Fenofibrate and rosiglitazone improve quality of lipoproteins in patients with type 2 diabetes mellitus.
BACKGROUND
Particle size distribution in both HDL and LDL is reflected in the fractional esterification rate of cholesterol by lecithin cholesterol acyltransferase (LCAT) in plasma depleted of apoB containing lipoproteins (FER(HDL)). We studied FER(HDL) in a group of patients with type 2 diabetes and determined the impact of two different PPAR agonists (fenofibrate and rosiglitazone) on this marker of lipoprotein particle quality.


METHODS
66 patients with type 2 diabetes (26 women) and 32 control subjects (19 women) were included in the study. 33 patients received fenofibrate and 33 rosiglitazone as add on therapy. Average duration of treatment was 4 months. Plasma lipoprotein glucose levels were determined using an automated analyzer (COBAS Mira, Roche). LDL cholesterol concentrations were calculated by Friedewald formula. FER(HDL) was determined by a radioassay after precipitating apo-B containing particles of plasma. The assays were performed at baseline and at the end of each treatment. SPSS base program was used for statistical evaluation.


RESULTS
Both fenofibrate and rosiglitazone resulted in a significant decrease of FER(HDL) (24.62 +/- 11.27%/h vs. 19.93 +/- 10.34%/h; 20.0 +/- 6.1%/h vs. 15.8 +/- 5.8%/h, p < 0.001). Rosiglitazone was significantly more effective in FER(HDL) lowering than fenofibrate (p < 0,02)


CONCLUSIONS
Both fenofibrate and rosiglitazone improve FER(HDL) in patients with type 2 diabetes. The effect is more pronounced for rosiglitazone. Qualitative change of plasma lipoproteins reflected by FER(HDL) can contribute to antiatherogenic action of PPAR agonists. On contrary, changes of lipoprotein composition induced by PPAR agonists cannot explain adverse cardiovascular effects observed in some large clinical trials with PPAR agonists.
Vrablík
Michal
M
3rd Department of Medicine, 1st Faculty of Medicine, Charles University, Czech Republic. vrablikm@seznam.cz
Dobiásová
Milada
M
Stulc
Tomás
T
Kasalová
Zdislava
Z
Dolezalová
Radka
R
Prázný
Martin
M
Fait
Tomas
T
Ceska
Richard
R
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D011345:Fenofibrate / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D011237:Predictive Value of Tests; D012307:Risk Factors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D015415:Biomarkers; D008078:Cholesterol, LDL; D008074:Lipoproteins; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D011345:Fenofibrate