title: Impaired glucose tolerance in adolescent offspring of diabetic mothers. Relationship to fetal hyperinsulinism.
abstract: OBJECTIVE
  To test the hypothesis that long-term postnatal development may be modified by metabolic experiences in utero.
  
  
  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 < 5 years, 5.4% at 5-9 years, and 19.3% at 10-16 years. The 88 offspring of diabetic mothers (12.3 +/- 1.7 years), when compared with 80 control subjects of the same age and pubertal stage, had higher 2-h glucose (6.8 +/- 1.4 vs. 5.7 +/- 0.9 mmol/l, P < 0.001) and insulin (660 +/- 720 vs. 455 +/- 285 pmol/l, P < 0.03) concentrations. The 17 subjects with IGT 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.
authors.affiliation: Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Silverman
authors.forename: B E
authors.initials: BE
authors.lastname: Metzger
authors.forename: N H
authors.initials: NH
authors.lastname: Cho
authors.forename: C A
authors.initials: CA
authors.lastname: Loeb
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000375:Aging; D000653:Amniotic Fluid / Q000737:chemistry; D001786:Blood Glucose / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D016640:Diabetes, Gestational / Q000235:genetics*; D005260:Female; D018149:Glucose Intolerance / Q000453:epidemiology* / Q000235:genetics; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000032:analysis; D008297:Male; D009035:Mothers; D009679:Nuclear Family; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000235:genetics*; D015995:Prevalence; D012016:Reference Values; D012727:Sex Characteristics; D013737:Testis / Q000033:anatomy & histology
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin