Skeletal health in adolescents with poorly controlled type 1 diabetes: results from a randomized controlled trial.

Poorly controlled type 1 diabetes (T1D) has been associated with impaired bone health, but the mechanisms remain unclear. We aimed to investigate whether changes in glycemic control and glucose variability are associated with skeletal health and to evaluate the roles of insulin-like growth factor I (IGF-I) and advanced glycation end-products (AGEs) in bone mineral accrual. This longitudinal study included adolescents with poorly controlled T1D (HbA1c >9%/75 mmol/mol), who underwent dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months. Glycemic control was assessed using glycohemoglobin (HbA1c), continuous glucose monitoring (CGM) parameters, and glycemic load. Serum IGF-I and AGEs, specifically methyl-glyoxal-hydro-imidazolone (MG-HI), were measured. Correlation analyses and linear regression models were used to evaluate the associations between glycemic markers, IGF-I, AGEs and bone parameters. Altogether, 37 adolescents (48.6 % female) with T1D, with mean HbA1c 9.9% (85 mmol/mol), were followed up from mean age of 14.3 for 12 months. DXA-derived bone mineral density (BMD) z-scores at lumbar spine, proximal femur, and total body less head were approximately 0.5 SDS lower than reference values (p=0.005-0.04). The only significant change in BMD z-scores during the 12-month follow-up was an increase in proximal femur in girls. In the whole group, an increase in IGF-1 was associated with BMD accrual, while changes in HbA1c, time in range, or MG-HI were not. No vertebral fractures were detected. Despite lower BMD in adolescents with poorly controlled T1D, neither changes in glycemic control nor MG-HI levels correlated significantly with bone health measures, while increase of IGF-1 was associated with BMD accrual. Future studies should explore alternative AGEs and use advanced bone imaging techniques to better understand skeletal fragility in T1D.