Diabetic Schwann cells suffer from nerve growth factor and neurotrophin-3 underproduction and poor associability with axons.

Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs also provide a microenvironment favoring neural regeneration partially due to production of several neurotrophic factors. Dysfunction of SCs may also play an important role in the pathogenesis of peripheral nerve diseases such as diabetic peripheral neuropathy where hyperglycemia is often considered pathogenic. In order to study the impact of diabetes mellitus (DM) upon the regenerative capacity of adult SCs, we investigated the differential production of the neurotrophic factors nerve growth factor (NGF) and neurotrophin-3 (NT3) by SCs harvested from the sciatic nerves of murine models of type 1 DM (streptozotocin treated C57BL/6J mice) and type 2 DM (LepR(-/-) or db/db mice) or non-diabetic cohorts. In vitro, SCs from diabetic and control mice were maintained under similar hyperglycemic and euglycemic conditions respectively. Mature SCs from diabetic mice produced lower levels of NGF and NT3 under hyperglycemic conditions when compared to SCs in euglycemia. In addition, SCs from both DM and non-DM mice appear to be incapable of insulin production, but responded to exogenous insulin with greater proliferation and heightened myelination potentiation. Moreover, SCs from diabetic animals showed poorer association with co-cultured axons. Hyperglycemia had significant impact upon SCs, potentially contributing to the pathogenesis of diabetic peripheral neuropathy.

Presence of neuropathic pain may explain poor performances on olfactory testing in diabetes mellitus patients.

Olfactory dysfunction in neurodegenerative conditions such as Parkinson's syndrome and Alzheimer's disease can hallmark disease onset. We hypothesized that patients with diabetes mellitus, a condition featuring peripheral and central neurodegeneration, would have decreased olfaction abilities. We examined participants with diabetic peripheral neuropathy, participants with diabetes without diabetic peripheral neuropathy, and control participants in blinded fashion using standardized Sniffin' Sticks. Diabetic peripheral neuropathy severity was quantified using the Utah Early Neuropathy Scale. Further subcategorization of diabetic peripheral neuropathy based on presence of neuropathic pain was performed with Douleur Neuropathique 4 Questionnaires. Participants with diabetes had decreased olfactory sensitivity, impaired olfactory discrimination abilities, and reduced odor identification skills when compared with controls. However, loss of olfaction ability was, at least partially, attributed to presence of neuropathic pain on subcategory assessment, although pain severity was not associated with dysfunction. Those participants with diabetes without diabetic peripheral neuropathy and those with diabetic peripheral neuropathy without neuropathic pain had similar olfactory function as controls in general. The presence of neuropathic pain, associated with limited attention and concentration, may explain at least a portion of the olfactory dysfunction witnessed in the diabetic patient population.

Increased gait variability in diabetes mellitus patients with neuropathic pain.

AIMS: Gait dysfunction in subjects with diabetes mellitus (DM) contributes to falling and subsequent injuries. Using a portable device (GaitMeter™), we measured gait parameters in DM patients with and without diabetic peripheral neuropathy (DPN) during flat surface walking. We hypothesized that DM patients with DPN and neuropathic pain (NeP) would have greater gait step variability than those with DPN without NeP. METHODS: Subjects with DPN and at least moderate NeP (DPN-P), DPN without NeP (DPN-NoP), DM without DPN, and control subjects without DM were assessed. Our outcome measure was gait variability for step length and velocity. DPN severity was quantified using the Toronto Clinical Scoring System and the Utah Early Neuropathy Score. Falls and their outcomes were retrospectively quantified. RESULTS: Each cohort contained≥20 subjects. Durations of DM and HbA1C were greatest amongst DPN cohorts. DPN-P participants had greater variability of step length and step velocity, except for DM only participants. DPN-P participants also reported greater risk of hospitalizations for fall-related injuries, and greater fear of falling. Modest negative relationships emerged for step length with step velocity, reported falls and pain severity. CONCLUSIONS: NeP contributes to gait variability, potentially contributing to the risk of falling in DM patients.