Clinical Heterogeneity in Monogenic Diabetes Caused by Mutations in the Glucokinase Gene (GCK-MODY).
- Antonio L. Cuesta-Muñoz, MD, PHD (alcm{at}fundacionimabis.org)(1),
- Tiinamaija Tuomi, MD, PHD(2),
- Nadia Cobo-Vuilleumier, MSC(1),
- Hanna Koskela, PHD(2),
- Stella Odili, BA3),
- Amanda Stride, MRCP(4),
- Carol Buettger, BA(3),
- Timo Otonkoski, MD(5),
- Philippe Froguel, MD, PHD(6),
- Joseph Grimsby, PHD(7),
- Maria Garcia-Gimeno, PHD(8) and
- Franz M. Matschinsky, MD, PHD (matsch{at}mail.med.upenn.edu)(3)
- 1IMABIS Foundation and Center for the Study of Pancreatic Beta-cell Diseases. Carlos Haya University Hospital, Málaga, Spain
- 2Research Program for Molecular Medicine, Helsinki University; Department of Medicine, Helsinki University Hospital and, Genetic Institute, Folkhalsan Research Center, Helsinki, Finland
- 3Department of Biochemistry and Biophysics and Diabetes Research Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
- 4Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter, EX2 5DW, UK
- 5Hospital for Children and Adolescents and Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
- 6CNRS, UMR 8090, Institute of Biology, Pasteur Institute, Lille, France
- 7Department of Metabolic Diseases, Hoffmann-La Roche, Nutley, New Jersey
- 8Biomedicine Institute of Valencia (CSIC) and CIBER of Rare Diseases (CIBERER) (M. A. G.-G., P.S.), Valencia, Spain
Abstract
Objective: To evaluate the heterogeneity in the clinical expression in a family with GCK-MODY.
Research design and methods: Members (three generations) of the same family presented either with overt neonatal hyperglycemia, marked postprandial hyperglycemia or glucosuria. HOMAIR, insulinogenic and disposition indices were calculated. OGTT results in the glucokinase(GCK)-mutation carriers from this family were compared with those from other subjects with GCK mutations in the same codon (GCK261), with other missense and other types of GCK mutations in different codons from the European-MODY-Consortium database (GCKm).
Results: Mutation G261R was found in the glucokinase gene. During OGTT, glucose (p=0.02) and insulin (p=0.009) response at 2-hours as well as 2h glucose increment (GCK261 vs. other missense GCK-mutations, p=0.003) were significantly higher in GCK261 than in GCKm carriers.
Conclusions: Differing from other GCKm carriers, the glucose and insulin response to oral glucose was significantly higher in GCK261 carriers indicating clinical heterogeneity in GCK-MODY.
Footnotes
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- Received May 8, 2009.
- Accepted October 27, 2009.
- Copyright © American Diabetes Association
