In vivo evidence of reduced nodal and paranodal conductances in type 1 diabetes

Abstract

ObjectivesDiabetic neuropathy is a debilitating complication of diabetes. Animal models of type 1 diabetes (T1DM) suggest that functional and structural changes, specifically axo-glial dysjunction, may contribute to neuropathy development. The present study sought to examine and characterise early sensory axonal function in T1DM patients in the absence of clinical neuropathy. MethodsThirty patients with T1DM (15M:15F) without neuropathy underwent median nerve sensory and motor axonal excitability studies to examine axonal function. A verified mathematical model of human motor and sensory axons was used to elucidate the underlying causes of observed alterations. ResultsCompared to controls (NC), T1DM patients demonstrated significant axonal excitability abnormalities in sensory and motor axons. These included marked reductions in sensory and motor subexcitability during the recovery cycle (T1DM 7.9±0.4:10.4±0.6%, NC 10.4±0.7:15.4±1.2%, P<0.01) and during hyperpolarizing threshold electrotonus at 10–20ms (T1DM −75.5±0.8:−69.7±0.8%, NC −78.4±1:−72.7±0.9%, P<0.01). Mathematical modelling demonstrated that these changes were due to reduced nodal Na+ currents, nodal/paranodal K+ conductances and Na+/K+ pump dysfunction, consistent with axo-glial dysjunction as outlined in animal models of T1DM. ConclusionsThe study provided support for the occurrence of early changes in nodal and paranodal conductances in patients with T1DM. SignificanceThese data indicate that axonal excitability techniques may detect early changes in diabetic patients, providing a window of opportunity for prophylactic intervention in T1DM.