A UK/Canada Collaboration on the genetics of long-term diabetes complications and their risk factors among people with type 1 diabetes

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Over 100,000 Canadians and 380,000 in the UK overall have type 1 diabetes. People with type 1 diabetes require lifelong insulin injections to replace insulin synthesized by specialized cells in their pancreas that have died due to an immune process. Currently there are few treatments to prevent or delay the underlying destruction of insulin producing cells. However recent studies have shown that many people with type 1 diabetes do in fact still produce small amounts of insulin. This is important because these people have less severe diabetes: they require lower doses of insulin; have better control of their blood sugar levels; are at lower risk for the development of low blood sugar; and also importantly at lower risk for long-term complications of diabetes, including eye, kidney and heart diseases which are major health problems. However, we have little understanding of the factors that result in differences in insulin production capacity between people with type 1 diabetes. Genetics provides a unique opportunity to identify causal factors for important biomedical measures, such as varying insulin production in people with type 1 diabetes. We already conducted a pilot study where we identified genetic variations different locations in the genome that are related to insulin production and have shown that residual insulin production is very strongly genetically determined. However we showed that only a small percentage of the genetic contribution is from known genes so that there are important genes still to discover. Furthermore we showed that age at onset of diabetes is one determinant of residual insulin production but that the genes determining age at onset only capture a small percentage of the genetic determination of residual insulin production. In this project we will use data and samples from ten different studies, with a total of ~12,200 people with type 1 diabetes, to allow us to identify the genetic factors that influence residual insulin production, age at onset and also glycaemic control separating those genes that influence these traits together from those that have specific effects on each trait. It is important to bring the collaboration together in order to maximise the size of the study to make it as powerful as possible and also to ensure standardised approach as that also increases the power for discovery. This would be the largest and most comprehensive study of this topic to date.Identifying the genetic factors is the first step to understanding the mechanisms, which could ultimately be used to develop new approaches to help preserve insulin production in people with type 1 diabetes. The work will also lead to ways to identify which people with diabetes are most appropriate participants for which clinical trials which will accelerate drug development programmes. Since insulin production is also abnormal in many people with type 2 diabetes, which affects over 2 million Canadians and over 4 million in the UK overall, the discoveries about pancreatic cell function that we will make will also lead to important insights and accelerate development of new treatments for some people with type 2 diabetes.