Effects of continuous subcutaneous insulin infusion on the microstructures, mechanical properties and bone mineral compositions of lumbar spines in type 2 diabetic rats

Background: Continuous subcutaneous insulin infusion (CSII) for the treatment of type 2 diabetes (T2D) can improve the structure and strength of femur of rats, but the effect of CSII treatment on the lumbar spine of T2D rats is unknown. The purpose of this study is to investigate the effects of CSII on the microstructure, multi-scale mechanical properties and bone mineral composition of the lumbar spine in T2D rats. Methods: Seventy 6-week-old male Sprague–Dawley (SD) rats were divided into two batches, each including Control, T2D, CSII and Placebo groups, and the duration of insulin treatment was 4-week and 8-week, respectively. At the end of the experiment, the rats were sacrificed to take their lumbar spine. Microstructure, bone mineral composition and nanoscopic-mesoscopic-apparentand-macroscopic mechanical properties were evaluated through micro-computed tomography (micro-CT), Raman spectroscopy, nanoindentation test, nonlinear finite element analysis and compression test. Results: It was found that 4 weeks later, T2D significantly decreased trabecular thickness (Tb.Th), nanoscopic-apparent and partial mesoscopic mechanical parameters of lumbar spine (P < 0.05), and significantly increased bone mineral composition parameters of cortical bone (P < 0.05). It was shown that CSII significantly improved nanoscopic-apparent mechanical parameters (P < 0.05). In addition, 8 weeks later, T2D significantly decreased bone mineral density (BMD), bone volume fraction (BV/TV) and macroscopic mechanical parameters (P < 0.05), and significantly increased bone mineral composition parameters of cancellous bone (P < 0.05). CSII treatment significantly improved partial mesoscopic-macroscopic mechanical parameters and some cortical bone mineral composition parameters (P < 0.05). Conclusions: CSII treatment can significantly improve the nanoscopic-mesoscopic-apparent-macroscopic mechanical properties of the lumbar spine in T2D rats, as well as the bone structure and bone mineral composition of the lumbar vertebrae, but it will take longer treatment time to restore the normal level. In addition, T2D and CSII treatment affected bone mineral composition of cortical bone earlier than cancellous bone of lumbar spine in rat. Our study can provide evidence for clinical prevention and treatment of T2D-related bone diseases.