Type 1 Diabetes

Type 1 diabetes happens when the immune system destroys the beta cells of the pancreas — the only cells in the body that make insulin. Without insulin, glucose cannot get from the blood into the cells that need it, so it accumulates in the blood while the body starves. It is treated by replacing the insulin, for life.

It is not a milder or earlier version of type 2

The two conditions share a name because they share a symptom: too much glucose in the blood. Almost everything underneath is different.

• Type 1 is autoimmune. The immune system attacks the beta cells, and the pancreas stops making insulin at all. It usually begins in childhood or early adulthood, though it can start at any age.
• Type 2 is metabolic. Insulin is still made, but the body responds to it poorly and production eventually falls behind. It is strongly linked to weight, activity and age.

The distinction matters practically. Nothing about diet or exercise causes type 1 or prevents it, and a person with type 1 cannot stop needing insulin. Our type 2 page covers the other one, and the genetics on the two pages barely overlap.

What the genetics actually looks like

Type 1 diabetes has one of the strongest inherited components of any common disease, and the numbers are worth stating precisely. Genetic factors account for roughly half of the total risk. Of that genetic half, about half again comes from a single region: HLA, the cluster of genes that tells the immune system what belongs to the body and what does not.

That is a very unusual shape. In most common diseases the genetic contribution is spread thinly across thousands of positions with no single region dominating. Here one region does most of the work, which is why HLA typing has real predictive value in type 1 diabetes and almost none in type 2.

The rest of the genetic risk is spread across dozens of other regions, each contributing a little. A 2009 study combining a genome-wide scan with earlier work — 7,514 people with type 1 diabetes and 9,045 reference samples — found 41 distinct locations associated with the disease. Most of them sit in or near genes with immune roles, which is what you would expect for a disease the immune system causes.

The three positions on this page

None of these is in the HLA region, and none of them is why anyone develops type 1 diabetes. They are outside-HLA signals — part of the thinner spread of risk — and they are here because they were replicated properly.

Two come from the Wellcome Trust Case Control Consortium follow-up published in 2007, which took the strongest hits from the original scan and tested them again in 4,000 people with type 1 diabetes, 5,000 controls and 2,997 families. Surviving that is what separates a real association from a lucky one.

The third comes from the 2009 meta-analysis above. All three sit near genes involved in immune signalling, which is the pattern rather than the exception.

What a genotype here does and does not tell you

It does not tell you whether you will develop type 1 diabetes, and it is not used to decide anything clinically. Diagnosis is made from blood glucose, from autoantibodies against the beta cells, and from the clinical picture — not from these positions.

Where genetics does get used in type 1 diabetes, it is HLA typing, usually in research settings or in families with an affected child, and usually alongside autoantibody testing rather than instead of it. A person with the highest-risk HLA types still very probably does not develop the disease.

If you are worried about a child

The signs of new type 1 diabetes in a child are specific and worth knowing, because it can develop quickly: drinking a great deal, passing urine often, losing weight without trying, and unusual tiredness. That combination is a same-day question for a doctor, not a genetics question. A blood glucose test answers it in minutes.