J Clin Invest 106(4): 473-481

Obesity and insulin resistance

Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

Address correspondence to: Barbara B. Kahn, Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Boston, Massachusetts 02215, USA. Phone: (617) 667-5422; Fax: (617) 667-2927; E-mail: ude.dravrah.puorgerac@nhakb.

The association of obesity with type 2 diabetes has been recognized for decades, and the major basis for this link is the ability of obesity to engender insulin resistance. Insulin resistance is a fundamental aspect of the etiology of type 2 diabetes and is also linked to a wide array of other pathophysiologic sequelae including hypertension, hyperlipidemia, atherosclerosis (i.e., the metabolic syndrome, or syndrome X), and polycystic ovarian disease (1). Although many details of the mechanisms by which the enlarged adipose tissue mass that defines obesity causes systemic insulin resistance remain unknown, the past several years have witnessed an explosive increase in our understanding of what may now be referred to as the adipo-insulin axis. There are also grounds for considering the related possibility that insulin resistance and hyperinsulinemia, in addition to being caused by obesity, can contribute to the development of obesity. In this Perspective, we will review recent progress, highlight areas of controversy or uncertainty, and suggest approaches to clarifying the unresolved issues.

Acknowledgments

This work was supported by grants from the NIH (RO1 DK-43051, RO1 DK-28082, and PO1 DK-56116) and a grant from Eli Lilly and Co. The authors recognize many additional contributions to the field which they were unable to cite due to a limitation in the number of references. The authors thank Young-Bum Kim for expert assistance.

Acknowledgments

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