Insulin resistance in healthy prepubertal twins.

Abstract

To evaluate insulin sensitivity (S(I)) in prepubertal twins and to examine the relation to reduced birth weight, prematurity, and peroxisome proliferator-activated receptor-gamma (PPAR gamma) polymorphism. Fifty twins (birth weight SDS, -0.7 +/- 0.2; gestation, 33.5 +/- 0.5 weeks; and body mass index SDS, -0.04 +/- 0.2) were studied at 8.2 +/- 0.3 years. S(I) was measured by Bergman's minimal model from a 90 minutes frequently sampled intravenous glucose test. Twenty control children (height SDS, -1.7 +/- 0.3; birth weight SDS, -0.3 +/- 0.2; and gestation of 39.2 +/- 0.7 weeks) were also evaluated at 7.0 +/- 0.4 years. The PPAR gamma T-variant polymorphism was evaluated in 41 twins. Values are expressed as mean +/- SEM, or 95% confidence intervals. S(I) was reduced in twins compared with control subjects, (12.7 [11-15] versus 23.0 [16.8-31.4] 10(-4) min(-1) microU/mL, respectively, P=.005). The reduction in S(I) was independent of prematurity and birth weight and zygosity (P<.0001). There was no difference in S(I), even in twin pairs with >20% difference in birth weight (P=.9). The PPAR gamma heterozygote T-variant polymorphism was present in 7 of 41, with a further reduction in S(I) (P=.03) and a later gestation (P=.03). These twins also had increased fat mass (P=.02) but with similar fat free mass (P=.14). Twin children, independent of prematurity or birth weight, had a marked reduction in S(I). To use twins as a model to study the fetal origins of adult diseases for glucose homeostasis is not valid.