GENETIC AND ENVIRONMENTAL-INFLUENCES ON INSULIN LEVELS AND THE INSULIN-RESISTANCE SYNDROME - AN ANALYSIS OF WOMEN TWINS

Multiple factors may determine insulin resistance and the insulin resi stance syndrome. The contributions of genes and environment to the dis tribution of fasting insulin levels and to the associations of fasting insulin with elements of the syndrome were evaluated in the second ex amination of the Kaiser Permanente Women Twins Study (Oakland, Califor nia, 1989-1990). Subjects included 556 white women (165 monozygous twi n pairs, 113 dizygous pairs; 455 women with normal glucose tolerance, 75 with impaired glucose tolerance, and 26 with non-insulin-dependent diabetes by World Health Organization criteria). The intraclass correl ation coefficients for log fasting insulin for monozygous and dizygous twin pairs were 0.64 and 0.40, respectively. After adjustment for age , behavioral factors, and body mass index, the estimated classic herit ability was 0.53 (p = 0.003). Commingling analysis of fasting insulin indicated the presence of four distributions (P < 0.001), consistent w ith at least one, and perhaps two, genes influencing this trait. In an unmatched multiple regression model among women from monozygous twin pairs only, log fasting insulin was independently associated with body mass index (p < 0.0001), waist/hip ratio (p = 0.02), and glucose into lerance (p = 0.04), but not with triglycerides, high density lipoprote in cholesterol, or hypertension. After removal of genetic influences b y analysis of monozygous intrapair differences, only body mass index ( p < 0.0001) remained independently related to fasting insulin. The aut hors conclude that, in addition to significant genetic influences on f asting insulin, environmental or behavioral factors (particularly nong enetic variation in obesity) are important determinants of fasting ins ulin and the insulin resistance syndrome. Am J Epidemiol 1996;143:323- 32.