Importance of familial factors in associations between offspring birth weight and parental risk of type-2 diabetes.

BACKGROUND It is hypothesized that associations found between birth weight and subsequent risk of type-2 diabetes are due to inherited genes affecting both fetal growth and metabolism of insulin. METHODS To study whether there is a familial (shared environmental and genetic) link between birth weight and type-2 diabetes, the authors used a sample of 11,411 Swedish like-sexed twins born from 1926 to 1958 with at least one offspring, to study the association between offspring birth weight for gestational age and parental risk of type-2 diabetes. RESULTS Decreasing offspring birth weight for gestational age (with 1 SD) was associated with an increased risk of type-2 diabetes among father's [odds ratio (OR)=1.72, 95% confidence interval (CI): 1.33-2.23] and decreased risk among mothers (OR=0.43, 95% CI: 0.30-0.62), independent of grand parental and parental socio-economic status and parental smoking. In paired twin analysis, the association between offspring birth weight and mothers with risk of type-2 diabetes was similar within- and between-twin pairs, whereas father's risk was slightly smaller within than between pairs (OR(Between)=1.90, 95% CI: 1.10-3.28, and OR(Within)=1.71, 95% CI: 1.10-2.67, respectively). CONCLUSIONS The well-established association between paternal type-2 diabetes and offspring birth weight seems to primarily be due to as yet unidentified non-shared environmental factors. However, familial factors shared within twin pairs may contribute to the association.