Incretin Effect and Glucagon Responses to Oral and Intravenous Glucose in Patients with Maturity Onset Diabetes of the Young - Type 2 and Type 3

TY - JOUR

T1 - Incretin Effect and Glucagon Responses to Oral and Intravenous Glucose in Patients with Maturity Onset Diabetes of the Young - Type 2 and Type 3

AU - Ostoft, Signe H

AU - Bagger, Jonatan I

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Holst, Jens Juul

AU - Knop, Filip K

AU - Vilsbøll, Tina

PY - 2014/8

Y1 - 2014/8

N2 - Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous subgroup of non-autoimmune 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 1a (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 gluca-gon response to oral glucose remain unaffected in GCK-diabetes, reflecting important pathogenetic differences between the two MODY forms.

AB - Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous subgroup of non-autoimmune 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 1a (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 gluca-gon response to oral glucose remain unaffected in GCK-diabetes, reflecting important pathogenetic differences between the two MODY forms.

U2 - 10.2337/db13-1878

DO - 10.2337/db13-1878

M3 - Journal article

C2 - 24677712

SN - 0012-1797

VL - 63

SP - 2838

EP - 2844

JO - Diabetes

JF - Diabetes

IS - 8

ER -