Search Results (1,687)

Background: In patients with type 2 diabetes mellitus (T2DM), angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are first-line antihypertensive treatments with important cardiovascular benefits, but their impacts on coronary-specific inflammation are unknown. Pericoronary adipose tissue (PCAT) attenuation, as assessed by coronary computed tomography angiography (CCTA), serves as a specific biomarker for coronary inflammation. Here, we aim to assess whether treatment with ACE-I or ARB is correlated with lower PCAT attenuation. Methods: In this retrospective observational study, we analyzed 223 patients with T2DM and coronary atherosclerosis who underwent CCTA from 1 January 2017 to 1 September 2024 at our institution. PCAT attenuation was measured in the proximal right coronary artery. Propensity score matching and multivariate linear regression analyses were performed for comparisons. Results: Of the 223 patients (mean age of 64.9 ± 8.8 years, 69.1% male), 122 patients were on ACE-I or ARB (ACE-I/ARB). ACE-I/ARB users had similar PCAT attenuation as their counterparts after propensity score matching (−72.1 ± 7.5 and −71.7 ± 8.1 HU, respectively; p = 0.722). Subgroup analysis in patients with glomerular filtration rate (GFR) < 90 mL/min revealed lower PCAT attenuation in ACE-I/ARB users (−74.8 ± 6.6 vs. −71.4 ± 7.1 HU; p = 0.038), with a significant interaction between these two factors in the multivariate analysis (p = 0.047). Other antihypertensive treatments (beta blockers, dihydropyridine calcium channel blockers, and thiazides) were not linked with lower coronary inflammation. Conclusions: In T2DM patients with coronary atherosclerosis, we did not find an association between ACE-I/ARB treatment and lower coronary inflammation as defined by PCAT attenuation, although such a relationship may exist in those with reduced GFRs. Full article

The COVID-19 pandemic disrupted diabetes care globally and created a complex bidirectional health crisis. Recent forecasting efforts using pre-pandemic data projected substantial increases in diabetes mortality through 2030, raising concerns about achieving Sustainable Development Goal (SDG) 3.4. However, these projections did not account for pandemic-related disruptions to health systems and chronic disease management. The newly released Global Burden of Disease (GBD) 2023 data, covering the pandemic period through 2023, now provide a comprehensive empirical reference for assessing COVID-19’s observed impact on diabetes trends. This perspective adopts a forecast reconciliation and interpretation approach by examining counterfactual pre-pandemic diabetes mortality projections alongside GBD 2023 data, thereby shedding light on how pandemic-era mortality diverged from pre-pandemic trajectories. Critically, we note that insulin-dependent diabetes mellitus (IDDM, Type 1) and non-insulin-dependent diabetes mellitus (NIDDM, Type 2) have distinct etiologies and pandemic vulnerabilities, a distinction this article addresses. The evidence is striking: by 2023, global diabetes deaths had already exceeded 2.0 million per year, surpassing the 2030 upper forecast bound of 1.91 million, seven years ahead of the forecast horizon. NIDDM was the primary driver, with deaths crossing 1.9 million per year in 2023. These findings underscore the urgent need to strengthen diabetes prevention and management strategies as the world recovers from the pandemic-era disruptions in health systems and chronic disease care. Full article

Carpal tunnel syndrome (CTS) is the most common compressive mononeuropathy. In patients with type 2 diabetes mellitus (T2DM), chronic hyperglycemia, microangiopathy, and systemic inflammation increase the vulnerability of peripheral nerves to compression. This study aimed to assess the relationship between CTS severity and clinical, metabolic, inflammatory, and electrophysiological parameters in patients with T2DM. A cross-sectional study was conducted from June 2023 to June 2024, involving patients diagnosed with T2DM. Electrophysiological assessment of the upper and lower limbs was performed using a four-channel electromyography apparatus. Clinical and anthropometric data and laboratory parameters were obtained, as well as the results of nerve conduction studies (NCS). One hundred and twenty-three patients with T2DM were included in the study. The prevalence of moderate-to-severe forms of CTS was 43.9%, and bilateral involvement was present in 21.95% of patients. Patients with moderate-to-severe CTS had significantly higher hemoglobin A1c (HbA1c) (p = 0.004), glycemia (p < 0.001), and Triglyceride–Glucose Index (p = 0.018) compared with those without CTS/with mild forms. The number of monocytes was significantly higher in the group with moderate-to-severe forms (p = 0.012), suggesting a chronic inflammatory state. In the logistic regression analysis, hemoglobin HbA1c emerged as an independent predictor of CTS severity, with each 1% increase associated with approximately a 60% higher risk of moderate/severe CTS. NCS analysis showed significant correlations between median nerve parameters and those of the lower-limb peripheral nerves, particularly the tibial and sural nerves, suggesting an association with generalized diabetic peripheral neuropathy. Professional activity was significantly associated with moderate-to-severe CTS (OR = 3.5). CTS is a common complication in patients with T2DM and is associated with worse glycemic control, insulin resistance, systemic inflammation, and peripheral neuropathic damage. Full article

Epidemiological and biological evidence indicate a close connection between Alzheimer’s disease (AD) and type-2 diabetes mellitus. Glucose transporter 1 (GLUT1), encoded by the SLC2A1 gene, has a major role in glucose metabolism, the dysregulation of which has been implicated in both diseases. We conducted a case-control association study in a sample of 439 non-diabetic patients with late-onset AD and 304 cognitively healthy, non-diabetic elderly controls to determine the potential risk for developing AD associated with SLC2A1 rs841847 polymorphism. The rs841847 C/C genotype occurrence was higher in the AD group (AD: 60.4%, controls: 50.7%), while the minor T allele-containing genotypes were more frequent among controls (AD: 39.6%, controls: 49.3%). A multivariate logistic regression model adjusted for age, sex, and apolipoprotein E (APOE) ε4 status (ε4 allele carriers versus non-carriers) demonstrated that carriers of the T allele had a significantly reduced risk for AD compared to C/C homozygotes (OR = 0.672; 95% CI: 0.493–0.916; p = 0.012). Although the rs841847 polymorphism has been linked to type-2 diabetes mellitus, the present study investigated this gene variant in AD for the first time. Our findings indicate a moderate protective effect for the rs841847 T allele on the susceptibility to AD. We demonstrated the rs841847 polymorphism as a candidate single nucleotide polymorphism for further examination as a predisposing genetic factor for AD. Full article

The global burden of type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise at an alarming pace, with substantial pathophysiological overlap driven by insulin resistance, visceral obesity, and chronic low-grade inflammation. MASLD may progress to metabolic dysfunction-associated steatohepatitis (MASH), with increased risk of cirrhosis and hepatocellular carcinoma. Glucagon-like peptide 1 (GLP-1)-based therapies have transformed the management of T2DM and obesity. They exert pleiotropic effects whose basis remains incompletely understood. Concurrently, Akkermansia muciniphila has emerged as a keystone gut microbiota species with demonstrated hepatoprotective potential in preclinical models of MASLD/MASH. This narrative review positions A. muciniphila simultaneously as a target of GLP-1-mediated microbiome remodeling and as an independent modulator of hepatoprotection in MASLD/MASH. A structured search of PubMed, Scopus, and Web of Science (last searched: 12 April 2026) was conducted using terms related to Akkermansia muciniphila, GLP-1 receptor agonists, MASLD/MASH and T2DM. A total of 174 records were identified. Of these, 148 were excluded due to duplication or non-relevant study design. 26 studies (23 preclinical, 3 clinical) were included in the synthesis, directly addressing A. muciniphila. Preclinical evidence demonstrates that liraglutide, semaglutide, exenatide, and tirzepatide increase A. muciniphila abundance, while A. muciniphila in turn enhances endogenous GLP-1 secretion via the P9/ICAM-2 axis, forming a hypothetical positive feedback loop. A working mechanistic model integrating these bidirectional interactions is proposed, alongside a discussion of current limitations and future research priorities, including microbiome-guided clinical trials in MASLD/MASH populations. Full article

Background/Objectives: Children and adolescents with type 1 diabetes mellitus (T1DM) may be particularly vulnerable to vitamin D deficiency; however, its association with glycemic control remains incompletely understood. This study aimed to determine the prevalence of vitamin D deficiency among children and adolescents with T1DM and to evaluate its relationship with glycemic control. Methods: This cross-sectional study enrolled individuals aged 1–18 years diagnosed with T1DM. Serum 25-hydroxyvitamin D concentrations were assessed, with deficiency defined as <20 ng/mL, insufficiency as 20–29 ng/mL, and sufficiency as ≥30 ng/mL. Glycemic control was defined as HbA1c < 9.0% (controlled) versus ≥9.0% (poor control). Multivariable logistic regression was performed to assess the independent association of 25-hydroxyvitamin D with glycemic control. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were conducted to evaluate the diagnostic and potential clinical utility of 25-hydroxyvitamin D levels. Results: A total of 266 participants were included; their median age was 13.0 years (IQR: 10.0–15.0), with a slight male predominance (56.8%). Overall, 64.3% of patients had suboptimal 25-hydroxyvitamin D status, including 30.1% with deficiency and 34.2% with insufficiency. Patients with poor glycemic control had significantly lower 25-hydroxyvitamin D levels compared to those with controlled diabetes (21.0 ng/mL [IQR: 17.0–26.0] vs. 35.0 ng/mL [IQR: 28.0–45.0], p < 0.001). A strong negative correlation was observed between HbA1c and 25-hydroxyvitamin D levels (Spearman’s ρ = −0.651, p < 0.001). Vitamin D insufficiency was significantly associated with poor glycemic control (aOR = 4.74, 95% CI: 2.48–9.32), while vitamin D deficiency was associated with substantially greater odds (aOR = 40.59, 95% CI: 15.55–129.23). The optimal cut-off for predicting poor control was 26.5 ng/mL, achieving a sensitivity of 75.5% and specificity of 82.2%. Decision curve analysis confirmed that the 25-hydroxyvitamin D model provided superior net benefit compared to treat-all and treat-none strategies across a threshold probability range of 32–85%. Conclusions: Vitamin D deficiency and insufficiency are highly prevalent among children and adolescents with T1DM. Lower 25-hydroxyvitamin D levels are independently associated with poorer glycemic control. Serum 25-hydroxyvitamin D demonstrates good diagnostic accuracy and potential clinical utility for risk stratification. Screening for 25-hydroxyvitamin D status and consideration of supplementation may serve as an adjunctive strategy to support metabolic management in this population. Full article

Background/Objectives: Teachers are often the first adults responsible for supporting students with type 1 diabetes mellitus (T1DM) during the school day. This study assessed schoolteachers’ diabetes-related knowledge, attitudes, emergency readiness, and routine school practices in Jordan. Methods: A cross-sectional online survey was conducted among teachers working in public and private schools in Jordan between February and April 2026. The final sample included 604 teachers. Multivariable relationships were examined using path analysis in R with full information maximum likelihood. Results: The median age was 43 years (IQR: 38–47), 88.6% of participants were women, and 15.9% had received prior diabetes-related training. Median composite scores were 11/14 (IQR: 9–12) for knowledge, 43/50 (IQR: 39–46) for attitudes, 23/35 (IQR: 18–28) for emergency readiness, and 24/30 (IQR: 20–26) for routine practices. The path model showed close fit indices (chi-square(1) = 0.243, p = 0.622; CFI = 1.00; RMSEA = 0.00; SRMR = 0.001), although these indices were interpreted cautiously because the model had only one degree of freedom. Greater knowledge was associated with more favorable attitudes (beta = 0.374, p < 0.001), and more favorable attitudes were associated with better emergency readiness (beta = 0.141, p < 0.001) and routine practices (beta = 0.244, p < 0.001). Teachers with prior diabetes-related training also reported higher attitudes, emergency readiness, and routine practice scores. Conclusions: Jordanian teachers appeared willing to support students with diabetes, but this willingness was not matched by consistent emergency preparedness. Targeted training and stronger school-level protocols are needed to improve the safety and quality of diabetes care in schools. Full article

Background/Objectives: The rising prevalence of childhood obesity has coincided with increasing incidence of type 1 diabetes mellitus (T1DM), raising questions regarding their potential bidirectional interaction. This systematic review evaluated the association between obesity and T1DM risk, as well as post-diagnostic weight trajectories and metabolic outcomes in pediatric populations. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed, Embase, and Scopus were searched for studies published between January 2010 and January 2026. Eligible studies included observational and interventional research in children and adolescents addressing T1DM and obesity; reviews, case reports, and non-English studies were excluded. Risk of bias was assessed using Joanna Briggs Institute tools. Due to heterogeneity, results were synthesized narratively. Results: Sixty-seven studies were included. Population-based data showed a positive association between higher BMI and incident T1DM, with obesity associated with a twofold increased risk (HR 2.05, 95% CI 1.58–2.66) and a 25% increase per 1-SD BMI increment. Insulin resistance (IR) indices correlated with BMI and predicted faster progression to clinical T1DM in autoantibody-positive individuals. At diagnosis, 20–30% of children were overweight or obese, increasing to 30–40% during follow-up. Excess adiposity was associated with higher insulin requirements and increased prevalence of hypertension and dyslipidemia. Longitudinal data indicate that BMI standard deviation scores rise with age, diabetes duration, and pubertal stage, with higher insulin doses and intensive insulin therapy contributing to weight gain. Conversely, some large cohort studies report no linear association between BMI and incident T1DM, indicating heterogeneity across populations. The limitations of this review include the predominance of observational studies, heterogeneous methodologies, and limited generalizability beyond predominantly European and North American pediatric populations. Conclusions: Overall, the evidence supports a bidirectional relationship: obesity may increase T1DM risk and accelerate disease progression, while T1DM-related factors promote weight gain after diagnosis. These findings highlight the importance of integrating weight management strategies into routine pediatric T1DM care. Full article

Background/Objectives: The rising global burden of type 2 diabetes mellitus (T2DM) demands multifaceted and more effective treatment strategies beyond monotherapy to achieve optimal metabolic control. The study aimed to evaluate the integrated effects of SGLT2 inhibitors and metformin in newly diagnosed T2DM patients on biochemical parameters, clinical outcomes and hormonal changes. Methods: This prospective longitudinal study was conducted at the Department of Biochemistry, Baqai Medical University, in collaboration with the Baqai Institute of Diabetology and Endocrinology. A total of 120 newly diagnosed T2DM patients were enrolled and stratified into three groups (n = 40): Group 1 (SGLT2 inhibitors only), Group 2 (SGLT2 inhibitors + metformin), and Group 3 (metformin only). Patients were followed for six months with data collection at baseline, at 3 months and 6 months. Anthropometric indices (weight, BMI, waist and hip circumferences, WHR), biochemical markers (FBS, HbA1c, lipid profile, uric acid, serum creatinine, HOMA-IR), and hormonal levels (insulin, glucagon) were assessed at baseline, first follow-up, and second follow-up. ANOVA, post hoc, Bonferroni and Tukey’s tests were applied; p-value < 0.05 was considered significant. Results: The findings indicate that Group 2 showed the greatest improvement in anthropometric parameters, particularly waist and hip circumferences (p < 0.01). Group 3 demonstrated the most significant improvement in glycemic indices and lipid profile (p < 0.01). HOMA-IR significantly decreased in Group 3 from baseline to the first follow-up (p < 0.01). While insulin levels remain insignificantly different among all groups. Glucagon levels declined significantly from baseline to the second follow-up in all groups, with a more pronounced decrease in Group 3 (p < 0.01). Serum creatinine and uric acid levels showed significant reductions from baseline to the second follow-up in Group 1 and Group 2 (p < 0.05). However, given the observational design, these associations should not be interpreted as causal evidence of renoprotection. Conclusions: Within the limitations of this observational study, early differences among treatment regimens were observed, though metabolic outcomes became statistically comparable across groups by six months. These hypothesis-generating findings suggest potential benefits of early combination therapy that require confirmation in randomized controlled trials. Given the substantial within-group variability and non-randomized design, no definitive conclusions about therapeutic associations can be drawn from these data. Full article

Background: Diabetic retinopathy (DR) and chronic kidney disease (CKD) are among the leading causes of disability in individuals with type 1 diabetes mellitus (T1DM). However, the genetic architecture of these complications remains poorly understood. Genome-wide studies demonstrate significant interpopulation heterogeneity, while candidate gene studies yield conflicting results due to limited power. Independent replication of previously obtained results in separate cohorts, with appropriate intergroup comparisons, is essential for identifying the most significant biomarkers of microvascular complications in T1DM. Purpose: To search for associations of the most significant polymorphic variants rs55703767, rs72831309, rs118124843, rs9344715, rs183937294, rs4293393, rs12917707, rs77924615, rs11864909, rs9622363, rs73885319, rs2523989, rs3825932, rs763361, rs12708716, rs2292239, and rs4948088 with the risk of developing T1DM and its complications—DR and CKD. Methods: The study involved 618 individuals, including 522 patients with T1DM undergoing inpatient treatment at the Endocrinology Research Centre, as well as 96 control individuals without T1DM. Among the T1DM patients, 232 had concurrent CKD and retinopathy, while 80 were free of both microvascular complications. A comparison of allele and genotype frequencies of 17 single-nucleotide polymorphisms (SNPs) was conducted between the T1DM group and the control group, as well as an intergroup comparison between individuals with and without complications. Results: The rs2292239 (ERBB3) locus is associated with an increased risk (p_bonf = 0.001, OR = 2.02), while rs55703767 (COL4A3) is associated with a decreased risk of developing T1DM in general (p = 0.01846, OR = 0.42). rs9344715 (AKIRIN2) is associated with the risk of diabetic nephropathy (p = 0.03996, OR = 1.29), while PDILT variants rs77924615 (OR = 0.57, p_bonf = 0.045) and rs11864909 (OR = 0.41, p_bonf = 0.0105) with DR. Conclusions: The study identified potential genetic markers for the risk of type 1 diabetes and its microvascular complications. The results require further verification in an independent, expanded cohort. Consideration of genetic factors confirmed the independent contribution of the identified variants, supporting their value as promising biomarkers for risk stratification and personalized prevention of T1DM complications. Full article

Osteoporosis and hyperglycemia are increasingly recognized as dual public health concerns in T1DM. However, the precise molecular mechanisms by which exercise ameliorates these conditions, particularly the contribution of mechanosensitive channels such as Piezo1, remain incompletely elucidated. To explore these mechanisms, T1DM mice were subjected to a 6-week treadmill training protocol (15 m/min, 20 min/day, 6 days/week) to evaluate the functions of exercise on diabetic osteoporosis and hyperglycemia. Exercise intervention markedly improved bone quality in T1DM mice, alleviating osteoporotic manifestations, as evidenced by enhanced mechanical strength, restored bone microarchitecture, and normalized histomorphology. Concurrently, exercise significantly reduced hyperglycemia. To clarify the role of Piezo1, mechanical stretch was applied to Piezo1-knockout MC3T3-E1 (Piezo1^−/−) cells in vitro, mimicking the mechanical stimulation induced by exercise. Consistent with the in vivo results, mechanical stimulation facilitated osteogenic differentiation and glucose metabolism through Piezo1-mediated mechanotransduction. Importantly, these beneficial effects were substantially abrogated in Piezo1^−/− cells, highlighting the central role of Piezo1. Collectively, these findings demonstrate that Piezo1-mediated mechanotransduction constitutes a critical factor by which exercise mitigates osteoporosis and hyperglycemia in T1DM mice. This study provides a framework for the development of new therapeutic strategies targeting Piezo1-mediated mechanotransduction for T1DM management. Full article

Background/Objectives: Regular physical exercise is strongly recommended for individuals with type 1 diabetes mellitus (T1DM) because of its beneficial effects on cardiovascular fitness, insulin sensitivity, metabolic control, and overall health. Nevertheless, participation in physical activity remains limited, largely due to the fear of exercise-induced hypoglycemia and glycemic instability. Glycemic responses to exercise in T1DM are influenced by the interaction between exercise modality, circulating insulin levels, nutritional status, and diabetes technologies. Continuous aerobic exercise, resistance training, high-intensity interval exercise, and mixed intermittent activities elicit distinct metabolic and hormonal responses, resulting in heterogeneous glycemic trajectories. This narrative review aimed to provide a clinically oriented synthesis of the physiological mechanisms underlying exercise-related glycemic fluctuations in T1DM and to discuss integrated insulin- and carbohydrate-based strategies to support safer participation in physical activity in the context of modern diabetes technologies. Methods: A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and complementary searches in Google Scholar to identify experimental studies, observational studies, systematic reviews, consensus statements, and clinical guidelines focused on exercise-related glycemic responses in individuals with T1DM. Only articles published in English were considered. Evidence was selected and synthesized according to relevance to exercise modality, insulin therapy strategies, carbohydrate management, and diabetes technologies, including continuous glucose monitoring, continuous subcutaneous insulin infusion, and automated insulin delivery systems. The final narrative synthesis was based on 44 selected studies, reviews, consensus statements, and guidance documents considered most relevant to the objectives of this narrative review. Results: Available evidence indicates that continuous moderate-intensity aerobic exercise is most consistently associated with progressive glucose declines and increased risk of hypoglycemia, particularly when performed in the presence of elevated insulin on board. In contrast, resistance exercise and short-duration high-intensity or anaerobic exercise more frequently induce stable glycemia or transient hyperglycemia through adrenergic stimulation and increased hepatic glucose output. Mixed and intermittent exercise modalities often produce more variable responses depending on exercise sequencing, nutritional status, and insulin exposure. Across studies, integrated adjustment of basal and prandial insulin doses together with individualized carbohydrate supplementation emerged as the most effective strategy to reduce exercise-related glycemic instability. Continuous glucose monitoring and insulin pump technologies improved glucose trend awareness and management flexibility; however, physical exercise remains a challenging condition for current automated insulin delivery algorithms and still requires active user-driven decision-making. Conclusions: Exercise management in T1DM should be based on an individualized interpretation of exercise modality, glucose trends, insulin exposure, and nutritional context rather than on fixed glucose thresholds alone. Combining anticipatory insulin adjustments, tailored carbohydrate strategies, and appropriate use of diabetes technologies may substantially reduce glycemic variability and improve confidence toward physical activity participation. Structured education and individualized clinical guidance remain essential to translate physiological knowledge into effective real-world exercise management. Full article

The VHL–HIF-1α–VEGF axis regulates angiogenesis and metabolism. Beyond oncology, pVHL is essential for pancreatic β-cell function and is reduced in hypercaloric diet (HCD)-induced type 2 diabetes mellitus (T2DM). This study aimed to overexpress pVHL in pancreatic tissue and evaluate its effects on blood glucose levels and the expression of proteins related to glucose metabolism in the pancreas. HCD-induced diabetic C57BL/6 and BALB/c mice received a single intrapancreatic injection of an adenoviral vector (1 × 10¹² viral particles) encoding the murine Vhlh gene (AdVHL) to induce transient pVHL overexpression. The glycemic delta (post-load glucose minus fasting) and net incremental area under the curve (niAUC) were determined on days 3, 6, 9, 12, and 15 post-treatment, as the peak in GFP overexpression (used as a surrogate reporter of transduction efficiency) was detected between days 9 and 12. Immunohistochemistry (IHC) and immunofluorescence (IF) were used to assess the expression of pVHL, HIF-1α, GLUT-1, GLUT-2, and insulin in pancreatic tissue. AdVHL treatment significantly decreased the glycemic delta and niAUC in mice with T2DM (p < 0.01). On day 15 after treatment, HIF-1α and GLUT-1 expression were markedly reduced in AdVHL-treated mice (p < 0.01), while GLUT-2 and insulin were significantly increased (p < 0.01). These results were reproduced in both mouse strains. Transient overexpression of pVHL in pancreatic tissue of mice with T2DM was associated with decreased glucose levels and changes in the expression of proteins related to glucose metabolism in the pancreas, resembling a healthier phenotype than that of mice with T2DM. These findings support an important functional role of the pVHL–HIF-1α axis in pancreatic physiology, provide a proof-of-concept for further mechanistic and translational studies, and implicate pVHL in the altered glucose metabolism observed in T2DM. Full article

Background: The immune mechanism of diabetic kidney disease (DKD) has not yet been fully elucidated. This study aimed to characterize circulating lymphocyte subsets in patients with type 2 diabetes mellitus (T2DM), with a particular focus on DKD-related immune alterations and prognosis. Methods: Circulating T cells, B cells and NK cells were identified by flow cytometry. The primary endpoint was all-cause mortality, and overall survival was defined as the time from enrollment to death from any cause or last follow-up. Associations between lymphocyte subsets, inflammatory indices and renal function parameters were analyzed. Cox regression was used to identify factors associated with overall survival in patients with DKD and in the whole T2DM cohort. A prognostic nomogram was developed in the whole T2DM cohort to estimate 1-, 2-, 3-, and 5-year overall survival (OS) probabilities. Model performance was evaluated using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Mendelian randomization (MR) was performed as a further exploratory analysis to assess whether immune-related traits were genetically associated with DKD susceptibility, with inverse variance weighting (IVW) as the primary analytical method. Results: In total, 74 T2DM patients were divided into DKD (stage 3–4 of chronic kidney disease) and non-DKD groups. Median follow-up duration was 34.6 months. DKD patients exhibited elevated levels of NK cells, the monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). In patients with DKD, higher PLR and serum creatinine (SCr) were associated with poorer overall survival, whereas CD4⁺CD25⁺ T cell frequency was not significant after adjustment. In the whole T2DM cohort, higher frequency of circulating CD4⁺CD25⁺ T cells were associated with improved survival (HR 0.920, 95% CI 0.858–0.986, p = 0.019), whereas elevated PLR and SCr were linked to poorer outcomes. The exploratory nomogram incorporating CD4⁺CD25⁺ T cells, PLR, and SCr, showed acceptable internal performance in this cohort. As a separate exploratory analysis, MR suggested that genetically proxied CD4 expression on activated CD4 regulatory T cells was associated with a lower risk of DKD. Conclusions: DKD was associated with higher mortality and elevated MLR-, NLR-, PLR-, and NK cell levels in patients with T2DM. In patients with DKD, PLR and SCr were associated with overall survival, supporting the prognostic relevance of systemic inflammation and renal dysfunction. Individual lymphocyte subsets were not independently associated with survival in the DKD cohort after adjustment, whereas CD4⁺CD25⁺ T cell frequency provided additional prognostic information in the whole extended T2DM cohort analysis. Further validation is warranted. Full article

Diabetes Mellitus is a chronic metabolic disorder characterized by elevated blood glucose due to defects in insulin secretion or action, or both, leading to serious short- and long-term complications if not effectively managed. However, there is limited qualitative evidence exploring how youths diagnosed with Type 1 Diabetes Mellitus (T1DM) experience disease onset, management, complications, emotional adaptation, and education within the South African public healthcare system. The study aims to investigate the lived experiences of youths living with T1DM in a selected public hospital in Limpopo province, South Africa. The objectives were to explore and describe the lived experiences of youths living with T1DM. A qualitative, explorative, descriptive, and contextual design was used to gain a thorough understanding of the experiences of youths living with T1DM. A non-probability sampling technique was used to select 12 participants using a pre-determined criterion. Data were collected through individual semi-structured interviews using an interview guide. The data were analyzed using Colaizzi’s method, where themes and sub-themes were developed with the inclusion of an independent coder. Measures to ensure trustworthiness and ethical considerations were adhered to throughout the study. The findings revealed that, despite the participants sharing the same diagnosis, they experience multiple interrelated barriers that significantly hindered effective self-care management, such as limited access to diabetic diet, glucometers and supplies, treatment and informational-related barriers, school-related challenges, transportation constraints and inadequate social support. Furthermore, the findings highlighted gaps in early recognition of symptoms, standardized diabetes education, psychosocial support, and continuity of care. The study recommends the need for holistic, patient-centred, and contextualized interventions that do not only address medical management but the socioeconomic, educational, and psychological needs of youths. Full article