Peripheral sensation and RIC inhibition: is diabetic peripheral neuropathy just the tip of the iceberg?

Abstract

Remote ischemic conditioning (RIC) is a therapeutic intervention, known for reducing irreversible damage caused by ischemia-reperfusion injury. Demonstrating great promise in preclinical studies, this outcome has not been consistently reproduced in larger clinical studies. The diabetic state has shown a variable response to RIC. Diabetic sensorimotor polyneuropathy (DSPN) is one of the factors limiting the protective effects of RIC; this was first identified in the 2012 Jensen study. However, the presence of neuropathy or DSPN is still very rarely included in participant characteristics, despite widely accepted evidence that DSPN inhibits the protective effects of RIC. Even if it became standard practice to report the presence and type of neuropathy in RIC studies involving patients with diabetes, much more information is required about the inhibitory effects of DSPN on RIC. The extent of its impact needs to be determined. We argue that a failure to adequately identify peripheral sensory neuropathy, especially DSPN, in study participants may be an important but overlooked confounding factor in RIC research. This review aims to identify and address numerous overlooked questions regarding DSPN, its precursors and its subtypes, and their interactions with RIC. Finally, a series of recommendations are made with respect to RIC studies likely to involve participants with DSPN or similar peripheral sensory impairments, that may assist the transition to clinical practice.