| dc.description.abstract | Diabetes is a global epidemic affecting approximately 537 million people worldwide, which can lead to multiple complications. Non-enzymatic glycation (NEG), a post-translational modification process that is highly accelerated in diabetes-related persistent hyperglycemia (high blood glucose concentration) and oxidative stress, has been identified to be one of the important causes for multiple tissues and organs damage. One of the comorbid conditions is bone fragility and individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) have higher risk of fracture than people without diabetes. This elevation of fracture risk in diabetes cannot be solely explained by bone mass or fall incidences and is currently underestimated by standard of care tools that measure bone mineral density (BMD). Therefore, the bone quality in T1D and T2D independently of BMD needs to be investigated to understand the pathogeneses and mechanisms of the increased bone fragility in diabetes. With the comprehensive understanding of the mechanisms which diabetes induces skeletal fragility, the risk of fracture in people with diabetes can be properly evaluated and managed. Similarly to bone fragility, diabetes could also significantly affect the severity and clinical outcomes of several respiratory diseases, for example, COVID-19. At the time when the hospital and intensive care units (ICUs) were at full capacity/overcrowded with COVID-19 cases, such as seen during the early stage of the pandemic, proper evaluation of diabetes severity and its impact for COVID-19 outcomes at the time of admission could help proper monitoring and management of subsequent care. In this work, we discuss the examination of the cortical and trabecular bone compositional and organizational quality at the material level under the influence of T1D and T2D. Using microindentation, Raman spectroscopy, Fourier transform infrared spectroscopy, and small angle X-ray scattering, we were able to identify and measure the alterations in T2D mineral crystal nanoscale morphology and organic matrix composition, as well as changes in T1D bound-water content. Using data analytics, the association between longitudinal HbA1c, commonly used medications, and two-year fracture risk was assessed in a large cohort with 157,439 T2D individuals, providing important clinical input on assessment, management and reduction of fracture risk in people with T2D through monitoring and management of the longitudinal glycemic control, and the use of metformin and/or DPP4 inhibitors. In a different cohort, we also identified that circulating biomarkers of glycation and oxidative stress including carboxymethyl-lysine (CML), pentosidine, and f2-isoprostanes are independently associated with fracture risk among T2D individuals. The role of these circulating biomarkers in T2D fracture risk was also determined at given BMD levels. Furthermore, using similar data analytic methods in another large T2D cohort, we identified that the two- to three-year longitudinal glycemic control is most significantly associated to COVID-19-related severity in people with T2D, and the combined use of metformin and insulin, as well as the use of corticosteroids are effective to prevent T2D patients from becoming critically ill from COVID-19. | |
