Endocrine Abstracts

Background: It is now generally accepted that diabetes increases fracture risk, whereby in patients with type 1 diabetes areal bone mineral density (aBMD) is decreased while in type 2 diabetes (T2DM) it is preserved or even increased (1). In case of insulin resistance, being the precursor state of T2DM, large cross-sectional data could not find a significant correlation between insulin resistance and aBMD (2), but longitudinal studies are lacking.

Objective: To assess the impact of insulin resistance on the evolution of aBMD over time in young healthy men.

Methods: In 999 young healthy men aged 25-45, aBMD at the level of the femoral neck, total hip and lumbar spine was measured using dual energy x-ray absorptiometry (DXA) as part of the SIBLOS study. Insulin sensitivity was assessed using the calculation of the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR, which is the product of fasting glucose with fasting insulin, divided by a constant). After an average period of 11.5±1.9 years, these measurements were repeated as part of the SIBLOS-extension (SIBEX) study in 670 participants. Annual percent changes (%/y) in aBMD were calculated to correct for the varying duration between the two time points. Univariate and multivariate analysis was performed using linear mixed effects modelling.

Results: Mean±SD aBMD decreased between SIBLOS and SIBEX at all three measurement sites, namely 0.45±0.52 %/y at the femoral neck, -0.23±0.41 %/y at the total hip and -0.13±0.46 %/y at the lumbar spine. This decrease was less pronounced in participants with higher levels of baseline HOMA-IR (i.e. higher level of insulin resistance; β=0.184 [0.110–0.257, P < 0.001], β=0.179 [0.106–0.253, P < 0.001] and β=0.155 [0.081–0.229, P < 0.001] respectively). After correction for baseline age, weight and height, these relationships maintained significance (β=0.150 [0.068–0.233, P < 0.001], β=0.143 [0.059–0.227, P < 0.001] and β=0.122 [0.037–0.208, P = 0.005] respectively). However, after additional correction for body composition (total body lean mass and fat mass), the association remained significant only at the femoral neck (β=0.090 [0.004–0.177], P = 0.040).

Conclusion: In a population of non-diabetic mid-adult men, higher HOMA-IR levels at baseline seem to protect against age-related aBMD loss, especially at the level of the femoral neck. This finding is consistent with insulin being considered a bone forming hormone. However, it is important to realize that bone strength depends on many other factors than aBMD alone.

References: 1. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2007;18(4):427-44.

2. Verroken C, Zmierczak HG, Goemaere S, Kaufman JM, Lapauw B. Insulin Resistance Is Associated With Smaller Cortical Bone Size in Nondiabetic Men at the Age of Peak Bone Mass. J Clin Endocrinol Metab. 2017;102(6):1807-15.