Diabetes Over View

Maturity Onset Diabetes of the Young

Maturity-Onset Diabetes of the Young or MODY affects 1-2% of people with diabetes, although it often goes unrecognized

The 3 main features of MODY are:

1. Diabetes often develops before the age of 25
2. Diabetes runs in families from one generation to the next
3. Diabetes may be treated by diet or tablets and does not always need insulin treatment

MODY runs in families because of a change in a single gene which is passed on by affected parents to their children. We call this Autosomal Dominant Inheritance. All children of an affected parent with MODY have a 50% chance of inheriting the affected gene and developing MODY themselves.

There are different types of MODY. By finding out which type of MODY a person has the most appropriate treatment for them can be determined. Knowing the type of MODY a person has also means we can advise them about how their diabetes will progress in the future. As it runs in families, it is important to advise other family members of their risk of inheriting it.

MODY is caused by a change in a single gene. 5 genes have been identified that account for 87% of UK MODY:

HNF1-α
Glucokinase
HNF1-β (including Renal Cysts and Diabetes (RCAD))
HNF4-α
IPF1

Changes in these different genes lead to different types of MODY. For more information about these different types of MODY please click on one of the above. There are still more genes to identify as 13% of MODY is not yet accounted for

Hepatic Nuclear Factor 1 Alpha (HNF1-α)

HNF1-α is one of the genes in the body. Changes in the HNF1-α gene result in the most common form of MODY accounting for 70% of cases. It causes diabetes by lowering the amount of insulin that is produced by the pancreas. It allows insulin to be produced normally in childhood but the amount of insulin reduces as you get older.

The diabetes caused by HNF1-α usually develops during adolescence or the early twenties, although some people may not be diagnosed until middle or old age. There seems to be an increasing need for treatment as the patient gets older and so most patients go on to need either tablets or insulin to stop their blood sugar (glucose) becoming too high. It is important to keep blood glucose controlled in this type of MODY as it can lead to diabetic complications affecting the small blood vessels in the eyes and kidneys. This can be prevented if blood glucose levels are kept well controlled. Annual reviews of patients with HNF1-α is recommended for complication screening.

The age at which people with HNF1-α develop diabetes varies. In our UK series of 171 patients with HNF1-a mutations, 63% of patients with diabetes were diagnosed by 25 years, 79% by 35 years and 96% by 55 years. One thing that our research shows is that keeping physically active and slim helps to keep the blood glucose controlled. This is no different from the advice we would give to anybody with diabetes. Children, and brothers and sisters of people with MODY have a higher risk of developing diabetes at a younger age than other members of the population. Approximately half the children of somebody with maturity onset diabetes of the young will develop diabetes themselves. Family members of a patient known to have MODY should be aware of the symptoms of diabetes and to have their blood glucose measured if they are concerned that they may have it.

Glucokinase

Glucokinase is a gene which plays an important role in recognising how high the blood glucose (or sugar) is in the body. It acts as the “glucose sensor” for the pancreas, so that when the blood glucose rises, the amount of insulin produced also increases. This means that the blood glucose does not become too high.

If there is a change in the glucokinase gene this means that it works slightly differently. It means the blood glucose is “reset” at a higher level than in people without this change. In people without a change in glucokinase, the blood glucose is usually around 4-6 mmol/l but in people with a change in the glucokinase gene, it is typically raised to between 6 and 8 mmol/l. A diagnosis of diabetes is made if the blood sugar is higher than 7 mmol/l. It is very rare for people with a change in the glucokinase gene’s blood glucose to be high enough to give symptoms or to need treatment other than changes in diet. Unlike patients with other types of diabetes, there is very little change in the blood glucose level over the years.

Normally, the blood glucose being raised is only picked up on a routine test and the only time that it is important to pick it up, is during pregnancy. In pregnancy, mothers may need insulin to keep the blood glucose controlled well enough for the unborn baby. It is extremely rare for there to be diabetes complications (changes in the eyes or kidneys) as a result of MODY caused by changes in glucokinase gene. This is probably because the blood glucose levels do not go too high.

Children, and brothers and sisters of people with MODY have a higher risk of developing diabetes at a younger age than other members of the population. Approximately half the children of somebody with maturity onset diabetes of the young will develop diabetes themselves. Family members of a patient known to have MODY should be aware of the symptoms of diabetes and to have their blood glucose measured if they are concerned that they may have it.

Hepatocyte nuclear factor-1ß gene.

RCAD (Renal Cysts And Diabetes) is a newly described familial cystic kidney syndrome associated with mutations in the hepatocyte nuclear factor-1ß gene.

Clinical presentations:

• Unexplained familial renal cystic disease
  • Renal cysts may be detected in utero
  • Early onset non-insulin dependent diabetes
  • Genital tract malformations
  • Hyperuricaemia and early onset gout
• Histological presentations:
  • Cystic renal dysplasia
  • Oligomeganephronia
  • Glomerulocystic disease