Latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy.

AIM: To assess if latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy. METHODS: Participants with LADA (n=31), Type 2 diabetes (n=31) and healthy control participants without diabetes (n=31) underwent a detailed assessment of neurologic deficits, quantitative sensory testing, electrophysiology, skin biopsy and corneal confocal microscopy. RESULTS: The groups were matched for age (healthy control without diabetes: 53.5±9.1 vs. Type 2 diabetes: 58.0±6.5 vs. LADA: 53.2±11.6 years), duration of diabetes (Type 2 diabetes: 10.0±8.3 vs. LADA: 11.0±9.1 years) and blood pressure. However, BMI (P=0.01) and triglycerides (P=0.0008) were lower and HbA1c (P=0.0005), total cholesterol (P=0.01) and HDL (P=0.002) were higher in participants with LADA compared with Type 2 diabetes. Peroneal motor nerve conduction velocity (P=0.04) and sural sensory nerve conduction velocity (P=0.008) were lower in participants with latent autoimmune diabetes in adults compared with Type 2 diabetes. Intra-epidermal nerve fibre density (P=0.008), corneal nerve fibre density (P=0.003) and corneal nerve branch density (P=0.006) were significantly lower in participants with LADA compared with Type 2 diabetes. There were no significant differences in the other neuropathy parameters. CONCLUSIONS: Despite comparable age and duration of diabetes, participants with LADA demonstrate more severe neuropathy and particularly small fibre neuropathy, compared with participants with Type 2 diabetes.

Visual complications in diabetes mellitus: beyond retinopathy.

Diabetic retinopathy is the most common cause of vision loss in people with diabetes mellitus; however, other causes of visual impairment/loss include other retinal and non-retinal visual problems, including glaucoma, age-related macular degeneration, non-arteritic anterior ischaemic optic neuropathy and cataracts. Additionally, when a person with diabetes complains of visual disturbance despite a visual acuity of 6/6, abnormalities in refraction, contrast sensitivity, straylight and amplitude of accommodation should be considered. We review and highlight these visual problems for physicians who manage people with diabetes to ensure timely referral and treatment to limit visual disability, which can have a significant impact on daily living, especially for those participating in sports and driving.

NerveCheck: An inexpensive quantitative sensory testing device for patients with diabetic neuropathy.

AIMS: Sensory neuropathy is central to the development of painful neuropathy, and foot ulceration in patients with diabetes. Currently, available QST devices take considerable time to perform and are expensive. NerveCheck is the first inexpensive ($500), portable QST device to perform both vibration and thermal testing and hence evaluate diabetic peripheral neuropathy (DPN). This study was undertaken to establish the reproducibility and diagnostic validity of NerveCheck for detecting neuropathy. METHODS: 130 subjects (28 with DPN, 46 without DPN and 56 control subjects) underwent QST assessment with NerveCheck; vibration perception and thermal testing. DPN was defined according to the Toronto criteria. RESULTS: NerveCheck's intra correlation coefficient for vibration, cold and warm sensation testing was 0.79 (95% LOA: -4.20 to 6.60), 0.86 (95% LOA: -1.38 to 2.72) and 0.71 (95% LOA: -2.36 to 3.83), respectively. The diagnostic accuracy (AUC) for vibration, cold and warm sensation testing was 86% (SE: 0.038, 95% CI 0.79-0.94), 79% (SE: 0.058, 95% CI 0.68-0.91) and 72% (SE: 0.058, 95% CI 0.60-0.83), respectively. CONCLUSIONS: This study shows that NerveCheck has good reproducibility and comparable diagnostic accuracy to established QST equipment for the diagnosis of DPN.

Clinical and diagnostic features of small fiber damage in diabetic polyneuropathy.

Small fiber neuropathy represents a significant component of diabetic sensorimotor polyneuropathy (DSPN) which has to date been ignored in most recommendations for the diagnosis of DSPN. Small fibers predominate in the peripheral nerve, serve crucial and highly clinically relevant functions such as pain, and regulate microvascular blood flow, mediating the mechanisms underlying foot ulceration. An increasing number of diagnostic tests have been developed to quantify small fiber damage. Because small fiber damage precedes large fiber damage, diagnostic tests for DSPN show good sensitivity but moderate specificity, because the gold standard which is used to define DSPN is large fiber-weighted. Hence new diagnostic algorithms for DSPN should acknowledge this emerging data and incorporate small fiber evaluation as a key measure in the diagnosis of DSPN, especially early neuropathy.

The diagnostic accuracy of Neuropad for assessing large and small fibre diabetic neuropathy.

AIMS: Neuropad is a simple visual indicator test, with moderate diagnostic performance for diabetic peripheral neuropathy. As it assesses sweating, which is a measure of cholinergic small nerve fibre function, we compared its diagnostic performance against established measures of both large and, more specifically, small fibre damage in patients with diabetes. METHODS: One hundred and twenty-seven participants (89 without diabetic peripheral neuropathy and 38 with) aged 57 ± 9.7 years underwent assessment with Neuropad, large nerve fibre assessments: Neuropathy Disability Score, vibration perception threshold, peroneal motor nerve conduction velocity; small nerve fibre assessments: neuropathy symptoms (Diabetic Neuropathy Symptoms score) corneal nerve fibre length and warm perception threshold. RESULTS: Neuropad has a high sensitivity but moderate specificity against large fibre neuropathy assessments: Neuropathy Disability Score (> 2) 70% and 50%, vibration perception threshold (> 14 V) 83% and 53%, and peroneal motor nerve conduction velocity (< 42 m/s) 81% and 54%, respectively. However, the diagnostic accuracy of Neuropad was significantly improved against corneal nerve fibre length (< 14 mm/mm2) with a sensitivity and specificity of 83% and 80%, respectively. Furthermore, the area under the curve for corneal nerve fibre length (85%) was significantly greater than with the Neuropathy Disability Score (66%, P = 0.01) and peroneal motor nerve conduction velocity (70%, P = 0.03). For neuropathic symptoms, sensitivity was 78% and specificity was 60%. CONCLUSIONS: The data show the improved diagnostic performance of Neuropad against corneal nerve fibre length. This study underlines the importance of Neuropad as a practical diagnostic test for small fibre neuropathy in patients with diabetes.

Automatic analysis of diabetic peripheral neuropathy using multi-scale quantitative morphology of nerve fibres in corneal confocal microscopy imaging.

Diabetic peripheral neuropathy (DPN) is one of the most common long term complications of diabetes. Corneal confocal microscopy (CCM) image analysis is a novel non-invasive technique which quantifies corneal nerve fibre damage and enables diagnosis of DPN. This paper presents an automatic analysis and classification system for detecting nerve fibres in CCM images based on a multi-scale adaptive dual-model detection algorithm. The algorithm exploits the curvilinear structure of the nerve fibres and adapts itself to the local image information. Detected nerve fibres are then quantified and used as feature vectors for classification using random forest (RF) and neural networks (NNT) classifiers. We show, in a comparative study with other well known curvilinear detectors, that the best performance is achieved by the multi-scale dual model in conjunction with the NNT classifier. An evaluation of clinical effectiveness shows that the performance of the automated system matches that of ground-truth defined by expert manual annotation.