The aim of this study was to evaluate the beta cell and
incretin function in patients with HNF4A and HNF1A
MODY during a test meal. Clinical characteristics and biochemical data (
glucose,
proinsulin,
insulin,
C-peptide,
GLP-1 and GIP) during a test meal were compared between
MODY patients from eight different families. BMI-matched T2D and healthy subjects were used as two separate control groups. The early phase of insulin secretion was attenuated in HNF4A, HNF1A
MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A
MODY: 93.8 ± 57.0, HNF1A
MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). Markedly reduced levels of
proinsulin were found in HNF4A
MODY compared to T2D and that tended to be so also in HNF1A
MODY (HNF4A
MODY: 3.7 ± 1.2, HNF1A
MODY: 8.3 ± 3.8 vs. T2D: 26.6 ± 14.3). Patients with HNF4A
MODY had similar total
GLP-1 and GIP responses as controls (
GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A
MODY: 1,257.0 ± 999.3, HNF1A
MODY: 697.1 ± 818.4) but with a different secretion pattern. The AUC
insulin during the test meal was strongly correlated with the GIP secretion (Correlation coefficient 1.0, P < 0.001). No such correlation was seen for
insulin and
GLP-1. Patients with HNF4A and HNF1A
MODY showed an attenuated early phase of insulin secretion similar to T2Ds. AUC
insulin during the test meal was strongly correlated with GIP secretion, whereas no such correlation was seen for
insulin and
GLP-1. Thus, GIP may be a more important factor for insulin secretion than
GLP-1 in
MODY patients.