The genetic abnormality in the beta cell determines the response to an oral glucose load
The genetic abnormality in the beta cell determines the response to an oral glucose load
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DOI：
10.1007/s00125-001-0770-9
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发表时间：
2002-03-01
期刊：
影响因子：
8.2
通讯作者：
Hattersley, AT
中科院分区：
文献类型：
--
作者：
Stride, A;Vaxillaire, M;Hattersley, AT
目的/假设。我们评估了导致青年人成熟型糖尿病（MODY）的基因遗传原因如何改变对口服葡萄糖耐量试验（OGTT）的反应。我们研究了来自7个欧洲中心的362名MODY受试者的OGTT; 245名有葡萄糖激酶基因突变，117名有肝细胞核因子-1 α（HNF-1 α）基因突变。BMI和年龄在基因定义的组中相似。2%葡萄糖激酶受试者和46% HNF-1 α受试者的空腹血糖（FPG）低于5.5 mmol/l（p < 0.0001）。葡萄糖激酶受试者的FPG高于HNF-1a受试者（[平均值+/- SD] 6.8 +/- 0.8 vs 6.0 +/- 1.9 mmol/l，p < 0.0001），较低的2小时值（8.9 +/- 2.3 vs 11.2 +/- 5.2 mmol/l，p < 0.0001）和较低的OGTT增量（2小时-空腹）（2.1 +/- 2.3 vs 5.2 +/- 3.9 mmol/l，p < 0.0001）。归类为糖尿病的相对比例取决于是否使用空腹（38% vs 22%，葡萄糖激酶vs HNF-1 α）或2小时值（19% vs 44%）。在葡萄糖激酶受试者中，空腹血糖值和2小时血糖值不相关（r =-0.047，p = 0.65），但在HNF-1 α受试者中，空腹血糖值和2小时血糖值密切相关（r = 0.8，p < 0.001）。在整个OGTT中，葡萄糖激酶受试者的胰岛素浓度较高。β细胞缺陷的遗传原因导致空腹血糖和对口服葡萄糖负荷的反应存在明显差异，这有助于MODY的诊断性基因检测。OGTT结果不仅反映了高血糖的程度，也反映了潜在的病因。
Aims/hypothesis. We assessed how the role of genes genetic causation in causing maturity-onset diabetes of the young (MODY) alters the response to an oral glucose tolerance test (OGTT).Methods. We studied OGTT in 362 MODY subjects, from seven European centres; 245 had glucokinase gene mutations and 117 had Hepatocyte Nuclear Factor-1 alpha (HNF-1alpha) gene mutations.Results. BMI and age were similar in the genetically defined groups. Fasting plasma glucose (FPG) was less than 5.5 mmol/l in 2% glucokinase subjects and 46% HNF-1alpha subjects (p < 0.0001). Glucokinase subjects had a higher FPG than HNF-1a subjects ([means +/- SD] 6.8 +/- 0.8 vs 6.0 +/- 1.9 mmol/l, p < 0.0001), a lower 2-h value (8.9 +/- 2.3 vs 11.2 +/- 5.2 mmol/l, p < 0.0001) and a lower OGTT increment (2-h - fasting) (2.1 +/- 2.3 vs 5.2 +/- 3.9 mmol/l, p < 0.0001). The relative proportions classified as diabetic depended on whether fasting (38% vs 22%, glucokinase vs HNF-1alpha) or 2-h values (19% vs 44%) were used. Fasting and 2-h glucose values were not correlated in the glucokinase subjects (r = -0.047, p = 0.65) but were strongly correlated in HNF-1alpha subjects (r = 0.8, p < 0.001). Insulin concentrations were higher in the glucokinase subjects throughout the OGTT.Conclusion/interpretation. The genetic cause of the beta-cell defect results in clear differences in both the fasting glucose and the response to an oral glucose load and this can help diagnostic genetic testing in MODY. OGTT results reflect not only the degree of hyperglycaemia but also the underlying cause.