The accelerator hypothesis and increasing incidence of type 1 diabetes.
OBJECTIVE
To summarize the relevance of the 'accelerator hypothesis' to type 1 diabetes pathogenesis and examine if recent evidence supports the hypothesis. The 'accelerator hypothesis' proposes 'three processes in type 1 diabetes which variably accelerate the loss of beta cells through apoptosis: constitution, insulin resistance and autoimmunity'.


RESULTS
Insulin resistance is an independent risk factor for progression to clinical type 1 diabetes in people with islet autoimmunity. Higher bodyweight is also associated with type 1 diabetes development although no longitudinal studies have simultaneously assessed bodyweight and insulin resistance in preclinical diabetes. Currently, there is no evidence for the view that accelerated beta-cell apoptosis is due to insulin resistance in the pathogenesis of type 1 diabetes.


CONCLUSIONS
Insulin resistance accelerates development of type 1 diabetes in people with islet autoimmunity and insulin deficiency. The increasingly 'obesogenic' environment which promotes insulin resistance could account for the rising incidence of type 1 diabetes.
Fourlanos
Spiros
S
Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia. Spiros.Fourlanos@mh.org.au
Harrison
Leonard C
LC
Colman
Peter G
PG
D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000209:etiology* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D015994:Incidence; D007333:Insulin Resistance / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism; D012307:Risk Factors