What To Know About Maturity Onset Diabetes Of The Young (MODY)
Susie Perkowitz, a longtime endurance runner, never felt this way after a race. After completing a 120-mile run in Colorado, she was so foggy-headed and unsteady on her feet that she thought she might pass out. Once she was home in Chicago, she shared her symptoms with her sister, a registered nurse, then promptly went to the ER. Doctors ran a series of tests, including an A1C blood test. Their diagnosis: Perkowitz had type 2 diabetes.
She began taking the oral medication metformin to help reduce her blood glucose. But it made her sick and her blood glucose didn’t budge. “I was so dizzy, shaky, weak, and nauseous that I could barely get out of bed for the first few months,” recalls Perkowitz. Even on her best days, she didn’t have the energy to run, which had long been her passion. And spells of blurry vision, which she’d had for years and wrote off as tired eyes, became more frequent and pronounced. Eventually, she learned that she had severe diabetic retinopathy in both eyes, a result of poorly managed blood glucose.
“Knowing that the treatment I was receiving was ineffective, the situation felt hopeless, like I was destined to get sicker and sicker and I wouldn’t have a future,” she says. It never dawned on her that she had been misdiagnosed.
Finally, three years later, in 2016, she was referred to a new doctor, who ordered a different set of tests. Genetic testing revealed her true diagnosis: She had maturity onset diabetes of the young, or MODY.
MODY is a much less common form of diabetes than type 1 and type 2—and it’s quite different. While several genes and other factors contribute to the development of type 1 and type 2 diabetes, MODY results from an alteration, or defect, in a single gene. That’s why it’s referred to as “monogenic.”
So far, researchers have identified at least 13 types of MODY, each one caused by a different gene. Of those, three types account for more than 80 percent of MODY diagnoses. Overall, though, MODY makes up fewer than 3 percent of all diagnosed diabetes cases, according to a study published in 2012 in Diabetologia; however, the study authors acknowledge, this number may underestimate the true number of people with MODY.
“People with MODY are usually diagnosed under the age of 40, but it can happen at any age,” says Liana Billings, MD, an endocrinologist and the director of the Personalized Medicine in Diabetes Consultation Clinic at NorthShore University HealthSystem in Skokie, Illinois. “Not only is the MODY diagnosis often delayed, but some people go undiagnosed.”
Wrong Diagnosis, Wrong Treatment
Because physicians encounter MODY so infrequently, if ever, they seldom consider it when they see a patient who has the hallmarks of diabetes, such as high fasting blood glucose and a high A1C. So, almost by default, they diagnose the better-known varieties: type 1 or type 2.
When young, thin people have diabetes symptoms, such as weight loss and frequent urination, doctors often think type 1, says endocrinologist and epidemiologist Miriam Udler, MD, PhD, a MODY researcher and director of the Massachusetts General Hospital Diabetes Genetics Clinic in Boston. However, type 1 diabetes is an autoimmune disease that produces certain antibodies in your blood. If tests fail to show you have those antibodies, you may not have type 1.
“But sometimes antibodies are not checked,” says Udler. The result: an incorrect diagnosis of type 1 diabetes, followed by a prescription for insulin when another drug, such as a sulfonylurea, may be more effective. “Insulin is expensive, it requires a pump or several injections a day, and it increases the risk of low blood glucose,” Udler says.
When a doctor rules out type 1, however, often the only other possibility considered is type 2, says Udler, especially among people in their late 20s or 30s, as was Perkowitz. An estimated 80 to 90 percent of people with MODY are misdiagnosed, says MODY specialist Rochelle Naylor, MD, a pediatric endocrinologist at the University of Chicago and coinvestigator for the Kovler Monogenic Diabetes Registry. “And having the wrong diagnosis can make the doctor choose the wrong treatment.”
The Diagnosis Is Right
After finally receiving a MODY diagnosis, Perkowitz went off metformin. Her doctor prescribed a sulfonylurea to increase her insulin production. “My blood glucose normalized instantly, and I felt a million times better,” she says. “It was almost miraculous.”
This is a typical outcome for people with two specific types of the disease: HNF1A-MODY and HNF4A-MODY (the kind Perkowitz has). “Both respond well to a sulfonylurea,” says Udler. “It lifts the burden of daily care, especially for those taking insulin. Their diabetes not only becomes much better controlled, but there’s a lot of anxiety relief when they get the right diagnosis.”
Many people with HNF1A-MODY or HNF4A-MODY won’t need another medication; however, a sulfonylurea won’t work for everyone. Its effects may begin to wane, or it may lead to recurring low blood glucose (hypoglycemia). Other drugs can be helpful, but more research must be done in order to determine the most effective treatments. “At this point, we have to take a personalized approach with each person who has MODY,” says Billings. “We’re only at the beginning of understanding the best ways to treat MODY.”
For Perkowitz, treatment has been transformative. Since that visit to the ER in 2013, her A1C has gone from 10.1 percent to 5.3 percent. “It’s lower than it’s ever been,” she says.
If you have HNF1A-MODY or HNF4A-MODY, you probably won’t need to see a specialist, though you and your primary care doctor may want to consult a MODY expert to establish a plan for switching from your current treatment to a MODY-specific treatment, says Naylor. For the other, rarer forms of MODY (which will often require insulin), or in cases where genetic testing does not return a clear result, “you definitely want to consult with a specialist,” she says.
Unfortunately, MODY experts, like MODY itself, are not common. Naylor encourages people with MODY to reach out to the University of Chicago’s Monogenic Diabetes Registry (see “MODY Meeting Place,” below).
Naylor says that more research is underway to determine how best to identify who has MODY in a timely manner. Currently, years often pass before receiving a proper diagnosis, as happened to Perkowitz. Once you’ve been diagnosed with MODY, your specialist may recommend genetic testing for the rest of your family or a consultation with a genetic counselor.
As a patient advocate for the Monogenic Diabetes Research and Advocacy Project at the University of Maryland School of Medicine in Baltimore, Perkowitz works to raise awareness about MODY. And she encourages people who struggle to manage their diabetes to talk to their doctors about it. Her message: “If you’re following the standard treatment and it doesn’t help, get a second opinion.”
Now that she’s on an effective treatment, she’s getting back to her normal life—and to running. Her next race: the 120-mile TransRockies Run. The six-day race represents a full-circle moment for Perkowitz. “It’s the race I did just before my diagnosis,” she says.
MODY at a Glance
What is MODY?
Maturity onset diabetes of the young (MODY) is a type of diabetes caused by a defect in a single gene.
How common is it?
It’s rare. Only 1 to 3 percent of people with diabetes have MODY.
Those who inherit a gene responsible for MODY (13 have been identified) may eventually develop it. If one of your parents has MODY, you have a 50 percent chance of inheriting it and a high probability of developing MODY if the gene is inherited. Because genes play such a significant role in the development of MODY, your family history can provide key clues that may help your health care provider accurately diagnose you.
How is it treated?
Some types require insulin; others are treated with sulfonylureas. Research has yet to determine the best treatments for all types.
No Meds Needed
Of the three most common types of MODY, one requires no treatment at all. GCK-MODY, which results from a mutation in a gene called glucokinase, causes a slight but noticeable and persistent uptick in blood glucose. But because the elevation in glucose is so modest, and stopping treatment is not thought to alter the risk of disease-related complications, it doesn’t require treatment. The only people with GCK-MODY who might benefit from treatment are pregnant women.
MODY Meeting Place
The Monogenic Diabetes Registry at the University of Chicago encourages people whose diabetes has a known genetic cause to join the registry. If you think you have MODY and meet certain criteria—listed on the website—you can sign up to be screened. The registry has several goals: to accurately diagnose people with MODY, to provide a true count of people with this uncommon form of diabetes, to learn more about its causes, and to develop better treatments. Get more info at monogenicdiabetes.uchicago.edu/mody-registry.