There is currently no means of preventing type 1 diabetes in children, and the accelerator hypothesis offers an alternative approach. Sugar (glucose) levels in the blood stream are held within a narrow range by the hormone insulin. Diabetes is a state of abnormally high blood sugar, which develops when the beta cells of the pancreas that make insulin can no longer make enough. There are thought to be two types of diabetes - type 2 diabetes, due to metaboliccauses, and Type 1 diabetes (T1D). T1D which is widely believed to result from destruction of the beta cells by a faulty and aggressive immune system (autoimmunity). The incidence of type 1 diabetes has increased five-fold in the past 40 years, but clinical trials in humans to prevent it, based on the autoimmunity hypothesis and using immunotherapy, have not so far been successful, and the autoimmunity paradigm has been questioned. The accelerator hypothesis outlined here proposes an alternative mechanism for type 1 diabetes, which is currently being tested in the autoimmune diabetes Accelerator Prevention Trial (adAPT), a randomised controlled trial (RCT) designed to prevent T1D in children.
Video Accelerator hypothesis
Background
Observations made in the 1960s and 70s led doctors to conclude that there were two types of diabetes - type 1 caused by a faulty immune system (autoimmunity), and type 2 by loss of responsiveness to insulin (metabolic). However, while metabolic medications have been shown to prevent type 2 diabetes, immune medications have not proved successful in type 1. The accelerator hypothesis questions the autoimmunity paradigm, and offers an alternative explanation.
Maps Accelerator hypothesis
Concept
The accelerator hypothesis is concerned with the rate or tempo of beta cell loss. Beta-cell loss is a normal part of aging, and in this sense we are all moving towards diabetes. Fortunately, most of us have enough beta cells to get by but if, for any reason, their loss is accelerated, diabetes is likely to develop. Modern living makes undue demands for insulin, which stresses the beta cells and shortens their survival. Stressed beta cells also send out signals that are picked up by the immuune system in the small number of people who have a particularly reactive set of genes - so called 'immunoreactive genes'. The immune response in such people is inflammatory, and accelerates the loss of beta cells still further, propelling the diabetes into childhood. According to the accelerator hypothesis, T1D is a state of critical beta cell loss reached early in life in genetically susceptible people in whom beta cell stress provokes a destructive immune reaction. The accelerator hypothesis differs (critically) from the autoimmunity hypothesis by placing beta cell stress before the immune response, rather than after it. Accordingly, the accelerator prevention trial seeks to protect the beta cell from stress believing that, in so doing, the immune reaction that characterises T1D can be avoided. The faster loss of beta inevitably means a higher incidence and earlier presentation of T1D, which are the key observations in T1D epidemiology of recent years. Unlike type 2 diabetes, which is closely linked to obesity and therefore more predictable, T1D is linked to a gene which is uncommon and randomly distributed in the population. It can strike at any time, but seldom does so more than once in a family.
Hypothesis
The accelerator hypothesis turns cause and effect around - where autoimmunity was thought to be the driving force, it now becomes the response. However, the immune response to beta cell stress is by its nature inflammatory and, where the inflammation is genetically most intense, it secondarily accelerates the loss of beta cells. By default, diabetes presenting in childhood typically combines an accelerated prodrome with classic genotype and an immune reaction detectable by the presence of beta-cell antibodies in the blood stream.
Evidence for and against
Independent evidence suggests that acceleration in disease progression accounts for the rising incidence of childhood diabetes. Evidence for the hypothesis has been set out in a number of reviews, and its early predictions have held firm in several reports worldwide, though not in all, and for diverse reasons,.
Implications
The accelerator hypothesis anticipates that measures to protect the beta cell from stress will reduce the incidence of T1D, but it does not dismiss autoimmunity. The immune reaction interpreted as a causal pathology by the autoimmunity hypothesis is regarded by the accelerator hypothesis as a physiological response to beta cell stress. It nevertheless remains inflammatory in its own right, and the secondary accelerator that pushes diabetes into childhood. Crucially, according to the hypothesis, there would be no immune response in the first place without beta cell stress. If the accelerator interpretation of events is correct, T1D becomes amenable to prevention by avoidance of the factors which stress the beta cell, or protection of the beta cell from them. The difference from type 2 diabetes is the immune genotype, the wild card distributed randomly throughout the population that explains how T1D turns up randomly in families who have never known it before.
References
Source of the article : Wikipedia
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