Pathways Linking Birth Weight and Insulin Sensitivity in Early Adolescence: A Double Mediation Analysis.

Purpose: We examined pathways linking birth weight, weight gain from 0 to 2 years, and adiposity during childhood with insulin sensitivity in early adolescence. Methods: Data were from a longitudinal cohort of 630 Quebec white children with a parental history of obesity (Quebec Adipose and Lifestyle Investigation in Youth study). In a subsample of children born at term (n = 395), weight-for-length z score (zWFL) from 0 to 2 years were computed. At 8 to 10 years, the percentage of body fat was assessed using dual energy X-ray absorptiometry. At 10 to 12 years, the Matsuda insulin sensitivity index (ISI) and the homeostasis model assessment for insulin resistance were determined. A linear regression-based approach for mediation analysis was used to estimate the distinct pathways linking zWFL at 0 to 2 years to insulin sensitivity. Results: Every additional unit in zWFL at birth was associated with a 10% (95% CI, 5.26% to 14.85%) increase in the Matsuda ISI in early adolescence, independently of the weight at 0 to 2 years and in childhood. An indirect effect of zWFL at birth on the Matsuda ISI was also observed but in the opposite direction (-4.44; 95% CI, -7.91 to -1.05). This relation was mediated by childhood adiposity but not by weight gain from 0 to 2 years. The indirect effect of weight gain from 0 to 2 years, via childhood adiposity, also led to lower insulin sensitivity (-4.83%, 95% CI, -7.34 to -2.53). The findings were similar for the homeostasis model assessment for insulin resistance or when restricted to children with appropriate-for-gestational-age birth weights. Conclusions: A greater birth weight-for-length resulted in improved insulin sensitivity in early adolescence. However, in the presence of excess childhood adiposity, both a greater birth weight and a faster rate of weight gain from 0 to 2 years resulted in lower insulin sensitivity.