The growth and refinement in rat T2DM models over the past 2 decades have been accompanied by an increased focus on improving the consistency of protocols used to objectively measure and report DPN. While rat and mouse models of T1DM and T2DM have been reviewed previously, here we sought to evaluate the quality of DPN phenotyping, specifically in rat models of T2DM. Research has sought to develop preclinical models that allow for the metabolic comorbidities associated with T2DM to be studied, such as obesity, hypertension, dyslipidemia, inflammation, and insulin resistance, thus requiring modifications to the high dose streptozotocin (STZ) model of T1DM. The consequences of these distinct pathophysiological mechanisms were highlighted by a meta-analysis demonstrating that glycaemic control, the only accepted disease modifying treatment, is less effective for DPN symptoms in individuals with T2DM than T1DM. ĭPN is common in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), though it has long been recognised they have distinct pathophysiological mechanisms. ![]() Despite dramatic effects of DPN on quality of life and healthcare costs, there are still no effective disease modifying treatments other than strict glycaemic control and pain management. These initial manifestations can progress to physical impairments (e.g., loss of balance) and an increased risk of falls, foot ulceration, amputation and mortality. DPN manifests as a distal symmetric polyneuropathy affecting the lower extremities in a length-dependent fashion and is primarily a disorder of sensory dysfunction characterized by pain, allodynia, numbness, and insensate feet. A consequence of the rising global prevalence of diabetes and prediabetes is a corresponding increase in DPN. Despite such high prevalence, the basic disease mechanisms of DPN are yet to be deciphered. Diabetic peripheral neuropathy (DPN) is the most prevalent complication in diabetes, affecting more than 50% of long-term type 2 patients. In 2019, the International Diabetes Federation estimated that 463 million adults are living with diabetes and 374 million with impaired glucose tolerance, predicted to rise to 700 million and 548 million, respectively, by 2045. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development.ĭiabetes is a global health concern that cuts across socioeconomic status and national boundaries. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. ![]() ![]() Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |