The adverse effects of diabetes on osteoarthritis: update on clinical evidence and molecular mechanisms.

Projected increases in the prevalence of both diabetes mellitus (DM) and osteoarthritis (OA) ensure their common co-existence. In an era of increasing attention to personalized medicine, understanding the influence of common comorbidities such as DM should result in improved care of patients with OA. In this narrative review, we summarize the literature addressing the interactions between DM and OA spanning the years from 1962 to 2014. We separated studies depending on whether they investigated clinical populations, animal models, or cells and tissues. The clinical literature addressing the influence of DM on OA and its therapeutic outcomes suggests that DM may augment the development and severity of OA and that DM increases risks associated with joint replacement surgery. The few high quality studies using animal models also support an adverse effect of DM on OA. We review strengths and weaknesses of the common rodent models of DM. The heterogeneous literature derived from studies of articular cells and tissues also supports the existence of biochemical and biomechanical changes in articular tissues in DM, and begins to characterize molecular mechanisms activated in diabetic-like environs which may contribute to OA. Increasing evidence from the clinic and the laboratory supports an adverse effect of DM on the development, severity, and therapeutic outcomes for OA. To understand the mechanisms through which DM contributes to OA, further studies are clearly necessary. Future studies of DM-influenced mechanisms may shed light on general mechanisms of OA pathogenesis and result in more specific and effective therapies for all OA patients.