Low birthweight and metabolic abnormalities in twins with increased susceptibility to Type 2 diabetes mellitus

Aims To evaluate the role of environmental intra-uterine factors in determi ning the birthweights of twins with increased susceptibility to diabetes an d discordant for abnormal responses to the oral glucose tolerance test (OGT T) and verify the possible association of within-pair birthweight differenc es and metabolic abnormalities in adult life. Methods Forty-six monozygotic (MZ) and 32 dizygotic (DZ) twins were enrolle d; 13 MZ twins were discordant for impaired glucose tolerance (IGT) and/or hyperinsulinaemia compared to their co-twins. Results The 13 MZ discordant twins showed significantly lower birthweights than their normal co-twins (P < 0.001). When dividing all twins in those wi th the highest birthweights within the couple and those with the lowest, al l subjects with abnormal OGTT were found in the latter group (P < 0.0001). Within-pair birthweight difference was significantly higher in MZ twins wit h abnormal OGTT and the metabolic syndrome compared to normal MZ twins. The relative risk of developing the metabolic syndrome was 8.7 (1.6-46.9) when comparing the higher tertile of within-pair birthweight differences (great er than or equal to 0.450 kg) to the two lower tertiles (< 0.450 kg). Logis tic regression analysis confirmed within-pair birthweight difference as a s ignificant predictor of abnormal responses to the OGTT and the metabolic sy ndrome. Conclusions These data suggest a causative role for environmental intra-ute rine factors on the determination of birthweight and support the hypothesis that within-pair birthweight difference, rather than an absolute low birth weight, is responsible for the metabolic abnormalities in the adult life.