Relationships of HDL Cholesterol, ApoA-I, and ApoA-II With Homocysteine and Creatinine in Patients With Type 2 Diabetes Treated With Fenofibrate

OBJECTIVE: The purpose of this study was to determine fenofibrate-induced changes in plasma high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) A-I, and apolipoprotein (apo) A-II and how they relate to changes in plasma homocysteine and creatinine. METHODS AND RESULTS: FIELD was a double-blind placebo-controlled trial done in Australia, New Zealand, and Finland. All FIELD subjects were included except those who started statin therapy or permanently discontinued fenofibrate. Patients were randomized to receive daily micronized fenofibrate (200 mg) or matching placebo and were followed up for a median of 5 years. Plasma HDL-C, apoA-I, apoA-II, homocysteine, and creatinine were measured. There was an inverse relationship between baseline homocysteine levels and HDL-C in the placebo (P=0.07 for linear trend) and fenofibrate groups (P<0.0001) and apoA-I (P<0.001, both groups). The increases in homocysteine and creatinine in the fenofibrate group correlated positively (P<0.0001). The greater the increase in homocysteine induced by fenofibrate, the smaller the increases in HDL-c and apoA-I (P<0.0001 for linear trends). There was a highly significant and positive relationship between fenofibrate-induced changes in homocysteine and apoA-II levels. CONCLUSIONS: PPAR alpha agonists that have a more robust effect on HDL-C and apoA-I would be desirable.