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

Mohamed Mahmoud,Gundula Schulze-Tanzil,Alexander Auffarth,Maria Kokozidou

doi:10.3390/cells9102208

Mohamed Mahmoud, Gundula Schulze-Tanzil + Show 2 more

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https://doi.org/10.3390/cells9102208

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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.

Highlights

Low back pain (LBP) is one of the most common public health disorders in developed countries, with prevalence rates ranging from 12% to 35%
By further evaluation another four publications were excluded; two of them discussed the diabetic animal models used in intervertebral disc disease (IVDD), including rodents, but they were not related to IVDD
The third one was excluded because it discussed the role of adiponectin, mainly found in obese individuals, but it did not address any diabetes mellitus (DM) model [71], and the fourth excluded study dealt with a spinal injury in diabetic rats as one unit and not with IVDD as the main subject of this study [72]

Summary

Introduction

Low back pain (LBP) is one of the most common public health disorders in developed countries, with prevalence rates ranging from 12% to 35%. LBP affects up to 85% of people around the world and occurs at some point in their lives [1,2]. Degeneration of the intervertebral disc (IVDD) is considered to be an important underlying cause of LBP [3,4], back, neck, and radicular pains [5]. IVDs lay between the vertebrae in an alternating fashion giving to the spine its shape, flexibility, and high mobility in different axes and planes. IVDs represent up to 25% of the total spine length and act as distributors of loading and thereby resist compressive loads as well as tensile and shearing stresses [6,7]. The IVD is composed mainly of an external fibrous ring called annulus fibrosus (AF)

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