Diabetes Mellitus As a Risk Factor for Intervertebral Disc Degeneration: a Critical Review

Purpose: To examine to what extent diabetes mellitus (DM) is implicated as a distinct mechanism in intervertebral disc degeneration (IVDD).

Methods: The published clinical and laboratory data relevant to this matter are critically reviewed. A total of 12 clinical studies evaluate the association between DM and degenerative changes such as IVDD, spinal stenosis (SS) and IVD herniation. A total of 34 laboratory research papers evaluate the association between DM and IVDD.

Results: There are 7 studies that correlate DM with IVDD, 4 of them showing that DM is a significant risk factor for degeneration, and 3 of them failing to establish any association. Three studies demonstrate significant association between DM and SS. However, 2 of these studies also include patients with IVD herniation that failed to demonstrate any correlation with DM. Two other studies indicate a significant association between DM and lumbar disc herniation. Multiple different mechanisms, acting independently or interactively, cause tissue damage leading to IVDD including: microangiopathy of the subchondral vertebral endplate, cellular senescence, cell death (through apoptosis or autophagy), hyperglycaemia, advance glycation end products, adipokines, and cytokines (through oxidative, osmotic, and inflammatory mechanisms).

Conclusion: The clinical evidence is not consistent, but weakly supports the relationship between DM and IVDD. However, the laboratory studies consistently suggest that DM interferes with multipronged aberrant molecular and biochemical pathways that provoke IVDD. Taken as a whole, the strong laboratory evidence and the weak clinical studies implicate DM as a distinct contributing factor for IVDD. These slides can be retrieved under Electronic Supplementary Material.