Loos Ruth J F, Phillips David I W, Fagard Robert, Beunen Gaston, Derom Catherine, Mathieu Chantal, Verhaeghe Johan, Vlietinck Robert
Center for Human Genetics, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium.
Diabetes Care. 2002 Dec;25(12):2191-6. doi: 10.2337/diacare.25.12.2191.
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.
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.
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.
These novel findings suggest that in twin pregnancies, maternal factors are more important than fetoplacental factors in determining glucose-insulin metabolism in the offspring.
有充分证据表明低出生体重与成年人的葡萄糖耐量异常及糖尿病相关。我们开展了一项双生子研究,以区分影响双胞胎双方的母体因素、每个双胞胎独有的胎儿胎盘因素,以及可能构成这种关联基础的遗传因素。
我们从东佛兰德前瞻性双生子调查中确定了423对双胞胎(250对同卵双胞胎和173对异卵双胞胎),他们出生于1964年至1982年之间。本研究收集的数据包括母亲孕期的身体组成和体重增加情况、双胞胎的出生体重及孕周。这些双胞胎(年龄在18 - 34岁之间)前往一个研究中心测量身高、体重、腰臀比,以及空腹血糖、胰岛素原和胰岛素浓度。
在出生体重不一致的双胞胎对中,我们几乎没有发现证据表明体重较轻的双胞胎在成年后有异常的葡萄糖 - 胰岛素代谢。然而,孕前母亲低BMI及分娩时母亲年龄较大均与后代高胰岛素血症及胰岛素抵抗证据相关。母亲BMI每降低一个单位,空腹胰岛素增加1.3%(95%CI 0.1 - 2.6%),母亲年龄每增加一岁,空腹胰岛素增加1.1%(0.02 - 2.0%)。这些关联独立于双胞胎的BMI、腰臀比及其合子类型。
这些新发现表明,在双胎妊娠中,母体因素在决定后代葡萄糖 - 胰岛素代谢方面比胎儿胎盘因素更重要。