05:09am Saturday 16 December 2017

Dietary changes may prevent autoimmunity that leads to type 1 diabetes in at-risk babies: NEJM study

This just-released research data comes from the world’s largest and longest-running type 1 diabetes prevention trial. The study, conducted by researchers at the University of Helsinki and The Hospital for Sick Children (SickKids), is published in today’s advance online edition of the New England Journal of Medicine.

The decade-long pilot study of 230 newborns – now over 10 years old –- is part of the Trial to Reduce Insulin-dependent Diabetes in the Genetically at Risk (TRIGR). TRIGR ultimately aims to determine whether early weaning of infants to foreign protein diets (cow’s milk formulas) is an environmental risk factor for the development of type 1 diabetes years later.

Type 1 diabetes occurs when insulin-producing beta cells in the pancreas are lost due to autoimmunity in people with genetic susceptibility. TRIGR’s initial double-blind, randomized pilot study, which began in 1995, involved infants in Finland who were genetically at high risk of developing type 1 diabetes, having one or more family members with the disease and several specific risk genes.

Participating babies were either weaned to conventional cow’s milk-based formula or to a formula typically given to babies who are allergic to cow’s milk. The hypoallergenic milk is made with casein, a protein found in cheese, which is extensively hydrolyzed (broken down into amino acids, the building blocks of proteins). Breastfeeding was encouraged in the study and formula was given when breast milk was not available.

In this pilot study, children were observed up to the age of 10, measuring blood samples for disease-associated autoimmunity, which precedes the onset of overt diabetes. The research team found that the hydrolyzed formula reduced the emergence of diabetes-predictive autoantibodies (immune proteins that mistakenly attack the body’s own cells) by about 50 per cent over the 10-year observation period.

“This is the first tangible human data set that give us – and the many families with diabetes risk –great hope that diabetes, one of our big genetic diseases, may become preventable in a substantial number of possible cases,” says Dr. Michael Dosch, co-author of the study, Senior Scientist in Neurosciences & Mental Health at SickKids and Professor in the Departments of Immunology and Paediatrics at the University of Toronto. “This is a great milestone in the more than 20-year international TRIGR trial, which repeats the pilot study in several thousand babies on three continents.”

While weaning to the hydrolyzed formula protected children from developing disease-associated autoimmunity by the age of 10, Dosch notes that it won’t be known for many years whether the onset of diabetes was actually prevented, or simply delayed. However, even if it is only delayed, other studies have shown that even a slightly later onset can result in less aggressive diabetes.  He also points out that not all children who develop diabetes-associated autoimmunity will eventually develop diabetes.

Earlier animal studies, which were conducted nearly 30 years ago at SickKids, demonstrated the same reduction in autoimmunity, explains Dosch, who is also the trial’s co-founder and Science Chair of TRIGR. “It’s gratifying to see such promising results in translational research.”

The next phase of the trial is currently underway at nearly 100 diabetes centres on three continents. More than a quarter of the participants are Canadian. TRIGR is expected to end in 2017, but the scientists are contemplating extending the study to continue following the participants and track future disease onset.

Reducing these markers of progressive autoimmunity o has, until now, been an unattainable goal, Dosch explains. And the fact that the researchers achieved it by using a non-toxic substance that is not a drug could ultimately be a significant step forward in the prevention of type 1 diabetes.

Dosch’s lab would be relocated to the Brain & Behaviour neighbourhood in the new SickKids Research & Learning Tower. This will encourage interactions with colleagues from other scientific disciplines to improve our understanding of type 1diabetes and other autoimmune conditions.

The study is supported by the Academy of Finland; the European commission; the Juvenile Diabetes Foundation International; Helsinki University Central Hospital; the University of Helsinki, the Finnish Diabetes Research Foundation; the Novo Nordisk Foundation; the Medical Research Foundation of Tampere University Hospital; the Dorothea Olivia, Karl Walter and Jarl Walter Perklen Foundation; the Liv och Halsa Fund, the Canadian Institutes of Health Research and SickKids Foundation.

About The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally.  Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system.  SickKids is proud of its vision of Healthier Children. A Better World.™ For more information, please visit www.sickkids.ca

About SickKids Research & Learning Tower
SickKids Research & Learning Tower will bring together researchers from different scientific disciplines and a variety of clinical perspectives, to accelerate discoveries, new knowledge and their application to child health — a different concept from traditional research building designs.  The Tower will physically connect SickKids science, discovery and learning activities to its clinical operations.  Designed by award-winning architects Diamond + Schmitt Inc. and HDR Inc. with a goal to achieve LEED® Gold Certification for sustainable design, the Tower will create an architectural landmark as the eastern gateway to Toronto’s Discovery District.  SickKids Research & Learning Tower is funded by a grant from the Canada Foundation for Innovation and community support for the ongoing fundraising campaign. For more information, please visit www.buildsickkids.com.

For more information, please contact:

Matet Nebres
Manager, Media Relations
Communications and Public Affairs
The Hospital for Sick Children
Tel: 416-813-6380
Fax: 416-813-5328
e-mail: matet.nebres@sickkids.ca

Suzanne Gold
Communications Specialist – Media Relations
Communications and Public Affairs
The Hospital for Sick Children
Tel: 416-813-7654 ext. 2059
Fax: 416-813-5328
e-mail: suzanne.gold@sickkids.ca


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