Trial reportCirculation2022
Insulin Prevents Hypercholesterolemia by Suppressing 12α-Hydroxylated Bile Acids.
Trial report in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Bridging epigenetics and pharmacology through systematic reviews tailored to WBS methodology: the triangle decision-making model as a pioneering translational biological drug delivery system.Frontiers in medicine · 2025Pooled it
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation.Science advances · 2026Article
- Manganese availability determines insulin sensitivity by enhancing Akt activity.bioRxiv : the preprint server for biology · 2026Article
- Increased LDL-C reduction with ezetimibe in ketogenic diet-induced hypercholesterolemia.Lipids in health and disease · 2026Article
- Triglyceride-Rich Lipoprotein Metabolism and Cardiovascular Risk in Diabetes: Bedside to Bench to Bedside.Circulation research · 2026Review
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- Gut microbiota drives the metabolic dysregulation in obesity-prone individuals by impairing GDCA-mediated activation of brown adipose thermogenesis and ileal GLP-1 secretion.Acta pharmaceutica Sinica. B · 2026Article
- Management of dyslipidaemia in patients with comorbidities: facing the challenge: type 2 diabetes mellitus.European heart journal. Cardiovascular pharmacotherapy · 2025Review
- Differential roles of individual bile acid in physiology and disease.Pharmacological research · 2025Review
- Bile acid metabolism in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- Impact of blood lead and manganese levels on metabolic dysfunction-associated steatotic liver disease prevalence: insights from NHANES (2017-2020).BMC gastroenterology · 2025Article
- Effects ofFrontiers in pharmacology · 2025Article
- Host-driven remodeling of rumen microbiota supports lactation metabolism in buffalo.Frontiers in microbiology · 2025Article
- HSDL2 links nutritional cues to bile acid and cholesterol homeostasis.Science advances · 2024Article
- MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosis.PeerJ · 2024Article
- Type 2 diabetes mellitus related sarcopenia: a type of muscle loss distinct from sarcopenia and disuse muscle atrophy.Frontiers in endocrinology · 2024Review
- Metabolic systems approaches update molecular insights of clinical phenotypes and cardiovascular risk in patients with homozygous familial hypercholesterolemia.BMC medicine · 2023Article
- Intestinal Cholesterol Absorption in Diabetes Mellitus.Journal of atherosclerosis and thrombosis · 2023Article
- Review
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundThe risk of cardiovascular disease in type 1 diabetes remains extremely high, despite marked advances in blood glucose control and even the widespread use of cholesterol synthesis inhibitors. Thus, a deeper understanding of insulin regulation of cholesterol metabolism, and its disruption in type 1 diabetes, could reveal better treatment strategies.
methodsTo define the mechanisms by which insulin controls plasma cholesterol levels, we knocked down the insulin receptor, FoxO1, and the key bile acid synthesis enzyme, CYP8B1. We measured bile acid composition, cholesterol absorption, and plasma cholesterol. In parallel, we measured markers of cholesterol absorption and synthesis in humans with type 1 diabetes treated with ezetimibe and simvastatin in a double-blind crossover study.
resultsMice with hepatic deletion of the insulin receptor showed marked increases in 12α-hydroxylated bile acids, cholesterol absorption, and plasma cholesterol. This phenotype was entirely reversed by hepatic deletion of
conclusionsInsulin, by inhibiting FoxO1 in the liver, reduces 12α-hydroxylated bile acids, cholesterol absorption, and plasma cholesterol levels. Thus, type 1 diabetes leads to a unique set of derangements in cholesterol metabolism, with increased absorption rather than synthesis. These derangements are reversed by ezetimibe, but not statins, which are currently the first line of lipid-lowering treatment in type 1 diabetes. Taken together, these data suggest that a personalized approach to lipid lowering in type 1 diabetes may be more effective and highlight the need for further studies specifically in this group of 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.