The LDIflare: A novel test of C-fiber function demonstrates early neuropathy in type 2 diabetes

• Published in: Diabetes care Vol. 27; no. 12; pp. 2930 - 2935
• Main Authors: KRISHNAN, Singhan T. M, RAYMAN, Gerry
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.12.2004
• Subjects: Associated diseases and complications; Biological and medical sciences; Body Mass Index; Brachial Plexus - physiopathology; Care and treatment; Diabetes; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic neuropathies; Diabetic Neuropathies - diagnosis; Diabetic Neuropathies - physiopathology; Diagnosis; Diagnostic Techniques, Neurological; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Glycated Hemoglobin A - analysis; Humans; Male; Medical procedures; Medical sciences; Medical treatment; Middle Aged; Nerve Fibers - physiology; Neurology; Pressure; Reference Values; Reproducibility of Results; Type 2 diabetes; United States; Endocrinopathy; Type 2 diabetes; Human; Nervous system diseases; Laser dopplerometry; Metabolic diseases; Exploration; Early; Diagnosis; Neuropathy; Nerve fiber C
• ISSN: 0149-5992
• DOI: 10.2337/diacare.27.12.2930

The aim of this study was to evaluate a novel method for assessing the axon reflex and to determine its value in detecting neuropathy in type 2 diabetes. The neurogenic flare response to nociceptive stimuli is mediated by an axon reflex involving small unmyelinated C-fibers. We developed a method to assess this reflex involving skin heating to 44 degrees C to evoke the flare followed by scanning the site using a laser Doppler imager (LDI) to measure the area; we termed this method LDIflare. To confirm its neurogenic nature, we examined the LDIflare in eight healthy subjects before and after topical administration of anesthesia. We used this technique to detect C-fiber neuropathy in people with type 2 diabetes. A total of 36 subjects were studied: 12 subjects with neuropathy (group DN), 12 subjects without neuropathy (group DC), and 12 age- and sex-matched control subjects (group NC). For comparison, small-fiber function was also assessed using the Computer Aided Sensory Evaluator-IV (CASE IV) (WR Medical Electronics, Stillwater, MN). In the eight healthy control subjects, LDIflare was markedly reduced after topical administration of anesthesia (1.62 [1.45-1.72] vs. 5.2 cm2 [3.9-5.9], P <0.0001), confirming its neurogenic nature. Similarly, in neuropathic subjects, LDIflare was significantly smaller compared with normal and diabetic control subjects (LDIflare area: DN 1.3 cm2 [0.9-1.8], NC 5.5 cm2 [3.9-5.8], and DC 2.8 cm2 [2.5-3.8]; P <0.0001 and P=0.01, respectively). The group without neuropathy (DC) also demonstrated a reduced flare compared with the NC group (P=0.01). In contrast, C-fiber function assessed by evaluating the quantitative thermal thresholds (CASE IV) did not detect a difference between the latter two groups. This study confirms the neurogenic nature of the LDIflare and clearly demonstrates loss of C-fiber function in neuropathic subjects with type 2 diabetes. Moreover, it demonstrates C-fiber dysfunction before its detection by other currently available methods, including CASE IV. The LDIflare seems to be a simple objective method to detect early neuropathy and may be of value in assessing therapeutic interventions aimed at preventing or reversing C-fiber dysfunction.