The EarlyBird Diabetes Study recruited 307 healthy 5y-olds randomly from Plymouth primary schools during 2000/2001, and observed them in detail at six-month intervals to the age of 16 in 2011/2012. The aim of the study was to document the natural history of metabolic health in contemporary children, many of whom are overweight or obese. The study asked the question "Which children develop insulin resistance and why?" and was predicated on the Accelerator Hypothesis for type 1 diabetes published in 2001. Insulin resistance is a metabolic state, related largely (but not entirely) to obesity, that renders the tissues of the body less sensitive to insulin, and is believed to underpin the rise in diabetes, cardiovascular disease and cancer that has characterised the past 50 years. The study was directed by Professor Terry Wilkin and co-ordinated by Dr Linda Voss of Exeter University Medical School.
Contents
Design
EarlyBird was a classic observation study of contemporary British children (1995-96 birth cohort) observed at six-month intervals over a period of 12 years from 5-16y. It combined objective measures of auxology, body composition (DEXA), physical activity (accelerometry) and metabolic rate (GEM) with annual blood samples to test a wide range of metabolic measures. By way of analogy, 300 5y-old children were lined up in rank order, the start gun was fired, and snapshots were taken every six months as the children progressed toward the finish line at 16y. Most ran straight, but many deviated out of lane towards insulin resistance and diabetes. The study was able to identify which children developed insulin resistance, and to answer in large part why.
Key findings
Longitudinal analysis can explore associations in a way that cross-sectional studies cannot. EarlyBird established early on that insulin resistance is no longer associated with birth weight (a surrogate for gestational nutrition) – rather, the driver in contemporary children is weight gained during the early years. It showed how the large majority of excess weight gained by a child before puberty was gained before 5y. Obesity is not the result of inactivity in children, but the cause, and physical activity imposed at one time of day is compensated for – with remarkable precision – at another, supporting the concept of the ‘activitystat’, and questioning the value of imposing physical activity as a means of weight reduction in childhood. It went on to establish that today’s obese girls are largely the daughters of obese mothers (not fathers), and obese boys the sons of obese fathers (not mothers). The offspring of normal weight parents are no heavier than they were a generation ago. Children who have the privilege of sports clubs record no more activity than those who do not and, worryingly, parents are unaware of their children's overweight. Height, like weight, is dependent on nutrition and, while the focus has been on overweight, there is evidence that many of today’s children are overheight, with independent metabolic consequences. Finally, EarlyBird offers unique evidence that the stress of insulin resistance among overweight children erodes their insulin production to the point where over 20% of the cohort showed evidence of pre-diabetes by the age of 16 years (in preparation). This is the most worrying spectre of all to have emerged from the EarlyBird study, because pre-diabetes frequently spells diabetes within a few years.
Impact
EarlyBird published more than 60 peer-reviewed papers, gave over 70 podium presentations at scientific meetings, and was invited to address national and international audiences on more than 50 occasions. The study is known around the world, and was widely disseminated in the media (The Times, The Telegraph, The Observer, The Independent), BBC Radio 4's Today Programme, Case Notes, Am I Normal? and Inside Health), and television's Panorama, News at 10 and Discovery Channel). It was invited to address/advise the CDC (Atlanta), the NIH (Washington), the UK Cross-Party Parliamentary Committees on Obesity and Diabetes, the Department of Health and the Montreal International Think-tank on Obesity.
Legacy
EarlyBird's archive of DNA and serum has been shared for epigenetic and metabolomic studies with the University of Southampton and the Nestle Institute of Health Sciences/Ecole Polytechnique Federale de Lausanne. Epigenetics and metabolomics are new sciences and EarlyBird's archive, amounting to 12 annual blood samples alongside detailed clinical measurements on each of 300 healthy children, is unique. It has recently been possible to launch ‘EarlyBird 2’, a final sweep of the cohort at 19/20y when the severely confounding influence of puberty will have passed, and the metabolic outcomes can be fully explored. Finally, the autoimmune diabetes Accelerator Prevention Trial (adAPT), a clinical trial to test the Accelerator Hypothesis on which EarlyBird was predicated, is now under way in Scotland, funded by JDRF.