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)

  1. Delphine Martin, MD1,
  2. Christine Bellanné-Chantelot, PHD2,
  3. Inge Deschamps, MD1,
  4. Philippe Froguel, MD, PHD3,
  5. Jean-Jacques Robert, MD, PHD1 and
  6. Gilberto Velho, MD, PHD4
  1. 1Department of Pediatric Diabetology, AP-HP Hôpital Necker-Enfants Malades, Paris, France
  2. 2Department of Genetics, AP-HP Groupe Hospitalier Pitié-Salpétrière, Paris, France
  3. 3CNRS, UMR 8090, Institute of Biology, Pasteur Institute, Lille, France
  4. 4INSERM, Unité 695, Paris, France
  1. Corresponding author: Dr. Gilberto Velho, velho{at}bichat.inserm.fr


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.


  • Published ahead of print at http://care.diabetesjournals.org on 14 April 2008.

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    • Accepted April 4, 2008.
    • Received October 18, 2007.
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  1. Diabetes Care vol. 31 no. 7 1321-1323
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