Why is HDL functionally deficient in type 2 diabetes?
High-density lipoprotein (HDL) particles exert a spectrum of atheroprotective activities that can be deficient in type 2 diabetes. Key mechanisms leading to the formation of functionally deficient HDL involve 1) HDL enrichment in triglycerides and depletion in cholesteryl esters with conformational alterations of apolipoprotein A-I; 2) glycation of apolipoproteins and/or HDL-associated enzymes; and 3) oxidative modification of HDL lipids, apolipoproteins, and/or enzymes. Available data identify hypertriglyceridemia, with concomitant compositional modification of the HDL lipid core and conformational change of apolipoprotein A-I, as a driving force in functional alteration of HDL particles in type 2 diabetes. Therapeutic options for correcting HDL functional deficiency should target hypertriglyceridemia by normalizing circulating levels of triglyceride-rich lipoproteins.
Kontush
Anatol
A
INSERM Unité 551, Pavillon Benjamin Delessert, Hôpital de Pitié, 83 boulevard de l'Hôpital, 75651 Paris Cedex 13, France. kontush@chups.jussieu.fr
Chapman
M John
MJ
D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000172:deficiency* / Q000378:metabolism
D008075:Lipoproteins, HDL