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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 Biddinger
Published 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.
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