Corneal confocal microscopy: a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy.

Objective: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies.

Research Design And Methods: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM).

Results: Corneal sensation decreased significantly (P = 0.

Abnormal LDIflare but normal quantitative sensory testing and dermal nerve fiber density in patients with painful diabetic neuropathy.

Objective: Abnormal small nerve fiber function may be an early feature of diabetic neuropathy and may also underlie painful symptoms. Methods for assessing small-fiber damage include quantitative sensory testing (QST) and determining intraepidermal nerve fiber density. We recently described a reproducible physiological technique, the LDIflare, which assesses small-fiber function and thus may reflect early dysfunction before structural damage.

Reduced vascular endothelial growth factor expression and intra-epidermal nerve fiber loss in human diabetic neuropathy.

Objective: To assess the relevance of vascular endothelial growth factor (VEGF) in the maintenance of peripheral nerve integrity in diabetic neuropathy we have assessed the expression of VEGF and intra-epidermal nerve fiber density (IENFD) in skin biopsy samples from diabetic patients.

Research Design And Methods: Fifty-three diabetic patients and 12 nondiabetic control subjects underwent neurological evaluation, electrophysiology, quantitative sensory, and autonomic function testing. Dermal blood flow responses were evaluated with laser Doppler flowmetry.

Neurovascular factors in wound healing in the foot skin of type 2 diabetic subjects.

Objective: Delayed wound healing in diabetic patients without large-vessel disease has been attributed to microvascular dysfunction, neuropathy, and abnormal cellular and inflammatory responses. The role of these abnormalities has mainly been examined in animal models. Few studies have been undertaken in diabetic patients, and those that have are limited due to analysis in wounds from chronic ulcers.

Surrogate markers of small fiber damage in human diabetic neuropathy.

Surrogate markers of diabetic neuropathy are being actively sought to facilitate the diagnosis, measure the progression, and assess the benefits of therapeutic intervention in patients with diabetic neuropathy. We have quantified small nerve fiber pathological changes using the technique of intraepidermal nerve fiber (IENF) assessment and the novel in vivo technique of corneal confocal microscopy (CCM). Fifty-four diabetic patients stratified for neuropathy, using neurological evaluation, neurophysiology, and quantitative sensory testing, and 15 control subjects were studied.

Impaired skin microvascular reactivity in painful diabetic neuropathy.

Objective: The pathogenesis of painful diabetic neuropathy (PDN) is not clear. Following our in vivo observations of increased sural nerve epineurial blood flow in patients with PDN, we investigated the cutaneous microcirculation of the foot by laser Doppler flowmetry to determine if the epineurial findings were just confined to the nerve or more widespread in other vascular beds.

Research Design And Methods: We measured foot skin vasodilator responses to acetylcholine (Ach) and sodium nitroprusside (SNP) and vasoconstrictor responses to sympathetic (deepest possible gasp) stimulation in 5 healthy control subjects, 10 non-neuropathic diabetic (NND) patients, 10 diabetic patients with painless neuropathy (PLDN), and 8 diabetic patients with PDN.

Recent developments in the assessment of efficacy in clinical trials of diabetic neuropathy.

A large number of measures may be employed in clinical practice and for epidemiologic studies to quantify and risk stratify diabetic patients with neuropathy. However, not all measures are suitable for assessing the benefits of therapeutic intervention. Therefore, for the purpose of this review we focus on measures that may be employed to define the efficacy of interventions in clinical trials of human diabetic neuropathy.

Understanding the impact of painful diabetic neuropathy.

Painful neuropathy is a common and often distressing complication of diabetes. It has considerable impact on the social and psychological well-being of affected individuals. There are two distinct forms of painful neuropathy: an acute and self-limiting form that resolves within a year or a chronic form that can go on for years.