BACKGROUND: Older adults with type 2 diabetes mellitus (T2DM) are at high risk of both cardiovascular complications and cognitive decline, with major implications for independence and self-management. Endothelial dysfunction and impaired angiogenic capacity may play a key role. This study investigated the association between circulating angiogenic T cells (Tang cells) and cognitive function in older adults with T2DM and explored the potential impact of glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy. METHODS: A cross-sectional study was conducted on 154 T2DM patients aged 60-80 years, treated either with GLP-1 receptor agonist (GLP-1RA) plus metformin or metformin alone. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Circulating CD3+CD31+CXCR4+ Tang cells were quantified by flow cytometry. Propensity score matching was applied to control for age, body weight and HbA1c. RESULTS: In the overall cohort, higher Tang cell levels were significantly associated with better cognitive performance (MoCA, r = 0.423; MMSE, r = 0.428; both P < 0.001). After matching, 35 patients in each treatment group were included in the comparative analysis. The GLP-1RA + MET group showed significantly higher circulating Tang cell levels than the MET group, both in absolute counts and as percentage of CD3+ T cells (P < 0.001). CONCLUSIONS: Circulating Tang cell levels are positively associated with cognitive function in older adults with T2DM. GLP-1RA therapy is associated with higher Tang cell levels compared with metformin alone, suggesting a potential association with mechanisms related to endothelial repair in diabetes-related cognitive impairment in older age.

BACKGROUND: Diabetes mellitus (DM) remains a major cause of morbidity and mortality. Poor glycaemic control is a key determinant of diabetes-related complications, and vitamin D deficiency has emerged as a potential contributor to impaired glycaemic control. End-stage renal disease is one of the most severe complications of DM, imposing substantial individual and public health burdens. This study aimed to determine the prevalence and risk factors of vitamin D deficiency among patients with type 2 diabetes mellitus (T2DM) and to evaluate its association with glycaemic control and renal function. METHODS: In this cross-sectional study, 100 patients with T2DM and 100 age- and sex-matched controls were recruited. Ethical approval was obtained, and informed consent was provided by all participants. Clinical data were collected, and physical examinations were performed. Blood samples were analysed for serum vitamin D, fasting blood glucose, 2-hour postprandial glucose, serum creatinine, lipid profile, albumin, calcium, and phosphate. Nephropathy was assessed using the urinary albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Data were analysed using SPSS version 23. RESULTS: The mean age of patients and controls was 53.0 ± 10.3 years and 52.9 ± 11.2 years, respectively (p = 0.933), with comparable sex distribution. Chronic kidney disease (stage ≥ 3) was present in 12.0% of T2DM patients and 4.0% of controls. Among T2DM patients, 14.0% had vitamin D deficiency (25(OH)D ≤ 20 ng/mL) and 31.0% had insufficiency (20-<30 ng/mL), compared with 5.0% and 20.0%, respectively, among controls. Vitamin D deficiency was more frequent in older participants and in males. A higher proportion of T2DM patients with vitamin D deficiency had nephropathy (93%) compared with those without deficiency. Independent predictors of vitamin D deficiency included increasing age (aOR = 1.086, 95% CI: 1.011-1.167; p = 0.024), male sex (aOR = 12.282, 95% CI: 2.661-56.688; p = 0.001), and higher glycated haemoglobin levels (aOR = 2.438, 95% CI: 1.511-3.934; p < 0.001). CONCLUSIONS: Vitamin D deficiency is common among individuals with T2DM and is associated with male sex, advancing age, poor glycaemic control, and nephropathy. CLINICAL TRIAL NUMBER: Not applicable.

OBJECTIVE: This systematic review aimed to evaluate the outcomes of dental implant therapy in patients with diabetes mellitus (DM), focusing on survival rates, peri-implant health, the impact of glycemic control, and the efficacy of adjunctive therapies. METHODS: Following PRISMA 2020 guidelines, a comprehensive search of multiple databases was conducted up to July 2025. Included studies reported on implant outcomes in diabetic patients or relevant animal models. The methodological quality of the included studies was assessed using appropriate tools such as CONSORT, STROBE, and ARRIVE checklists. RESULTS: Out of 3,637 identified records, 54 studies were included. While overall implant survival rates in diabetic patients were often high (> 90-95%), diabetes, particularly when poorly controlled (HbA1c > 8%), was consistently associated with significantly worse outcomes. These included greater marginal bone loss (MBL), higher probing depths, increased bleeding on probing, and elevated levels of peri-implant inflammatory markers (e.g., IL-6, TNF-α) compared to non-diabetic controls. Well-controlled diabetics (HbA1c ≤ 7%) often had outcomes comparable to non-diabetics. Adjunctive antimicrobial photodynamic therapy (aPDT) proved effective in improving clinical parameters and reducing inflammation. Preclinical studies on advanced implant surfaces, such as bioactive coatings and 3D-printed porous structures, showed enhanced osseointegration in diabetic conditions. CONCLUSION: Dental implant therapy can be successful in well-controlled diabetic patients. However, poor glycemic control significantly increases the risk of peri-implant complications and failure. Successful long-term outcomes necessitate stringent glycemic control, meticulous treatment planning, aggressive maintenance, and the potential application of advanced adjunctive therapies.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by metabolic and inflammatory disturbances beyond hyperglycemia. Hepatokines such as adropin have emerged as regulators of insulin resistance and vascular function, yet the comparative metabolic effects of sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase 4 (DPP-4) inhibitors on adropin remain unclear. This study compared the effects of empagliflozin versus sitagliptin, each added to metformin, on serum adropin, insulin resistance, glycemic control, lipid profile, and inflammation in adults with T2DM. METHOD: In this single-center, randomized, open-label, parallel-group superiority trial with blinded outcome assessment and blinded statistical analysis, 100 adults with inadequately controlled type 2 diabetes mellitus (HbA1c ≥ 7.5%) receiving stable metformin therapy were allocated in a 1:1 ratio to receive empagliflozin 10 mg once daily or sitagliptin 100 mg once daily for a 12-week intervention period. The co-primary outcomes were changes in circulating adropin concentrations and insulin resistance, assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes included changes in HbA1c, fasting insulin, lipid parameters, body weight, and tumor necrosis factor-α (TNF-α). All analyses were conducted according to the intention-to-treat principle. RESULT: Ninety‑four participants completed the intervention; all were included in analyses. Serum adropin increased from 291 ± 133 to 362 ± 124 pg/mL with empagliflozin and from 299 ± 98 to 358 ± 126 pg/mL with sitagliptin (time effect: F = 19.67, p < .001). HOMA‑IR declined from 10.08 ± 4.44 to 6.65 ± 2.50 with empagliflozin and from 9.28 ± 2.97 to 7.15 ± 1.80 with sitagliptin (interaction: F = 4.85, p = .032, partial η² = 0.09). HbA1c decreased from 8.10 ± 0.53 to 7.04 ± 1.18 with empagliflozin and from 8.29 ± 0.66 to 7.62 ± 0.68 with sitagliptin (interaction: F = 4.30, p = .043, η² = 0.081). TNF‑α fell from 44.12 ± 21.52 to 30.78 ± 15.93 in empagliflozin and from 43.93 ± 21.33 to 37.65 ± 17.96 in sitagliptin (time effect: F = 37.09, p < .001). Empagliflozin produced greater reductions in fasting insulin (- 3.43 ± 2.34 µIU/mL vs. - 2.13 ± 1.17 µIU/mL, interaction p = .036), triglycerides (- 42.5 ± 23.9 mg/dL vs. - 21.9 ± 14.5 mg/dL, interaction p = .005), and a larger HDL‑C increase (+ 5.8 ± 3.1 mg/dL vs. + 3.3 ± 2.5 mg/dL, interaction p = .017). Body weight and BMI decreased similarly in both groups (time effect p < .001, no interaction). No serious adverse events occurred. CONCLUSION: Both empagliflozin and sitagliptin improved metabolic and inflammatory markers and were associated with comparable increases in circulating adropin. Empagliflozin conferred broader metabolic benefits, particularly in insulin resistance, glycemic control, and lipid profile. The parallel rise in adropin across treatment groups highlights its potential role as a treatment-responsive biomarker rather than a drug-specific effect. TRIAL REGISTRATION: This trial was prospectively registered with the Iranian Registry of Clinical Trials (IRCT ID: IRCT20160625028627N8) on May 27, 2025 (Trial ID: 83720). The complete trial record is accessible at https://irct.behdasht.gov.ir/user/trial/83720/view.

BACKGROUND: Hemodialysis patients with diabetes experience substantial symptom burden that is significantly associated with lower levels of self-care behaviors. While comfort-based nursing interventions have been shown to reduce symptom severity, the specific mechanisms through which symptom burden relates to self-care agency remain unclear. This study aimed to examine the relationships among symptom burden, comfort, and self-care agency in hemodialysis patients with diabetes, and to determine whether comfort mediates the association between symptom burden and self-care agency. METHODS: A descriptive, cross-sectional study was conducted at a hemodialysis unit in Türkiye between May and December 2024. Ethical approval was obtained from the Ethics Committee of Health Sciences at Süleyman Demirel University (Decision No: 75/20, Date: 04/29/2024), and the study was conducted in accordance with the Declaration of Helsinki. A total of 125 hemodialysis patients with diabetes (mean age 66.31 ± 10.45 years) were recruited using convenience sampling. Data were collected using the Dialysis Symptom Index, Hemodialysis Comfort Scale, and Self-Care Agency Scale. Mediation analysis using the Baron and Kenny approach with bootstrap confidence intervals was performed. RESULTS: Symptom burden and self-care agency were significantly negatively correlated (r = - 0.402, p < 0.001), representing a moderate-sized association. Comfort showed no significant correlation with symptom burden (r = - 0.126, p = 0.160) or self-care agency (r = 0.117, p = 0.194). No significant mediating effect of comfort was observed in the relationship between symptom burden and self-care agency (indirect effect β = 0.005, 95% CI: -0.014 to 0.024). Symptom burden was directly and negatively associated with self-care agency (β = -0.407, p < 0.001). Taken together, these findings do not provide empirical support for the hypothesized mediation mechanism in which comfort serves as an intermediary in the pathway from symptom burden to self-care agency. The direct association between symptom burden and self-care agency was significant and unchanged after the inclusion of comfort in the model, further confirming the absence of a mediating role. CONCLUSIONS: Symptom burden was directly and negatively associated with self-care agency, independent of comfort levels, in diabetic hemodialysis patients. This relationship was not mediated by comfort. Healthcare professionals should prioritize direct, targeted symptom management interventions to improve self-care behaviors, rather than relying primarily on general comfort-enhancement approaches.

BACKGROUND: Cardiovascular diseases (CVDs) caused by diabetes pose a significant health burden. CVD risk communication refers to the process of conveying CVD risk information to the public or patients at the individual and community levels and encouraging them to adopt effective preventive measures. However, Chinese general practitioners (GPs) do not adequately communicate CVD risks to their patients. Training may enhance the risk communication skills of GPs. Therefore, this pilot study aims to develop, implement, and preliminarily evaluate a tailored training program to enhance the skills of GPs in communicating cardiovascular risks to people with diabetes. METHODS: This is a pilot study employing a mixed-methods approach for evaluation of an educational intervention.The curriculum was designed via a literature review and discussions with experts from general practice, endocrinology, and cardiology. Following Kern's six-step teaching model, the training was delivered through a 4-session (160-min) training program. GPs from local community health service centers were invited to participate in the training program. Participants' learning outcomes were assessed using quantitative methods, while qualitative assessments focused on their experiences and perceptions of the learning process. RESULTS: One male GP and nine female GPs from 10 different community health service centers participated in the training. Post-training knowledge test scores (71.50 ± 10.55) were significantly higher than pre-training scores (47.50 ± 9.20), with a mean difference of 24.00 (95% CI: 16.31, 31.69; P < 0.001). Post-training qualitative interviews revealed enhanced participant attitudes, knowledge, and skills, with a positive impact on clinical practice. Participants suggested further refining communication elements, incorporating video demonstrations, and revising assessment materials to optimize the training program. CONCLUSION: The training program developed in this study preliminarily demonstrates feasibility, effectiveness, and wide acceptance and offers an innovative educational framework for type 2 diabetes management. Despite the inherent limitations of the pilot study, such as its limited sample size and single-center design, this work establishes a crucial foundation for subsequent curriculum refinement, expansion of the training scale, and evaluation of long-term outcomes.

PURPOSE: T1 signal intensity ratio (SIR) on MRI has not been rigorously evaluated as a noninvasive method to detect pancreatic fibrosis in patients undergoing surgery for recurrent acute (RAP) and chronic pancreatitis (CP). The aim of our study was to evaluate the association between histologic fibrosis score (FS) and T1 SIR and contrast enhancement of the pancreas on MRI among patients with RAP and CP undergoing total pancreatectomy with islet autotransplantation (TPIAT). METHODS: Patients who underwent MRI < 6 months before TPIAT between 2011 and 2023 were classified into 3 groups: definite CP (n = 23) and indeterminate CP (n = 11) by M-ANNHEIM criteria; and RAP defined as ≥ 2 episodes of imaging-documented acute pancreatitis (n = 22). The perilobular and intralobular fibrosis of each surgical biopsy was scored from 0 to 6. The FS was the sum of perilobular and intralobular fibrosis (0-12). We measured the T1 signal intensity of the pancreas and reference organs using pre-contrast T1-weighted fat-saturated (T1WFS) sequences to obtain the T1 SIR. We also measured the T1 signal intensity of the pancreas in the pre-contrast, arterial, venous, and delayed phases. RESULTS: A total of 56 patients were included. The median FS was 6.25 (range 0-12). Pancreas-to-spleen T1 SIR (p = 0.004) and pancreas-to-paraspinal T1 SIR (p = 0.03) were significantly associated with pancreatic fibrosis after adjusting for age, BMI, exocrine insufficiency, fat fraction, diabetes mellitus, and clinical diagnosis. Analysis of the enhancement curves showed that the venous phase of T1 signal intensity can differentiate between indeterminate CP, RAP and definite CP (p < 0.004 for all). CONCLUSION: Both the T1 SIR of the pancreas-to-spleen and pancreas-to-paraspinal muscle show an independent association with fibrosis. T1 SIR demonstrates a significant association with histologically quantified pancreatic fibrosis and may serve as a promising noninvasive imaging biomarker pending further validation.

BACKGROUND/OBJECTIVES: Well-established cardiometabolic disease (CMD) prevention strategies emphasize maintaining a balanced diet, regular physical activity, and a normal weight. The role of time-restricted eating (TRE; ≤12 h daily eating window) in improving cardiometabolic health remains elusive. This systematic review and meta-analysis of observational studies investigated the associations between TRE and cardiometabolic health in adults. SUBJECTS/METHODS: We systematically searched PubMed, the Cochrane Library, Web of Science, and CINAHL for observational studies examining the association between TRE and cardiometabolic markers in adults for all articles published up to January 13, 2025. Risk of bias was assessed using the NIH Quality Assessment Tool. Qualitative and random-effects meta-analyses were performed if ≥3 studies reported the same outcome; otherwise, results were summarized narratively. RESULTS: 12 cross-sectional and 6 cohort studies were included. Meta-analysis of cross-sectional studies showed no significant association between TRE and abdominal obesity (OR = 0.96; 95% CI: 0.86-1.07; I² = 59%), metabolic syndrome (OR = 1.04; 95% CI: 0.90-1.19; I² = 32%), elevated blood pressure/hypertension (OR = 1.04; 95% CI: 0.971.12; I² = 0%), reduced high-density lipoprotein cholesterol (OR = 0.94; 95% CI: 0.83-1.06; I² = 78%), elevated triglycerides (OR = 1.06; 95% CI: 0.99-1.14; I² = 0%), and prediabetes/type 2 diabetes mellitus (OR = 1.04; 95% CI: 0.96-1.12; I² = 50%). Due to insufficient data, no conclusions could be drawn about prospective associations. CONCLUSIONS: To date, cross-sectional data have not consistently demonstrated associations between TRE and cardiometabolic health in community-dwelling adults. Until stronger real-world evidence emerges, the priority should remain on established CMD prevention strategies. REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: PROSPERO registration number: CRD42023390410.

Visceral fat accumulation is a key factor in the onset of cardiometabolic diseases, including hypertension. Metabolic Score for Visceral Fat (METS-VF) is an innovative, non-invasive metric developed to estimate visceral fat based on commonly accessible clinical parameters. A total of 13,822 participants were included in this cross-sectional analysis. METS-VF was calculated using a validated formula incorporating age, sex, metabolic score for insulin resistance, waist-to-height ratio. Hypertension was defined based on measured blood pressure or self-reported physician diagnosis. Logistic regression models were used to estimate the association between METS-VF and hypertension, adjusting for sociodemographic, clinical, and dietary covariates. Subgroup, threshold effect, and ROC analyses were conducted to assess robustness and predictive ability. External validation was conducted using 8400 fasting participants from the China Health and Retirement Longitudinal Study (CHARLS) 2011 baseline cohort. METS-VF was positively associated with hypertension. In model 3, participants in the highest METS-VF quartile had substantially higher odds of hypertension (OR: 5.82, 95% CI 4.76-7.11, P < 0.001). A threshold effect was observed at a METS-VF value of 6.42. Subgroup analyses confirmed the consistency of associations across various demographic and clinical strata. Notably, high intake of protein and unsaturated fatty acids attenuated this association. ROC analysis showed METS-VF had the best discriminatory power for hypertension (AUC = 0.749) compared to BMI, WHtR and METS-IR. In the CHARLS external validation cohort, METS-VF also showed the highest AUC among the evaluated indices (AUC = 0.668), and logistic regression confirmed a consistent positive association with hypertension. METS-VF was significantly associated with prevalent hypertension and showed better discriminatory performance than traditional adiposity indices. External validation in CHARLS supports the robustness of these findings, although prospective validation is still warranted.

Maternal diabetes is associated with increased systemic inflammation and has been linked to adverse neonatal outcomes, including developmental delays that persist into early childhood. In this study we sought to characterize and compare the maternal levels and fetal cord-blood levels of the inflammatory markers C-reactive protein (CRP) and IL-6, as well as the neurotrophin brain-derived neurotrophic factor (BDNF) between mothers with pre-gestational Type-1 diabetes (T1DM) or Type-2 diabetes (T2DM), and non-diabetic controls (nonDM).A prospective cohort design was employed, analyzing biomarker concentrations during the third trimester in 98 pregnant women ages 18-40 years of age including 16 participants with T1DM, 49 participants with T2DM and 33 control participants matched for gestational age and body mass index (BMI) to control for confounding factors such as obesity. Plasma samples were collected at 28-30 weeks, 34-36 weeks, delivery, and from cord blood. The biomarkers CRP, IL-6, and BDNF were measured using standardized assays, and concentrations were compared among groups using ANOVA.In T2DM mothers, CRP levels were 2x higher in the third trimester as compared to nonDM controls. In T1DM mothers, IL6 levels were 3x lower than nonDM controls and 3.4x lower than T2DM. While not reaching statistical significance, cord-blood levels of IL6 were higher in T2DMs than other groups (p = 0.052). When examining BDNF levels, no differences were observed between groups.This study emphasizes the importance of addressing inflammation-related risks in pregnancies affected by diabetes. Targeted interventions may mitigate adverse neonatal outcomes and improve health trajectories. Future research should explore direct pathways linking maternal inflammation to fetal neural function to inform clinical strategies.

OBJECTIVE: To analyze the relationship between serum resistin and irisin concentrations and the morphological characteristics of atherosclerotic plaques assessed by optical coherence tomography (OCT) in patients with coronary artery disease. METHODS: A cross-sectional observational study was conducted on 51 patients. In addition to recording comorbidities, irisin and resistin levels were measured using ELISA, and structural plaque parameters (fibroatheroma, neovascularization, calcification, and macrophages) were assessed using OCT. Age- and sex-adjusted regression models were constructed to evaluate the associations of both biomarkers with comorbidities and plaque characteristics. Regression coefficients (β), 95% confidence intervals (95% CI), and p-values were reported. RESULTS: In the overall patient population, irisin levels were significantly associated with the presence of fibroatheromas (β=8.98 [0.20-17.77]; p=0.045) and neovascularization (β=6.48 [0.47-12.49]; p=0.035). In patients with acute coronary syndrome (ACS), this biomarker showed a stronger association with fibroatheroma (β=11.25 [2.83-19.66]; p=0.010) and neovascularization (β=8.83 [2.38-15.29]; p=0.009). Resistin levels were higher in patients with diabetes mellitus (β=2.41 [0.10-4.72]; p=0.041) were not associated with plaque morphological characteristics. CONCLUSIONS: In patients with coronary artery disease, irisin is associated with fibroatheroma and neovascularization, particularly in the context of ACS. In these patients, resistin is related to diabetes mellitus but not to atherosclerotic plaque features. Both biomarkers may represent different pathophysiological pathways in atherosclerosis.

CONTEXT: Anorexia nervosa (AN) is associated with severe metabolic and endocrine alterations, including growth hormone (GH) resistance and reduced insulin-like growth factor 1 (IGF-1). The longitudinal behavior of IGF-1 during treatment remains incompletely characterized. OBJECTIVE: To evaluate IGF-1 levels in current and weight restored AN, determine metabolic correlates, and examine longitudinal changes during clinical treatment. DESIGN: Cross-sectional analysis in a population-based cohort and longitudinal analysis in a clinical cohort. SETTING: UK Biobank (UKB) and a specialist eating disorder clinic. PARTICIPANTS: (i) UKB: 129 adult women with current AN, 2,380 weight restored AN, and 2,380 healthy controls (HC) matched for age, sex, and BMI. (ii) Clinical cohort: 189 adult women with AN assessed at baseline and 12-month follow-up. MAIN OUTCOMES MEASURES: Plasma IGF-1 levels; secondary metabolic and reproductive hormones including GH, insulin, glucose, FT3, and gonadal hormones. RESULTS: Across the UKB groups, IGF-1 levels showed a graded pattern: lowest in current AN, medium in weight restored AN, and highest in HC. In the clinical cohort, IGF-1 correlated positively with insulin, glucose, and FT3, and negatively with GH, consistent with GH resistance. IGF-1 levels increased significantly over 12 months of treatment (p = 0.003), with higher BMI at baseline predicting greater increases. Higher IGF-1 levels were associated with greater likelihood of menstrual function independent of BMI (p < 0.001). CONCLUSIONS: IGF-1 appears reduced in current AN and may only partly normalize with weight restoration. IGF-1 may reflect metabolic state and reproductive function, suggesting value as an indicator of severity and treatment response.

BACKGROUND AND OBJECTIVE: Patients with psoriasis and concomitant diabetes mellitus (DM) may be vulnerable to diabetes-related adverse events (DM-AEs). This study aimed to evaluate the incidence of DM-AEs associated with systemic treatments used in patients with psoriasis and DM. METHODS: We conducted a prospective cohort study using data from the BIOBADADERM registry. We calculated incidence rates (IRs) of DM-AEs for each systemic treatment class, including biologics (tumor necrosis factor [TNF] inhibitors, interleukin [IL]-12/23 inhibitors, IL-17 inhibitors, and IL-23 inhibitors), conventional systemic therapies (methotrexate [MTX], cyclosporine, and acitretin), and apremilast (APR). The primary outcome was the adjusted incidence rate ratio (aIRR) for DM-AEs comparing patients receiving MTX with those receiving other systemic therapies using Poisson regression models adjusted for potential confounders. RESULTS: The study included 732 patients, 1401 treatment cycles, and 2865 person-years (PYs) of follow-up. APR (aIRR, 0.30; 95%CI, 0.10-0.60) was associated with a significantly lower risk of DM-AEs compared with MTX. Cyclosporine (aIRR, 7.50; 95%CI, 3.30-17.30) and acitretin (aIRR, 2.10; 95%CI, 1.20-3.70) were associated with a higher risk compared with MTX. CONCLUSIONS: Among patients with psoriasis and DM, APR was associated with a lower incidence of DM-AEs, whereas cyclosporine and acitretin were associated with higher incidences compared with MTX.

OBJECTIVES: Pregestational diabetes (PDM) and gestational diabetes mellitus (GDM) have increased in the U.S., with persistent racial/ethnic disparities. We examined PDM and GDM prevalence and associated social determinants of health (SDOH) across disaggregated racial/ethnic subgroups in California. METHODS: We included 1,627,679 pregnant women with singleton births (2013-2022) from the California birth certificate database. We estimated age-standardized prevalence, annual percent change (APC), and prevalence ratios (PRs) for SDOH associated with PDM and GDM. RESULTS: From 2013 to 2022, PDM prevalence increased 1.8-fold (0.4% to 0.7%; APC = 7.7%) and GDM increased 1.5-fold (4.8% to 7.2%; APC = 5.1%). Asian and Hawaiian/Pacific Islander experienced the largest APC for both PDM (10.6%) and GDM (6.4%). Hawaiian/Pacific Islander (2.1%) and Hmong (1.3%) women had the highest PDM prevalence, while Hmong (12.1%) and Asian Indian (10.5%) women had the highest GDM. Lower education level was associated with higher PDM (PR = 1.76 [1.67, 1.85]) and GDM (1.15 [1.13, 1.17]). Foreign-born was associated with lower PDM (0.91 [0.87, 0.96]), but higher GDM (1.24 [1.22, 1.25]), with large variations across subgroups. Prenatal Medicaid vs. private insurance was associated with higher GDM, excepting Korean and Vietnamese. CONCLUSIONS: PDM and GDM prevalence increased across all racial/ethnic groups in California, with pronounced heterogeneous SDOH associations across disaggregated subgroups.

Current therapies for diabetes mellitus, a highly prevalent chronic metabolic disorder, rarely achieve etiological intervention and are limited by poor patient compliance and significant side effects. Extracellular vesicles (EVs), nanoscale carriers of intercellular communication, offer a promising therapeutic alternative due to their high biocompatibility, low immunogenicity, and inherent capacity for delivering biomolecules to specific targets. This review systematically synthesizes recent progress in EV-based strategies for diabetes. First, we examine how mammalian-derived EVs (such as from mesenchymal stem cells and immune cells) directly protect and restore pancreatic β-cells, restore immune tolerance, and ameliorate systemic insulin resistance. Second, we highlight the emerging potential of plant-derived EVs, which allow for oral administration and modulate metabolism via gut-organ axes. We further discuss the engineering of EVs into targeted drug delivery systems, with a focus on breakthroughs in oral insulin delivery and their applications in treating diabetic complications, including nephropathy, chronic wounds, and liver-brain axis-related disorders. Finally, we outline the key challenges of standardization, scalable production, and clinical translation, proposing a roadmap for future research. This comprehensive analysis underscores the potential of EVs to provide transformative strategies for diabetes management through multifaceted mechanisms and innovative engineering strategies.

Diabetes mellitus exacerbates myocardial ischemia/reperfusion injury (MI/RI), but the underlying mechanisms remain unclear. The present study identifies advanced glycation end-products (AGEs) as a key pathological mediator. Upon hypoxia/reoxygenation (H/R) stimulation, AGEs-primed cardiomyocytes exhibited drastic mitochondrial oxidative damage, characterized by elevated mitochondrial reactive oxygen species (mtROS), loss of mitochondrial membrane potential, depletion of ATP, and increased release of mitochondrial DNA and cytochrome c. Mechanistically, AGEs impaired the mitochondrial antioxidant defense via the RAGE-Nrf2-SOD2 axis. Furthermore, AGEs activated the AIM2-ZBP1 PANoptosome, triggering PANoptosis characterized by concurrent upregulation of cleaved caspase-3, GSDMD, and p-MLKL. Mitochondrial oxidative damage was established as the causal upstream event, as a mitochondria-targeted antioxidant or RAGE silencing attenuated PANoptosis, while mtROS inducer (antimycin A) directly activated PANoptosis. Therapeutically, combination treatment with pyridoxamine (an AGEs inhibitor) and empagliflozin (an SGLT2 inhibitor) in diabetic mice potently suppressed AGEs accumulation, mitigated mitochondrial damage and PANoptosis, and significantly improved cardiac recovery post-MI/R. Thus, targeting the AGEs-mitochondrial damage-PANoptosis axis via combined pyridoxamine and empagliflozin represents a promising strategy to alleviate diabetic MI/RI.

Fermented foods and beverages represent dynamic biological ecosystems that integrate microbial communities, bioactive metabolites, and host interactions to promote health across nutritional, functional, and therapeutic domains. This comprehensive narrative review synthesizes current evidence on medicinal and edible fermented products, focusing on their bioactive generation, molecular mechanisms, and systemic health outcomes mediated by the gut microbiome. Fermentation processes, driven by lactic acid bacteria, yeasts, and mixed consortia, transform substrates into 31 key bioactives, including short-chain fatty acids (SCFAs), bioactive peptides, exopolysaccharides (EPS), and modified polyphenols. These compounds arise through microbial proteolysis, glycolysis, and biotransformation, enhancing bioavailability and functionality compared to unfermented counterparts. Mechanistically, bioactives strengthen gut barrier integrity via tight-junction upregulation and mucin production; modulate immunity through Toll-like receptor activation and T-cell differentiation; regulate metabolism by improving glucose/lipid profiles; and mitigate inflammation via NF-κB inhibition and Nrf2 activation. Gut microbiota-host crosstalk extends these effects systemically, influencing the gut-brain axis and extra-intestinal organs. Epidemiological and clinical data link regular consumption particularly of yogurt, kimchi, and kefir-to reduced risks of colorectal cancer (dose-response patterns), type 2 diabetes (8-15% HbA1c reductions), cardiovascular disease (5-10% cholesterol lowering), and enhanced immune resilience (20-35% fewer infections). Benefits also encompass gastrointestinal health (IBS symptom relief), neuroprotection (cognitive improvements), and cancer prevention. Despite promising findings, challenges persist in standardization, microbial viability during processing, and long-term human trials. Future directions emphasize multi-omics integration, AI-driven precision fermentation, and personalized interventions to validate fermented products as evidence-based therapeutics, bridging traditional practices with modern nutrition science.

OBJECTIVE: As part of the 2025 diabetes and technology (dt)-report, this study explored indications for use, barriers to adoption, and perceived functionality of smart pens. METHODS: An online survey conducted between November and December 2024 gathered responses from diabetes specialists and diabetes educators (health care professionals [HCPs]) in Germany (DE), Austria (AT), Switzerland (CH), and Spain (ES). Participants estimated the proportion of individuals with diabetes who would benefit from smart pens, rated the significance of specific functions, and evaluated barriers on 5-point scales. RESULTS: The survey included 1294 HCPs (69.2% DE, 9.7% AT, 7.0% CH; 14.1% ES). Current usage of smart pens is estimated at 4% to 15% for people with type 1 diabetes and 3% to 6% for those with type 2 diabetes. However, the indication rate is markedly higher, ranging from 51% to 73% for people with type 1 and up to 69% for those with type 2 with intensive insulin therapy. Most valued features included reminders for missed insulin doses (4.4 ± 0.7), bolus dose suggestions (4.1 ± 0.8), integration with continuous glucose monitoring (CGM) apps (4.1 ± 0.8), and temperature alerts (3.7 ± 1.0). Basal insulin suggestions were considered less important (3.3 ± 1.1). No significant differences were found between physicians and diabetes educators. Major barriers included preference for disposable pens (57%), limited device options (54%), and high cost (53%). Among DE respondents, concerns over cost reimbursement rose compared to the 2024 dt-report. CONCLUSION: Smart pens are underutilized compared to expectations. Cost and reimbursement remain the predominant barriers, while reminder functionality stands out as the most valued feature.

BACKGROUND: To assess the accuracy of a continuous glucose monitoring (CGM) system under hyperglycemic conditions, we conducted a steamed bread meal tolerance test (SBMTT) in hospitalized patients aged 18 years or older with type 1and 2 diabetes mellitus. METHODS: Hospitalized adults with diabetes wore a Sibionics CGM (GS1) sensor, which was placed at least 48 hours prior to the test. Participants subsequently underwent an SBMTT containing 75 g of carbohydrates. Plasma glucose (PG) was measured at 0, 30, 60, 120, and 180 minutes. Accuracy was evaluated by calculating the mean absolute relative difference (MARD), %15/15, %20/20, %30/30, and %40/40 agreement rates. Clinical accuracy was assessed using the Diabetes Technology Society (DTS) error grid analysis. The time lag between CGM and PG was calculated. RESULTS: A total of 580 matched CGM-PG pairs from 116 participants were analyzed. The overall MARD was 11.83%, with agreement rates of 69.5% (%15/15), 86.2% (%20/20), 98.3% (%30/30), and 99.7% (%40/40). Diabetes Technology Society error grid analysis showed 100% of the CGM points falling into zones A and B, with 86% in zone A and 14% in zone B. After minimizing MARD, the overall CGM lag time was 5 minutes, but it increased during rapid glucose rise (0-60 minutes), reaching 10 minutes at 30 minutes and 20 minutes at 60 minutes. CONCLUSIONS: Continuous glucose monitoring maintained good accuracy during hyperglycemic challenges in hospitalized patients with diabetes. The time lag was influenced by the rate of glucose change, showing prolongation during the rapid glucose rise phase (0-60 minutes).

Type 2 diabetes mellitus (T2DM) is an issue that has risen in prevalence rates globally necessitating new and more complex modes of treatment that surpass the conventional pharmacotherapy. This has been made possible by the development of the thermoresponsive sol-gel depot systems that utilizes the phase transition between amphiphilic block copolymer which is temperature dependent in order to form a in-situ semi-solid reservoir after the drug is subcutaneously injected to allow for sustained release of near zero-order release of a drug over a prolonged period. The review is a critical analysis of the physicochemical fundamentals of the thermoresponsible sol-gel systems such as polymer chemistry, rheological behaviour and polymer-drug interaction that defines therapeutic output. The low critical solution temperature (LCST) behaviour is of particular concern in PEG-PLGA -PEG triblock copolymer, Pluronic systems and in new stimulus sensitive polymers. They are systematically evaluated when used with peptide-based antidiabetic therapeutics such as insulin analogues and GLP-1 receptors agonists. Even some of the more advanced techniques of formulations are covered including nanoparticle constructed depots and glucose powered hydrogels. Such critical questions in translations as burst release, thermomechanical instability, immunogenicity, and regulatory limitations are of heightened interest. It is an integration of polymer science, nanotechnology and pharmaceutical engineering review that provides a mechanistic nature in the rational development of the next-generation long-acting injectable depot systems.

Nuclear factor κB (NF-κB)-inducing kinase (NIK) is a critical component of the noncanonical NF-κB pathway and an important regulator of immune response. NIK deficiency causes loss of lymph nodes, disruption of lymphoid organ structure and deficits in B-cell formation and immunoglobulin production. In this study, we generated adipocyte-specific NIK-knockout (Adipo-NIK-KO) mice to study the role of this protein in adipose tissue metabolism. We found that NIK depletion in mouse primary adipocytes potentiates thermogenic capacity without altering the differentiation of these cells. Loss of NIK in adipocytes stimulated Fibroblast growth factor 21 (FGF21)-induced expression of thermogenic genes, including Uncoupling protein 1 (UCP1) and mitochondrial uncoupled respiration. In fact, enhanced browning of subcutaneous fat depots was detected in Adipo-NIK-KO mice, which also had elevated energy expenditure. These mice exhibited improved glucose tolerance and insulin sensitivity and reduced hepatic lipid deposition upon diet-induced obesity. Similarly, inhibition of NIK by a specific small molecule enhanced metabolic rate and glucose homeostasis in obese mice. Therefore, NIK inhibition holds therapeutic potential for reversing glucose intolerance and insulin resistance associated with obesity.

BACKGROUND: Continuous glucose monitoring (CGM) is a wearable medical device that continuously tracks blood glucose levels through a small sensor implanted typically on the abdomen, arm, or buttocks of the patient with diabetes to ensure real-time tracking of blood glucose. Many systematic literature reviews (SLRs) explored the efficacy of CGM versus self-monitoring of blood glucose (SMBG) in different patient populations. OBJECTIVE: To conduct an umbrella review of existing SLRs and perform a meta-analysis of their underlying primary studies to compare CGM versus SMBG in terms of glycated hemoglobin (Hb1Ac). METHODS: This is an umbrella review (overview of reviews) of studies assessing CGM efficacy compared with SMBG. PubMed, EMBASE, and Web of Science databases were searched systematically between January 2000 and February 2024. To avoid double counting of overlapping data across reviews, quantitative synthesis was conducted at the level of the primary studies identified within the SLRs. Data extracted included HbA1c measurements, population characteristics (diabetes type/age category/Insulin regimen), study characteristics (study design/follow-up duration), and device type were collected. AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews) checklist and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool were used to appraise the quality of the included SLRs. Effect sizes with corresponding 95% confidence intervals (CIs) of the individual included studies of HbA1c were synthesized using the DerSimonian-Laird method with random effects model. Meta-regression was performed to explore the impact of different variables on the treatment effect. RESULTS: Forty SLRs were included in the review with a total of 78 261 patients. Continuous glucose monitoring achieved greater reduction in HbA1c than in the control group (absolute mean difference: 0.31% (95% CI 0.26%-0.36%). While the direction of effect favored CGM across subgroups, high unexplained heterogeneity was observed ( = 89.7%). CONCLUSION: This is the first overview of SLRs involving quantitative primary-level meta-analysis of studies of patients with diabetes of all ages and all CGM devices. While CGM devices show a significant overall benefit in reducing HbA1c, the high unexplained heterogeneity suggests that results should be generalized with caution, as the degree of benefit may vary across different clinical settings.

OBJECTIVES: To evaluate the effectiveness of continuous glucose monitoring (CGM) in women with gestational diabetes mellitus (GDM), with a focus on maternal and neonatal outcomes. METHODS: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were systematically searched up to March 2026 for randomized controlled trials. Pooled mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. RESULTS: Twelve studies involving 1639 women with GDM were included. The CGM use significantly improved time in range (MD = 2.52, 95% CI = 1.37 to 3.67) and was associated with a higher proportion of women requiring pharmacotherapy (RR = 1.15, 95% CI = 1.01 to 1.32). No significant differences were observed in maternal hemoglobin A1c (HbA1c) (MD = -0.11, 95% CI = -0.24 to 0.01), cesarean section (RR = 0.97, 95% CI = 0.85 to 1.10), large for gestational age (RR = 0.64, 95% CI = 0.40 to 1.02), macrosomia (RR = 1.13, 95% CI = 0.73 to 1.74), or neonatal hypoglycemia (RR = 0.86, 95% CI = 0.67 to 1.11). CONCLUSIONS: The CGM use in women with GDM significantly improves time in range and increases the use of pharmacotherapy, but it yields no significant differences in other maternal, neonatal, or glycemic outcomes.

Childhood emotional abuse and neglect (CEAN) are adverse experiences that are often underrecognized for their long-lasting impacts on health. Despite research having demonstrated a link between childhood adversity and diabetes, the association between CEAN and the timing of diabetes diagnosis, along with their sociodemographic patterns, remains poorly understood. This cross-sectional survey collected data on CEAN from 306 Saudi individuals diagnosed with diabetes. Employing a culturally modified version of the self-report Childhood Trauma Questionnaire-Short Form, the severity of CEAN was evaluated using composite scores (none, moderate, or severe) derived from the questionnaire items. Chi-square tests were used to examine associations among abuse severity, sociodemographic variables, and age at diagnosis, with Cramér's V calculated to determine the effect size. Multivariable logistic regression was performed to adjust for potential confounders. Severe emotional abuse was reported by 38.9% of the participants, and severe neglect by 22.2%. Severity levels of both emotional maltreatment and neglect were significantly correlated with sex, age group, marital status, educational attainment, occupation, and age at diagnosis (all P < .05). Greater severity of both emotional abuse and neglect was correlated with an older age at diabetes diagnosis, demonstrating linear trends. CEAN are prevalent among individuals with diabetes and are significantly associated with sociodemographic factors and age at diagnosis. In multivariable logistic regression analysis, adjusting for age and sex, emotional abuse was independently correlated with an earlier age at diabetes diagnosis (adjusted odds ratio = 2.62, 95% confidence interval: 1.25-5.49, P = .011). These findings underscore the enduring impact of early-life emotional adversity on health and highlight the need to incorporate trauma informed and socially responsive strategies in diabetes management and prevention.