CONTEXT: 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.

OBJECTIVE: 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.

DESIGN: Data from the EPICOM performed in 2012-2013 was included.

SETTING: A follow-up study of a nationwide register study.

PATIENTS: 278 adolescents index offspring whose mothers had T1D and 303 matched controls.

MAIN OUTCOME MEASURE: Bone mineral content (BMC) determined by a DXA scan and the interaction with IGF-I and insulin sensitivity.

RESULTS: 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.

CONCLUSION: 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.