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Diabetes Care Publish Ahead of Print published online ahead of print April 14, 2008
DOI: 10.2337/dc07-2017
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Original Research

Long-term follow-up of OGTT-derived glucose tolerance, insulin secretion and insulin sensitivity indices in subjects with glucokinase mutations (MODY2)

Delphine Martin, MD1, Christine Bellanné-Chantelot, PhD2, Inge Deschamps, MD1, Philippe Froguel, MD, PhD3, Jean-Jacques Robert, MD, PhD1 and Gilberto Velho, MD, PhD4

1AP-HP Hôpital Necker - Enfants Malades, Department of Pediatric Diabetology, Paris, France
2AP-HP Groupe Hospitalier Pitié-Salpétrière, Department of Genetics, Paris, France
3CNRS, UMR 8090, Institute of Biology, Pasteur Institute, Lille, France
4INSERM, Unité 695, Paris, France

velho{at}bichat.inserm.fr

ABSTRACT

Objective: We investigated the natural history of 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 of indices 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% (m±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 glucokinase-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.


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