Diabetologia

, Volume 45, Issue 3, pp 427–435

The genetic abnormality in the beta cell determines the response to an oral glucose load

  • A. Stride
  • M. Vaxillaire
  • T. Tuomi
  • F. Barbetti
  • P. R. Njølstad
  • T. Hansen
  • A. Costa
  • I. Conget
  • O. Pedersen
  • O. Søvik
  • R. Lorini
  • L. Groop
  • P. Froguel
  • A. T. Hattersley
Article

DOI: 10.1007/s00125-001-0770-9

Cite this article as:
Stride, A., Vaxillaire, M., Tuomi, T. et al. Diabetologia (2002) 45: 427. doi:10.1007/s00125-001-0770-9

Abstract.

Aims/hypothesis:

We assessed how the role of genes genetic causation in causing maturity-onset diabetes of the young (MODY) alters the response to an oral glucose tolerance test (OGTT).

Methods:

We studied OGTT in 362 MODY subjects, from seven European centres; 245 had glucokinase gene mutations and 117 had Hepatocyte Nuclear Factor –1 alpha (HNF-1α) gene mutations.

Results:

BMI and age were similar in the genetically defined groups. Fasting plasma glucose (FPG) was less than 5.5 mmol/l in 2 % glucokinase subjects and 46 % HNF-1α subjects (p < 0.0001). Glucokinase subjects had a higher FPG than HNF-1α subjects ([means ± SD] 6.8 ± 0.8 vs 6.0 ± 1.9 mmol/l, p < 0.0001), a lower 2-h value (8.9 ± 2.3 vs 11.2 ± 5.2 mmol/l, p < 0.0001) and a lower OGTT increment (2-h – fasting) (2.1 ± 2.3 vs 5.2 ± 3.9 mmol/l, p < 0.0001). The relative proportions classified as diabetic depended on whether fasting (38 % vs 22 %, glucokinase vs HNF-1α) or 2-h values (19 % vs 44 %) were used. Fasting and 2-h glucose values were not correlated in the glucokinase subjects (r = –0.047, p = 0.65) but were strongly correlated in HNF-1α subjects (r = 0.8, p < 0.001). Insulin concentrations were higher in the glucokinase subjects throughout the OGTT.

Conclusion/interpretation:

The genetic cause of the beta-cell defect results in clear differences in both the fasting glucose and the response to an oral glucose load and this can help diagnostic genetic testing in MODY. OGTT results reflect not only the degree of hyperglycaemia but also the underlying cause. [Diabetologia (2002) 45: 427–435]

Keywords Maturity-onset diabetes of the young MODY hepatocyte nuclear factor-1 alpha glucokinase oral glucose tolerance test genetics. 
Download to read the full article text

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • A. Stride
    • 1
  • M. Vaxillaire
    • 2
  • T. Tuomi
    • 3
  • F. Barbetti
    • 4
  • P. R. Njølstad
    • 5
  • T. Hansen
    • 6
  • A. Costa
    • 7
  • I. Conget
    • 7
  • O. Pedersen
    • 6
  • O. Søvik
    • 5
  • R. Lorini
    • 8
  • L. Groop
    • 9
  • P. Froguel
    • 2
  • A. T. Hattersley
    • 1
  1. 1.Department of Diabetes and Vascular Medicine, Postgraduate School of Medicine and Health Science, University of Exeter, Exeter, UKGB
  2. 2.Department of Human Genetics, Pasteur Institute, Lille, FranceFR
  3. 3.Helsinki University Central Hospital, Department of Medicine, Division of Endocrinology, Helsinki, FinlandFI
  4. 4.IBCIT Biomedical Science Park, S. Raffaele, Rome, ItalyIT
  5. 5.Department of Paediatrics, Haukeland Hospital, University of Bergen, Bergen, NorwayNO
  6. 6.Steno Diabetes Center, Gentofte, DenmarkDK
  7. 7.Endocrinology and Diabetes Unit, IDIBAPS, Faculty of Medicine, University of Barcelona, Barcelona, SpainES
  8. 8.Department of Paediatrics, University of Genoa, Genova, ItalyIT
  9. 9.Department of Endocrinology, University Hospital MAS, Lund University, Malmo, SwedenSE

Personalised recommendations