Stride A, Vaxillaire M, Tuomi T, Barbetti F, Njølstad P R, Hansen T, Costa A, Conget I, Pedersen O, Søvik O, Lorini R, Groop L, Froguel P, Hattersley A T
Department of Diabetes and Vascular Medicine, Postgraduate School of Medicine and Health Science, University of Exeter, Exeter, UK.
Diabetologia. 2002 Mar;45(3):427-35. doi: 10.1007/s00125-001-0770-9.
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).
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.
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-1 alpha subjects ( p < 0.0001). Glucokinase subjects had a higher FPG than HNF-1 alpha 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-1 alpha) 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-1 alpha 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.
目的/假设：我们评估了基因遗传病因在导致青年发病的成年型糖尿病（MODY）中的作用如何改变口服葡萄糖耐量试验（OGTT）的反应。
我们研究了来自七个欧洲中心的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-1α（HNF-1α）基因突变。
在基因定义的组中，体重指数（BMI）和年龄相似。2%的葡萄糖激酶受试者和46%的HNF-1α受试者空腹血糖（FPG）低于5.5 mmol/L（p<0.0001）。葡萄糖激酶受试者的FPG高于HNF-1α受试者（[均值±标准差]6.8±0.8 vs 6.0±1.9 mmol/L，p<0.0001），2小时值较低（8.9±2.3 vs 11.2±5.2 mmol/L，p<0.0001），OGTT增加值（2小时-空腹）较低（2.1±2.3 vs 5.2±3.9 mmol/L，p<0.0001）。分类为糖尿病的相对比例取决于使用的是空腹值（38%对22%，葡萄糖激酶对HNF-1α）还是2小时值（19%对44%）。在葡萄糖激酶受试者中，空腹血糖和2小时血糖值不相关（r=-0.047，p=0.65），但在HNF-1α受试者中相关性很强（r=0.8，p<0.001）。在整个OGTT过程中，葡萄糖激酶受试者的胰岛素浓度较高。
结论/解读：β细胞缺陷的遗传病因导致空腹血糖和口服葡萄糖负荷反应均存在明显差异，这有助于MODY的诊断性基因检测。OGTT结果不仅反映高血糖程度，还反映潜在病因。
