Authors: Sagen, J. V.; Pearson, E. R.¹; Johansen, A.²; Spyer, G.¹; Søvik, O.; Pedersen, O.²; Njølstad, P. R.; Hattersley, A. T.¹; Hansen, T.²

Source: Diabetic Medicine, Volume 22, Number 4, April 2005 , pp. 406-409(4)

Publisher: Wiley-Blackwell

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/l (421, 1647) and 1933 min pmol/l (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/l (1126, 3172) and 2250 min pmol/l (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.

Diabet. Med. 22, 406–409 (2005)

Keywords: MODY3; sulphonylurea; insulin secretion

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1464-5491.2005.01439.x

Affiliations: 1: Department of Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, UK 2: Steno Diabetes Centre and Hagedorn Research Institute, Copenhagen, Denmark

Publication date: 2005-04-01

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