The Predisposition to Obesity and Diabetes in Offspring of Diabetic Mothers

The hypothesis of fuel-mediated teratogenesis (1) proposes that intrauterine exposure to an excess of fuels (for example, glucose) causes permanent fetal changes. In pregnancies complicated by diabetes, this would lead to malformations, greater birth weight, and an increased risk of developing type 2 diabetes in later life. Recently, obesity in the offspring has been included as an outcome in pregnancies complicated by diabetes. The hypothesis is now widely accepted, although the relatively few studies that have examined the question are poorly comparable and focus almost exclusively on growth and glucose regulation. This article reviews the evidence that intrauterine exposure to maternal diabetes conveys high risks for obesity and type 2 diabetes in the offspring, in addition to genetic predisposition, and regardless of maternal diabetes type. It also discusses potential mediators as well as possible public health consequences of fuel-mediated teratogenesis driven by maternal hyperglycemia in utero. Development in a diabetic intrauterine environment results in excess fetal growth. While maternal glucose freely crosses the placenta, maternal insulin does not (1). The developing fetal pancreas responds to this increased glucose load by producing additional insulin, which in turn, acts as a fetal growth hormone promoting growth and adiposity (1). Only two studies have prospectively examined the role of exposure to diabetes in utero on childhood growth, later obesity, and risk for type 2 diabetes in the offspring: the Pima Indian Study and the Diabetes in Pregnancy Study at Northwestern University in Chicago. ### Growth and risk for obesity Researchers at the Diabetes in Pregnancy Center at Northwestern University in Chicago have reported excessive growth in a multiethnic population of offspring of women with diabetes during pregnancy, including both gestational diabetes mellitus (GDM) and insulin-treated preexistent diabetes (2). Children were examined at birth, at age 6 months, and annually to age 8 years. The symmetry index (an obesity index …