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Impact of Lean Body Mass and Insulin Sensitivity on the IGF-1-Bone Mass Axis in Adolescence: the EPICOM Study
Rikke Beck Jensen1, Birgitte Bytoft2, Zuzana Lohse3
1Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Insights
Lean mass mediates the relationship between insulin-like growth factor-1 (IGF-1) and bone mass in adolescents. Insulin resistance (IR) did not affect this IGF-1-bone mass connection in offspring of mothers with type 1 diabetes.
Area of Science:
- Endocrinology
- Pediatric Endocrinology
- Bone Metabolism
Background:
- Insulin-like growth factor-1 (IGF-1) influences muscle and bone growth and glucose homeostasis.
- Offspring of mothers with diabetes during pregnancy face higher risks of insulin resistance (IR).
Purpose of the Study:
- To investigate if bone mass is reduced in adolescents born to mothers with type 1 diabetes (T1D).
- To examine the influence of IR on the relationship between IGF-1 and bone mass in these offspring.
Main Methods:
- Utilized data from the EPICOM study (2012-2013), a follow-up to a nationwide register study.
- Included 278 adolescent offspring of mothers with T1D and 303 matched controls.
- Measured bone mineral content (BMC) via dual-energy x-ray absorptiometry, assessing interactions with IGF-1 and insulin sensitivity.
Main Results:
- No significant differences in BMC, bone mineral density, or height were observed between offspring groups.
- IGF-1 levels did not differ, but insulin-like growth factor-binding protein 3 was higher in index boys.
- Statistical analysis revealed IGF-1 predicted BMC/height, with lean mass acting as a mediator. IGF-1 and IR were positively associated.
Conclusions:
- Lean mass serves as an intermediary in the IGF-1-bone mass relationship among adolescents.
- Insulin resistance (IR) does not appear to moderate the IGF-1 and bone mass connection in this cohort.
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.
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