Associations of Abnormal Maternal Glucose Regulation in Pregnancy with Offspring Adiposity, Insulin Resistance, and Adipokine Markers during Childhood and Adolescence

Abstract

To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence. Project Viva is a prospective pre-birth cohort (n = 2,128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used two-step oral glucose challenge testing to screen for gestational diabetes mellitus (GDM). In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n=1107), early adolescence (n=1027), and mid-adolescence (n=693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for pre-pregnancy body mass index (BMI). At mid-adolescence (17.1 [0.8] years old), offspring of mothers with GDM (n=27) had a higher BMI z-score (β; 95%Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15 mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (HOMA-IR, 0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, (HOMA-IR), and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated towards the null after adjustment for maternal pre-pregnancy BMI. Exposure to GDM is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peri-pubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities.