Preserved insulin response to tolbutamide in hepatocyte nuclear factor-1α mutation carriers

J. V. Sagen (Lead / Corresponding author), E. R. Pearson, A. Johansen, G. Spyer, O. Søvik, O. Pedersen, P. R. Njølstad, A. T. Hattersley, T. Hansen

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Abstract

Aims: Diabetic subjects with mutations in the gene encoding hepatocyte nuclear factor (HNF)-1α (MODY3) are prone to develop hypoglycaemia at low doses of glibenclamide, interpreted as sulphonylurea hypersensitivity. The present study was undertaken to compare the plasma insulin responses to glucose and tolbutamide in HNF-1α mutation carriers with those of healthy control subjects.

Methods: Seven mutation carriers; three normoglycaemic, two with impaired glucose tolerance, and two with newly detected diabetes, underwent an oral glucose tolerance test and a tolbutamide-modified intravenous glucose tolerance test with measurements of plasma insulin. Twenty-two healthy subjects served as controls.

Results: The plasma insulin response to intravenous glucose was reduced in the HNF-1α mutation carriers compared to the control subjects, with an area under the curve (median (interquartile range)) of 812 min pmol/1 (421, 1647) and 1933 min pmol/1 (1521, 2908), respectively (P = 0.03). In striking contrast, the plasma insulin response to tolbutamide was preserved, with an area under the curve of 2109 min pmol/1 (1126, 3172) and 2250 min pmol/1 (1614, 3276) in the mutation carriers and control subjects, respectively.

Conclusions: HNF-1α mutation carriers are characterized by preserved tolbutamide-induced insulin secretion. Compared to healthy subjects, our MODY3 individuals did not show any increased serum insulin response to tolbutamide, suggesting that HNF-1α mutation carriers are not characterized by sulphonylurea hypersensitivity.

Original languageEnglish
Pages (from-to)406-409
Number of pages4
JournalDiabetic Medicine
Volume22
Issue number4
Early online date21 Mar 2005
DOIs
Publication statusPublished - Apr 2005

Keywords

  • Insulin secretion
  • MODY3
  • Sulphonylurea

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    Sagen, J. V., Pearson, E. R., Johansen, A., Spyer, G., Søvik, O., Pedersen, O., Njølstad, P. R., Hattersley, A. T., & Hansen, T. (2005). Preserved insulin response to tolbutamide in hepatocyte nuclear factor-1α mutation carriers. Diabetic Medicine, 22(4), 406-409. https://doi.org/10.1111/j.1464-5491.2005.01439.x