Type 2 diabetes in grandparents and birth weight in offspring and grandchildren in the ALSPAC study.

OBJECTIVE: To examine the association between a history of type 2 diabetes and birth weight of offspring and grandchildren.
DESIGN: Prospective observational study. Diabetic status, as reported by mothers (F1 generation) was collected on grandparents (F0) of babies (F2) born to mothers (F1) who participated in a study of maternal and child health. Associations between risk of grandparental diabetes and birth weight in mothers (F1) and grandchildren (F2) were analysed using linear and logistic regression.
SETTING: Avon: comprising of the city of Bristol and surrounding areas. PARTICIPANTS: 12 076 singleton babies (F2), their parents (F1) and maternal and paternal grandparents (F0).
RESULTS: Women (F1) who had no parents with type 2 diabetes had lower birth weights than women with one or two diabetic parents, after controlling for the age of both parents. There was a U shaped association between maternal birth weight and grandmaternal diabetes, but no evidence of an association with grandpaternal diabetes. The grandchildren of maternal grandparents with type 2 diabetes were more likely to be in the top tertile of birth weight than grandchildren of non-diabetics. There was evidence for an inverted U shaped association between birth weight of grandchildren and diabetes in paternal grandmothers.
CONCLUSIONS: This is the first study to show intergenerational associations between type 2 diabetes in one generation and birth weight in the subsequent two generations. While the study has limitations mainly because of missing data, the findings nevertheless provide some support for the role of developmental intrauterine effects and genetically determined insulin resistance in impaired insulin mediated growth in the fetus.