Diabetes: 1 and 2, or one and the same? Progress with the accelerator hypothesis.
The accelerator hypothesis was published in 2001, and proposes that that type 1 and type 2 diabetes are the same disorder of insulin resistance set against different genetic backgrounds. The different genes modulate (variably accelerate) the tempo of beta cell loss and thereby determine the age at onset and incidence of the disease. Some of the predictions made by the hypothesis have been met by data not available when the hypothesis was first proposed. Principle among these is the expectation - now born out in five independent studies - that age at onset should be inversely related to BMI, a surrogate for insulin resistance. This article updates the hypothesis, provides evidence to support the predictions and offers arguments to counter challenges that have appeared in print. Finally, it proposes a randomised controlled trial to test the principle that a reduction in blood glucose, by reducing the load on beta cells, will slow the tempo of their destruction and reduce the incidence of type 1 diabetes.
Department of Endocrinology & Metabolism, Peninsula Medical School, Plymouth, Devon, UK. T.Wilkin@pms.ac.uk
Terence J
TJ
Wilkin
D000293:Adolescent; D017668:Age of Onset; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000145:classification / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000145:classification / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000473:pathology / Q000502:physiology; D008297:Male; D008954:Models, Biological; D015430:Weight Gain