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Diabetes 55:3550-3555, 2006
DOI: 10.2337/db06-0827
© 2006 by the American Diabetes Association
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Irbesartan Treatment Reduces Biomarkers of Inflammatory Activity in Patients With Type 2 Diabetes and Microalbuminuria

An IRMA 2 Substudy

Frederik Persson1, Peter Rossing1, Peter Hovind1, Coen D.A. Stehouwer2, Casper Schalkwijk2, Lise Tarnow1, and Hans-Henrik Parving1,3

1 Steno Diabetes Center, Gentofte, Denmark
2 Department of Medicine, University Hospital Maastricht, Maastricht, the Netherlands
3 Diabetes Center, Institution for Faculty of Health Sciences, Aarhus, Denmark

Address correspondence and reprint requests to Frederik Persson, Steno Diabetes Center, Niels Steensenvej 2, DK-2820 Gentofte, Denmark. E-mail: frip{at}steno.dk

Abbreviations: AGE, advanced glycation end product; AT1, angiotensin II type 1; GEE, generalized estimating equation; hs-CRP, high-sensitivity C-reactive protein; IL, interleukin; IRMA 2, Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria; RAAS, renin-angiotensin-aldosterone system; REVERSAL, Reversal of Atherosclerosis with Aggressive Lipid Lowering; sICAM-1, soluble intercellular adhesion molecule-1; sVCAM-1, soluble vascular cell adhesion molecule-1; TGF, transforming growth factor

The impact of irbesartan treatment on biomarkers of low-grade inflammation, endothelial dysfunction, growth factors, and advanced glycation end products (AGEs) during the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study was evaluated. IRMA 2 was a 2-year multicenter, randomized, double-blind trial in patients comparing irbesartan (150 or 300 mg once daily) versus placebo. The primary end point was onset of overt nephropathy. A subgroup (n = 269, 68%) was analyzed for biomarkers at baseline and after 1 and 2 years. High-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, fibrinogen, adhesion molecules, transforming growth factor-ß, and AGE peptides were assessed. Irbesartan treatment yielded significant changes in hs-CRP (based on generalized estimating equation regression coefficient) with a 5.4% decrease per year versus a 10% increase per year in the placebo group (P < 0.001). Fibrinogen decreased 0.059 g/l per year from baseline versus placebo’s 0.059 g/l increase per year (P = 0.027). IL-6 showed a 1.8% increase per year compared with placebo’s 6.5% increase per year (P = 0.005). Changes in IL-6 were associated with changes in albumin excretion (P = 0.04). There was no treatment effect on the other biomarkers. Irbesartan (300 mg once daily) reduces low-grade inflammation in this high-risk population, and this may reduce the risk of micro- and macrovascular disease.


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Copyright © 2006 by the American Diabetes Association.