ArticleThe Journal of clinical investigation2019
Increased apolipoprotein C3 drives cardiovascular risk in type 1 diabetes.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05653518 (Using Closed-Loop Artificial Pancreas Technology to Reduce Glycemic Variability and Subsequently Improve Cardiovascular Health in Type 1 Diabetes), which is not on this map. Cited by 68 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Using Closed-Loop Artificial Pancreas Technology to Reduce Glycemic Variability and Subsequently Improve Cardiovascular Health in Type 1 Diabetes
Who cites it
68 citing papers in PubMed, 106 citations in OpenAlex.
- Hemoglobin A1c Variability Metrics Predict Coronary Artery Calcium and Cardiovascular Events in Type 1 Diabetes: The CACTI Study.The Journal of clinical endocrinology and metabolism · 2023Trial
- ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials.Nature medicine · 2021Trial
- Triglyceride-Rich Lipoprotein Metabolism and Cardiovascular Risk in Diabetes: Bedside to Bench to Bedside.Circulation research · 2026Review
- Kidney-Vascular Metabolic Crosstalk: Altered Lipoproteins in CKD.Circulation research · 2026Review
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Apolipoprotein C3 exacerbates vascular calcification by promoting ferroptosis via the TLR2/AMPK pathway in vascular smooth muscle cells.Redox biology · 2026Article
- Elevated apolipoprotein C3 heightens atherosclerosis risk by mediating arterial accumulation of free cholesterol and local inflammation in diabetes.Research square · 2025Article
- Atherosclerosis in diabetes mellitus: novel mechanisms and mechanism-based therapeutic approaches.Nature reviews. Cardiology · 2025Review
- Diabetes-Driven Atherosclerosis: Updated Mechanistic Insights and Novel Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Relevance of Lipoprotein Composition in Endothelial Dysfunction and the Development of Hypertension.International journal of molecular sciences · 2025Review
- Molecular Regulation and Therapeutic Targeting of VLDL Production in Cardiometabolic Disease.Cellular and molecular gastroenterology and hepatology · 2025Review
- Article
- Multifaceted Role of Apolipoprotein C3 in Cardiovascular Disease Risk and Metabolic Disorder in Diabetes.International journal of molecular sciences · 2024Review
- Interaction Between Primary Hyperlipidemias and Type 2 Diabetes: Therapeutic Implications.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2024Review
- Relationship of apolipoprotein C-III proteoform composition with ankle-brachial index and peripheral artery disease in the Multi-Ethnic Study of Atherosclerosis (MESA).Atherosclerosis · 2024Article
- Imbalance of APOB Lipoproteins and Large HDL in Type 1 Diabetes Drives Atherosclerosis.Circulation research · 2024Article
- A novel mouse model of familial combined hyperlipidemia and atherosclerosis.Acta pharmacologica Sinica · 2024Article
- Elevated apolipoprotein C3 augments diabetic kidney disease and associated atherosclerosis in type 2 diabetes.JCI insight · 2024Article
- A High-Throughput PIXUL-Matrix-Based Toolbox to Profile Frozen and Formalin-Fixed Paraffin-Embedded Tissues Multiomes.Laboratory investigation; a journal of technical methods and pathology · 2024Article
- Apolipoprotein C3: form begets function.Journal of lipid research · 2024Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
Type 1 diabetes mellitus (T1DM) increases the risk of atherosclerotic cardiovascular disease (CVD) in humans by poorly understood mechanisms. Using mouse models of T1DM-accelerated atherosclerosis, we found that relative insulin deficiency rather than hyperglycemia elevated levels of apolipoprotein C3 (APOC3), an apolipoprotein that prevents clearance of triglyceride-rich lipoproteins (TRLs) and their remnants. We then showed that serum APOC3 levels predict incident CVD events in subjects with T1DM in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. To explore underlying mechanisms, we investigated the impact of Apoc3 antisense oligonucleotides (ASOs) on lipoprotein metabolism and atherosclerosis in a mouse model of T1DM. Apoc3 ASO treatment abolished the increased hepatic Apoc3 expression in diabetic mice - resulting in lower levels of TRLs - without improving glycemic control. APOC3 suppression also prevented arterial accumulation of APOC3-containing lipoprotein particles, macrophage foam cell formation, and the accelerated atherosclerosis in diabetic mice. Our observations demonstrate that relative insulin deficiency increases APOC3 and that this results in elevated levels of TRLs and accelerated atherosclerosis in a mouse model of T1DM. Because serum levels of APOC3 predicted incident CVD events in the CACTI study, inhibiting APOC3 might reduce CVD risk in T1DM patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.