Myeloperoxidase and paraoxonase-1 in type 2 diabetic patients.
OBJECTIVE
Reduced high density lipoproteins (HDL) and increased oxidative stress are features of type 2 diabetes. Myeloperoxidase is an oxidative enzyme partly associated with HDL and causing HDL dysfunction. It is an independent risk factor for cardiovascular disease. Paraoxonase-1 is an HDL-associated enzyme that protects against cardiovascular disease and is reduced in diabetes. The present study examined if serum myeloperoxidase was (i) increased in type 2 diabetes, (ii) correlated with paraoxonase-1 activity.


RESULTS
The study was based on cross-sectional analyses of serum myeloperoxidase and paraoxonase-1 in type 2 diabetic patients and non-diabetic participants, with and without cardiovascular disease. Serum myeloperoxidase concentrations were not increased in type 2 diabetic patients without cardiovascular disease compared to non-diabetic controls. They were significantly higher in type 2 patients and non-diabetic patients with angiographically confirmed coronary disease. HDL-associated myeloperoxidase was correlated with serum myeloperoxidase (r=0.80, p<0.001) but not HDL-cholesterol (r=0.08) or apolipoprotein AI (r=0.08). Multivariate analyses showed serum myeloperoxidase to be an independent determinant of paraoxonase activities (arylesterase, p=0.024; paraoxonase, p=0.026).


CONCLUSIONS
Myeloperoxidase is an independent, negative determinant of paraoxonase-1 activity, which may be one mechanism by which it promotes HDL dysfunction and increases cardiovascular risk. Increased serum myeloperoxidase is not a feature of type 2 diabetes in the absence of overt cardiovascular disease. The level of HDL-associated myeloperoxidase is determined by the serum concentration of the enzyme suggesting that, in the context of reduced HDL concentrations in diabetic patients, myeloperoxidase may have a greater impact on HDL function.
Jornayvaz
F R
FR
Service of Endocrinology, Diabetes and Nutrition, Department of Internal Medicine, Faculty of Medicine, Geneva University, Geneva, Switzerland.
Brulhart-Meynet
M-C
MC
James
R W
RW
D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D043303:Aryldialkylphosphatase / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000453:epidemiology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018384:Oxidative Stress / Q000502:physiology*; D009195:Peroxidase / Q000097:blood*; D011237:Predictive Value of Tests; D012307:Risk Factors
C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D009195:Peroxidase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human