年轻起病的成年型糖尿病患者的餐后肠降血糖素和胰岛激素反应及二肽基肽酶 4 酶活性。

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

机构信息

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

出版信息

Eur J Endocrinol. 2015 Aug;173(2):205-15. doi: 10.1530/EJE-15-0070. Epub 2015 May 7.

DOI:10.1530/EJE-15-0070

PMID:25953829

Abstract

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 1α (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/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).

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.

摘要

目的

肠促胰岛素在青少年发病的成年型糖尿病（MODY）的病理生理学中的作用尚不清楚。

方法

我们研究了葡萄糖激酶（GCK）糖尿病（MODY2）和肝细胞核因子 1α（HNF1A）糖尿病（MODY3）患者以及匹配的健康个体（CTRLs）餐后血浆胰高血糖素、肠促胰岛素（胰高血糖素样肽 1（GLP1）和葡萄糖依赖性胰岛素释放肽（GIP））和二肽基肽酶 4（DPP4）酶活性的反应。

结果

所有组的胰高血糖素基线值均相似（MODY2：7±1pmol/l；MODY3：6±1pmol/l；CTRLs：8±2pmol/l，P=0.787），但 MODY3 患者的胰高血糖素餐后升高（曲线下面积（AUC）838±108min×pmol/l）与 CTRLs（182±176min×pmol/l，P=0.005）相比，并且与 MODY2 患者的反应相比，MODY3 患者的胰高血糖素餐后升高趋势更大（410±154min×pmol/l，P=0.063）。各组的血浆 GIP 和 GLP1 的峰值浓度和 AUC 相似。MODY3 患者的空腹 DPP4 活性增加（17.7±1.2mU/ml）与 CTRLs（13.6±0.8mU/ml，P=0.011）相比，但活性量与 MODY2 患者相似（15.0±0.7mU/ml，P=0.133）。