Distribution of in vivo insulin action in Pima Indians as mixture of three normal distributions
RIS ID
62776
Abstract
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 X2 = 14.3 with 4 df P < .01) or a mixture of two normal distributions (X2 = 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.
Publication Details
Bogardus, C., Lillioja, S., Nyomba, B., Zurlo, F., Swinburn, B., Esposito-Del Puente, A., Knowler, W. C., Ravussin, E., Mott, D. & Bennett, P. H. (1989). Distribution of in vivo insulin action in Pima Indians as mixture of three normal distributions. Diabetes, 38 (11), 1423-1432.