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 β-cell defect. However, the development of insulin resistance may have an important role in the deterioration of the glucose tolerance and in the long-term evolution of the disorder.