Brakes on the accelerator: the journey of accelerator hypothesis from “the missing link” to “an evolving concept”
Keywords:Accelerator hypothesis, Childhood diabetes, Type 1 diabetes, Type 2 diabetes, BMI, Obesity, Insulin resistance, Children
The incidence of Type 1 diabetes (T1D) has increased significantly over the past few decades but the causes for this increase are poorly understood and hence the strategies for preventing T1D are difficult to design. T1D is characterised by autoimmune destruction of pancreatic β-cells resulting in insulin deficiency as opposed to Type 2 diabetes (T2D) characterised by weight driven insulin resistance (IR). The accelerator hypothesis (AH), proposed by the late Prof Terence Wilkin in 2001 offers an alternative mechanism for T1D and a different approach to prevention of T1D. This hypothesis considers both T1D and T2D as one and proposes that obesity driven IR is the key factor that may lead to either type of diabetes. It thus offers an easy explanation for the increasing worldwide incidence of childhood diabetes which is paralleled by the increase in childhood obesity rates. However, one of the key predictions of AH that the obesity related IR accelerates the onset of diabetes and hence heavier children should develop diabetes at a younger age, has remained a matter of debate since the hypothesis was first proposed. Since the inception of AH, the results of a number of studies which aimed at testing the hypothesis in diverse patient populations have shown support or opposed this key prediction. This article discusses the relevance of AH in the context of data from these studies.
Wilkin TJ. The Accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes. Diabetologia. 2001;44:914-22.
Johansson C, Samuelsson U, Ludvigsson J. A high weight gain in early life is associated with an increased risk of type 1 (insulin-dependent) diabetes. Diabetologia. 1994;37:91-4.
Lammi N, Moltchanova E, Blomstedt PA, Tuomilehto J, Eriksson JG, Karvonen M. Childhood BMI trajectories and the risk of developing young adult-onset diabetes. Diabetologia. 2009;52:408-14.
Porter JR, Barrett TG. Braking the accelerator hypothesis? Diabetologia. 2004;47:352-3.
Dayal D, Samprathi M, Jayaraman D, Kohat D, Bhalla AK. Secular trends of body mass index in North Indian children with Type 1 diabetes do not support the Accelerator Hypothesis. Clin Endocrinol (Oxf). 2016;84:338-41.
Ranjani H, Mehreen TS, Pradeepa R, Anjana RM, Garg R, Anand K, et al. Epidemiology of childhood overweight & obesity in India: A systematic review. Indian J Med Res. 2016;143:160-74.
Dayal D, Jain H, Attri SV, Bharti B, Bhalla AK. Relationship of High Sensitivity C-Reactive Protein Levels to Anthropometric and other Metabolic Parameters in Indian Children with Simple Overweight and Obesity. J Clin Diagn Res. 2014;8:PC05-8.
Dayal D, Saini AG, Jayashree M, Singhi S, Kumar R, Samprati M, Singh M. Hospital based incidence, patterns of presentation and outcome of Type 1 diabetes: 12 years’ data from a tertiary care center in North India. Int J Diabetes Dev Ctries. 2015;35:103–7.
Elding Larsson H, Vehik K, Haller MJ, Liu X, Akolkar B, Hagopian W, et al. Growth and Risk for Islet Autoimmunity and Progression to Type 1 Diabetes in Early Childhood: The Environmental Determinants of Diabetes in the Young Study. Diabetes. 2016;65:1988-95.
Ferrara CT, Geyer SM, Liu YF, Evans-Molina C, Libman IM, Besser R, et al. Excess BMI in Childhood: A Modifiable Risk Factor for Type 1 Diabetes Development? Diabetes Care. 2017;40:698-701.
Meah FA, DiMeglio LA, Greenbaum CJ, Blum JS, Sosenko JM, Pugliese A, et al. The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants. Diabetologia. 2016;59:1186-95.
Winkler C, Marienfeld S, Zwilling M, Bonifacio E, Ziegler AG. Is islet autoimmunity related to insulin sensitivity or body weight in children of parents with type 1 diabetes? Diabetologia. 2009;52:2072-8.
Wilkin TJ. The accelerator hypothesis–an evolving concept. Facta Universitatis, Series: Medicine and Biology 2015;17:49-53.
Wilkin T, Greene S, McCrimmon R. Testing the accelerator hypothesis: a new approach to type 1 diabetes prevention (adAPT 1). Diabetes Obes Metab. 2016;18:3-5.
Channanath AM, Elkum N, Al-Abdulrazzaq D, Tuomilehto J, Shaltout A, Thanaraj TA. Ethnic differences in association of high body mass index with early onset of Type 1 diabetes - Arab ethnicity as case study. PLoS One. 2017;12:e0175728.