Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controls.
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.


METHODS
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.
Mackness
B
B
University Department of Medicine, Manchester Royal Infirmary, Manchester, UK.
Durrington
P N
PN
Boulton
A J M
AJ
Hine
D
D
Mackness
M I
MI
D000328:Adult; D001161:Arteriosclerosis / Q000473:pathology; D043303:Aryldialkylphosphatase; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology*; D018450:Disease Progression; D004950:Esterases / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human