Maturity onset diabetes of the young type 2 (MODY2): Insight from an extended family

Abstract

Aims: To assess long-term outcome of patients with maturity onset diabetes of the young, type 2 (MODY2) in a unique large cohort of patients with the same genetic and environmental background.

Methods: We prospectively evaluated 162 patients aged 5 to 82 years, belonging to the same extended family living in the same village. All patients underwent molecular testing for the glucokinase (GCK) gene mutation identified in the proband, and were categorized into three groups (MODY2, type 2 diabetes and controls).

Results: The 5.5-year-old proband had the c.1278_1286del mutation in the GCK and was diagnosed with MODY2. Forty-two out of 162 participants were positive for the mutation and 39 had type 2 diabetes. Patients were followed for a mean 10.2 ± 3.7 years (range 0-14). Mean fasting blood glucose and HbA1c increased significantly over the years in MODY2 patients (133 vs. 146 mg/dL; 6.9% vs. 8.2%, respectively). Increase in HbA1c occurred only in the obese/overweight subgroups. Twenty-five percent of MODY2 patients developed diabetes complications, all were above 40 years of age.

Conclusions: Although MODY2 commonly has a benign disease course, weight gain is a risk factor for diabetes complications, requiring life-long follow-up and in some patients, medical intervention.

Keywords: Glucokinase (GCK); Maturity onset diabetes of the young type 2 (MODY2); Type 2 diabetes.