OBJECTIVE: There is strong evidence that low birth weight is associated with glucose intolerance and diabetes in adults. We have carried out a twin study to distinguish among maternal influences, which affect both twins; fetoplacental influences, which are unique to each twin; and the genetic factors that may underlie this association. RESEARCH DESIGN AND METHODS: We identified a sample of 423 twin pairs (250 monozygotic and 173 dizygotic) from the East Flanders Prospective Twin Survey who were born between 1964 and 1982. Data collected in this study included the mother's body composition and weight gain during pregnancy, the twins' birth weights, and gestational age. The twins (aged 18-34 years) attended a research center for measurement of height, weight, and waist-to-hip ratio as well as fasting glucose, proinsulin, and insulin concentrations. RESULTS: Among twin pairs discordant for birth weight, we found little evidence that the lighter twin had abnormal glucose-insulin metabolism in adult life. However, both a low prepregnancy maternal BMI and older maternal age at delivery were associated with hyperinsulinemia and evidence of insulin resistance in the offspring. Fasting insulin increased by 1.3% (95% CI 0.1-2.6%) per unit fall in maternal BMI and by 1.1% (0.02-2.0%) per year increase in maternal age. These associations were independent of the twins' BMI and waist-to-hip ratio and their zygosity. CONCLUSIONS: These novel findings suggest that in twin pregnancies, maternal factors are more important than fetoplacental factors in determining glucose-insulin metabolism in the offspring.