Gemfibrozil increases paraoxonase activity in type 2 diabetic patients. A new hypothesis of the beneficial action of fibrates?
OBJECTIVE
The constellation of elevated triglycerides and decreased high-density lipoprotein is recognised as a risk factor for CAD and constitutes the major dyslipidemia in type 2 diabetes. The high-density lipoprotein associated paraoxonase activity can inhibit low-density lipoprotein oxidation and has an antiatherogenic effect. To determine the effect of gemfibrozil on the dyslipidemia and serum paraoxonase activity in patients with type 2 diabetes.


METHODS
Fifty-six type 2 diabetic patients with associated hypertriglyceridemia were involved. They were investigated for the effect of twice daily 600 mg of gemfibrozil on serum cholesterol, triglycerides, apolipoproteins, fibrinogen level, body mass index and glycated hemoglobin. Serum paraoxonase activity was measured spectrophotometrically.


RESULTS
After three months, it was observed that under the effect of gemfibrozil, serum triglyceride level was significantly decreased (from median: 3.46 mmol/l quartiles: q1=2.92 q3=5.28 to median 2.20 mmol/l quartiles: q1=1.79 q3=3.65; p<0.001) while protective high-density lipoprotein (from 1.02 +/- 0.22 mmol/l to 1.13 +/- 0.28 mmol/l; p=0.05) and apolipoprotein A(1) (from 1.56 +/- 0.33 g/l to 1.72 +/- 0.29; p<0.01) levels were significantly increased. Serum paraoxonase activity was found to be significantly increased (from median: 100.2 U/l quartiles: q1=60.1 q3=152.7 to median 118.7 U/l quartiles: q1=80.1 q3=171.0; p<0.001) after gemfibrozil treatment. The total cholesterol, low-density lipoprotein, apolipoprotein B, lipoprotein (a), glycated hemoglobin and fibrinogen levels were not significantly changed during the three-month treatment period. The standardized paraoxonase activity for HDL and apo A(1) were not significantly changed. Paraoxonase activity did not correlate with the concentration of glycohemoglobin and the duration of diabetes.


CONCLUSIONS
Twice daily administration of 600 mg of gemfibrozil is effective in type 2 diabetic patients with associated hypertriglyceridemia. It favorably lowers lipid levels, and improves antioxidant status by increasing serum paraoxonase activity.
Balogh
Z
Z
Medical and Health Science Center, University of Debrecen, 1st Department of Medicine, Hungary. baloghz@ibel.dote.hu
Seres
I
I
Harangi
M
M
Kovács
P
P
Kakuk
G
G
Paragh
G
G
D000328:Adult; D001053:Apolipoproteins / Q000097:blood; D043303:Aryldialkylphosphatase; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D004950:Esterases / Q000097:blood*; D005260:Female; D015248:Gemfibrozil / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D000960:Hypolipidemic Agents; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol; D004950:Esterases; D043303:Aryldialkylphosphatase; D015248:Gemfibrozil