Insulin resistance in healthy prepubertal twins

Objectives To evaluate insulin sensitivity (SI) in prepubertal twins and to examine the relation to reduced birth weight, prematurity, and peroxisome proliferator-activated receptor-gamma (PPARgamma) polymorphism. Study design Fifty twins (birth weight SDS, -0.7 +/- 0.2; gestation. 33.5 +/- 0.5 weeks; and body mass index SIDS, -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 PPARgamma T-variant polvmorphisni was evaluated in 41 twins. Values are expressed as mean +/-SEM, or 95% confidence intervals. Results 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) muU/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). Conclusions 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.