This study aimed to investigate the relationships between visit-to-visit variability in HbA1c and fasting plasma glucose (FPG) and atherosclerotic markers in persons with type 2 diabetes mellitus (T2DM), employing epidemiological analyses and Mendelian randomization (MR) techniques. Between January 2001 and December 2020, 2290 persons with T2DM (1307 men and 983 women) who underwent evaluation for atherosclerosis screening were enrolled in a management program at a medical center in Taiwan. To assess potential causal relationships among the coefficient of variation (CV) of HbA1c (HbA1c-CV), FPG-CV, and markers of atherosclerosis, we conducted a 2-stage multivariable regression analysis using 22 and 21 single nucleotide polymorphisms as instrumental variables for HbA1c and FPG, respectively. A total of 2290 individuals with T2DM were included, with a mean age of 61.79 years, and 57% were male. In the epidemiological analysis, after multivariable adjustment, the odds ratios for an ankle-brachial index (ABI) < 0.9 in the third and fourth quartiles compared with the first quartile were 3.15 (95% confidence interval [CI]: 1.80-5.50) and 4.29 (95% CI: 2.44-7.56), respectively, for FPG-CV, and 1.67 (95% CI: 1.06-2.62) and 1.65 (95% CI: 1.01-2.70), respectively, for HbA1c-CV. In the MR analysis, comparing the fourth quartile with the first quartile, the odds ratios for ABI < 0.9 and brachial-ankle pulse wave velocity (baPWV) ≥ 1800 cm/s were 2.78 (95% CI: 1.84-4.19) and 1.58 (95% CI: 1.23-2.02), respectively, for the unweighted genetic risk score predicting FPG-CV. Epidemiological and MR analyses provide evidence that FPG variability is significantly associated with atherosclerosis, as indicated by the ABI.

Type 2 diabetes mellitus (T2DM) and malignant neoplasms are among the most prevalent chronic diseases worldwide. When coexisting, they substantially increase morbidity and mortality. However, national trends in mortality among patients with coexisting T2DM and malignant neoplasms in the United States remain underexplored. We analyzed U.S. death certificates from the CDC WONDER database for individuals aged ≥ 25 years who died between 1999 and 2024 with both T2DM and malignant neoplasms listed anywhere on the death certificate (underlying or contributing causes). Age-adjusted mortality rates (AAMRs) and annual percent change (APC) were calculated by year, sex, age group, race/ethnicity, geographic region, and urbanization status. From 1999 to 2024, 357,910 U.S. deaths occurred among individuals in whom both Type 2 Diabetes Mellitus and Malignant Neoplasms were listed on the death certificate. The AAMR rose from 6.37 to 17.2 per 100,000, with an overall APC of + 3.84%. Men exhibited higher mortality than women. Older adults bore the greatest burden, though middle-aged adults also showed a sharp proportional rise. Hispanic and Asian populations experienced the steepest increases. The West region showed the most pronounced growth. State-level variation exceeded fivefold, with Nebraska reporting the highest AAMR and Nevada the lowest. nonmetropolitan areas maintained higher mortality throughout, but metropolitan areas demonstrated a steeper rise, narrowing the rural-urban gap. Mortality among individuals with coexisting T2DM and malignant neoplasms has risen substantially in the U.S., with disproportionate increases among men, minority populations, and urban residents. These findings highlight the urgent need for integrated strategies addressing diabetes control, cancer prevention, and health equity across demographic and geographic subgroups.

Diabetes mellitus (DM) is a chronic, multisystemic metabolic disorder characterized by hyperglycemia resulting from absolute or relative insulin resistance (IR) in peripheral tissues. Diabetic foot ulcers, arising from peripheral arterial disease (a macrovascular complication) and neuropathy (a microvascular complication), represent a major cause of morbidity among diabetic patients. Asprosin is a diabetogenic adipokine involved in glucose metabolism and IR. This study aimed to investigate whether serum asprosin plays a role in the progression of diabetes and the development of diabetic foot ulcers. This comparative cross-sectional observational study included 3 groups: 32 patients with diabetic foot ulcers, 31 patients with type 2 diabetes mellitus (T2DM) without ulcers, and 27 healthy controls. Demographic data (age, gender, family history, body mass index), biochemical parameters, culture results, and serum asprosin levels were evaluated. Serum asprosin concentrations were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Serum asprosin levels differed significantly among the groups (P < .001), being lowest in the control group. Both the diabetic foot and T2DM groups exhibited significantly higher asprosin levels compared to controls (P < .001), although there was no significant difference between the 2 diabetic groups. Additionally, asprosin levels were not significantly affected by the presence of wound infection, positive culture growth, or elevated acute-phase reactants. In this study, serum asprosin was not found to be associated with the development of peripheral complications of diabetes. Further studies with larger cohorts are warranted to clarify the role of asprosin in diabetic vascular and metabolic pathophysiology.

This study aimed to explore the risk of overall extracranial bleeding events with tirofiban in patients with acute ischemic stroke (AIS) and diabetes mellitus and analyze the impact of blood glucose control on this risk. A single-center retrospective cohort study design was used, including 100 patients with AIS and diabetes mellitus admitted between April 2023 and November 2025. Propensity score matching was used to divide patients into the tirofiban group (50 cases) and the control group (50 cases). The primary outcome was the incidence of overall extracranial bleeding events within 7 days after medication administration. Secondary outcomes included types of extracranial bleeding (e.g., gingival bleeding), thrombocytopenia, and neurological function outcomes. Multivariable logistic regression and subgroup analysis were conducted to assess independent risk factors. The incidence of overall extracranial bleeding events in the tirofiban group was 32.0%, significantly higher than the 16.0% in the control group (risk ratio = 2.00, 95% confidence interval = 1.11-3.60, P = .021). Gingival bleeding (10.0% vs 2.0%, P = .047) and thrombocytopenia (10.0% vs 2.0%, P = .047) occurred more frequently in the tirofiban group. Multivariable analysis showed that tirofiban treatment (adjusted odds ratio = 2.45, P = .018) and admission random blood glucose (adjusted odds ratio = 1.22, P = .032) were independent risk factors for overall extracranial bleeding events. Subgroup analysis revealed that in patients with hemoglobin A1c ≥7.5%, the bleeding risk associated with tirofiban was higher (odds ratio = 3.33, 95% confidence interval = 1.05-10.56, P-interaction = .04). In patients with AIS and diabetes mellitus, tirofiban treatment did not significantly increase the risk of intracranial hemorrhage, but it significantly raised the risk of extracranial bleeding events (especially gingival bleeding) and thrombocytopenia. This risk was more pronounced in patients with poor blood glucose control. Comprehensive monitoring of bleeding signs and enhanced glucose management are required in clinical practice.

Visceral adiposity (metabolic dysregulation) plays a role in chronic inflammation and contributes to many chronic diseases. However, it is unclear whether visceral adiposity index (VAI) can be used to predict arthritis-diabetes risk. In our study, we investigated this connection and explored the potential of VAI as a noninvasive and clinically feasible candidate tool. We used data from CHARLS, China Health and Retirement Longitudinal Survey of Chinese adults 45 years old or above. VAI (per increase in interquartile range and quartiles) and incident arthritis-diabetes comorbidity were analyzed using multivariate logistic regression analyses adjusted for sociodemographic, lifestyle and clinical confounders. Predictive power was assessed using receiver-operating characteristic curves. Dose-response and effect changes among subgroups (e.g., gender, smoking) were also investigated. VAI has a positive correlation with arthritis-diabetes comorbidity. After full adjustment (Model 3), each increase in interquartile range of VAI increases the risk by 10% (odds ratio = 1.10, 95% confidence interval = 1.04-1.17). Individuals in the highest VAI quartile (Q4) have a significantly higher risk (odds ratio = 4.30, 95% confidence interval = 2.18-9.30) than those in the lowest quartile (Q1), with a significant dose-response trend (P for trend 0.001). The fully adjusted model had moderate discriminative ability (area under the curve = 0.703, consistent with the full result). Subgroup analyses showed consistent positive associations between VAI and arthritis-diabetes comorbidity in female participants and nonsmokers. A nonlinear dose-response curve showed that the comorbidity risk increases with increasing VAI. Increased VAI independently contributes to a higher risk of arthritis-diabetes comorbidity in middle-aged/elderly Chinese adults, with significant nonlinearity, subgroup heterogeneity, and robustness after confounder adjustment. Targeted visceral adiposity reduction in high-risk subgroups may be a potential strategy for reducing comorbidity burden, which needs to be verified by subsequent interventional studies, and it may provide a basis for chronic disease precision prevention in this population.

Obesity is a chronic multifactorial disease characterized by excess adiposity and persistent low-grade systemic inflammation, contributing substantially to cardiometabolic morbidity and mortality. Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist approved for chronic weight management, promotes weight loss by reducing appetite, delaying gastric emptying, and decreasing energy intake while also demonstrating potential anti-inflammatory effects. Although semaglutide has shown promising efficacy for weight reduction, an updated evaluation of its efficacy and safety in nondiabetic individuals with overweight or obesity is warranted.

A systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Scopus, and CINAHL were searched from inception to March 2025 for randomized controlled trials evaluating subcutaneous semaglutide in adults with overweight or obesity without type 2 diabetes mellitus. The primary outcome was the percentage change in body weight from baseline. Secondary outcomes included overall gastrointestinal adverse events, nausea, vomiting, diarrhea, constipation, treatment discontinuation due to adverse events, and serious adverse events. Pooled estimates were calculated using a random-effects model.

Four randomized controlled trials involving 3613 participants met the eligibility criteria. Semaglutide produced significantly greater weight loss than placebo (mean difference: -11.85%; 95% confidence interval [CI]: -12.81 to - 10.90; P < .00001). Overall gastrointestinal adverse events were significantly more frequent with semaglutide, with nausea, vomiting, diarrhea, and constipation representing the most commonly reported events. Treatment discontinuation due to adverse events was also significantly higher in the semaglutide group (RR 2.62, 95% CI: 1.70-4.03; P = .001). Serious adverse events, including acute pancreatitis and cholelithiasis, were uncommon.

Subcutaneous semaglutide is an effective treatment for weight reduction in adults with overweight or obesity without type 2 diabetes mellitus but is associated with an increased risk of gastrointestinal adverse events, particularly nausea, vomiting, diarrhea, and constipation, as well as higher treatment discontinuation. Serious adverse events were rare. Further long-term randomized trials are needed to evaluate the durability of weight loss and the long-term safety profile of semaglutide.

Provisional stenting has become the default treatment strategy for most coronary bifurcation lesions However, in some clinical and anatomical settings, final two-stent implantation may yield better cardiovascular outcomes. This study aimed to identify preprocedural clinical and angiographic predictors associated with greater benefit from final two-stent implantation in coronary artery bifurcation lesions and to guide patient selection for this strategy.

We analyzed 5333 patients with coronary bifurcation lesions (mean age 66.2 years; 76% male) from the BIFURCAT registry, an international merged dataset combining the COBIS III and RAIN registries. All patients received second-generation drug-eluting stents; 82% underwent final single-stent and 18% final two-stent implantation. The primary endpoint was major adverse cardiac events (MACE)-a composite of all-cause death, myocardial infarction, and target lesion revascularization-at 2 years. Multivariable Cox regression with interaction testing was used to identify preprocedural clinical and angiographic predictors of differential benefit from two-stent implantation.

Six predictors demonstrated a statistically significant interaction with final one stent and two stent implantation groups: diabetes mellitus, main vessel reference diameter > 3.0 mm, main vessel lesion length < 20 mm, side branch lesion length ≥ 20 mm, non-left main lesion, and severe coronary artery calcification. Each variable was assigned one point to construct the Bifurcation Two-Stent (BTS) score. In patients with a BTS score < 4 (80% of the cohort), final two-stent implantation was associated with significantly higher MACE rates compared with single-stent implantation (HR: 2.04; 95% CI: 1.64-2.56; P < 0.001). Conversely, patients with a BTS score ≥ 4 (approximately 20% of the cohort) demonstrated significantly lower MACE with two-stent implantation (HR: 0.56; 95% CI: 0.35-0.89; P = 0.014), driven primarily by a reduction in hard endpoints including death and myocardial infarction. These findings remained consistent after adjustment for procedural variables and antiplatelet therapy.

The BTS score may help identify patients with coronary bifurcation lesions who are most likely to benefit from final two-stent implantation. In patients with BTS score ≥ 4, final two-stent implantation was associated with lower MACE and hard clinical endpoints, supporting a selective rather than routine two-stent strategy in bifurcation PCI.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of cardiovascular events and frequently coexists with other atherosclerosis risk factors, including obesity, metabolic syndrome, sleep apnea, and insulin resistance. Lipoprotein(a) [Lp(a)] is a low-density lipoprotein-like particle bound to apolipoprotein(a), that has been studied to have pro-thrombotic and pro-inflammatory properties and is an established independent risk factor for atherosclerotic disease. However, the association between MASLD and Lp(a) and their impact on long-term clinical outcomes have not been evaluated previously.

We performed a secondary analysis of the prospectively collected data from the Multi-Ethnic Study of Atherosclerosis (MESA). Baseline MASLD was defined as either a liver-to-spleen (L:S) attenuation ratio less than 1.0 or liver attenuation <40 HU on computed tomography (CT) imaging, excluding individuals with excess alcohol consumption (>15 drinks/week for men and > 10 drinks/week for women) and the presence of at least one cardiometabolic risk factor, including elevated BMI or waist circumference, type 2 diabetes mellitus, hypertension, hypertriglyceridemia, or reduced HDLC. Baseline Lp(a) levels were measured using a latex-enhanced turbidimetric immunoassay (Denka Seiken, Tokyo, Japan).

Median Lp(a) levels were significantly lower in those with baseline MASLD compared to those without MASLD (11.9 vs 18.1 mg/dL, p-value <0.001). Individuals with MASLD and low Lp(a) levels (≤ 50 mg/dL) had a significantly higher risk of all-cause mortality compared to those without MASLD and with low Lp(a) (HR 1.28; 95% CI: 1.025-1.56), independent of traditional cardiovascular risk factors. Additionally, individuals with baseline MASLD and elevated Lp(a) were independently associated with an increased risk of hard cardiovascular disease (HR 2.07, 95% CI: 1.39-3.09), compared to individuals without MASLD and with Lp(a) ≤ 50 mg/dL.

MASLD is independently associated with lower levels of Lp(a). Patients with baseline MASLD and elevated levels of Lp(a) exhibit nearly twice the risk of cardiovascular diseases as compared to the cohort with no MASLD and lower Lp(a) levels. Importantly, even in the absence of elevated Lp(a), MASLD is associated with increased all-cause mortality. These findings suggest that while Lp(a) is a strong contributor to cardiovascular risk, MASLD itself is an independent determinant of long-term mortality.

Patients with diabetes mellitus (DM) exhibit increased susceptibility to various infectious diseases, and DM represents a critical underlying risk factor for cryptococcosis. However, how diabetic metabolic dysregulation specifically affects host immune responses against Cryptococcus neoformans remains poorly understood. In this study, we investigated anti-cryptococcal immune responses using a streptozotocin (STZ)-induced DM model established in CnT-II transgenic mice, which harbor abundant Cryptococcus-specific CD4⁺ T cells. Inducing DM directly in these CnT-II mice enabled direct evaluation of antigen-specific immunity. DM mice, which exhibit decreased systemic reduced glutathione (GSH) under chronic hyperglycemia, showed exacerbated cryptococcal infection, characterized by significantly higher pulmonary fungal burdens, decreased IFN-γ levels, reduced survival rates, and defective granuloma formation. In vitro assays using splenocytes from uninfected DM mice revealed significantly impaired cryptococcal antigen-specific Th1 responses, expanded Treg cells, and increased PD-1 expression on CD4⁺ T cells compared with controls. Specifically, cross-combination cultures of isolated splenic CD4⁺ T cells and dendritic cells demonstrated that this Th1 impairment was intrinsic to DM-derived T cells, whereas DM-derived dendritic cells had no effect. Additionally, macrophages cultured under high-glucose conditions showed significantly decreased nitric oxide (NO) production and fungicidal activity. Importantly, exogenous GSH supplementation successfully restored both Th1 differentiation and NO production, whereas Treg cell expansion and defective macrophage fungicidal activity were GSH-independent. Taken together, our findings demonstrate how metabolic redox imbalance compromises coordinated host immunity against C. neoformans, offering potential redox-targeted therapeutic insights for diabetic hosts.

Human immunodeficiency virus (HIV) infection, HIV medications and type 2 diabetes mellitus adversely affects kidney function including erythropoiesis. However, studies evaluating the coexisting effects of these conditions on serum erythropoietin (EPO) levels and the hematological profile of those affected in southern Nigeria are scarce. In this study, 128 adults between the ages of 18 and 59 years were selected from designated health facilities in southern Nigeria. They were divided into four groups (n=32 persons per group). Fasting/random blood sugar (FBS/RBS) levels, complete blood count (CBC), glycated heamoglobin (HBA1C), serum levels of erythropoietin were determined using standard methods. Results show a significant increase (P < 0.05) in serum EPO and total red blood cell count (TRBC) in the HIV only group compared to other groups. The total white blood cell count (TWBC), platelets count and platelet/lymphocyte rato increased in the diabetic plus HIV group. The FBS/RBS and theHBA1C levels increased in the diabetic and diabetic plus HIV groups compared to others. Increased erythropoiesis, depicted by increased serum EPO and TRBC could be attributable to improved use of HIV medications and improved lifestyle among the HIV positive patients on treatment. Poorly controlled T2DM with resultant increased HBA1C levels in the diabetic and diabetic plus HIV groups was responsible for the increase in TWBC and platelet count, likely due to impaired immune function leading to sepsis in these groups.