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Leif Groop

Leif Groop

Principal investigator

Leif Groop

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

Author

  • A Stride
  • M Vaxillaire
  • T Tuomi
  • F Barbetti
  • PR Njolstad
  • T Hansen
  • A Costa
  • I Conget
  • O Pedersen
  • O Sovik
  • R Lorini
  • Leif Groop
  • P Froguel
  • AT Hattersley

Summary, in English

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-1alpha) 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-1alpha subjects (p < 0.0001). Glucokinase subjects had a higher FPG than HNF-1a 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-1alpha) 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-1alpha 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.

Department/s

  • Genomics, Diabetes and Endocrinology

Publishing year

2002

Language

English

Pages

427-435

Publication/Series

Diabetologia

Volume

45

Issue

3

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • oral glucose tolerance test
  • glucokinase
  • alpha
  • hepatocyte nuclear factor-1
  • maturity-onset diabetes of the young
  • MODY
  • genetics

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1432-0428