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Keywords:

  • coronary heart disease;
  • glycation;
  • lipid hydroperoxides;
  • paraoxonase-1;
  • Type 2 diabetes

Abstract

Aims  High-density lipoprotein (HDL) protects against atherosclerosis development. Defective functioning of HDL in Type 2 diabetes may be one cause of increased cardiovascular disease associated with Type 2 diabetes. HDL modulates low-density lipoprotein and cell membrane oxidation through the action of paraoxonase-1 (PON1), which is one of the major mechanisms by which HDL is anti-atherogenic.

Methods  We have compared the ability of HDL from Type 2 diabetic patients without coronary heart disease (CHD) (n = 36) to metabolize membrane lipid hydroperoxides with HDL from healthy control subjects (n = 19) and people with CHD but no diabetes (n = 37).

Results  HDL from subjects with Type 2 diabetes and CHD metabolized 20% less membrane hydroperoxides than HDL from control subjects (P < 0.05). The PON1-192RR was least efficient in all the study groups. PON1 was glycated in vivo: (7.5% control, 12% CHD, 17% Type 2 diabetes P < 0.01) with QQ isoforms most glycated. In vitro glycation of PON1 reduced its ability to metabolize membrane hydroperoxides by 50% (P < 0.001); however, glyoxidation reduced it by 80% (P < 0.001). In the control group only there was a significant negative correlation between PON1 activity and the ability of HDL to metabolize membrane hydroperoxides (r = −0.911, P < 0.001).

Conclusions  HDL from Type 2 diabetic patients without CHD has decreased ability to metabolize membrane lipid hydroperoxides, which could lead to increased susceptibility to cardiovascular disease.