What is maturity onset diabetes of the young (MODY)? How does it differ from types 1 and 2 diabetes? — Caroline Luke, FNP, New York City

MODY is an inherited form of diabetes primarily caused by defects in beta-cell function and secretion; approximately 2% of all individuals with diabetes have MODY. The condition is commonly misdiagnosed as either type 1 or type 2 diabetes. The nomenclature of MODY is being replaced by the more accurate name of “genetic defects in beta-cell function.”

There are actually eight different autosomal-dominant genetic mutations associated with MODY, so these patients present clinically with a strong family history of diabetes. Mutations in glucokinase, hepatocyte nuclear factor-4-alpha, hepatocyte nuclear factor-1-alpha, insulin promoter factor-1, and neurogenic differentiation factor-1 can all adversely affect various beta-cell functions.

The most common mutations seen in adults are glucokinase (formerly known as MODY-2) and hepatocyte nuclear factor-4-alpha (formerly known as MODY-3). Glucokinase is sometimes thought of as the glucose sensor for the beta cell, and mutations in glucokinase usually result in a slightly higher glucose threshold for insulin secretion in the beta cell.

Clinically, this is manifested by mild, stable fasting hyperglycemia, and mild elevations in the hemoglogin A1c. Interestingly, MODY-2 does not typically improve with insulin or oral diabetes therapies. Characteristics of MODY-3 include decreased insulin secretion, but these patients are quite sensitive to sulfonylurea drugs when used to correct hyperglycemia.

In differentiating patients with MODY from type 1 and type 2 diabetes, remember that individuals with MODY are not insulin-resistant (unlike those with type 2 diabetes) and usually have some beta-cell secretory capacity (unlike those with type 1 diabetes). While genetic testing is available for MODY, it is quite expensive (N Engl J Med. 2001;345:971-980). — Kathy Pereira, MSN, FNP-BC, assistant professor, co-coordinator, family nurse practitioner program, Duke University School of Nursing, Durham, N.C. (158-1)