Worldwide, the prevalence of diabetes is increasing, leading to a growing global burden in health care costs and significant losses in quality of life. One debilitating condition linked to type 2 (“adult onset”) diabetes is back pain. Type 2 diabetes appears to increase the risk of back pain, which is often caused by the degeneration of intervertebral discs, the flexible shock-absorbing tissue located between rigid vertebral bones in the spine. Understanding the underlying causes of such tissue failure in diabetes is important in helping to prevent and treat symptoms.
“When we began designing this study, we recognized that there are statistical associations between diabetes and a number of different disc pathologies,” said Aaron Fields, associate professor of orthopaedic surgery at the University of California San Francisco. “So we wondered, what are the mechanisms by which type 2 diabetes affects disc biomechanical behavior?”
To answer this question, the researchers turned to small-angle x-ray scattering (SAXS) at Advanced Light Source (ALS) Beamline 7.3.3. They compared the nanostructures of discs from diabetic rats with those from lean, age-matched control animals. A tension/compression stage in the beamline allowed the researchers to compress the discs as they were exposed to the x-ray beam.
Intervertebral discs contain collagen fibers arranged in sheets, where the fibers in one sheet are offset from the fibers in neighboring sheets by roughly ±60° angles from vertical. Healthy discs can sustain large amounts of compression with little fiber damage because the fibers in the sheets move like the crossed beams of a scissor lift—the angle between the fibers of neighboring sheets increases without stretching individual fibers.
The SAXS data showed that collagen fibers in healthy discs indeed stretch and rotate during disc compression. In contrast, the collagen in diabetic discs was stiffer, stretching and rotating less, and leading to earlier plastic, nonrecoverable damage. Biochemical analyses revealed that discs from diabetic animals had significantly higher concentrations of cross-links in the collagen fibers, effectively hindering the fibers’ ability to slide and stretch.
Taken together, the findings reveal that type 2 diabetes impairs efficient and low-energy elastic deformation mechanisms—reorientation, stretching, and straightening of collagen fibers—thereby altering whole-disc behavior and inducing the earlier onset of nonrecoverable plastic deformation.
J.L. Rosenberg, E. Schaible, A. Bostrom, A.A. Lazar, J.L. Graham, K.L. Stanhope, R.O. Ritchie, T.N. Alliston, J.C. Lotz, P.J. Havel, C. Acevedo, A.J. Fields, “Type 2 diabetes impairs annulus fibrosus fiber deformation and rotation under disc compression in the UCD-T2DM rat model,” PNAS Nexus 2, pgad363 (2023), doi:10.1093/pnasnexus/pgad363.
