What is Monogenic Diabetes?

What is Monogenic Diabetes?

• Monogenic diabetes is a rare type caused by a single gene mutation.
• There are over 10 types of MODY (maturity-onset diabetes of the young).
• It makes up about 1-2% of all diabetes cases, but could be up to 5%.
• Monogenic diabetes has traits of both type 1 and type 2.
  • It’s often misdiagnosed as type 1 or type 2 diabetes.

How Do You Treat Monogenic Diabetes?

• It’s important to know if you have MODY because its treatment is different from type 1 or type 2 diabetes.
• Some people with MODY don’t need insulin and can manage with diet and exercise.
  • Others take a medicine called sulfonylurea.
• Some may need insulin, especially as they get older.
• The body with MODY still makes insulin, but not always at the right time or in the right way.

There are Two Main Forms of Monogenic Diabetes (with subtypes in each):

• Neonatal diabetes is usually found in babies from birth to six months old, but sometimes it’s diagnosed later. Babies with this type of diabetes are often given insulin, but they can also take pills called sulfonylurea to treat it.
• MODY (Maturity Onset Diabetes of the Young) is usually diagnosed in kids or young adults. There are 11 types of MODY. Some people only have high blood sugar, while others have more health problems. To know if someone has MODY and which type, they need a genetic test, and it’s easier if other family members have it.

• • HNF1-alpha gene—This type is common and can generally be treated with sulfonylurea agents. (MODY 3)
  • HNF1-beta gene—this can cause kidney cysts, abnormalities of the uterus, and gout. Insulin treatment is often needed. (MODY 5)
  • Glucokinase gene—very mild and usually requires no treatment. This type of MODY does not seem to cause the complications of diabetes. (MODY 2)

Inheritance

• Monogenic diabetes is passed down through a gene from one parent. You only need one copy of the gene to get diabetes. It often runs in families, but sometimes it can happen by chance. To diagnose it, doctors use genetic testing to find the gene that affects insulin production.
• Monogenic diabetes patients are also usually antibody negative (though there are cases where low levels of antibodies have been detected).

When Should I Suspect I Have MODY?

People with MODY often have:

1. A diagnosis of diabetes before six months of age (which is neonatal diabetes).
2. A family history of MODY.
3. A strong family history of diabetes, either “type 1” or “type 2” diagnosed at a younger age (teens, 20’s or 30’s.)
4. Diabetes that doesn’t seem to fit a “type 1” category (meaning negative antibodies, no diabetic ketoacidosis (DKA)) or “type 2” (meaning not overweight, with central fat or an older onset).

Tests for MODY

1. Test antibodies for type 1 diabetes, such as anti-GAD antibodies or Zinc transporter antibodies (ZnT8)—these are generally negative or low in people with MODY. High titers generally mean type 1 diabetes.
2. If on insulin, you can measure a C-peptide level. This tells you if your body is still making insulin. If you are on insulin injections and you have had diabetes for several years, a high or high normal C-peptide level could mean you have MODY.
3. Genetic testing for MODY—these are blood tests sent off to a genetics lab. Often these tests are quite expensive and are variably covered by insurance. It is important to “shop around” in advance so you know the cost upfront. Labs vary in terms of their charges. In some cases, your health care provider will need to write a prior authorization letter to your insurance company. It may be helpful to look at the information on the University of Chicago Monogenic Diabetes Registry.

Editor’s Note: This content has been verified by Anne Peters, MD, a professor of clinical medicine at the Keck School of Medicine of the University of Southern California and the Director of the USC Clinical Diabetes Programs. Dr. Peters is an active member is an active member on the Beyond Type 1 Science Advisory Committee.