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).
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.


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 in the long-term evolution of the disorder.
Martin
Delphine
D
Department of Pediatric Diabetology, AP-HP Hôpital Necker-Enfants Malades, Paris, France.
Bellanné-Chantelot
Christine
C
Deschamps
Inge
I
Froguel
Philippe
P
Robert
Jean-Jacques
JJ
Velho
Gilberto
G
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005941:Glucokinase / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000201:enzymology; D008297:Male; D009154:Mutation
D001786:Blood Glucose; D007328:Insulin; D005941:Glucokinase