Glycoprotein non-metastatic melanoma protein B promotes pyroptosis of macrophages induced by homocysteine associated with the upregulation of the NOX-2/ NF-κB signaling pathway.

Depression after a stroke is the most frequent and burdensome neuropsychiatric post-stroke complication. This study aimed to determine the relationship between post-stroke depression (PSD) and the levels of homocysteine (HCY) in patients with spontaneous intracerebral hemorrhage (SICH). We collected data from patients with hemorrhagic stroke (HS) admitted to the hospital and recorded their demographic and clinical characteristics. We also searched for information regarding HAM-D17 (Hamilton Depression) scores and HCY levels at 3m, the use of antidepressant medications and folic acid during the follow-up period in the group of patients diagnosed with PSD and hyperhomocysteinemia (HHcy) in the acute phase. A total of 1,852 patients were included. 642 (34.7%) patients with PSD and 598 (32.3%) patients with HHcy, 364 (19.7%) patients with both conditions. A link between depression and low HCY level has similarly been found in patients with HS (OR, 1.549; 95% CI, 1.358-1.768). Additionally, left-sided stroke, anterior circulatory stroke, intraventricular hemorrhage, symptoms of paralysis or dysarthria, and higher NIHSS scores occurred more often in the PSD group. Compared to the antidepressant medications (ADM) group, HAM-D17 scores decreased significantly in the ADM plus folic acid group at the end of 3m (P = 0.036). On the basis of our data, PSD was significantly more frequent in patients with HHcy in patients with SICH at the acute phase. The location of hemorrhage and the severity of the disease are significantly correlated with the incidence of PSD. Oral doses of folic acid and ADM showed significant improvements in the HAM-D17 scores for the patients with comorbid PSD and HHcy.

Betaine acts as a methyl donor and has been proposed as a potential substitute for methionine (Met) to reduce feed costs. This study aimed to investigate the optimal replacement value of betaine for dietary Met in broilers aged 22 to 42 days. A total of 1,440 male broilers were randomly divided into 6 treatments (6 replicates/pen). The positive control (PC) received a standard diet (0.53% Met), while the negative control (NC) received a low-Met diet (0.33% Met) with 2000 mg/kg betaine. Four additional groups received the NC diet supplemented with 0.05%, 0.10%, 0.15%, or 0.20% Met. Data were analyzed using one-way ANOVA and three regression models. Results indicated that Met deficiency significantly impaired growth performance: final body weight (BW) decreased from 1696 g (PC) to 1604 g (NC) (P < 0.001), while the feed-to-gain ratio (F/G) increased from 1.87 to 2.01. No significant differences were observed in slaughter performance (P > 0.05). Regarding metabolism, the NC group exhibited significantly elevated serum homocysteine (19.42 vs. 7.94 μmol/L) and hepatic ALT activity (11.77 vs. 4.35 U/g prot), alongside reduced hepatic BHMT activity (17.47 vs. 103.14 ng/mg prot, P < 0.001). Furthermore, Met deficiency downregulated the mRNA expression of genes related to one-carbon metabolism and intestinal tight junctions (relative expression ∼0.20 vs. 1.00 in PC, P < 0.05). Supplementation with 0.10% Met restored these parameters to levels statistically equivalent to the PC group. One-slope straight broken line and two-slope straight broken line regression analysis of the F/G ratio (R2 = 0.8598) determined the optimal replacement dose to be 0.1474% Met, corresponding to a 27.81% substitution efficiency.

To investigate differences in neuropsychological characteristics between patients with Alzheimer's disease (AD) with and without sarcopenia, and to examine their associations with serum homocysteine (HCY) levels. A total of 41 patients with AD diagnosed at a memory clinic with Aβ-PET confirmation were enrolled, including 21 patients with sarcopenia (ADSa) and 20 without sarcopenia (ADNSa). In addition, 35 cognitively normal individuals were recruited as normal controls (NCs) from a health examination center. Demographic characteristics, sarcopenia-related parameters, neuropsychological assessments, and serum HCY levels were collected. Group differences in neuropsychological performance and HCY levels were compared, and partial correlation analyses were performed after adjustment for potential confounders. HCY levels were significantly higher in the AD group than in the NC group. The AD group had a higher prevalence of sarcopenia, and its muscle strength, mass, and physical function were significantly worse than those of the NC group (all p < 0.05). The AD-NSa group performed worse on neuropsychological tests such as MoCA, DST, BNT, and AFT. After adjusting for confounding factors, HCY was positively correlated with CDR and five-times sit-to-stand test scores and negatively correlated with MMSE, DSST, and ASMI scores (all p < 0.01). Using a logistic regression model to calculate the odds ratio (OR), the significant correlation between HCY levels and AD status remained after adjusting for potential confounding factors (all p < 0.01). Elevated serum HCY levels are significantly associated with sarcopenia and multidimensional cognitive impairment in patients with AD. In an AD cohort with amyloid pathology confirmed by Aβ-PET, this study provides the first integrative analysis of the associations among HCY, sarcopenia, and cognitive function. These findings suggest that HCY may represent a potential biomarker linking the comorbidity of AD and sarcopenia and may offer a theoretical basis for dual-target interventions addressing both HCY metabolism and muscle function in this vulnerable population.

Integrated biomarker analysis in type 2 diabetes: soluble CD36, glycine, homocysteine, miR-375, and miR-126

BackgroundVitamin B12 and folate deficiencies are associated with cognitive decline, yet evidence for their role in mild cognitive impairment (MCI) remains inconclusive, particularly how it differs across genders.ObjectiveTo evaluate the prevalence of vitamin B12, vitamin B9, Homocysteine, and hemoglobin levels among male and female urban, community-dwelling elderly individuals with MCI and to assess gender-specific differences in these biochemical parameters.MethodsA cross-sectional study was conducted among 128 urban, community-dwelling elderly individuals (60 + years) with MCI in South India. Serum levels of vitamin B12, folate, homocysteine, and hemoglobin were evaluated alongside cognitive assessment. Multiple regression analysis was performed to evaluate the association between biomarkers and cognitive function adjusting for sociodemographic variables.ResultsThis study revealed a high prevalence of vitamin B12 (78.1%), folate (99.2%) deficiencies and anemia (64.1%), alongside elevated homocysteine levels in 87.5% of participants. No significant association was found between mean scores of cognition in MCI and vitamin B12, folate, or homocysteine levels. Females had significantly lower mean hemoglobin levels than males (p = 0.03). Cognitive scores were relatively higher in females despite their lower socioeconomic status and hemoglobin levels.ConclusionsGender disparities in hemoglobin levels highlight the importance of addressing nutritional inequities. However, vitamin B12 and folate levels may not strongly influence MCI. Routine assays for these vitamins in elderly individuals with cognitive impairment should be reconsidered in resource-constrained settings.

From retina to triple-monitoring: One-carbon metabolism in diabetic retinopathy.

Identifying individuals with vitamin B12 (B12) deficiency is challenging due to poor harmonization across total B12 assays. To establish clinically meaningful thresholds for the Roche assay, we characterized B12 concentrations associated with deficiency by comparing individuals with macrocytic anemia and other anemia subtypes or no anemia. We retrospectively analysed 10years of laboratory data from adults tested for total B12 and folate (Roche Cobas), homocysteine (Abbott Architect), and haematological parameters (Sysmex XE/XN). Individuals receiving vitamin supplementation or with isolated folate deficiency were excluded. Anemia subtypes (normocytic, microcytic, macrocytic) were classified using red blood cell count, hemoglobin concentration, and mean corpuscular volume relative to reference intervals. Among 5,147 subjects (median age 65years; 25th-75th percentile: 49-77), 36.8 % had anemia. Total B12 concentrations decreased by 2.3 ng/L for each 1 μmol/L increase in homocysteine and by 6.8 ng/L per decade of age increase (p<0.0001). Macrocytic anemia (9.4 % of subjects), was associated with a mean reduction of 18.6 ng/L in B12 levels compared with no anemia and microcytic anemia. Mean homocysteine concentrations rose progressively, from 15.9 to 21.5 μmol/L and then to 34.9 μmol/L, as total B12 concentrations fell in the intervals: 342-447 ng/L, 341-258 ng/L, and 257-<50 ng/L, respectively. Among individuals investigated for anemia, macrocytosis, a hallmark of B12 depletion, supports that total B12 concentrations≤257 ng/L measured using the Roche assay likely reflect severe deficiency. Levels between 258 and 341 ng/L may indicate early depletion and warrant confirmation through elevated homocysteine concentrations.

In recent years, the impact of lipoprotein(a) (Lp(a)) on the prognosis of coronary heart disease has been increasingly recognized. Lp(a) is an independent risk factor for cardiovascular disease, and studies have shown that homocysteine (HCY) may influence the association between Lp(a) and the risk of recurrent cardiovascular events. This study investigates the association between Lp(a) levels and recurrent cardiovascular events in patients with varying HCY concentrations. We conducted a 36-month follow-up on 530 patients with coronary heart disease and divided them into low-Lp(a) and high-Lp(a) groups based on Lp(a) levels. The incidence rates of major adverse cardiovascular events (MACE) and acute coronary events (ACE) were compared between the two groups. The association between elevated Lp(a) and cardiovascular risk in different subgroups(based on HCY concentration) was analyzed using Kaplan-Meier curves and Cox proportional hazards models. Elevated Lp(a) remained a significant risk factor for both MACE (HR = 2.07, 95% CI = 1.37-3.12, P = 0.001) and ACE (HR = 2.83, 95% CI = 1.67-4.81, P = 0.001) overall. In subgroup analyses, elevated Lp(a) in patients with moderate-to-high HCY levels constituted a high-risk cohort for MACE and ACE occurrence (HR = 1.87, 95% CI = 1.01-3.46, P = 0.046;HR = 2.85, 95% CI = 1.32-6.18, P = 0.008). Among those with low HCY levels, elevated Lp(a) showed no association with either MACE or ACE (P > 0.05). When HCY is elevated, patients with increased Lp(a) experience amplified risk of recurrent cardiovascular events. This association shifts when HCY is at low levels. Future efforts should emphasize combined assessment of Lp(a) and HCY and explore targeted intervention strategies to reduce residual cardiovascular risk.

Diabetic retinopathy (DR) is a leading cause of preventable vision loss, yet current therapies primarily address late, VEGF-driven vascular complications rather than early upstream drivers. Emerging evidence indicates that early DR originates from metabolic stress within the retinal neurovascular unit, where dysregulated lipid metabolism, oxidative stress, and inflammation precede visible microvascular damage. Disturbances in polyunsaturated fatty acid (PUFA) metabolism, together with related metabolic stressors such as elevated homocysteine (Hcy), drive lipid dysregulation, oxidative stress, and inflammation preceding visible microvascular damage, promoting endothelial dysfunction and blood-retinal barrier (BRB) breakdown. Hyperglycemia shifts retinal lipid composition toward oxidation-prone omega-6 PUFAs and activates lipoxygenase (LOX), cyclooxygenase (COX), and cytochrome P450 (CYP450) eicosanoid pathways. LOX-derived metabolites such as 12- and 15-HETE stimulate NADPH oxidase, disrupt tight junctions, and promote inflammatory signaling in endothelial and Müller cells. COX-2-driven prostaglandin E2 signaling increases vascular permeability, while CYP450 metabolites and their soluble epoxide hydrolase (sEH) derived products exert context-dependent effects on vascular integrity. Elevated Hcy further enhances oxidative stress and NF-κB activation, amplifying PUFA-mediated inflammatory signaling. These mechanisms identify modifiable upstream targets that complement glycemic control. Higher dietary omega-3 intake and lower omega-6:omega-3 ratios are associated with reduced DR risk, particularly in well-controlled diabetes. Omega-3-rich diets, exercise, and correction of folate and B-vitamin deficiencies may help improve systemic inflammation and retinal barrier integrity. Integrating lipid pathway modulation, nutritional support, and metabolic control with careful ocular monitoring may help slow the progression of DR before irreversible blindness occurs.

Hyperhomocysteinemia, a metabolic disorder characterized by elevated plasma homocysteine levels increases the risk of multiple neurological disorders, including ischemic stroke. We previously demonstrated that under hyperhomocysteinemic conditions, ischemic injury activates GluN2A-containing NMDA receptor (GluN2A-NMDARs) in neurons, which along with the activation of the canonical pathway of ischemic brain injury involving GluN2B-containing NMDARs (GluN2B-NMDARs) exacerbates brain damage. To elucidate the underlying molecular mechanisms, we now investigated whether an early onset of neuroinflammation contributes to the enhanced ischemic brain damage under hyperhomocysteinemic conditions. Using rodent models of middle cerebral artery occlusion, we show that predisposition to hyperhomocysteinemia leads to early onset of brain damage, with increased neuronal COX2 expression and PGE2 level in the ipsilateral hemisphere within 6 h of reperfusion. Pharmacological inhibition of GluN2A-NMDAR reduces this neuroinflammatory response, and mice lacking neuronal COX2 reduces ischemic brain damage. Additionally, rapid activation of neuronal NFκB is observed within 6 h of reperfusion, and pharmacological inhibition of GluN2A-NMDARs or NFκB, as well as selective deletion of neuronal NFκB-RelA subunit reduces the inflammatory response. These findings identify GluN2A-NMDAR mediated neuronal NFκB activation as the molecular trigger for upregulating COX2/PGE2 pathway and microglial activation, highlighting a novel pro-inflammatory role of GluN2A-NMDAR in ischemic brain injury under hyperhomocysteinemic conditions.

Patient: Male, 52-year-oldFinal Diagnosis: Pernicious anemia • superior ssagittal sinus thrombosisSymptoms: SeizureClinical Procedure: —Specialty: Hematology • General and Internal MedicineObjective: Unusual clinical courseBackgroundSuperior sagittal sinus thrombosis is an uncommon but serious cerebrovascular disorder, often linked to a hypercoagulable state. One less common etiology of hypercoagulability is elevated homocysteine levels due to vitamin B12 deficiency caused by pernicious anemia, a process that usually also results in concurrent megaloblastic anemia. We describe a patient who developed superior sagittal sinus thrombosis despite normal hemoglobin and hematocrit values.Case ReportA 52-year-old man presented to the emergency department with first-time tonic-clonic seizure. Brain magnetic resonance imaging revealed thrombosis of the superior posterior segment of the superior sagittal sinus. Additional studies demonstrated deep vein thrombosis in the right peroneal vein. Extensive evaluation for potential prothrombotic causes revealed an elevated homocysteine level and vitamin B12 deficiency. The patient had serologic evidence of pernicious anemia; antibodies against intrinsic factor and gastric parietal cells were present. Despite the pernicious anemia diagnosis, his hemoglobin level was normal. High-dose oral vitamin B12 was administered to correct the deficiency and alleviate the hypercoagulable state. The patient was initially anticoagulated with a heparin infusion to treat the superior sagittal sinus thrombosis; therefore, intramuscular injections of vitamin B12 were avoided during hospitalization. He was ultimately discharged home with prescriptions for apixaban and intramuscular injections of vitamin B12.ConclusionsPatients presenting with thrombotic events should be thoroughly evaluated for an underlying hypercoagulable state to ensure appropriate treatment and prevent complications. This case highlights the importance of considering hyperhomocysteinemia induced by vitamin B12 deficiency as a cause of thrombosis, even in patients with normal hemoglobin levels.

Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular disease (CVD) morbidity and mortality, yet the biological mechanisms linking psychological trauma to cardiovascular risk remain incompletely understood. Disruptions in one-carbon metabolism, reflected by elevated homocysteine and altered folate and vitamin B12 levels, contribute to vascular inflammation and endothelial dysfunction and may represent a modifiable pathway linking PTSD to CVD. The purpose of this study was to examine relationships among physiological biomarkers (homocysteine, folate, vitamin B12), PTSD diagnosis, PTSD treatment participation, and CVD risk in a veteran population. A quantitative, comparative retrospective chart review was conducted among 279 U.S. veterans with documented homocysteine levels. CVD risk was categorized as high or low-to-moderate based on metabolic and vascular risk factors. Logistic regression, odds ratios, and chi-square analyses were used to examine predictors of CVD risk and elevated homocysteine. The Neuman Systems Model guided variable selection and interpretation. Elevated homocysteine was significantly associated with age, gender, race, systolic blood pressure, folate, vitamin B12, PTSD diagnosis (OR = 4.31, 95% CI [1.36-13.61]), and CVD risk (OR = 3.50, 95% CI [1.01-12.05]). Participation in PTSD treatment was significantly associated with homocysteine levels (OR = 6.43, 95% CI [2.02-20.45]). Findings support homocysteine as a clinically relevant biomarker linking PTSD and cardiovascular risk. The association between PTSD treatment and homocysteine suggests psychological interventions may influence biological pathways relevant to cardiovascular health, underscoring the value of biomarker-informed nursing assessment in trauma-exposed populations.

Isolated third, fourth, and sixth cranial nerve palsies (CNP) in elderly people occur commonly due to microvascular ischemia. Ischemic isolated CNP share several atherosclerotic risk factors that are responsible for stroke which include hypertension, diabetes mellitus and dyslipidemia. Hyperhomocysteinemia is atherogenic and hence is also considered as an independent risk factor for stroke. So indirectly, elevated homocysteine in CNP may act as a risk factor for stroke. To determine the incidence of isolated ischemic CNP secondary to elevated serum homocysteine (predisposing them to a greater risk of stroke), and if serum homocysteine levels need to be checked routinely in all isolated CNP by neuro-ophthalmologists. This is a retrospective case study, in which 66 patients diagnosed with ischemic isolated CNP were enrolled. Informed written consent was obtained from all who participated in this study. Data of these patients were collected from the electronic medical records and were analyzed. Complete anterior, posterior segment and neuro-ophthalmic examinations were done, in addition to routine blood investigations and serum homocysteine. The mean age was 55 years old. Gender wise, 74.24% affected were males and 25.76% were females. The sixth nerve was affected in 68.18% cases. Of 66 patients, 37 cases (56.06%) had elevated serum homocysteine. In patients > 40 years and without any systemic risk factors, 63.2% had elevated serum homocysteine. In patients < 40 years and without systemic risk, 66.7% had high serum homocysteine levels. In cases without systemic risk factors, serum homocysteine may indirectly act as a risk factor for developing stroke in patients having isolated ischemic CNP. According to our study, patients with or without risk factors and those above 40 years, 56.06% patients with isolated ocular motor palsy had elevated serum homocysteine. This implies that the level of elevated serum homocysteine was statistically significant (P < 0.05) in these patients; thus, indirectly showing a greater predilection towards developing a stroke. In this small pilot study, we show that even in neuro-ophthalmology serum homocysteine should be routinely checked for all patients with isolated ischemic CNP. This might reduce the incidence of patients developing a stroke.

Rationale:Although vitamin B12 deficiency is a well-known complication following total gastrectomy, subacute combined degeneration (SCD) rarely develops beyond 5 years postoperatively. Eight-year latency cases are rarely reported, especially when combined with chronic alcohol use, which accelerates neurologic decline and worsens prognosis. This report aims to present a rare case of delayed SCD after total gastrectomy in a patient with chronic alcoholism, emphasizing the importance of lifelong vitamin B12 monitoring in high-risk individuals.Patient concerns:A 49-year-old man presented with progressive quadriparesis and sensory disturbances eight years after total gastrectomy for gastric cancer. He also had a significant history of chronic alcohol consumption, raising suspicion for multifactorial vitamin B12 deficiency.Diagnoses:Laboratory tests revealed severe vitamin B12 deficiency, pancytopenia, and elevated homocysteine and methylmalonic acid levels. Cervical spine magnetic resonance imaging revealed T2-weighted hyperintensity in the dorsal columns, consistent with SCD.Interventions:The patient received vitamin B12 supplementation and underwent a comprehensive rehabilitation program aimed at improving motor function.Outcomes:After rehabilitation, he regained independent ambulation using a cane.Lessons:This case shows an unusually prolonged latency of SCD after total gastrectomy and is notable for the coexistence of 2 established risk factors: gastrectomy and chronic alcoholism. It emphasizes the importance of lifelong surveillance of vitamin B12 status to prevent avoidable and potentially irreversible neurologic complications in high-risk populations.

Nasal septum deviation (NSD) is a common anatomic condition that may cause chronic upper airway obstruction, leading to hypoxia and hypercapnia with potential systemic consequences. Chronic hypoxia has been suggested to contribute to endothelial dysfunction through increased oxidative stress and elevated serum homocysteine levels. Homocysteine is a sulfur-containing amino acid with well-established atherogenic properties and is recognized as an independent cardiovascular risk factor. The aim of this study was to investigate the effect of septoplasty on serum homocysteine levels in patients with NSD and to evaluate changes in subjective nasal obstruction symptoms. This prospective, controlled, and comparative study included 67 patients aged 18 to 50 years with NSD and at least 1 year of nasal obstruction symptoms who underwent septoplasty, along with 67 age- and sex-matched healthy controls. Individuals with systemic diseases, smoking history, or vitamin B12 or folate deficiency were excluded. In the patient group, visual analog scale (VAS) and nasal obstruction symptom evaluation (NOSE) scores, as well as serum homocysteine levels, were measured preoperatively and at postoperative month 1. Blood samples were obtained under fasting conditions before 10:00 am and analyzed using a validated immunoassay method. In the control group, all measurements were performed once. Statistical analyses were conducted using the Wilcoxon signed-rank test and the Mann-Whitney U test. Postoperatively, VAS and NOSE scores showed a significant decrease in the patient group (P<0.001). Serum homocysteine levels were also significantly reduced after surgery (P=0.001). No statistically significant difference was observed between postoperative homocysteine levels in the patient group and those of the control group (P=0.377). Septoplasty not only effectively alleviates nasal obstruction symptoms related to NSD but may also reduce serum homocysteine levels, potentially modulating cardiovascular risk. These findings suggest that septoplasty may provide systemic benefits beyond local symptomatic improvement.

Background/Objectives: Takayasu arteritis is an important non-atherosclerotic cause of ischemic stroke in young adults. However, the relative contribution of systemic inflammation, inherited thrombophilia, and supra-aortic hemodynamic impairment to cerebrovascular events in these patients remains insufficiently defined. This study aimed to evaluate the relative impact of systemic inflammatory activity, hereditary and acquired thrombophilia markers, and supra-aortic vascular involvement on cerebrovascular ischemic events in patients with digital subtraction angiography (DSA) confirmed supra-aortic Takayasu arteritis. Methods: A retrospective cross-sectional analysis was conducted in consecutively evaluated patients with non-atherosclerotic inflammatory stenosis or occlusion of the carotid, subclavian, or vertebral arteries confirmed by digital subtraction angiography. Age- and sex-matched hospital-based individuals without autoimmune, thrombotic, or cerebrovascular diseases served as controls. Laboratory assessments including erythrocyte sedimentation rate, lipoprotein(a), homocysteine, antinuclear antibody, rheumatoid factor, antiphospholipid antibodies, and a hereditary thrombophilia panel were obtained 4-6 weeks after clinical presentation during a stable clinical phase. Results: Among 46 patients with Takayasu arteritis, 21 patients presented with ischemic stroke. The stroke-positive subgroup demonstrated higher inflammatory activity and a slightly greater prevalence of supra-aortic occlusive lesions, particularly involving the common carotid, internal carotid, and subclavian arteries. Although lipoprotein(a) levels showed statistical differences between groups, mean values remained within reference ranges and were not clinically elevated. The distribution of hereditary thrombophilia variants and the prevalence of elevated homocysteine levels did not differ significantly between groups. Clinical outcomes were favorable overall, with no mortality and functional independence achieved in the majority of stroke-positive patients. Conclusions: These findings suggest that systemic inflammation and supra-aortic hemodynamic impairment may play a more prominent role than inherited thrombophilia in the development of cerebrovascular ischemic events in patients with Takayasu arteritis. Selective rather than routine thrombophilia testing may therefore be appropriate in selected clinical contexts, while careful control of inflammatory activity and continuous vascular monitoring remain essential components of management.

Background:Residual cardiovascular risk remains substantial despite aggressive low-density lipoprotein cholesterol (LDL-C) lowering in coronary heart disease (CHD). Consequently, this elevated risk has spurred the search for non-lipid targets, such as homocysteine (HCY). However, the combined effect of HCY with LDL-C and the overall potential for combined risk stratification remain unclear.Methods:This retrospective cohort study included patients with CHD confirmed by coronary angiography or computed tomography angiography at the General Hospital of Ningxia Medical University between January 2019 and December 2021. Participants were stratified by baseline LDL-C levels (<1.8 vs. ≥1.8 mmol/L) and HCY (<15 vs. ≥15 μmol/L). Major adverse cardiovascular events (MACEs) were employed as the primary endpoint, defined as a composite of all-cause death, stroke, non-fatal myocardial infarction, or unplanned revascularization.Results:A total of 744 MACEs were recorded during the 25-month follow-up. Elevated levels of LDL-C (adjusted hazard ratio (aHR) = 1.38, 95% confidence interval (CI): 1.09–1.73) and HCY (aHR = 1.47, 95% CI: 1.19–1.81) were independently associated with a higher risk of MACEs. The risk was synergistic when both factors were elevated, as patients in the high LDL-C and high HCY group had a significantly increased risk (aHR = 1.97, 95% CI: 1.34–2.90) compared to the reference group with low levels.Conclusion:LDL-C and HCY are independent predictors of MACEs in patients with CHD, and the combined use of these indices improves risk stratification. Thus, integrating these indices into clinical practice could improve personalized management strategies and outcomes in this high-risk population.

BACKGROUND Functional vitamin B12 deficiency, also known as metformin-associated cobalamin deficiency, can occur in patients receiving metformin due to impaired gastrointestinal absorption of vitamin B12. This condition can coexist with diabetic neuropathy and may result in impaired myelin formation in the spinal cord and peripheral nerves, leading to subacute combined degeneration of the spinal cord. This report describes a patient with diabetes mellitus and metformin-associated functional vitamin B12 deficiency who presented with subacute combined degeneration of the spinal cord and gastrointestinal symptoms. CASE REPORT A 57-year-old man with a 1-year history of metformin therapy for type 2 diabetes mellitus presented with anorexia, vomiting, weight loss, and gait ataxia. Neurological examination revealed impaired superficial sensation at the T10 to L1 level and bilaterally diminished patellar reflexes. Despite a normal serum vitamin B12 level, further metabolic evaluation revealed a substantially elevated homocysteine level. Electromyography demonstrated peripheral neuropathy in the right upper limb, involving both motor and sensory axons. Spinal magnetic resonance imaging showed characteristic T2 hyperintensity of the dorsal columns. Based on these findings, a definitive diagnosis of subacute combined degeneration was made. The patient was promptly treated with high-dose intramuscular vitamin B12 supplementation and supportive care, resulting in clinically significant improvement in subsequent weeks. CONCLUSIONS This case of metformin-associated cobalamin deficiency with subacute combined degeneration of the spinal cord highlights the importance of monitoring vitamin B12 status and neurological symptoms in patients with metformin-treated diabetes.

Objective: The aim of this study was to evaluate serum homocysteine levels in obese children and adolescents and to examine their relationships with insulin resistance, metabolic risk factors, and vitamin B12, folate, and vitamin D status. Methods: A single-center, retrospective cross-sectional observational study included 102 children and adolescents with obesity attending a tertiary pediatric obesity clinic. Clinical, anthropometric, and biochemical data were analyzed. Group comparisons were performed according to obesity severity and presence of hyperhomocysteinemia. Correlation analyses and multivariable linear regression were conducted to identify independent predictors of serum homocysteine levels. Results: The median serum homocysteine level was 9.5 (7.82-11.8) µmol/L, and hyperhomocysteinemia was present in 27.5% of cases. Insulin resistance was significantly more prevalent in children with severe obesity compared to those with obesity (90.6% vs. 64.3%; OR 5.29, 95% CI 1.41-29.8; p = 0.008). Serum homocysteine levels were positively correlated with age, BMI, fasting glucose, insulin, and HOMA-IR, and negatively correlated with vitamin B12 and folate levels (all p < 0.05). Folate deficiency was significantly more common in participants with hyperhomocysteinemia (33.3% vs. 6.7%; OR 6.82, 95% CI 1.80-29.37; p = 0.002). In multivariable regression analysis, age (β = 0.433; p = 0.001) and folate levels (β = -0.235; p = 0.032) were independently associated with serum homocysteine concentrations. Conclusions: Hyperhomocysteinemia is present in approximately one-quarter of children with obesity and may represent a relevant metabolic alteration in this population. Although serum homocysteine levels were correlated with insulin resistance in univariable analyses, multivariable regression analysis identified age and folate levels as independent determinants. These findings highlight the potential clinical importance of evaluating folate status in children with obesity, particularly in those with elevated homocysteine levels. Prospective studies are warranted to determine whether folate supplementation can effectively reduce homocysteine levels and improve long-term cardiometabolic risk in pediatric obesity.