Long-term follow-up of infants of mothers with type 1 diabetes: evidence for hereditary and nonhereditary transmission of diabetes and precursors.
OBJECTIVE
To estimate the impact of type 1 diabetes during pregnancy on transgenerational genetically caused and/or fuel-mediated amplification of types 1 and 2 diabetes and to estimate the impact of elevated amniotic fluid insulin levels.


METHODS
A total of 75 white offspring of type 1 diabetic mothers and 49 control subjects of similar age and pubertal stage were examined at 5-15 years of age. All offspring had an oral glucose tolerance test. Glucose, insulin, and C-peptide were measured at 0, 30, 60, and 120 min after loading. Lipids and autoimmune antibodies were measured in fasting plasma.


RESULTS
Of the 75 offspring, 4 (5.3%) had overt diabetes, and 16 of 71 (22.5%) had autoimmune antibodies. Offspring of diabetic mothers had significantly higher BMI; symmetry indexes; cholesterol, glucose, insulin, and C-peptide levels; and insulin resistance than control subjects. With the exception of cholesterol, these values were significantly elevated in offspring who had elevated amniotic fluid insulin levels (>8 microU/ml, >48 pmol/l) during pregnancy compared with normoinsulinemic offspring and control subjects.


CONCLUSIONS
Offspring of type 1 diabetic mothers have an increased risk for diabetes later in life. The relative risk for type 1 and type 2 diabetes is 71.6 and 3.2, respectively. Type 2 diabetes-associated risk factors, such as high BMI; elevated glucose, insulin, and C-peptide levels; and insulin resistance, are related to the fetal metabolic experience in utero, as reflected by amniotic fluid insulin concentration.
Weiss
P A
PA
Department of Obstetrics and Gynecology, University of Graz, Austria.
Scholz
H S
HS
Haas
J
J
Tamussino
K F
KF
Seissler
J
J
Borkenstein
M H
MH
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D018392:Genomic Imprinting; D005858:Germany; D006801:Humans; D007328:Insulin / Q000097:blood*; D008055:Lipids / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D009035:Mothers; D011247:Pregnancy; D011254:Pregnancy in Diabetics; D044465:White People
D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D008055:Lipids; D002784:Cholesterol