Postprandial incretin and islet hormone responses and dipeptidyl-peptidase 4 enzymatic activity in patients with maturity onset diabetes of the young
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Postprandial incretin and islet hormone responses and dipeptidyl-peptidase 4 enzymatic activity in patients with maturity onset diabetes of the young. / Østoft, Signe Harring; Bagger, Jonatan Ising; Hansen, Torben; Hartmann, Bolette; Pedersen, Oluf; Holst, Jens Juul; Knop, Filip Krag; Vilsbøll, Tina.
I: European Journal of Endocrinology, Bind 173, Nr. 2, 01.08.2015, s. 205-215.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Postprandial incretin and islet hormone responses and dipeptidyl-peptidase 4 enzymatic activity in patients with maturity onset diabetes of the young
AU - Østoft, Signe Harring
AU - Bagger, Jonatan Ising
AU - Hansen, Torben
AU - Hartmann, Bolette
AU - Pedersen, Oluf
AU - Holst, Jens Juul
AU - Knop, Filip Krag
AU - Vilsbøll, Tina
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Objective: The role of the incretin hormones in the pathophysiology of maturity onset diabetes of the young (MODY) is unclear. Design: We studied the postprandial plasma responses of glucagon, incretin hormones (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)), and dipeptidyl-peptidase 4 (DPP-4) enzymatic activity in patients with glucokinase (GCK)-diabetes (MODY2), hepatocyte nuclear factor 1α (HNF1A)-diabetes (MODY3), and in matched healthy individuals (CTRLs). Subjects and methods: Ten patients with GCK-diabetes (age: 43±5 years; BMI: 24±2 kg/m2; FPG: 7.1±0.3 mmol/l: HbA1c: 6.6±0.2%), 10 patients with HNF1A-diabetes (age: 31±3 years (mean ± SEM); body mass index (BMI): 24±1 kg/m2; fasting plasma glucose (FPG): 8.9±0.8 mmol/l; haemoglobin A1c (HbA1c): 7.0±0.3%), and 10 CTRLs (age: 40±5 years; BMI: 24±1 kg/m2; FPG: 5.1±0.1 mmol/l; HbA1c: 5.3±0.1%) were examined with a liquid test meal. Results: All groups exhibited similar baseline values of glucagon (7±1 (GCK-diabetes), 6±1 pmol/l (HNF1A-diabetes), 8±2 (CTRLs), P=0.787), but patients with HNF1A-diabetes exhibited postprandial hyperglucagonaemia (area under curve (AUC): 838±108 min×pmol/l) compared to CTRLs (182±176 min×pmol/l, P=0.005) and tended to have a greater response than patients with GCK-diabetes (410±154 min×pmol/l, P=0.063). Similar peak concentrations and AUCs for plasma GIP and plasma GLP-1 were observed across the groups. Increased fasting DPP-4-activity was seen in patients with HNF1A-diabetes (17.7±1.2 mU/ml) vs. CTRLs (13.6±0.8, P=0.011), but was similar to patients with GCK-diabetes (15.0±0.7 mU/ml, P=0.133). Conclusions: The pathophysiology of HNF1A-diabetes includes exaggerated postprandial glucagon responses and increased fasting DPP-4 enzymatic activity, but normal postprandial incretin responses in both patients with GCK-diabetes and HNF1A-diabetes.
AB - Objective: The role of the incretin hormones in the pathophysiology of maturity onset diabetes of the young (MODY) is unclear. Design: We studied the postprandial plasma responses of glucagon, incretin hormones (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)), and dipeptidyl-peptidase 4 (DPP-4) enzymatic activity in patients with glucokinase (GCK)-diabetes (MODY2), hepatocyte nuclear factor 1α (HNF1A)-diabetes (MODY3), and in matched healthy individuals (CTRLs). Subjects and methods: Ten patients with GCK-diabetes (age: 43±5 years; BMI: 24±2 kg/m2; FPG: 7.1±0.3 mmol/l: HbA1c: 6.6±0.2%), 10 patients with HNF1A-diabetes (age: 31±3 years (mean ± SEM); body mass index (BMI): 24±1 kg/m2; fasting plasma glucose (FPG): 8.9±0.8 mmol/l; haemoglobin A1c (HbA1c): 7.0±0.3%), and 10 CTRLs (age: 40±5 years; BMI: 24±1 kg/m2; FPG: 5.1±0.1 mmol/l; HbA1c: 5.3±0.1%) were examined with a liquid test meal. Results: All groups exhibited similar baseline values of glucagon (7±1 (GCK-diabetes), 6±1 pmol/l (HNF1A-diabetes), 8±2 (CTRLs), P=0.787), but patients with HNF1A-diabetes exhibited postprandial hyperglucagonaemia (area under curve (AUC): 838±108 min×pmol/l) compared to CTRLs (182±176 min×pmol/l, P=0.005) and tended to have a greater response than patients with GCK-diabetes (410±154 min×pmol/l, P=0.063). Similar peak concentrations and AUCs for plasma GIP and plasma GLP-1 were observed across the groups. Increased fasting DPP-4-activity was seen in patients with HNF1A-diabetes (17.7±1.2 mU/ml) vs. CTRLs (13.6±0.8, P=0.011), but was similar to patients with GCK-diabetes (15.0±0.7 mU/ml, P=0.133). Conclusions: The pathophysiology of HNF1A-diabetes includes exaggerated postprandial glucagon responses and increased fasting DPP-4 enzymatic activity, but normal postprandial incretin responses in both patients with GCK-diabetes and HNF1A-diabetes.
U2 - 10.1530/EJE-15-0070
DO - 10.1530/EJE-15-0070
M3 - Journal article
C2 - 25953829
VL - 173
SP - 205
EP - 215
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 2
ER -
ID: 137418800