Incretin Effect and Glucagon Responses to Oral and Intravenous Glucose in Patients With Maturity-Onset Diabetes of the Young—Type 2 and Type 3
- Signe H. Østoft1,2,3⇑,
- Jonatan I. Bagger1,2,3,
- Torben Hansen3,4,
- Oluf Pedersen3,
- Jens J. Holst2,3,
- Filip K. Knop1,2,3 and
- Tina Vilsbøll1
- 1Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
- 2Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark
- 3Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
- 4Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
- Corresponding author: Signe H. Østoft, .
Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous subgroup of nonautoimmune diabetes, constituting 1–2% of all diabetes. Because little is known about incretin function in patients with MODY, we studied the incretin effect and hormone responses to oral and intravenous glucose loads in patients with glucokinase (GCK)-diabetes (MODY2) and hepatocyte nuclear factor 1α (HNF1A)-diabetes (MODY3), respectively, and in matched healthy control subjects. Both MODY groups exhibited glucose intolerance after oral glucose (most pronounced in patients with HNF1A-diabetes), but only patients with HNF1A-diabetes had impaired incretin effect and inappropriate glucagon responses to OGTT. Both groups of patients with diabetes showed normal suppression of glucagon in response to intravenous glucose. Thus, HNF1A-diabetes, similar to type 2 diabetes, is characterized by an impaired incretin effect and inappropriate glucagon responses, whereas incretin effect and glucagon response to oral glucose remain unaffected in GCK-diabetes, reflecting important pathogenetic differences between the two MODY forms.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1878/-/DC1.
- Received December 12, 2013.
- Accepted March 20, 2014.
- © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.