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Science 307 (5708): 373-375

Copyright © 2005 by the American Association for the Advancement of Science

How Obesity Causes Diabetes: Not a Tall Tale

Mitchell A. Lazar

Abstract: The epidemic of obesity-associated diabetes is a major crisis in modern societies, in which food is plentiful and exercise is optional. The biological basis of this problem has been explored from evolutionary and mechanistic perspectives. Evolutionary theories, focusing on the potential survival advantages of "thrifty" genes that are now maladaptive, are of great interest but are inherently speculative and difficult to prove. Mechanistic studies have revealed numerous fat-derived molecules and a link to inflammation that, together, are hypothesized to underlie the obesity-diabetes connection and thereby represent prospective targets for therapeutic intervention.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104–6149, USA.

E-mail: lazar{at}

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