Maturity-Onset Diabetes of the Young (MODY) is an autosomal dominant form of diabetes typically occurring before age 25 and caused by a primary insulin secretion defect. MODY is not a single entity but represents nine classifications with genetic, metabolic, and clinical heterogeneity. MODY is estimated to affect approximately 1-2% of people with diabetes, although this may be an underestimate since the genetic etiology of this type of diabetes often goes undiagnosed.

Main features of MODY patients include the following: 1) Hyperglycemia usually diagnosed before age 25 years in at least 1 family member. 2) Autosomal dominant inheritance through at least 3 generations, and a phenotype shared by diabetic family members. 3) Absence of insulin therapy or significant C-peptide levels even in a patient on insulin treatment for several years after diagnosis.

The MODY panel tests for genetic mutations that cause MODY types 1, 2, and 3.

MODY 3 (HNF1A): This is the most common form of MODY, causing 60% of cases. It shares with MODY 1 the progressive hyperglycemia, risk for microvascular complications, and increasing need for treatment with sulfonylureas as the disease progresses. Approximately 1/3 of patients will ultimately require insulin to maintain euglycemia. Compared to MODY 1, patients with MODY 3 tend to have a lower renal threshold for glycosuria and a normal rather than reduced circulating lipoproteins and triglycerides, often with an elevated HDL. Despite the high HDL, the risk for coronary artery disease is increased in these patients.

MODY 2 (GCK): Approximately 25% of MODY is caused by mutations in the glucokinase (GCK) gene. It is associated with a mild form of nonprogressive hyperglycemia that is usually managed with diet alone. Individuals with GCK MODY rarely have overt symptoms of diabetes, and diabetes-associated complications are rare. These individuals are often diagnosed with diabetes or glucose intolerance on routine screening, particularly during pregnancy. Approximately 2-4% of gestational diabetes may be due to GCK mutations.

MODY 1 (HNF4A): Accounting for ~3% of MODY cases, MODY 1 is caused by mutations in the β-cell transcription factor gene, HNF4A. It has a similar presentation to MODY 3, including progressive hyperglycemia and microvascular complications. 30-40% of patients require sulfonylurea drugs or insulin over time.