Insulin Prevents Hypercholesterolemia by Suppressing 12α-Hydroxylated Bile Acids.
Ivana SemovaAmy E LevensonJoanna KrawczykKevin BullockMary E GearingAlisha V LingKathryn A WilliamsJi MiaoStuart S AdamsonDong-Ju ShinSatyapal ChaharMark J GrahamRosanne M CrookeLee R HageyDavid VicentSarah D de FerrantiSrividya KidambiAndrew T ChanSudha B BiddingerPublished in: Circulation (2022)
Insulin, 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.
Keyphrases
- type diabetes
- glycemic control
- low density lipoprotein
- cardiovascular disease
- end stage renal disease
- signaling pathway
- ejection fraction
- newly diagnosed
- chronic kidney disease
- prognostic factors
- transcription factor
- cardiovascular events
- machine learning
- pi k akt
- mouse model
- coronary artery disease
- combination therapy
- weight loss