Prenatal exposures and glucose metabolism in adulthood: are effects mediated through birth weight and adiposity?
OBJECTIVE
Birth weight has been associated with the risk of type 2 diabetes in several studies. We investigated whether prenatal influences on birth weight (gestational age, parity, preeclampsia, prepregnancy BMI, smoking during pregnancy, and socioeconomic position [SEP]) were associated with glucose metabolism in midlife and the role of birth weight for gestational age (BGA) and adult adiposity in mediating these associations.


METHODS
Data from 7,518 participants of the 1958 British Birth Cohort with information on A1C at age 45 years were analyzed. Associations between prenatal exposures and A1C > or =6% were examined using a series of logistic regression models. The basic model consisted of all prenatal factors (except parity) adjusted for sex and family history of type 2 diabetes. Further adjustments included BGA only, concurrent adiposity only (BMI and waist circumference), and BGA plus adiposity.


RESULTS
In the basic model, preeclampsia (odds ratio 1.78 [95% CI 1.14-2.80]), prepregnancy BMI > or =25 kg/m(2) (1.90 [1.45-2.47]), maternal smoking (1.33 [1.04-1.71]), and manual SEP (1.87 [1.36-2.58]) were independently associated with A1C at 45 years of age. Adjustment for BGA had little impact on the prenatal factors/A1C associations, whereas adjustment for adult adiposity at 45 years substantially reduced associations for prepregnancy BMI, smoking during pregnancy, and SEP.


CONCLUSIONS
Prenatal exposures were related to blood glucose levels in mid-adulthood. Associations for several prenatal factors were largely mediated through adult adiposity but surprisingly not through birth weight. Prenatal exposures are likely to have the strongest effect on glucose metabolism indirectly through their influence on adiposity.
Thomas
Claudia
C
Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK. c.thomas@ich.ucl.ac.uk
Hyppönen
Elina
E
Power
Chris
C
D000273:Adipose Tissue / Q000033:anatomy & histology*; D001724:Birth Weight; D015992:Body Mass Index; D049628:Body Size; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005260:Female; D005865:Gestational Age; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology*; D010298:Parity; D011225:Pre-Eclampsia / Q000453:epidemiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
D006442:Glycated Hemoglobin