Long-term follow-up of oral glucose tolerance test-derived glucose tolerance and insulin secretion and insulin sensitivity indexes in subjects with glucokinase mutations (MODY2).

摘要

OBJECTIVE: We investigated the natural history of glucokinase (GCK)-related maturity-onset diabetes of the young type 2 (MODY2), notably the factors associated with deterioration of hyperglycemia over time. RESEARCH DESIGN AND METHODS: We report an 11-year follow-up of glucose tolerance and indexes of insulin secretion and insulin sensitivity derived from oral glucose tolerance tests in 33 MODY2 subjects. RESULTS: The variation between tests of glucose tolerance (expressed as the area under the glucose curve) was 6.9 +/- 3.2% (mean +/- SEM), but individual results ranged from -20 to 61%. Deterioration of glucose tolerance between tests was associated with decreased insulin sensitivity, while insulin secretion remained stable. CONCLUSIONS: Glucose tolerance can remain stable over many years in subjects with MODY2 due to the relative stability of the GCK-related beta-cell defect. However, the development of insulin resistance may have an important role in the deterioration of the glucose tolerance and inthe long-term evolution of the disorder.