Gestational Diabetes Leads to the Development of Diabetes in Adulthood in the Rat

Abstract

We have developed a model of gestational diabetes in the rat to determine whether an altered metabolic intrauterine milieu is directly linked to the development of diabetes later in life. Uteroplacental insufficiency is induced in the pregnant rat on day 19 of gestation. Sham-operated animals serve as controls. Offspring are growth retarded at birth; however, they catch up by 5–7 weeks of age. At ∼8 weeks of age, they are bred to normal males. During pregnancy, these animals develop progressive hyperglycemia and hyperinsulinemia accompanied by impaired glucose tolerance and insulin resistance. Offspring, designated as infants of a diabetic mother (IDMs), are heavier at birth and remain heavy throughout life. IDMs are insulin resistant very early in life, and glucose homeostasis is progressively impaired. Defects in insulin secretion are detectable as early as 5 weeks of age. By 26 weeks of age, IDMs are overtly diabetic. These data demonstrate that the altered metabolic milieu of the diabetic pregnancy causes permanent defects in glucose homeostasis in the offspring that lead to the development of diabetes later in life.