Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood: sibling study in a prospective cohort of 280,866 men from 248,293 families.

BACKGROUND Maternal diabetes mellitus in pregnancy results in greater offspring adiposity at birth. It is unclear whether it is associated with greater adiposity into adulthood, and if so, whether this is via intrauterine mechanisms or shared familial characteristics. METHODS AND RESULTS A record-linkage prospective cohort study of 280,866 singleton-born Swedish men from 248,293 families was used to explore the intrauterine effect of maternal diabetes mellitus on offspring body mass index (BMI) in early adulthood. Maternal diabetes mellitus during pregnancy was associated with greater mean BMI at age 18 in their sons. The difference in BMI was similar within brothers and between nonsiblings. BMI of men whose mothers had diabetes mellitus during their pregnancy was on average 0.94 kg/m² greater (95% confidence interval [CI], 0.35 to 1.52) than in their brothers born before their mother was diagnosed with diabetes, after adjustment for birth year, maternal age, parity and education, birth weight, gestational age, and age at assessment of BMI. Early-pregnancy BMI was positively associated with son's BMI between nonsiblings, but there was no association within brothers. Adjustment of the maternal diabetes-offspring BMI association for maternal BMI did not alter the association either within brothers or between nonsiblings. Results were also robust to sensitivity analyses restricting the within-sibling analyses to siblings born within 3 years of each other. CONCLUSION Maternal diabetes mellitus has long-term consequences for greater BMI in offspring; this association is likely to be via intrauterine mechanisms, and is independent of maternal BMI in early pregnancy.