What is Monogenic Diabetes?


Editor’s Note: This article is part of our library of resources for Forms of Diabetes. 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. 

What is Monogenic Diabetes?

Monogenic diabetes is a rare type of diabetes that’s caused by a single gene mutation. There are currently over 10 different types of maturity onset diabetes of the young (MODY) and with new genetic testing more are being uncovered. It accounts for about 1-2 percent of all diabetes cases, though its prevalence may actually be up to 5 percent. It has characteristics of both type 1 and type 2, and is often misdiagnosed as one of those more common types.

How do you treat Monogenic diabetes?

The reason it is important to know whether or not you have MODY is because treatment is often different than it would be if you had “classical” type 1 or type 2 diabetes. Patients are sometimes unnecessarily put on insulin.  Some types of MODY are easily managed without medication, through diet and exercise.  Others require an oral medication known as a sulfonylurea agent.  Finally some types require treatment with insulin, especially as people grow older.  With MODY the body still makes its own insulin, but not always at the right time, in the correct way.

There are two main forms of Monogenic diabetes (with subtypes in each):

  • Neonatal diabetes is usually diagnosed in infants from birth to six months, though diagnosis may occur later in some cases. Often these infants are started on insulin, but this type of diabetes can be treated with pills known as sulfonylurea agents.
  • MODY (Maturity Onset Diabetes of the Young) is usually diagnosed in late childhood to adulthood. There are currently 11 types of MODY.  A few types are listed below.  Some have only abnormal blood glucose levels and others have additional abnormalities.  A person needs genetic testing to determine if they have MODY and what type it is, although if other family members have it then it is easier to find out what the type of MODY.
    • HNF1-alpha gene—This type is common and can generally 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)

Because this is a genetic type of diabetes, the abnormalities are present from birth, but other than with neonatal diabetes there are often no signs or symptoms of diabetes.  This means that may not be diagnosed until later, when a person happens to have a blood test and finds that their blood glucose level is elevated.  Alternatively, knowing that it runs in the family can lead to earlier testing in other family members.


  • Monogenic diabetes is usually passed on in an autosomal dominant gene, (a sex independent gene that’s inherited from one of the parents). This means only one copy of the mutation is needed to develop diabetes. There is usually a strong family history of diabetes and in multiple generations, (although it’s possible for someone to have a spontaneous mutation). Diagnosis, therefore, involves genetic testing for these diabetes-causing gene mutations that disrupt 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 means 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.

Read A Mom’s Intuition and a Rare Diagnosis by Christine Heath.