Diabetes Genetics Clinic

About the Program

The Diabetes Genetics Clinic at MGH is a specialty clinic for patients with known or suspected genetic forms of diabetes. Genetic forms of diabetes include Maturity Onset Diabetes of the Young (MODY) and mitochondrial diabetes. We offer consultation and genetic testing for genetic forms of diabetes.

Our purpose

Many patients and providers encounter cases of diabetes that seem atypical. It’s not quite type 1 or not quite type 2 diabetes. Monogenic diabetes is often undiagnosed or misdiagnosed. Our goal is to help both patients and providers diagnose genetic forms of diabetes in order to improve diabetes management. We also offer on-going care to individuals with monogenic diabetes.

Our Focus

• Diagnose and care for individuals and families with genetic forms of diabetes (see list of disorders below).
• Improve management of these conditions by learning from patients and families
• Increase research on these disorders by working closely with families
• Educate providers and families about monogenic diabetes

Who Should Be Evaluated at the Diabetes Genetics Clinic?

• Patients and families who have a diagnosis of a monogenic diabetes (see condition list below)
• Patients suspected by themselves or their clinician to have monogenic diabetes.
• Patients in whom a variant of uncertain significance (VUS) has been identified in a gene associated with monogenic diabetes.
• Patients with atypical diabetes.

List of some conditions seen in the Diabetes Genetics Clinic

• Maturity onset diabetes of the young (MODY) caused by HNF1A, HNF4A, GCK, HNF1B, PDX1, or other suspected genes
• Mitochondrial Diabetes
• Lipodystrophy
• Neonatal Diabetes

Frequently Asked Questions

Q: What is Monogenic Diabetes?

A: Monogenic diabetes is diabetes caused by a genetic variant in one gene. Two major categories are Neonatal Diabetes, which is generally diagnosed in the first nine months of life, and Maturity Onset Diabetes of the Young, which is generally diagnosed in childhood or adulthood.

Q: What is MODY?

A: Maturity Onset Diabetes of the Young (MODY) is a rare form of diabetes caused by changes in the DNA that are passed down in families.

People with MODY tend to develop diabetes a younger age (usually before age 30), however the condition is often not recognized and can be misdiagnosed as type 1 or type 2 diabetes.

Making the diagnosis of MODY is important because it may impact treatment.

Q: What causes MODY?

A: Genetic changes in certain genes cause MODY. Clinical genetic testing is available for the genes that most commonly cause the disease, which include HNF1A, GCK, HNF4A, PDX1, and HNF1B.

Q: What are the risk factors for MODY?

A: Risk factors for MODY include:

• Age, typically onset of diabetes before age 30
• Strong family history of diabetes (often a parent affected)
• Normal weight (as compared to patients with type 2 diabetes often being overweight)
• Negative diabetes antibody results (as compared to type 1 diabetes)
• Detectable C-peptide many years after diagnosis
• Chronic mildly elevated fasting blood sugars (100-140 mg/dl)

Q: What are the symptoms of MODY?

A: Symptoms of MODY may include:

• Symptoms of type 1 or type 2 diabetes
• Many individuals with MODY have no symptoms at all. Particularly those with mutations in GCK MODY may never develop any symptoms.

Q: How is MODY diagnosed?

A: MODY is diagnosed with a blood test that looks for alterations in the genes that most commonly cause the disease, including HNF1A, GCK, HNF4A, PDX1, and HNF1B.

Genetic testing is offered at the Mass General Diabetes Genetics Clinic. Since MODY is not common and genetic testing is expensive, it is recommended that patients be assessed by a clinician familiar with the condition before testing is pursued.

Q: How is MODY treated?

A: Your health care provider will recommend treatment based on which gene is causing the condition:

GCK MODY: Usually no treatment is necessary. Blood sugars remain mildly elevated, but it is not thought to be dangerous or lead to typical diabetic complications.

HNF1A and HNF4A MODY: Patients often respond well to a sulfonylurea type of oral diabetes medication (pills) from a group of medications called sulfonyureas. If a patient is already on insulin, sometimes the insulin can be stopped, and instead the patient’s sugar levels can be controlled with the pill.

Q: What are the complications of MODY?

A: Except for GCK MODY, all other forms of MODY have the same complications as type 1 and type 2 diabetes. GCK MODY on its own is not thought to cause any clinically important complications.

Q: Will you help me interpret my direct to consumer genetic testing results?

A: Most of the direct to consumer genetic testing options available involve looking at common genetic variants that only slightly increase the risk of type 1 or type 2 diabetes. Our clinic currently focuses on genetic variants are not included in most of these panels because they are less common. These less common variants have a much larger impact on risk of diabetes, and they are generally identified by tests looking at the full genetic sequence of a selected gene or set of a genes.

Learn more

The following websites provide more information on MODY:

• Monogenic Diabetes Research and Advocacy Project (MDRAP)
• National Institute of Diabetes and Digestive and Kidney Diseases
• University of Exeter
• University of Chicago

Research

Dr. Udler is running a government-funded study to look for genetic causes of diabetes in individuals who test negative for the most common forms of monogenic diabetes. This study is intended for individuals who had testing for MODY which came back negative, but there is a strong suspicion that they have a genetic form of diabetes.

We are also a recruitment site for a new government-funded study of individuals with atypical diabetes.