Effects of rosiglitazone on postprandial leukocytes and cytokines in type 2 diabetes.

Abstract

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.

METHODS AND 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.

CONDENSED ABSTRACT:

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.

• Authors: J P H van Wijk, M Castro Cabezas, B Coll, J Joven, T J Rabelink, E J P de Koning
• Journal: Atherosclerosis (Atherosclerosis) Vol. 186 Issue 1 Pg. 152-9 (May 2006) ISSN: 0021-9150 [Print] Ireland
• PMID: 16137694 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cytokines
• Hypoglycemic Agents
• Thiazolidinediones
• Rosiglitazone

Topics

• Adult
• Aged
• Biomarkers (blood)
• Cross-Over Studies
• Cytokines (blood, drug effects)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Hypoglycemic Agents (therapeutic use)
• Leukocyte Count
• Leukocytes (drug effects)
• Male
• Middle Aged
• Postprandial Period (drug effects)
• Prospective Studies
• Rosiglitazone
• Thiazolidinediones (therapeutic use)
• Treatment Outcome