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The chronic inflammation observed during type 2 diabetes (T2D) is associated with spinal pathologies, including intervertebral disc (IVD) degeneration and chronic spine pain. Despite confounding factors, such as obesity, studies show that, after adjusting for age, body mass index and genetics (e.g. twins), patients with T2D experience disproportionate severity of IVD degeneration and/or back pain than individuals without T2D. We hypothesized that chronic T2D fosters a proinflammatory microenvironment within the IVD that promotes degeneration and disrupts homeostasis. To test this, we evaluated two common mouse models of T2D - leptin-receptor deficient (db/db) mice and mice with a chronic high-fat diet and impaired β-cell function (STZ-HFD). IVDs of STZ-HFD mice exhibited more severe degeneration and elevated chemokine expression than controls. RNA sequencing further revealed extensive transcriptional dysregulation in STZ-HFD IVDs not observed in db/db IVDs. STZ-HFD IVDs expressed enzymes that enhance advanced glycation end product precursors, impaired non-AGE DAMP pathways and suppressed RAGE turnover. These results suggest that, under controlled genetic and environmental conditions, the STZ-HFD model more accurately reflects the multifactorial inflammatory milieu characteristic of T2D-induced IVD degeneration.
González et al. (Mon,) studied this question.