European Journal of Clinical Investigation · 2002 · 129 citations · 28 references
Life SciencesBiochemistryInternal MedicineDiabetologyGenetic EpidemiologyLipid BiochemistryCardiovascular DiseaseDiabetes MellitusOxidative StressDiabetes-associated Cardiac RiskDiabetes-related Genetic RiskDiabetic ComplicationsOxidative Stress In Cardiovascular DiseaseOxidative Stress In DiabetesOxidative Stress Injury
BACKGROUND: The oxidation of low-density lipoprotein (LDL) is central to current theories on the initiation and progression of atherosclerosis. Type 1 diabetes is associated with an increase in oxidative stress, which may be responsible for the increased susceptibility to coronary heart disease seen in type 1 diabetes. High-density lipoprotein (HDL) associated paraoxonase (PON1) can retard the oxidation of LDL. DESIGN: Paraoxonase activity, concentration and genotype were therefore investigated in 152 people with type 1 diabetes and 282 healthy controls. These parameters were also investigated in the group with type 1 diabetes in relation to the presence of diabetic complications. RESULTS: Both PON1 activity and concentration were significantly lower by 16.7% and 19.2% (both P < 0.05) in the type 1 diabetes group. These differences were independent of the PON1 coding region polymorphisms. The distribution of PON1 activity and mass were the same in both populations, i.e. for the PON1-192 polymorphism RR > RQ > QQ and for the PON1-55 polymorphism LL > LM > MM. There were no differences in either the PON1 polymorphisms, PON1 activity and concentration in people with type 1 diabetes in the presence or absence of micro and macro vascular complications of diabetes. CONCLUSIONS: Low PON1 activity may contribute to the increased atherosclerosis found in type 1 diabetes by reducing the ability of HDL to retard LDL oxidation despite the frequently-found increased HDL in type 1 diabetes when good glycaemic control is established.
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A. D. Watson, J A Berliner, Susan Hama et al. · Journal of Clinical Investigation · 1995 · 1.2K citations · Full text
Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis
Diana M. Shih, Lingjie Gu, Yu-Rong Xia et al. · Nature · 1998 · 1.1K citations