Effects of rosiglitazone on postprandial leukocytes and cytokines in type 2 diabetes.
OBJECTIVE
We postulated that in type 2 diabetes, the postprandial phase is a pro-inflammatory state that can be modulated by PPAR-gamma agonists. For this purpose, we determined the effects of rosiglitazone (8 mg/d) on postprandial leukocyte counts and pro-inflammatory cytokines (IL-6 and IL-8) in patients with type 2 diabetes.


RESULTS
A randomized, 8-week, cross-over, placebo-controlled, double-blind clinical trial was performed in 19 patients with type 2 diabetes. Standardized 6-h oral fat-loading tests were performed after each treatment period. During placebo treatment, blood leukocytes increased to a maximum 6-h postprandially, due to significant increases in neutrophils and lymphocytes. Concomitant postprandial increases were observed for IL-6 and IL-8, the major chemokines responsible for leukocyte recruitment. Rosiglitazone reduced the incremental area under the curves (dAUCs) for IL-6 (-63%, p<0.01) and IL-8 (-16%, p<0.05). The dAUC for leukocytes decreased with 37% (p<0.05), due to a specific reduction of neutrophils (-39%, p<0.05).


CONCLUSIONS
Rosiglitazone attenuated the postprandial increases of neutrophils, IL-6 and IL-8 in patients with type 2 diabetes. Since inflammation is a major force driving atherosclerosis, and man lives in a postprandial period most part of the day, a reduced inflammatory response after a meal may delay progression of atherosclerosis.


CONCLUSIONS
We postulated that in type 2 diabetes, the postprandial phase is a pro-inflammatory state that can be modulated by PPAR-gamma agonists. Rosiglitazone attenuated the postprandial increases of neutrophils, IL-6 and IL-8 in patients with type 2 diabetes. These effects may contribute to cardiovascular risk reduction.
van Wijk
J P H
JP
Department of Internal Medicine, University Medical Center Utrecht, G02.402, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. j.p.h.vanwijk@azu.nl
Cabezas
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Rabelink
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D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood* / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects*; D011446:Prospective Studies; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
D015415:Biomarkers; D016207:Cytokines; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone