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Prediabetes Tied to Smaller Bone Size

Insulin resistance is inversely and independently associated with bone size in young men without diabetes, according to a new study.

In type 2 diabetes, fracture risk is increased despite preserved areal bone mineral density. Although this apparent paradox may in part be explained by insulin resistance affecting bone structure and/or material properties, few studies have investigated the association between insulin resistance and bone geometry.

The purpose of the study was to explore the association of men with and without diabetes at the age of peak bone mass. There were 996 men without diabetes ages 25-45 years who were recruited in a cross-sectional, population-based sibling-pair study at a university research center.

The authors suggest that insulin resistance itself may alter bone accrual and thus partially explain the elevated fracture risk seen among patients with type 2 diabetes despite normal bone densities.

Specifically, the investigators found that trabecular and cortical bone size was reduced in individuals with insulin resistance, even after researchers controlled for body composition, muscle size, and sex steroid levels, implying that diabetic bone fragility is an early consequence of the underlying pathophysiology.

The team suggests several direct and indirect pathways by which insulin resistance could affect bone size, such as impaired insulin signaling, fat-mass– or adiposity-associated pathways, and modulation of the muscle-bone relationship at weight-bearing sites.

Lead author Charlotte Verroken, MD, stated that, “the relationship between insulin resistance and bone geometry most likely results from a combination of factors, including direct effects of insulin resistance on bone as well as non-direct factors such as fat mass and physical activity.”

Dr. Verroken noted, however, that further research will be needed to determine whether preventing the progression of insulin resistance and, in turn, type 2 diabetes “also prevents the development or progression of bone fragility.”

“The findings furthermore underscore the importance of paying attention to bone health in patients with type 2 diabetes, and I think it is important for clinicians to realize that, instead of being a long-term complication, bone fragility is probably present already at, or even before, the diagnosis of type 2 diabetes mellitus.”

For the current analysis, they examined 996 men ages 25 to 45 years taking part in the SIBLOS study (J Bone Miner Res. 2008; DOI:10.1359/jbmr.081260). None of the participants were receiving antidiabetic drugs or had fasting glucose levels ≥125mg/dL.(7 mmol/L). The participants completed questionnaires on their medical history, medication use, smoking status, and calcium intake. Physical activity was assessed using a short-form questionnaire (Am J Clin Nutr. 1982;36: 936-942).

Fasting serum samples were used to determine insulin resistance via the homeostasis model assessment of insulin resistance (HOMA-IR), while bone geometry was determined with peripheral quantitative computed tomography at the distal radius and the radial and tibial shaft.

The study included 415 brother pairs, 89 singletons, 23 triplets, and two sets of four brothers. Slightly more than half of the men (54.5%) had a normal body mass index, and the mean relative body fat and lean mass were 19.6% and 76.9%, respectively.

In analyses taking into account participant age, height, and weight, HOMA-IR was significantly inversely associated with trabecular area at the distal radius, cortical area, polar strength-strain index (SSIp), the periosteal and endosteal circumference at the radial and tibial shafts, and cortical thickness at the tibia.

Compared with non–insulin-resistant participants, men with insulin resistance had a significantly smaller trabecular area at the distal radius, a smaller cortical thickness, and increased endosteal expansion at the radial shaft, and, at the radial and tibial shafts, a smaller cortical area and smaller periosteal and endosteal circumferences, as well as lower bone strength.

When the team took into account lean and fat mass instead of weight, there were significant inverse associations between HOMA-IR and trabecular area, cortical area, periosteal and endosteal circumference, and SSIp.

The associations between HOMA-IR and trabecular and cortical bone geometry were unaffected by taking into account physical activity, muscle torque, and grip strength, although there were attenuations in the relationships when taking into account jump force.

“Furthermore, the presence of an association between insulin resistance and bone geometry in this nondiabetic population confirms our hypothesis that diabetes-associated bone fragility might develop early as a consequence of insulin resistance, rather than being a late complication of type 2 diabetes.”

From the results, it was concluded that insulin resistance is inversely associated with trabecular and cortical bone size. These associations persist after adjustment for body composition, muscle size or function, or sex steroid levels.

Practice Pearls:

  • There is independent effect of insulin resistance on bone geometry.
  • Bone geometry was not affected when taking into account physical activity, muscle torque, and grip strength.
  • The study shows the importance of identifying diabetes early and monitoring bone health.

The research was published online on December 21 in the Journal of Clinical Endocrinology & Metabolism.