INTRODUCTION: The prevalence of diabetes mellitus and its micro vascular and macro vascular complications have been increasing among diabetic patients in Ethiopia. Diabetic nephropathy (DN) is one of the most serious complication of diabetes which leads to end-stage renal disease and other complication of diabetes mellitus. A small number of investigations were carried out in Ethiopia, and the incidence of DN was the main source of data for these studies. Therefore, this study was aimed to estimate time to diabetic nephropathy and its predictors among adult diabetes mellitus patients at public general and referral hospital of South Wollo Zone, Amhara National Regional State, Northeast Ethiopia. METHODS: Retrospective follow up study was conducted among 408 adult diabetes mellitus patients who were on follow up at public general and referral hospital of South Wollo zone from December 10, 2012 to December 9, 2022. Data were entered into Epidata version 4.6, and then exported to Stata version 14 for further statistical analysis. Kaplan Meier survival curve was used to estimate the cumulative survival time and Log rank test was used to compare the survival time between different categories of the predictor variables. Multivariable Cox proportional hazards model was fitted to identify predictors of time to diabetic nephropathy. RESULT: Overall, 71 (17.4%) of the study participants developed diabetic nephropathy with incidence density of 2.35/1000 person-months (95% CI; 1.86, 2.97) and Median survival time of this study was 98 [95% CI: 95 -105] months. Sex [AHR: 0.293, 95%CI: 0.154, 0.555], hypertension [AHR: 1.81, 95% CI: 1.01, 3.24], HbA1C [AHR: 1.93, 95% CI: 1.069, 3.49] and HDL [AHR: 0.399, 95% CI: 0.225, 0.708] were predictors of time to diabetic nephropathy. CONCLUSION AND RECOMMENDATION: The median survival time of this study was 98 [95% CI: 95 -105] months which was relatively long time compared with previous study. Sex, hypertension, HbA1c and HDL were predictors of time to diabetic nephropathy.

OBJECTIVES: Type 2 diabetes (T2DM) is a growing public health concern, particularly in the Middle East and North Africa (MENA) region, where prevalence rates continue to rise. Social determinants of health, including material needs security and food security, play a critical role in diabetes management, yet their interrelated effects remain underexplored. This study aims to examine the relationship between material needs security and food security among Lebanese adults with T2DM of low socioeconomic status. METHODS: A cross-sectional study was conducted on 299 Lebanese adults with T2DM recruited from three primary health care centers. Participants completed validated questionnaires assessing sociodemographic factors and food security. Material needs security score was computed based on ownership and access for certain house utilities, as well as car ownership. Unadjusted and adjusted logistic regression models were conducted to evaluate associations between material needs security and food security. RESULTS: Higher material needs security was significantly associated with food security in both the unadjusted and adjusted regression models (odds ratio = 1.26, 95% confidence interval: 1.06-1.49, = 0.007). Food and material needs insecurities were more prevalent among females and individuals with lower income, lower education, and lack of health insurance. CONCLUSION: This study highlights the strong association between material needs security and food security in Lebanese adults with T2DM, emphasizing the importance of addressing social determinants in diabetes management. Policies targeting financial stability, food security interventions, and access to health care are essential to improving health outcomes in vulnerable populations.

BACKGROUND: SARS-CoV-2 infection is frequently associated with metabolic disorders. This study aimed to analyze the epidemiological, clinical, and biological characteristics of patients hospitalized for COVID-19 in Morocco and to evaluate the factors associated with hyperglycemia at admission. METHODS: A retrospective, single-center observational study was conducted on 472 patients hospitalized for RT-PCR-confirmed COVID-19 at the El Jadida Provincial Hospital Center (Morocco). Patients were classified into three groups according to fasting plasma glucose and history of diabetes: normoglycemic patients, hyperglycemic patients, and type 2 diabetes (T2D) patients. Demographic, clinical, biological, and radiological data were collected from medical records for admissions between April 2020 and January 2021. Hyperglycemia was defined as a fasting plasma glucose ≥ 126 mg/dL with no prior diagnosis of diabetes. METHODS: Of the 472 patients included, 38.8% were normoglycemic, 31.3% had hyperglycemia without a history of diabetes, and 29.9% had T2D. Hyperglycemic patients presented with more severe forms of COVID-19, with lower oxygen saturation, more extensive lung involvement, and marked biological abnormalities, including elevated leukocytes, neutrophils, AST, ALT, and the neutrophil-to-lymphocyte ratio. Lymphopenia and eosinopenia were also more frequent in these patients. In univariate analysis, advanced age, low SpO, elevated AST and ALT levels, neutrophilia, and severe COVID-19 were significantly associated with hyperglycemia. After adjustment for age, sex, comorbidities, and COVID-19 severity, independent predictors of hyperglycemia included elevated ALT (OR = 1.68,  = 0.037), higher neutrophil count (OR = 1.11,  = 0.003), a higher neutrophil-to-lymphocyte ratio (OR = 1.13,  < 0.001), and lymphopenia (OR = 0.54,  = 0.014). CONCLUSION: Admission hyperglycemia was associated with greater COVID-19 severity and marked biological abnormalities. As this cross-sectional study did not include post-discharge follow-up, these findings represent associations rather than evidence of incident diabetes; nonetheless, post-discharge metabolic monitoring of hyperglycemic patients appears warranted.

BACKGROUND: First-degree relatives (FDRs) of people with type 2 diabetes mellitus (T2DM) are considered as a high-risk group to develop T2DM. This study aimed to determine the prevalence of prediabetes and diabetes and assess the agreement among three standard diagnostic criteria in this population. METHODS: A cross-sectional study of 1,029 FDRs of people with T2DM was conducted. Anthropometric, blood pressure, and biochemical assessments, including fasting plasma glucose (FPG), HbA1c, lipid profile, and a 2-hour oral glucose tolerance test (OGTT), were performed. Agreement between diagnostic criteria was assessed using kappa statistics, and multivariable logistic regression identified the factors associated with dysglycemia. RESULTS: According to a single diagnostic criterion, the prevalence of diabetes and prediabetes in FDRs with undiagnosed diabetes was 9.2% and 39.1%, respectively. Prediabetes prevalence based on FPG, 2-hour OGTT (2-h PG), and HbA1c was 18.4%, 18.0%, and 30.9%, respectively; while diabetes was identified in 2.3%, 6.0%, and 6.7% of the population. The three criteria showed fair-to-moderate agreement, with the highest concordance between 2-h PG and HbA1c. Older age, overweight/obesity, and hypertension were associated with higher odds for both conditions. In addition, men were at higher risk of diabetes than women. CONCLUSION: Our findings support a substantial burden of prediabetes and diabetes among FDRs of people with T2DM. Among the three standard criteria, FPG showed the lowest diagnostic performance to detect prediabetes and diabetes. While OGTT has practical limitations, HbA1c represents a feasible and informative tool for large-scale screening in high-risk groups.

PURPOSE: Gum Arabic () has shown a vital effect in improving glycemic, lipid, and cardiometabolic outcomes in adults. However, its overall effect remains uncertain because findings have been inconsistent across studies for weight, BMI, FBG, and HbA1c, and no quantitative meta-analysis has established its pooled effect. This study aimed to evaluate the effects of oral Gum Arabic (GA) supplementation, compared with placebo, on glycemic, lipid, and cardiometabolic outcomes in adults, including healthy individuals and those with type 2 diabetes mellitus and/or metabolic syndrome. METHODS: We systematically searched PubMed, Cochrane Central, and Scopus for RCT studies comparing any dose of oral GA to Placebo or the standardized treatment. Outcomes assessed were BMI, weight, FBG, HbA1c, and lipid parameters. Statistical analysis was performed using RevMan, with I² statistics for heterogeneity with a random-effects model. RESULTS: Six RCTs (476 participants) met the inclusion criteria and were included. GA showed significant reduction in BMI (MD - 0.38; 95% CI: -0.47, - 0.29;  < 0.0000; I²= 0%; Fig. 2), weight (MD - 1.00; 95% CI: -1.59, - 0.41;  = 0.0009; I²= 0%; Fig. 3), and FBG (MD - 29.76; 95% CI: -51.88, - 7.65;  = 0.008; I²= 93%; Fig. 4). Sub-analysis of healthy versus non-healthy patients showed a statistically significant reduction of weight in the healthy group (MD - 0.99; 95% CI: -1.58, - 0.40;  = 0.001; I²= 0%; Fig. 10). CONCLUSION: GA showed some effect on lowering weight, BMI, and glycemic control in adults. Findings suggest that GA may be a promising nutritional intervention for managing cardiometabolic risk factors and weight reduction in adults. However, these results should be taken cautiously due to the limited number of trials, short follow-up periods, and high heterogeneity for fasting blood glucose. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-026-02034-y.

BACKGROUND: Atrial fibrillation (Afib) and type 2 DM (T2DM) are common conditions associated with substantial cardiovascular morbidity and mortality. However, data on the burden of Afib among patients with T2DM in sub-Saharan Africa remain limited. This study aimed to determine the prevalence, clinical features, and factors associated with Afib among adults with T2DM at Hoima Regional Referral Hospital (HRRH), western Uganda. METHODS: A hospital-based cross-sectional study was conducted among 355 adults with T2DM attending HRRH. Participants underwent clinical evaluation, glycated hemoglobin (HbA1c) testing, and 12-lead electrocardiography (ECG) for Afib diagnosis. Logistic regression analysis was used to identify factors associated with Afib, with statistical significance set at p < 0.05. RESULTS: The prevalence of Afib was 7.9% (28/355). Patients with Afib commonly presented with palpitations, dizziness, fatigue, chest pain, and dyspnea, with tachycardia and irregular pulse frequently observed on examination. In multivariable analysis, hypertension (aOR 3.027, 95% CI 1.419-6.431; p = 0.020), human immunodeficiency virus (HIV) infection (aOR 2.026, 95% CI 1.738-6.538; p = 0.048), body mass index (BMI ≥ 25 kg/m²) (aOR 3.014, 95% CI 1.242-7.930; p = 0.029), and poor glycemic control (HbA1c ≥ 8%) (aOR 3.813, 95% CI 1.762-8.265; p = 0.007) were independently associated with Afib. CONCLUSION: Afib is relatively common among adults with T2DM in western Uganda, affecting nearly one in ten patients. Hypertension, HIV infection, obesity, and poor glycemic control were significant associated factors. Integrating ECG screening into diabetes care, particularly for high-risk patients may improve early detection and management in resource-limited settings.

Patients with type 2 diabetes mellitus (T2DM) have elevated risk for aortic stenosis (AS). The impact of diabetes on prognosis and clinical progression in AS is not well documented. In this study we try to assess if patients with T2DM and AS have faster clinical progression compared to patients without diabetes. By linkage of nationwide Swedish registries, we identified 16,116 T2DM and AS individuals (cases) and compared them with 31,066 matched comparators (AS without diabetes) from general population concerning clinical progression, defined as progression from AS diagnosis to hospitalization for heart failure, aortic valve replacement, mortality, and composite outcome of these endpoints. Kaplan-Meier curves were used to compare outcomes between cases and comparators and Cox proportional hazards analyses to account for confounders. AS individuals (total 47,182, 16,116 cases and 31,066 comparators) had mean age 71 years. The cases were younger, men predominated (58% versus 53%) and had more comorbidities. During follow-up, cases had faster clinical progression- 11% higher hazard for valve replacement (95% CI 1.04-1.18), 14% higher hazard for heart failure hospitalization (95% CI 1.03-1.26) and 4% higher hazard for composite outcome (95% CI 1.01-1.08), but with no mortality excess (HR1.00, 95%CI 0.97-1.05). Preexisting T2DM seems to be linked to moderately more rapid clinical progression in AS.

Platelet activation, endothelial dysfunction, and stress-responsive endocrine signaling have emerged as important components of the complex biological processes underlying type 2 diabetes mellitus (T2DM), extending beyond the classical concepts of glucotoxicity and lipotoxicity. This review proposes a hypothesis-generating conceptual framework in which platelet activation, fibroblast growth factor 21 (FGF21), and growth differentiation factor 15 (GDF15) represent partly independent yet biologically interconnected stress-response pathways that may converge within the pancreatic islet microenvironment during disease progression. Activated platelets contribute to vascular inflammation and endothelial dysfunction through soluble mediators and extracellular vesicles, whereas FGF21 and GDF15 are induced by oxidative stress, mitochondrial dysfunction, and activation of integrated cellular stress responses as adaptive endocrine signals that promote mitochondrial homeostasis, endothelial integrity, and cellular resilience. Under persistent metabolic stress, sustained vascular injury, impaired adaptive signaling, and progressive endothelial dysfunction may collectively reduce the capacity of these protective mechanisms to preserve β-cell function. Rather than representing a proven transition point, the pancreatic islet microenvironment is proposed as a biologically plausible convergence site where vascular injury, adaptive endocrine responses, and intrinsic β-cell stress may interact. Although direct mechanistic evidence linking these pathways remains limited, this conceptual framework integrates current experimental and clinical evidence, identifies important mechanistic knowledge gaps, and provides a foundation for future mechanistic studies, integrated biomarker development, disease stratification, and precision medicine strategies in T2DM.

Nutrient overload induces a state of chronic, low-grade inflammation termed metaflammation, which contributes to the development of metabolic disorders, such as type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). As a nutrient-sensitive organelle, the endoplasmic reticulum (ER) is highly vulnerable to systemic metabolic burden. When its adaptive capacity is exceeded, ER stress (ERS) activates the unfolded protein response (UPR) and drives cellular dysfunction. This review delineates how the canonical UPR sensors transduce metabolic stress into pro-inflammatory signaling cascades. By engaging key transcriptional regulators and inflammasome complexes, these pathways drive the production of inflammatory mediators, including cytokines, chemokines, and bioactive lipids, such as leukotrienes (LTs) and prostaglandins. Subsequently, the review discusses the organ-specific consequences of ERS in the liver, pancreas, adipose tissue, vascular endothelium, and hypothalamus, highlighting how this stress sustains a self-reinforcing cycle of tissue injury and metabolic dysfunction. Emerging therapeutic strategies are also summarized, ranging from broad-spectrum chemical chaperones to precision UPR modulators and organ-targeted delivery systems aimed at disrupting this pathogenic axis and restoring metabolic homeostasis.

Diabetic cardiovascular disease remains the leading cause of mortality in patients with diabetes, underscoring the urgent need for effective therapeutic strategies to improve clinical outcomes and prevent major adverse cardiovascular events in this high-risk population. Metformin, a widely prescribed antihyperglycemic agent, not only lowers blood glucose levels but also modulates multiple intracellular signaling pathways, thereby exerting pleiotropic effects. The present study aimed to evaluate the cardioprotective effects of metformin and elucidate its underlying molecular mechanisms in myocardial ischemia-reperfusion injury. Accordingly, we established in vivo diabetic models and in vitro hyperglycemic conditions to assess the effects of metformin on myocardial tissue in diabetes. The results demonstrated that metformin treatment significantly ameliorated cardiac dysfunction and attenuated myocardial morphological abnormalities in diabetic rats subjected to ischemia-reperfusion, and concurrently improved cardiomyocyte viability under hyperglycemic conditions. Moreover, metformin enhanced autophagy, promoted mitophagic activity, and restored mitochondrial homeostasis-effects that were further validated using compound C in cultured cardiomyocytes under hyperglycemic conditions. Collectively, these findings indicate that metformin confers cardioprotection against myocardial ischemia-reperfusion injury (MIRI) through activation of AMP-activated protein kinase (AMPK) and its downstream signaling cascades, thereby regulating mitophagic processes.

This review provides an overview of current evidence on the presence, distribution, and physiological role of glucagon-like peptide-1 (GLP-1) receptors in skin tissue. Although GLP-1 receptor agonists are primarily used to treat type 2 diabetes mellitus and obesity, increasing evidence suggests that they may also have direct effects on the skin. This review examines the available research on GLP-1 receptor expression in major skin cell types, including keratinocytes, dermal fibroblasts, and the cutaneous microvascular endothelium. The strength of the evidence is evaluated according to the species studied, the experimental model used, and the method of receptor detection, including gene expression, protein identification, and functional activity. Differences in findings across animal models, cultured cells, and human tissue are also considered. In addition, this review distinguishes between skin effects that are likely mediated by direct activation of GLP-1 receptors within cutaneous tissue and those that occur indirectly through systemic metabolic improvement or modulation of immune and inflammatory pathways.

BACKGROUND: Studies on the association between weight change and serum uric acid (SUA) or hyperuricemia (HUA) remain limited, and the underlying mechanisms remain unclear. OBJECTIVE: This study aimed to explore the relationships between weight change and SUA or HUA among Chinese adults, and to assess the mediating role of insulin resistance (IR). METHODS: We analyzed data from participants who underwent at least two annual health examinations between January 2015 and May 2025. Weight change (%) was calculated as (follow-up value - baseline value)/baseline value. Generalized linear models and logistic regression were used to examine the associations of weight change with SUA and HUA, while mediation analysis was applied to evaluate the mediating effects of IR indices. RESULTS: A total of 16,688 eligible participants was included, with 15.0% having HUA. The median follow-up duration was 2.00 (1.00, 4.00) years. Each 1-standard deviation (SD) increase in weight change was associated with a 10.48 μmol/L increase in SUA, and a 30.0% higher risk of HUA. Atherogenic index of plasma (AIP), triglyceride-glucose index (TyG), triglyceride-glucose body mass index (TyG-BMI), and the metabolic score for insulin resistance (METS-IR) were positively linearly associated with SUA and HUA. All four IR indices partially mediated the associations of weight change with SUA levels and HUA risk. Compared with individuals with stable weight, the weight loss group was associated with a significantly lower HUA risk, while the weight gain group had a 78% higher HUA risk. CONCLUSIONS: Weight gain was associated with the elevated SUA levels and increased HUA risk, and insulin resistance may be one of the underlying mechanisms.

Semaglutide is a glucagon-like peptide-1 receptor agonist widely used for the treatment of type 2 diabetes and obesity. Despite its clinical efficacy, oral administration remains challenging because of its limited gastrointestinal stability, poor epithelial permeability, and low affinity for lipid-based delivery systems. In the present study, a combined hydrophobic ion pairing (HIP) and solid lipid nanoparticle (SLN) approach was explored to improve semaglutide incorporation and delivery-related properties. Semaglutide was complexed with the cationic lipid DOTAP at different molar ratios (1:0-1:18) and subsequently incorporated into cetyl palmitate-based SLNs produced by microfluidic mixing using a herringbone device. The resulting formulations were characterized in terms of particle size, ζ-potential, encapsulation efficiency, morphology, solid-state organization, colloidal stability, release behavior, mucus interaction, cytocompatibility, and epithelial permeability. Among the various formulations prepared, the one prepared with a molar ratio semaglutide: DOTAP of 1:18 and a peptide concentration of 10% (w/w) (F10) showed the best results, combining particle sizes of less than 300 nm with almost complete encapsulation efficiency and a highly positive ζ-potential. FTIR, DSC, TGA and SAXS analyses confirmed the correct formation of the complex and its incorporation into the lipid matrix. The F10 formulation demonstrated good stability under simulated gastrointestinal conditions and a sustained-release profile. The formulation also exhibited strong interactions with mucus, whilst retaining the ability to diffuse through the mucin network. Cytocompatibility studies demonstrated acceptable cell viability at relevant concentrations, whilst permeability experiments through Caco-2 monolayers revealed an approximately 6-fold increase in apparent permeability compared to free semaglutide. Therefore, these findings indicate that the combination of DOTAP-mediated hydrophobic ion pairing and microfluidic-assisted SLN production represents a potentially promising strategy for improving semaglutide encapsulation, gastrointestinal stability, and epithelial transport, while maintaining a favorable balance between mucus interaction and mucodiffusion.

BACKGROUND AND AIMS: Sarcopenia in older adults with diabetes may encompass clinically distinct phenotypes. We examined whether body composition-defined phenotypes differed in diabetes complications, insulin resistance-related metabolic features, and continuous glucose monitoring (CGM)-derived glycemic profiles. METHODS: This cross-sectional study included 109 adults aged 70 years or older with diabetes and frailty. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People 2 criteria; adiposity was defined using body mass index, body fat percentage, and central obesity. Analyses were mainly descriptive; exploratory logistic regression assessed poor CGM time in range (TIR), defined as TIR below 70%. RESULTS: Sarcopenia was identified in 86 participants (78.9%). After exclusion of 2 participants in a small non-sarcopenic with adiposity subgroup, 107 participants formed three phenotypes. Sarcopenic obesity showed an insulin resistance-related cluster comprising greater central adiposity, higher triglycerides and TyG index, metabolic syndrome in all participants, and greater insulin requirements. Sarcopenia without adiposity showed more neuropathy, albuminuria, cerebrovascular disease, and lower TIR despite similar glycated hemoglobin. Glycated hemoglobin was the only independent correlate of poor TIR; phenotype was not significant overall. CONCLUSIONS: Phenotypes showed distinct clinical, insulin resistance-related, and CGM profiles. These preliminary findings support phenotype-aware assessment but require confirmation in larger longitudinal studies before informing management.

This study investigated the effect of low-level laser therapy (LLLT) on the pulpal alterations caused by tooth movement in diabetic rats. Forty-eight Wistar rats were divided into control (CTR), diabetic (DBT), and LLLT-treated counterparts. Diabetes was induced with alloxan, and orthodontic movement was performed for 13 days. LLLT (780 nm, 35 J/cm) was applied every 48 h for 7 days. Histological analyses assessed inflammation, stromal cell density (SCD), blood vessel count (BVC), odontoblastic layer thickness (OLT), and collagen deposition at 7 and 13 days. In 7 days, the DBT group showed significantly increased inflammation (p < 0.01), and decreased blood vessel count (p < 0.001) and cell rates (p < 0.01) compared to CTR. The DBT/LT group presented inflammatory, vascular, and cell rates comparable to CTR, meaning LLLT reversed these changes. However, DBT/LT still showed significantly increased collagenization at both 7 (p < 0.05) and 13 days (p < 0.001). LLLT attenuates diabetes-exacerbated histological pulpal damage during orthodontic movement, supporting its potential as an adjunctive therapy in hyperglycemic conditions.

BACKGROUND: Recent studies suggest a decreased risk of dementia in patients treated with glucagon-like peptide-1 receptor agonist (GLP-1 RA). In this study, we compare the risk of dementia associated with GLP-1 RA versus long-acting insulin in adults aged over 50 years with type 2 diabetes (T2DM) using real-world administrative data from a large Taiwan cohort DESIGN: A population-based retrospective cohort study SETTING: We analyzed 10,783 propensity score-matched pairs of adults with T2DM who initiated either GLP-1 RA or long-acting insulin from Taiwan's National Health Insurance Research Database (2011-2021). MEASUREMENTS: Primary outcome was new-onset dementia; secondary outcomes included dementia requiring treatment and specific dementia subtypes (Alzheimer's disease, vascular dementia, and unspecified dementia). Hazard ratios (HRs) were estimated using Cox models. RESULTS: Analysis of matched pairs identified 375 cases of newly diagnosed dementia. The incidence rate was 4.86 per 1,000 person-years in GLP-1 RA users versus 7.56 in insulin users. GLP-1 RA use was associated with significantly lower risk of overall dementia (HR 0.64, 95% CI 0.46-0.89, P=0.0072) and unspecified dementia (HR 0.41, 95% CI 0.24-0.68, P=0.0006), but not for Alzheimer's disease (HR 1.48, 95% CI 0.61-3.63, P=0.3867) or vascular dementia (HR 1.66, 95% CI 0.21-13.03, P=0.6324). Among GLP-1 RAs, both liraglutide (HR 0.40, 95% CI 0.20-0.80, P=0.0091) and dulaglutide (HR 0.42, 95% CI 0.19-0.92, P=0.0311) showed significant protective effects against unspecified dementia. CONCLUSIONS: GLP-1 RA use was associated with lower dementia risk versus long-acting insulin in T2DM patients, especially with liraglutide and dulaglutide. As observational, causality requires confirmation from randomized controlled trials.

BACKGROUND: Composite grafting is a commonly used treatment option for Allen Zone II fingertip amputations; however, reported survival rates vary considerably across studies. Although several clinical and injury-related factors have been suggested to influence graft survival, independent predictors of failure and clinically meaningful ischemia duration thresholds remain insufficiently defined. This study aimed to identify independent clinical predictors of composite graft survival and to explore, secondarily, whether ischemia duration is associated with graft failure. METHODS: Forty-two patients who underwent composite grafting due to Allen Zone II fingertip amputation between December 2021 and June 2023 were retrospectively evaluated. Baseline variables were collected from hospital records and surgical notes. Ischemia duration was calculated as the number of hours between the injury and the start of surgery. Diabetes mellitus (DM) and other comorbidities were verified using diagnostic codes and patient histories. The primary outcome measure was graft survival at 6 weeks postoperatively; necrosis affecting more than 25% of the graft surface area was defined as failure. Group comparisons, univariate and multivariate logistic regression, and receiver operating characteristic (ROC) curve analysis were performed. Because of the limited number of outcome events and quasi-complete separation in the data, the multivariable model was additionally fitted using Firth's penalised likelihood method. RESULTS: Graft survival was achieved in 23 cases (54.8%), while 19 cases (45.2%) resulted in failure. Factors associated with graft failure included older age, longer ischemia duration, presence of DM, and crush/avulsion type injuries. In further analysis, DM and crush/avulsion injury mechanism emerged as the most important independent predictors of graft failure, whereas age and ischemia duration were less influential when considered alongside other variables. Penalised estimates were more conservative than unpenalised ones but preserved both associations (DM, OR 12.63; crush/avulsion mechanism, OR 12.29). In exploratory ROC analysis an ischemia duration threshold of 4.3 h was associated with failure, although ischemia duration was not an independent predictor. Overall, the combined evaluation of clinical variables demonstrated strong ability to distinguish between successful and unsuccessful graft outcomes. CONCLUSIONS: In cases of Allen Zone II fingertip amputations, the crush/avulsion mechanism and DM are the strongest independent predictors of composite graft failure. An ischemia duration exceeding 4.3 h was associated with failure in exploratory analysis but was not an independent predictor. Preoperative assessment of these parameters may inform patient selection, pending prospective validation.

AIMS: Few studies have examined menopause's impact on health outcomes in women living with Type 1 diabetes mellitus (T1D). We compared physical, diabetes-related, and psychosocial outcomes between premenopausal and postmenopausal women with T1D. METHODS: A cross-sectional analysis of 211 women aged 40-60 years from the BETTER registry (121 premenopausal; 90 postmenopausal). Outcomes included physical complications (retinopathy, neuropathy, cardiovascular disease [CVD], falls), diabetes management (HbA1c, insulin doses, hypoglycemia, medication), and psychosocial outcomes (depressive symptoms, fear of hypoglycemia [FOH]). Overlap weighting balanced covariates between groups; weighted regression models estimated associations as risk ratios (RR) for binary and mean differences (MD) for continuous outcomes (95% CI). RESULTS: In weighted models, postmenopausal women had higher risks of CVD (RR 3.31 [1.07-10.23]), neuropathy (RR 2.22 [1.17-4.21]), retinopathy (RR 2.20 [1.15-4.23]), falls (RR 2.64 [1.73-4.03]), and moderate-to-severe depressive symptoms (RR 1.48 [1.01-2.17]), and lower odds of antihypertensive (RR 0.57 [0.38-0.84]) and lipid-lowering prescriptions (RR 0.68 [0.54-0.86]), and elevated diabetes distress (RR 0.80 [0.68-0.95]). Insulin doses, HbA1c, hypoglycemia frequency, and FOH did not differ. CONCLUSIONS: Postmenopausal women with T1D showed less favourable physical and psychosocial health profiles than premenopausal women, underscoring the need for prospective studies to clarify these associations.

AIM: To compare all-cause mortality in adults with T2D initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP-4is) using a large multinational real-world dataset. METHODS: We conducted a retrospective, multinational, active-comparator, new-user cohort study using de-identified electronic health records from TriNetX (2015-2019). Adults aged >18 years with T2D who initiated a SGLT2i or DPP-4i after ≥12 months of continuous therapy were eligible. Propensity score matching (1:1 nearest neighbor) yielded 161,950 patients per group. All-cause mortality over 5 years was evaluated using a Cox proportional-hazards model to estimate hazard ratios and 95% confidence intervals. Kaplan-Meier curves were generated to compare cumulative mortality between groups. Sensitivity analyses and external validation in an independent Hong Kong/Singapore cohort were performed. RESULTS: Among 449,295 eligible patients, 161,950 initiated a SGLT2i and 161,950 initiated a DPP-4i after matching. Over 5 years, all-cause mortality was markedly lower in the SGLT2i group (9965 deaths; 6.2%) than in the DPP-4i group (27,330 deaths; 16.9%). Kaplan-Meier estimates showed cumulative mortality rates of 13.16% and 26.05% in the SGLT2i and DPP-4i groups, respectively. SGLT2i use was associated with a significantly reduced mortality risk (Hazard ratios 0.513; 95% confidence intervals 0.502-0.525; P < 0.001). Subgroup analyses revealed consistent reductions in mortality across sex, age categories, and baseline glycemic control levels. External validation confirmed improved survival associated with SGLT2i therapy. Collectively, these findings demonstrate a robust survival advantage of SGLT2is over DPP-4is. CONCLUSIONS: SGLT2is were consistently associated with significantly lower all-cause mortality than DPP-4is. These results underscore their clinical value and support SGLT2is as a preferred therapeutic option for patients with T2D.

Glucagon-like peptide-1 receptor is a key target for type 2 diabetes, but current peptide agonists suffer from low oral bioavailability and poor adherence, highlighting the clinical significance of developing small-molecule modulators. Starting from the lead compound V-0219, a series of novel oxazole-containing small-molecule positive allosteric modulators of GLP-1R were designed and synthesized via a scaffold hopping strategy. Systematic structure-activity relationship studies led to the identification of compound 5b, which exhibited superior GLP-1R potentiating activity (44.8% at 10 μM) compared to the lead. Mechanistic studies demonstrated that 5b enhances GLP-1(7-36)- and GLP-1(9-36)-induced cAMP accumulation, directly binds to and stabilizes the GLP-1R protein, and exerts glucose-lowering effects in a GLP-1R-dependent manner. In oral glucose tolerance tests in hGLP-1R knock-in mice, 5b demonstrated modestly improved glucose-lowering efficacy compared to V-0219. In addition, 5b exhibited lower cytotoxicity, favorable metabolic stability in mouse liver microsomes and plasma, and acceptable oral exposure. Collectively, 5b, as a lead compound for orally available small-molecule GLP-1R modulators, warrants further investigation and holds promise for the treatment of type 2 diabetes and related metabolic disorders.

PURPOSE OF REVIEW: Lipoprotein(a) [Lp(a)] remains a well-established, genetically determined predictor of cardiovascular risk due to its pro-atherogenic and pro-thrombotic effects. This review examines the paradoxical relationship between Lp(a) and metabolic dysfunction-associated steatotic liver disease (MASLD), where Lp(a) levels decline with advanced fibrosis despite persistently elevated cardiovascular disease (CVD) risk. RECENT FINDINGS: Studies consistently show an inverse association between Lp(a) and MASLD severity. Evidence suggests that lower Lp(a) levels are a consequence of hepatic dysfunction rather than protective against cardiovascular disease. Additionally, selective hepatic insulin resistance increases VLDL production, diverting apoB100 from Lp(a) assembly, while insulin directly suppresses apolipoprotein(a) synthesis. Genetic variants linked to MASLD may further impair hepatic lipid secretion and reduce Lp(a). Lower Lp(a) levels in MASLD likely reflect impaired hepatic synthetic function rather than reduced cardiovascular risk. Recognizing this paradox may improve risk stratification and interpretation of Lp(a) in patients with MASLD.

PURPOSE: Obstructive sleep apnea (OSA) is closely associated with obesity and fluid retention. Our previous study suggested that, in patients with heart failure, the sodium-glucose cotransporter 2 inhibitor, tofogliflozin, promotes diuresis and weight loss and improves OSA severity. However, whether changes in the apnea-hypopnea index (AHI) are chronologically associated with body composition parameters remains unclear. METHODS: We enrolled 10 patients (six men) with OSA. They received tofogliflozin (20 mg) daily for 6 months. The AHI was assessed using WatchPAT at baseline, 3, and 6 months. Body composition, including water content and fat mass, was also measured. AHI changes measured using the WatchPAT peripheral arterial tonometry-derived AHI (pAHI) and their correlations with changes in body composition parameters were analyzed. RESULTS: Tofogliflozin administration significantly reduced pAHIs at 3 and 6 months compared to baseline, but more at 3 months, whereas body weight and body water content decreased over time. The %Δbody water content did not correlate with %ΔpAHI at 3 months (r = 0.47, p = 0.139), but there was a significant correlation at 6 months (r = 0.57, p = 0.047). The %Δbody weight and %Δfat mass reduction were significantly associated with improvement in %ΔpAHI at 3 months (r = 0.65, p = 0.042 and r = 0.66, p = 0.044, respectively), but no correlations were observed at 6 months. CONCLUSIONS: Tofogliflozin significantly improved OSA severity at 3 and 6 months; however, more improvements were observed at 3 months. These improvements were accompanied by gradual reductions in body water content, especially from baseline to 6 months. In contrast, body weight and fat mass reduction impacted the OSA severity in the early stages.

OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes mellitus and obesity. Their metabolic, anti-inflammatory, and osteogenic effects raise important questions regarding their influence on spinal fusion. To date, no systematic review has specifically investigated how GLP-1RAs influence outcomes following the common anterior cervical discectomy and fusion (ACDF). This study aimed to evaluate the association between perioperative GLP-1RA use and outcomes following ACDF. METHODS: Following PRISMA guidelines, MEDLINE, Embase, PubMed, and the Cochrane Library were searched from inception to February 2026 for studies evaluating GLP-1RA exposure in the context of ACDF. Eligible studies included human observational cohort studies. Data were extracted independently by two reviewers. RESULTS: Eight retrospective cohort studies analysing 311,402 ACDF patients were included, of whom 8,182 were GLP-1RA users matched to non-users. Random-effects meta-analysis demonstrated significantly lower odds of pseudarthrosis among GLP-1RA users at 6 months (OR = 0.60, 95% CI: 0.52 to 0.71; I² = 16.6%), 12 months (OR = 0.62, 95% CI: 0.53 to 0.73; I² = 39.1%), and 24 months (OR = 0.67, 95% CI: 0.57 to 0.79; I² = 34.9%). Findings for reoperation, dysphagia, deep vein thrombosis, and readmission were heterogeneous and inconsistent across studies. CONCLUSION: Perioperative GLP-1RA use was associated with lower odds of pseudarthrosis. However, evidence regarding other postoperative complications remains inconclusive. Future prospective studies are required to further elucidate the impact of GLP-1RA use on ACDF outcomes. LEVEL OF EVIDENCE: Level III, therapeutic study.

PURPOSE: To evaluate potential racial and ethnic disparities in the utilization of faricimab-svoa in the management of macular edema (ME) and neovascular age-related macular degeneration (nAMD). METHODS: A retrospective cohort study using the TriNetX database analyzed patients diagnosed with nAMD, type 2 diabetes with diabetic macular edema (DME), or retinal vein occlusion macular edema (RVO ME), grouped by Hispanic ethnicity, African American (AA) race, and non-Hispanic, non-AA controls. Propensity score matching was conducted for age, gender, diabetes mellitus, essential hypertension, obesity, ischemic heart disease, and atherosclerotic heart disease. The primary outcome was faricimab-svoa injection incidence at any time point after diagnosis. Odds ratios (ORs) were calculated between cohorts. RESULTS: Of 49,568 AA patients (mean [SD] age at injection, 68.3 [14.4] years; 58.5% women) with a diagnosis of nAMD or ME, 55 received faricimab injection (OR 0.162; 95% CI, 0.122-0.215) compared to 338 in the control group of the same size. A similar relationship was noted for Hispanic patients (mean [SD] age at injection, 66.6 [13.5] years; 50.1% women) who received the injection (25 of 13,520) compared to non-Hispanic patients (91 of 13,520) (OR 0.273; 95% CI, 0.176-0.426). CONCLUSION: Faricimab is underutilized in the management of ME and nAMD in patients with AA race and Hispanic ethnicity compared to propensity score matched controls.

INTRODUCTION: Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM) and a leading cause of vision impairment in developed countries. Macular pigment optical density (MPOD) assessment provides a non-invasive method for evaluating in vivo changes in macular pigment. In this study, we investigated macular pigment alterations in eyes of patients with type 2 DM without clinically detectable DR using an autofluorescence-based MPOD (AF-MPOD) technique. METHODS: This was an observational, cross-sectional study including patients with type 2 DM without signs of DR and age- and gender-matched healthy controls. Confocal autofluorescence-based MPOD imaging was used to quantify macular pigment changes within the central 6.0° eccentricity. Retinal structural and microvascular alterations were also assessed using optical coherence tomography (OCT) and OCT angiography (OCTA). The primary outcome measure was the quantitative assessment of AF-MPOD parameters. Secondary outcomes included the evaluation of OCT and OCTA alterations and the exploratory identification of distinct imaging phenotypes among diabetic patients. RESULTS: Forty eyes from patients with type 2 DM and 40 control eyes were included. Eyes from patients with DM showed significantly reduced AF-MPOD parameters and lower OCTA vessel density compared with healthy control eyes (all adjusted p < 0.001). Inner retinal thinning was also observed. Glycemic control was inversely associated with AF-MPOD values and vessel density, whereas higher body mass index showed strong associations with AF-MPOD reduction. AF-MPOD parameters remained independently associated with OCTA-derived vascular metrics after multivariable adjustment. CONCLUSIONS: Our findings suggest that an early, interconnected neurovascular-metabolic retinal dysfunction may be detectable before the onset of clinically visible DR. AF-MPOD assessment may provide complementary imaging information on early retinal involvement in DM and warrants further validation in longitudinal studies. CLINICAL TRIAL REGISTRATION: Protocol ID: PNRR-MAD-2022-12376008; ClinicalTrials.gov Identifier: NCT06582472.