title: Postprandial incretin and islet hormone responses and dipeptidyl-peptidase 4 enzymatic activity in patients with maturity onset diabetes of the young.
abstract: OBJECTIVE
  The role of the incretin hormones in the pathophysiology of maturity onset diabetes of the young (MODY) is unclear.
  
  
  METHODS
  We studied the postprandial plasma responses of glucagon, incretin hormones (glucagon-like peptide 1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP)) and dipeptidyl-peptidase 4 (DPP4) enzymatic activity in patients with glucokinase (GCK) diabetes (MODY2) and hepatocyte nuclear factor 1α (HNF1A) diabetes (MODY3) as well as in matched healthy individuals (CTRLs).
  
  
  METHODS
  Ten patients with MODY2 (mean age ± S.E.M. 43 ± 5 years; BMI 24 ± 2 kg/m(2); fasting plasma glucose (FPG) 7.1 ± 0.3 mmol/l: HbA1c 6.6 ± 0.2%), ten patients with MODY3 (age 31 ± 3 years; BMI 24 ± 1 kg/m(2); FPG 8.9 ± 0.8 mmol/l; HbA1c 7.0 ± 0.3%) and ten CTRLs (age 40 ± 5 years; BMI 24 ± 1 kg/m(2); FPG 5.1 ± 0.1 mmol/l; HbA1c 5.3 ± 0.1%) were examined with a liquid test meal.
  
  
  RESULTS
  All of the groups exhibited similar baseline values of glucagon (MODY2: 7 ± 1 pmol/l; MODY3: 6 ± 1 pmol/l; CTRLs: 8 ± 2 pmol/l, P=0.787), but patients with MODY3 exhibited postprandial hyperglucagonaemia (area under the curve (AUC) 838 ± 108 min × pmol/l) as compared to CTRLs (182 ± 176 min × pmol/l, P=0.005) and tended to have a greater response than did patients with MODY2 (410 ± 154 min × pmol/l, P=0.063). Similar peak concentrations and AUCs for plasma GIP and plasma GLP1 were observed across the groups. Increased fasting DPP4 activity was seen in patients with MODY3 (17.7 ± 1.2 mU/ml) vs CTRLs (13.6 ± 0.8 mU/ml, P=0.011), but the amount of activity was similar to that in patients with MODY2 (15.0 ± 0.7 mU/ml, P=0.133).
  
  
  CONCLUSIONS
  The pathophysiology of MODY3 includes exaggerated postprandial glucagon responses and increased fasting DPP4 enzymatic activity but normal postprandial incretin responses both in patients with MODY2 and in patients with MODY3.
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark s.ostoft@dadlnet.dk.
authors.forename: Signe Harring
authors.initials: SH
authors.lastname: Østoft
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark.
authors.forename: Jonatan Ising
authors.initials: JI
authors.lastname: Bagger
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark.
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark.
authors.forename: Filip Krag
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D005215:Fasting / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D054795:Incretins / Q000097:blood*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D054795:Incretins; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4