Deakin University
Browse

File(s) under permanent embargo

Distribution of in vivo insulin action in Pima Indians as mixture of three normal distributions

journal contribution
posted on 1989-01-01, 00:00 authored by C Bogardus, S Lillioja, B L Nyomba, F Zurlo, Boyd Swinburn, A Esposito-Del Puente, W C Knowler, E Ravussin, D M Mott, P H Bennett
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 fits 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.

History

Journal

Diabetes

Volume

38

Issue

11

Pagination

1423 - 1432

ISSN

0012-1797

Publication classification

CN.1 Other journal article

Usage metrics

    Research Publications

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC