The study provides insight into the potential mechanisms underlying diabetes-related disc tissue damage

Type 2 diabetes changes the behavior of the discs in the spine, making them stiffer and also causes the discs to change shape earlier than normal. As a result, the disc’s ability to withstand pressure is compromised. That’s one of the findings of a new rodent study by a team of engineers and physicians from the University of California, San Diego, UC Davis, UCSF and the University of Utah.

Low back pain is a major cause of disability, often associated with intervertebral disc degeneration. People with type 2 diabetes are at higher risk for back pain and disc-related problems. However, the exact mechanisms of disc degeneration remain unclear.

Investigating the biomechanical properties of the intervertebral disc is crucial to understanding the disease and developing effective strategies for the management of low back pain. The research team was co-led by Claire Acevedo, a faculty member in the Department of Mechanical and Aerospace Engineering at the University of California, San Diego, and Aaron Fields, a professor in the Department of Orthopedic Surgery at UC San Francisco.

“These findings provide new insight into the potential mechanisms underlying diabetes-related disc tissue damage and may inform the development of preventive and therapeutic strategies for this debilitating condition.” write the researchers.

The study highlights that nanoscale deformation mechanisms of collagen fibrils serve to compressive load the intervertebral disc. In type 2 diabetes, these mechanisms are compromised, resulting in collagen fragility. These findings provide new insight into the potential mechanisms underlying diabetes-related disc tissue damage and may inform the development of preventive and therapeutic strategies for this debilitating condition.

The researchers used synchrotron small-angle X-ray scattering (SAXS), an experimental technique that examines the deformation and orientation of collagen fibrils at the nanoscale. They wanted to investigate how changes in collagen behavior contribute to changes in the disc’s ability to withstand compression.

They compared discs from healthy rats to those from rats with type 2 diabetes (the UC Davis rat model). The healthy rats showed that the collagen fibrils rotate and stretch when the discs are compressed, allowing the disc to dissipate energy efficiently.

“In diabetic rats, the way the vertebral discs dissipate energy under compression is significantly reduced: diabetes reduces the rotation and stretch of collagen fibrils, indicating a reduced ability to handle pressure.” write the researchers.

Further analysis showed that discs from diabetic rats exhibited stiffness of collagen fibrils, with a higher concentration of non-enzymatic cross-links. This hyperglycemia-induced increase in collagen cross-linking limited plastic deformations through fibril sliding. These findings highlight that fibril reorientation, straightening, stretching, and sliding are critical mechanisms that facilitate whole-disc compression. Type 2 diabetes disrupts these efficient deformation mechanisms, leading to altered biomechanics of the entire disc and a more fragile (low-energy) behavior.

The team published their findings in the December 2023 issue of PNAS Nexus.

This research was supported by the Research Allocation Committee at UCSF (AJF), ​​the Core Center for Musculoskeletal Biology and Medicine at UCSF (AJF), ​​the Office of the President of the University of California (PJH), the National Institutes of Health ( R01 DK095980, R01 HL107256, R01 HL121324, P30 AR066262, R01 AR070198), the University of Utah (JLR), and the Advanced Light Source (ALS07392; TNA, CA).