Pulmonary embolism (PE) and diabetes mellitus share an intertwined cardiometabolic pathway that contributes to poor prognosis and higher mortality among patients. However, national trends in PE-related mortality involving diabetes remain underexplored.

Mortality data were extracted from the CDC WONDER Multiple Cause of Death database (1999-2024) using ICD-10 codes I26 for pulmonary embolism and E10-E14 for diabetes mellitus. Joinpoint regression was used to estimate APC (Annual Percent Change) and AAPC (Average Annual Percent Change). A p-value < 0.05 was considered statistically significant.

Between 1999 and 2024, the co-recorded pulmonary embolism and diabetes on death certificates showed 82,241 deaths, with the most deaths being recorded at the medical facility (61.29%). The overall AAMR rose significantly from 1.08 in 1999 to 1.88 in 2024, with an associated AAPC of 1.98 (95% CI: 1.10 to 2.87; p < 0.001). Widening gender gaps were observed, where males demonstrated higher mortality throughout the period. In 1999, men had an AAMR of 1.11, while women had an AAMR of 1.05. In 2024, it was 2.19 (AAPC: 2.44; 95% CI: 1.45 to 3.45; p < 0.001) in males and 1.63 (AAPC: 1.46; 95% CI: 0.18 to 2.76; p = 0.02) in females. Non-Hispanic Black individuals had the highest AAMR in 2024, at 4.01 (AAPC: 1.29; p = 0.06), followed by non-Hispanic White individuals (AAMR: 1.73), Hispanic or Latino individuals (AAMR: 1.59), and NH Other (AAMR: 0.98). Rural areas had steeper increases (AAPC: 3.32; p < 0.001) with AAMR rising from 1.30 in 1999 to 2.70 in 2020, compared to urban areas (AAPC: 2.34%; p < 0.001), which rose from 1.04 to 1.85 over the same period. Geographically, the West showed the steepest long term increase (AAPC: 2.48) followed by the South (2.09). States with the highest AAMRs included the District of Columbia (2.36) and Mississippi (2.08); states with the lowest AAMRs included Hawaii (0.62) and Nevada (0.64).

PE and diabetes related mortality have increased significantly from 1999 to 2024, with disproportionate burden in males, rural and Southern populations. The results emphasize the need for improved cardiometabolic risk stratification and equitable access to healthcare in vulnerable populations.

The online version contains supplementary material available at https://doi.org/10.1007/s40200-026-02092-2.

Patients with diabetic foot ulcers (DFU) have a high cardiovascular risk. We evaluated the association of baseline total serum magnesium (Mg) with major adverse cardiovascular events (MACE) without presuming a causal or therapeutic effect.

This single-center retrospective cohort included 1,176 patients with active DFU admitted from 2015 through 2022. The endpoint was the first MACE, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Cox models estimated hazard ratios (HRs) per 0.1 mmol/L and per standard deviation (SD) of Mg and by data-defined quartile groups. The extended model additionally adjusted for HbA1c, eGFR, albumin, log-transformed C-reactive protein, HDL-C, and LDL-C. Restricted cubic splines used four knots. Competing-risk, renal-function, complete-case, prior-cardiovascular-disease, time-specific, and propensity-score-matched analyses were performed.

During a median follow-up of 3.6 years, 304 MACE events occurred, including 216 cardiovascular deaths and 88 combined nonfatal myocardial infarctions or strokes. In the extended model, each 0.1 mmol/L higher Mg was associated with lower MACE hazard (HR 0.87, 95% CI 0.80-0.95; p=0.002); the HR per SD was 0.83 (95% CI 0.74-0.94; p=0.002). The spline model supported an overall (p<0.001) and nonlinear (p<0.001) association. An exploratory two-change-point model selected 0.83 and 0.99 mmol/L, but profile-likelihood regions were broad (0.75-0.85 and 0.95-1.10 mmol/L). Results were directionally consistent in competing-risk and other sensitivity analyses. In 324 matched pairs, the high (>0.80 mmol/L) versus low (≤0.80 mmol/L) contrast was associated with lower MACE hazard (pair-stratified HR 0.60, 95% CI 0.39-0.92; p=0.020), whereas the continuous estimate was less precise (HR 0.85, 95% CI 0.71-1.01; p=0.070).

Baseline serum Mg was independently associated with MACE risk in patients with DFU, with an exploratory nonlinear pattern. The data-derived change points are not therapeutic boundaries and require external prospective validation. These observational findings do not establish benefit from Mg supplementation.

Metabolically healthy obesity (MHO) is commonly defined by the absence of metabolic syndrome-related abnormalities despite obesity. However, conventional clinical definitions may overlook substantial metabolic heterogeneity and hidden cardiometabolic risk. We aimed to identify metabolomic signatures distinguishing MHO from metabolically unhealthy obesity (MUHO), evaluate their discriminatory performance, and determine whether metabolomic profiling could further characterize heterogeneity within conventionally defined MHO.

We analyzed 13215 UK Biobank adults with obesity and available clinical biomarker and NMR-based metabolomic data. Metabolic health was defined using triglycerides, HDL cholesterol, hypertension, fasting glucose, type 2 diabetes, and lipid-lowering medication use. Univariable logistic regression and LASSO regression were used for metabolite selection. Logistic regression and XGBoost models were developed using clinical variables, metabolomic markers, and their combination. A weighted metabolic signature score was applied within the MHO group to characterize cross-sectional metabolic and clinical heterogeneity, and proteomic analyses were performed in approximately 1408 participants.

A six-metabolite signature comprising HDL_size, S_HDL_CE, XL_HDL_TG, GlycA, M_VLDL_C, and Omega_3 was selected. The combined clinical-metabolomic model showed better discrimination than clinical variables alone in the test set, with AUCs of 0.78 and 0.69, respectively. Within MHO, higher metabolomic score was associated with higher triglycerides, HbA1c, waist-to-hip ratio, lower HDL cholesterol, and greater metabolic and cardiovascular comorbidity burden. Proteomic analyses identified 10 metabolite-associated core proteins implicating lipoprotein remodeling, adipokine signaling, inflammation, and vascular-related pathways.

A six-metabolite signature distinguished MHO from MUHO and revealed hidden metabolic risk within conventionally defined MHO, provides a metabolomic framework for refining obesity phenotyping and warrants further validation before clinical translation.

Ecnoglutide, a novel long-acting GLP-1 receptor agonist, is considered a promising therapeutic option for the treatment of diabetes. This study aims to evaluate the efficacy and safety of ecnoglutide in adults with type 2 diabetes and to further investigate its dose-time relationship.

This study followed the PRISMA guidelines and systematically searched PubMed, Web of Science, Embase, and Cochrane Library, with the search updated through February 2026. Randomized controlled trials comparing ecnoglutide with placebo or the active control, dulaglutide, were included. The primary outcome was the change in HbA1c (%). Secondary outcomes included FPG, PPG, 7-point SMBG, body weight, adverse events, and serious adverse events. Risk of bias was assessed using the Cochrane RoB-2 tool. Meta-analyses employed a random-effects model, and mean differences and risk ratios were calculated with 95% confidence intervals.

Three randomized controlled trials involving 977 participants were included. Compared with placebo, ecnoglutide significantly reduced HbA1c (MD = -1.40, 95% CI -1.65, -1.14, p < 0.00001), FPG (MD = -1.98, 95% CI -2.34, -1.63, p < 0.00001), PPG (MD = -4.88, 95% CI -6.32, -3.44, p < 0.00001), and body weight (MD = -2.16, 95% CI -2.62, -1.71, p < 0.00001). Additionally, compared with the placebo group, the incidence of adverse events was higher in the ecnoglutide group (OR = 2.03, 95% CI 1.24-3.32, p = 0.005), while there was no significant difference in the incidence of serious adverse events. Dose-response analysis showed that ecnoglutide exhibited a clear dose-dependent relationship for HbA1c, FPG, and body weight at doses ranging from 0.4 to 1.2 mg, while PPG was less affected by dose. Time-response analysis indicated that the hypoglycemic efficacy of ecnoglutide peaked around week 35 and subsequently plateaued, whereas body weight exhibited a sustained linear downward trend.

Ecnoglutide significantly improved glycemic control and reduced body weight, although it was associated with a higher incidence of adverse events without increasing serious adverse events. Despite these promising findings, the evidence remains limited and requires confirmation in larger, multicenter randomized controlled trials.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420261327235, identifier CRD420261327235.

Sarcopenia is a common geriatric syndrome that substantially impairs physical function, mobility, and quality of life in older patients with type 2 diabetes mellitus. However, evidence regarding factors associated with sarcopenia in this population remains fragmented and inconsistent, and previous studies have often included mixed-age populations or provided limited quantitative synthesis specifically focused on older adults. Therefore, this systematic review and meta-analysis aimed to comprehensively identify and quantify the associations between clinical factors and sarcopenia in older patients with type 2 diabetes mellitus, thereby providing age-specific evidence for clinical assessment, early identification, and individualized management.

Relevant studies examining factors associated with sarcopenia in older patients with type 2 diabetes mellitus were systematically searched in six databases: PubMed, Web of Science, Embase, the Cochrane Library, CNKI, and Wanfang Data. The search covered the period from database inception to January 2026. Study characteristics, participant characteristics, potential associated factors, and sarcopenia-related outcomes were extracted. The methodological quality of the included cross-sectional studies was assessed using the AHRQ checklist. Meta-analyses were conducted using Review Manager version 5.3. Continuous variables were pooled using mean differences or standardized mean differences, and dichotomous variables were pooled using odds ratios. Publication bias and small-study effects were assessed using funnel plots and Egger's regression test when at least 10 studies were available for a given outcome. For outcomes with substantial heterogeneity, REML-based 95% prediction intervals and exploratory univariable meta-regression analyses were conducted when sufficient data were available. The certainty of evidence for each pooled outcome was assessed using the GRADE approach.

A total of 19 cross-sectional studies involving 4,727 older patients with type 2 diabetes mellitus were included. The included studies were of moderate to high methodological quality, with no low-quality studies identified. Sarcopenia was diagnosed using different criteria, including the Asian Working Group for Sarcopenia 2014 criteria, the AWGS 2019 criteria, the European Working Group on Sarcopenia in Older People criteria, and the revised EWGSOP2 criteria. Meta-analysis showed that patients with sarcopenia were significantly older than those without sarcopenia, and had a longer duration of diabetes, higher fasting blood glucose levels, higher HbA1c levels, lower body mass index, and lower hemoglobin levels. No statistically significant associations were observed for male sex, total cholesterol, triglycerides, HDL-C, LDL-C, serum albumin, 25(OH)D, hypertension, smoking exposure, insulin therapy, or coronary/ischemic heart disease. Although sensitivity analyses generally supported the directional stability of the main findings, substantial heterogeneity remained for several outcomes, and all REML-based 95% prediction intervals crossed the null value. Exploratory meta-regression identified geographic region as a significant moderator only for HbA1c. Egger's tests did not indicate statistically significant small-study effects for outcomes with sufficient studies. The certainty of evidence was rated as low for HDL-C, hypertension, and insulin therapy and as very low for all other pooled outcomes, primarily because of the cross-sectional study design, substantial inconsistency, and imprecision.

In conclusion, older age, lower BMI, longer diabetes duration, higher fasting blood glucose, higher HbA1c, and lower hemoglobin levels were associated with sarcopenia in older patients with type 2 diabetes mellitus. However, the certainty of evidence was low to very low, and substantial heterogeneity and prediction intervals crossing the null value indicate that the magnitude and presence of these associations may vary across populations and clinical settings. These findings may heighten clinical suspicion during guideline-based sarcopenia assessment but should not be regarded as evidence of independent prediction, validated screening thresholds, or causality. Future prospective studies with standardized measurements and comprehensive adjustment for confounders are required.

https://www.crd.york.ac.uk/prospero/, identifier CRD420261301123.

Diabetic kidney disease (DKD) lacks accessible, cost-effective biomarkers for early screening. Given the distinct clearance pathways of free prostate-specific antigen (FPSA, renally excreted) and total prostate-specific antigen (TPSA, hepatically metabolized), this study investigated the association between serum FPSA/TPSA ratio and estimated glomerular filtration rate (eGFR) in male patients with type 2 diabetes mellitus (T2DM).

In this real-world cross-sectional study, 4,487 male patients with T2DM were retrospectively enrolled. eGFR was determined using the Kidney Disease: Improving Global Outcomes (KDIGO)-recommended Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C (Cr-CysC) equation. Multivariable linear regression and subgroup analyses were conducted to elucidate the independent effect of the FPSA/TPSA ratio on eGFR, with adjustment for age, prostate-specific diseases, and metabolic confounders.

Baseline TPSA levels remained stable across renal function stages (median 0.9ng/ml, P = 0.524), minimizing interference from macroscopic prostate pathologies. After adjustment for age and metabolic profiles, the FPSA/TPSA ratio exhibited a robust independent negative association with eGFR (β = -0.2, P < 0.001). This inverse correlation remained consistent across all clinical subgroups (P for interaction > 0.05), with a more pronounced predictive trend among elderly patients (≥ 65 years). Notably, our multivariable models also captured the chronic kidney disease "lipid paradox", whereby higher triglyceride levels paradoxically correlated with preserved eGFR (β = 0.51, P = 0.018).

An elevated serum FPSA/TPSA ratio is a robust, non-invasive indicator of declining eGFR in male patients with T2DM and may improve DKD risk stratification and early clinical warning without additional economic burden.

Serum uric acid (SUA) has been linked to vascular injury, but its impact on stroke risk in diabetic patients-a population inherently prone to cerebrovascular events-remains uncertain, and whether a threshold effect exists is unclear.

We included 3718 diabetic patients from two clinical centers. Multivariable-adjusted Cox proportional hazards models with stepwise covariate adjustment were used to assess associations between SUA and overall stroke and its subtypes. Kaplan-Meier curves estimated cumulative incidence across SUA quartiles. Restricted cubic spline regression examined dose-response relationships and potential threshold effects, and sex-stratified analyses were also performed.

Elevated SUA was significantly associated with increased risks of stroke and subtypes. The highest SUA quartile showed a significantly higher cumulative risk. RCS revealed threshold effects: risks of stroke, ischemic stroke, and hemorrhagic stroke increased when SUA exceeded 335, 330, and 340 μmol/L, respectively. Sex-stratified analyses yielded consistent findings, with thresholds at 335 μmol/L for males and 350 μmol/L for females.

In conclusion, this observational study confirms a significant association between SUA and stroke risk in diabetic patients with a threshold effect, suggesting potential clinical value for monitoring and urate-lowering therapy. However, sex-specific threshold findings should be interpreted cautiously as hypothesis-generating, and prospective randomized controlled trials are needed for validation.

We investigated the association between tongue characteristics and musculoskeletal (MSK) pain in patients with type 2 diabetes mellitus (T2DM) and explored potential noninvasive tongue-based biomarkers.

This cross-sectional study enrolled 586 patients with T2DM (420 without and 166 with MSK pain) between January 2023 and December 2024 at the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine. Tongue images were obtained using a standardized tongue-imaging device. Color parameters in the Lab and RGB color spaces were extracted from the tongue proper and coating. Multivariate logistic regression was used to examine associations between individual tongue parameters and MSK pain. Principal component analysis was applied separately to tongue proper and coating parameters to derive composite scores, and latent profile analysis (LPA) was used to identify tongue-based subgroups.

After adjustment for confounders, higher TC-b (Odds ratio [OR], 1.26; 95% confidence interval [CI], 1.151-1.379; P<0.001) and CC-b (OR, 1.199; 95% CI, 1.111-1.294; P<0.001) values were significantly associated with an increased risk of MSK pain. The tongue-proper composite score was positively associated with MSK pain risk (OR, 1.649; 95% CI, 1.240-2.193; P<0.001), whereas the tongue-coating composite score showed a negative association (OR, 0.586; 95% CI, 0.425-0.807; P=0.001). LPA identified five distinct tongue-imaging subgroups, including one subgroup with high TC-b and CC-b that exhibited a significantly higher risk of MSK pain.

Tongue color characteristics are associated with MSK pain in patients with T2DM and may serve as potential noninvasive biomarkers for the auxiliary assessment of MSK pain. Prospective studies are needed to clarify their clinical relevance and potential utility.

Traditional Moroccan herbal teas are widely consumed and have been traditionally used for managing chronic metabolic disorders, particularly type 2 diabetes mellitus (T2DM). Although these preparations have a long history of ethnomedicinal use, their phenolic composition and biological activities remain insufficiently characterized. Scientific validation is needed to support their traditional application and provide evidence for their potential relevance to T2DM management. This study aimed to characterize the phenolic profile, antioxidant potential, and carbohydrate-digestive enzyme inhibitory activity of 21 traditional Moroccan herbal teas used for glycaemic control.

Phenolic constituents were identified and quantified using HPLC-MS. Antioxidant capacity was evaluated through DPPH, ABTS, and FRAP assays. Inhibitory effects on α-amylase and α-glucosidase were assessed in vitro. Correlation analyses were conducted to explore associations between phenolic constituents and biological activities.

Marked variability in total phenolic content (TPC) was observed, with Mentha × piperita and Thymus broussonetii exhibiting the highest levels at 883.2 ± 13.0 and 746.8 ± 22.4 mg GAE/g dry weight, respectively. Antioxidant activity varied substantially among the investigated teas, with T. broussonetii (FRAP reducing power: 423.6 ± 9.8 µg/mL) and Mentha rotundifolia (162.6 ± 0.6 µg/mL) showing significant reducing capacities. TPC exhibited strong positive correlations with antioxidant indices (r = 0.93-0.96). Pelargonium graveolens presented potent α-amylase inhibition (IC₅₀ = 2.98 ± 1.7 µg/mL), whereas Mentha viridis and Calamintha officinalis were among the most active α-glucosidase inhibitors (IC₅₀ = 1.9 ± 0.4 and 1.2 ± 0.1 µg/mL, respectively). Negative correlations were found between rutin (r = - 0.49) and gallic acid (r = - 0.44) contents and α-amylase IC₅₀ values.

The investigated Moroccan herbal teas exhibited variable antioxidant and digestive-enzyme inhibitory activities that were associated with their phenolic composition. Variability among samples may reflect differences in plant species and environmental or agronomic factors. These findings provide comparative in vitro evidence supporting the traditional use of Moroccan herbal teas and highlight several species as promising sources of bioactive phenolics. However, the present findings do not establish therapeutic efficacy, and further in vivo, mechanistic, pharmacokinetic, and clinical studies are required to confirm their efficacy, safety, and clinical relevance.

Post-traumatic lymphedema (PTL) is an underrecognized complication of severe limb trauma and is characterized by persistent limb swelling. Patients with open fractures of the lower leg may be more susceptible to PTL, and clinical factors such as extensive soft-tissue injury, wound infection, and repeated surgical procedures may be associated with lymphatic injury and local inflammation. However, the clinical factors associated with PTL in this population remain unclear. This study aimed to identify factors associated with PTL after open fractures of the lower leg.

We retrospectively screened 129 patients treated for open fractures of the lower leg between March 2023 and March 2025. After excluding one patient who underwent amputation and seven who were lost to follow-up, 121 patients were included and assessed for post-traumatic lymphedema at 6 months after the initial operation. Binary logistic regression was used to identify associated factors.

Of the 121 patients, 41 (33.88%) developed PTL. Multivariable logistic regression showed that increasing age (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.02-1.09; P = 0.002), postoperative infection (OR = 5.15, 95% CI 1.25-21.19; P = 0.023), and skin and soft-tissue necrosis-related defects (OR = 5.76, 95% CI 2.04-16.31; P < 0.001) were associated with PTL. Diabetes mellitus did not reach statistical significance, although the point estimate was elevated (OR = 8.00, 95% CI 0.77-82.97; P = 0.081). In the extended sensitivity model, increasing age and postoperative infection remained associated with PTL, whereas the associations of the two injury-severity indicators were attenuated. In the alternative injury-severity model, Gustilo-Anderson type IIIB/IIIC injury was associated with PTL.

Increasing age and postoperative infection were consistently associated with PTL after open fractures of the lower leg. Skin and soft-tissue necrosis-related defects and Gustilo-Anderson type IIIB/IIIC injuries showed model-dependent associations. These findings may support targeted postoperative surveillance.