Distribution of In Vivo Insulin Action in Pima Indians as Mixture of Three Normal Distributions
Distribution of In Vivo Insulin Action in Pima Indians as Mixture of Three Normal Distributions
复制标题
皮马印第安人体内胰岛素作用的分布为三种正态分布的混合
DOI：
10.2337/diab.38.11.1423
复制
发表时间：
1989
期刊：
影响因子：
7.7
通讯作者：
P. Bennett
中科院分区：
文献类型：
--
作者：
C. Bogardus;S. Lillioja;B. Nyomba;F. Zurlo;B. Swinburn;A. E. Puente;W. Knowler;E. Ravussin;D. Mott;P. Bennett
如果一个基因产生了胰岛素抵抗，而环境影响又造成了一些额外的差异，那么如果该基因是显性的或隐性的，胰岛素的作用可能是两个正态分布的混合分布，或者如果该基因是共显性的，胰岛素的作用可能是三个正态分布的混合分布。为了估计最大胰岛素刺激葡萄糖摄取率(MAXMS)，对245名非糖尿病皮马印第安人(男性126人，女性119人)进行了高胰岛素-正常血糖钳夹试验。通过迭代极大似然估计，将5个模型(分别为1、2、3、4或5个分量，每个模型服从正态分布，具有共同的方差)拟合到MaxM的频率分布。三组分模型的拟合效果明显好于单一正态分布(χ2=14.3，4 df P&t；.01)或两种正态分布的混合分布(χ2=9.9，2 df，P&t；.01)。四个或五个正态分布的混合并不比三个正态分布的混合更好地拟合数据。分布的第一部分占总分布的23%，第二部分占48%，第三部分占29%。同样，空腹血浆胰岛素浓度的频率分布以及由MaxM和空腹胰岛素得出的主成分得分最适合于三个正态分布的混合。这些结果与假设一致，即在PIMA中，胰岛素抵抗是由具有共显性遗传模式的单基因决定的。对家系进行的研究表明，分离分析可以证明或反驳这一遗传假说。
If a single gene produced insulin resistance, with environmental effects creating some additional variance, insulin action might be distributed as a mixture of two normal distributions if the gene is dominant or recessive or as a mixture of three normal distributions if the gene is codominant. To estimate maximal insulin-stimulated glucose uptake rates (MaxMs), hyperinsulinemic-euglycemic clamps were performed on 245 nondiabetic Pima Indians (126 men, 119 women). Five models (for 1, 2, 3, 4, or 5 components each, normally distributed with a common variance) were fitted to the frequency distribution of MaxM by iterative maximum-likelihood estimation. The three-component model fit the data significantly better than a single normal distribution (χ2 = 14.3 with 4 df P < .01) or a mixture of two normal distributions (χ2 = 9.9 with 2 df, P < .01). Mixtures of four or five normal distributions did not fit the data significantly better than a mixture of three normal distributions. The first component of the distribution comprised 23%, the second 48%, and the third 29% of the total distribution. Similarly, the frequency distributions of fasting plasma insulin concentrations and a principal component score derived from MaxM and fasting insulin were best fitted by a mixture of three normal distributions. These results are consistent with the hypothesis that among Pimas, insulin resistance is determined by a single gene with a codominant mode of inheritance. Segregation analyses of studies performed in pedigrees are indicated to prove or disprove this genetic hypothesis.
严重胰岛素抵抗综合征患者及其父母的胰岛素结合和红细胞胰岛素受体自身磷酸化缺陷。
DOI：
10.1210/jcem-64-3-549
发表时间：
1987
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Grigorescu,F;Herzberg,V;King,G;Meistas,M;Elders,J;Frazer,T;Kahn,CR
通讯作者：
Kahn,CR