Impact of Lean Body Mass and Insulin Sensitivity on the IGF-1–Bone Mass Axis in Adolescence: the EPICOM Study

• Published in: The journal of clinical endocrinology and metabolism 2021-02, Vol.106 (2), p.e772-e781
• Main Authors: Jensen, Rikke Beck, Bytoft, Birgitte, Lohse, Zuzana, Johnsen, Sine Knorr, Nielsen, Morten Frost, Oturai, Peter Sandor, Højlund, Kurt, Damm, Peter, Clausen, Tine D, Jensen, Dorte M
• Format: Article
• Language: English
• Subjects: Adolescence; Analysis; Body mass; Bone growth; Bone mass; Bone mineral content; Bone mineral density; Bones; Cognitive ability; Density; Dextrose; Diabetes; Diabetes mellitus (insulin dependent); Dual energy X-ray absorptiometry; Environmental effects; Epigenetic inheritance; Epigenetics; Glucose; Homeostasis; Insulin; Insulin resistance; Insulin-like growth factor I; Insulin-like growth factor-binding protein 3; Insulin-like growth factors; Lean body mass; Offspring; Physiological aspects; Protein binding; Type 1 diabetes
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa861

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