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The accelerator hypothesis: insulin resistance as the central cause of type 1 and type 2 diabetes

International Journal of Obesity volume 34, pages 210–211 (2010)Cite this article

I read with interest the review by Wilkin1 discussing the ‘accelerator’ hypothesis. I commend the author for bravely attempting to unite the type 1 and type 2 disease classifications and advance the theory of diabetes pathogenesis; however, one must play devil's advocate when necessary. The author proposes that in type 1 diabetes ‘the driver, according to accelerator hypothesis, is insulin resistance’, much as in type 2 diabetes. I urge the consideration of two cases, which, although hypothetical, I think we can agree are characteristic of many individuals who develop diabetes.

One is a child of normal weight from a middle-class family of European ethnicity. Viral infection in this child results in the infection of pancreatic β cells (as has been observed previously2), and a natural immune response ensues. Depending on the child's genetic background,3, 4, 5 this may include autoimmune responses that ultimately cause β-cell destruction. In the face of compromised insulin production capacity, whether this child develops elevated blood glucose will depend on how effective the remaining insulin functions. When this scenario is played out across a population of genetically high-risk individuals, those with greater insulin resistance are more likely to develop diabetes, as has been observed in a number of studies (for example, see Bingley et al.6) and cited by the author. The true causative agent, however, is the initial interplay of the virus–immune system, which creates the insult to β cell survival. In this circumstance, insulin resistance is not the driver of the development of disease, but a covariate. This is not to say that interventions to improve insulin sensitivity in high-risk individuals are misguided—providing some kind of alleviation of the insulin production burden facing β cells at this critical time may offer some hope of avoiding diabetes. This is a vastly different theoretical underpinning from that proposed by the author, however, whereby insulin resistance is in fact the primary insult, and subsequent inflammation and autoimmune β-cell destruction arise from insulin-resistance-induced upregulation of the β-cell.

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References

  1. Wilkin TJ . The accelerator hypothesis: a review of the evidence for insulin resistance as the basis for type I as well as type II diabetes. Int J Obes (Lond) 2009; 33: 716–726.

    Article  CAS  Google Scholar 

  2. Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG . The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia 2009; 52: 1143–1151.

    Article  CAS  Google Scholar 

  3. Nejentsev S, Walker N, Riches D, Egholm M, Todd JA . Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 2009; 324: 387–389.

    Article  CAS  Google Scholar 

  4. Butty V, Campbell C, Mathis D, Benoist C, DPT-1 Study Group. Impact of diabetes susceptibility loci on progression from pre-diabetes to diabetes in at-risk individuals of the diabetes prevention trial-type 1 (DPT-1). Diabetes 2008; 57: 2348–2359.

    Article  CAS  Google Scholar 

  5. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA et al. The Type 1 Diabetes Genetics Consortium. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 2009; 41: 703–707.

    Article  CAS  Google Scholar 

  6. Bingley PJ, Mahon JL, Gale EA, European Nicotinamide Diabetes Intervention Trial Group. Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT). Diabetes Care 2008; 31: 146–150.

    Article  CAS  Google Scholar 

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Acknowledgements

I am supported by a scholarship from the National Heart Foundation of New Zealand.

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  1. Edgar National Centre for Diabetes Research and Centre for Neuroendocrinology, University of Otago, Dunedin, New Zealand

    C Booker

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Correspondence to C Booker.

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Booker, C. The accelerator hypothesis: insulin resistance as the central cause of type 1 and type 2 diabetes. Int J Obes 34, 210–211 (2010). https://doi.org/10.1038/ijo.2009.190

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