People with a change in the HNF1A gene are highly likely to develop diabetes. Typically, they do not have diabetes in childhood but develop diabetes during adolescence or early twenties, although some people are diagnosed later. It is important to keep blood glucose controlled in this type of diabetes as it can lead to diabetic complications such as damage to the small blood vessels in the eyes and kidneys. This can be prevented if blood glucose levels are kept well controlled. The risk of coronary heart disease is also raised in HNF1A even though levels of the ‘healthy’ cholesterol HDL are usually high, so early treatment (at least from the age of 40) with cholesterol lowering medications to protect the heart is recommended. People with changes in the HNF1A gene often pass increased amounts of glucose in their urine so may have glucose detected on urine testing when their blood glucoses are normal.
Individuals with HNF1A diabetes are often particularly sensitive to the blood glucose lowering effects of a group of tablets called sulphonylureas. Sulphonylureas include Gliclazide, Glipizide, Glibenclamide (Glyburide) and Tolbutamide and they work by stimulating the pancreas to produce insulin. Early after the diagnosis of diabetes blood glucose control is often better in those with HNF1A diabetes with sulphonylureas rather than insulin. However there is often an increasing need for treatment as the affected individual gets older and so most people will progress to needing the addition of other tablets or a background dose of insulin in combination with sulphonylureas to stop their blood glucose becoming too high. This progression may take place over many years. Those with HNF1A diabetes who are overweight or with a higher HbA1c may also require a background dose of insulin in combination with sulphonylureas to achieve good blood glucose control. People with HNF1A diabetes who have been taking insulin from diagnosis prior to a genetic test may be able to stop insulin and convert to sulphonylureas instead. Keeping physically active and slim is still important and helps to keep the blood glucose controlled. This is no different from the advice we would give to anybody with diabetes.
It is very likely that a change in the HNF1A gene was also present in one of your parents and would have caused them to have diabetes as well. This does not mean that your diabetes will be identical to theirs and there can be considerable variation within the family. In particular, just because a parent or other family member has had ill health resulting from their diabetes, this does not mean that you will have a similar problem, particularly if your blood glucose is well controlled.
There is a 50% chance of the affected gene being passed on from a parent at conception. This means each child has a 1 in 2 chance of inheriting the affected gene and if they have inherited the affected gene they will go on to develop diabetes themselves. Children and brothers and sisters of people with HNF1A MODY who have inherited the same change in the HNF1A gene have a 63% chance of developing diabetes by the age of 25 years and 96% chance by the age of 55 years. Family members of an individual known to have HNF1A MODY should be aware of the symptoms of diabetes and have their HbA1c measured if they are concerned. Because other types of diabetes such as type 1 and type 2 diabetes are common in the population, it is important that your family members with diabetes have a genetic test to confirm that they also have HNF1A diabetes. Pre-symptomatic genetic testing (to see if they have inherited the same change in the gene) is also possible – please see the section on pre-symptomatic genetic testing on our website.
Maggie Shepherd +44 (0) 1392 408261 or by email to m.shepherd1@nhs.net
