Variation in genetic risk explains which people develop type 1 diabetes in later life

by Barbara Hewitt on September 13, 2017

Having certain genetic variants could explain why people can develop type 1 diabetes at markedly different ages, including later in life, new research has found.

The study from scientists at the University of Exeter in England is the first to suggest there is a specific genetic predisposition for late onset type 1 diabetes.


Type 1 diabetes is caused by an autoimmune attack in the body killing off the insulin producing beta cells in the pancreas, eventually leaving most people with a lifelong dependency on insulin.

It typically affects children and young adults but can affect people older than 30 when it is referred to as late onset type one diabetes. One example is the British Prime Minister Theresa May who was diagnosed early in 2013 at the age of 56. Often, people with late onset T1D have their condition confused with type 2 diabetes, which is much more common in older adults.

It is already known that certain groups of genes associated with regulation of the immune system in humans are known to be linked to the risk of developing type 1 diabetes with the major genetic determinants being the DR3 and DR4 alleles (or variants) of a group of genes called the HLA complex.

The strongest risk occurs when these risk alleles occur in pairs which can either be homozygous (DR3/DR3 or DR4/DR4), or compound heterozygous (DR3/DR4) genotypes.

This study, conducted by Dr Nick Thomas and Professor Andrew Hattersley of the university’s Medical School, aimed to investigate whether the increased risk of type 1 diabetes that is observed in children and young adults with the DR3 and DR4 genotypes persists into adulthood.

The team analysed the development of type 1 diabetes in a population of 120,000 individuals from the UK Biobank from birth to age 60 in subjects selected from the highest risk HLA groups.

They found that although the highest risk genotypes made up just 6.4% of the UK population, they contributed 61% of all cases of type 1 diabetes and within these high risk groups there were marked differences in both the likelihood of developing the condition and the average age of diagnosis.

The study found that all three major genotypes greatly increase the risk of type 1 diabetes throughout life, but a population analysis shows for the first time that DR4/DR4 specifically predisposes to type 1 diabetes over 30 years of age and carriers of this genotype have the highest risk for the disease.

‘This is clear evidence that type 1 diabetes after 30 years is not just a delayed version of type 1 diabetes before 30. Further work is needed to understand these differences,’ the study said.

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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