Abstract Context Insulin-like growth factor-1 (IGF-1) is involved in the growth of muscle and bone mass and contributes to glucose homeostasis. The offspring of mothers with diabetes during pregnancy have an increased risk of insulin resistance (IR). Objective We hypothesized that bone mass was decreased in the offspring of mothers with type 1 diabetes (T1D), and that the IGF-1–bone mass relationship would be negatively influenced by IR. Design Data from the Epigenetic, Genetic and Environmental Effects on Growth, Metabolism and Cognitive Functions in Offspring of Women with Type 1 Diabetes (EPICOM) study performed from 2012 to 2013 were included. Setting This work is a follow-up study of a nationwide register study. Patients A total of 278 adolescent index offspring whose mothers had T1D and 303 matched controls were studied. Main Outcome Measure Bone mineral content (BMC) determined by a dual-energy x-ray absorptiometry scan and the interaction with IGF-1 and insulin sensitivity were measured. Results There was no difference in BMC, bone mineral density, height (SD score [SDS]), or BMC/height between index and control offspring. IGF-1 (SDS) did not differ between the groups but insulin-like growth factor-binding protein 3 (SDS) was higher in index boys compared to controls (B = .31 [95% CI, 0.06-0.57], P = .02). The statistical path analysis showed that IGF-1 predicted BMC/height (B = .24 [95% CI, 0.02-0.45], P = .03), but lean mass was a mediator of this. IGF-1 and the homeostatic model assessment of IR were positively associated (B = .75 [95% CI, 0.37-1.12], P < .001). There was no moderating effect of the interaction between IR and IGF-1 on lean mass in the entire cohort (B = .005 [95% CI, –0.03 to 0.04], P = .81) or when analyzing index cases and controls separately. Conclusion We found that lean mass was an intermediary factor in the IGF-1–bone mass relationship in a large cohort of adolescents, and this relationship was not moderated by IR.