Maternal blood glucose level and offspring glucose-insulin homeostasis: what is the role of offspring adiposity?

Aims/hypothesis The aim of this work was to investigate the association of maternal HbA(1c)during mid-pregnancy with biomarkers of glucose-insulin homeostasis during early childhood (4-7 years of age) and to assess whether and how offspring adiposity at birth and at age 4-7 years mediates this relationship among 345 mother-child pairs in the Healthy Start Study. Methods The exposure was maternal HbA(1c)(mmol/mol) measured at 20-34 gestational weeks and categorised into tertiles. The outcomes were offspring fasting glucose, 1/insulin, HOMA2-IR, and HOMA2-B at age 4-7 years. The mediators were per cent fat mass (%FM) at birth, %FM at age 4-7 years, and the sum of the two as a metric of cumulative adiposity. Mediation analyses were conducted via a counterfactual-based approach. All models accounted for maternal race/ethnicity, offspring age and sex. Results There was a significant total effect of maternal HbA(1c)on offspring glucose and 1/insulin. Specifically, we observed a positive trend across tertiles of HbA(1c)and offspring glucose (ptrend <0.001), and an inverse trend across tertiles of HbA(1c)and offspring 1/insulin (ptrend = 0.04). For instance, compared with offspring of women in the lowest tertile of HbA(1c), those whose mothers were in the second and third tertiles had 0.04 mmol/l (95% CI -0.05, 0.13) and 0.17 mmol/l (95% CI 0.08, 0.26) higher fasting glucose concentrations at age 4-7 years, respectively. Adjustment for pre-pregnancy BMI did not appreciably change the results. We found no evidence of mediation by offspring adiposity at any life stage. Conclusions/interpretation Offspring of women with higher HbA(1c)during pregnancy had higher fasting glucose and lower insulin sensitivity by early childhood. These relationships were largely unaffected by the child's own adiposity.