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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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.

Original languageEnglish
JournalEuropean Journal of Endocrinology
Issue number2
Pages (from-to)205-215
Number of pages11
Publication statusPublished - 1 Aug 2015

ID: 137418800