Impact of lean body mass and insulin sensitivity on the IGF-I-bone mass axis in adolescence: the EPICOM study.
Insulin-like growth factor-I (IGF-I) is involved in growth of muscle and bone mass and contributes to glucose homeostasis. Offspring of mothers with diabetes during pregnancy have an increased risk of insulin resistance.We hypothesized that bone mass was decreased in offspring of mothers with type 1 diabetes (T1D), and that IGF-I-bone mass relationship would be negatively influenced by insulin resistance.Data from the EPICOM performed in 2012-2013 was included.A follow-up study of a nationwide register study.278 adolescents index offspring whose mothers had T1D and 303 matched controls.Bone mineral content (BMC) determined by a DXA scan and the interaction with IGF-I and insulin sensitivity.There was no difference in BMC, BMD, height (SDS) or BMC/height between index and control offspring. IGF-I (SDS) did not differ between the groups but IGFBP-3 (SDS) was higher in index boys compared to controls (B:0.31 (95%CI 0.06-0.57), p=0.02). The statistical path analysis showed that IGF-I predicted BMC/height (B:0.24 (95%CI 0.02-0.45), p=0.03), but lean mass was a mediator of this. IGF-I and HOMA-IR were positively associated (B:0.75 (95%CI 0.37-1.12), p=0.0001). There was no moderating effect of the interaction between insulin resistance and IGF-I on lean mass in the entire cohort (B:0.005 (95% CI -0.03-0.04), p=0.81) or when analyzing index cases and controls separately.we found that lean mass was an intermediary factor in the IGF-I-bone mass relationship in a large cohort of adolescents, and this relationship was not moderated by insulin resistance.