US researchers have confirmed that a common version of a gene involved in controlling blood sugar levels increases the risk of Type 2 diabetes (T2D). Researchers based at the Massachusetts General Hospital in Boston investigated variants of the TCF7L2 gene in people taking part in the Diabetes Prevention Program (DPP), a large clinical trial involving adults at risk of the condition. The gene was originally linked to T2D by a team from Icelandic biotechnology company deCODE. The new study, published in the New England Journal of Medicine, shows that even people with a high genetic risk can substantially lower their chances of developing T2D by making healthy lifestyle changes.
People with diabetes cannot regulate their blood sugar levels properly, either because their pancreas is not making enough insulin, or because the body becomes resistant to its effects. Type 2 diabetes (T2D) usually affects people over the age of 40. It is more common in overweight, inactive people, and those with a family history of the disease, which suggests that genetic factors are also involved.
In January 2006, the deCODE team reported the analysis of DNA from more than 2000 patients and healthy controls, living in Iceland, Denmark and the US. They focused on the TCF7L2 gene because it makes a protein that had previously been linked to the control of blood sugar levels. They identified one particular variant of the gene that is more common in people with T2D than in unaffected people. They calculated that those who inherit one copy of the gene variant have a 45 per cent increased risk of developing the disease, whereas people who inherit a double dose have a 140 per cent higher chance of doing so.
The DPP trial, begun in 1995, ended in 2001 - a year earlier than planned because the results were so clear: it showed that adults with blood glucose levels higher than normal, but not in the diabetic range, can dramatically cut their chances of developing the condition by cutting calories in their diet and increasing their activity levels. In the latest study, the researchers found that 40 per cent of the trial participants had inherited one copy of the 'at-risk' TCF7L2 gene variant, while ten per cent had inherited two copies. 'For the ten per cent who inherited two copies of the variant, the risk of developing diabetes is about 80 per cent higher than it is for non-carriers', said lead author Jose Florez.
The findings also show that the at-risk variant appears to be linked to a decrease in the amount of insulin produced by the body, rather than an increase in resistance to its effects. However, Florez stresses that 'researchers need to learn more about this gene before they can even begin to translate the discovery into a drug treatment that benefits people with diabetes or those at risk'. In an accompanying editorial, UK geneticists Stephen O'Rahilly and Nicholas Wareham conclude that while the race to find genetic variants underlying common diseases had 'a somewhat faltering start', it has now entered 'a fast-moving, exciting, and highly productive phase'.