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

Research output: Contribution to journalArticlepeer-review


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-1 α) 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.

Original languageEnglish
Pages (from-to)427-435
Number of pages9
Issue number3
Publication statusPublished - 2002


  • Genetics
  • Glucokinase
  • Hepatocyte nuclear factor-1 alpha
  • Maturity-onset diabetes of the young
  • MODY
  • Oral glucose tolerance test

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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