Effects of short-term fenofibrate treatment on circulating markers of inflammation and hemostasis in patients with impaired glucose tolerance.
BACKGROUND
Apart from lowering lipid levels, peroxisome proliferator-activated receptor (PPAR) alpha activators (fibrates) produce many other favorable effects that may contribute to their clinical effectiveness in dyslipidemic and diabetic patients.


OBJECTIVE
The objective of this study was to compare the impact of a short-term treatment with fenofibrate and the American Heart Association (AHA) step 1 diet on systemic inflammation, hemostasis, and monocyte secretory function in relationship with their metabolic actions.


METHODS
This was a prospective, randomized, placebo-controlled trial involving the group of 91 ambulatory patients with impaired glucose tolerance (IGT) (diagnosed on the basis of the American Diabetes Association criteria), randomly divided into three groups, simultaneously treated for 30 d with the AHA step 1 diet (n = 30), micronized fenofibrate (267 mg/d, n = 31), or placebo (n = 30). The control group included 34 age-, sex-, and weight-matched subjects with normal glucose tolerance. Eighty-six (95%) patients and all control subjects completed the study.


METHODS
Plasma markers of inflammation and hemostasis and monocyte release of proinflammatory cytokines were measured.


RESULTS
Compared with subjects with normal glucose tolerance, IGT patients exhibited higher plasma levels/activities of fibrinogen, factor VII, plasminogen activator inhibitor-1, high-sensitivity C-reactive protein, and oxidized low-density lipoproteins. Lipopolysaccharide-activated monocytes from IGT patients released significantly more TNF-alpha, IL-1beta, IL-6, and monocyte chemoattractant protein-1 in comparison with monocytes from control subjects. Thirty-day treatment with fenofibrate but not with the AHA step 1 diet: 1) improved lipid/lipoprotein profile and glucose metabolism, and 2) reversed or alleviated all the above-mentioned abnormalities. The favorable effects of fenofibrate on plasma high-sensitivity C-reactive protein and on monocyte release of TNF-alpha, IL-1beta, IL-6, and monocyte chemoattractant protein-1 did not correlate with its action on plasma lipids but was related to the improvement in insulin sensitivity and weakly to free fatty acid-lowering action.


CONCLUSIONS
Our study is the first to show that relatively small disturbances in glucose metabolism are associated with marked and multidirectional abnormalities in plasma markers of inflammation and hemostasis and in monocyte secretory function. Moreover, fenofibrate may exhibit early pleiotropic effects in patients with IGT.
Department of Clinical Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland.
Boguslaw
B
Okopień
Robert
R
Krysiak
Zbigniew S
ZS
Herman
D000328:Adult; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004032:Diet; D005260:Female; D011345:Fenofibrate / Q000009:adverse effects / Q000627:therapeutic use*; D005340:Fibrinogen / Q000378:metabolism; D018149:Glucose Intolerance / Q000097:blood* / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006487:Hemostasis / Q000187:drug effects*; D006728:Hormones / Q000097:blood; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood* / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism
D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D006728:Hormones; D000960:Hypolipidemic Agents; D008055:Lipids; D008074:Lipoproteins; D005340:Fibrinogen; D011345:Fenofibrate