Impaired Glucose Tolerance in Adolescent Offspring of Diabetic Mothers: Relationship to fetal hyperinsulinism

OBJECTIVE: To test the hypothesis that long-term postnatal development may be modified by metabolic experiences in utero. RESEARCH DESIGN AND METHODS: We enrolled offspring of women with pregestational diabetes (this included insulin-dependent diabetes mellitus IDDM and non-insulin-dependent diabetes mellitus NIDDM) and gestational diabetes in a prospective study from 1977 through 1983. Fetal beta-cell function was assessed by measurement of amniotic fluid insulin (AFI) at 32-38 weeks gestation. Postnatally, plasma glucose and insulin were measured yearly from 1.5 years of age after fasting and 2 h after 1.75 g/kg oral glucose. Control subjects had a single oral glucose challenge at 10-16 years. RESULTS: In offspring of diabetic mothers, the prevalence of impaired glucose tolerance (IGT) (2-h glucose concentration > 7.8 mmol/l) was: 1.2% at 10 years of age (9 boys and 8 girls) include one girl with NIDDM. IGT was not associated with the etiology of the mother's diabetes (gestational versus pregestational) or macrosomia at birth. IGT was found in only 3.7% (1 of 27) of adolescents whose AFI was normal ( < or = 100 pmol/l) and 33.3% (12 of 36) of those with elevated AFI (P < 0.001). Although most of the children with IGT are obese, AFI and obesity are independently associated with IGT by multiple logistic analysis. CONCLUSIONS: In confirmation of our original hypothesis, IGT in the offspring is a long-term complication of maternal diabetes. Excessive insulin secretion in utero, as assessed by AFI concentration, is a strong predictor of IGT in childhood.