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Diabetes
  Genes Can Cause MODY

By Amy Adams, MS

Reviewed By Jeremy Walston, MD


 

A small subgroup of people with Type 2 diabetes develop the disease in their 20s rather than in their 50s or 60s. Most people in this group have a strong family history of diabetes and are less likely to be obese than other Type 2 diabetics. These people, who account for less than five percent of Type 2 diabetes cases, have maturity onset diabetes of the young (MODY).

In order to classify as MODY:

  • The patient must have Type 2 rather than Type 1 diabetes.
  • The age of onset for at least one family member must be younger than 25.
  • The disease must be controllable without insulin for at least two years — either through diet and exercise or by taking medication that helps the body use insulin more effectively.
 
 
 

Mode of Inheritance

People develop MODY by inheriting a gene that predisposes them to the disease. Because of the way MODY genes are inherited, a person only has to inherit a mutated version of the gene from one parent in order to be at risk. This means that if either parent has MODY, the offspring have a 50 percent chance of inheriting a gene that puts them at risk for diabetes. This pattern of inheritance is called autosomal dominant.

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MODY Genes

So far, scientists have identified five genes that can put a person at risk for developing MODY, and they are continuing to look for more. Each of these genes interferes with the normal release of insulin by the pancreas. (This is in contrast to Type 1 diabetics, who fail to produce insulin because the immune system destroys the insulin-producing cells.) With too little insulin being produced, cells of the body are unable to use the sugar glucose for fuel.

 

Although there are five genes that cause MODY, only three are well understood:

  • HNF-4alpha: Although this was the first gene discovered, it is responsible for diabetes in only a small number of MODY families. A mutation in this gene causes a severe form of diabetes. In fact, 30 percent of people with a mutation in HNF-4alpha require insulin to control their diabetes.
  • GCK: This is the most common gene that is mutated in MODY families, accounting for 50 to 60 percent of MODY cases. It normally helps regulate how the pancreas releases insulin in response to glucose. People with a mutation in GCK develop a relatively mild form of diabetes that rarely requires insulin for treatment.
  • HNF-1alpha: Mutations in this gene account for roughly 25 percent of MODY families. People with a mutation in HNF-1alpha develop a more serious form of diabetes and are at high risk for eye disease.

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Genetic Testing

If you have a family history of MODY, you might wonder if there is a genetic test to help you figure out if you (or other family members) are at risk. Although most MODY families have a mutation in one of the identified MODY genes, there is no commercially available test for MODY. (Some labs will do genetic testing in MODY families for research purposes).

At this time, whether or not you carry a MODY gene the only way to prevent or delay Type 2 diabetes is to exercise regularly and maintain a weight that is appropriate for your height.

References

Stoffel, M. and Duncan, S. A. (1997). The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci USA, 94, 13209-13214.

Velho, G., et al. (1992). Primary pancreatic beta-cell secretory defect caused by mutations in glucokinase gene in kindreds of maturity onset diabetes of the young. Lancet, 340, 444-448.

Yamagata, K., et al. (1996). Mutations in the hepatocyte nuclear factor-1alpha gene in maturity- onset diabetes of the young (MODY3) [see comments]. Nature, 384, 455-458.

 

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