Does Type II Diabetes Induce Early Senescence and Degeneration in Human Intervertebral Discs? A Tissue Biomarker Evaluation
G. Sudhir, SUBALAKSHMI BALASUBRAMANIAM, Vignesh Jayabalan, Sandhya Sundaram, Venkatesh Kumar, Karthik Kailash
Abstract
BACKGROUND: Diabetes mellitus is one of the leading causes of morbidity resulting in multi-organ dysfunction. Animal studies have shown that hyperglycemia results in stress-induced senescence through the p16-pRb pathway, thereby accelerating early disc degeneration. There is a paucity of literature on the effect of hyperglycemia in human intervertebral disc cells. We aimed to analyze the effect of diabetes mellitus in human intervertebral disc cells. METHODS: This is a prospective study done in patients with degenerative disc disease. Patients were categorized into a control group (no diabetes: 26 patients) and a study group (type 2 diabetes for > 3 years: 24 patients). All patients underwent either discectomy or transforaminal lumbar interbody fusion and the removed disc was transported to pathology department. Tissue was prepared and histopathological grading was done followed by immunohistochemistry studies using antibodies for MMP-1, p21, p16, and pRb. RESULTS: Samples from diabetic patients had severe (grade 2) degenerative changes compared with the control group (grade 1). Changes were more intense in the nucleus pulposus with increased cellularity and clustering of chondrocytes, and disorganization and loss of nuclear matrix. Immunohistochemical staining for MMP1, p16, and pRb was more intense (Q score = 4) whereas the staining for p21 was less intense (Q score = 1) in the diabetic group compared with the control group. CONCLUSION: Our study demonstrates that type 2 diabetes mellitus accelerates stress-induced senescence in human intervertebral discs resulting in early disc degeneration. Also, the severity of disc degeneration is severe compared with the normal subjects. CLINICAL RELEVANCE: Hyperglycemia can affect the intervertebral discs similar to other organs and hence adequate control of blood glucose in diabetics can prevent the disc degeneration, which is the initiator of degeneration cascade in spine.