Background: The relationship between circulating lipid levels and the risk for heart failure (HF) is controversial. We aimed to examine this association, and whether it is modified by the duration of diabetes or treatment regimens in people with type 2 diabetes mellitus. Methods: Individuals (n=2,439,978) who underwent health examinations in 2015 to 2016 were identified from the Korean National Health Information Database. Subjects were categorized according to the duration of diabetes (new-onset, <5, 5–10, or ≥10 years) and number of antidiabetic medications. Incident HF was defined according to the International Classification of Diseases, 10th Revision (ICD-10) code I50 as the primary diagnosis during hospitalization. The risk for HF was estimated using multivariate Cox proportional hazard analysis. Results: During a median follow-up of 4.0 years, 151,624 cases of HF occurred. An inverse association between low-density lipoprotein cholesterol (LDL-C) levels and incident HF was observed in the new-onset diabetes group, with an approximately 25% lower risk in those with LDL-C levels of 100–129, 130–159, and ≥160 mg/dL, compared to those with levels <70 mg/dL. However, J-shaped associations were noted in the long-standing diabetes group, with a 16% higher risk in those with LDL-C level ≥160 mg/dL, compared to those with levels <70 mg/dL. Similar patterns were observed in the relationship between total cholesterol or non-high-density lipoprotein cholesterol and the risk for HF, and when subjects were grouped according to the number of antidiabetic medications instead of diabetes duration. Conclusion Different associations between lipid levels and the risk for HF were noted according to disease progression status among individuals with diabetes.

Objective: The association of lipid parameters with cardiovascular disease (CVD) and the impact of kidney function on this association have not been thoroughly evaluated in patients with type 2 diabetes mellitus (T2DM). Methods: Using the Korean National Health Insurance Service Cohort database, we identified 2,343,882 subjects with T2DM in 2015–2016. Baseline lipid levels and kidney function were evaluated and followed up until December 2020. Subjects were classified into three groups according to their estimated glomerular filtration rate (eGFR): ≥60, 30–59, or <30 mL/min/ 1.73 m2 . We analyzed the diabetes group with eGFR ≥60 and low-density lipoprotein cholesterol (LDL-C) <70 mg/dL as a reference group. Results: The risk of CVD began to increase at LDL-C ≥100 mg/dL in the eGFR ≥60 mL/min/m2group. The risk of CVD in the eGFR 30–59 mL/min/m2 group was increased by 43%, even in the LDL-C <70 mg/dL, and the risk increased progressively with LDL-C category. Among subjects with eGFR 30–59 mL/min/m2 , LDL-C 70–99, 100–129, 130–159, and ≥160 mg/ dL were significantly associated with the risk of CVD, with hazard ratio (95% confidence interval) of 1.48 (1.43–1.53), 1.54 (1.49–1.60), 1.55 (1.48–1.63), and 1.88 (1.77–2.00), respectively. In the eGFR <30 mL/min/m2 group, a 3.3-fold increased risk of CVD was seen, even at LDL-C <70 mg/dL. Conclusion The cutoff levels of LDL-C that increase CVD risk in patients with T2DM depend on kidney function, which influences the relationship between LDL-C and CVD risk in patients with T2DM.

Objective: The association of lipid parameters with cardiovascular disease (CVD) and the impact of kidney function on this association have not been thoroughly evaluated in patients with type 2 diabetes mellitus (T2DM). Methods: Using the Korean National Health Insurance Service Cohort database, we identified 2,343,882 subjects with T2DM in 2015–2016. Baseline lipid levels and kidney function were evaluated and followed up until December 2020. Subjects were classified into three groups according to their estimated glomerular filtration rate (eGFR): ≥60, 30–59, or <30 mL/min/ 1.73 m2 . We analyzed the diabetes group with eGFR ≥60 and low-density lipoprotein cholesterol (LDL-C) <70 mg/dL as a reference group. Results: The risk of CVD began to increase at LDL-C ≥100 mg/dL in the eGFR ≥60 mL/min/m2group. The risk of CVD in the eGFR 30–59 mL/min/m2 group was increased by 43%, even in the LDL-C <70 mg/dL, and the risk increased progressively with LDL-C category. Among subjects with eGFR 30–59 mL/min/m2 , LDL-C 70–99, 100–129, 130–159, and ≥160 mg/ dL were significantly associated with the risk of CVD, with hazard ratio (95% confidence interval) of 1.48 (1.43–1.53), 1.54 (1.49–1.60), 1.55 (1.48–1.63), and 1.88 (1.77–2.00), respectively. In the eGFR <30 mL/min/m2 group, a 3.3-fold increased risk of CVD was seen, even at LDL-C <70 mg/dL. Conclusion The cutoff levels of LDL-C that increase CVD risk in patients with T2DM depend on kidney function, which influences the relationship between LDL-C and CVD risk in patients with T2DM.

Background: The relationship between circulating lipid levels and the risk for heart failure (HF) is controversial. We aimed to examine this association, and whether it is modified by the duration of diabetes or treatment regimens in people with type 2 diabetes mellitus. Methods: Individuals (n=2,439,978) who underwent health examinations in 2015 to 2016 were identified from the Korean National Health Information Database. Subjects were categorized according to the duration of diabetes (new-onset, <5, 5–10, or ≥10 years) and number of antidiabetic medications. Incident HF was defined according to the International Classification of Diseases, 10th Revision (ICD-10) code I50 as the primary diagnosis during hospitalization. The risk for HF was estimated using multivariate Cox proportional hazard analysis. Results: During a median follow-up of 4.0 years, 151,624 cases of HF occurred. An inverse association between low-density lipoprotein cholesterol (LDL-C) levels and incident HF was observed in the new-onset diabetes group, with an approximately 25% lower risk in those with LDL-C levels of 100–129, 130–159, and ≥160 mg/dL, compared to those with levels <70 mg/dL. However, J-shaped associations were noted in the long-standing diabetes group, with a 16% higher risk in those with LDL-C level ≥160 mg/dL, compared to those with levels <70 mg/dL. Similar patterns were observed in the relationship between total cholesterol or non-high-density lipoprotein cholesterol and the risk for HF, and when subjects were grouped according to the number of antidiabetic medications instead of diabetes duration. Conclusion Different associations between lipid levels and the risk for HF were noted according to disease progression status among individuals with diabetes.

Background: The relationship between circulating lipid levels and the risk for heart failure (HF) is controversial. We aimed to examine this association, and whether it is modified by the duration of diabetes or treatment regimens in people with type 2 diabetes mellitus. Methods: Individuals (n=2,439,978) who underwent health examinations in 2015 to 2016 were identified from the Korean National Health Information Database. Subjects were categorized according to the duration of diabetes (new-onset, <5, 5–10, or ≥10 years) and number of antidiabetic medications. Incident HF was defined according to the International Classification of Diseases, 10th Revision (ICD-10) code I50 as the primary diagnosis during hospitalization. The risk for HF was estimated using multivariate Cox proportional hazard analysis. Results: During a median follow-up of 4.0 years, 151,624 cases of HF occurred. An inverse association between low-density lipoprotein cholesterol (LDL-C) levels and incident HF was observed in the new-onset diabetes group, with an approximately 25% lower risk in those with LDL-C levels of 100–129, 130–159, and ≥160 mg/dL, compared to those with levels <70 mg/dL. However, J-shaped associations were noted in the long-standing diabetes group, with a 16% higher risk in those with LDL-C level ≥160 mg/dL, compared to those with levels <70 mg/dL. Similar patterns were observed in the relationship between total cholesterol or non-high-density lipoprotein cholesterol and the risk for HF, and when subjects were grouped according to the number of antidiabetic medications instead of diabetes duration. Conclusion Different associations between lipid levels and the risk for HF were noted according to disease progression status among individuals with diabetes.

Objective: The association of lipid parameters with cardiovascular disease (CVD) and the impact of kidney function on this association have not been thoroughly evaluated in patients with type 2 diabetes mellitus (T2DM). Methods: Using the Korean National Health Insurance Service Cohort database, we identified 2,343,882 subjects with T2DM in 2015–2016. Baseline lipid levels and kidney function were evaluated and followed up until December 2020. Subjects were classified into three groups according to their estimated glomerular filtration rate (eGFR): ≥60, 30–59, or <30 mL/min/ 1.73 m2 . We analyzed the diabetes group with eGFR ≥60 and low-density lipoprotein cholesterol (LDL-C) <70 mg/dL as a reference group. Results: The risk of CVD began to increase at LDL-C ≥100 mg/dL in the eGFR ≥60 mL/min/m2group. The risk of CVD in the eGFR 30–59 mL/min/m2 group was increased by 43%, even in the LDL-C <70 mg/dL, and the risk increased progressively with LDL-C category. Among subjects with eGFR 30–59 mL/min/m2 , LDL-C 70–99, 100–129, 130–159, and ≥160 mg/ dL were significantly associated with the risk of CVD, with hazard ratio (95% confidence interval) of 1.48 (1.43–1.53), 1.54 (1.49–1.60), 1.55 (1.48–1.63), and 1.88 (1.77–2.00), respectively. In the eGFR <30 mL/min/m2 group, a 3.3-fold increased risk of CVD was seen, even at LDL-C <70 mg/dL. Conclusion The cutoff levels of LDL-C that increase CVD risk in patients with T2DM depend on kidney function, which influences the relationship between LDL-C and CVD risk in patients with T2DM.

Background: The relationship between circulating lipid levels and the risk for heart failure (HF) is controversial. We aimed to examine this association, and whether it is modified by the duration of diabetes or treatment regimens in people with type 2 diabetes mellitus. Methods: Individuals (n=2,439,978) who underwent health examinations in 2015 to 2016 were identified from the Korean National Health Information Database. Subjects were categorized according to the duration of diabetes (new-onset, <5, 5–10, or ≥10 years) and number of antidiabetic medications. Incident HF was defined according to the International Classification of Diseases, 10th Revision (ICD-10) code I50 as the primary diagnosis during hospitalization. The risk for HF was estimated using multivariate Cox proportional hazard analysis. Results: During a median follow-up of 4.0 years, 151,624 cases of HF occurred. An inverse association between low-density lipoprotein cholesterol (LDL-C) levels and incident HF was observed in the new-onset diabetes group, with an approximately 25% lower risk in those with LDL-C levels of 100–129, 130–159, and ≥160 mg/dL, compared to those with levels <70 mg/dL. However, J-shaped associations were noted in the long-standing diabetes group, with a 16% higher risk in those with LDL-C level ≥160 mg/dL, compared to those with levels <70 mg/dL. Similar patterns were observed in the relationship between total cholesterol or non-high-density lipoprotein cholesterol and the risk for HF, and when subjects were grouped according to the number of antidiabetic medications instead of diabetes duration. Conclusion Different associations between lipid levels and the risk for HF were noted according to disease progression status among individuals with diabetes.

Objective: The association of lipid parameters with cardiovascular disease (CVD) and the impact of kidney function on this association have not been thoroughly evaluated in patients with type 2 diabetes mellitus (T2DM). Methods: Using the Korean National Health Insurance Service Cohort database, we identified 2,343,882 subjects with T2DM in 2015–2016. Baseline lipid levels and kidney function were evaluated and followed up until December 2020. Subjects were classified into three groups according to their estimated glomerular filtration rate (eGFR): ≥60, 30–59, or <30 mL/min/ 1.73 m2 . We analyzed the diabetes group with eGFR ≥60 and low-density lipoprotein cholesterol (LDL-C) <70 mg/dL as a reference group. Results: The risk of CVD began to increase at LDL-C ≥100 mg/dL in the eGFR ≥60 mL/min/m2group. The risk of CVD in the eGFR 30–59 mL/min/m2 group was increased by 43%, even in the LDL-C <70 mg/dL, and the risk increased progressively with LDL-C category. Among subjects with eGFR 30–59 mL/min/m2 , LDL-C 70–99, 100–129, 130–159, and ≥160 mg/ dL were significantly associated with the risk of CVD, with hazard ratio (95% confidence interval) of 1.48 (1.43–1.53), 1.54 (1.49–1.60), 1.55 (1.48–1.63), and 1.88 (1.77–2.00), respectively. In the eGFR <30 mL/min/m2 group, a 3.3-fold increased risk of CVD was seen, even at LDL-C <70 mg/dL. Conclusion The cutoff levels of LDL-C that increase CVD risk in patients with T2DM depend on kidney function, which influences the relationship between LDL-C and CVD risk in patients with T2DM.

Purpose: We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data. Materials and Methods: The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type. Results: Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite. Conclusion Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.

Purpose: By utilizing both protein and mRNA expression patterns, we can identify more detailed and diverse immune cells, providing insights into understanding the complex immune landscape in cancer ecosystems. Materials and Methods: This study was performed by obtaining publicly available Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) data of peripheral blood mononuclear cells (PBMCs) from the Gene Expression Omnibus database. A total of 94674 total cells were analyzed, of which 32412 were T cells. There were 228 protein features and 16262 mRNA features in the data.The Seurat package was used for quality control and preprocessing, principal component analysis was performed, and Uniform Manifold Approximation and Projection was used to visualize the clusters. Protein and mRNA levels in the CITE-seq were analyzed. Results: We observed that a subset of T cells in the clusters generated at the protein level divided better. By identifying mRNA markers that were highly correlated with the CD4 and CD8 proteins and cross-validating CD26 and CD99 markers using flow cytometry, we found that CD4 + and CD8+ T cells were better discriminated in PBMCs. Weighted Nearest Neighbor clustering results identified a previously unobserved T cell subset. Conclusion In this study, we used CITE-seq data to confirm that protein expression patterns could be used to identify cells more precisely. These findings will improve our understanding of the heterogeneity of immune cells in the future and provide valuable insights into the complexity of the immune response in health and disease.