Atherosclerosis 186 (2006) 152–159 Effects of rosiglitazone on postprandial leukocytes and cytokines in type 2 diabetes J.P.H. van Wijk a,∗ , M. Castro Cabezas a,b , B. Coll c , J. Joven c , T.J. Rabelink d , E.J.P. de Koning d a Department of Internal Medicine, University Medical Center Utrecht, G02.402, P.O. Box 85500, 3508 GA Utrecht, The Netherlands b Department of Internal Medicine, St. Franciscus Gasthuis Rotterdam, The Netherlands c Centre de Recerca Biom` edica, Hospital Universitari de Sant Joan, Reus, Spain d Department of Nephrology, Leiden University Medical Center, The Netherlands Received 20 April 2005; received in revised form 29 June 2005; accepted 4 July 2005 Available online 30 August 2005 Abstract Objective: We postulated that in type 2 diabetes, the postprandial phase is a pro-inflammatory state that can be modulated by PPAR- 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- 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. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Rosiglitazone; Postprandial; Leukocytes; Inflammation; Type 2 diabetes; Cardiovascular disease 1. Introduction Cardiovascular disease (CVD) is the main cause of mor- tality in patients with type 2 diabetes [1]. There is increasing awareness that chronic subclinical inflammation plays an important role in the pathogenesis of atherosclerosis [2,3]. Markers of inflammation, such as blood leukocyte counts, C-reactive protein (CRP) and monocyte chemoattractant ∗ Corresponding author. Tel.: +31 30 250 64 71; fax: +31 30 251 83 28. E-mail address: j.p.h.vanwijk@azu.nl (J.P.H. van Wijk). protein-1 (MCP-1) are independent predictors of future CVD [4–10]. Even subjects with a low CRP concentration are at increased cardiovascular risk if they have a blood leukocyte count in the higher 25th percentile [11]. Differ- ential leukocyte counts (e.g. monocytes and neutrophils) are also related to CVD [5,7]. Interestingly, the best association with CVD has been demonstrated for neutrophils [5]. Their role in the pathophysiology of atherosclerosis is not entirely clear, as these cells are absent in the atherosclerotic lesion until it is ruptured [8]. However, upon activation, resident and recruited neutrophils may affect endothelial function via 0021-9150/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2005.07.001