Postprandial incretin and islet hormone responses and dipeptidyl-peptidase 4 enzymatic activity in patients with maturity onset diabetes of the young

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 (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 1a (HNF1A) diabetes (MODY3) as well as in matched healthy individuals (CTRLs). Subjects and methods: Ten patients with MODY2 (mean age±S.E.M. 43±5 years; BMI 24±2 kg/m2; 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/m2; FPG 8.9±0.8 mmol/l; HbA1c 7.0±0.3%) and ten 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 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 minXpmol/l) as compared to CTRLs (182±176 minXpmol/l, P=0.005) and tended to have a greater response than did patients with MODY2 (410±154 minXpmol/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). Conclusion: 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.

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 (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 1a (HNF1A) diabetes (MODY3) as well as in matched healthy individuals (CTRLs). Subjects and methods: Ten patients with MODY2 (mean age±S.E.M. 43±5 years; BMI 24±2 kg/m2; 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/m2; FPG 8.9±0.8 mmol/l; HbA1c 7.0±0.3%) and ten 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 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 minXpmol/l) as compared to CTRLs (182±176 minXpmol/l, P=0.005) and tended to have a greater response than did patients with MODY2 (410±154 minXpmol/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). Conclusion: 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.

U2 - 10.1530/eje-15-0070

DO - 10.1530/eje-15-0070

M3 - Journal article

C2 - 25953829

SN - 0804-4643

VL - 173

SP - 205

EP - 215

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 2

ER -