Weight loss lifestyle intervention and bone health hormonal markers in type 2 diabetes: analysis from look AHEAD study

CONTEXT: Intensive lifestyle interventions (ILI) in people with type 2 diabetes (T2D) not only promote weight loss but are also associated with bone loss and increased fracture risk. The hormonal mechanisms regulating calcium metabolism that may underlie these changes remain to be investigated. OBJECTIVE: To evaluate the association between a weight loss-targeted ILI on 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), and vitamin D-binding protein (VDBP) in adults with T2D. METHODS: We derived data from a randomly selected subset of participants (n = 123) from Look AHEAD (Action for Health in Diabetes), a randomized controlled trial comparing ILI (caloric restriction and physical activity) with diabetes support and education (DSE) in adults with overweight/obesity and T2D. Covariate-adjusted linear mixed regressions were used to examine the effect of ILI on changes in 25(OH)D, PTH, and VDBP at year 1 (weight-loss nadir) and year 4. RESULTS: At year 1, 25(OH)D had an ILI-related increase of 2.04 ng/mL (95% CI: 0.20, 3.88) and PTH had an ILI-related suppression of -6.75 pg/mL (95% CI: -11.4, 2.13). By year 4, these effects were no longer observed as DSE had a delayed increase in 25(OH)D and PTH returned to baseline levels in both groups. No significant treatment effect was observed for VDBP. CONCLUSION: Intensive lifestyle intervention was associated with an increase in 25(OH)D and suppression of PTH elevation during the period of maximal weight loss. These findings suggest that weight loss-targeted lifestyle interventions may influence hormones regulating calcium metabolism, highlighting the need to examine whether such hormonal alterations contribute to bone mineralization during weight loss.