Circulating adipokines and the protective effects of hyperinsulinemia in inflammatory bowel disease

Valentini, Luzia; Wirth, Eva Katrin; Schweizer, Ulrich; Hengstermann, Susanne; Schaper, Lennart; Koernicke, Thomas; Dietz, Ekkehart; Norman, Kristina; Buning, Carsten; Winklhofer-Roob, Brigitte M.; Lochs, Herbert; Ockenga, Johann

doi:10.1016/j.nut.2008.07.020

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Volume 25, Issue 2 , Pages 172-181, February 2009

Circulating adipokines and the protective effects of hyperinsulinemia in inflammatory bowel disease

Luzia Valentini, Ph.D.
- Department of Gastroenterology, Hepatology and Endocrinology, Campus Mitte, Charité–Universitätsmedizin Berlin, Berlin, Germany
- Corresponding author. Tel.: +49-30-450-514-113; fax: +49-30-450-514-923
Eva Katrin Wirth, M.Sc.
- Institute for Experimental Endocrinology, Charité–Universitätsmedizin Berlin, Berlin, Germany
Ulrich Schweizer, Ph.D.
- Institute for Experimental Endocrinology, Charité–Universitätsmedizin Berlin, Berlin, Germany
Susanne Hengstermann, Ph.D.
- Department of Gastroenterology, Hepatology and Endocrinology, Campus Mitte, Charité–Universitätsmedizin Berlin, Berlin, Germany
Lennart Schaper, M.D.
- Department of Gastroenterology, Hepatology and Endocrinology, Campus Mitte, Charité–Universitätsmedizin Berlin, Berlin, Germany
Thomas Koernicke, M.D.
- Department of Gastroenterology, Hepatology and Endocrinology, Campus Mitte, Charité–Universitätsmedizin Berlin, Berlin, Germany
Ekkehart Dietz, Ph.D.
- Institute for Biometry and Clinical Epidemiology, Charité–Universitätsmedizin Berlin, Berlin, Germany
Kristina Norman, Ph.D.
- Department of Gastroenterology, Hepatology and Endocrinology, Campus Mitte, Charité–Universitätsmedizin Berlin, Berlin, Germany
Carsten Buning, M.D.
- Department of Gastroenterology, Hepatology and Endocrinology, Campus Mitte, Charité–Universitätsmedizin Berlin, Berlin, Germany
Brigitte M. Winklhofer-Roob, M.D., Ph.D.
- Human Nutrition and Metabolism Research and Training Centre, Karl-Franzens University, Graz, Austria
Herbert Lochs, M.D., Ph.D.
- Department of Gastroenterology, Hepatology and Endocrinology, Campus Mitte, Charité–Universitätsmedizin Berlin, Berlin, Germany
Johann Ockenga, M.D., Ph.D.
- Department of Gastroenterology, Hepatology and Endocrinology, Campus Mitte, Charité–Universitätsmedizin Berlin, Berlin, Germany

Received 16 January 2008; accepted 25 July 2008. published online 13 October 2008.

Abstract

Objective

Adipokines are fat-derived hormones and cytokines with immune-modulating and metabolic properties. Most of them are associated with insulin resistance. The aim of the present investigation was to evaluate circulating levels of adipokines and glucose homeostasis in patients with inflammatory bowel disease (IBD) and to evaluate possible associations with the course and characteristics of the disease.

Methods

Serum leptin, resistin, visfatin, retinol-binding protein-4, adiponectin, glucose, insulin, and inflammatory parameters were analyzed in 93 patients with inactive IBD (49 with Crohn's disease [CD], 44 with ulcerative colitis [UC]), 35 patients with active IBD (18 with CD, 17 with UC), and 37 age- and body mass index–matched healthy controls. Ninety-two patients were followed for 6 mo.

Results

Leptin was similar in patients with IBD and controls, whereas resistin and visfatin were increased in patients with active disease but not in those in remission. In active and inactive disease, adiponectin was decreased (P < 0.001) and retinol-binding protein-4 was increased (P < 0.001) compared with controls. About 60% of patients with IBD showed increased levels of insulin, whereas serum glucose remained normal, resulting in increased homeostasis model assessment values in most patients. Hyperinsulinemia was associated with the decrease in adiponectin (r = −0.572, P < 0.001) and proved to be an independent protective factor for 6-mo maintenance of remission (P = 0.016).

Conclusion

IBD led to largely similar alterations in circulating adipokines and hyperinsulinemia in patients with CD and those with UC. The unexpected protective effect of hyperinsulinemia on relapse rate denotes the role of the metabolic–inflammatory response as a modulator in IBD.

Keywords: Crohn's disease, Ulcerative colitis, Adiponectin, Retinol-binding protein-4, Resistin, Visfatin, Leptin, Pathophysiology, Adaptive mechanisms