| المستخلص: |
High density lipoprotein (HDL) plays a crucial role in protecting against cardiovascular disease (CVD) by acquiring cholesterol from peripheral tissues and transporting it to the liver for clearance in a process known as “reverse cholesterol transport’. Differences in HDL lipid composition in type-2 diabetes (T2D) may alter HDL functionality and increase risk of CVD. In this study, it is hypothesised that HDL lipid composition in T2D is altered compared with control and pre-diabetic individuals, and this change may contribute adversely to HDL functionality. To test this hypothesis, the lipid composition of plasma and HDL were determined by tandem mass spectrometry in patients with normoglycemia (N=5), pre-diabetes (N=5), and T2D (N=5); HDL functionality was determined by cholesterol efflux measures using whole plasma. Compared with normoglycemic controls, T2D was associated with significant enrichment in dihydroceramide (dhCer) and diacylglycerol in plasma and HDL; further enrichment of phosphatidylglycerol and triglycerides were observed in plasma only whereas odd chain phosphatidylcholine (odd PC) was lower in HDL only. Compared with pre-diabetics, T2D was associated with increased plasma dhCer and reductions in HDL sphingomyelin, odd chain PC, alkylphosphatidylcholine, and phosphatidylcholine plasmalogen (all p<0.05). Cholesterol efflux was not significantly different between study groups. This is the first report examining the differences in lipid composition of plasma and HDL in pre-diabetes and T2D. The findings are consistent with the notion that hypertriglyceridemia, hyperinsulinemia and hyperglycemia are the primary drivers of HDL dysfunction in pre-diabetes and T2D. This is reflected in part by alterations in the lipid composition which may correspond to the stage of disease. Enrichment of plasma and HDL with dhCer is associated with insulin
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