The Relationship between Diabetes Mellitus Type II and Intervertebral Disc Degeneration in Diabetic Rodent Models: A Systematic and Comprehensive Review

Abstract

The number of diabetic patients grows constantly worldwide. Many patients suffer simultaneously from diabetes mellitus type 2 (T2DM) and intervertebral disc disease (IVDD), suggesting a strong link between T2DM and IVDD. T2DM rodent models provide versatile tools to study this interrelation. We hypothesized that the previously achieved studies in rodents approved it. Performing a search in the publicly available electronic databases according to our inclusion (e.g., experimental study with clearly outlined methods investigating IVDD in diabetic rodent models) and exclusion (e.g., non-experimental) criteria, we included 23 studies from 1992 to 2020 analyzing different aspects of IVDD in diabetic rodents, such as on pathogenesis (e.g., effects of hyperglycemia on IVD cells, sirtuin (SIRT)1/p53 axis in the interrelation between T2DM and IVDD), risk factors (e.g., high content of advanced glycation end-products (AGEs) in modern diets), therapeutical approaches (e.g., insulin-like growth factor (IGF-I)), and prophylaxis. Regarding their quality, 12 studies were classified as high, six as moderate, and five as low. One strong, 18 moderate, and three mild evidences of the link between DM and IVDD in rodents were found, while only one study has not approved this link. We concluded that T2DM has a devastating effect on IVD, particularly in advanced cases, which needs to be further evaluated.

Advanced Glycation End Product Inhibitor Pyridoxamine Attenuates IVD Degeneration in Type 2 Diabetic Rats

“…Various animal models have been employed to study T2DM [ 28 , 29 ]. The Zucker Diabetic Sprague-Dawley (ZDSD) animal model is a favorable model because it displays the gradual development of diabetes, mimicking the pathogenesis of human T2DM [ 30 ].…”

IGF Signaling in Intervertebral Disc Health and Disease

“…The addition of IGF1 to the culture of intervertebral disc cells has been shown to prevent the senescence of annulus fibrosus (AF) cells and promote the synthesis of proteoglycan in NP cells (Gruber et al, 2008). IGF1 treatment is considered to be a strategy to inhibit IVD degeneration in under T2DM conditions (Mahmoud et al, 2020). In recent years, tissue engineering and gene therapy technologies can provide sustained release of growth factors (Zhang et al, 2006).…”

Therapeutic Screening of Herbal Remedies for the Management of Diabetes

“…Untreated DM harms the minute blood vessels of some organs such as the kidney, heart, eye, and nervous system [54]. Hence, diabetic nephropathy [55], cardiomyopathy [56], retinopathy [57], and diabetic foot infection [58] are well-known adverse outcomes.…”