innovative treatments for delivering personalized care strategies to mitigate the growing burden of these conditions. These efforts are crucial for improving outcomes in this vulnerable population. Full article

Over 100 years after its commercialization, the insulin administration method still needs elementary education. Such observation contrasts with technological progress constantly elaborating new (e.g., weekly) insulin preparations, capable of mimicking the pharmacokinetics of insulin produced by the human pancreas and exploring alternatives to injection. However, insulin administration remains anchored to the subcutaneous route, thus creating the conditions for lipohypertrophies (LHs), a still too frequent and ubiquitously widespread skin complication that, despite being avoidable with an adequate educational path, affects up to 60% of patients and even more. Considering that there are approximately 580 million adult diabetic people in the world today, at least half of whom (290 million) self-inject insulin, should 50% of the latter have LH, approximately 145 million people and even more? Considering that there are approximately 580 million adult diabetic people in the world today, at least half of whom (290 million) self-inject insulin, should 50% of the latter have LH, approximately 145 million people would suffer from such a complication, thus causing a severe problem for the global health system. Indeed, besides being unsightly, LHs cause poor glycemic control, large glucose variability, and frequent unexplained hypoglycemia, and display a strong correlation with micro- and macrovascular complications, inevitably worsening the quality of life of diabetic people. In this narrative review, after a brief description of the alternative routes of administration to subcutaneous injections, we will recall the causes, consequences, and possible corrective actions of LHs, stigmatizing the fundamental role of therapeutic education and hoping that all this can interest all the actors who revolve around the management of insulin therapy, which is too often underestimated and hastily addressed by health professionals, who probably prefer to dedicate time to titration of therapy. Ultimately, our aim is to provide the reader with a practical review of injection errors resulting from incorrect insulin injection techniques, analyzing the leading causes of error and the consequences of these errors, while also providing advice and suggestions to overcome all this. Full article

Introduction/Aim: Type 1 diabetes (T1D) challenges glycemic control, with sleep disturbances affecting insulin sensitivity and glucose variability. This study aimed to observe sleep quality in T1D patients and glycemic outcomes, particularly at bedtime hours. Methods: This retrospective observational study, conducted at an Italian clinical center, included T1D patients using Medtronic devices. Sleep quality was assessed using the Italian version of the Pittsburgh Sleep Quality Index (PSQI), and glycemic outcomes were analyzed with CGM data. Descriptive statistics and non-parametric tests were applied for statistical comparisons. Results: Of 45 patients, four were excluded, leaving 41 for analysis. The mean PSQI score was 6.0 ± 4.1, with 36.6% showing poor sleep quality. No significant differences in age, sex, BMI, or diabetes duration were found. Poor sleepers had a higher time above range level 2 (TAR2) (6.3 ± 6.2%) compared to good sleepers (4.1 ± 5.0%). During bedtime hours, poor sleepers showed a significantly higher TAR2 (6.7 ± 7.2% vs. 3.3 ± 6.2%, p = 0.013). Conclusions: Poor sleep quality is associated with increased nocturnal hyperglycemia in T1D patients. Enhancing sleep quality may contribute to improved glycemic control, particularly during nighttime. Future research should explore targeted sleep interventions in diabetes care, and specific lifestyle-based healthcare programs are recommended to optimize glycemic outcomes. Full article

Background/Objectives: We evaluated the effects of glucagon-like peptide-1 receptor agonists (GLP1-RAs) on body weight and metabolic parameters in people with HIV and diabetes (PWHD) receiving maintenance therapy with integrase inhibitor, using a real-world study design. Methods: PWHD on integrase inhibitors-based antiretroviral therapies for at least 6 months, and treated with GLP1-RAs for at least 3 months, were included in this retrospective study. The primary study outcome was the absolute and relative change in body weight, as assessed during routine outpatient visits. Secondary analyses included evaluating the impact of GLP1-RAs on additional metabolic parameters, such as serum glucose, glycated hemoglobin, and LDL-cholesterol. Results: A total of 25 PWHD (74% males, mean age 65 ± 7 years, with 16% having a body mass index > 30 Kg/m²) receiving GLP1-RAs-based antihyperglycemic therapy were identified from our hospital database. No significant effects of GLP1-RAs on body weight were observed (absolute reduction −1.9 ± 3.0 Kg; relative reduction −2.2 ± 3.7%). Treatment with GLP1-RAs was associated with a progressive and significant reduction in serum glucose and glycated hemoglobin, with no observed impact on LDL cholesterol. Conclusions: Long-term GLP1-RA treatment significantly reduced serum glucose and glycated hemoglobin in overweight PWHD with no effects on body weight. Full article

Background: Diabetes-related distress (DD) significantly impacts self-management and quality of life (QoL) in individuals with type 1 diabetes (T1D). While previous research has established a strong link between DD and glycemic control in type 2 diabetes, the relationship remains less consistent in T1D. Additionally, continuous glucose monitoring (CGM) has been shown to improve glycemic outcomes, yet its effects on self-management and QoL are still debated. This study aimed to examine the relationship between DD, self-management efficacy (SME), and QoL in T1D, incorporating both physiological and behavioral indicators. Furthermore, differences between CGM-users and non-users were investigated. Methods: A cross-sectional study including 108 T1D patients was conducted. Participants completed several validated self-report measures, including the Diabetes Distress Scale (DDS), Diabetes Self-Management Questionnaire (DSMQ), and Audit of Diabetes-Dependent Quality of Life (ADDQoL-19). HbA1c levels and CGM usage were retrieved from medical records. Structural equation modeling (SEM) was used to examine the relationships between DD, self-management, and QoL. Results: Distress level (DDS) had a significant negative effect on SME (β = −0.47, p < 0.001), suggesting that higher distress levels are associated with lower self-management. In contrast, SME showed no significant impact on quality of life (β = 0.03, p = 0.779). However, the relationship between quality of life and distress was significant and negative (β = −0.37, p < 0.001), meaning that higher distress levels are linked to a lower quality of life. No significant differences in DD, SME, HbA1c, or QoL were found among CGM users and non-users. Conclusions: DD significantly impacts self-management and QoL in individuals with T1D. Therefore, incorporating PROs on DD and on behavioral aspects of self-management alongside HbA1c levels in clinical care is essential for optimizing treatment plans and improving physical health outcomes. While CGM technology facilitates glucose regulation, it does not inherently improve QoL, which is more closely linked to distress. Full article

Diabetes mellitus (DM) is a chronic metabolic disorder associated with late diagnosis due to the absence of early symptoms in patients. Cutaneous manifestations of DM often serve as indicators of insulin resistance and vary with disease progression, highlighting severity and systemic involvements. With an increasing global burden and rapidly rising prevalence, skin findings associated with DM have become more crucial for the rapid identification and treatment of underlying metabolic processes. However, current challenges in identification include inaccurate or missed detection in darker-skinned populations, which may be attributed to the lack of inclusion of diverse skin types in textbooks and research studies. This review provides clinicians with comprehensive updates on the diagnosis and treatment of cutaneous signs, complications, comorbidities, medication-associated side effects associated with DM, and the treatment of these manifestations. Full article

Continuous glucose monitoring (CGM) and flash glucose monitoring (FGM) systems have revolutionized diabetes management by delivering real-time, dynamic insights into blood glucose levels. This article provides a concise overview of the evolution of CGM technology, highlights emerging innovations in the field and explores current and potential future applications (including insulin management, early diagnostics, predictive modeling, diabetes education and integration into automated insulin delivery (AID) systems) of CGM in healthcare. Full article

Background/Objectives: The chronic metabolic condition of hyperglycemia in type-2 diabetics is known to cause various neurological disorders and compromise recovery from brain insults. Previously, we reported a delayed and reduced glial cell response and a greater neuronal cell death in different brain regions of diabetic, db/db, mice following cerebral hypoxic- ischemic injury. In this study, we explored the changes in baseline activation of astrocytes and microglia and its impact on vascular permeability in different brain regions. Methods: The numbers of activated astrocytes (GFAP-positive) and microglia/macrophage (Iba-1-positive) in the motor cortex, caudate and hippocampal regions of 12-week old, type-2 diabetic db/db and non-diabetic db/+ mice were quantitated. The leakage of serum IgG and loss of occludin, a tight junctional protein observed in the cortex and caudate of db/db mice, indicated a compromised blood brain barrier. Results: Results indicated significant differences in activation of glial cells in the cortex and caudate along with increased vessel permeability in diabetic mice. Conclusions: The study suggests that a constant activation of glial cells in the diabetic brain may be the cause of impaired inflammatory response and/or degenerating cerebral blood vessels which contribute to neuronal cell death upon CNS injury. Full article

Objectives: To describe the association of race with type 2 diabetes complications and determine if differences in rates of complications exist between racial/ethnic groups of adult type 2 diabetes patients in the United States. Additionally, we model the odds of in-hospital patient mortality across racial/ethnic groups. Methods: A retrospective cohort study was conducted using data from the 2018 National Inpatient Sample of Healthcare Cost and Utilization Project, including 97,314 unweighted and 486,500 weighted adults with type 2 diabetes. Chi-square analysis was used to determine the association of race with diabetes complications, along with z-tests to determine the differences in complication rates of 11 different complications between racial/ethnic groups and binary logistic regression to model in-hospital mortality. Results: Our analysis revealed significant racial/ethnic disparities in both complication rates and odds of in-hospital mortality. Whites had the lowest rate of complications overall, except for arthropathy/oral complications (18.8%) and foot/skin ulcers (18.2%), while Black/African Americans had the highest rates of hyperosmolarity (7.3%), ketoacidosis (21.2%), neurological complications (8.9%), and hyperglycemia (13.4%). Asian/Pacific Islanders had the highest rates of hypoglycemia (17.6%) as well as kidney (7.2%) and ophthalmic (0.3%) complications, and Hispanics the highest rates of circulatory complications (19.0%). Hispanic ethnicity was associated with 10.6% reduced odds of in-hospital mortality, and Asian/Pacific Islanders and Other races had increased odds of mortality by 25.2% and 27.0%, respectively. Notably, neurological (OR = 0.278, 95% CI: 0.111, 0.702) complications and hyperglycemia (OR = 0.304, 95% CI: 0.124, 0.749) were associated with a reduction in mortality odds by 62.2% and 69.6%, possibly reflecting the study’s focus on in-hospital rather than all-cause or 30-day mortality. Conclusions: We demonstrated disparities in both rates of type 2 diabetes complications and odds of mortality between different racial/ethnic groups. These results lay groundwork for future research into the root causes of these disparities and highlight the importance of targeting interventions and equitable case for those most at risk. Full article