The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study.
OBJECTIVE
The primary objective was to determine the effect of statin-fibrate combination therapy on inflammatory biomarkers in patients with diabetes.


BACKGROUND
Atherosclerosis is a long-term, chronic inflammatory disease that is exacerbated in patients with diabetes.


METHODS
Patients (n = 300) with type II diabetes, mixed dyslipidemia (2 or more of low-density lipoprotein > or =100 mg/dl, triglycerides > or =200 mg/dl, or high-density lipoprotein <40 mg/dl), and no history of coronary heart disease were randomly assigned to receive simvastatin 20 mg, fenofibrate 160 mg, or a combination of simvastatin 20 mg and fenofibrate 160 mg daily. At 12 weeks after randomization, we measured levels of high-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA(2)).


RESULTS
At 12 weeks, median hsCRP was significantly reduced (-14.6%, p = 0.004) from baseline, but the effect did not differ between treatments. The effect was greatest among patients with baseline hsCRP levels >2.0 mg/l (fenofibrate = -18.9%, p = 0.002 vs. baseline; simvastatin = -24.8%, p < 0.0001; combination = -27.3%, p = 0.002). Likewise, median Lp-PLA(2) levels in the overall study population were significantly reduced (-16.8%, p < 0.0001), and the effect did not differ among treatments. This effect also was greatest among patients with increased baseline levels of Lp-PLA(2) greater than the median of 320.9 ng/ml (fenofibrate = -41.3%, p < 0.0001; simvastatin = -47.5%, p < 0.0001; combination = -46.8%, p < 0.0001).


CONCLUSIONS
Simvastatin, fenofibrate, and combination therapy each lowered hsCRP and Lp-PLA(2). These anti-inflammatory effects were most pronounced among patients with increased baseline levels. Combination therapy was no more effective than either form of monotherapy. (The DIACOR Study; http://www.clinicaltrials.gov/ct/show/NCT00309712?order=1).
Muhlestein
Joseph B
JB
Cardiovascular Department, LDS Hospital, Salt Lake City, Utah 84143, USA. brent.muhlestein@intermountainmail.org
May
Heidi T
HT
Jensen
Jonathan R
JR
Horne
Benjamin D
BD
Lanman
Richard B
RB
Lavasani
Farangis
F
Wolfert
Robert L
RL
Pearson
Robert R
RR
Yannicelli
H Daniel
HD
Anderson
Jeffrey L
JL
D050197:Atherosclerosis / Q000097:blood* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D010741:Phospholipases A / Q000097:blood; D054467:Phospholipases A2; D019821:Simvastatin / Q000627:therapeutic use
D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D002097:C-Reactive Protein; D002784:Cholesterol; D019821:Simvastatin; D010741:Phospholipases A; D054467:Phospholipases A2; D011345:Fenofibrate