THE ACCELERATOR HYPOTHESIS – AN EVOLVING CONCEPT
Abstract
Clinical trials designed to prevent type 1 diabetes (T1D) based on the autoimmunity paradigm have proved disappointing, and have not so far translated into patient benefit. Meanwhile, the incidence of T1D continues to rise. The accelerator hypothesis explores the role of weight gain in childhood diabetes, as both islet cell immunity and T1D are associated with BMI. Insulin resistance, which results largely from weight gain, increases insulin demand, and demand puts stress on beta cells, which accelerates their apoptotic loss. An immune response to the stress in those who are genetically predisposed (‘autoimmunity’) hastens the loss further, and may explain by default why autoimmunity is a feature of diabetes in the young. The accelerator hypothesis was proposed in 2001 and, like most hypothesis, has evolved over the years.
Key words: Accelerator hypothesis, type 1 diabetes, clinical trial, insulin resistance,classification of diabetes, tempo in diabetes, hybrid diabetes
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