Pediatric Review

International Journal of Obesity (2009) 33, 716–726; doi:10.1038/ijo.2009.97; published online 9 June 2009

The accelerator hypothesis: a review of the evidence for insulin resistance as the basis for type I as well as type II diabetes

T J Wilkin1

1Department of Endocrinology and Metabolism, Peninsula College of Medicine and Dentistry (Plymouth Campus), UK

Correspondence: Professor TJ Wilkin, Professor of Endocrinology and Metabolism, Peninsula Medical School (Plymouth Campus), University Medicine, Level 7, Derriford Hospital, Plymouth PL6 8DH, UK. E-mail: T.Wilkin@pms.ac.uk

Received 7 December 2008; Revised 16 February 2009; Accepted 11 April 2009; Published online 9 June 2009.

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Abstract

Although some 40 years have passed since type I diabetes was first defined, its cause remains unknown. The autoimmunity paradigm of immune dysregulation has not offered an explanation for its rising incidence, nor means of preventing it, and there is arguably good reason to consider alternatives. The accelerator hypothesis is a singular, unifying concept that argues that type I and type II diabetes are the same disorder of insulin resistance, set against different genetic backgrounds. The hypothesis does not deny the role of autoimmuniy, only its primacy in the process. It distinguishes type I and type II diabetes only by tempo, the faster tempo reflecting the more susceptible genotype and (inevitably) earlier presentation. Insulin resistance is closely related to the rise in overweight and obesity, a trend that the hypothesis deems central to the rising incidence of all diabetes in the developed and developing world. Rather than overlap between the two types of diabetes, the accelerator hypothesis envisages overlay—each a subset of the general population differing from each other only by genotype. Indeed, it views type I and type II diabetes as a continuum, where the infinitely variable interaction between insulin resistance and genetic response determines the age at which beta-cell loss becomes critical. Adult diabetes is not viewed as an entity, but rather as diabetes presenting in adulthood. Childhood diabetes, similarly, is diabetes presenting in childhood. The increasing incidence of both is primarily the result of lifestyle change and the rise in body weight that has resulted

Keywords:

accelerator hypothesis, tempo, overweight, insulin resistance, diabetes

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