Type 1 diabetes may be two conditions that need different treatments

Diabetes is generally thought to come in two forms: type 1 and type 2. But a study suggests type 1 diabetes could be two separate conditions, meaning there are more forms than we realised.

People with diabetes tend to have high blood sugar levels. This is because they either lack or don't respond to insulin, a hormone that allows sugar to be taken up by our cells and either converted to energy or stored. Those who have type 1 diabetes develop it because their immune system attacks the cells in the pancreas that make insulin.

The age at which a person is diagnosed with type 1 diabetes seems to be linked to the severity of their symptoms. "A child diagnosed before the age of 5 is likely to have a more severe form of disease than someone over 30," says Sarah Richardson at the University of Exeter, UK.

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To find out why, Richardson and her colleagues looked at 32 pancreas samples from young people with diabetes who died in the 1950s. They found two distinct categories. In one, some pancreases didn't appear to make insulin properly and experienced a stronger immune system attack.

In the other category, the pancreas samples contained fewer immune cells and there were also signs that they were better at making insulin. The immune attack appears totally different in these two categories, says Richardson.

Different categories

The researchers then looked at blood samples taken from 171 people who had been diagnosed with type 1 diabetes before they turned 30. They found the same pattern: people seemed to fall into one of the two categories, depending on how well their pancreases made insulin.

These categories seem to correspond with age. People whose type 1 diabetes involved poor insulin production and a stronger immune attack tended to be younger, says Richardson. Her team calls this group "endotype 1". In the study, "pretty much everyone under the age of 7 falls into this category", says Richardson.

People diagnosed when they were 13 or older tended to fall into the category made up of individuals whose pancreases had fewer immune cells, which the team calls "endotype 2". Those aged between 7 and 12 when diagnosed could fall in either category.

At the moment, "the outcome is the same - they both need insulin - but they may have got there through a different pathway", says Richardson. In future, she thinks the two types may do best with different treatments. People who have endotype 2 might benefit from treatment that preserves the pancreas cells that make insulin, but we don't have any treatments like that yet.

At the moment, type 1 diabetes is treated with insulin, although researchers have been trialling new immunotherapies that kill the immune cells that attack the pancreas. So far, clinical trials in adults haven't been promising. But the treatment might work better in younger children because immune cells seem to play more of a role in their disease, says Richardson.

In 2018, researchers based in Sweden and Finland classified almost 15,000 people with diabetes into one of five categories - not just two - based on their age, body mass index, blood sugar, and insulin production and sensitivity. Richardson and her team say one of the endotypes seems to align with one of these five categories, but the other doesn't, which she says makes it possible there may be six types of diabetes.

Journal reference: Diabetologia, DOI: 10.1007/s00125-020-05115-6