To boldly go—or to go too boldly? The accelerator hypothesis revisited

Gale, E.A.M.

doi:10.1007/s00125-007-0726-9

Cited by 29 publications

(25 citation statements)

References 26 publications

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“…It has been previously proposed that impaired insulin action (insulin resistance) as well as a priori impaired beta-cell function may contribute to the development of islet autoimmunity and type 1 diabetes [7]. Our data support part of this assumption by suggesting that ge- netic susceptibility for beta-cell dysfunction (through SLC30A8 SNP) in the presence of autoimmunity leads to accelerated progression of beta-cell destruction and early manifestation of the disease.…”

Section: Resultssupporting

confidence: 83%

SLC30A8 (ZnT8) Polymorphism is Associated with Young Age at Type 1 Diabetes Onset

Gohlke

Ferrari²,

Koczwara³

et al. 2008

Rev Diabet Stud

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■ AbstractIt was recently shown that the major allele of the SLC30A8 (zinc transporter 8, ZnT8) single nucleotide polymorphism (SNP) rs13266634 was associated with type 2 diabetes and with reduced insulin secretion in non-diabetic relatives. Because of its role in beta-cell function, we hypothesized that this candidate SNP may confer increased susceptibility for beta-cell destruction in type 1 diabetes. We analyzed SLC30A8 genotypes in 874 patients with type 1 diabetes and 1021 control subjects. No difference in allele and genotype frequencies of the SLC30A8 SNP rs13266634 was found between patients and controls. Analysis with respect to age at type 1 diabetes onset, however, showed that patients with a diabetes onset before age 5 years had an increased prevalence of the cytosine (C) allele (risk allele, 82%) and the homozygous CC genotype (65%) compared to patients who developed type 1 diabetes after age 5 years (67% and 49%; p < 0.01) and compared to controls (69% and 48%; p < 0.03). These data suggest that genetic susceptibility for beta-cell dysfunction in the presence of autoimmunity may lead to accelerated progression and early manifestation of the disease.

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Section: Resultssupporting

confidence: 83%

SLC30A8 (ZnT8) Polymorphism is Associated with Young Age at Type 1 Diabetes Onset

Gohlke

Ferrari²,

Koczwara³

et al. 2008

Rev Diabet Stud

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“…This increase has been suggested to be associated with the ‘accelerator hypothesis’ [6]. Although this hypothesis is not universally accepted [7], it predicts that higher BMI is associated with younger age at type 1 diabetes diagnosis [8], which has been demonstrated in some studies [9], [10], [11].…”

Section: Introductionmentioning

confidence: 89%

Increasing Incidence and Age at Diagnosis among Children with Type 1 Diabetes Mellitus over a 20-Year Period in Auckland (New Zealand)

et al. 2012

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BackgroundWe aimed to evaluate the incidence of type 1 diabetes mellitus in children <15 years of age (yr) in the Auckland region (New Zealand) over 20 years (1990–2009).MethodsWe performed a retrospective review of all patients <15 yr diagnosed with type 1 diabetes, from an unselected complete regional cohort.ResultsThere were 884 new cases of type 1 diabetes, and age at diagnosis rose from 7.6 yr in 1990/1 to 8.9 yr in 2008/9 (r2 = 0.31, p = 0.009). There was a progressive increase in type 1 diabetes incidence among children <15 yr (p<0.0001), reaching 22.5 per 100,000 in 2009. However, the rise in incidence did not occur evenly among age groups, being 2.5-fold higher in older children (10–14 yr) than in the youngest group (0–4 yr). The incidence of new cases of type 1 diabetes was highest in New Zealand Europeans throughout the study period in all age groups (p<0.0001), but the rate of increase was similar in New Zealand Europeans and Non-Europeans. Type 1 diabetes incidence and average annual increase were similar in both sexes. There was no change in BMI SDS shortly after diagnosis, and no association between BMI SDS and age at diagnosis.ConclusionsThere has been a steady increase in type 1 diabetes incidence among children <15 yr in Auckland over 20 years. Contrary to other studies, age at diagnosis has increased and the greatest rise in incidence occurred in children 10–14 yr. There was little change in BMI SDS in this population, providing no support for the ‘accelerator hypothesis’.

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“…4 The accelerator hypothesis is a singular, unifying theory that attempts to establish a common basis for type I and type II diabetes. First published in 2001, 6 it is now supported in whole, [7][8][9][10][11] or in part, 12 by six independent clinical studies, has been the subject of three editorials [13][14][15] and has more than 100 citations in the literature. The hypothesis argues that type I and type II diabetes are the same disorder of insulin resistance set against different genetic backgrounds.…”

Section: The Issuementioning

confidence: 99%

“…[13][14][15] Adjustment is part of hypothesis building, and the aim of this commentary is to update the evidence and to review the hypothesis in the light of the critiques that it has received.…”

Section: The Issuementioning

confidence: 99%

The accelerator hypothesis: a review of the evidence for insulin resistance as the basis for type I as well as type II diabetes

Wilkin

2009

Int J Obes

131

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Although some 40 years have passed since type I diabetes was first defined, its cause remains unknown. The autoimmunity paradigm of immune dysregulation has not offered an explanation for its rising incidence, nor means of preventing it, and there is arguably good reason to consider alternatives. The accelerator hypothesis is a singular, unifying concept that argues that type I and type II diabetes are the same disorder of insulin resistance, set against different genetic backgrounds. The hypothesis does not deny the role of autoimmuniy, only its primacy in the process. It distinguishes type I and type II diabetes only by tempo, the faster tempo reflecting the more susceptible genotype and (inevitably) earlier presentation. Insulin resistance is closely related to the rise in overweight and obesity, a trend that the hypothesis deems central to the rising incidence of all diabetes in the developed and developing world. Rather than overlap between the two types of diabetes, the accelerator hypothesis envisages overlayFeach a subset of the general population differing from each other only by genotype. Indeed, it views type I and type II diabetes as a continuum, where the infinitely variable interaction between insulin resistance and genetic response determines the age at which b-cell loss becomes critical. Adult diabetes is not viewed as an entity, but rather as diabetes presenting in adulthood. Childhood diabetes, similarly, is diabetes presenting in childhood. The increasing incidence of both is primarily the result of lifestyle change and the rise in body weight that has resulted

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To boldly go—or to go too boldly? The accelerator hypothesis revisited

Cited by 29 publications

References 26 publications

SLC30A8 (ZnT8) Polymorphism is Associated with Young Age at Type 1 Diabetes Onset

SLC30A8 (ZnT8) Polymorphism is Associated with Young Age at Type 1 Diabetes Onset

Increasing Incidence and Age at Diagnosis among Children with Type 1 Diabetes Mellitus over a 20-Year Period in Auckland (New Zealand)

The accelerator hypothesis: a review of the evidence for insulin resistance as the basis for type I as well as type II diabetes

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