Diagnosing Diabetic Neuropathy: Something Old, Something New

Abstract

There are potentially many ways of assessing diabetic peripheral neuropathy (DPN). However, they do not fulfill U.S. Food and Drug Administration (FDA) requirements in relation to their capacity to assess therapeutic benefit in clinical trials of DPN. Over the past several decades symptoms and signs, quantitative sensory and electrodiagnostic testing have been strongly endorsed, but have consistently failed as surrogate end points in clinical trials. Therefore, there is an unmet need for reliable biomarkers to capture the onset and progression and to facilitate drug discovery in DPN. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging modality for in vivo evaluation of sensory C-fibers. An increasing body of evidence from multiple centers worldwide suggests that CCM fulfills the FDA criteria as a surrogate endpoint of DPN.

Reduced association between dendritic cells and corneal sub‐basal nerve fibers in patients with fibromyalgia syndrome

“…Time for image acquisition did not exceed 5 minutes in any case and no participant suffered from corneal or visual complications afterwards . Per patient, six different images of the sub‐basal nerve plexus from the central cornea, three from each eye, were chosen by an observer blinded to group allocation, based on image quality, overall contrast, correct focal plane, and absence of artifacts as previously recommended . Coded images were assessed off‐line by a second investigator unaware of the study objectives.…”

Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy

“…Morphometric quantification of intraepidermal nerve fibers (IENF) is considered the gold standard for small fiber neuropathy evaluation, even though the invasive nature of the procedure (skin biopsy) obviates its use in longitudinal and interventional studies. Alternatively, corneal confocal microscopy (CCM) is a more appealing technique as it offers a non-invasive mean to follow corneal sub-basal fibers' progressive loss [22,28]. Interestingly, it has been recently suggested that CCM fulfills the Food and Drug Administration (FDA) criteria as a valid surrogate endpoint of DPN [28].…”

“…Alternatively, corneal confocal microscopy (CCM) is a more appealing technique as it offers a non-invasive mean to follow corneal sub-basal fibers' progressive loss [22,28]. Interestingly, it has been recently suggested that CCM fulfills the Food and Drug Administration (FDA) criteria as a valid surrogate endpoint of DPN [28]. Taking into account the aforementioned possibilities for disease assessment, a broad consensus on DPN's diagnostic criteria was provided by the Toronto diabetic neuropathy expert group, who suggested the use of abnormal NCS with a clinical symptom or sign as the minimal criteria for DPN diagnosis confirmation [22].…”

“…Currently, and apart from the management of painful neuropathic symptoms, there are no approved disease-modifying therapies for DPN [28]. Systematic failures of new therapeutic opportunities highlight the need for rodent animal models that closely recapitulate the human disorder, a prime experimental scenario for the development and testing of disease-based pharmacological options [19].…”

Use of parenteral vitamin B complexes in treatment of polyneuropathy

“…Из витаминных комплексов при лечении полинейропатии предпочтение отдается витаминам группы В, которые оказывают метаболическое влияние на аксональный транспорт и процессы миелинизации в периферических нервных волокнах. Кроме того, воздействие витаминов группы В, и в первую очередь тиамина, на центральную нервную систему опосредовано через метаболизм ГАМК и серотонина, что вызывает анальгетический эффект [11,12].…”